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doi.org/10.26434/chemrxiv.8977673.v1
Engaging Aldehydes in CuH-Catalyzed Reductive Coupling Reactions:Stereoselective Allylation from 1,3-Diene PronucleophilesChengxi Li, Kwangmin Shin, Richard Liu, Stephen L. Buchwald
Submitted date: 22/07/2019 • Posted date: 23/07/2019Licence: CC BY-NC-ND 4.0Citation information: Li, Chengxi; Shin, Kwangmin; Liu, Richard; Buchwald, Stephen L. (2019): EngagingAldehydes in CuH-Catalyzed Reductive Coupling Reactions: Stereoselective Allylation from 1,3-DienePronucleophiles. ChemRxiv. Preprint.
Recently, CuH-catalyzed reductive coupling processes involving carbonyl compounds and imines hasbecome an attractive alternative to traditional methods for stereoselective addition to carbonyls due to theability to use readily accessible and stable olefin-derived pronucleophiles as surrogates for organometallicreagents. However, the inability to use aldehydes, which traditionally reduce too rapidly in the presence ofcopper hydride complexes to be viable substrates, has been a major limitation. We show that by exploitingrelative concentration effects through slow addition, we can invert this intrinsic reactivity and achieve thereductive coupling of 1,3-dienes with aldehydes. Using this method, both aromatic and aliphatic aldehydescan be transformed to valuable products with high levels of diastereo- and enantioselectivity and in thepresence of many useful functional groups. Furthermore, using a combination of theoretical (DFT) andexperimental methods, important mechanistic features of this reaction related to stereo- and chemoselectivitywere uncovered.
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Engaging Aldehydes in CuH-Catalyzed Reductive Coupling Reac-
tions: Stereoselective Allylation from 1,3-Diene Pronucleophiles
Chengxi Li,† Kwangmin Shin,† Richard Y. Liu, and Stephen L. Buchwald*
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
ABSTRACT: Recently, CuH-catalyzed reductive coupling processes involving carbonyl compounds and imines has become an at-
tractive alternative to traditional methods for stereoselective addition to carbonyls due to the ability to use readily accessible and
stable olefin-derived pronucleophiles as surrogates for organometallic reagents. However, the inability to use aldehydes, which tra-
ditionally reduce too rapidly in the presence of copper hydride complexes to be viable substrates, has been a major limitation. We
show that by exploiting relative concentration effects through slow addition, we can invert this intrinsic reactivity and achieve the
reductive coupling of 1,3-dienes with aldehydes. Using this method, both aromatic and aliphatic aldehydes can be transformed to
valuable products with high levels of diastereo- and enantioselectivity and in the presence of many useful functional groups. Further-
more, using a combination of theoretical (DFT) and experimental methods, important mechanistic features of this reaction related to
stereo- and chemoselectivity were uncovered.
■ INTRODUCTION
The addition of nucleophilic organometallic reagents, such
as those based on Mg (Grignard), B, Si, Sn and Zn, to carbonyl
derivatives is a key reaction for C–C bond formation.1 Accord-
ingly, the development of methods to accomplish this transfor-
mation in a catalytic, stereoselective manner have been the sub-
ject of widespread research efforts.2 Recently, breakthroughs in
transition metal catalysis have enabled the use of olefin-derived
nucleophiles, one of the most convenient and readily available
classes of compounds, as surrogates of traditional organometal-
lic reagents in carbonyl addition processes.3-10 Following pio-
neering work by Krische using Rh4a,b, Ru5, Ir6, and Ni cata-
lysts,7e several research groups, including ours, have developed
a number of CuH-catalyzed processes for reductive C–C bond
formation from π-unsaturated pronucleophiles (Figure 1A).9,10
Each of these metals is associated with distinct catalytic
mechanisms and complementary reactivity, and hence, features
respective advantages and deficiencies. In the case of Cu, the
most notable advantages include mild conditions, high stereose-
lectivity, and exceptional tolerance for polar functional
groups.9,10 On the other hand, the proclivity of CuH intermedi-
ates to participate in direct reduction of carbonyl compounds
has so far limited the generality of this strategy: to date, only
the functionalization of ketones and imines using relatively ac-
tivated alkenes such as allenes, enynes, styrenes have been suc-
cessfully accomplished (Figure 1B).9,10 The conspicuous ab-
sence of aldehydes, the most common class of electrophiles in
carbonyl addition reactions, can be explained by the rate of their
direct reaction with CuH species, which is sufficiently high that
the olefinic partner typically does not have the chance to partic-
ipate in hydrocupration.11
With the aim of addressing this important limitation, we
herein report the expansion of the scope of CuH-catalyzed re-
ductive olefin–carbonyl coupling to aldehyde starting materials,
using a combination of ligand-conferred regioselectivity and ki-
netic control through metered addition. To prove our concept,
we selected 2-substituted 1,3-dienes as relatively unactivated
model pronucleophiles (Figure 1B). 2-Substituted allyl groups
are difficult to introduce using stoichiometric organometallic
reagents, and few catalytic methods have been reported for their
stereoselective installation.2,12
Figure 1. Overview of CuH-catalyzed reductive coupling of π-
unsaturated pronucleophiles with carbonyl derivatives.
Considering previous mechanistic studies,9f we envisioned
that our proposed transformation would proceed through hydro-
cupration of a diene to generate a mixture of allylcopper com-
plexes represented by II (Figure 1C). One or more of these spe-
cies could engage an aldehyde coupling partner in a stereose-
lective migratory insertion process to form the copper alkoxide
III, from which metathesis with a hydrosilane (IV) would re-
generate LCuH (I) and the desired product (V) in silyl-protected
form. Clearly, the diene hydrocupration must be faster than the
rapid direct reduction of the aldehyde, which is contrary to the
intrinsic kinetic preferences of these elementary reactions (18.5
vs. 13.9 kcal/mol calculated free energy barriers for diene and
aldehyde hydrocupration respectively, see below). In this article,
we describe the optimization of a reaction system that displays
this inverted chemoselectivity, its applications to the highly re-
gio-, diastereo- and enantioselective allylation of both aliphatic
and aromatic aldehydes, and mechanistic studies that explain
the origin of these selectivities.
■ RESULTS AND DISCUSSION
We initiated our study by examining reactions of p-
anisaldehyde (1a) and 2-phenyl-1,3-butadiene (1b) under re-
action conditions previously described for CuH-catalyzed
ketone allylation.9e,f With (S,S)-QuinoxP*(L1) as the ligand,
the desired product 1 was obtained in 48% yield, with exclu-
sive branched-selectivity and excellent preference for the in-
dicated diastereomer (11:1 dr). However, the major diastere-
omer was formed with only a moderate level of enantiose-
lectivity (68:32 er, Table 1, entry 1). No desired homoallylic
alcohol 1 was obtained when (R)-DTBM-SEGPHOS (L2)
was used as the ligand: complete reduction of the aldehyde
was observed instead (Table 1, entry 2). JosiPhos13 deriva-
tive SL-J011-1 (L3), a ligand which had been employed with
good results in ketone allylation,9f was also examined. The
corresponding test reaction provided 1 in moderate (57%)
yield, with 8:1 dr and 85:15 er (Table 1, entry 3). Further
evaluation of commercially available common chiral ligands
revealed (S,S)-Ph-BPE (L4) to be optimal (Table 1, entry 4),
providing 75% yield of 1 was obtained with excellent dr
(21:1) and er (96.5:3.5). Table 1. Evaluation of Reaction Conditions for the CuH-Catalyzed
Allylation of 4-Methoxybenzaldehyde.a
Entry Ligand Cat.
(%)
Temp.
(°C)
Yieldb
1 (%)
dr erc
(major)
1 L1 5 rt 48 11:1 68:32
2 L2 5 rt 0 -- --
3 L3 5 rt 57 8:1 85:15
4 L4 5 rt 75 21:1 96.5:3.5
5 L4 5 40 71 24:1 95.5:4.5
6 L4 1 rt 90 13:1 94:6
7 L4 1 0 94 13:1 95:5
8 d L4 1 0 33 9:1 95:5
9 e L4 1 0 97 10:1 91:9
aConditions: 1a (0.1 mmol, 1 equiv), 1b (2 equiv), Cu(OAc)2 (0.01
or 0.05 equiv), ligand (0.012 or 0.06 equiv), dimethoxy(me-
thyl)silane (4.0 equiv) in solvent (0.2 mL). 1a was added slowly by
syringe pump (1.0 mol/L, 1.0 uL/min); see the Supporting Infor-
mation for details. bYield and diastereomeric ratio were determined
by 1H NMR spectroscopy of the crude reaction mixture, using di-
bromomethane as an internal standard. cEnantiomeric ratio was de-
termined by HPLC or SFC analysis on commercial chiral columns,
and the relative configuration of 1 was determined by comparing
its NMR and optical rotation data with reported data.14 dWithout
metered addition. eWith slower addition rate (1.0 mol/L, 0.5
uL/min).
With a slight increase in reaction temperature (40 ˚C),
both the yield and er diminished slightly (Table 1, entry 5).
Furthermore, the results were very sensitive to the catalyst
loading: excellent yield (90%) was achieved without losing
high diastereo- and enantioselectivity (13:1 dr, 94:6 er) by
decreasing the catalyst loading from 5.0 to 1.0 mol% (Table
1, entry 6). Lowering the temperature to 0 ˚C proved to be
beneficial, increasing the yield to 94% (Table 1, entry 7). Me-
tered addition of the aldehyde is also important for this allyla-
tion process: by adding the aldehyde in a single batch at the start
of the reaction, only 33% of target product could be observed.
However, extremely slow addition rates will decrease the enan-
tioselectivity slightly and are not advantageous for the yield
(Table 1, entry 8 and 9).
We next explored the scope of the asymmetric reductive
coupling of aldehydes with 1,3-dienes. As depicted in Table 2,
a range of chiral homoallylic alcohols were prepared in excel-
lent yields and levels of enantiomeric purity. Simple benzalde-
hyde was successfully transformed into the corresponding
homoallylic alcohol 2 in good yield with moderate diasterose-
lectivity, but high enantioselectivity. Notably, aliphatic primary
(3, 4), secondary (5), and tertiary (6) aldehydes were also com-
patible substrates with our protocol, providing uniformly excel-
lent yield, dr and er. Using ferrocenecarboxaldehyde, we ob-
tained enantiomerically enriched ferrocene derivative 7. Fur-
thermore, substrates containing heterocycles, such as a furan (8),
a thiophene (9) and an indole (10), were all tolerated under the
reaction conditions. A thioether could also be effectively con-
verted into secondary alcohol 11 with good stereoselectivity.
Next, we assessed the scope of 1,3-diene pronucleophiles
(Table 2). The reaction proceeded efficiently with dienes bear-
ing electron-donating (7, 8) or electron-withdrawing (9, 10) aryl
substituents at 2-position. Various heterocycles are well toler-
ated on the diene component, including a thiophene and an in-
dole, reacting efficiently with both aromatic and aliphatic alde-
hyde partners (11-14) with excellent diastereo- and enantiose-
lectivity.
2-Alkyl substituted dienes could also be effectively con-
verted. For instance, 2-cyclohexyl-1,3-butadiene coupled well
with a range of vinyl (15) and aliphatic aldehydes (16-18) with
high selectivities, although the yields are moderate. In particular,
simple aliphatic aldehydes such as acetaldehyde are suitable
starting materials for this reaction (16). Even extreme steric
bulk on both components could be tolerated: using pivaldehyde
and an adamantyl-substituted diene, homoallyl alcohol 19 was
obtained with moderate yield (48%) and excellent diastereo-
and enantioselectivity (>20:1 dr, 99.5:0.5 er). Finally, a natu-
rally occurring diene, myrcene, proved to be an effective rea-
gent, providing 20 with good yield and useful stereoselectivity.
Table 2. Evaluation of the Scope of the Aldehyde Allylation with Branched Dienes.a
aYields indicate the isolated yield of product as a mixture of two diastereomers on a 1.0 mmol scale. Diastereomeric ratios were determined
by 1H NMR spectroscopy for both the crude and purified products; enantiomeric ratios were determined by HPLC, SFC or chiral GC analysis
on commercial chiral columns. Yields, diastereomeric ratios, and enantiomeric ratios are the averages for two identical runs. See Supporting
Information for full details.
■ MECHANISTIC STUDIES
By analogy to other copper-catalyzed reductive olefin–ke-
ton9b,f and olefin–imine coupling9a reactions, we proposed that
the current reaction proceeds through the mechanism illustrated
in Figure 1C. Previous computational and experimental inves-
tigations of related transformations have revealed, in intricate
detail, the sequence of events and controlling factors that dictate
the regio-, diastereo- and enantioselectivity observed in these
transformations.9f However, we were interested in several ques-
tions pertaining to the mechanism and selectivity that are par-
ticular to this aldehyde allylation. First, we wanted to confirm
the feasibility of our proposed series of elementary steps, as
well as their relative rates, their reversibility, and the identity of
the selectivity-determining step(s). It is important to note, how-
ever, that metered addition of the aldehyde, which presumably
maintains a low steady-state concentration of aldehyde, is cru-
cial to obtaining high yields of product. Thus, it is necessary
that our model to account for this effect. Second, we hoped to
explain the stereochemical outcome of our reaction. Specifi-
cally, our rationale should both identify the step(s) that control
the diastereo- and enantioselectivity (allylcopper isomerization,
C–C bond formation, -bond metathesis, or a combination
thereof), as well as the specific ligand–substrate interactions re-
sponsible for destabilizing the disfavored stereoisomeric path-
ways. Finally, we wanted to confirm experimentally that com-
peting aldehyde vs. diene insertion into a copper(I) hydride
complex determines the chemoselectivity with regard to reduc-
tion vs. the desired coupling.
Figure 2. Computed energy profiles for CuH-catalyzed allylation (blue) and reduction (red) of benzaldehyde (1c). These calculations
were performed at the M06-2X/SDD–6-311+G(d,p)/SMD(toluene)//B3LYP/SDD–6-31G(d) level of theory. Standard free energies
are relative to infinitely separated I and reactants (1c and 1b). See the Supporting Information for details.
Figure 3. Stereochemical model for the CuH-catalyzed aldehyde allylation process. DFT-optimized lowest energy transition state
structures for the C–C bond formation step, leading to the major stereoisomer (left), the minor diastereomer (middle) and the minor
enantiomer (right) of product 2. See the Supporting Information for details.
We first turned to DFT-based modeling to address the first
two questions. The computed Gibbs free energy profile, using
model diene 1b and benzaldehyde (1c) as model substrates, is
shown in Fig. 2. Starting from L*CuH (I), where L* = (S,S)-
Ph-BPE, irreversible hydrocupration of 1b takes place prefer-
entially through its s-cis conformation and with facial selectiv-
ity to generate the S enantiomer of branched allylcopper com-
plex IIa. We found that (S)-IIa can isomerize rapidly to a nearly
isoenergetic linear isomer IIb-cis, in which the Ph and Me al-
kene substituents are mutually cis. While this isomerization is
associated with an energetic barrier of 7.1 kcal/mol (TS3-cis),
there also exists a second, slower isomerization pathway (13.0
kcal/mol barrier) leading to more stable linear isomer IIb-trans
(4.0 kcal/mol more stable than IIa), in which the Ph and Me are
mutually trans.
In accordance with the Curtin–Hammett principle, the iso-
mer of II (e.g., IIa, IIb-cis, IIb-trans) through which the reac-
tion proceeds will depend on the rate of the subsequent addition
step relative to the isomerization processes. However, prior to
further elaboration on this aspect, we first need to more pre-
cisely consider the effect of slow addition of aldehyde on the
mechanistic model in general. While it is conventional to plot
energy diagrams using standard thermodynamic parameters,
(i.e., those at 1 M solution for solutes), true relative free ener-
gies depend on the concentrations of the species involved. In
cases where two reactants might have concentrations differing
by many orders of magnitude during steady-state catalyst turn-
over, it is particularly important to consider relative concentra-
tion effects in the interpretation of an energy diagram.15
Accordingly, in the reaction under consideration, we noted
that the metered addition of aldehyde over several hours should
ensure that the concentration of the aldehyde is very low rela-
tive to the other reactants. The presence of this concentration
disparity is equivalent to raising the free energy of all states
wherein aldehyde is associated with the catalyst (Figure 2, high-
lighted in grey) relative to states in which the aldehyde is free
(in white). Indeed, we find that if, by relative concentration ef-
fects, TS1 is raised in energy by more than about 4.6 kcal/mol
relative to TS2a, hydrocupration can be favored over direct re-
duction of the aldehyde, as is observed in the reaction.
A less obvious consequence is that the reaction of the cop-
per allyl species is also slowed, which has implications on re-
versibility of allylcopper isomerization. We examined eight di-
astereomeric transition states for allylcopper addition to the al-
dehyde (Figure 4, boxed and labeled TS4-cis/trans). Consider-
ing standard free energies alone, it would appear that reaction
of the cis-allyl complex IIb-cis through (S,S)-TS4-cis is suffi-
ciently facile that competing isomerization to the more stable
IIb-trans should be kinetically precluded. However, with spe-
cies highlighted in grey raised in energy by the amount (>4.6
kcal/mol) required to avoid direct aldehyde reduction, reaction
of IIb-cis with aldehyde through the TS4-cis transition states
necessarily become more challenging than reversible isomeri-
zation to IIb-trans. In this scenario, the predicted major reac-
tion pathway (highlighted in blue) proceeds through (S,R)-TS4-
trans, leading to the diastereomer of product that is experimen-
tally observed to be predominant ((S,R)-V).
We next examined the transition state structures to eluci-
date the origin of stereoselectivity in the addition step. Mono-
meric complexes of Ph-BPE-ligated copper are known adopt a
conformation whose steric profile is well approximated by a
quadrant model.16 For instance, in the preferred six-membered
cyclic transition state (Figure 3, left panel),17 the largest substit-
uents of both the allyl component and the aldehyde component
are directed into the less hindered (white) quadrants during the
C–C bond formation. In contrast, minor enantiomer of product
can form if the aldehyde attacks the opposite face of the diene
(Figure 3, center panel). However, a steric clash is created be-
tween the aryl substituent of the diene and the Ph substituent of
the ligand (bottom-right quadrant), which destabilizes this
structure. Furthermore, unfavorable steric interactions between
the aldehyde substituent and the other Ph group on the ligand
(top-left quadrant) causes the structure to distort from its ideal,
chair-shaped cyclic geometry. Finally, a minor diastereomer
can form if, relative to the favored transition state, the opposite
face of the aldehyde is attacked (Figure 3, right panel). The
dominant destabilizing interaction in this case is between the
aldehyde substituent and the Ph group of Ph-BPE in the top-left
quadrant. Overall, this model determines the correct sense of
selectivity, although the magnitude is somewhat overestimated
relative to experiment (95:5 er, 5:1 dr).
We also performed kinetic experiments to further explore
the effect of slow addition on the chemoselectivity of our reac-
tion (Figure 4). Under the standard conditions, except with no
diene present, the reduction of aldehydes is extremely rapid. In
our experiment, benzaldehyde was fully consumed within 40
min, forming the silyl-protected benzyl alcohol (Figure 4, top
panel). If a single equivalent of diene is added at the beginning
of the reaction, the corresponding reductive coupling product is
observed to form in a roughly 1:9 ratio with the reduction prod-
uct (Figure 4, middle panel). Notably, however, the overall con-
sumption of starting material has been retarded, with the reac-
tion now requiring over 3 h to reach full consumption of starting
material. Finally, when a large excess of diene is added at the
beginning of the reaction (5.0 equiv diene, Figure 4, bottom
panel), the reductive coupling product is observed to form at a
higher ratio relative to the reduction product. Simultaneously,
the total consumption of starting material is further retarded.
Two conclusions can be drawn from these data. First, the
correlation of the product-to-reduction ratio with the diene-to-
aldehyde concentration ratio supports the proposed the role of
slow addition in our mechanistic scheme. In Figure 2, higher
concentration of diene lowers the energy of the blue pathway
relative to the red pathway, and therefore leads to increased for-
mation of the coupling product. Second, the seemingly inhibi-
tory effect of the diene explains why the slow addition protocol
must be conducted over a relatively long timespan (~3.5 h), in
spite of the fact that we are trying to outcompete an extremely
rapid reaction (half-life on the order of several min). Under the
conditions of our protocol, at large excesses of diene relative to
aldehyde, the rate of both the reduction and desired coupling
are slow.
Figure 4. Kinetic profiles of the competing reductive coupling
and reduction processes as a function of diene concentration.
See the Supporting Information for experimental details.
■ CONCLUSION
In summary, we have developed a highly efficient copper-
catalyzed allylation of aldehydes using dienes as allylmetal sur-
rogates. Computational studies were performed which indicate
that a reversible isomerization of copper(I) allyl species is
formed, from which reaction of the trans-linear isomer with the
aldehyde yields the major stereoisomer of product. Transition
state models are provided, which show the specific steric inter-
actions between ligand and substrates that are responsible for
the stereoselectivity. Finally, kinetic experiments were per-
formed, demonstrating effect of aldehyde–diene relative con-
centration on the chemoselectivity of this reaction.
■ ASSOCIATED CONTENT
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.
Experimental procedures and characterization data for all
compounds (PDF)
NMR spectra (PDF)
SFC and HPLC traces (PDF)
Computational details and Cartesian coordinates of opti-
mized geometries (PDF)
■ AUTHOR INFORMATION
Corresponding Author
ORCID
Chengxi Li: 0000-0003-3904-0299
Kwangmin Shin: 0000-0002-1708-2351
Richard Y. Liu: 0000-0003-0951-6487
Stephen L. Buchwald: 0000-0003-3875-4775
Author Contribution †These authors contributed equally.
Notes The authors declare no competing financial interest.
■ ACKNOWLEDGMENT
Research reported in this publication was supported by the Na-
tional Institutes of Health (GM122483, GM058160-17S1) and
Basic Science Research Program through the National Re-
search Foundation of Korea (NRF) funded by the Ministry of
Education (2018R1A6A3A03011441, K.S.).The content of this
communication solely reflects the research and opinion of the
authors and does not necessarily represent the official views of
the NIH. Solvias AG is acknowledged for a generous gift of SL-
J011-1 and Nippon Chemical is thanked for a kind donation of
(S,S)-QuinoxP*. We are grateful to Dr. Christine Nguyen for
advice on the preparation of this manuscript.
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addition of π-unsaturated pronucleophiles to carbonyl
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Perry, I. B.; Buchwald, S. L. Copper-Catalyzed
Enantioselective Addition of Styrene-Derived Nucleophiles to
Imines Enabled by Ligand-Controlled Chemoselective
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Catalyzed Asymmetric Addition of Olefin-Derived
Nucleophiles to Ketones. Science 2016, 353, 144–150. (c) Liu,
R. Y.; Yang, Y.; Buchwald, S. L. Regiodivergent and
Diastereoselective CuH-Catalyzed Allylation of Imines with
Terminal Allenes. Angew. Chem., Int. Ed. 2016, 55, 14077–
14080. (d) Tsai, E. Y.; Liu, R. Y.; Yang, Y.; Buchwald, S. L. A
Regio- and Enantioselective CuH-Catalyzed Ketone Allylation
with Terminal Allenes. J. Am. Chem. Soc. 2018, 140, 2007–
2011. (e) Liu, R. Y.; Zhou, Y.; Yang, Y.; Buchwald, S. L. En-
antioselective Allylation Using Allene, a Petroleum Cracking
Byproduct. J. Am. Chem. Soc. 2019, 141, 2251–2256. (f) Li, C.;
Liu, R. Y.; Jesikiewicz, L. T.; Yang, Y.; Liu, P.; Buchwald, S.
L. CuH-Catalyzed Enantioselective Ketone Allylation with 1,3-
Dienes: Scope, Mechanism, and Applications. J. Am. Chem.
Soc. 2019, 141, 5062–5070.
(10) For selected reports by other research groups, see: (a)
Saxena, A.; Choi, B.; Lam, H. W. Enantioselective Copper-
Catalyzed Reductive Coupling of Alkenylazaarenes with
Ketones. J. Am. Chem. Soc. 2012, 134, 8428–8431. (b) Gui, Y.-
Y.; Hu, N.; Chen, X.-W.; Liao, L.; Ju, T.; Ye, J.-H.; Zhang, Z.;
Li, J.; Yu, D.-G. Highly Regio- and Enantioselective Copper-
Catalyzed Reductive Hydroxymethylation of Styrenes and 1,3-
Dienes with CO2. J. Am. Chem. Soc. 2017, 139, 17011–17014.
(c) Li, K.; Shao, X.; Tseng, L.; Malcolmson, S. J. 2-Azadienes
as Reagents for Preparing Chiral Amines: Synthesis of 1,2-
Amino Tertiary Alcohols by Cu-Catalyzed Enantioselective
Reductive Couplings with Ketones. J. Am. Chem. Soc. 2018,
140, 598–601. (d) Shao, X.; Li, K.; Malcolmson, S. J.
Enantioselective Synthesis of Anti-1,2-Diamines by Cu-
Catalyzed Reductive Couplings of Azadienes with Aldimines
and Ketimines. J. Am. Chem. Soc. 2018, 140, 7083–7087. (e)
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Org. Lett. 2019, 21, 3576–3580.
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C.; Sugiura, M.; Kobayashi, S. Stereospecific, Enantioselective
Allylation of Α‐Hydrazono Esters by Using Allyltrichloro-
silanes with BINAP Dioxides as Neutral‐Coordinate
Organocatalysts. Angew. Chem., Int. Ed. 2004, 43, 6491–6493.
(e) Kotani, S.; Hashimoto, S.; Nakajima, M. Chiral Phosphine
Oxide BINAPO as a Lewis Base Catalyst for Asymmetric
Allylation and Aldol Reaction of Trichlorosilyl Compounds.
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B.; Ma, S.; Lee, H.; Gonnella, N. C.; Gao, J.; Li, W.; Tan, Z.;
Reeves, J. T. et al. Asymmetric Methallylation of Ketones
Catalyzed by a Highly Active Organocatalyst 3,3′-F2-BINOL.
Org. Lett. 2013, 15, 1710–1713. (g) Silverio, D. L.; Torker, S.;
Pilyugina, T.; Vieira, E. M.; Snapper, M. L.; Haeffner, F.;
Hoveyda, A. H. Simple Organic Molecules as Catalysts for
Enantioselective Synthesis of Amines and Alcohols. Nature
2013, 494, 216.
(13) Colacot, T. J. A Concise Update on the Applications of
Chiral Ferrocenyl Phosphines in Homogeneous Catalysis
Leading to Organic Synthesis. Chem. Rev. 2003, 103, 3101–
3118.
(14) Smith, A. B.; Kim, W.-S.; Tong, R. Uniting Anion Relay
Chemistry with Pd-Mediated Cross Coupling: Design, Synthe-
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pins. Org. Lett. 2010, 12, 588–591.
(15) In general, away from equilibrium, the Gibbs free energy
of reaction ∆G differs from the standard free energy of reaction
∆G‡ by a quantity related to the reaction quotient Q:
∆G – ∆G‡ = RT ln Q
In our system of interest, the aldehyde concentration is presum-
ably maintained at a very low value, meaning that states involv-
ing free aldehyde are lowered in free energy relative to those
involving the aldehyde bound to the catalyst. Although this ef-
fect is not reflected in Figure 2, which shows only the standard
free energies, it is a useful mnemonic to associate the effect of
decreasing the steady-state aldehyde concentration with raising
the energies of the grey-highlighted states relative to the white
ones.
(16) (a) Kagan, H. B.; Dang, T.-P. Asymmetric Catalytic
Reduction with Transition Metal Complexes. I. Catalytic
System of Rhodium(I) with (-)-2,3-0-Isopropylidene-2,3-
Dihydroxy-1,4-Bis(Diphenylphosphino)Butane, a New Chiral
Diphosphine. J. Am. Chem. Soc. 1972, 94, 6429–6433. (b) Ka-
gan, H. B. In Asymmetric Catalysis; Morrison, J. D., Ed.; Aca-
demic Press: New York, 1985; Vol. 5, pp 1−339. (c) Whitesell,
J. K. C2-Symmetry and Asymmetric Induction. Chem. Rev.
1989, 89, 1581–1590. (d) Walsh, P.; Kowzlowski, M. Funda-
mentals of Asymmetric Catalysis; University Science Books:
Sausalito, CA, 2008.
(17) For an example of allylation of carbonyl compounds via
six-membered Zimmerman-Traxler transition state, see: (a)
Grayson, M. N.; Krische, M. J.; Houk, K. N. Ruthenium-
Catalyzed Asymmetric Hydrohydroxyalkylation of Butadiene:
The Role of the Formyl Hydrogen Bond in Stereochemical
Control. J. Am. Chem. Soc. 2015, 137, 8838–8850. For a review,
see: (b) Mejuch, T.; Gilboa, N.; Gayon, E.; Wang, H.; Houk, K.
N.; Marek, I. Axial Preferences in Allylation Reactions via the
Zimmerman–Traxler Transition State. Acc. Chem. Res. 2013,
46, 1659–1669.
Table of Contents Graphic:
download fileview on ChemRxivManuscript-final.pdf (1.00 MiB)
Supporting Information S 1
Engaging Aldehydes in CuH-Catalyzed Reductive Coupling Reactions:
Stereoselective Allylation from 1,3-Diene Pronucleophiles
Chengxi Li,† Kwangmin Shin,† Richard Y. Liu, and Stephen L. Buchwald*
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts
02139, United States
*Correspondence to: [email protected].
Contents
I. General InformationS2
II. Preparation of Starting MaterialsS3
III. General Procedures for CuH-Catalyzed Aldehyde Allylation ReactionsS6
IV. Characterization Data for Allylation ProductsS7
V. Additional Experiment to Confirm the Absolute Configuration of Allylation
Product of Aliphatic Aldehydes with 1,3-Dienes S24
VI. Other Explored ExamplesS25
VII. General Procedure for Kinetics Experiments S26
VIII. Computational Studies S27
IX. References S67
Supporting Information S 2
I. General Information.
General reagent information. All reactions were performed under a nitrogen
atmosphere using the indicated method in the general procedures. Toluene and
tetrahydrofuran (THF) were purchased from J.T. Baker in CYCLE-TAINER® solvent
delivery kegs and purified by passage under argon pressure through two packed columns
of neutral alumina and copper(II) oxide. Copper(II) acetate was purchased from Strem
and used as received. 1,2-bis((2S,5S)2,5-diphenylphospholano)ethane ((S,S)-Ph-BPE) and
1,2-bis((2R,5R)2,5-diphenylphospholano)ethane ((R,R)-Ph-BPE) ligands were purchased
from Namena Corp. and stored in a nitrogen-filled glove box. JosiPhos ligand (R)-1-
{(SP)-2-[Bis[4-(trifluoromethyl)-phenyl]phosphino]ferrocenyl}ethyldi-tert-
butylphosphine (JosiPhos SL-J011-1) was a gift from Solvias and stored in a nitrogen-
filled glove box. (R)-DTBM-SEGPHOS was purchased from Takasago. (S,S)-QuinoxP*
was donated by Nippon Chemical Industrial Co., Ltd. and stored in a nitrogen-filled
glove box. Dimethoxy(methyl)silane (DMMS) was purchased from Tokyo Chemical
Industry Co. (TCI) and stored in a nitrogen-filled glove box for long term storage.
(Caution: Dimethoxy(methyl)silane (DMMS, CAS: 16881-77-9) is listed by several
vendors (TCI, Alfa Aesar) SDS or MSDS as H318, a category I Causes Serious Eye
Damage. Other vendors (Sigma-Aldrich, Gelest) list DMMS as H319, a category II Eye
Irritant. DMMS should be handled in a well-ventilated fumehood using proper
precaution as outlined for the handling of hazardous materials in prudent practices in the
laboratory.1 At the end of the reaction, ammonium fluoride in methanol should be
carefully added to the reaction mixture. The resulting reaction mixture should be stirred
for at least 30 min or the time indicated in the detailed reaction procedure. All other
solvents and commercial reagents were used as received from Alfa Aesar, Acros
Organics, Chem-Impex, Combi-blocks, Sigma-Aldrich, Strem or TCI, unless otherwise
noted. Flash column chromatography was performed using 40-63 µm silica gel
(SiliaFlash® F60 from Silicycle), or with the aid of a Biotage Isolera Automated Flash
Chromatography System using prepacked SNAP silica cartridges (10-100 g). Organic
solutions were concentrated under reduced pressure using a Buchi rotary evaporator.
General analytical information. All new compounds were characterized by NMR
spectroscopy, IR spectroscopy, elemental analysis or high-resolution mass spectrometry,
optical rotation (if applicable), and melting point analysis (if solids). 1H, 13C, 19F and 31P
NMR spectra were recorded in CDCl3 or C6D6 on a Bruker 400 or 500 MHz instrument.
Chemical shifts for 1H NMR are reported as follows: chemical shift in reference to
residual CHCl3 at 7.26 ppm (δ ppm), multiplicity (s = singlet, br s = broad singlet, d =
doublet, t = triplet, q = quartet, sex = sextet, sep = septet, ddd = doublet of double of
doublets, td = triplet of doublets, m = multiplet), coupling constant (Hz), and integration.
Chemical shifts for 13C NMR are reported in terms of chemical shift in reference to the
Supporting Information S 3
CDCl3 solvent signal (77.16 ppm). IR spectra were recorded on a Thermo Scientific
Nicolet iS5 spectrometer (iD5 ATR, diamond) and are reported in terms of frequency
of absorption (cm-1). Melting points were measured on a Mel-Temp capillary melting
point apparatus. Optical rotations were measured using a Jasco P-1010 digital polarimeter.
Elemental analyses were performed by Atlantic Microlabs Inc., Norcross, GA. High-
resolution mass spectra were recorded on a JEOL AccuTOF LC-Plus 46 DART system
and on an Agilent Technologies 6545 Q-TOF LC/MS system. Achiral gas
chromatography (GC) analyses were performed on an Agilent 7890A gas chromatograph
with an FID detector using a J & W DB-1 column (10 m, 0.1 mm I.D.). Enantiomeric
ratios (er’s) were determined by chiral SFC analysis using a Waters Acquity UPC2
instrument, Agilent 1200 Series HPLC (high performance liquid chromatography) or
Agilent 7890A GC analysis using a chiral stationary phase. Specific columns and
analytical methods are provided in the experimental details for individual compounds; the
wavelengths of light used for chiral analyses are provided with the associated
chromatograms. Thin-layer chromatography (TLC) was performed on silica gel 60Å F254
plates (SiliaPlate from Silicycle) and visualized with UV light or potassium
permanganate stain. Preparatory thin-layer chromatography (Prep-TLC) was performed
on silica gel GF with UV 254 (20 x 20 cm, 1000 microns, catalog # TLG-R10011B-341
from Silicycle) and visualized with UV light. The syringe pumps (PHD 2000 and PHD
Ultra) were purchased from Harvard Apparatus. Isolated yields reported in Table 2 of the
manuscript reflect the average values from two independent runs.
II. Preparation/Acquistion of Starting Materials
Aldehydes. All aldehydes were purchased from Alfa Aesar, Acros Organics, Chem-
Impex, Combi-blocks, Sigma-Aldrich or TCI and were used as received.
Preparation of 2-Substituted 1,3-Dienes. Dienes S1, S2 and S5-7 are known
compounds and were synthesized by a previously reported procedure.2
Preparation of Diene S3.2
Supporting Information S 4
- Step 1 (Synthesis of enol phosphate S3’)
An oven-dried 500 mL round bottom flask equipped with a magnetic stir bar was
evacuated and backfilled with argon. The flask was then charged with 3'-
fluoroacetophenone (6.1 mL, 50 mmol, 1.0 equiv) and anhydrous THF (180 mL). The
solution was cooled to -78 °C and LiHMDS (1.0 M in THF, 65 mL, 65 mmol, 1.3 equiv)
was added dropwise over 50 min via syringe pump. The resulting solution was allowed to
stir at -78 °C for 30 min. Diethyl chlorophosphate (10.9 mL, 75 mmol, 1.5 equiv) was
then added dropwise over 20 min via syringe pump and the reaction mixture was further
stirred at -78 °C for 3 h. The reaction mixture was allowed to warm to room temperature
and was quenched with sat. NH4Cl solution. The resulting mixture was transferred to a
separatory funnel and extracted with EtOAc (70 mL x 3). The combined organic layers
were dried over MgSO4, filtered, and concentrated under reduced pressure. The crude
product was purified by silica gel column chromatography (EtOAc/hexanes = 100/0 to
50/50) to afford the desired enol phosphate S3’ as an orange oil (7.5 g, 55% yield). 1H
NMR (500 MHz, CDCl3) δ 7.387.26 (m, 3H), 7.057.02 (m, 1H), 5.29 (dq, J = 12.8,
2.5 Hz, 2H), 4.25–4.17 (m, 4H), 1.35 (tt, J = 7.0, 1.3 Hz, 6H) ppm. 13C NMR (126 MHz,
CDCl3) δ: 162.8 (d, J = 245.4 Hz), 151.1 (dd, J = 7.8, 2.4 Hz), 136.6 (dd, J = 7.5, 7.5 Hz),
129.9 (d, J = 8.2 Hz), 120.9 (d, J = 3.0 Hz), 115.9 (d, J = 21.2 Hz), 112.3 (d, J = 23.6 Hz),
98.3 (d, J = 3.7 Hz), 64.6 (d, J = 6.0 Hz), 16.1 (d, J = 6.7 Hz) ppm. 19F NMR (471 MHz,
CDCl3) δ: -112.9 (m) ppm. 31P NMR (203 MHz, CDCl3) δ: -6.4 (m) ppm. IR: 2986,
1634, 1585, 1444, 1268, 1200, 1006, 918 cm-1. HRMS (ESI) Calcd. m/z for
[C12H16FO4P+H]+: 275.0843. Found: 275.0848.
- Step 2 (Synthesis of Diene S3)
An oven-dried 300 mL round bottom flask equipped with a magnetic stir bar was charged
with (dppe)NiCl2 (0.71 g, 1.35 mmol, 5 mol%). Then, the flask was evacuated and
backfilled with argon. Anhydrous THF (100 mL) was added and the resulting mixture
was cooled to 0 °C. Enol phosphate S3’ (7.4 g, 27 mmol, 1.0 equiv) was subsequently
added. Vinylmagesium bromide solution (1.0 M in THF, 30 mL, 30 mmol, 1.1 equiv)
was added dropwise over 40 min via syringe pump. The reaction mixture was warmed to
room temperature then stirred for 2 h. At this point the reaction mixture was cooled to
0 °C and quenched by the addition of sat. NH4Cl solution. The solution was then
transferred to a separatory funnel and extracted with Et2O (50 mL x 3). The combined
organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure.
The crude product was purified by silica gel column chromatography (100% pentane as
an eluent) to afford the desired diene S3 as a colorless liquid (1.6 g, 41% yield). 1H NMR
(400 MHz, CDCl3) δ: 7.347.29 (m, 1H), 7.127.10 (m, 1H), 7.066.98 (m, 2H), 6.60
(dd, J = 17.4, 10.6 Hz, 1H), 5.335.18 (m, 4H) ppm. 13C NMR (101 MHz, CDCl3) δ:
162.6 (d, J = 245.4 Hz), 147.1 (d, J = 2.1 Hz), 142.0 (d, J = 7.6 Hz), 137.6, 129.6 (d, J =
8.3 Hz), 123.9 (d, J = 2.9 Hz), 117.4, 117.4, 115.2 (d, J = 21.7 Hz), 114.3 (d, J = 21.1 Hz)
Supporting Information S 5
ppm. 19F NMR (376 MHz, CDCl3) δ: -113.8 (m) ppm. IR: 2931, 2534, 2332, 1611, 1581,
1486, 1436, 1265, 1213, 992, 905, 782 cm-1. HRMS (DART) Calcd. m/z for
[C10H9F+H]+: 149.0761. Found: 149.0760.
Preparation of Diene S4.2
- Step 1 (Synthesis of enol phosphate S4’)
An oven-dried 500 mL round bottom flask equipped with a magnetic stir bar was
evacuated and backfilled with argon. The flask was then charged with 3-acetylthiophene
(4.4 g, 35 mmol, 1.0 equiv) and anhydrous THF (120 mL). The solution was cooled to -
78 °C and LiHMDS (1.0 M in THF, 46 mL, 46 mmol, 1.3 equiv) was added dropwise
over 40 min via syringe pump. The resulting solution was allowed to stir at -78 °C for 30
min. Diethyl chlorophosphate (7.6 mL, 53 mmol, 1.5 equiv) was then added dropwise
over 20 min via syringe pump and the reaction mixture was stirred at -78 °C for an
additional 3 h. The reaction mixture was warmed to room temperature and quenched with
sat. NH4Cl solution (c.a. 100 mL). The resulting mixture was transferred to a separatory
funnel and extracted with EtOAc (70 mL x 3). The combined organic layers were dried
over MgSO4, filtered, and concentrated under reduced pressure. The crude product was
purified by silica gel column chromatography (EtOAc/hexanes = 100/0 to 50/50) to
afford the desired enol phosphate S4’ as an orange oil (6.7 g, 73% yield). 1H NMR (400
MHz, CDCl3) δ: 7.467.45 (m, 1H), 7.287.26 (m, 1H), 7.217.19 (m, 1H), 5.155.13
(m, 2H), 4.254.15 (m, 4H), 1.35 (tt, J = 7.2, 1.4 Hz, 6H) ppm. 13C NMR (101 MHz,
CDCl3) δ: 148.7 (d, J = 7.5 Hz), 136.7 (d, J = 7.4 Hz), 126.3, 124.9, 122.6, 96.6 (d, J =
3.6 Hz), 64.5 (d, J = 6.1 Hz), 16.1 (d, J = 6.7 Hz) ppm. 31P NMR (162 MHz, CDCl3) δ: -
6.4 (m) ppm. IR: 2982, 1634, 1267, 1197, 1165, 999, 920, 795, 870 cm-1. HRMS (ESI)
Calcd. m/z for [C10H15O4PS+H]+: 263.0501. Found: 263.0503.
- Step 2 (Synthesis of Diene S4)
An oven-dried 300 mL round bottom flask equipped with a magnetic stir bar was charged
with (dppe)NiCl2 (0.63 g, 1.2 mmol, 4 mol%). Then, the flask was evacuated and
backfilled with argon. Anhydrous THF (90 mL) was added and the resulting mixture was
cooled to 0 oC. Enol phosphate S4’ (7.9 g, 30 mmol, 1.0 equiv) was subsequently added.
Vinylmagesium bromide solution (1.0 M in THF, 32 mL, 32 mmol, 1.05 equiv) was
added dropwise over 30 min via syringe pump. The reaction mixture was warmed to
room temperature and stirred for 1 h. At this point the reaction mixture was cooled to
0 °C and quenched with sat. NH4Cl solution (c.a. 40 mL). The solution was then
transferred to a separatory funnel and extracted with Et2O (60 mL x 3). The organic
Supporting Information S 6
layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The
crude product was purified by silica gel column chromatography (100% pentane as an
eluent) to afford the desired diene S4 as a colorless liquid (1.7 g, 42% yield). All of the
spectroscopic data matched that reported in the literature.3
III. General Procedure for CuH-Catalyzed Aldehyde Allylation
Reactions.
In a nitrogen-filled glovebox, an oven-dried screw-cap reaction tube (Fisherbrand, 20 x
150 mm, catalog no. 1495937C) equipped with a stir bar was charged with Cu(OAc)2 (1.8
mg, 0.01 mmol, 1.0 mol %) and (S,S)-Ph-BPE (6.1 mg, 0.012 mmol, 1.2 mol %),
followed the addition of toluene (0.2 mL) via syringe (Note: addition of the exact amount
of copper catalyst and ligand is crucial for reaction efficiency). The reaction mixture was
stirred at room temperature for 3 min before the addition of the diene (2.0 mmol, 2.0
equiv) and DMMS (490 L, 4.0 mmol, 4.0 equiv), sequentially, via syringe. The reaction
vessel was capped (Cap: Kimble Chase Open Top S/T Closure catalog no. 73804-15425;
Septum: Thermo Scientific 1.3 mm silicone/PTFE catalog no. B7995-18) and removed
from the glovebox. The cap was wrapped in parafilm and the reaction tube was then
placed in an ice/water bath at 0 °C and stirring was commenced (Note: When R2 =
cyclohexyl or adamantyl, The reaction mixture was stirred at room temperature for 30
min before being placed in an ice/water bath at 0 °C). A stock solution of aldehyde was
prepared in a glovebox by dissolving 2.0 mmol of aldehyde in ca. 2 mL of toluene (1.0 M,
2 mL volumetric flask was used to prepare the stock solution, see Figure S1) Then, 1.0
mL of this aldehyde stock solution (1.0 mmol, 1.0 equiv) was slowly added to the
reaction vessel via syringe pump (addition rate - 5 μL/min). The resulting reaction
mixture was stirred at 0 °C (Note: the reaction temperature should be maintained at 0 °C
until the addition of the aldehyde is completed) and allowed to slowly warm to room
temperature overnight (18 h). After the reaction was completed as judged by GC-MS, a
saturated solution of NH4F in MeOH (ca. 10 mL) was carefully added to quench the
reaction (Caution: gas evolution was observed). The mixture was allowed to stir for 30
min at room temperature, diluted with EtOAc (ca. 15 mL), stirred for an additional 20
min at room temperature and then filtered through a short plug of Celite (2.0 cm) eluting
with additional EtOAc (ca. 20 mL). The solvent was removed under reduced pressure
with the aid of a rotary evaporator. At this point, the combined yield (of the
diastereomers) and the diastereomeric ratio (dr) were determined by 1H NMR
spectroscopic analysis using dibromomethane or 1,1,2,2-tetrachloroethane as an internal
Supporting Information S 7
standard (Note: The dr was determined by 1H NMR of the purified compound when it was
unable to be determined by 1H NMR of the unpurified reaction mixture due to the
complexity of the spectrum). The crude reaction mixture was purified by flash column
chromatography with the aid of a Biotage Isolera instrument to afford the desired product.
Enantiomeric ratios (er’s) were determined by chiral SFC analysis using a Waters
Acquity UPC2 instrument or HPLC or GC analysis using a chiral stationary phase.
Figure S1. Volumetric flask
IV. Characterization Data for Allylation Products.
(1S,2R)-1-(4-methoxyphenyl)-2-methyl-3-phenylbut-3-en-1-ol (1): The general
procedure was followed using 1.0 mL of a 1.0 M stock solution of 4-
methoxybenzaldehyde (136 mg, 1.0 mmol, 1.0 equiv) in toluene and buta-1,3-dien-2-
ylbenzene (260 mg, 2.0 mmol, 2.0 equiv). The crude reaction mixture was purified with
the aid of a Biotage Isolera system (25 g SNAP cartridge, 2% EtOAc/hexanes for 3
column volume (CV), then 2-5% EtOAc/hexanes for 10 CV, then 5-10% EtOAc/hexanes
for 5 CV, then 10-15% EtOAc/hexanes for 10 CV) to afford the title compound as a
colorless oil (220 mg, 82%), which slowly became a white solid after storing in a -20 °C
freezer. 1H NMR analysis [integration of methyl resonances at 1.11 (major) and 0.90
(minor) ppm] of the unpurified reaction mixture indicated a 12:1 dr. The absolute
Supporting Information S 8
configuration of the major stereoisomer was assigned as (1S,2R) by analogy with product
2.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 7.367.28 (m, 5H), 7.22 (d, J = 8.5
Hz, 2H), 6.84 (d, J = 8.9 Hz, 2H), 5.38 (s, 1H), 5.20 (s, 1H), 4.66 (d, J = 4.0 Hz, 1H),
3.79 (s, 3H), 3.10 (p, J = 6.7 Hz, 1H), 1.79 (br s, 1H), 1.11 (d, J = 7.0 Hz, 3H) ppm. 13C
NMR (101 MHz, CDCl3) δ: 158.7, 152.0, 142.5, 135.1, 128.5, 127.7, 127.2, 126.8, 114.2,
113.6, 74.1, 55.4, 45.7, 12.7 ppm. SFC analysis (AD-H column, scCO2/MeOH = 95/5 to
60/40, 2.5 mL/min) indicated a 95:5 er: tR (minor) = 4.85 min, tR (major) = 5.12 min.
Properties for mixture of diastereomers:
M.P. 5759 oC. IR: 3455 (-OH, broad), 2969, 2835, 1608, 1511, 1246, 1172, 1033, 905,
827, 774, 701 cm-1. [α]D24 = +74.1, (c = 1.00, CHCl3). Anal. Calcd. For C18H20O2: C,
80.56; H, 7.51. Found: C, 80.85; H, 7.45.
Duplicate experiment - Yield: 91%, 244 mg; dr: 11:1; er: 96:4. Average yield: 87%.
(1S,2R)-2-methyl-1,3-diphenylbut-3-en-1-ol (2): The general procedure was followed
using 1.0 mL of a 1.0 M stock solution of benzaldehyde (106 mg, 1.0 mmol, 1.0 equiv) in
toluene and buta-1,3-dien-2-ylbenzene (260 mg, 2.0 mmol, 2.0 equiv). The crude reaction
mixture was purified with the aid of a Biotage Isolera system (25 g SNAP cartridge, 2%
EtOAc/hexanes for 3 CV, then 2-5% EtOAc/hexanes for 10 CV, then 5-10%
EtOAc/hexanes for 10 CV) to afford the title as a colorless oil (209 mg, 88%). 1H NMR
analysis [integration of methyl resonances at 1.13 (major) and 0.95 (minor) ppm] of the
unpurified reaction mixture indicated a 5:1 dr. The absolute configuration of the major
stereoisomer was assigned as (1S,2R) by comparison of the specific optical rotation of the
isolated major diastereomer with the reported specific rotation value.4
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 7.42 (m, 9H), 7.29 (m,
1H), 5.44 (s, 1H), 5.26 (s, 1H), 4.74 (d, J = 3.6 Hz, 1H), 3.18 (dt, J = 10.6, 5.3 Hz, 1H),
1.88 (br s, 1H), 1.13 (d, J = 6.9 Hz, 3H) ppm. 13C NMR (101 MHz, CDCl3) δ: 151.8,
142.8, 142.2, 128.5, 128.1, 127.6, 127.0, 126.7, 125.9, 114.2, 74.0, 45.4, 12.1 ppm. SFC
analysis (OJ-H column, scCO2/MeOH = 95/5 to 60/40, 2.5 mL/min) indicated a 94:6 er: tR
(minor) = 3.65 min, tR (major) = 4.37 min. [α]D23 = +56.9, (c = 2.00, C6D6).
Supporting Information S 9
Properties for mixture of diastereomers:
IR: 3457 (-OH, broad), 3024, 2972, 1492, 1447, 1059, 1021, 978, 905, 755, 701 cm-1.
[α]D24 = +67.0, (c = 1.00, CHCl3). HRMS (DART) Calcd. m/z for [C17H18O-OH]+:
221.1325. Found: 221.1329.
Duplicate experiment - Yield: 83%, 197 mg; dr: 5:1; er: 95:5. Average yield: 86%.
(3R,4R)-4-methyl-1,5-diphenylhex-5-en-3-ol (3): The general procedure was followed
using 1.0 mL of a 1.0 M stock solution of 3-phenylpropanal (134 mg, 1.0 mmol, 1.0
equiv) in toluene and buta-1,3-dien-2-ylbenzene (260 mg, 2.0 mmol, 2.0 equiv). The
crude reaction mixture was purified with the aid of a Biotage Isolera system (25 g SNAP
cartridge, 100% hexanes for 1 CV, then 0-8% EtOAc/hexanes for 4 CV, then 8%
EtOAc/hexanes for 10 CV) to afford the title compound as a colorless oil (174 mg, 65%). 1H NMR analysis [integration of methyl resonances at 1.27 (major) and 1.21 (minor) ppm]
of the unpurified reaction mixture indicated a 9:1 dr. The absolute configuration of the
major stereoisomer was assigned as (3R,4R) by analogy.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 7.407.29 (m, 7H), 7.247.20 (m,
3H), 5.42 (s, 1H), 5.17 (s, 1H), 3.64m 2.952.80 (m, 2H), 2.702.62 (m,
1H), 1.911.85 (m, 2H), 1.64 (br s, 1H), 1.27 (d, J = 6.9 Hz, 3H) ppm. 13C NMR (101
MHz, CDCl3) δ: 152.3, 142.3, 142.2, 128.5, 128.4, 128.4, 127.6, 126.7, 125.8, 113.7,
72.1, 43.3, 36.5, 32.7, 13.2 ppm. SFC analysis (OD-H column, scCO2/MeOH = 95/5 to
60/40, 2.5 mL/min) indicated a 98:2 er: tR (minor) = 4.42 min, tR (major) =4.85 min.
Properties for mixture of diastereomers:
IR: 3434 (-OH, broad), 3085, 3057, 3024, 2932, 1625, 1494, 1452, 1269, 1030, 900, 779,
748, 699 cm-1. [α]D24 = +89.1, (c = 1.00, CHCl3). HRMS (DART) Calcd. m/z for
[C19H22O-OH]+: 249.1638. Found: 249.1645.
Duplicate experiment - Yield: 70%, 187 mg; dr: 9:1; er: 98:2. Average yield: 68%.
Supporting Information S 10
(3R,4R,6S)-3,6,10-trimethyl-2-phenylundeca-1,9-dien-4-ol (4): The general procedure
was followed using 1.0 mL of a 1.0 M stock solution of (S)-3,7-dimethyloct-6-enal (154
mg, 1.0 mmol, 1.0 equiv) in toluene and buta-1,3-dien-2-ylbenzene (260 mg, 2.0 mmol,
2.0 equiv). The crude reaction mixture was purified with the aid of a Biotage Isolera
system (25 g SNAP cartridge, 2% EtOAc/hexanes for 3 CV, then 2-5% EtOAc/hexanes
for 10 CV, then 5-10% EtOAc/hexanes for 10 CV ) to afford the title compound as a
clear oil (229 mg, 80%). 1H NMR analysis of the unpurified reaction mixture indicated a
>20:1 dr (resonances that are typical of the minor diastereomer could not be detected).
The absolute configuration of the major stereoisomer was assigned as (3R,4R,6S) by
analogy.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 7.357.27 (m, 5H), 5.36 (s, 1H),
5.12 (s, 1H), 5.07 (t, J = 6.8 Hz, 1H), 3.63 (dt, J = 8.6, 3.8 Hz, 1H), 2.79 (qd, J = 6.8, 3.7
Hz, 1H), 2.031.88 (m, 2H), 1.67 (s, 3H), 1.58 (s, 3H), 1.631.48 (m, 2H), 1.35 (br s,
1H), 1.321.09 (m, 3H), 1.20 (d, J = 7.0 Hz, 3H), 0.83 (d, J = 6.5 Hz, 3H) ppm. 13C
NMR (101 MHz, CDCl3) δ: 152.6, 142.5, 131.2, 128.5, 127.6, 126.7, 124.9, 113.5, 70.3,
43.8, 42.3, 37.8, 29.5, 25.9, 25.6, 19.3, 17.8, 13.3 ppm. Chiral GC analysis
(HYDRODEX -3 P, 25 m*0.25 mm, initial: Value: 100 °C, hold 20 min; Ramp 1: rate:
0.3 °C/min, value: 160 °C, hold 20 min; Ramp 2: rate: 0.5 °C/min, value: 220 °C, hold 20
min) indicated a 98.5:1.5 er (dr): tR (minor) = 283.89 min, tR (major) = 289.87 min.
Properties for mixture of diastereomers:
IR: 3445 (-OH, broad), 2958, 2922, 1620, 1490, 1449, 1374, 1089, 1023, 966, 895, 774,
699 cm-1. [α]D24 = +72.9, (c = 1.00, CHCl3). Anal. Calcd. For C20H30O: C, 83.86; H,
10.56. Found: C, 83.91; H, 10.72.
Duplicate experiment - Yield: 74%, 213 mg; er (dr): >20:1. Average yield: 77%.
Supporting Information S 11
(1R,2R)-1-cyclohexyl-2-methyl-3-phenylbut-3-en-1-ol (5): The general procedure was
followed using 1.0 mL of a 1.0 M stock solution of cyclohexanecarbaldehyde (112 mg,
1.0 mmol, 1.0 equiv) in toluene and buta-1,3-dien-2-ylbenzene (260 mg, 2.0 mmol, 2.0
equiv). The crude reaction mixture was purified with the aid of a Biotage Isolera system
(25 g SNAP cartridge, 2% EtOAc/hexanes for 3 CV, then 2-5% EtOAc/hexanes for 10
CV, 5-10% EtOAc/hexanes for 10 CV, then 10-15% EtOAc/hexanes for 5 CV) to afford
the title compound as a colorless oil (200 mg, 82%). 1H NMR analysis of the unpurified
reaction mixture indicated a >20:1 dr (resonances that are typical of the minor
diastereomer could not be detected). The absolute configuration of the major
stereoisomer was assigned as (1R,2R) by analogy.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 7.367.26 (m, 5H), 5.40 (s, 1H),
5.16 (s, 1H), 3.123.03 (m, 2H), 1.991.93 (m, 1H), 1.771.61 (m, 4H), 1.501.40 (m,
2H), 1.331.03 (m, 3H), 1.16 (d, J = 6.7 Hz, 3H), 0.970.80 (m, 2H) ppm. 13C NMR
(101 MHz, CDCl3) δ: 152.7, 142.2, 128.5, 127.7, 126.7, 114.0, 75.9, 40.2, 39.5, 29.9,
29.1, 26.5, 26.3, 26.0, 11.7 ppm. SFC analysis (AD-H column, scCO2/MeOH = 95/5 to
60/40, 2.5 mL/min) indicated a 96:4 er: tR (major) = 3.45 min, tR (minor) = 3.55 min.
Properties for mixture of diastereomers:
IR: 3479 (-OH, broad), 2920, 2849, 1442, 1257, 973, 900, 777, 699 cm-1. [α]D24 = +100.7,
(c = 1.00, CHCl3). Anal. Calcd. For C17H24O: C, 83.55; H, 9.90. Found: C, 83.55; H,
9.73.
Duplicate experiment - Yield: 81%, 199 mg; dr: >20:1; er: 98:2. Average yield: 82%.
(3S,4R)-2,2,4-trimethyl-5-phenylhex-5-en-3-ol (6): The general procedure was
followed using 1.0 mL of a 1.0 M stock solution of pivalaldehyde (86 mg, 1.0 mmol, 1.0
equiv) in toluene and buta-1,3-dien-2-ylbenzene (260 mg, 2.0 mmol, 2.0 equiv). The
crude reaction mixture was purified with the aid of a Biotage Isolera system (25 g SNAP
cartridge, 2% EtOAc/hexanes for 3 CV, then 2-5% EtOAc/hexanes for 10 CV, then 5-10%
EtOAc/hexanes for 10 CV) to afford the title compound as a colorless oil (198 mg, 91%). 1H NMR analysis [integration of tert-butyl resonances at 0.97 (major) and 0.94 (minor)
ppm] of the unpurified reaction mixture indicated a >20:1 dr. The absolute configuration
of the major stereoisomer was assigned as (3S,4R) by analogy.
Supporting Information S 12
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 7.417.28 (m, 5H), 5.36 (s, 1H),
5.19 (s, 1H), 3.24 (d, J = 2.1 Hz, 1H), 3.15 (q, J = 6.7 Hz, 1H), 1.54 (br s, 1H), 1.25 (d, J
= 6.9 Hz, 3H), 0.97 (s, 9H) ppm. 13C NMR (101 MHz, CDCl3) δ: 154.8, 142.5, 128.5,
127.6, 126.9, 113.2, 78.7, 39.3, 35.7, 27.3, 13.9 ppm. Chiral GC analysis (HYDRODEX
-3 P, 25 m*0.25 mm, initial: Value: 70 °C, hold 50 min; Ramp 1: rate: 1 °C/min, value:
100 °C, hold 10 min; Ramp 2: rate: 0.8 °C/min, value: 220 °C, hold 20 min) indicated a
>99.5:0.5 er: tR (minor) = 157.14 min, tR (major) =157.71 min.
Properties for mixture of diastereomers:
IR: 3509 (-OH, broad), 2953, 2870, 1625, 1468, 1369, 1239, 1186, 1056, 973, 898, 779,
701 cm-1. [α]D24 = +57.9, (c = 1.00, CHCl3). Anal. Calcd. For C15H22O: C, 82.52; H,
10.16. Found: C, 82.76; H, 10.12.
Duplicate experiment - Yield: 83%, 182 mg; dr: >20:1; er: 99.5:0.5. Average yield: 87%.
(1S,2R)-3-(4-methoxyphenyl)-2-methyl-1-ferrocenylbut-3-en-1-ol (7): The general
procedure was followed using 1.0 mL of a 1.0 M stock solution of ferrocene-
carboxaldehyde (214 mg, 1.0 mmol, 1.0 equiv) in toluene and 1-(buta-1,3-dien-2-yl)-4-
methoxybenzene (320 mg, 2.0 mmol, 2.0 equiv). The crude reaction mixture was purified
with the aid of a Biotage Isolera system (25 g SNAP cartridge, 2% EtOAc/hexanes for 3
CV, then 2-5% EtOAc/hexanes for 10 CV, then 5-10% EtOAc/hexanes for 10 CV, then
10-10% EtOAc/hexanes for 5 CV) to afford the title compound as a red resin (321 mg,
85%). 1H NMR analysis [integration of methyl resonances at 1.20 (major) and 0.99
(minor) ppm] of the unpurified reaction mixture indicated a 8:1 dr. The absolute
configuration of the major stereoisomer was assigned as (1S,2R) by analogy.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 7.26 (d, J = 8.7 Hz, 2H), 6.87 (d, J =
8.7 Hz, 2H), 5.29 (s, 1H), 5.08 (s, 1H), 4.41 (dd, J = 4.9, 1.9 Hz, 1H), 4.31 (d, J = 2.2 Hz,
1H), 4.204.11 (m, 8H), 3.84 (s, 3H), 2.902.79 (m, 1H), 2.02 (d, J = 2.1 Hz, 1H), 1.20
(d, J = 6.9 Hz, 3H) ppm. 13C NMR (101 MHz, CDCl3) δ: 159.1, 151.3, 135.2, 127.8,
113.7, 112.2, 92.8, 72.1, 69.4, 68.5, 68.5, 68.1, 67.7, 67.6, 65.5, 55.4, 45.4, 14.7 ppm.
SFC analysis (OD-H column, scCO2/MeOH = 95/5 to 60/40, 2.5 mL/min) indicated a
95.5:4.5 er: tR (minor) = 5.85 min, tR (major) = 6.43 min.
Supporting Information S 13
Properties for mixture of diastereomers:
IR: 3559 (-OH, broad), 3083, 2972, 2901, 1610, 1506, 1454, 1239, 1182, 1106, 1033,
900, 836, 744 cm-1. [α]D23 = +15.9, (c = 1.00, CHCl3). HRMS (DART) Calcd. m/z for
[C22H24O2Fe]+: 376.1120. Found: 376.1128.
Duplicate experiment - Yield: 95%, 357 mg; dr: 7:1; er: 95:5. Average yield: 90%.
(1S,2R)-1-(furan-3-yl)-3-(4-methoxyphenyl)-2-methylbut-3-en-1-ol (8): The general
procedure was followed using 1.0 mL of a 1.0 M stock solution of furan-3-carbaldehyde
(96 mg, 1.0 mmol, 1.0 equiv) in toluene and 1-(buta-1,3-dien-2-yl)-4-methoxybenzene
(320 mg, 2.0 mmol, 2.0 equiv). The crude reaction mixture was purified with the aid of a
Biotage Isolera system (25 g SNAP cartridge, 2% EtOAc/hexanes for 3 CV, then 2-5%
EtOAc/hexanes for 10 CV, then 5-10% EtOAc/hexanes for 10 CV, then 10-10%
EtOAc/hexanes for 5 CV) to afford the title compound as a light yellow oil (222 mg,
86%) . 1H NMR analysis [integration of methyl resonances at 1.20 (major) and 1.04
(minor) ppm] of the unpurified reaction mixture indicated a 8:1 dr. The absolute
configuration of the major stereoisomer was assigned as (1S,2R) by analogy.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 7.417.37 (m, 2H), 7.337.29 (m,
2H), 6.916.88 (m, 2H), 6.34 (t, J = 1.4 Hz, 1H), 5.36 (d, J = 1.1 Hz, 1H), 5.15 (t, J = 1.2
Hz, 1H), 4.69 (t, J = 3.5 Hz, 1H), 3.84 (s, 3H), 3.113.04 (m, 1H), 1.79 (d, J = 3.2 Hz,
1H), 1.20 (d, J = 7.0 Hz, 3H) ppm. 13C NMR (101 MHz, CDCl3) δ: 159.3, 150.8, 143.0,
139.5, 134.6, 127.8, 127.6, 113.9, 112.9, 108.8, 68.7, 55.4, 44.4, 13.1 ppm. SFC analysis
(OJ-H column, scCO2/MeOH = 95/5 to 60/40, 2.5 mL/min) indicated a 97:3 er: tR (minor)
= 3.85 min, tR (major) = 4.04 min.
Properties for mixture of diastereomers:
IR: 3438 (-OH, broad), 2967, 2835, 1603, 1508, 1248, 1179, 1023, 831, 751 cm-1. [α]D23
= +60.9, (c = 1.00, CHCl3). HRMS (DART) Calcd. m/z for [C16H18O3-OH]+: 241.1223.
Found: 241.1231.
Duplicate experiment - Yield: 86%, 221 mg; dr: 8:1; er: 97:3. Average yield: 86%.
Supporting Information S 14
(1S,2R)-3-(3-fluorophenyl)-2-methyl-1-(thiophen-3-yl)but-3-en-1-ol (9): The general
procedure was followed using 1.0 mL of a 1.0 M stock solution of thiophene-3-
carbaldehyde (112 mg, 1.0 mmol, 1.0 equiv) in toluene and 1-(buta-1,3-dien-2-yl)-3-
fluorobenzene (296 mg, 2.0 mmol, 2.0 equiv). The crude reaction mixture was purified
with the aid of a Biotage Isolera system (25 g SNAP cartridge, 2% EtOAc/hexanes for 2
CV, then 2-5% EtOAc/hexanes for 15 CV, then 5-10% EtOAc/hexanes for 10 CV) to
afford the title compound as a colorless oil (230 mg, 88%). 1H NMR analysis [integration
of methyl resonances at 1.19 (major) and 1.02 (minor ppm)] of the unpurified reaction
mixture indicated a 7:1 dr. The absolute configuration of the major stereoisomer was
assigned as (1S,2R) by analogy.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 7.347.25 (m, 2H), 7.187.09 (m,
2H), 7.05-6.90 (m, 3H), 5.42 (s, 1H), 5.26 (s, 1H), 4.78 (d, J = 4.6 Hz, 1H), 3.08~3.15 (m,
1H), 1.90 (d, J = 2.4 Hz, 1H), 1.19 (d, J = 6.9 Hz, 3H) ppm. 13C NMR (101 MHz, CDCl3)
δ: 162.9 (d, J = 245.6 Hz), 150.6 (d, J = 2.0 Hz), 144.8 (d, J = 7.3 Hz), 144.4, 130.0 (d, J
= 8.5 Hz), 125.8, 125.8, 122.4 (d, J = 2.9 Hz), 121.0, 115.1, 114.4 (d, J = 21.3 Hz), 113.7
(d, J = 21.8 Hz), 72.2, 45.1, 13.4 ppm. 19F NMR (376 MHz, CDCl3) δ: -113.2 (m) ppm.
HPLC analysis (OD-H column, Hexane/IPA = 96/4, 0.8 mL/min) indicated a 97:3 er: tR
(major)= 13.11min, tR (minor) = 15.44 min.
Properties for mixture of diastereomers:
IR: 3424 (-OH, broad), 3100, 2981, 1613, 1575, 1482, 1430, 1265, 1196, 1016, 902, 872,
784, 729 cm-1. [α]D23 = +52.6, (c = 1.00, CHCl3). HRMS (DART) Calcd. m/z for
[C15H15FOS-OH]+: 245.0795. Found: 245.0802.
Duplicate experiment - Yield: 81%, 213 mg; dr: 7:1; er: 97.5:2.5. Average yield: 85%.
Supporting Information S 15
tert-butyl 3-((1S,2R)-3-(3-fluorophenyl)-1-hydroxy-2-methylbut-3-en-1-yl)-1H-indole
-1-carboxylate (10): The general procedure was followed using using 2.0 mL of a 0.5 M
stock solution of tert-butyl 3-formyl-1H-indole-1-carboxylate (245 mg, 1.0 mmol, 1.0
equiv) in tetrahydrofuran and 1-(buta-1,3-dien-2-yl)-3-fluorobenzene (296 mg, 2.0 mmol,
2.0 equiv). The crude reaction mixture was purified with the aid of a Biotage Isolera
system (25 g SNAP cartridge, 100% hexanes for 2 CV, then 0-12% EtOAc/hexanes for 5
CV, then 12% EtOAc/hexanes for 9 CV) to afford the title compound as a yellow resin
(310 mg, 79%). 1H NMR analysis [integration of methyl resonances at 1.18 (major) and
0.92 (minor) ppm] of the purified title compound indicated a 8:1 dr. The absolute
configuration of the major stereoisomer was assigned as (1S,2R) by analogy.
Major diastereomer: 1H NMR (400 MHz, C6D6) δ: 8.45 (br s, 1H), 7.64 (s, 1H), 7.52 (d,
J = 7.8 Hz, 1H), 7.277.22 (m, 1H), 7.167.12 (m, 1H), 6.956.91 (m, 1H), 6.856.82
(m, 2H), 6.746.69 (m, 1H), 5.11 (s, 1H), 5.04 (s, 1H), 4.77 (d, J = 4.6 Hz, 1H), 3.16 (p,
J = 6.9 Hz, 1H), 1.73 (s, 1H), 1.36 (s, 9H), 1.18 (d, J = 6.9 Hz, 3H) ppm. 13C NMR (101
MHz, C6D6) δ: 163.6 (d, J = 245.4 Hz), 151.5 (d, J = 2.0 Hz), 150.2, 145.8 (d, J = 7.2 Hz),
136.7, 130.3 (d, J = 8.4 Hz), 129.5, 125.1, 123.7, 123.7 (d, J = 7.1 Hz), 123.2, 123.0 (d, J
= 2.8 Hz), 120.3, 116.3, 115.2, 114.7 (d, J = 8.1 Hz), 114.5 (d, J = 8.7 Hz), 83.5, 70.2,
44.3, 28.2, 14.2 ppm. 19F NMR (471 MHz, C6D6) δ: -113.1 (m) ppm. HPLC analysis
(OD-H column, Hexane/IPA = 97/3, 0.8 mL/min) indicated a 99.5:0.5 er: tR (minor) =
12.23 min, tR (major) = 15.01 min.
Properties for mixture of diastereomers:
IR: 3498 (-OH, broad), 2977, 2929, 1726, 1577, 1449, 1366, 1253, 1153, 1080, 1014,
760, 746 cm-1. [α]D23 = +42.2, (c = 1.00, CHCl3). HRMS (DART) Calcd. m/z for
[C24H26FNO3-OH]+: 378.1864. Found: 378.1864.
Duplicate experiment: Yield: 79%, 311 mg; dr: 8:1; er: 98.5:1.5. Average yield: 79%.
(1S,2R)-2-methyl-1-(4-(methylthio)phenyl)-3-(thiophen-3-yl)but-3-en-1-ol (11): The
general procedure was followed using 1.0 mL of a 1.0 M stock solution of 4-
(methylthio)benzaldehyde (152 mg, 1.0 mmol, 1.0 equiv) in toluene and 3-(buta-1,3-dien-
2-yl)thiophene (272 mg, 2.0 mmol, 2.0 equiv). The crude reaction mixture was purified
with the aid of a Biotage Isolera system (25 g SNAP cartridge, 2% EtOAc/hexanes for 2
CV, then 2-10% EtOAc/hexanes for 15 CV, then 10-15% EtOAc/hexanes for 10 CV) to
Supporting Information S 16
afford the title compound as a light yellow oil (261 mg, 90%). 1H NMR analysis
[integration of methyl resonances at 1.09 (major) and 0.96 (minor) ppm] of the unpurified
reaction mixture indicated a 6:1 dr. The absolute configuration of the major stereoisomer
was assigned as (1S,2R) by analogy.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 7.327.20 (m, 7H), 5.53 (s, 1H),
5.17 (s, 1H), 4.77 (d, J = 3.8 Hz, 1H), 3.103.04 (m, 1H), 2.48 (s, 3H), 1.91 (s, 1H), 1.09
(d, J = 7.0 Hz, 3H) ppm. 13C NMR (101 MHz, CDCl3) δ: 145.8, 142.8, 139.9, 137.0,
126.6, 126.6, 126.3, 126.0, 120.7, 112.8, 77.6, 74.1, 45.5, 16.2, 12.3 ppm. HPLC
analysis (OD-H column, Hexane/IPA = 95/5, 0.8 mL/min) indicated a 94:6 er: tR (minor)
= 18.04 min, tR (major) = 20.26 min.
Properties for mixture of diastereomers:
IR: 3457 (-OH, broad), 3107, 2979, 2915, 1620, 1492, 1400, 1260, 1089, 1009, 983, 902,
791 cm-1. [α]D23 = +61.4, (c = 1.00, CHCl3). HRMS (DART) Calcd. m/z for [C16H18OS2-
OH]+: 273.0766. Found: 273.0763.
Duplicate experiment - Yield: 93%, 270 mg; dr: 6:1; er: 94:6. Average yield: 92%.
(2R,3R)-3-methyl-4-(thiophen-3-yl)pent-4-en-2-ol (12): The general procedure was
followed using using 1.0 mL of a 1.0 M stock solution of acetaldehyde (44 mg, 1.0 mmol,
1.0 equiv) in toluene and 3-(buta-1,3-dien-2-yl)thiophene (272 mg, 2.0 mmol, 2.0 equiv).
The crude reaction mixture was purified with the aid of a Biotage Isolera system (25 g
SNAP cartridge, 2% EtOAc/hexanes for 3 CV, then 2-5% EtOAc/hexanes for 10 CV,
then 5-10% EtOAc/hexanes for 10 CV) to afford the title compound as a colorless oil
(156 mg, 86%). 1H NMR analysis [integration of resonances of two methyl groups at
1.23 (major, 3H), 1.24 (major, 3H) and 1.17 (minor, 3H x 2) ppm] of the unpurified
reaction mixture indicated a >20:1 dr. The absolute configuration of the major
stereoisomer was assigned as (2R,3R) by analogy.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 7.327.28 (m, 1H), 7.247.22 (m,
2H), 5.51 (s, 1H), 5.11 (s, 1H), 3.903.84 (m, 1H), 2.792.72 (m, 1H), 1.57 (s, 1H), 1.24
(d, J = 6.3 Hz, 3H), 1.23 (d, J = 7.0 Hz, 3H) ppm. 13C NMR (101 MHz, CDCl3) δ: 146.5,
143.1, 126.3, 125.8, 120.6, 111.9, 69.2, 44.8, 20.9, 13.4 ppm. Chiral GC analysis
(HYDRODEX -3 P, 25 m*0.25 mm, initial: Value: 100 °C, hold 20 min; Ramp 1: rate:
Supporting Information S 17
0.3 °C/min, value: 160 °C, hold 20 min; Ramp 2: rate: 0.5 °C/min, value: 220 °C, hold 20
min) indicated a 99:1 er: tR (minor) = 131.24 min, tR (major) = 134.03 min.
Properties for mixture of diastereomers:
IR: 3403 (-OH, broad), 3100, 2967, 2927, 1622, 1456, 1369, 1250, 1087, 898, 789 cm-1.
[α]D23 = +58.9, (c = 1.00, CHCl3). HRMS (ESI) Calcd. m/z for [C10H14OS+Na]+:
205.0658. Found: 205.0654.
Duplicate experiment - Yield: 82%, 149 mg; dr: >20:1; er: 99:1. Average yield: 84%.
(1R,2R)-1-cyclohexyl-2-methyl-3-(thiophen-3-yl)but-3-en-1-ol (13): The general
procedure was followed using 1.0 mL of a 1.0 M stock solution of
cyclohexanecarbaldehyde (112 mg, 1.0 mmol, 1.0 equiv) in toluene and 3-(buta-1,3-dien-
2-yl)thiophene (272 mg, 2.0 mmol, 2.0 equiv). The crude reaction mixture was purified
with the aid of a Biotage Isolera system (25 g SNAP cartridge, 2% EtOAc/hexanes for 3
CV, then 2-5% EtOAc/hexanes for 10 CV, then 5-10% EtOAc/hexanes for 10 CV, then
10-10% EtOAc/hexanes for 5 CV) to afford the title as a colorless oil (206 mg, 82%). 1H
NMR analysis [integration of vinylic resonances at 5.33 (major) and 5.25 (minor) ppm]
of the unpurified reaction mixture indicated a >20:1 dr. The absolute configuration of the
major stereoisomer was assigned as (1R,2R) by analogy.
Major diastereomer: 1H NMR (400 MHz, C6D6) δ: 6.98 (dd, J = 5.0, 1.5 Hz, 1H),
6.916.83 (m, 2H), 5.33 (d, J = 1.0 Hz, 1H), 4.96 (d, J = 1.1 Hz, 1H), 3.19 (dd, J = 8.1,
3.3 Hz, 1H), 2.882.82 (m, 1H), 2.16 (d, J = 12.8 Hz, 1H), 1.701.63 (m, 2H), 1.601.50
(m, 2H), 1.50 (m, 1H), 1.29 (s, 1H), 1.21 (m, 3H), 1.10 (d, J = 6.9 Hz, 3H),
0.920.80 (m, 2H) ppm. 13C NMR (101 MHz, C6D6) δ: 147.4, 143.5, 126.8, 126.1, 121.0,
112.4, 76.7, 41.0, 40.2, 30.3, 29.9, 27.2, 27.0, 26.7, 12.7 ppm. HPLC analysis (AD-H
column, Hexane/IPA = 96/4, 0.8 mL/min) indicated a 94:6 er: tR (minor) = 11.30 min, tR
(major) = 12.37 min.
Properties for mixture of diastereomers:
IR: 3476 (-OH, broad), 3100, 2922, 2849, 1625, 1449, 1255, 1087, 973, 890, 786 cm-1.
[α]D23 = +61.8, (c = 1.00, CHCl3). HRMS (DART) Calcd. m/z for [C15H22OS-OH]+:
233.1359. Found: 233.1370.
Supporting Information S 18
Duplicate experiment - Yield: 79%, 197 mg; dr: >20:1; er: 98:2. Average yield: 81%.
tert-butyl 3-((3R,4R)-4-hydroxy-3-methylpent-1-en-2-yl)-1H-indole-1-carboxylate
(14): The general procedure was followed using 1.0 mL of a 1.0 M stock solution of
acetaldehyde (44 mg, 1.0 mmol, 1.0 equiv) in toluene and tert-butyl 3-(buta-1,3-dien-2-
yl)-1H-indole-1-carboxylate (539 mg, 2.0 mmol, 2.0 equiv). The crude reaction mixture
was purified with the aid of a Biotage Isolera system (25 g SNAP cartridge, 2%
EtOAc/hexanes for 2 CV, then 2-10% EtOAc/hexanes for 10 CV, then 10-20%
EtOAc/hexanes for 10 CV, then 20-30% EtOAc/hexanes for 10 CV) to afford the title
compound as a colorless resin (286 mg, 91%). 1H NMR analysis [integration of vinylic
resonances at 5.34 (major) and 5.39 (minor) ppm] of the unpurified reaction mixture
indicated a 13:1 dr. The absolute configuration of the major stereoisomer was assigned as
(3R,4R) by analogy.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 8.19 (d, J = 8.4 Hz, 1H), 7.74 (d, J =
7.9 Hz, 1H), 7.58 (s, 1H), 7.36 (ddd, J = 8.4, 7.2, 1.3 Hz, 1H), 7.29 (td, J = 7.4, 7.0, 1.1
Hz, 1H), 5.57 (s, 1H), 5.34 (s, 1H), 3.893.83 (m, 1H), 2.692.77 (m, 1H), 1.71 (s, 9H),
1.57 (s, =1H), 1.29 (d, J = 6.9 Hz, 3H), 1.23 (d, J = 6.3 Hz, 3H) ppm. 13C NMR (101
MHz, CDCl3) δ: 149.8, 144.4, 135.8, 129.4, 124.7, 123.0, 122.9, 122.7, 120.4, 115.5,
114.1, 84.1, 69.3, 46.3, 28.3, 21.0, 13.3 ppm. HPLC analysis (OD-H column,
Hexane/IPA = 95/5, 0.8 mL/min) indicated a 99:1 er: tR (major) = 7.22 min, tR (minor) =
7.94 min.
Properties for mixture of diastereomers:
IR: 3431 (-OH, broad), 2974, 2932, 1729, 1625, 1447, 1362, 1250, 1156, 1061, 917, 763,
744 cm-1. [α]D23 = +22.5, (c = 1.00, CHCl3). HRMS (DART) Calcd. m/z for
[C19H25NO3+H]+: 316.1907. Found: 316.1917
Duplicate experiment - Yield: 84%, 264 mg; dr: 14:1; er: 98.5:1.5. Average yield: 88%.
Supporting Information S 19
(3R,4S)-5-((E)-benzylidene)-2-cyclohexyl-3-methyldec-1-en-4-ol (15): The general
procedure was followed (Note: The reaction mixture was stirred at room temperature for
30 min before placed in an ice/water bath at 0 °C) using 1.0 mL of a 1.0 M stock solution
of (E)-2-benzylidene-heptanal (202 mg, 1.0 mmol, 1.0 equiv) in toluene and buta-1,3-
dien-2-ylcyclohexane (272 mg, 2.0 mmol, 2.0 equiv). The crude reaction mixture was
purified with the aid of a Biotage Isolera system (25 g SNAP cartridge, 100% hexanes for
2 CV, then 0-8% EtOAc/hexanes for 5 CV, then 8% EtOAc/hexanes for 5 CV) to afford
the title compound as a colorless oil (280 mg, 82%). 1H NMR analysis [integration of
allylic resonances at 4.25 (major) and 4.08 (minor) ppm] of the unpurified reaction
mixture indicated a 10:1 dr. The absolute configuration of the major stereoisomer was
assigned as (3R,4S) by analogy.
Major diastereomer: 1H NMR (400 MHz, C6D6) δ: 7.347.31 (m, 2H), 7.21 (t, J = 7.7 Hz,
2H), 7.09 (m, 1H), 6.93 (s, 1H), 4.95 (s, 1H), 4.93 (s, 1H), 4.26 (m, 1H),
2.59 (m, 2H), 2.09 (m, 1H), 1.89 (m, 2H), 1.741.68 (m, 3H), 1.63
(m, 2H), 1.56 (m, 2H), 1.261.14 (m, 7H), 1.17 (d, J = 7.0 Hz, 3H), 1.091.01 (m,
2H), 0.840.80 (m, 3H) ppm. 13C NMR (101 MHz, C6D6) δ: 158.9, 143.6, 139.3, 129.5,
128.9, 126.9, 126.3, 109.1, 75.1, 45.4, 42.9, 34.5, 33.3, 32.7, 29.8, 29.2, 27.8, 27.5, 27.0,
23.1, 14.5, 13.9 ppm. SFC analysis (OD-H column, scCO2/MeOH = 95/5 to 60/40, 2.5
mL/min) indicated a 95:5 er: tR (major) = 3.28 min, tR (minor) = 3.37 min.
Properties for mixture of diastereomers:
IR: 3486 (-OH, broad), 2924, 2849, 1643, 1449, 1113, 886, 748, 694 cm-1. [α]D23 = -1.32,
(c = 1.00, CHCl3). HRMS (DART) Calcd. m/z for [C24H36O-OH]+: 323.2733. Found:
323.2740.
Duplicate experiment - Yield: 80%, 274 mg; dr: 10:1; er: 95.5:4.5. Average yield: 81%.
Supporting Information S 20
(2R,3R)-4-cyclohexyl-3-methylpent-4-en-2-ol (16): The general procedure was
followed (Note: The reaction mixture was stirred at room temperature for 30 min before
placed in an ice/water bath at 0 °C) using 1.0 mL of a 1.0 M stock solution of
acetaldehyde (44 mg, 1.0 mmol, 1.0 equiv) in toluene and buta-1,3-dien-2-ylcyclohexane
(272 mg, 2.0 mmol, 2.0 equiv). The crude reaction mixture was purified with the aid of a
Biotage Isolera system (25 g SNAP cartridge, 2% EtOAc/hexanes for 2 CV, then 2-5%
EtOAc/hexanes for 10 CV, then 5-10% EtOAc/hexanes for 10 CV, then 10-15%
EtOAc/hexanes for 5 CV) to afford the title compound as a colorless oil (96 mg, 53%). 1H NMR analysis [integration of vinylic resonances at 4.76 (major) and 4.82 (minor) ppm]
of the unpurified reaction mixture indicated a >20:1 dr. The absolute configuration of the
major stereoisomer was assigned as (2R,3R) by analogy.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 4.87 (s, 1H), 4.76 (s, 1H), 3.73 (p, J
= 6.1 Hz, 1H), 2.10 (qd, J = 6.9, 4.9 Hz, 1H), 1.821.61 (m, 7H), 1.30 (m, 4H),
1.17 (d, J = 6.3 Hz, 3H), 1.08 (m, 1H) 1.04 (d, J = 6.9 Hz, 3H) ppm. 13C NMR (101
MHz, CDCl3) δ: 158.9, 107.7, 69.2, 45.7, 44.9, 33.7, 32.6, 27.1, 26.9, 26.4, 20.9, 14.3.
Chiral GC analysis (HYDRODEX -3 P, 25 m*0.25 mm, initial: Value: 100 °C, hold 20
min; Ramp 1: rate: 0.3 °C/min, value: 160 °C, hold 20 min; Ramp 2: rate: 0.5 °C/min,
value: 220 °C, hold 20 min) indicated a 94:6 er: tR (minor) = 87.99 min, tR (major) = 90.42
min.
Properties for mixture of diastereomers:
IR: 3377 (-OH, broad), 2977, 2927, 2853, 1636, 1440, 1366, 1262, 1080, 1025, 883, 751
cm-1. [α]D23 = +8.1, (c = 1.00, CHCl3). HRMS (ESI) Calcd. m/z for [C12H22O+H]+:
183.1743. Found: 183.1745.
Duplicate experiment - Yield: 48%, 88 mg; dr: >20:1; er: 93:7. Average yield: 50%.
Supporting Information S 21
(1R,2R)-3-cyclohexyl-1-cyclopropyl-2-methylbut-3-en-1-ol (17): The general
procedure was followed (Note: The reaction mixture was stirred at room temperature for
30 min before placed in an ice/water bath at 0 °C) using 1.0 mL of a 1.0 M stock solution
of cyclopropanecarbaldehyde (70 mg, 1.0 mmol, 1.0 equiv) in toluene and buta-1,3-dien-
2-ylcyclohexane (272 mg, 2.0 mmol, 2.0 equiv). The crude reaction mixture was purified
with the aid of a Biotage Isolera system (25 g SNAP cartridge, 100% hexanes for 2 CV,
then 0-7% EtOAc/hexanes for 5 CV, then 7% EtOAc/hexanes for 7 CV) to afford the title
compound as a clear oil (144 mg, 69%). 1H NMR analysis [integration of vinylic
resonances at 4.81 (major) and 4.85 (minor) ppm] of the unpurified reaction mixture
indicated a 15:1 dr. The absolute configuration of the major stereoisomer was assigned as
(1R,2R) by analogy.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 4.89 (s, 1H), 4.81 (s, 1H), 2.81 (dd,
J = 8.2, 4.3 Hz, 1H), 2.35 (qd, J = 7.0, 4.1 Hz, 1H), 1.851.63 (m, 7H), 1.281.16 (m,
4H), 1.12 (d, J = 7.0 Hz, 3H), 1.05 (m, 2H), 0.56 (m, 2H), 0.36 (m, 1H),
0.220.16 (m, 1H) ppm. 13C NMR (101 MHz, CDCl3) δ: 158.6, 107.9, 77.6, 45.0, 44.2,
33.7, 32.4, 27.1, 26.9, 26.5, 15.5, 14.3, 3.4, 2.8. Chiral GC analysis (HYDRODEX -3 P,
25 m*0.25 mm, initial: Value: 100 °C, hold 20 min; Ramp 1: rate: 0.3 °C/min, value:
160 °C, hold 20 min; Ramp 2: rate: 0.5 °C/min, value: 220 °C, hold 20 min) indicated a
97:3 er: tR (minor) = 145.42 min, tR (major) = 145.93 min.
Properties for mixture of diastereomers:
IR: 3422 (-OH, broad), 3081, 2929, 2856, 1639, 1447, 1260, 1011, 978, 888, 751 cm-1.
[α]D24 = +35.9, (c = 1.00, CHCl3). HRMS (ESI) Calcd. m/z for [C14H24O-OH]+:
191.1794. Found: 191.1792.
Duplicate experiment -Yield: 62%, 130 mg; dr: 14:1; er: 97:3. Average yield: 66%.
(1R,2R)-3-cyclohexyl-1-cyclopentyl-2-methylbut-3-en-1-ol (18): The general
procedure was followed (Note: The reaction mixture was stirred at room temperature for
30 min before placed in an ice/water bath at 0 °C) using 1.0 mL of a 1.0 M stock solution
of cyclopentanecarbaldehyde (98 mg, 1.0 mmol, 1.0 equiv) in toluene and buta-1,3-dien-
2-ylcyclohexane (272 mg, 2.0 mmol, 2.0 equiv). The crude reaction mixture was purified
with the aid of a Biotage Isolera system (25 g SNAP cartridge, 2% EtOAc/hexanes for 3
CV, then 2-5% EtOAc/hexanes for 10 CV, then 5-10% EtOAc/hexanes for 10 CV) to
Supporting Information S 22
afford the title compound as a colorless oil (138 mg, 58%). 1H NMR analysis [integration
of methyl resonances at 1.00 (major) and 0.96 (minor) ppm] of the unpurified reaction
mixture indicated a >20:1 dr. The absolute configuration of the major stereoisomer was
assigned as (1R,2R) by analogy.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 4.93 (s, 1H), 4.82 (s, 1H), 3.24 (dd,
J = 8.5, 2.9 Hz, 1H), 2.32 (qd, J = 7.1, 2.9 Hz, 1H). 1.971.52 (m, 15H), 1.42 (m,
6H), 1.00 (d, J = 7.0 Hz, 3H) ppm. 13C NMR (101 MHz, CDCl3) δ: 159.0, 108.1, 76.2,
44.6, 43.1, 42.2, 34.1, 32.6, 30.6, 29.2, 27.2, 26.9, 26.5, 25.8, 25.6, 12.2 ppm. Chiral GC
analysis (HYDRODEX -3 P, 25 m*0.25 mm, initial: Value: 70 °C, hold 50 min; Ramp
1: rate: 1.0 °C/min, value: 100 °C, hold 10 min; Ramp 2: rate: 0.8 °C/min, value: 220 °C,
hold 20 min) indicated a 95:5 er: tR (minor) = 179.01 min, tR (major) = 179.58 min.
Properties for mixture of diastereomers:
IR: 3486 (-OH, broad), 2924, 2858, 1639, 1449, 1262, 1070, 969, 890, 753 cm-1. [α]D24 =
+25.2, (c = 1.00, CHCl3). HRMS (DART) Calcd. m/z for [C16H28O+H]+: 237.2213.
Found: 237.2220.
Duplicate experiment: Yield: 56%, 133 mg; dr: >20:1; er: 95:5. Average yield: 57%.
(3S,4R)-5-((3R,5R,7R)-adamantan-1-yl)-2,2,4-trimethylhex-5-en-3-ol (19): The
general procedure was followed (Note: The reaction mixture was stirred at room
temperature for 30 min before placed in an ice/water bath at 0 °C) using 1.0 mL of a 1.0
M stock solution of pivalaldehyde (86 mg, 1.0 mmol, 1.0 equiv) in toluene and
(3R,5R,7R)-1-(buta-1,3-dien-2-yl)adamantane (377 mg, 2.0 mmol, 2.0 equiv). The crude
reaction mixture was purified with the aid of a Biotage Isolera system (25 g SNAP
cartridge, 2% EtOAc/hexanes for 3 CV, then 2-5% EtOAc/hexanes for 10 CV, then 5-10%
EtOAc/hexanes for 10 CV, then 10-10% EtOAc/hexanes for 5 CV) to afford the title
compound as a white solid (145 mg, 52%). 1H NMR analysis of the unpurified reaction
mixture indicated a >20:1 dr (resonances that are typical of the minor diastereomer could
not be detected). The absolute configuration of the major stereoisomer was assigned as
(3S,4R) by analogy.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 5.02 (d, J = 1.1 Hz, 1H), 4.89 (d, J =
1.2 Hz, 1H), 3.17 (d, J = 1.3 Hz, 1H), 2.74 (q, J = 6.9 Hz, 1H), 2.032.00 (m, 3H),
Supporting Information S 23
1.741.63 (m, 13H), 1.05 (d, J = 7.0 Hz, 3H), 1.00 (s, 9H) ppm. 13C NMR (101 MHz,
CDCl3) δ: 165.6, 107.3, 80.5, 41.0, 39.1, 37.1, 36.4, 33.6, 28.7, 27.6, 16.6 ppm. Chiral
GC analysis (HYDRODEX -3 P, 25 m*0.25 mm, initial: Value: 100 °C, hold 20 min;
Ramp 1: rate: 0.3 °C/min, value: 160 °C, hold 20 min; Ramp 2: rate: 0.5 °C/min, value:
220 °C, hold 20 min) indicated a 99.5:0.5 er: tR (major) = 264.69 min, tR (minor) = 267.85
min.
Properties for mixture of diastereomers:
M.P. 64-66 oC. IR: 3531 (-OH, broad), 2908, 2846, 1632, 1447, 1359, 1267, 1113, 1063,
966, 902, 765 cm-1. [α]D24 = +10.4, (c = 1.00, CHCl3). HRMS (DART) Calcd. m/z for
[C19H32O-OH]+: 259.2420. Found: 259.2419.
Duplicate experiment - Yield: 44%, 121 mg; dr: >20:1; er: 99.5:0.5. Average yield: 48%.
(1S,2R)-1-adamantan-1-yl)-2,7-dimethyl-3-methyleneoct-6-en-1-ol (20): The general
procedure was followed using 1.0 mL of a 1.0 M stock solution of adamantane-1-
carbaldehyde (164 mg, 1.0 mmol, 1.0 equiv) in toluene and myrcene (272 mg, 2.0 mmol,
2.0 equiv). The crude reaction mixture was purified with the aid of a Biotage Isolera
system (25 g SNAP cartridge, 2% EtOAc/hexanes for 3 CV, then 2-5% EtOAc/hexanes
for 10 CV, then 5-10% EtOAc/hexanes for 10 CV, then 10-10% EtOAc/hexanes for 5 CV)
to afford the title compound as a colorless oil (227 mg, 75%). 1H NMR analysis
[integration of allylic resonances at 3.04 (major) and 2.93 (minor) ppm] of the unpurified
reaction mixture indicated a 5:1 dr. The absolute configuration of the major stereoisomer
was assigned as (1S,2R) by analogy.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 5.145.11 (m, 1H), 4.84 (s, 1H),
4.83 (s, 1H), 3.03 (d, J = 2.0 Hz, 1H), 2.502.43 (m, 1H), 2.19 (m, 5H), 1.73
(m, 15H), 1.69 (s, 3H), 1.61 (s, 3H), 1.06 (d, J = 7.0 Hz, 3H) ppm. 13C NMR (101 MHz,
CDCl3) δ: 155.2, 131.8, 124.2, 108.9, 80.0, 39.4, 39.1, 37.3, 35.6, 28.7, 28.6, 26.8, 25.8,
17.9, 14.2 ppm. Chiral GC analysis (HYDRODEX -3 P, 25 m*0.25 mm, initial: Value:
100 °C, hold 20 min; Ramp 1: rate: 0.2 °C/min, value: 160 °C, hold 20 min; Ramp 2: rate:
0.4 °C/min, value: 220 °C, hold 20 min) indicated a 85:15 er: tR (minor)= 433.81 min, tR
(major) = 435.00 min.
Supporting Information S 24
Properties for mixture of diastereomers:
IR: 3514 (-OH, broad), 2972, 2901, 2851, 1634, 1445, 1378, 1106, 985, 888, 817, 760
cm-1. [α]D23 = +7.2, (c = 1.00, CHCl3). HRMS (DART) Calcd. m/z for [C21H34O-OH]+:
285.2577. Found: 285.2588.
Duplicate experiment: Yield: 71%, 216 mg; dr: 5:1; er: 85:15. Average yield: 73%.
V. Additional Experiment to Confirm the Absolute Configuration of
Allylation Product of Aliphatic Aldehydes with Dienes
To confirm the absolute configuration of the products of allylation of aliphatic aldehydes
with dienes, allylation of pentanal with 2-phenyl-1,3-butadiene was conducted under the
standard reaction conditions. The absolute configuration of the major diastereomer of the
product is (3R, 4R) by comparison of NMR and specific optical rotation value from the
literature.4
(3R,4R)-3-methyl-2-phenyloct-1-en-4-ol (P1): The general procedure was followed
using 1.0 mL of a 1.0 M stock solution of pentanal (86 mg, 1.0 mmol, 1.0 equiv) in
toluene and buta-1,3-dien-2-ylbenzene (260 mg, 2.0 mmol, 2.0 equiv). The crude reaction
mixture was purified with the aid of a Biotage Isolera system (25 g SNAP cartridge, 0%
EtOAc/hexanes for 2 CV, then 0-10% EtOAc/hexanes for 19 CV) to afford the title
compound as a colorless oil (167 mg, 76%). 1H NMR analysis [integration of methyl
resonances at 1.19 (major) and 1.15 (minor) ppm] of the unpurified reaction mixture
indicated a 14:1 dr.
Major diastereomer: 1H NMR (400 MHz, CDCl3) δ: 7.377.27 (m, 5H), 5.37 (d, J = 1.1
Hz, 1H), 5.14 (dd, J = 1.2, 1.2 Hz, 1H), 3.533.48 (m, 1H), 2.882.82 (m, 1H),
1.521.24 (m, 7H), 1.19 (d, J = 7.0 Hz, 3H), 0.88 (t, J = 7.0 Hz, 3H) ppm. 13C NMR
(101 MHz, CDCl3) δ: 152.4, 142.3, 128.4, 127.5, 126.6, 113.4, 72.2, 42.8, 34.3, 28.4,
Supporting Information S 25
22.7, 14.0, 12.5 ppm. SFC analysis (AD-H column, scCO2/MeOH = 95/5 to 60/40, 2.5
mL/min) indicated a 98.5:1.5 er: tR (major) = 2.67 min, tR (minor) = 2.80 min.
Properties for mixture of diastereomers:
IR: 3443 (-OH, broad), 2956, 2931, 2872, 1493, 1459, 1443, 1270, 1074, 899, 777 cm-1.
[α]D23 = +95.9, (c = 1.09, CHCl3). HRMS (DART) Calcd. m/z for [C15H22O-OH]+:
201.1638. Found: 201.1642.
NMR and specific optical rotation value in the literature4: 1H NMR (500 MHz, CDCl3) δ: 7.377.28 (m, 5H), 5.37 (d, J = 1.0 Hz, 1H), 5.14 (d, J =
1.0 Hz, 1H), 3.50 (m, 1H), 2.85 (m, 1H), 1.86 (br s, 1H), 1.201.51 (m, 6H), 1.04 (d, J =
6.5 Hz, 3H), 0.89 (t, J = 7.0 Hz, 3H) ppm. 13C NMR (125 MHz, CDCl3) δ: 152.6, 142.5,
128.6, 127.7, 126.8, 113.7, 72.4, 43.0, 34.5, 28.7, 22.9, 14.2, 12.7 ppm. [α]D25 = +65.6, (c
= 1.09, CHCl3).
VI. Other Explored Examples
Supporting Information S 26
VII. General Procedure for Kinetics Experiments
In a nitrogen-filled glovebox, five oven-dried screw-cap reaction tubes (Fisherbrand, 20 x
150 mm, catalog no. 1495937C), each equipped with stir bars, were charged with
Cu(OAc)2 (1.8 mg, 0.01 mmol, 2.0 mol %) and (S,S)-Ph-BPE (5.1 mg, 0.01 mmol, 2.0
mol %), followed the addition of dry toluene (0.2 mL) via syringe. After the reaction
mixtures were stirred at room temperature for 3 min, the diene (indicated equiv) and
DMMS (245 μL, 2.0 mmol, 4.0 equiv) were added to each tube via syringe. The reaction
vessels were capped (Cap: Kimble Chase Open Top S/T Closure catalog no. 73804-
15425; Septum: Thermo Scientific 1.3 mm silicone/PTFE catalog no. B7995-18) and
removed from the glovebox. The caps were wrapped in parafilm and the reaction tubes
were then placed in a rt water bath and stirred. Benzaldehyde (51 μL, 0.5 mmol, 1.0 equiv)
was added to each tube quickly via a glass microsyringe, and a timer was started. After
the indicated time, according to the quenching schedule shown below, a saturated
solution of NH4F in MeOH (ca. 5 mL) was carefully added to quench one of the reactions
(Caution: gas evolution was observed). The mixture was allowed to stir for 30 min at
room temperature, diluted with EtOAc (ca. 10 mL), stirred for an additional 20 min at
room temperature and then filtered through a short plug of Celite (2.0 cm) eluting with
additional EtOAc (ca. 10 mL). The solvent was removed under reduced pressure with the
aid of a rotary evaporator. At this point, the reaction mixture was analyzed by 1H NMR
spectroscopic analysis using 1,1,2,2-tetrachloroethane as an internal standard. The yield
of product represents the combined yield of the two diastereomers, which were formed
with roughly 5:1 dr.
0 equiv diene 1 equiv diene 5 equiv diene
Time (min)
Reduction (%)
SM (%)
Reduction (%)
Product (%)
SM (%)
Reduction (%)
Product (%)
SM (%)
0 0 100 0 0 100 0 0 100
5 56 44
10 78 22
15 90 10 42 3 55 13 5 82
30 100 0 65 5 30 30 11 59
60 81 8 11 51 15 34
90 88 10 2 64 21 15
180 100 0 89 11 0 65 33 2
Supporting Information S 27
VIII. Computational Studies
Computational Details. All reported calculations were performed using the ORCA
software5 or GAUSSIAN 036. Images of the 3D structures were rendered using
CYLView.7 The geometry of all reactants and transition states were optimized using the
B3LYP functional in the gas phase. In these geometry optimizations, a mixed basis set of
SDD for Cu and 6-31G(d) for all other atoms was used. Ground and transition state
geometries were validated by vibrational analysis at the same level, showing zero and one
imaginary frequencies respectively. Single point energies were calculated using the M06-
2X8,9 functional on a mixed basis set of SDD for Cu and 6-311+G(d,p) for all other atoms.
In these energy calculations, the SMD solvation model10 with toluene as solvent was
applied. The reported Gibbs free energies and enthalpies include zero-point and thermal
corrections calculated at 298 K using B3LYP/SDD–6-31G(d).
Cartesian Coordinates and Calculated Thermodynamic Parameters for Optimized
Structures
LCuH (I) Charge: 0
Multiplicity: 1
Imaginary Frequencies: 0
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2197.962326
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2197.415915
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2197.801093
Total Gibbs Free Energy: -2197.254682
Geometry:
P 0.91624 -1.34014 0.05164
C 0.11148 -3.06361 -0.13559
C 1.24485 -3.99333 -0.61602
C 2.53054 -3.53502 0.08225
C 2.67830 -2.01458 -0.17445
H 1.00707 -5.04232 -0.40020
H 1.38185 -3.91269 -1.70166
H 3.41456 -4.07303 -0.28018
H 2.46118 -3.72170 1.16176
P -0.91617 1.34009 0.05158
C -0.11109 3.06338 -0.13608
C -1.24432 3.99323 -0.61660
C -2.53007 3.53530 0.08183
C -2.67813 2.01488 -0.17468
H -1.00630 5.04221 -0.40101
H -1.38145 3.91240 -1.70219
H -3.41399 4.07342 -0.28066
H -2.46064 3.72216 1.16131
H -0.11655 -3.33247 0.90334
H 2.92082 -1.88233 -1.23758
Cu -0.00055 0.00031 1.76199
C -0.63951 0.43109 -1.56906
H -0.62528 1.12401 -2.41907
Supporting Information S 28
H -1.51915 -0.21313 -1.68554
C 0.63931 -0.43148 -1.56913
H 0.11700 3.33243 0.90279
H -2.92047 1.88258 -1.23785
C 1.19310 3.06586 -0.90360
C 3.66558 2.96178 -2.26433
C 2.38165 2.74114 -0.22619
C 1.27259 3.34474 -2.27639
C 2.49668 3.29575 -2.94894
C 3.60332 2.68392 -0.89615
H 2.34432 2.52452 0.83934
H 0.37940 3.61388 -2.83236
H 2.53314 3.52318 -4.01139
H 4.50257 2.41780 -0.34798
H 4.61632 2.92415 -2.78932
C -3.75640 1.33506 0.64378
C -5.82731 0.13659 2.13362
C -3.61845 1.12743 2.02579
C -4.94712 0.92881 0.02459
C -5.97619 0.33636 0.76013
C -4.64410 0.53322 2.76181
H -2.69414 1.40249 2.52684
H -5.07108 1.08082 -1.04577
H -6.89258 0.03401 0.25925
H -4.51165 0.37369 3.82853
H -6.62446 -0.32629 2.70935
C 3.75636 -1.33459 0.64418
C 5.82689 -0.13587 2.13434
C 4.94740 -0.92881 0.02529
C 3.61788 -1.12634 2.02604
C 4.64335 -0.53202 2.76222
C 5.97628 -0.33623 0.76100
H 5.07175 -1.08127 -1.04496
H 2.69332 -1.40102 2.52685
H 4.51049 -0.37201 3.82882
H 6.89292 -0.03426 0.26035
H 6.62389 0.32710 2.71020
C -1.19273 -3.06639 -0.90307
C -3.66522 -2.96271 -2.26381
C -1.27219 -3.34535 -2.27586
C -2.38131 -2.74180 -0.22568
C -3.60300 -2.68478 -0.89564
C -2.49628 -3.29656 -2.94841
H -0.37894 -3.61438 -2.83181
H -2.34400 -2.52513 0.83983
H -4.50228 -2.41874 -0.34748
H -2.53272 -3.52405 -4.01084
H -4.61597 -2.92522 -2.78880
H -0.00058 -0.00166 3.31401
H 0.62493 -1.12446 -2.41908
H 1.51893 0.21273 -1.68585
TS1 Charge: 0
Multiplicity: 1
Imaginary Frequencies: 1
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2543.526883
Supporting Information S 29
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2542.878705
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2543.327127
Total Gibbs Free Energy: -2542.678949
Geometry:
P -0.75622 0.06472 1.35905
C -0.22381 -1.13375 2.74351
C -1.21406 -0.88732 3.89669
C -2.58938 -0.65206 3.25971
C -2.42640 0.45589 2.18890
H -1.22151 -1.73165 4.59720
H -0.93107 0.00366 4.47186
H -3.34509 -0.36010 3.99851
H -2.94603 -1.57550 2.78557
P 1.48852 1.09504 -0.83810
C 1.09865 2.56114 -2.00164
C 2.46276 3.06027 -2.52087
C 3.37830 1.83575 -2.64241
C 3.33317 1.10239 -1.27894
H 2.34577 3.58998 -3.47418
H 2.91473 3.76822 -1.81515
H 4.40865 2.11187 -2.89612
H 3.02080 1.16505 -3.43527
H -0.45772 -2.11463 2.31032
H -2.27467 1.40516 2.71955
Cu -0.19826 -0.48756 -0.78846
C 1.52627 1.75947 0.91453
H 1.89061 2.79386 0.93584
H 2.26831 1.13980 1.43133
C 0.17340 1.67088 1.64755
H 0.58755 2.06293 -2.83384
H 3.80575 1.77185 -0.54562
C 0.13759 3.57776 -1.42355
C -1.73205 5.36998 -0.29739
C -1.24488 3.34140 -1.52430
C 0.56157 4.73418 -0.75118
C -0.36343 5.62275 -0.19670
C -2.16974 4.22256 -0.96426
H -1.59364 2.44619 -2.03361
H 1.62088 4.95657 -0.66149
H -0.00962 6.51549 0.31294
H -3.23126 4.00665 -1.04703
H -2.45026 6.06210 0.13423
C 4.08665 -0.21530 -1.25254
C 5.62196 -2.58086 -1.27031
C 3.49018 -1.45176 -1.53745
C 5.46201 -0.18805 -0.96828
C 6.22564 -1.35504 -0.97898
C 4.25378 -2.62233 -1.54381
H 2.42097 -1.52844 -1.70954
H 5.93943 0.76212 -0.73530
H 7.28866 -1.30716 -0.75612
H 3.76506 -3.56993 -1.75413
H 6.21154 -3.49406 -1.27672
C -3.60834 0.62044 1.25910
C -5.85979 0.93937 -0.40591
C -4.36501 1.80043 1.28960
Supporting Information S 30
C -3.99796 -0.39762 0.37513
C -5.11250 -0.24038 -0.44838
C -5.48201 1.96125 0.46641
H -4.07831 2.60091 1.96864
H -3.42101 -1.31595 0.31338
H -5.38709 -1.04138 -1.12901
H -6.05746 2.88263 0.51195
H -6.72786 1.06116 -1.04848
C 1.25995 -1.11118 3.04001
C 4.04908 -1.05882 3.45814
C 1.81042 -0.41656 4.12680
C 2.13400 -1.78698 2.16919
C 3.51361 -1.75639 2.37154
C 3.19249 -0.39369 4.33572
H 1.16482 0.10495 4.82739
H 1.72583 -2.32365 1.31559
H 4.16761 -2.27255 1.67438
H 3.59626 0.14497 5.18949
H 5.12355 -1.03767 3.61981
H -1.15352 -0.70846 -2.06859
H 0.32028 1.84486 2.72060
H -0.49826 2.45514 1.27840
C -0.50958 -2.41102 -1.97087
O 0.37588 -2.56124 -1.05924
H -0.17877 -2.26094 -3.01078
C -1.84661 -3.08634 -1.86338
C -2.17764 -3.80346 -0.70734
C -2.74633 -3.06458 -2.93668
C -3.39926 -4.47332 -0.61874
H -1.45697 -3.83590 0.10404
C -3.96569 -3.73364 -2.85075
H -2.48939 -2.50842 -3.83606
C -4.29824 -4.43760 -1.68777
H -3.64750 -5.03120 0.28099
H -4.65691 -3.71095 -3.68957
H -5.24792 -4.96211 -1.62095
Copper alkoxide 11 Charge: 0
Multiplicity: 1
Imaginary Frequencies: 0
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2543.570203
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2542.919609
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2543.375184
Total Gibbs Free Energy: -2542.724589
P -1.31942 -0.12779 -1.40115
C -0.61787 -0.54452 -3.13061
C -1.80414 -0.37155 -4.10259
C -2.65427 0.79288 -3.57923
C -2.96898 0.49760 -2.09147
H -1.44749 -0.19874 -5.12546
H -2.42196 -1.27799 -4.12752
H -3.58195 0.91761 -4.15022
H -2.09854 1.73631 -3.65908
P 0.18179 -1.05054 1.36540
C -0.70860 -1.04710 3.05472
Supporting Information S 31
C 0.07609 -2.05039 3.92385
C 1.55818 -1.90239 3.55668
C 1.66689 -2.03883 2.01765
H -0.10792 -1.87113 4.99019
H -0.23974 -3.07957 3.71190
H 2.18493 -2.65344 4.05162
H 1.92999 -0.91813 3.87013
H 0.07967 0.28290 -3.31069
H -3.65901 -0.35719 -2.06791
Cu 0.11114 0.86820 0.19045
C -0.68436 -2.33155 0.29751
H -1.08243 -3.14642 0.91438
H 0.10539 -2.75719 -0.33382
C -1.80282 -1.74686 -0.58989
H -0.49360 -0.04189 3.43788
H 1.45605 -3.08721 1.76696
C -2.21238 -1.18857 2.96291
C -5.01597 -1.36306 2.68199
C -2.98562 -0.04862 2.68035
C -2.87561 -2.41594 3.11035
C -4.26391 -2.50123 2.97429
C -4.36993 -0.13253 2.53467
H -2.49226 0.91392 2.56392
H -2.31524 -3.31659 3.34342
H -4.75609 -3.46224 3.10076
H -4.93929 0.76295 2.30212
H -6.09523 -1.43198 2.57574
C 3.01247 -1.67619 1.42633
C 5.54230 -1.05964 0.35176
C 3.49367 -0.35752 1.43043
C 3.82287 -2.67868 0.87450
C 5.07918 -2.37639 0.34421
C 4.74468 -0.04929 0.89516
H 2.88098 0.44376 1.83435
H 3.46738 -3.70709 0.86309
H 5.69376 -3.17056 -0.07270
H 5.08405 0.98234 0.89168
H 6.51650 -0.81996 -0.06609
C -3.61053 1.64466 -1.33519
C -4.89363 3.77341 -0.00825
C -4.99350 1.61928 -1.10055
C -2.87410 2.75466 -0.88825
C -3.51510 3.80672 -0.23085
C -5.63363 2.67318 -0.44554
H -5.57625 0.76401 -1.43761
H -1.79418 2.79738 -1.01125
H -2.92509 4.65093 0.11557
H -6.70729 2.63313 -0.27875
H -5.38621 4.59545 0.50471
C 0.17819 -1.82972 -3.18878
C 1.72700 -4.19203 -3.18048
C -0.38465 -3.06256 -3.55314
C 1.53649 -1.80652 -2.82669
C 2.30262 -2.97184 -2.81648
C 0.38257 -4.23043 -3.55200
H -1.42709 -3.12002 -3.85245
H 1.99531 -0.86150 -2.54432
Supporting Information S 32
H 3.34688 -2.92219 -2.52111
H -0.07486 -5.17176 -3.84602
H 2.32176 -5.10151 -3.18053
H 1.30201 3.05529 1.91017
H -2.11601 -2.49155 -1.33128
H -2.67818 -1.50902 0.02627
C 1.29365 3.42493 0.86411
H 0.92886 4.47135 0.93371
O 0.45833 2.69715 0.03163
C 2.74952 3.50259 0.40037
C 3.09486 3.21793 -0.92520
C 3.76362 3.89613 1.28477
C 4.41835 3.32700 -1.35883
H 2.30422 2.90932 -1.60218
C 5.08831 4.00802 0.85711
H 3.51190 4.11981 2.32103
C 5.42150 3.72309 -0.47086
H 4.66849 3.10329 -2.39386
H 5.86061 4.31607 1.55867
H 6.45158 3.81025 -0.80812
Reduction product VI Charge: 0
Multiplicity: 1
Imaginary Frequencies: 0
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -905.9735858
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -905.775381
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
905.8988498
Total Gibbs Free Energy: -905.700645
H 0.19071 -1.23226 -0.82542
C 0.47494 -0.77091 0.13191
H 0.33099 -1.53461 0.91155
C 1.93446 -0.36662 0.08089
C 2.38417 0.82215 0.66307
C 2.86384 -1.21900 -0.52879
C 3.74133 1.15171 0.63634
H 1.66317 1.48607 1.12766
C 4.22001 -0.89358 -0.55132
H 2.52395 -2.14353 -0.99242
C 4.66354 0.29579 0.03216
H 4.07786 2.08083 1.08948
H 4.92875 -1.56436 -1.03018
H 5.71906 0.55392 0.01200
O -0.35850 0.34528 0.41700
Si -2.01388 0.33465 0.27045
C -2.60584 1.92439 1.03729
H -3.68962 2.03027 0.92115
H -2.37691 1.93941 2.10824
H -2.12406 2.79610 0.58091
O -2.70787 -0.93572 1.05717
O -2.43574 0.15021 -1.32577
C -1.97182 0.99770 -2.36674
H -2.41363 2.00048 -2.28976
H -0.87852 1.09537 -2.35452
H -2.27431 0.56051 -3.32336
C -3.04541 -2.20616 0.51896
Supporting Information S 33
H -3.34817 -2.13228 -0.53109
H -2.19646 -2.89832 0.59667
H -3.87687 -2.61375 1.10293
Diene (1b), s-trans Charge: 0
Multiplicity: 1
Imaginary Frequencies: 0
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -195.306479
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -195.220821
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
195.264157
Total Gibbs Free Energy: -195.178498
Geometry:
C 0.01013 0.23842 -0.09769
C 0.55537 -0.90601 -0.70416
C 1.92403 -1.16622 -0.63554
C 2.77366 -0.29262 0.04712
C 2.24400 0.84489 0.65875
C 0.87534 1.10698 0.58633
H -0.09761 -1.58435 -1.24534
H 2.32799 -2.05146 -1.12000
H 3.83922 -0.49864 0.10364
H 2.89540 1.52795 1.19783
H 0.46305 1.98584 1.07427
C -1.44447 0.55580 -0.20795
C -1.84295 1.77083 -0.63397
H -2.89698 2.02778 -0.70428
H -1.13044 2.53460 -0.92971
C -2.45587 -0.44903 0.16060
H -3.48176 -0.16347 -0.07233
C -2.24013 -1.62493 0.76659
H -1.24597 -1.96309 1.04205
H -3.06754 -2.28384 1.01338
Diene (1b), s-cis Charge: 0
Multiplicity: 1
Imaginary Frequencies: 0
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -195.301526
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -195.216751
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
195.259461
Total Gibbs Free Energy: -195.174687
Geometry:
C 0.15827 0.18128 -0.00838
C 0.62383 -1.12312 0.23116
C 1.98979 -1.40491 0.25432
C 2.92031 -0.38888 0.02986
C 2.47260 0.91058 -0.22137
C 1.10765 1.19092 -0.24475
H -0.09339 -1.91706 0.42077
H 2.32681 -2.41945 0.45075
H 3.98461 -0.60810 0.04277
H 3.18855 1.70583 -0.41242
H 0.76779 2.19718 -0.47254
Supporting Information S 34
C -1.30217 0.47196 -0.00946
C -1.79212 1.65406 0.40972
H -2.85185 1.87932 0.34220
H -1.15200 2.42206 0.83334
C -2.20139 -0.59622 -0.50518
H -1.82874 -1.17720 -1.34920
C -3.39850 -0.89897 0.01089
H -3.78970 -0.38661 0.88621
H -4.02168 -1.67620 -0.42271
TS2a Charge: 0
Multiplicity: 1
Imaginary Frequencies: 1
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2584.988128
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2584.283346
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2584.773009
Total Gibbs Free Energy: -2584.068227
Geometry:
P -0.89403 -1.08548 0.75199
C 0.43195 -1.98110 1.80492
C -0.30801 -3.13546 2.51324
C -1.38558 -3.64769 1.55201
C -2.21161 -2.42196 1.09793
H 0.39582 -3.92480 2.80453
H -0.79119 -2.78357 3.43318
H -2.03618 -4.39629 2.01985
H -0.91629 -4.12568 0.68262
P -0.45486 2.04656 -0.21054
C -1.89832 3.20209 -0.70157
C -1.43710 4.61605 -0.30591
C 0.04534 4.72073 -0.67507
C 0.77683 3.50610 -0.05090
H -2.04235 5.38465 -0.80291
H -1.54664 4.77138 0.77485
H 0.49486 5.65852 -0.32723
H 0.15645 4.70192 -1.76665
H 1.08120 -2.42022 1.03973
H -2.76346 -2.05678 1.97465
Cu -0.28974 -0.07792 -1.19560
C -0.76697 1.64525 1.59591
H -1.29569 2.46726 2.09425
H 0.22442 1.56727 2.05676
C -1.53770 0.32822 1.80185
H -1.89385 3.14368 -1.79810
H 0.87314 3.69060 1.02655
C -3.26057 2.74502 -0.22530
C -5.78436 1.80042 0.61902
C -3.91529 1.70994 -0.91650
C -3.90091 3.29949 0.89351
C -5.15106 2.83334 1.31004
C -5.15924 1.23916 -0.49798
H -3.42992 1.25774 -1.77787
H -3.43682 4.11186 1.44466
H -5.62975 3.28536 2.17521
H -5.63474 0.42904 -1.04342
Supporting Information S 35
H -6.75734 1.44018 0.94274
C 2.15880 3.25401 -0.61157
C 4.75701 2.85536 -1.63740
C 2.36468 3.00545 -1.97813
C 3.28043 3.29379 0.22833
C 4.56774 3.09647 -0.27637
C 3.64852 2.80994 -2.48720
H 1.51251 2.95803 -2.65198
H 3.14306 3.48254 1.29063
H 5.42180 3.13607 0.39493
H 3.78309 2.62049 -3.54896
H 5.75736 2.70518 -2.03428
C -3.21039 -2.69768 -0.00249
C -5.11342 -3.27977 -2.00008
C -4.57954 -2.50297 0.22754
C -2.81028 -3.18685 -1.25578
C -3.75162 -3.47620 -2.24313
C -5.52501 -2.79085 -0.75958
H -4.90981 -2.12533 1.19294
H -1.75418 -3.33138 -1.46276
H -3.41950 -3.85306 -3.20707
H -6.58193 -2.63889 -0.55477
H -5.84562 -3.50722 -2.77034
C 1.28378 -1.06988 2.66151
C 2.90157 0.68932 4.16982
C 0.94511 -0.72701 3.98076
C 2.45687 -0.51782 2.11794
C 3.25492 0.35267 2.86095
C 1.74428 0.14244 4.72670
H 0.05526 -1.14468 4.44299
H 2.74554 -0.77788 1.10366
H 4.15704 0.76058 2.41328
H 1.46195 0.38711 5.74769
H 3.52561 1.36151 4.75300
H -1.10128 -0.16571 -2.58249
H -1.52988 0.05635 2.86426
H -2.58509 0.45725 1.50551
C 3.24171 -2.35352 -1.31682
C 4.33549 -1.51709 -1.60516
C 5.58553 -1.73394 -1.02373
C 5.77799 -2.79205 -0.13411
C 4.70357 -3.63188 0.16718
C 3.45545 -3.41241 -0.41410
H 4.21081 -0.70000 -2.30865
H 6.41334 -1.07444 -1.27293
H 6.75066 -2.95855 0.32143
H 4.83419 -4.45574 0.86459
H 2.62392 -4.06337 -0.15959
C 1.90498 -2.13766 -1.95584
C 1.14562 -3.22302 -2.26665
H 0.16913 -3.12061 -2.72966
H 1.51546 -4.23395 -2.13440
C 1.52635 -0.75557 -2.25081
H 2.21390 0.02776 -1.95495
C 0.47991 -0.40947 -3.15254
H 0.08467 -1.18694 -3.80112
H 0.52726 0.56556 -3.63017
Supporting Information S 36
TS2b Charge: 0
Multiplicity: 1
Imaginary Frequencies: 1
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2584.980335
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2584.280775
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2584.763902
Total Gibbs Free Energy: -2584.064342
Geometry:
C -2.75389 -3.21142 -1.31715
C -2.52742 -3.21271 0.07070
C -3.14752 -4.14617 0.90303
C -4.00494 -5.10907 0.36784
C -4.23271 -5.12956 -1.00957
C -3.61191 -4.19576 -1.83921
H -1.86518 -2.46624 0.49978
H -2.95924 -4.12076 1.97392
H -4.48448 -5.83853 1.01540
H -4.88899 -5.88080 -1.44222
H -3.77539 -4.23025 -2.91230
C -2.12641 -2.20705 -2.23402
C -2.90805 -1.62955 -3.18279
H -2.49343 -0.91670 -3.89189
H -3.96932 -1.84082 -3.26169
C -0.68950 -1.92670 -2.15479
H -0.30955 -1.32398 -2.97797
C 0.26645 -2.71700 -1.44412
H -0.08407 -3.61104 -0.93714
H 1.25792 -2.82462 -1.87224
P 1.71006 0.87472 -0.98793
C 1.44248 2.27216 -2.27499
C 2.85832 2.72814 -2.67714
C 3.73067 1.47387 -2.76464
C 3.56166 0.68786 -1.44150
H 2.83997 3.28710 -3.62114
H 3.27902 3.39819 -1.91740
H 4.78687 1.71514 -2.93421
H 3.40711 0.85675 -3.61218
P -0.54271 0.31838 1.37659
C -0.18074 -0.65240 2.99513
C -1.39259 -0.41114 3.92689
C -2.62173 -0.11847 3.05600
C -2.19537 0.97546 2.05081
H -1.54727 -1.27577 4.58353
H -1.21301 0.45143 4.57916
H -3.47625 0.21902 3.65460
H -2.94434 -1.01928 2.51686
H 1.00761 1.73782 -3.12984
H 4.10483 1.23212 -0.65829
Cu 0.17815 -0.80930 -0.46818
C 0.47843 1.88913 1.38246
H 0.63709 2.23878 2.40928
H -0.14605 2.63373 0.87515
C 1.83192 1.76112 0.66085
H -0.21901 -1.68978 2.64718
H -1.92594 1.86108 2.64446
Supporting Information S 37
C 1.19578 -0.42490 3.58223
C 3.80777 -0.03817 4.59137
C 2.25183 -1.27371 3.20703
C 1.47987 0.62127 4.47525
C 2.76967 0.81169 4.97596
C 3.54205 -1.08263 3.70280
H 2.05529 -2.08188 2.50767
H 0.68984 1.29440 4.79636
H 2.96006 1.62526 5.67144
H 4.33810 -1.75661 3.39690
H 4.81027 0.10785 4.98473
C -3.25969 1.39438 1.06058
C -5.33290 2.19979 -0.67304
C -3.63651 0.59330 -0.02751
C -3.93725 2.60747 1.25880
C -4.96785 3.00698 0.40654
C -4.66049 0.99415 -0.88697
H -3.12561 -0.34402 -0.21855
H -3.65718 3.24397 2.09590
H -5.48259 3.94770 0.58603
H -4.92168 0.35776 -1.72759
H -6.13376 2.50677 -1.34090
C 4.09215 -0.72862 -1.47621
C 5.15652 -3.34130 -1.54446
C 5.03340 -1.15022 -0.52679
C 3.69270 -1.64491 -2.46196
C 4.21971 -2.93579 -2.49843
C 5.56081 -2.44303 -0.55672
H 5.36010 -0.45515 0.24378
H 2.95836 -1.35052 -3.20763
H 3.89700 -3.62666 -3.27306
H 6.29159 -2.74432 0.18947
H 5.56689 -4.34699 -1.57335
C 0.46111 3.34605 -1.85852
C -1.42964 5.29851 -1.08081
C 0.86901 4.56832 -1.29996
C -0.91713 3.12475 -2.01765
C -1.85143 4.08809 -1.63547
C -0.06450 5.53402 -0.91611
H 1.92484 4.78487 -1.17124
H -1.27979 2.19495 -2.44884
H -2.91006 3.88225 -1.76191
H 0.28130 6.47435 -0.49395
H -2.15672 6.04975 -0.78443
H 0.92305 -2.17043 -0.00623
H 2.28469 2.75356 0.54358
H 2.51788 1.15619 1.26552
(S)-IIa Charge: 0
Multiplicity: 1
Imaginary Frequencies: 0
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2585.036974
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2584.328993
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2584.828111
Total Gibbs Free Energy: -2584.120130
Supporting Information S 38
Geometry:
P -0.82876 -0.64975 1.11017
C 0.30141 -1.69133 2.25030
C -0.66160 -2.50154 3.14353
C -1.87611 -2.87197 2.28503
C -2.40503 -1.56326 1.64842
H -0.15724 -3.38672 3.55010
H -0.99916 -1.90319 3.99911
H -2.66545 -3.35871 2.87029
H -1.57923 -3.57462 1.49615
P 0.27263 2.04638 -0.37092
C -0.91536 3.37080 -1.07072
C -0.11905 4.68932 -1.02640
C 1.32315 4.35333 -1.42065
C 1.79512 3.18467 -0.51946
H -0.56552 5.44088 -1.68941
H -0.12282 5.11174 -0.01373
H 1.99456 5.21360 -1.31412
H 1.36055 4.04822 -2.47426
H 0.77081 -2.39234 1.55031
H -2.84074 -0.95923 2.45583
Cu -0.02010 -0.21570 -1.05171
C -0.00912 2.05753 1.48743
H -0.29675 3.05650 1.83767
H 0.96661 1.82590 1.93171
C -1.04790 1.01634 1.94664
H -1.01215 3.08003 -2.12481
H 1.96328 3.58848 0.48735
C -2.30085 3.35193 -0.46214
C -4.88663 3.19341 0.66096
C -3.23404 2.40510 -0.91969
C -2.69473 4.22241 0.56494
C -3.97548 4.14515 1.11924
C -4.50997 2.32097 -0.36396
H -2.95157 1.72143 -1.71745
H -2.00796 4.97796 0.93456
H -4.25916 4.83585 1.90932
H -5.20477 1.57038 -0.72940
H -5.88201 3.13488 1.09296
C 3.06898 2.50703 -0.97678
C 5.47922 1.31694 -1.82885
C 3.14498 1.83823 -2.20916
C 4.22060 2.56129 -0.17956
C 5.41615 1.97277 -0.59895
C 4.33753 1.25147 -2.63220
H 2.26118 1.76044 -2.83697
H 4.18164 3.07351 0.77940
H 6.29776 2.03295 0.03429
H 4.37312 0.73954 -3.59025
H 6.40792 0.85984 -2.15961
C -3.46025 -1.75523 0.57966
C -5.48027 -2.16057 -1.34422
C -4.78767 -1.38553 0.83977
C -3.15918 -2.33087 -0.66534
C -4.16064 -2.53048 -1.61610
C -5.79170 -1.58669 -0.11046
H -5.03864 -0.93777 1.79934
Supporting Information S 39
H -2.13926 -2.61340 -0.91473
H -3.89917 -2.97447 -2.57278
H -6.81508 -1.29783 0.11640
H -6.25795 -2.31823 -2.08698
C 1.40712 -0.91290 2.92834
C 3.50470 0.58787 4.08113
C 1.25506 -0.30580 4.18505
C 2.63860 -0.76174 2.26729
C 3.67366 -0.01687 2.83292
C 2.29274 0.43525 4.75593
H 0.32515 -0.41471 4.73580
H 2.78516 -1.24131 1.30238
H 4.61248 0.08677 2.29572
H 2.15186 0.88988 5.73337
H 4.31172 1.16305 4.52726
H -1.53669 -0.82026 -3.76659
H -1.02251 0.92119 3.03858
H -2.05555 1.34967 1.67086
C 1.34377 -3.27307 -1.60006
C 2.67384 -2.81503 -1.55548
C 3.61357 -3.39063 -0.69758
C 3.25013 -4.43643 0.15355
C 1.93295 -4.90061 0.13174
C 0.99759 -4.32474 -0.72948
H 2.98532 -2.00916 -2.21209
H 4.63673 -3.02175 -0.70039
H 3.98111 -4.88249 0.82298
H 1.63046 -5.71309 0.78869
H -0.02606 -4.68900 -0.72912
C 0.33057 -2.67840 -2.53349
C -0.57511 -3.51228 -3.10361
H -1.32287 -3.15011 -3.80181
H -0.57005 -4.58197 -2.91721
C 0.38083 -1.20868 -2.75997
H 1.42426 -0.90525 -2.92540
C -0.45786 -0.71799 -3.94611
H -0.24256 -1.27158 -4.87768
H -0.26832 0.34528 -4.14357
TS3-cis Charge: 0
Multiplicity: 1
Imaginary Frequencies: 1
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2585.024815
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2584.316820
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2584.816747
Total Gibbs Free Energy: -2584.108753
Geometry:
C -2.04645 -2.97161 -1.59898
C -2.07836 -3.42244 -0.26670
C -3.12049 -4.22211 0.20386
C -4.16151 -4.59863 -0.64819
C -4.14378 -4.16736 -1.97551
C -3.09831 -3.36854 -2.44305
H -1.28177 -3.12152 0.40577
H -3.11959 -4.55240 1.24018
Supporting Information S 40
H -4.97183 -5.22427 -0.28307
H -4.94066 -4.46060 -2.65477
H -3.07827 -3.05521 -3.48257
C -0.93710 -2.12162 -2.14672
C -1.28463 -1.07351 -2.97292
H -0.52574 -0.51217 -3.51287
H -2.31968 -0.79629 -3.14138
C 0.45257 -2.38323 -1.75729
H 1.13448 -1.95306 -2.49803
C 0.93435 -3.77529 -1.36709
H 0.83824 -4.50585 -2.19000
H 1.99743 -3.73213 -1.10245
P 1.53384 1.20915 -0.82942
C 1.16648 2.73275 -1.93687
C 2.53957 3.35289 -2.25890
C 3.52656 2.19672 -2.44640
C 3.41053 1.28462 -1.20352
H 2.48034 3.99565 -3.14610
H 2.88468 3.98340 -1.43006
H 4.55809 2.54819 -2.56830
H 3.27296 1.63381 -3.35383
P -0.70036 0.09726 1.35212
C -0.24815 -1.01187 2.84931
C -1.37984 -0.81852 3.87886
C -2.68169 -0.62187 3.09306
C -2.42504 0.50684 2.06764
H -1.43260 -1.67387 4.56369
H -1.20126 0.07181 4.49447
H -3.52290 -0.36012 3.74596
H -2.95657 -1.54722 2.57030
H 0.78807 2.26833 -2.85652
H 3.84464 1.83203 -0.35649
Cu 0.16178 -0.68463 -0.64673
C 0.16657 1.73868 1.63080
H 0.27507 1.94494 2.70270
H -0.51663 2.49221 1.22130
C 1.53470 1.84509 0.93669
H -0.35335 -2.02050 2.43186
H -2.27324 1.43212 2.63985
C 1.18050 -0.86874 3.32647
C 3.88500 -0.61898 4.10411
C 2.19149 -1.60441 2.68306
C 1.55526 -0.00874 4.37047
C 2.89249 0.11336 4.75665
C 3.52764 -1.48011 3.06342
H 1.92510 -2.27207 1.86726
H 0.80263 0.56677 4.90134
H 3.15512 0.78040 5.57392
H 4.28669 -2.05702 2.54256
H 4.92425 -0.52571 4.40806
C -3.55214 0.75109 1.08929
C -5.73422 1.21479 -0.63488
C -3.94081 -0.21361 0.14764
C -4.27409 1.95211 1.14708
C -5.35686 2.18407 0.29592
C -5.02028 0.01595 -0.70552
H -3.39548 -1.14846 0.07183
Supporting Information S 41
H -3.98808 2.71314 1.87017
H -5.90636 3.11973 0.36523
H -5.29809 -0.74825 -1.42621
H -6.57702 1.39084 -1.29823
C 4.12615 -0.04286 -1.31204
C 5.52542 -2.48447 -1.50546
C 5.08917 -0.40028 -0.35771
C 3.87756 -0.93412 -2.36696
C 4.56832 -2.14152 -2.46400
C 5.78336 -1.60875 -0.45044
H 5.29939 0.27733 0.46693
H 3.12931 -0.68858 -3.11540
H 4.35477 -2.81749 -3.28750
H 6.53064 -1.86011 0.29818
H 6.06398 -3.42512 -1.58213
C 0.08547 3.65251 -1.41522
C -2.00249 5.28305 -0.43674
C 0.36134 4.79493 -0.64729
C -1.26012 3.34852 -1.68577
C -2.29311 4.14968 -1.20035
C -0.67157 5.60275 -0.16522
H 1.38816 5.07217 -0.42813
H -1.49674 2.46743 -2.27748
H -3.32351 3.88205 -1.41461
H -0.43128 6.48664 0.42041
H -2.80483 5.91324 -0.06234
H 0.40855 -4.20520 -0.50904
H 1.89422 2.88074 0.97668
H 2.26820 1.22511 1.46618
TS3-trans Charge: 0
Multiplicity: 1
Imaginary Frequencies: 1
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2585.021307
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2584.310081
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2584.810655
Total Gibbs Free Energy: -2584.099429
Geometry:
P -0.30535 -1.48447 0.57906
C 0.67769 -2.03762 2.12138
C 0.06396 -3.39720 2.52067
C -0.29543 -4.13562 1.22532
C -1.15478 -3.17270 0.37327
H 0.76386 -3.96742 3.14321
H -0.84732 -3.25411 3.11444
H -0.84276 -5.06586 1.41777
H 0.61805 -4.40779 0.68181
P -1.61306 1.88559 -0.49296
C -3.43330 2.51407 -0.43282
C -3.39224 3.84924 0.33038
C -2.14885 4.59199 -0.16697
C -0.93866 3.62881 -0.05802
H -4.31103 4.42976 0.17385
H -3.30253 3.67970 1.41131
H -1.95958 5.51320 0.39761
Supporting Information S 42
H -2.29202 4.88822 -1.21418
H 1.67479 -2.23504 1.71086
H -2.12169 -3.06234 0.88166
Cu 1.04204 -0.56515 -0.93634
C -1.44117 1.08174 1.20503
H -2.11184 1.56309 1.92703
H -0.41959 1.27988 1.54839
C -1.71865 -0.43434 1.19634
H -3.64041 2.74768 -1.48631
H -0.63941 3.58592 0.99665
C -4.43762 1.47144 0.00139
C -6.26768 -0.55517 0.73957
C -4.83939 0.48286 -0.91571
C -4.98226 1.42381 1.29373
C -5.88705 0.42271 1.65831
C -5.73902 -0.51890 -0.55409
H -4.43653 0.50433 -1.92596
H -4.71360 2.18019 2.02479
H -6.29911 0.41465 2.66434
H -6.03435 -1.26605 -1.28642
H -6.97486 -1.33003 1.02296
C 0.26565 4.05796 -0.86917
C 2.50689 4.91207 -2.35362
C 0.20980 4.15390 -2.26866
C 1.46697 4.39510 -0.23149
C 2.57918 4.81728 -0.96380
C 1.31581 4.57763 -3.00383
H -0.70528 3.88190 -2.78977
H 1.53195 4.32702 0.85250
H 3.50014 5.07218 -0.44568
H 1.25032 4.64138 -4.08690
H 3.36977 5.23990 -2.92705
C -1.42394 -3.60477 -1.05150
C -1.97514 -4.42971 -3.68918
C -2.74402 -3.70812 -1.51261
C -0.38155 -3.91923 -1.93764
C -0.65511 -4.32836 -3.24275
C -3.01977 -4.11585 -2.81939
H -3.56505 -3.46595 -0.84086
H 0.65228 -3.82305 -1.61698
H 0.16695 -4.56431 -3.91338
H -4.05110 -4.19025 -3.15463
H -2.18588 -4.74857 -4.70637
C 0.83508 -0.98951 3.20272
C 1.18425 1.02340 5.15116
C -0.07888 -0.84024 4.25738
C 1.93473 -0.11528 3.15120
C 2.10635 0.88167 4.11139
C 0.09415 0.15556 5.22165
H -0.93026 -1.50948 4.34394
H 2.66650 -0.22590 2.35434
H 2.96759 1.54163 4.04980
H -0.62439 0.24713 6.03219
H 1.31932 1.79584 5.90346
H 1.32223 -0.41513 -3.91549
H -1.98407 -0.77288 2.20505
H -2.57610 -0.66771 0.55494
Supporting Information S 43
C 4.26110 -0.83542 -0.69303
C 5.14476 0.25698 -0.70495
C 6.16519 0.37046 0.24012
C 6.32074 -0.60029 1.23177
C 5.44728 -1.68981 1.26424
C 4.43204 -1.80318 0.31364
H 5.03973 1.01419 -1.47601
H 6.84303 1.21971 0.19928
H 7.11172 -0.50855 1.97169
H 5.55375 -2.45112 2.03351
H 3.75443 -2.65251 0.34371
C 3.19018 -0.96847 -1.73348
C 2.90977 -2.20443 -2.22644
H 2.15622 -2.34761 -2.99503
H 3.50802 -3.07187 -1.96438
C 2.41402 0.22614 -2.10500
H 2.84964 1.14802 -1.71963
C 1.97274 0.39318 -3.56093
H 2.83360 0.43269 -4.25184
H 1.40882 1.32531 -3.67538
IIb-cis Charge: 0
Multiplicity: 1
Imaginary Frequencies: 0
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2585.042622
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2584.337516
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2584.831691
Total Gibbs Free Energy: -2584.126585
Geometry:
C -0.88416 3.57299 -1.41481
C -1.72952 3.74162 -0.30439
C -1.45282 4.69225 0.68225
C -0.31697 5.49869 0.58204
C 0.53266 5.34828 -0.51760
C 0.25195 4.39633 -1.49992
H -2.61480 3.11641 -0.22101
H -2.12803 4.80423 1.52768
H -0.10129 6.24224 1.34516
H 1.41221 5.98047 -0.61530
H 0.91344 4.29437 -2.35631
C -1.15877 2.52961 -2.45555
C -0.10374 1.48016 -2.61278
H -0.27401 0.91333 -3.53857
H 0.89016 1.94487 -2.68948
C -2.30708 2.54859 -3.17249
H -2.43005 1.75925 -3.91737
C -3.42555 3.55571 -3.12468
H -3.62765 3.96247 -4.12656
H -4.37448 3.11463 -2.77912
P -0.49617 -1.98326 -0.56847
C 0.47050 -3.23874 -1.64276
C -0.49485 -4.42294 -1.85834
C -1.90923 -3.84217 -1.96955
C -2.13005 -2.93681 -0.73252
H -0.21145 -4.99960 -2.74753
Supporting Information S 44
H -0.46217 -5.11286 -1.00591
H -2.67671 -4.62398 -2.01472
H -2.00451 -3.24562 -2.88635
P 1.01415 0.34493 1.12741
C 0.05213 1.29439 2.48257
C 1.13196 1.88516 3.41348
C 2.32362 2.28009 2.53425
C 2.69616 1.03902 1.68779
H 0.73303 2.73832 3.97580
H 1.46389 1.14227 4.14963
H 3.18446 2.61101 3.12764
H 2.04393 3.11340 1.87735
H 0.56310 -2.71042 -2.59969
H -2.19000 -3.59355 0.14605
Cu 0.03779 0.26447 -1.03551
C 1.13756 -1.43875 1.70928
H 1.21365 -1.49511 2.80192
H 2.08423 -1.80945 1.29728
C -0.02576 -2.32209 1.21685
H -0.38893 2.12748 1.92199
H 3.11640 0.28810 2.37031
C -1.07985 0.51694 3.11696
C -3.23589 -0.96342 4.18510
C -2.33827 0.51077 2.49037
C -0.92917 -0.22906 4.29635
C -1.99615 -0.95978 4.82556
C -3.40364 -0.22245 3.01235
H -2.47874 1.08657 1.57868
H 0.02266 -0.23777 4.81893
H -1.85528 -1.52463 5.74371
H -4.36051 -0.21651 2.49837
H -4.06454 -1.53228 4.59828
C 3.70049 1.28761 0.58422
C 5.62096 1.76008 -1.42521
C 3.43407 2.17878 -0.46826
C 4.94336 0.63935 0.60810
C 5.89761 0.87164 -0.38544
C 4.38532 2.41180 -1.46142
H 2.47377 2.68445 -0.52050
H 5.16877 -0.05238 1.41712
H 6.85720 0.36238 -0.34153
H 4.15782 3.10246 -2.26921
H 6.36016 1.94466 -2.20020
C -3.39097 -2.09805 -0.77940
C -5.79416 -0.62844 -0.88501
C -4.49995 -2.47361 -0.00749
C -3.50609 -0.96918 -1.60617
C -4.69554 -0.24120 -1.65629
C -5.69313 -1.74960 -0.05937
H -4.42839 -3.34519 0.64013
H -2.65653 -0.63743 -2.19706
H -4.75389 0.63552 -2.29494
H -6.54111 -2.06302 0.54459
H -6.71952 -0.05988 -0.92600
C 1.87025 -3.54049 -1.15405
C 4.50338 -3.97480 -0.22764
C 2.16997 -4.62310 -0.31294
Supporting Information S 45
C 2.92187 -2.68533 -1.52706
C 4.22182 -2.89382 -1.06716
C 3.47299 -4.83950 0.14287
H 1.38868 -5.31538 -0.01313
H 2.71409 -1.84302 -2.18343
H 5.01042 -2.20830 -1.36414
H 3.68019 -5.68968 0.78787
H 5.51606 -4.14471 0.12801
H -3.20084 4.39953 -2.46580
H 0.21460 -3.38060 1.37268
H -0.92900 -2.10107 1.79776
IIb-trans Charge: 0
Multiplicity: 1
Imaginary Frequencies: 0
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2585.039614
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2584.334054
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2584.825574
Total Gibbs Free Energy: -2584.120013
Geometry:
P -1.35276 -0.20697 1.45782
C -0.47478 -0.27029 3.15616
C -1.58398 -0.60459 4.17474
C -2.55003 -1.57754 3.48967
C -2.96949 -0.93804 2.14294
H -1.15566 -1.02240 5.09412
H -2.13485 0.30024 4.46005
H -3.43251 -1.78920 4.10496
H -2.05087 -2.53760 3.30429
P 0.02044 1.41758 -1.01450
C -1.00677 1.80271 -2.58341
C -0.27442 2.96870 -3.28028
C 1.22765 2.77043 -3.04544
C 1.42973 2.58893 -1.52177
H -0.52774 3.00284 -4.34701
H -0.57625 3.93110 -2.84890
H 1.81922 3.61810 -3.41117
H 1.58212 1.87778 -3.57680
H 0.16442 -1.15762 3.06447
H -3.61546 -0.08026 2.37324
Cu -0.06405 -0.87247 -0.40447
C -0.76309 2.37991 0.39526
H -1.18516 3.32860 0.04214
H 0.06951 2.62327 1.06604
C -1.83418 1.58395 1.16606
H -0.85028 0.90479 -3.19369
H 1.19800 3.55135 -1.04560
C -2.49530 1.93741 -2.34807
C -5.27046 2.07911 -1.83967
C -3.29412 0.78061 -2.34950
C -3.12048 3.16802 -2.09420
C -4.49369 3.23831 -1.84543
C -4.66362 0.84636 -2.09368
H -2.83199 -0.18369 -2.54915
H -2.54065 4.08630 -2.09884
Supporting Information S 46
H -4.95529 4.20473 -1.65898
H -5.25199 -0.06680 -2.09029
H -6.33834 2.13591 -1.64649
C 2.82551 2.18157 -1.10071
C 5.45370 1.50377 -0.34747
C 3.35128 0.91446 -1.39790
C 3.63877 3.10009 -0.42125
C 4.94371 2.76861 -0.04982
C 4.65236 0.57825 -1.02094
H 2.74375 0.17214 -1.91027
H 3.24640 4.08699 -0.18349
H 5.55867 3.49895 0.47053
H 5.03059 -0.41530 -1.24341
H 6.46627 1.23874 -0.05472
C -3.72324 -1.86113 1.20903
C -5.18748 -3.59825 -0.46033
C -5.08581 -1.64353 0.96098
C -3.10403 -2.96531 0.60122
C -3.82894 -3.82481 -0.22455
C -5.81458 -2.50315 0.13563
H -5.58314 -0.79304 1.42266
H -2.04318 -3.14362 0.75477
H -3.32757 -4.66991 -0.68854
H -6.87168 -2.31729 -0.03731
H -5.75051 -4.26895 -1.10384
C 0.42568 0.91113 3.44644
C 2.15307 3.10382 3.87289
C -0.00476 2.03973 4.16074
C 1.74388 0.90246 2.95797
C 2.59792 1.98586 3.16238
C 0.85099 3.12360 4.37379
H -1.01085 2.07842 4.56774
H 2.10304 0.03800 2.40385
H 3.60627 1.95569 2.76017
H 0.49604 3.98333 4.93652
H 2.81694 3.94792 4.03905
H 0.36197 -2.83655 -4.20894
H -2.07251 2.09159 2.10856
H -2.75782 1.53838 0.57659
C 3.01199 -2.94445 -0.85249
C 4.18943 -3.56032 -1.32070
C 5.25689 -3.83695 -0.46688
C 5.17614 -3.52178 0.89188
C 4.00825 -2.93516 1.38216
C 2.94351 -2.65735 0.52416
H 4.25333 -3.84909 -2.36545
H 6.14899 -4.31744 -0.86223
H 6.00476 -3.74365 1.55963
H 3.92458 -2.69229 2.43938
H 2.04062 -2.19857 0.91690
C 1.87544 -2.62936 -1.76994
C 0.50401 -2.62117 -1.19526
H -0.24731 -2.81545 -1.97203
H 0.39389 -3.39731 -0.42605
C 2.14363 -2.33188 -3.06905
H 3.17832 -2.27051 -3.39882
C 1.09111 -2.01983 -4.09743
Supporting Information S 47
H 1.53551 -1.83766 -5.08214
H 0.50222 -1.12617 -3.82930
(R,S)-TS4-cis Charge: 0
Multiplicity: 1
Imaginary Frequencies: 1
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2930.608476
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2929.797083
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2930.358773
Total Gibbs Free Energy: -2929.54738
Geometry:
C -2.13672 -1.56366 2.82431
C -3.38693 -1.03327 2.46022
C -4.19201 -0.38535 3.39865
C -3.76929 -0.25394 4.72355
C -2.53252 -0.77977 5.10185
C -1.72693 -1.42479 4.16219
H -3.72117 -1.12410 1.43290
H -5.15579 0.01562 3.09364
H -4.39992 0.24644 5.45390
H -2.19651 -0.69632 6.13264
H -0.77561 -1.85001 4.46966
C -1.25130 -2.25662 1.83804
C 0.08952 -1.82997 1.77215
H 0.82543 -2.50858 1.34254
H 0.46079 -1.21588 2.59073
C -1.78159 -3.22564 0.95245
H -1.00699 -3.78686 0.42648
C -2.99979 -4.06378 1.27059
H -2.72779 -4.93659 1.88547
H -3.47219 -4.45376 0.36155
Cu 0.11412 -0.33178 0.20308
H -3.76425 -3.50912 1.82025
C -6.10064 -2.62625 -2.17023
C -5.13021 -3.61579 -2.34773
C -3.81664 -3.38839 -1.93861
C -3.44932 -2.17065 -1.34112
C -4.42907 -1.17335 -1.18774
C -5.74197 -1.40387 -1.59236
H -7.12461 -2.80138 -2.48967
H -5.39653 -4.56348 -2.80915
H -3.06074 -4.15648 -2.08967
H -4.13193 -0.21560 -0.77156
H -6.48919 -0.62331 -1.46965
C -2.04395 -1.91891 -0.94701
O -1.65590 -0.73142 -0.68695
H -1.31904 -2.62785 -1.37902
P 0.77415 1.82059 0.79106
C 1.78408 1.95626 2.41652
C 1.46608 3.35430 2.98720
C 0.00303 3.66118 2.65664
C -0.18391 3.43166 1.13755
H 1.66480 3.38778 4.06555
H 2.10178 4.11749 2.52172
H -0.27651 4.68685 2.92561
Supporting Information S 48
H -0.66153 2.99102 3.21721
P 1.75851 -0.35397 -1.49515
C 1.06358 -0.19873 -3.26911
C 2.14336 -0.80397 -4.18649
C 2.73066 -2.01456 -3.45512
C 3.15135 -1.54788 -2.04011
H 1.72269 -1.07485 -5.16296
H 2.94577 -0.07947 -4.37453
H 3.58764 -2.44585 -3.98636
H 1.97365 -2.80569 -3.37867
H 1.29442 1.21689 3.06244
H 0.36725 4.22462 0.61401
C 2.74458 1.21720 -1.20451
H 3.21552 1.55855 -2.13498
H 3.54948 0.92889 -0.51830
C 1.92357 2.36532 -0.58735
H 0.21118 -0.88976 -3.25326
H 4.04967 -0.92641 -2.14862
C 0.52629 1.17336 -3.61929
C -0.53725 3.72529 -4.18454
C -0.75864 1.53484 -3.17508
C 1.26338 2.11366 -4.35478
C 0.73585 3.37710 -4.63623
C -1.28278 2.79749 -3.45156
H -1.33768 0.82410 -2.58996
H 2.25271 1.86528 -4.72707
H 1.32302 4.08612 -5.21476
H -2.27259 3.05624 -3.08673
H -0.94730 4.70729 -4.40582
C 3.46935 -2.66852 -1.07513
C 4.11979 -4.78229 0.67781
C 2.52307 -3.65414 -0.75094
C 4.74446 -2.76348 -0.50044
C 5.06979 -3.80901 0.36725
C 2.84343 -4.69963 0.11483
H 1.52195 -3.59919 -1.17100
H 5.49289 -2.01085 -0.73873
H 6.06816 -3.86407 0.79411
H 2.09349 -5.44949 0.35239
H 4.36914 -5.59793 1.35105
C -1.62496 3.47547 0.67762
C -4.32620 3.66914 -0.10251
C -2.06779 4.53287 -0.12953
C -2.55910 2.51016 1.08397
C -3.89598 2.60865 0.69919
C -3.40576 4.63231 -0.51794
H -1.35693 5.29004 -0.45390
H -2.24390 1.66636 1.69139
H -4.60112 1.85078 1.02929
H -3.72686 5.46395 -1.14021
H -5.36886 3.74325 -0.40022
C 3.24335 1.56977 2.30796
C 5.94054 0.75719 2.07208
C 4.25359 2.49453 1.99742
C 3.61894 0.22989 2.50566
C 4.94859 -0.17465 2.38675
C 5.58650 2.09358 1.88132
Supporting Information S 49
H 4.00880 3.54251 1.85227
H 2.85659 -0.50477 2.75184
H 5.20559 -1.21911 2.53906
H 6.34918 2.83152 1.64563
H 6.97840 0.44694 1.98491
H 2.59701 3.16159 -0.24727
H 1.26372 2.79815 -1.34820
(R,R)-TS4-cis Charge: 0
Multiplicity: 1
Imaginary Frequencies: 1
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2930.608944
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2929.798154
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2930.358754
Total Gibbs Free Energy: -2929.547964
Geometry:
C 1.45161 3.73579 -1.11082
C 1.41546 4.32123 0.16672
C 2.48926 5.07224 0.64897
C 3.62259 5.26729 -0.14275
C 3.67340 4.69721 -1.41696
C 2.60469 3.93313 -1.88968
H 0.53401 4.18684 0.78641
H 2.43761 5.50944 1.64315
H 4.45548 5.85899 0.22763
H 4.54464 4.85319 -2.04888
H 2.64660 3.49951 -2.88492
C 0.30234 2.95207 -1.66937
C 0.55707 1.60991 -2.08562
H -0.09012 1.22767 -2.87769
H 1.60726 1.34461 -2.21855
C -0.96469 3.53904 -1.74257
H -1.70136 2.96333 -2.30184
C -1.22709 5.02498 -1.71184
H -1.24308 5.43905 -2.73216
H -2.20289 5.25780 -1.26880
P -0.40762 -1.98526 -1.10594
C 0.69395 -2.45848 -2.60738
C -0.18511 -3.34425 -3.52560
C -1.65830 -2.99876 -3.26993
C -1.85261 -3.03746 -1.73647
H 0.09764 -3.20427 -4.57585
H -0.03162 -4.40519 -3.29683
H -2.33596 -3.70370 -3.76642
H -1.89904 -1.99760 -3.65264
P 1.08378 -0.48194 1.40893
C -0.02391 -0.07425 2.92230
C 0.93473 0.43147 4.03067
C 2.21444 0.97098 3.37292
C 2.67565 -0.11220 2.37451
H 0.43763 1.18993 4.64728
H 1.20933 -0.38848 4.70404
H 2.99657 1.17752 4.11334
H 2.01458 1.91224 2.84395
H 0.83355 -1.49347 -3.10689
Supporting Information S 50
H -1.62691 -4.06675 -1.42043
Cu 0.02136 0.30244 -0.51384
C 1.23013 -2.34026 1.22887
H 1.27333 -2.82102 2.21343
H 2.20674 -2.48541 0.75000
C 0.13059 -2.99562 0.37678
H -0.60226 0.77927 2.55448
H 2.87238 -1.02123 2.96075
C -1.01217 -1.15837 3.29671
C -2.89464 -3.18513 3.86623
C -2.29304 -1.14137 2.71727
C -0.69574 -2.21379 4.16697
C -1.62796 -3.21420 4.45187
C -3.22264 -2.14440 2.99404
H -2.55085 -0.34205 2.02705
H 0.28363 -2.26160 4.63531
H -1.36054 -4.01746 5.13399
H -4.19987 -2.11242 2.52026
H -3.61854 -3.96495 4.08732
C 3.91926 0.18495 1.56927
C 6.29215 0.70059 0.13592
C 3.99526 1.26259 0.67310
C 5.05184 -0.62814 1.72867
C 6.22913 -0.37543 1.02246
C 5.17061 1.51636 -0.03530
H 3.13402 1.90580 0.52120
H 5.01151 -1.46770 2.41962
H 7.09453 -1.01698 1.16878
H 5.20337 2.35843 -0.71982
H 7.20732 0.90540 -0.41380
C -3.25111 -2.71143 -1.25110
C -5.90173 -2.22734 -0.41910
C -4.17373 -3.76260 -1.12260
C -3.67791 -1.41056 -0.94796
C -4.99207 -1.17449 -0.53353
C -5.48682 -3.52739 -0.71575
H -3.85602 -4.77971 -1.34483
H -2.98071 -0.57911 -0.99682
H -5.29800 -0.16047 -0.29074
H -6.18146 -4.35869 -0.62459
H -6.92224 -2.03776 -0.09632
C 2.06820 -2.98553 -2.25425
C 4.65109 -3.86911 -1.52360
C 2.31630 -4.33810 -1.96914
C 3.14612 -2.08834 -2.16683
C 4.42151 -2.51983 -1.80154
C 3.59354 -4.77571 -1.61188
H 1.51159 -5.06550 -2.02934
H 2.97736 -1.03549 -2.37990
H 5.23057 -1.79894 -1.72799
H 3.75974 -5.82949 -1.40249
H 5.64385 -4.21059 -1.24311
H -0.46415 5.57639 -1.15556
H 0.44359 -4.00259 0.07669
H -0.78407 -3.10103 0.97337
C -5.83947 4.25351 -0.29131
C -4.89323 4.83574 0.55416
Supporting Information S 51
C -3.62788 4.26248 0.68822
C -3.29134 3.09320 -0.01337
C -4.25276 2.51434 -0.86143
C -5.51117 3.09237 -1.00152
H -6.82440 4.69986 -0.39904
H -5.13969 5.73677 1.10999
H -2.89356 4.71668 1.35017
H -3.99272 1.61684 -1.41291
H -6.24167 2.63915 -1.66716
C -1.96105 2.47721 0.17426
O -1.76232 1.24638 -0.03700
H -1.28662 3.02444 0.85050
(S,R)-TS4-cis Charge: 0
Multiplicity: 1
Imaginary Frequencies: 1
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2930.609002
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2929.796618
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2930.362463
Total Gibbs Free Energy: -2929.550079
Geometry:
C -0.34687 3.52713 -1.56252
C 0.62081 4.25142 -2.27852
C 1.12008 5.46154 -1.79156
C 0.67339 5.96368 -0.56735
C -0.28303 5.24986 0.15848
C -0.79282 4.04822 -0.33664
H 0.96598 3.86816 -3.23499
H 1.85390 6.01501 -2.37288
H 1.06272 6.90382 -0.18536
H -0.63873 5.63236 1.11224
H -1.53839 3.50007 0.22778
C -0.88245 2.24718 -2.12390
C 0.04374 1.21288 -2.36366
H -0.24160 0.43739 -3.07622
H 1.10122 1.47385 -2.37344
C -2.27538 2.09122 -2.31827
H -2.52491 1.23983 -2.95398
C -3.21014 3.26739 -2.50155
H -3.10180 3.71526 -3.50222
H -4.25667 2.96040 -2.40228
P 0.46336 -2.23654 -0.92196
C 1.77618 -2.72951 -2.21994
C 1.47166 -4.20003 -2.55800
C -0.05072 -4.32854 -2.65210
C -0.66643 -3.71905 -1.36690
H 1.97023 -4.50418 -3.48694
H 1.84004 -4.86300 -1.76512
H -0.37339 -5.36956 -2.77272
H -0.41169 -3.78193 -3.53210
P 1.27159 -0.06238 1.43760
C 0.10964 0.08180 2.95363
C 0.90682 0.85491 4.02907
C 1.88220 1.79676 3.31214
C 2.65029 0.93997 2.27971
Supporting Information S 52
H 0.22558 1.39587 4.69733
H 1.48350 0.16498 4.65687
H 2.57940 2.27739 4.00906
H 1.33520 2.59883 2.79930
H 1.50061 -2.12336 -3.09389
H -0.52629 -4.43992 -0.55175
Cu -0.01052 0.02826 -0.55509
C 2.01908 -1.78104 1.45418
H 2.20538 -2.11921 2.48067
H 2.99394 -1.67178 0.96426
C 1.17270 -2.83205 0.71241
H -0.67559 0.73954 2.56691
H 3.24635 0.20949 2.84451
C -0.55639 -1.20923 3.38131
C -1.85483 -3.61966 4.07866
C -1.79916 -1.55095 2.81901
C 0.01955 -2.10045 4.30094
C -0.62264 -3.29216 4.64658
C -2.44020 -2.74181 3.16252
H -2.24803 -0.87586 2.09553
H 0.97419 -1.86739 4.76433
H -0.15845 -3.96222 5.36608
H -3.40115 -2.97890 2.71340
H -2.35599 -4.54434 4.35302
C 3.58760 1.70890 1.37627
C 5.39038 3.18390 -0.21244
C 3.11839 2.63681 0.43274
C 4.97323 1.53324 1.50409
C 5.86942 2.26317 0.72089
C 4.01176 3.36592 -0.35317
H 2.05027 2.78957 0.30420
H 5.35502 0.81930 2.23096
H 6.93932 2.11353 0.84352
H 3.62154 4.07946 -1.07275
H 6.08369 3.75760 -0.82222
C -2.14492 -3.41420 -1.47282
C -4.91837 -2.94487 -1.69874
C -3.05161 -3.99940 -0.57789
C -2.65537 -2.58011 -2.48002
C -4.02660 -2.35101 -2.59573
C -4.42452 -3.76722 -0.68578
H -2.67726 -4.64775 0.21116
H -1.97603 -2.10001 -3.18009
H -4.39840 -1.70719 -3.38877
H -5.10729 -4.23586 0.01831
H -5.98640 -2.76704 -1.78931
C 3.19887 -2.37272 -1.84676
C 5.81759 -1.60373 -1.12656
C 4.10872 -3.30913 -1.33387
C 3.63379 -1.04510 -2.00174
C 4.92387 -0.66035 -1.64075
C 5.40644 -2.92845 -0.98001
H 3.81683 -4.34816 -1.21620
H 2.94424 -0.30502 -2.40037
H 5.22629 0.37677 -1.75112
H 6.09543 -3.67403 -0.59096
H 6.82481 -1.30759 -0.84645
Supporting Information S 53
H -3.03687 4.06232 -1.77091
H 1.75729 -3.75030 0.57194
H 0.29914 -3.09298 1.32148
C -6.20291 2.92868 1.19512
C -6.35256 2.15432 0.04165
C -5.25355 1.49162 -0.50307
C -3.98322 1.59202 0.08950
C -3.85060 2.35638 1.26118
C -4.94730 3.02288 1.80356
H -7.05830 3.44582 1.62185
H -7.32771 2.06356 -0.43055
H -5.37543 0.87755 -1.39284
H -2.88066 2.40046 1.74656
H -4.82731 3.61099 2.71034
C -2.83637 0.84286 -0.48079
O -1.78856 0.64124 0.22588
H -3.12211 0.07931 -1.21474
(S,S)-TS4-cis Charge: 0
Multiplicity: 1
Imaginary Frequencies: 1
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2930.613378
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2929.801701
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2930.362479
Total Gibbs Free Energy: -2929.550803
Geometry:
C 1.50500 0.58558 -3.49403
C 2.62392 1.37451 -3.17153
C 2.83232 2.61983 -3.76771
C 1.92799 3.10777 -4.71336
C 0.81703 2.33408 -5.05672
C 0.60954 1.09272 -4.45348
H 3.33623 1.00766 -2.43921
H 3.70386 3.20864 -3.49212
H 2.09122 4.07470 -5.18203
H 0.11235 2.69349 -5.80275
H -0.24799 0.49182 -4.74221
C 1.24496 -0.73808 -2.84277
C -0.06320 -0.95803 -2.32957
H -0.38229 -1.99317 -2.22012
H -0.85044 -0.30210 -2.69952
C 2.27071 -1.68212 -2.68860
H 1.93500 -2.65018 -2.31914
C 3.52217 -1.74614 -3.53038
H 3.40106 -2.47547 -4.34640
H 4.39324 -2.07938 -2.95129
Cu -0.04861 -0.34750 -0.28993
H 3.77165 -0.78796 -3.99409
C 5.66862 -4.42142 0.10882
C 6.07641 -3.16116 -0.33298
C 5.13833 -2.14223 -0.50215
C 3.77785 -2.36589 -0.23091
C 3.38036 -3.63631 0.22397
C 4.31599 -4.65309 0.38670
H 6.39766 -5.21648 0.24113
Supporting Information S 54
H 7.12579 -2.97031 -0.54311
H 5.46028 -1.15777 -0.83505
H 2.33115 -3.80208 0.44800
H 3.99528 -5.63144 0.73652
C 2.79731 -1.27112 -0.37527
O 1.67043 -1.32493 0.19913
H 3.21968 -0.29413 -0.64897
P -0.65578 1.84438 0.24335
C -1.68434 2.71060 -1.12707
C -1.30279 4.20658 -1.06270
C 0.15790 4.29861 -0.60955
C 0.28100 3.44796 0.67624
H -1.46497 4.68604 -2.03568
H -1.93068 4.73768 -0.33702
H 0.46419 5.33370 -0.41546
H 0.82387 3.90562 -1.38850
P -1.61862 -1.14132 1.29064
C -0.92251 -1.84870 2.92031
C -2.03954 -2.74520 3.48485
C -2.65531 -3.48859 2.29608
C -3.02485 -2.43692 1.21914
H -1.64895 -3.43307 4.24542
H -2.81664 -2.13978 3.96923
H -3.53996 -4.07060 2.58132
H -1.92672 -4.19922 1.88550
H -1.24789 2.29803 -2.04400
H -0.32292 3.93929 1.45144
C -2.59132 0.38492 1.79177
H -3.03087 0.25904 2.78934
H -3.42076 0.44804 1.07769
C -1.77061 1.68699 1.74536
H -0.11232 -2.50051 2.56875
H -3.92685 -1.91256 1.56001
C -0.30834 -0.81779 3.84261
C 0.89914 1.13454 5.48310
C 0.99279 -0.35487 3.57626
C -0.98811 -0.28680 4.94883
C -0.38933 0.67910 5.76276
C 1.58832 0.61267 4.38463
H 1.52904 -0.74902 2.71636
H -1.98761 -0.63310 5.19402
H -0.93308 1.06985 6.61940
H 2.58941 0.96311 4.15102
H 1.36477 1.88499 6.11656
C -3.30809 -3.02001 -0.14785
C -3.88968 -4.16110 -2.66088
C -2.32908 -3.73124 -0.86011
C -4.58016 -2.88934 -0.72204
C -4.87129 -3.45356 -1.96657
C -2.61599 -4.29686 -2.10209
H -1.32864 -3.83207 -0.44652
H -5.35287 -2.34276 -0.18563
H -5.86719 -3.34378 -2.38868
H -1.84178 -4.84115 -2.63642
H -4.11244 -4.60234 -3.62861
C 1.68709 3.29470 1.20918
C 4.32207 3.11722 2.19775
Supporting Information S 55
C 2.03340 3.86010 2.44421
C 2.68589 2.63390 0.47760
C 3.98895 2.54581 0.96647
C 3.33801 3.77595 2.93587
H 1.27285 4.37590 3.02646
H 2.43787 2.18448 -0.47935
H 4.74763 2.02760 0.38537
H 3.58347 4.22721 3.89396
H 5.33880 3.04993 2.57561
C -3.16102 2.37640 -1.13091
C -5.89300 1.64396 -1.14005
C -4.10859 3.10158 -0.39005
C -3.61874 1.28067 -1.88257
C -4.96474 0.91406 -1.88612
C -5.45800 2.74127 -0.39530
H -3.80079 3.96351 0.19435
H -2.90724 0.70543 -2.46889
H -5.28378 0.05699 -2.47287
H -6.17020 3.32454 0.18299
H -6.94355 1.36591 -1.14506
H -2.44279 2.54998 1.82505
H -1.08841 1.72530 2.60307
(R,S)-TS4-trans Charge: 0
Multiplicity: 1
Imaginary Frequencies: 1
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2930.611382
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2929.796959
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2930.367314
Total Gibbs Free Energy: -2929.552890
Geometry:
P 0.02846 -2.06334 -1.10793
C 1.19305 -2.45901 -2.57929
C 0.62749 -3.73345 -3.23803
C -0.89794 -3.65403 -3.15038
C -1.25813 -3.37012 -1.67423
H 0.98099 -3.82540 -4.27250
H 0.96712 -4.62995 -2.70484
H -1.38229 -4.57705 -3.49116
H -1.26988 -2.84406 -3.79097
P 1.29015 -0.34494 1.44358
C 0.11649 -0.22068 2.95991
C 0.97909 0.29129 4.13916
C 2.15345 1.09805 3.57307
C 2.79592 0.22096 2.47976
H 0.36590 0.88333 4.82899
H 1.37993 -0.54922 4.71714
H 2.88725 1.35327 4.34707
H 1.79255 2.04336 3.14764
H 0.99935 -1.62073 -3.26037
H -1.01104 -4.27220 -1.09918
Cu 0.06248 0.27435 -0.48899
C 1.74165 -2.14995 1.20556
H 1.89394 -2.63744 2.17608
H 2.71380 -2.12718 0.69683
Supporting Information S 56
C 0.73676 -2.96546 0.37574
H -0.56037 0.58222 2.65225
H 3.14588 -0.69728 2.97192
C -0.73458 -1.44375 3.23023
C -2.37825 -3.69952 3.66092
C -2.02180 -1.51788 2.67032
C -0.28869 -2.52528 4.00757
C -1.10125 -3.64083 4.22142
C -2.83422 -2.63241 2.88316
H -2.37405 -0.69785 2.04989
H 0.69788 -2.50285 4.46215
H -0.73506 -4.46204 4.83270
H -3.82284 -2.66499 2.43441
H -3.01248 -4.56532 3.83301
C 3.97359 0.81155 1.74209
C 6.23294 1.87618 0.42505
C 3.97846 2.13416 1.27336
C 5.12588 0.03705 1.53919
C 6.24473 0.56032 0.88938
C 5.09341 2.66003 0.61994
H 3.10640 2.76151 1.42802
H 5.14901 -0.98815 1.90191
H 7.12706 -0.05982 0.75345
H 5.07277 3.68588 0.26204
H 7.10321 2.29002 -0.07721
C -2.71782 -3.05680 -1.43549
C -5.47123 -2.57701 -1.05304
C -3.48539 -3.88271 -0.60201
C -3.35682 -1.98238 -2.07207
C -4.71788 -1.74322 -1.88390
C -4.84911 -3.64856 -0.41127
H -3.01013 -4.72237 -0.09971
H -2.78530 -1.31989 -2.71535
H -5.18852 -0.90166 -2.38483
H -5.42421 -4.30816 0.23380
H -6.53275 -2.39338 -0.91001
C 2.67297 -2.45083 -2.26566
C 5.43517 -2.34743 -1.68558
C 3.36788 -3.59862 -1.85222
C 3.39565 -1.25175 -2.38604
C 4.75835 -1.19663 -2.09611
C 4.73449 -3.54813 -1.56706
H 2.84903 -4.54818 -1.76100
H 2.87755 -0.35185 -2.70804
H 5.28927 -0.25350 -2.18629
H 5.25089 -4.45319 -1.25696
H 6.49871 -2.30924 -1.46601
H -2.44986 1.71159 -3.65084
H 1.19051 -3.91872 0.07711
H -0.13700 -3.20345 0.99355
C 0.25201 4.02504 -1.44885
C -0.19068 5.30836 -1.82085
C 0.49863 6.45567 -1.42810
C 1.65246 6.35227 -0.64987
C 2.11333 5.08638 -0.28176
C 1.42620 3.93982 -0.68005
H -1.06976 5.40595 -2.45022
Supporting Information S 57
H 0.13611 7.43237 -1.73918
H 2.18955 7.24504 -0.34025
H 3.01096 4.99448 0.32503
H 1.79003 2.95995 -0.39030
C -0.48704 2.80247 -1.88491
C 0.23594 1.60456 -2.16034
H -0.23887 0.92784 -2.87259
H 1.30535 1.72018 -2.33690
C -1.88661 2.86459 -1.90173
H -2.35040 3.83470 -1.75656
C -2.71894 1.81873 -2.58815
H -3.78432 2.06299 -2.53391
H -2.57453 0.83974 -2.11265
C -6.21211 3.29339 0.86565
C -5.19561 4.24805 0.97262
C -3.86777 3.87912 0.76893
C -3.53374 2.55165 0.45347
C -4.55906 1.59683 0.35691
C -5.88753 1.96893 0.55795
H -7.24834 3.57939 1.02666
H -5.43998 5.27858 1.21801
H -3.07625 4.62175 0.84995
H -4.29521 0.56949 0.12718
H -6.67399 1.22183 0.48088
C -2.11149 2.16372 0.27469
O -1.77051 0.94105 0.24909
H -1.38430 2.92275 0.59886
(R,R)-TS4-trans Charge: 0
Multiplicity: 1
Imaginary Frequencies: 1
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2930.611444
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2929.798900
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2930.367450
Total Gibbs Free Energy: -2929.554905
Geometry:
Cu 0.12346 -0.51163 -0.08473
H -0.31344 -4.79968 -1.43623
C -2.39239 -2.75945 1.60957
C -3.38589 -3.73126 1.82207
C -4.32255 -3.59665 2.84707
C -4.29303 -2.48236 3.68717
C -3.31230 -1.50708 3.49253
C -2.37445 -1.64671 2.47019
H -3.40868 -4.61431 1.19054
H -5.07466 -4.36831 2.99155
H -5.02392 -2.37534 4.48456
H -3.28273 -0.63010 4.13543
H -1.62848 -0.87520 2.30807
C -1.37462 -2.92559 0.52917
C -0.05122 -2.48043 0.77268
H 0.74059 -2.91988 0.16750
H 0.23245 -2.34767 1.81666
C -1.81354 -3.38969 -0.72042
H -2.81981 -3.79205 -0.77504
Supporting Information S 58
C -0.85235 -3.89800 -1.76702
H -1.37911 -4.15385 -2.69402
H -0.09216 -3.14575 -2.01669
C -6.60316 -1.59535 -1.71800
C -5.84106 -2.14694 -2.75114
C -4.44974 -2.06849 -2.71063
C -3.79521 -1.43751 -1.64020
C -4.57023 -0.88266 -0.60838
C -5.96077 -0.96554 -0.64719
H -7.68803 -1.65534 -1.74667
H -6.33145 -2.63446 -3.59016
H -3.85850 -2.49595 -3.51846
H -4.07043 -0.40860 0.22902
H -6.54727 -0.54122 0.16401
C -2.31240 -1.34542 -1.63847
O -1.70953 -0.43130 -0.99023
H -1.83593 -1.74772 -2.54677
P 1.94838 0.13479 -1.42163
C 1.44715 0.90981 -3.09852
C 2.60822 0.60508 -4.06642
C 3.16920 -0.77226 -3.69486
C 3.46884 -0.74468 -2.17880
H 2.26815 0.64658 -5.10851
H 3.40780 1.34863 -3.96266
H 4.07623 -1.01637 -4.26080
H 2.43118 -1.55228 -3.92259
P 0.55696 1.36670 1.32330
C 1.25998 0.84472 3.03176
C 0.67699 1.84328 4.05955
C -0.68131 2.32609 3.53683
C -0.45521 2.78580 2.07742
H 0.60044 1.37527 5.04845
H 1.33732 2.71163 4.17031
H -1.08646 3.14628 4.14156
H -1.42080 1.51430 3.56291
H 0.59244 0.29049 -3.39749
H 4.30353 -0.04736 -2.02678
C 1.88379 2.33908 0.42817
H 2.48002 2.93313 1.13110
H 1.32728 3.04280 -0.20237
C 2.81605 1.48302 -0.44557
H 0.77538 -0.12413 3.19798
H 0.23153 3.64328 2.12090
C 2.75487 0.61226 3.07053
C 5.53541 0.10558 3.06244
C 3.25738 -0.67936 2.83879
C 3.67930 1.64364 3.30393
C 5.05318 1.39346 3.30172
C 4.62953 -0.93189 2.83087
H 2.56169 -1.49548 2.65939
H 3.33132 2.65420 3.49797
H 5.74669 2.20887 3.49137
H 4.98655 -1.94029 2.64182
H 6.60472 -0.08825 3.06345
C -1.70564 3.23712 1.34972
C -4.05926 4.17203 0.11134
C -2.57488 2.34715 0.70267
Supporting Information S 59
C -2.03282 4.60252 1.35668
C -3.19810 5.06892 0.74762
C -3.74022 2.81256 0.08857
H -2.32997 1.29185 0.63716
H -1.36490 5.30845 1.84692
H -3.43003 6.13091 0.76736
H -4.39175 2.10437 -0.41614
H -4.96726 4.53007 -0.36708
C 3.85854 -2.06914 -1.56265
C 4.65277 -4.53189 -0.43566
C 5.06410 -2.18490 -0.85559
C 3.05780 -3.21435 -1.69410
C 3.44836 -4.43172 -1.13684
C 5.46034 -3.40250 -0.29748
H 5.70294 -1.31146 -0.74446
H 2.11771 -3.15545 -2.23413
H 2.80901 -5.30310 -1.25040
H 6.40377 -3.46749 0.23884
H 4.95781 -5.48130 -0.00405
C 0.95793 2.34001 -3.00674
C -0.02499 4.97105 -2.73468
C 1.78249 3.44631 -3.26106
C -0.37263 2.57846 -2.61822
C -0.85783 3.87862 -2.47800
C 1.29459 4.74938 -3.12954
H 2.81210 3.30240 -3.57481
H -1.02225 1.73408 -2.39965
H -1.88438 4.03475 -2.15932
H 1.95065 5.59059 -3.33944
H -0.40294 5.98454 -2.62976
H 3.39480 2.13127 -1.11523
H 3.53308 0.95047 0.19162
(S,S)-TS4-trans Charge: 0
Multiplicity: 1
Imaginary Frequencies: 1
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2930.606880
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2929.794693
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2930.367316
Total Gibbs Free Energy: -2929.555128
Geometry:
P 2.20956 0.68322 -1.01515
C 1.94002 1.86016 -2.51049
C 3.27211 1.87195 -3.29305
C 3.91803 0.49334 -3.13506
C 3.95088 0.18051 -1.62131
H 3.09926 2.13253 -4.34450
H 3.95389 2.62834 -2.88654
H 4.92955 0.45895 -3.55745
H 3.32653 -0.26827 -3.66045
P 0.04857 1.07388 1.46760
C 0.46705 0.00805 3.00566
C -0.23084 0.69081 4.20028
C -1.53109 1.31422 3.68581
C -1.15886 2.17925 2.46030
Supporting Information S 60
H -0.40817 -0.03128 5.00651
H 0.39758 1.48683 4.61761
H -2.02783 1.92638 4.44820
H -2.23753 0.52594 3.39732
H 1.20690 1.31080 -3.11313
H 4.64687 0.89094 -1.15462
Cu 0.00067 -0.32484 -0.43834
C 1.46206 2.28774 1.24969
H 1.80428 2.64487 2.22906
H 1.01536 3.14404 0.73013
C 2.66350 1.76184 0.44541
H -0.06489 -0.92390 2.78437
H -0.53143 3.00195 2.82917
C 1.93383 -0.33424 3.16720
C 4.66463 -1.02099 3.36658
C 2.44601 -1.46244 2.50206
C 2.81727 0.43854 3.93699
C 4.16885 0.09746 4.03747
C 3.79610 -1.79992 2.59733
H 1.77501 -2.06223 1.89243
H 2.45802 1.31146 4.47428
H 4.83179 0.70800 4.64579
H 4.16992 -2.66860 2.06305
H 5.71586 -1.28574 3.44452
C -2.32854 2.79724 1.73015
C -4.55790 4.03639 0.52012
C -3.42149 2.03668 1.28556
C -2.37181 4.18689 1.54192
C -3.47052 4.80318 0.94009
C -4.52738 2.65100 0.69707
H -3.41700 0.95677 1.40190
H -1.53664 4.79525 1.88193
H -3.48023 5.88275 0.81288
H -5.36992 2.04211 0.38304
H -5.42229 4.51165 0.06424
C 4.41388 -1.21945 -1.28590
C 5.36245 -3.81900 -0.74527
C 5.65743 -1.41902 -0.67029
C 3.65192 -2.34775 -1.62391
C 4.11889 -3.63406 -1.35592
C 6.13122 -2.70536 -0.40310
H 6.26337 -0.55676 -0.40018
H 2.67981 -2.21802 -2.09022
H 3.50781 -4.49250 -1.62186
H 7.10070 -2.83526 0.07127
H 5.72742 -4.82167 -0.53906
C 1.33337 3.20694 -2.17918
C 0.11988 5.67434 -1.52464
C 2.10861 4.32464 -1.82974
C -0.06363 3.35812 -2.19871
C -0.66595 4.57305 -1.87209
C 1.50933 5.54458 -1.50770
H 3.19228 4.25465 -1.81404
H -0.68451 2.50718 -2.46748
H -1.74883 4.65651 -1.88657
H 2.13356 6.39570 -1.24717
H -0.34540 6.62440 -1.27598
Supporting Information S 61
H 0.19700 -3.60802 -3.41373
H 3.29477 2.60386 0.13563
H 3.27634 1.11426 1.08324
C -3.22723 -1.62108 -2.17691
C -4.17325 -2.53752 -2.67300
C -5.52391 -2.20682 -2.77718
C -5.96888 -0.93929 -2.40105
C -5.04475 -0.01264 -1.91376
C -3.69753 -0.35028 -1.79563
H -3.84163 -3.51107 -3.01894
H -6.22606 -2.93777 -3.17075
H -7.01909 -0.67412 -2.49269
H -5.37171 0.98325 -1.62809
H -2.99756 0.37643 -1.39536
C -1.77269 -1.95919 -2.15750
C -0.81530 -0.90808 -2.30739
H 0.13597 -1.21443 -2.74501
H -1.19061 0.01493 -2.75128
C -1.38572 -3.28745 -1.95657
H -2.16842 -4.03738 -1.89908
C -0.01715 -3.79077 -2.34917
H 0.06771 -4.87027 -2.17848
H 0.77425 -3.30007 -1.76911
C -4.81467 -3.43036 2.13114
C -4.22737 -4.56999 1.57280
C -2.97414 -4.48521 0.97089
C -2.28592 -3.26258 0.91344
C -2.88006 -2.12703 1.48448
C -4.13571 -2.20980 2.08409
H -5.79199 -3.49461 2.60211
H -4.74661 -5.52429 1.61129
H -2.51625 -5.37359 0.53967
H -2.33902 -1.18723 1.44602
H -4.58836 -1.32190 2.51967
C -0.93034 -3.20164 0.31237
O -0.15576 -2.21384 0.47162
H -0.48333 -4.18714 0.11196
(S,R)-TS4-trans Charge: 0
Multiplicity: 1
Imaginary Frequencies: 1
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2930.617667
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2929.807125
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2930.372190
Total Gibbs Free Energy: -2929.561648
Geometry:
Cu 0.12307 -0.46790 0.12110
H -0.83448 -4.56094 -0.81903
C -2.14772 -2.38123 2.52241
C -3.22125 -3.18576 2.94789
C -3.88327 -2.93865 4.15088
C -3.48913 -1.87946 4.97008
C -2.41842 -1.07572 4.57257
C -1.75895 -1.32568 3.36916
H -3.52005 -4.03645 2.34355
Supporting Information S 62
H -4.70344 -3.58508 4.45357
H -4.00285 -1.68760 5.90839
H -2.09609 -0.24932 5.20215
H -0.93283 -0.69127 3.06452
C -1.42469 -2.66572 1.24518
C -0.03997 -2.33489 1.14622
H 0.53834 -2.91420 0.42797
H 0.48890 -2.20593 2.09099
C -2.16251 -3.15255 0.16170
H -3.19544 -3.43813 0.33062
C -1.49934 -3.71758 -1.06302
H -2.23970 -4.07189 -1.78675
H -0.88313 -2.95409 -1.56105
C -5.81575 -2.15212 -3.36650
C -6.07463 -2.01007 -1.99922
C -5.04908 -1.64887 -1.12891
C -3.74731 -1.42512 -1.60832
C -3.49929 -1.56025 -2.98395
C -4.52543 -1.92477 -3.85387
H -6.61546 -2.43276 -4.04695
H -7.07722 -2.17959 -1.61457
H -5.24831 -1.54156 -0.06443
H -2.49675 -1.36909 -3.35284
H -4.32158 -2.02708 -4.91700
C -2.67441 -1.01013 -0.67417
O -1.55737 -0.59081 -1.09880
H -3.01637 -0.71944 0.32689
P 1.76870 0.05158 -1.51517
C 1.06378 0.60595 -3.20551
C 2.11827 0.19828 -4.25392
C 2.74209 -1.12018 -3.78757
C 3.19974 -0.92093 -2.32253
H 1.66544 0.11284 -5.24962
H 2.90822 0.95596 -4.32743
H 3.58772 -1.42565 -4.41548
H 1.99841 -1.92584 -3.83912
P 0.65658 1.52379 1.23083
C 1.64711 1.36955 2.86422
C 1.31167 2.63799 3.67367
C -0.16531 2.95603 3.42499
C -0.37944 2.99083 1.89321
H 1.53308 2.49320 4.73842
H 1.91737 3.48721 3.33390
H -0.46539 3.91013 3.87465
H -0.79807 2.17987 3.87416
H 0.19833 -0.05783 -3.31818
H 4.05853 -0.23647 -2.33462
C 1.79783 2.44097 0.05321
H 2.42349 3.15660 0.60142
H 1.12779 3.02268 -0.59070
C 2.68537 1.53031 -0.81577
H 1.16300 0.52138 3.36509
H 0.12610 3.88837 1.51327
C 3.10843 1.01485 2.69006
C 5.80472 0.26507 2.30573
C 3.46938 -0.33200 2.51216
C 4.13038 1.97672 2.67773
Supporting Information S 63
C 5.46442 1.60556 2.48976
C 4.79884 -0.70479 2.31751
H 2.69426 -1.09424 2.51706
H 3.89569 3.02636 2.82619
H 6.23795 2.36944 2.49198
H 5.04473 -1.75240 2.17021
H 6.84281 -0.02216 2.16125
C -1.82771 3.05828 1.46012
C -4.53988 3.28502 0.71736
C -2.75550 2.06484 1.81085
C -2.28604 4.16327 0.72895
C -3.62818 4.27867 0.35959
C -4.09667 2.17776 1.44479
H -2.43405 1.19074 2.36975
H -1.58341 4.94470 0.44800
H -3.95975 5.14837 -0.20222
H -4.79619 1.39618 1.72930
H -5.58515 3.37122 0.43317
C 3.62146 -2.19170 -1.61841
C 4.46589 -4.57586 -0.36881
C 4.93911 -2.34036 -1.16386
C 2.73210 -3.26266 -1.43384
C 3.14882 -4.44151 -0.81620
C 5.36084 -3.52014 -0.54556
H 5.64463 -1.52343 -1.29953
H 1.70138 -3.17131 -1.76563
H 2.44121 -5.25510 -0.68077
H 6.39007 -3.61359 -0.20792
H 4.78977 -5.49540 0.11122
C 0.54927 2.02894 -3.25383
C -0.48731 4.65523 -3.27870
C 1.33550 3.11090 -3.68054
C -0.76871 2.29005 -2.83972
C -1.28085 3.58751 -2.85064
C 0.82223 4.41049 -3.69381
H 2.35466 2.94828 -4.01901
H -1.38400 1.46391 -2.49281
H -2.30096 3.76071 -2.52001
H 1.44874 5.23057 -4.03599
H -0.88721 5.66582 -3.29493
H 3.14843 2.12156 -1.61533
H 3.49653 1.11065 -0.20900
Copper alkoxide (S,R)-III Charge: 0
Multiplicity: 1
Imaginary Frequencies: 0
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2930.637277
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2929.826084
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2930.391069
Total Gibbs Free Energy: -2929.579875
Geometry:
Cu -0.28765 0.12500 0.00053
H 3.74476 3.38091 1.33925
C 6.20355 0.80930 0.47153
C 6.52732 1.82917 -0.44076
Supporting Information S 64
C 7.72303 1.80162 -1.15814
C 8.61988 0.74453 -0.99186
C 8.30731 -0.28404 -0.10066
C 7.11443 -0.25130 0.62047
H 5.84690 2.66555 -0.57473
H 7.95456 2.60935 -1.84816
H 9.54795 0.71820 -1.55705
H 8.98888 -1.12175 0.02540
H 6.86319 -1.07025 1.28760
C 4.95026 0.86506 1.27684
C 4.97701 0.52535 2.57662
H 4.08320 0.55160 3.19410
H 5.89658 0.22734 3.07254
C 3.03864 2.54232 1.29839
H 2.13762 2.85236 0.76493
H 2.75566 2.30270 2.33139
C 4.26555 -3.27873 -1.58969
C 4.23150 -3.24791 -0.19415
C 3.69009 -2.14249 0.47048
C 3.18001 -1.04946 -0.24228
C 3.21344 -1.09763 -1.64305
C 3.75235 -2.19714 -2.31148
H 4.68696 -4.13557 -2.10973
H 4.62869 -4.08260 0.37985
H 3.67308 -2.12326 1.55773
H 2.79671 -0.26175 -2.19710
H 3.77299 -2.21212 -3.39905
C 2.59096 0.17677 0.46391
O 1.48699 0.67791 -0.21546
H 2.34531 -0.13143 1.50087
P -2.00724 0.82059 -1.42130
C -2.25132 -0.19762 -3.02421
C -2.68561 0.82544 -4.09787
C -1.99841 2.15805 -3.77524
C -2.30140 2.47654 -2.29107
H -2.43480 0.46099 -5.10139
H -3.77208 0.97379 -4.07450
H -2.34837 2.97129 -4.42191
H -0.91343 2.07493 -3.92138
P -1.80001 -0.75053 1.44435
C -1.87242 0.19543 3.10483
C -2.22618 -0.86689 4.16729
C -1.56102 -2.18209 3.73950
C -1.98443 -2.44645 2.27421
H -1.90184 -0.54207 5.16332
H -3.31113 -1.02085 4.21857
H -1.85504 -3.02173 4.38020
H -0.46824 -2.09636 3.80397
H -1.22850 -0.51317 -3.26240
H -3.37874 2.67940 -2.21477
C -3.47045 -0.55914 0.60991
H -4.26992 -0.47895 1.35607
H -3.62328 -1.49932 0.06580
C -3.54756 0.62789 -0.37183
H -0.82522 0.48084 3.26085
H -3.06353 -2.65279 2.28484
C -2.68750 1.46992 3.05878
Supporting Information S 65
C -4.14772 3.87643 2.83958
C -2.07920 2.64771 2.58992
C -4.04076 1.52708 3.42453
C -4.76228 2.71927 3.31922
C -2.79946 3.83628 2.47415
H -1.02970 2.62782 2.30412
H -4.54240 0.64208 3.80501
H -5.80788 2.74013 3.61593
H -2.30596 4.72679 2.09515
H -4.71114 4.80190 2.75685
C -1.29456 -3.60867 1.59232
C -0.05655 -5.82681 0.37230
C 0.05413 -3.55665 1.20699
C -2.00901 -4.79210 1.35521
C -1.39738 -5.89461 0.75480
C 0.66669 -4.65313 0.59904
H 0.63045 -2.64833 1.36077
H -3.05594 -4.85101 1.64612
H -1.96973 -6.80361 0.58675
H 1.70644 -4.57732 0.29422
H 0.42139 -6.68039 -0.10119
C -1.55482 3.66806 -1.72734
C -0.21587 5.95707 -0.77490
C -2.24386 4.87155 -1.51692
C -0.17944 3.62471 -1.44372
C 0.48012 4.76231 -0.97458
C -1.58405 6.00847 -1.04591
H -3.31019 4.91953 -1.72924
H 0.38111 2.69941 -1.55444
H 1.54271 4.70787 -0.75568
H -2.13888 6.93103 -0.89427
H 0.30372 6.83848 -0.40829
C -3.08643 -1.44881 -2.86344
C -4.57388 -3.81734 -2.46863
C -4.48149 -1.45979 -3.02045
C -2.45395 -2.65261 -2.50832
C -3.18617 -3.82301 -2.30811
C -5.21675 -2.63190 -2.82834
H -5.00665 -0.55213 -3.30365
H -1.37366 -2.66971 -2.38314
H -2.66923 -4.73482 -2.02333
H -6.29528 -2.61585 -2.96360
H -5.14748 -4.72825 -2.32000
H -4.44796 0.53848 -0.99072
H -3.62646 1.56764 0.18823
C 3.66129 1.32406 0.59672
H 3.89284 1.61146 -0.43555
Reductive coupling product (S,R)-V Charge: 0
Multiplicity: 1
Imaginary Frequencies: 0
Electronic Energy (B3LYP/6-31G(d)-SDD(Cu)): -2930.637277
Gibbs Free Energy (B3LYP/6-31G(d)-SDD(Cu)): -2929.826084
Electronic Energy (M06-2X/6-311+G(d,p)-SDD(Cu)/SMD(toluene)): -
2930.391069
Total Gibbs Free Energy: -2929.579875
Supporting Information S 66
Geometry:
C 3.02951 -0.56781 0.21408
C 2.85539 -0.31793 -1.15901
C 3.95492 -0.20298 -2.00975
C 5.25190 -0.34653 -1.51200
C 5.43980 -0.60391 -0.15255
C 4.34096 -0.71465 0.69914
H 1.85191 -0.17996 -1.54913
H 3.79744 0.00308 -3.06561
H 6.10705 -0.26414 -2.17768
H 6.44375 -0.72946 0.24519
H 4.49237 -0.93937 1.75122
C 1.86442 -0.66604 1.13693
C 1.90580 -0.09191 2.34845
H 1.07818 -0.16127 3.04920
H 2.75833 0.49842 2.67081
C 0.64147 -1.47039 0.67788
H 0.83680 -1.84202 -0.33463
C 0.42524 -2.69546 1.58626
H 1.34241 -3.29107 1.63949
H -0.37806 -3.33561 1.20864
H 0.16765 -2.39439 2.60854
C -4.10849 -2.78897 -0.75771
C -4.02242 -2.34836 0.56322
C -2.90257 -1.63008 0.98981
C -1.85384 -1.34583 0.10808
C -1.95174 -1.79025 -1.21910
C -3.06931 -2.50584 -1.64898
H -4.97941 -3.34576 -1.09321
H -4.82838 -2.55693 1.26199
H -2.84520 -1.28151 2.01856
H -1.15115 -1.56230 -1.91745
H -3.13029 -2.84357 -2.68051
C -0.62730 -0.58445 0.58245
O -0.33035 0.48593 -0.32725
H -0.83296 -0.16758 1.57573
Si -0.84026 2.05451 -0.16525
C 0.28068 3.06987 -1.26125
H 0.16453 2.80081 -2.31760
H 0.06828 4.14072 -1.16512
H 1.32802 2.90153 -0.98969
O -2.43851 2.27351 -0.55087
O -0.73437 2.44230 1.43683
C -3.03638 1.95528 -1.79777
H -4.07640 2.29541 -1.77235
H -2.53030 2.45983 -2.63310
H -3.02550 0.87343 -1.97714
C -1.42743 3.50834 2.06831
H -2.49940 3.47941 1.84240
H -1.28709 3.40958 3.14944
H -1.02688 4.48295 1.75683
Supporting Information S 67
IX. References
(1) Prudent Practices in the Laboratory: Handling and Management of chemical
Hazards/Committee on Prudent Practices in the Laboratory: An Update. Board on
Chemical Sciences and Technology, Division of Earth and Life Studies, National
Research Council of the National Academies. Washington, D.C.: National Academies
Press, 2011.
(2) Fiorito, D.; Folliet, S.; Liu, Y.; Mazet, C. A General Nickel-Catalyzed Kumada
Vinylation for the Preparation of 2-Substituted 1,3-Dienes. ACS Catal. 2018, 8, 1392–
1398.
(3) Nguyen, K. D.; Herkommer, D.; Krische, M. J. Enantioselective Formation of All-
Carbon Quaternary Centers via C–H Functionalization of Methanol: Iridium-Catalyzed
Diene Hydrohydroxymethylation. J. Am. Chem. Soc. 2016, 138, 14210–14213.
(4) Smith, A. B.; Kim, W.-S.; Tong, R. Uniting Anion Relay Chemistry with Pd-
Mediated Cross Coupling: Design, Synthesis and Evaluation of Bifunctional Aryl and
Vinyl Silane Linchpins. Org. Lett. 2010, 12, 588–591.
(5) Neese, F. The ORCA Program System. WIREs Comput. Mol. Sci. 2012, 2, 73–78.
(6) Frisch, M. J. et al., Gaussian 03, Revision C.02. Gaussian, Inc., Wallingford CT
(2010).
(7) Legault, C. Y. CYLView, 1.0b. University of Sherbrooke, Quebec, Canada (2009).
(8) Zhao, Y.; Truhlar, D. G. The M06 suite of density functionals for main group
thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and
transition elements: two new functionals and systematic testing of four M06-class
functionals and 12 other functionals. Theor. Chem. Acc. 2008, 120, 215–241.
(9) Zhao, Y.; Truhlar, D. G. Density Functionals with Broad Applicability in Chemistry.
Acc. Chem. Res. 2008, 41, 157–167.
(10) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. Universal Solvation Model Based on
Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk
Dielectric Constant and Atomic Surface Tensions. J. Phys. Chem. B 2009, 113, 6378–
6396.
download fileview on ChemRxivSI-Main Text-final.pdf (1.23 MiB)
Compiled NMR Spectra For
Engaging Aldehydes in CuH-Catalyzed Reductive Coupling Reactions:
Stereoselective Allylation from 1,3-Diene Pronucleophiles
Chengxi Li,† Kwangmin Shin,† Richard Y. Liu, and Stephen L. Buchwald*
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139,
United States
*Correspondence to: [email protected].
download fileview on ChemRxivSI-NMR Spectra-final.pdf (5.19 MiB)
Compiled SFC, GC and HPLC Traces for
Engaging Aldehydes in CuH-Catalyzed Reductive Coupling Reactions:
Stereoselective Allylation from 1,3-Diene Pronucleophiles
Chengxi Li,† Kwangmin Shin,† Richard Y. Liu, and Stephen L. Buchwald*
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139,
United States
*Correspondence to: [email protected].
(1)
(2)
(3)
(4)
(5)
(6)
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(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(18)
(19)
(20)
minor diastereomer (mixture)
minor diastereomer (mixture)
(P1)
download fileview on ChemRxivSI-SFC, GC and HPLC Traces-final.pdf (2.06 MiB)