843–850.pdf

7/23/2019 843850.pdf

1/8

Evolution of Structure and Reactivity in a Series of Iconic Carbenes

Min Zhang,

Robert A. Moss,*

Jack Thompson,

and Karsten Krogh-Jespersen*

Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08903,United States

*S Supporting Information

ABSTRACT: We present experimental activation parameters for the reactions of six carbenes (CCl2, CClF,CF2, ClCOMe, FCOMe, and (MeO)2C) with six alkenes (tetramethylethylene, cyclohexene,1-hexene, methyl acrylate, acrylonitrile, and -chloroacrylonitrile). Activation energies range from1 kcal/mol for the addition of CCl2 to tetramethylethylene to 11 kcal/mol for the addition of FCOMeto acrylonitrile. A generally satisfactory analysis of major trends in the evolution of carbenic structure andreactivity is afforded by qualitative applications of frontier molecular orbital theory, although the observedentropies of activation appear to fall in a counterintuitive pattern. An analysis of computed cyclopropanationtransition state parameters reveals significant nucleophilic selectivity of (MeO)2C toward -chloroacrylonitrile.

1. INTRODUCTION

The correlation of structure and reactivity has been central tothe study of carbenes, since the early experiments of Hine,1

Doering,2 and Skell,3 and the theoretical considerations ofHoffmann4 and Houk.5 Our efforts in this endeavor have beenreviewed several times.6,7 Of particular interest has been the[1 + 2] cycloaddition of singlet carbenes to alkenes, wherein themeasurement and calculation of rates and activation parametershas continued to engage many investigators. Early studies ofarylhalocarbene additions to alkenes by laser flash photolysis(LFP) revealed that activation energies and enthalpies were

very low or even negative.

810

More generally, we may ask whatare the magnitudes of these parameters and how do they evolveas functions of carbene and alkene structures? Prior to 2007,the absence of conveniently obtained and appropriateprecursors for LFP studies of, e.g., the iconic dihalocarbenesprecluded experimental answers to these questions, but manypredictions were made.

On the basis ofrelativeactivation parameters, Skell concludedthat CCl2 additions to monoalkylethylenes were enthalpy-controlled but that entropic factors would dominate additionsto more highly alkylated olefins.11 Giese agreed that entropywould dominate CCl2 additions but suggested that enthalpywould control CF2 additions.

12 Houk offered a variationaltransition-state model that highlighted entropic factors in theadditions of reactive carbenes.13 His calculations supported theconclusions of Giese: CCl2 additions should lack enthalpicbarriers and be S-dominated, whereas CF2 additions wouldbeH-controlled.13Jorgensen also predicted entropic controlof CCl2additions.

14

Our recent syntheses of dichlorodiazirine (1),15 chloro-fluorodiazirine (2),16 and difluorodiazirine (3),17 coupled withthe availability of chloromethoxydiazirine (4),18 fluorome-thoxydiazirine (5),19 and dimethoxydiazirine (6),20 provideLFP precursors for six key carbenes (CCl2, ClCF, CF2,ClCOMe, FCOMe, and (MeO)2C), thus enabling a broadsurvey of activation parameters for carbene additions to alkenes.Our concerns include the dependence ofH, S, and G

on carbenic structure and stability and alkene structure, as wellas the possible operation of compensationbetween H andS, i.e. reciprocal behavior of H and S, a suspectedphenomenon in carbene additions.11

We have published several letters and communications

describing relevant data for CCl2,21

FCCl,21

CF2,17

ClCOMe,22

and FCOMe.23 In this full paper, we integrate the priorinformation, add new experimental and computational resultsfor (MeO)2C, and provide a synoptic discussion of the additionreactions of all six carbenes. Our strategy focuses on the threeevolutionary carbene sequences shown in Scheme 1, where

the substituent changes modulate decreases in carbenicelectrophilicity and concomitant increases in stability andnucleophilicity as one moves from left to right across eachsequence.

Received: November 14, 2011Published: December 28, 2011

Scheme 1. Three Evolutionary Carbene Sequences

Featured Article

pubs.acs.org/joc

2011 American Chemical Society 843 dx.doi.org/10.1021/jo2023558|J. Org. Chem. 2012, 77, 843850
http://localhost/var/www/apps/conversion/tmp/scratch_1/pubs.acs.org/jochttp://localhost/var/www/apps/conversion/tmp/scratch_1/pubs.acs.org/joc

7/23/2019 843850.pdf

2/8

2. THE CARBENES

The literature contains a number of parameters designed tomeasure carbenic reactivity, philicity, and stability; three ofthem are set out in Table 1 for the carbenes of Scheme1.5,24

The computed carbene LUMO energies, LUMO, increase fromCCl2 to (MeO)2C, reflecting increasingly potent electrondonation by each carbenes substituents into its formally vacantp (LUMO) orbital; cf. resonance hybrid7. This is accompanied

by decreasing carbenic electrophilicity as -electron donationfrom alkene reaction partners becomes energetically lesscompetitive. The same trend in LUMO is manifested at boththe HF/4-31G//STO-3G and the B3LYP/6-311++G(2d,p)levels. As anticipated, the LUMO energies are less positive(more negative) in the DFT than in the HF calculations.

The carbene HOMO () orbital energies in Table1 are notas regular in their dependence on the carbenic substituents. Inpart, these orbital energies are influenced by the electro-negativity of the carbenic substituents; viz. HOMOdecreases as

F replaces Cl (HOMO CCl2 > ClCF > CF2, and ClCOMe >FCOMe). The HOMO energies are less negative in the DFTthan in the HF calculations, as expected.

The CCl2 to (MeO)2C progression is accompanied by ageneral increase in Estab, a quantitative measure of carbenicstability relative to methylene, defined as the negative of thecomputed HF/4-31G//STO-3G [or B3LYP/6-311++G(2d,p)]energies of the isodesmic reactions defined in eq 1.5 As thecarbenes become more stable, we can anticipate an increase inthe activation energies for their additions to alkenes. Note thatthe predicted B3LYP stabilization energies are uniformly largerthan the HF/4-31G//STO-3G values. There are indications ofadditional stabilization (relative to the prior values), whenthe carbene contains a Cl atom. This most likely reflects

the particular inadequacy of the 4-31G (and STO-3G) basis setfor Cl.

+ + +

:CH CH X CH Y :CXY 2CHE

2 3 3 4stab

(1)

Table1 also contains the carbene selectivity indices, mCXY.24

These are empirical reactivity indices that reflect the selectivityof the carbene toward a standard set of alkylethylenes, rela-tive to the selectivity of CCl2. The mCXY index can be calcu-lated for a given carbene from eq2, where x,y represents thesum of theappropriateconstants for the X and Y substituentsof CXY.6,24 As mCXY increases, the carbenes philicity changesfrom electrophilic (CCl2, ClCF, CF2) to ambiphilic (ClCOMe)

to nucleophilic (FCOMe, (MeO)2C).6

= + +m 1.10 0.53CXY X,Y R X,Y I (2)

The literature also contains other parameters intended tocharacterize carbenic reactivity and philicity. Examples includeN, which tracks charge transfer between a carbene and analkene;25 the computed electron affinity and ionizationpotential of the carbene, which are related to the carbenesLUMO and HOMO orbital energies;26 and , the global

electrophilicity index of the carbene.27a Each of theseparameters correlates reasonably well with mCXY, leading tosimilar characterizations of carbenic philicity. We also note thenewly introduced carbene stabilization energies (CSE), basedon calculated heats of hydrogenation, as a measure of carbenicstability.27b The CSE tracks reasonably well with Estab.

5

3. THE ALKENES

The six carbenes of Scheme 1 span a broad range of stabilityand philicity (Table 1), so that we require a set of alkenereaction partners with a comparably wide range of electronicproperties. We chose three electron rich alkylethenes andthree electron deficient alkenes substituted with electronwithdrawing substituents. These substrates are shown in

Table 2, together with their derived (HOMO) and *

(LUMO) orbital energies from both experiment (i.e., valenceionization energies and vertical electron affinities, respec-tively)2833 and B3LYP/6-311++G(2d,p) computations (thiswork).

Trends are readily apparent in Table 2. From tetramethyl-ethylene (TME) to acrylonitrile (ACN), decreases as thealkenes electrons become more strongly bound.34 In thisorder, the alkenes become poorer electron donors, less nucleo-philic, and poorer substrates for electrophilic carbenes like CCl2.

6

Table 1. Quantitative Measures of Carbenic Reactivity

carbene LUMO,a,b eV HOMO,

a,b eV Estab,a,c kcal/mol mCXY

calcdd

CCl2 0.31 (3.74) 11.44 (7.50) 26.5 (45.5) 0.97

ClCF 1.03 (3.39) 11.98 (8.09) 42.8 (56.1) 1.22

CF2 1.89 (2.83) 13.38 (8.77) 62.8 (70.9) 1.47

ClCOMe 2.46 (1.91) 10.82 (6.97) 60.3 (72.7) 1.59

FCOMe 3.19 (1.36) 11.81 (7.36) 74.2 (84.1) 1.85

(MeO)2C 4.09 (0.42) 10.81 (6.37) 79.8 (92.0) 2.22aData from ref5. bHF/4-31G//STO-3G orbital energy. Orbital energies in parentheses are recalculated atthe B3LYP/6-311++G(2d,p) level (this

work). cDefined as the negative of the reaction energy of eq1computed at the HF/4-31G//STO-3G level.5Values in parentheses are computed atthe B3LYP/6-311++G(2d,p) level (this work). dCalculated carbene selectivity index from ref24.

Table 2. Experimental and Computed Orbital Energies (eV)of Alkenesa

alkene (HOMO) *(LUMO)

Me2CCMe2 8.27b (6.19) 2.27c (0.28)

cyclohexene 8.94b (6.66) 2.07c (0.28)

CH2CH-n-C4H9 9.48d(7.78) 1.84e (0.33)

CH2CHCOOMe 10.72f(7.85) 0.8f(1.69)

CH2CHCN 10.92g(8.26) 0.21c (1.99)

CH2CClCN 10.58g(8.15) 0.35h (2.31)

aValues in parentheses are computedorbital energies at the B3LYP/6-311++G(2d,p) level (this work). See theSupporting Informationfor

details. b

Reference28. c

Reference29. d

Reference30. e

Reference31.fReference32. gReference33. hEstimated fromHF/4-31G//STO-3Gcomputed energies scaled to the measured value29 for CH2CHCN.

The Journal of Organic Chemistry Featured Article

dx.doi.org/10.1021/jo2023558|J. Org. Chem. 2012, 77, 843850844

7/23/2019 843850.pdf

3/8

In contrast, as * decreases from TME through -chloro-acrylonitrile (ClACN), the alkenes become better electronacceptors, more electrophilic, and better substrates for nucleo-philic carbenes like (MeO)2C.

6 These reactivity trends can beconveniently interpreted by frontier molecular orbitaltheory,5,6,35 according to which stabilization of the cyclo-addition transition state (TS) depends inversely on the

magnitude of the differential energy () of the principalinteracting orbitals.36 In the case of a carbene-alkene cyclo-addition, these are the carbene p (LUMO) interacting with thealkene (HOMO), and the carbene (HOMO) interactingwith the alkene*(LUMO); cf. Figure1.5,6b,7 Orbital overlapis neglected in this qualitative analysis.

A smaller results in greater TS stabilization, lower Ea, anda faster addition reaction. The differentialenergies of the orbitalinteractions are expressed by eqs3 and4.6b IfE< N, thecarbene p/alkene orbital interaction will dominate the TS,charge transfer will be directed from alkene to carbene, andthe carbene will behave as an electrophile. IfN < E, thecarbene /alkene * orbital interaction will be dominant,charge will be transferred from the carbene to the alkene in theTS, and the carbene will behave as a nucleophile. IfE N,neither orbital interaction will dominate and the carbene will bean ambiphile, capable of strong interactions with either electron

rich alkenes(as an electrophile) or electron poor alkenes (as anucleophile).6

= = = pE CXY LU

C CHO

(3)

= = * =N C CLU

CXYHO

(4)

In any given pairing of a carbene from Table 1with an alkenefrom Table2, a qualitative estimate of carbenic reactivity andphilicity can be obtained by inserting the relevant orbitalenergies into eqs3and 4 and comparing the resultant EandN, cf. Tables S-1S-3 in the Supporting Information. Wecan thus rationalize the generally observed electrophilicity ofCCl2, nucleophilicity of (MeO)2C, and ambiphilicity of

ClCOMe.5,6,24

4. CARBENEALKENE ADDITIONS

Reactions of the six carbenes of Table 1with the six alkenes ofTable2would generate 36 sets of rate constants and activationparameters. However, not all of the carbene-alkene pairingslead to experimentally usable results. CCl2, the least stabilizedand most electrophilic ofthe carbenes, does afford quantitativeresults with all six alkenes,16a,37 but the more stabilized and lesselectrophilic ClCF and CF2 react well only with the mostelectron rich alkenes of Table 2 (TME, cyclohexene, and1-hexene). Their reactions with the electron poor alkenes,methyl acrylate (MeAcr), ACN, and ClACN, are too slow to

give good LFP data and too inefficient, compared to sidereactions, to yield decent relative rate data.

Similarly, the three more stable and more nucleophiliccarbenes (ClCOMe, FCOMe, and (MeO)2C) react well onlywith the more electrophilic, electron-poor alkenes of Table2(MeAcr, ACN, and ClACN), while reacting poorly or not at allwith the electron-rich alkenes TME, cyclohexene, and 1-hexene.

Indeed, with (MeO)2C, the most stable and most nucleophilicof our six carbenes, we could obtain usable data only withClACN, the most electrophilic of the alkenes.38,39

Thus, of 36 potential sets of carbenealkene additionreaction kinetics data, we could obtain only 19 usable data sets.Nevertheless, these results permit us to draw useful conclusionsconcerning the evolution of carbenic structure and reactivityacross the six carbenes of Scheme1 and Table1.

5. DIMETHOXYCARBENE

We measured kabs (kabs = the absolute rate constant for thebimolecular addition reaction) forthe addition of (MeO)2CtoClACN by LFP. LFP at 351 nm40 of dimethoxydiazirine639 inpentane (A

350 = 0.7) afforded (MeO)

2C, which absorbed as

reported39 at 255 nm. This p absorption was calculated toappear at 262 and 275 nm, respectively, for the cis, trans,and trans, trans conformers of (MeO)2C.

39 LFP at 25.1 Cgiveskabs= 5.01 10

5 M1 s1 for the addition of (MeO)2C toClACN, wherekabsderives from a correlation of the observedrate constants for the disappearance of the carbenes absorptionat 255 nm vs the concentration of ClACN in pentane at fiveconcentrations between 0.0 and 1.34 M ClACN; cf. Figure 2.

We previously (1988) measured this rate constant as 5.0 105

M1 s1.39

Next, kabs was similarly determined at an additional fourtemperatures between 272 and 303 K; cf. Figures S-1S-4 intheSupporting Information.An Arrhenius plot of ln kabsvs 1/Tappears in Figure3, where kabsvaries from 1.56 10

5 to 6.18 105 M1 s1 across a temperature range of 272.8303.3 K. Theslope and intercept of the least-squares correlation line afford

Ea= 7.44 kcal/mol, log A= 11.15 M1 s1, and S = 9.49 eu.

A second, independent determination of these parameters isillustrated by Figures S-5S-9 in the Supporting Information,leading to the Arrhenius correlation of Figure S-10, from which

Figure 1. Frontier molecular orbital interactions in carbene/alkeneadditions. Reprinted with permission from ref7.

Figure 2.LFP determination ofkabs for the addition of (MeO)2C toClACN at 298.2 K in pentane: kabs for carbene decay at 255 nm vs[ClACN]. kabs= 5.01 10

5 M1 s1, r= 0.997.



7/23/2019 843850.pdf

4/8

Ea= 7.50 kcal/mol, log A= 11.19 M1 s1, and S = 9.26 eu.

Average values of the activation parameters from the two

determinations areEa= 7.47 0.03 kcal/mol, log A = 11.7 0.02 M1 s1, and S = 9.38 0.12 eu.

Unfortunately, we could not obtain a good linear fit forkinetics experiments of (MeO)2C with ACN. The addition rateconstant at room temperature is 1.0 104 M1 s1, but thecarbene reacts too slowly to permit an adequate Arrheniusstudy.

Thermolysisof dimethoxydiazirine in ClACN gave a mixtureof ring-opened39 Zand E--cyanoacrylic acid methyl esters (8)with an E/Z ratio of 3:1, eq5. The NMR spectrum of the

mixture appears in the Supporting Information. Analogousreactions of (MeO)2C with MeAcr and ACN gave mixtures ofthe appropriate cyclopropanes and their ring-opened products.Stirring with small quantities of silica gel converted thesemixtures to ring-opened derivatives 9 and 10, respectively.39

We attempted to determine the reactivity of (MeO)2Ctoward MeACr and ACN, relative to ClACN, by competitionreactions with binary alkene mixtures. However, the productmixtures contained many byproducts (as well as 8,9, and10),and usable data could not be obtained.

6. DISCUSSION

The experimental activation parameters available to assess theevolutionary carbenesequences of Scheme 1are set out inTables35.7,17,2123,37 Consider first Table3 and sequenceAof Scheme1: CCl2, ClCF, and CF2. In the same order, LUMO,Estab, and mCXYincrease (Table1), and the carbenes becomemore stable and less reactive toward the electron rich alkenes ofTable2. These trends are regular, in part, because all nineaddition reactions of Table 3 are electrophilic, i.e., E LUMO (CCl2). In contrast,ClCOMe additions to MeAcr, ACN, and ClACN are allcontrolled byN. Now, N for MeOCCl addition to ACN

and ClACN is generally less than either Eor N for CCl2addition, and Ea is either similar (MeAcr) or lower (ACN,ClACN) for MeOCCl addition than for CCl2 addition. Notealso that Ea for CCl2 addition to ClACN is lower than foraddition to ACN, suggesting that these are nucleophilic CCl2additions, a conclusion supported by computational studies.37

Despite these trends in Ea (and H), G for CCl2

additions to all four alkenes is lower than for the analogousClCOMe additions. With TME, this is due to the 7 kcal/moldifference in Ea or H

favoring CCl2. For MeAcr, ACN, orClACN, however, G is lower for CCl2addition because S

favors CCl2over ClCOMe by9 11 eu (3 kcal/mol in theTS contribution to G), more than enough to overcomeany small differences in Ea or H

that favor ClCOMe. The

origin of the unfavorable S

attending the ClCOMe additionsmight reside in the need to restrict rotation of the methoxygroup in the addition TS, and the significantly greater stabilityof ClCOMe vs CCl2 (cf. Estab in Table1). The latter pointsuggests that the TS for ClCOMe addition to a given alkenewill be later, tighter, and more sterically demanding than theanalogous CCl2 TS.

Given the greater stability of (MeO)2C vs ClCOMe (Estab 19 kcal/mol), the 3.6 kcal/mol Ea advantage for ClCOMeover (MeO)2C addition to ClACN is understandable. Whatis not clear is why S is 1011 eu more favorable for theaddition of the more stable, more sterically demanding(MeO)2C. This entropy advantage makes (MeO)2C addition

to ClACN only marginally less favorable in G than ClCOMeaddition.

Lastly, we consider Table 5 and carbene sequence C ofScheme 1: ClCOMe, FCOMe, and (MeO)2C. Our analysishere is similar to that of sequence B. FCOMe is more stablethan ClCOMe by 1114 kcal/mol in Estab, and its(nucleophilic) additions to MeAcr, ACN, and ClACN all

have higher Eas than the comparable ClCOMe additions. Onthe other hand, S is more favorable for the FCOMeadditions,41 thus narrowing the differences in G. The latterfavors ClCOMe additions to the alkenes by 12 kcal/mol.For additions to ClACN, Ea increases in the expected order:ClCOMe < FCOMe < (MeO)2C, but S

becomes lessnegative in the same order,41 so that G for the addition of(MeO)2C is actually a bit more favorable than for the additionof FCOMe, and comparable to ClCOMe.

7. TS FOR ADDITION OF (MeO)2C TO ClACN

We have carried out electronic structure calculations (DFTB3LYP/6-311+G(d)) for the (MeO)2C + ClACN additionreaction (see Supporting Information for computationaldetails). The computed TS is shown in Figure4, and pertinent

TS parameters are listed in Table 6. Also included in Table6are analogous computed data for the TSs involving ClACNreacting with CCl2, ClCOMe, and FCOMe (previouslyavailable in the Supporting Information of ref 23). A closerexamination of the structural parameters and the net carbene-alkene charge transfer suggests significant nucleophiliccharacter for the (MeO)2CClACN interaction in the TS.

Figure4and the data in Table6show that in the (MeO)2C +ClACN TS, the approaching carbene is positioned on theoutsideof the unsubstituted alkene C1-atom (angle C3C1C2 = 105.9) with significantly different C(carbene)C-(alkene) distances (C1C3 = 1.989 ; C2C3 = 2.716 ).

Table 4. Activation Parameters for Carbene Additions: Sequence Ba

carbene alkeneb Ea log A H

S TS G

CCl2c,d TME 1.2 8.8 1.8 20 6.0 4.2

ClCOMee TME 5.8 8.0 5.2 24 7.2 12.4

CCl2f MeAcr 6.7 11.0 6.1 9.9 2.9 9.0

ClCOMee MeAcr 7.0 9.0 6.4 19.2 5.7 12.1

CCl2f ACN 6.9 11.0 6.3 9.8 2.9 9.2

ClCOMee ACN 6.4 9.1 5.8 18.9 5.6 11.4CCl2

f ClACN 5.4 11.2 4.8 9.1 2.7 7.5

ClCOMee ClACN 3.9 8.8 3.4 20.2 6.0 9.4

(MeO)2Cg ClACN 7.5 11.2 6.9 9.4 2.8 9.7

aSee footnotea in Table3. bSee footnoteb in Table3. cFrom ref21. dThe negativeEafor CCl2refers to 273 K < T< 304 K.eFrom ref22. fFrom

ref37. gThis work.

Table 5. Activation Parameters for Carbene Additions:Sequence Ca

carbene alkeneb Ea log A H

S TS G

ClCOMec MeAcr 7.0 9.0 6.4 19 5.7 12.1

FCOMed MeAcr 9.7 10.2 9.2 14 4.1 13.2

ClCOMec ACN 6.4 9.1 5.8 19 5.6 11.4

FCOMed

ACN 11.1 11.3 10.5

8.8 2.6 13.2ClCOMec ClACN 3.9 8.8 3.4 20 6.0 9.4

FCOMed ClACN 6.0 9.5 5.4 17 5.1 10.5

(MeO)2Ce ClACN 7.5 11.2 6.9 9.4 2.8 9.7

aSee notea in Table3; H is calculated at 303 K for FCOMe. bSeenoteb in Table3. cFrom ref22. dFrom ref23. eThis work.

Figure 4.Transition state for (MeO)2C addition to ClACN (B3LYP/6-311+G(d)): side view (left, with Me hydrogens omitted for clarity)and top view (right, in perspective). Color code: gray = C; red = O;green = Cl; blue = N; white = H.



7/23/2019 843850.pdf

6/8

Incipient bond formation is thus far more pronounced at theunsubstituted carbon, in keeping with the TS possessing somenucleophilic Michael addition character. The increase inC1C2 double bond length from the free alkene to the TSis significant (= 0.055 ), whereas the local geometry of thecarbene hardly changes from that of the free species. Thecarbene tilt angle, , defined as the angle between the bisectorof the XC-Y carbene and the alkene CC bond, is aqualitative indicator of the philicity of the carbene-alkene

addition: for a purely electrophilic carbene attack, would be0, whereas > 45indicates significant nucleophilic character.5

We compute = 65.1 for the (MeO)2C-ClACN TS. Thepuckering angle () at the unsubstituted carbon C1 is 19.1,with the CH2 group bending away from the approachingcarbene; the corresponding puckering angle () at thesubstituted carbon C2 is only about 6and bending is towardthe approaching carbene. The net electron-transfer between(MeO)2C and ClACN (Mulliken population analysis) is 0.16e,

f romthe carbene to the alkene, and the olefin polarizes so thatpartial negative charge is imposed on the C atom bearing theCN substituent and on Cl (relative to the free alkene). The TSstructural parameters just discussed, namely the geometricalrelation of the carbene to the alkene, the large value of the tilt

angle, the distinct asymmetry in C(carbene)C(alkene)distances, and the larger pyramidalization at C1 than at C2,together with the direction of charge transfer, all point to astrong nucleophilic component in the TS for (MeO)2C addingto ClACN.5

According to data presented in Table1, the order of stabilityfor the carbenes considered in Table6is (MeO)2C > FCOMe >ClCOMe CCl2. In keeping with the Hammond principlethat a more stable and less reactive intermediate traverses alater and more product-like TS, the values of, in particular, theCC and parameters in Table 6, clearly show that whenClACN is the alkene, the (MeO)2C and FCOMe TSs are laterthan that of the ClCOMe addition, which, in turn, is later thanthe TS for the CCl2 addition. Making a distinction between

FCOMe and (MeO)2C with respect to lateness

andnucleophilicity on the basis of geometrical TS parameters isperhaps subtle. Thus, both the C1C3 and C2C3 distances,which represent the forming CC bonds, are shorter (moreproduct-like) in the FCOMe TS, suggesting that FCOMe is themore nucleophilic carbene. A slightly larger TS elongationtoward the product C1C2 cyclopropane single bond in the(MeO)2C addition than in the FCOMe addition may pointtoward (MeO)2C being the more nucleophilic species.However, the computed tilt angle () and net charge transferare distinctly larger for the (MeO)2CClACN TS and hencestrongly favor greater nucleophilicity for (MeO)2C. It appearsthat the relatively long CC distances in the (MeO)2C

ClACN TS reflect the steric influence of the two methyl groupsin (MeO)2C, which prevent this carbene from approaching theterminus of the alkene as closely as FCOMe.

Computed activation parameters for ClACN reacting with(MeO)2C are presented in Table7. Also included in Table7

are analogous data for the TSs for ClACN reacting with CCl2,

ClCOMe, and FCOMe (previously available in the SupportingInformation of ref23). The computed activation parameters forthe most stable (MeO)2C conformer (trans, trans)

20 reactingwith ClACN areEa= 10.6 kcal/mol (corresponding to H

=10.0 kcal/mol) and S = 37.5 eu.42 As we observedpreviously,21,23 computed DFT activation parameters, partic-ularlyS, differ significantly from the measured values: Ea =7.5 kcal/mol and S = 9.4 eu for the (MeO)2C/ClACN pair(Table5). Although the experimental ordering ofEa(H

) isgenerally reproduced (MeO)2C > FCOMe > ClCOMe CCl2) and supports the notion expressed above that (MeO) 2Cis a more nucleophilic carbene than FCOMe, the computedEavalue is too low for CCl2 by 4 kcal/mol, whereas withClCOMe, FCOMe, and (MeO)2C the computed Eas are too

large by 34 kcal/mol, even though DFT generally tends tounderestimate reaction barrierheights (including when B3LYPfunctionals are employed).43 Inclusion of general solvationeffects in the calculations via a dielectric continuum modellowers the activation energies only minimally (

7/23/2019 843850.pdf

7/8

(31 to 37 e.u) than the measured values (9 to 24 eu,Tables4and5). As a result, the computed free energy barriers(G) tend to be dominated by their TS components, andare considerably larger than the experimental G values. Thedifferent physical phases used as references for the calculations(idealized gas phase) and the experiments (condensed liquidphase) undoubtedly play a role in the discrepancy. Thereduction in solution reaction entropies, relative to their(hypothetical) gas phase values, is presumably related at leastpartially to translational and rotational motions becoming morerestricted in the condensed phase.44 It appears from a simplecomparison of computed and calculated values that thereduction in S due to different reaction phases could amountto 1525 eu, but there does not appear to be a dependableway of applying a condensed phase correction to thecomputed results, and our current inability to rationalize thevariability and trends in the measured S values furthercomplicates progress in this matter.

We have proposed that precoordination of the carbene to thealkene may occur in some cases with the formation of weaklybound precursor complexes, potentially promoting a change inthe carbene-alkene resting stateand influencing both activationenergy and entropy parameters.21 Unfortunately, as yet we havebeen unable to convincingly demonstrate the viability of thisproposal by experiment or by computation for the presentcarbene-alkene sets, even though we have clearly documentedthe formation of stable complexes from carbenes interactingwith, e.g., aromatic solvent molecules.45 However, we wouldnot anticipate significant complex formation to occur for ahighly stabilized carbene such as (MeO)2C.

We continue to actively investigate the fundamental reasonsfor the discrepancies between measured and calculatedactivation parameters in carbene reactions. Although thepresent discussion has focused on computations using theB3LYP set of hybrid functionals, the discrepancies betweencomputed and measured activation parameters remain whenother functionals21 or even wave function-based methods areemployed. In the Supporting Information (Table S-4) webriefly present additional results for the activation parameterspertaining to the (MeO)2C/ClACN cycloaddition reaction,derived from computations with a number of differentexchange-correlation functionals as well as MP2 and CCSD(T)techniques. Whereas the activation enthalpies obtained spanapproximately a 10 kcal/mol range, the activation entropiesspan a much narrower range of only 5 eu and are always muchmore negative than the observed value. Surely, the potentialenergy surfaces governing reactions of carbenes are exceedinglyintricate.46,47 Perhaps a resolution to most of the disagreementscan be found from detailed considerations of the dynamics inthese reactions47 and studies of reaction trajectories instead of(or in addition to) classicaltransition state theory and potentialenergy surface calculations.7

8. CONCLUSION

In general, over the six carbenes of Table1and the six alkenesof Table2, the evolutionary trends inEaand H

expressed inTables 35 parallel expectations based on consideration ofEstab, E, and N. However, the evolutionary behavior ofS is neither as regular nor as predictable, resulting in somedisorder to otherwise anticipated trends in G. In fact, there issome evidence of the operation of reciprocal behavior ofH

and S. Compelling explanations for this counterintuitive

pattern and the noted discrepancies between computed andmeasured activation parameters are currently lacking.

9. EXPERIMENTAL SECTION

Diazirines. Preparative details have been published in full fordiazirines16. For 3,3-dichlorodiazirine (1), see ref15b. For 3-chloro-3-fluorodiazirine (2), see the Supporting Information of ref16a. For3,3-difluorodiazirine (3), see the Supporting Information of ref17. For

3-chloro-3-methoxydiazirine (4), see refs 18and 48. For 3-fluoro-3-methoxydiazirine (5), see ref19. For 3,3-dimethoxydiazirine (6), seeref49.

Activation Parameters. Activation parameters are collected inTables35. The table notes provide references to the original data forCCl2, ClCF, CF2, ClCOMe, and FCOMe. The (MeO)2C data aredescribed above.

ASSOCIATED CONTENT*S Supporting InformationFigures S-1S-10, NMR spectrum of E,Z-8, Tables S-1S-4,computational details, geometries, and energies of relevantspecies. This material is available free of charge via the Internetathttp://pubs.acs.org.

AUTHOR INFORMATIONCorresponding Author*E-mail: [email protected] (R.A.M.); [email protected](K.K.-J.)

Present AddressesSchool of Chemistry & Chemical Engineering, GuangxiUniversity, 100 Daxue Road, Nanning, 530004, China.Undergraduate exchange student from The University ofManchester, Manchester, England.

ACKNOWLEDGMENTSWe are grateful to the National Science Foundation and to thePetroleum Research Fund for financial support.

REFERENCES(1) Hine, J.; Ehrenson, S. J. J. Am. Chem. Soc.1958, 80, 824.(2) Doering, W. v. E.; Henderson, W. A. Jr. J. Am. Chem. Soc. 1958,

80, 5274.(3) Skell, P. S.; Garner, A. Y. J. Am. Chem. Soc. 1956, 78, 5430.(4) (a) Hoffmann, R.; Zeiss, G. D.; Van Dine, G. W.J. Am. Chem. Soc.

1968, 90, 1485. (b) Hoffmann, R.; Hayes, D. M.; Skell, P. S.J. Phys. Chem.1972, 76, 664.

(5) Rondan, N. G.; Houk, K. N.; Moss, R. A. J. Am. Chem. Soc.1980,102, 1770.

(6) (a) Moss, R. A.Acc. Chem. Res.1980,13, 58. (b) Moss, R. A. Acc.Chem. Res. 1989, 22, 15. (c) Moss, R. A. In Carbene Chemistry,Bertrand, G., Ed.; Dekker: New York, 2002; pp 57f.

(7) Moss, R. A. J. Org. Chem. 2010, 75, 5773.(8) Turro, N. J.; Lehr, G. F.; Butcher, J. A. Jr.; Moss, R. A.; Guo, W.

J. Am. Chem. Soc.1982, 104, 1754.(9) Moss, R. A.; Lawrynowicz, W.; Turro, N. J.; Gould, I. R.; Cha, Y.

J. Am. Chem. Soc.1986, 108, 7028.(10) Gould, I. R.; Turro, N. J.; Butcher, J. Jr.; Hacker, N. P.; Lehr, G.

F.; Moss, R. A.; Cox, D. P.; Guo., W.; Munjal, R. C.; Perez, L. A.;Fedorynski, M. Tetrahedron 1985, 41, 1587.

(11) Skell, P. S.; Cholod, M. S. J. Am. Chem. Soc. 1969, 91, 7131.(12) (a) Giese, B.; Meister, J. Angew. Chem., Int. Ed. Engl. 1978,17,

595. (b) Giese, B.; Lee, W.-B.; Meister, J. Ann.1980, 725. (c) Giese,B.; Lee, W.-B. Chem. Ber. 1981, 114, 3306.

(13) (a) Houk, K. N.; Rondan, N. G.; Mareda, J. Tetrahedron1985,41, 1555. (b) Houk, K. N.; Rondan, N. G.; Mareda, J. J. Am. Chem. Soc.1984, 106, 4291. (c) Houk, K. N.; Rondan, N. G. J. Am. Chem. Soc.1984, 106, 4293.


http://pubs.acs.org/mailto:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]://pubs.acs.org/

7/23/2019 843850.pdf

8/8

(14) Blake, J. F.; Wierschke, S. G.; Jorgensen, W. L. J. Am. Chem. Soc.1989, 111, 1919.

(15) (a) Chu, G.; Moss, R. A.; Sauers, R. R. J. Am. Chem. Soc.2005,127, 14206. (b) Moss, R. A.; Tian, J.; Sauers, R. R.; Ess, D. H.; Houk,K. N.; Krogh-Jespersen, K. J. Am. Chem. Soc. 2007, 129, 5167.

(16) (a) Moss, R. A.; Tian, J.; Sauers, R. R.; Skalit, C.; Krogh-Jespersen, K. Org. Lett. 2007, 9, 4053. (b) Moss, R. A.; Chu, G.;Sauers, R. R. J. Am. Chem. Soc.2005, 127, 2408.

(17) Moss, R. A.; Wang., L.; Krogh-Jespersen, K. J. Am. Chem. Soc.2009, 131, 2128.(18) Graham, W. H. J. Am. Chem. Soc.1965, 87, 4396.(19) Moss, R. A.; Fedorynski, M.; Terpinski, J.; Denney, D. Z.

Tetrahedron Lett.1986, 27, 419.(20) Moss, R. A.; Wlostowski, M.; Shen., S.; Krogh-Jespersen, K.;

Matro, A. J. Am. Chem. Soc. 1988, 110, 4443.(21) Moss, R. A.; Wang., L.; Zhang, M.; Skalit, C.; Krogh-Jespersen,

K.J. Am. Chem. Soc. 2008, 130, 5634.(22) Moss, R. A.; Wang, L.; Zhang, M. Org. Lett.2008, 10, 4045.(23) Moss, R. A.; Zhang, M.; Krogh-Jespersen, K. Org. Lett.2010,12,

3476.(24) Moss, R. A.; Mallon, C. B.; Ho, C.-T.J. Am. Chem. Soc.1977,99,

4105.(25) Mendez, F.; Garcia-Garibay, M. A.J. Org. Chem.1999,64, 7061.(26) Sander, W.; Kotting, C.; Hu bert, R.J. Phys. Org. Chem.2000,13,

561.(27) (a) Perez, P. J. Phys. Chem. A2003, 107, 522. (b) Gronert, S.;

Keeffe, J. R.; More OFerrall, R. A. J. Am. Chem. Soc. 2011,133, 3381.(28) Bieri, G.; Burger, F.; Heilbronner, E.; Maier, J. P. Helv. Chim.

Acta1977, 60, 2213.(29) Jordan, K. D.; Burrow, P. D. Acc. Chem. Res. 1978, 11, 341.(30) Masclet, P.; Grosjean, D.; Mouvier, G.; Dubois, J. J. Electron

Spectrosc. Relat. Phenom. 1973, 2, 225.(31) Kadifachi, S. Chem. Phys. Lett.1984, 108, 233.(32) Houk, K. N.; Sims, J.; Duke, R. E. Jr.; Strozier, R. W.; George, J.

K.J. Am. Chem. Soc. 1973, 95, 7287.(33) Houk, K. N.; Munchausen, L. J. Am. Chem. Soc.1976, 98, 937.(34) -Chloroacrylonitrile ( = 10.58 eV) is a better electron

donor than acrylonitrile (= 10.92 eV) because the formers chlorosubstituent can stabilize positive charge imposed on its olefinic carbon

by resonance donation of chlorine lone pair electrons. A similar effectis observed for vinyl chloride (= 10.15) vs ethene (= 10.52).

33

(35) (a) Houk, K. N. Acc. Chem. Res. 1975, 8, 361. (b) Fleming, I.Frontier Orbitals and Organic Chemical Reactions; Wiley: New York,1976.

(36) Given that DFT calculations tend to not reproduce theactivation parameters of these carbene-alkene addition reactionsreliably,21,23we prefer to use the older, qualitative FMO analysis here.

(37) Moss, R. A.; Zhang, M.; Krogh-Jespersen, K. Org. Lett.2009,11,1947.

(38) Additions of (MeO)2C have been observed with ACN andMeAcr,39 but we could not obtain either satisfactory LFP or relativerate data; see below.

(39) Moss, R. A.; Wlostowski, M.; Shen, S.; Krogh-Jespersen, K.;Matro, A. J. Am. Chem. Soc. 1988, 110, 4443.

(40) We used a XeF2excimer laser emitting 4256 ns pulses at 351nm with 5565 mJ power. For more details, see ref15b.

(41) It is unclear why, yet again, S is more favorable for additionsof the more stable carbene.

(42) The free energy difference between trans, trans and cis, trans(MeO)2C conformers is only 2.2 kcal/mol (B3LYP/6-311+G(d)),suggesting a trans, trans/cis, transconformer ratio near 50 at ambienttemperatures. However, the computed finding of a large barrier forinterconversion of the two species (G = 16.5 kcal/mol) implies thatthe rate for (re)population of the cis, trans conformer is notcompetitive with the measured rate of cycloaddition productformation. It is interesting to note though, that the computedactivation energy for the addition ofcis, trans (MeO)2C to ClACN isonlyEa= 7.2 kcal/mol (H

= 6.6 kcal/mol; S = 33.6 kcal/mol).

(43) Sousa, S. F.; Fernandes, P. A.; Ramos, M. J. J. Phys. Chem. A2007, 111, 10439.

(44) Mammen, M.; Shakhnovich, E. I.; Deutch, J. M.; Whitesides, G.M. J. Org. Chem. 1998, 63, 3821.

(45) See, for example: Wang, L.; Moss, R. A.; Thompson, J.; Krogh-Jespersen, K.Org. Lett. 2011, 13, 1198.

(46) See, for example: Albu, T. V.; Lynch, B. J.; Truhlar, D. G.;Goren, A. C.; Hrovat, D. A.; Borden, W. T.; Moss, R. A. J. Phys. Chem.

A.2002, 106, 532.(47) For the applicationof dynamics methodology to the additions ofCCl2and CF2to ethylene, see: Xu, L.; Doubleday, C. E.; Houk, K. N.

J. Am. Chem. Soc.2011, 133, 17848.(48) Smith, N. P.; Stevens, I. D. R.J. Chem. Soc., Perkin Trans. 2 1979,

213.(49) Du, X.-M.; Fan, H.; Goodman, J. L.; Kesselmayer, M. A.; Krogh-

Jespersen, K.; LaVilla, J. A.; Moss, R. A.; Shen, S.; Sheridan, R. S.J. Am.Chem. Soc. 1990, 112, 1920.



843–850.pdf

Documents

Transcript of 843–850.pdf