Vanadium-Catalyzed Selenide Oxidation with in situ [2,3] Sigmatropic Rearrangement: Scope and...
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![Page 1: Vanadium-Catalyzed Selenide Oxidation with in situ [2,3] Sigmatropic Rearrangement: Scope and Asymmetric Applications Campbell Bourland February 6, 2002.](https://reader035.fdocuments.us/reader035/viewer/2022081603/5697c0281a28abf838cd7168/html5/thumbnails/1.jpg)
Vanadium-Catalyzed Selenide Oxidationwith in situ [2,3] Sigmatropic Rearrangement: Scope and
Asymmetric Applications
Campbell Bourland
February 6, 2002
R' SeR
R'
SeRO
R'
OH
R"
R"R" VO(acac)2,TBHP
CH2Cl2, mol. sieves
-50°C; PBu3
1
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List of Abbreviations
e.e.
d.e.
TBHP
CHP
m-CPBA
acac
TBAF
SOS
ASOS
enantiomeric excess (% major enantiomer - % minor enantiomer)
diastereomeric excess (% major diastereomer - % minor diastereomer)
tert-butyl hydroperoxide
cumene hydroperoxide
meta-chloroperbenzoic acid
acetyl acetonate
tetrabutyl ammoniumfluoride
selenide oxidation with in situ [2,3] sigmatropic rearrangement
asymmetric selenide oxidation in situ [2,3] sigmatropic rearrangement2
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Importance of Allylic Alcohols
Rapamycinprostaglandins
H
H
HO
HO HO H
OH
O
O
O
Me
Me
Me
O
OH
OMe Me Me
OMeHOH
Me
O
N
O
O
OH
OMe
OH
H
Me
3
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Allylic Alcohols Useful as Precursors in Synthesis
Henbest and Wilson’s Asymmetric Epoxdiation:
Corey’s Asymmetric Epoxidation:
OHO
H
OCH3
Me
MeMe
OVO(acac)2
TBHP
OHO
H
OCH3
Me
MeMe
O
O
>20:1
Henbest, H. B.; Wilson, R. A. L. J. Chem. Soc. 1959, 1958.Corey, E. J.; Dittami, J. P. J. Am. Chem. Soc. 1985, 107, 256.
OH
m-CPBA
OH
O
10:1
4
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Application of Selenides to Synthesis
Selenoxide Syn-Elmination to form alkene:
The SOS reaction:
RSe [O]
R'
H
RSe
R'
HOR'
RSe
[O]R"
RSe
R"O OH
R"
SeO
R"
R
Se-O
cleavage
5
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Traditional Methods for Selenide Oxidation
Wirth, T. Tetrahedron 1999, 55, 1.
SePh
H2O2, 0-25°C
THF-MeOH, 71%
OH
Ph SePhm-CPBA, 25°C
MeOH, 90%
Ph
OH
6
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Selenoxide vs. Sulfoxide
Se
R
S
RO
R OS
R OSe
O
7Reich, H. J. et. al. J. Am. Chem. Soc. 1983, 105, 2503.
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Standard Protocol for Synthesis of the Allylic Selenides
R H
O
R OMe
OR'
R"R
R'
R"
DIBAL-H
o-nitrophenyl selenocyanatePBu3, THF
OH
R
R'
R"Se
NO2
Ph3P=CHCO2Me, CH2Cl2or
KHMDS, 18-crown-6, (CF3CH2O)2POCH2CO2Me
CH2Cl2
70-90%
90-99%
< 95%
8
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Development of Vanadium-Catalyzed SOS Reaction
R SeNO2R'
RR'
SeO
NO2
RR'
OSe
NO2
RR'
OH PBu3
VO(acac)2, CHP, CH2Cl2
4 Å mol. sieves-10°C, 30 min
9
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Utility of the Vanadium-Catazlyed SOS Reaction on (E)-Substrates
Carter, R. G.; Bourland, T. C. J. Chem. Soc. Chemm. Commun. 2000, 2031.
( )4 H
H
H
H
MeO
YieldR R''Entry
a
b
c
d
85%
75%
84%
80%
R'
H
H
H
H
R SeR''
R'
NO2
RR''
R' OHVO(acac)2, CHP
CH2Cl2, mol sieves,-10°C
10
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Utility of the Vanadium-Catazlyed SOS Reaction on Tri-Substituted and (Z) Substrates
CH3
YieldR R''Entry
a 70%
b
R'
H
( )4
c H
H
H
H 63%
86%
R SeR''
R'
NO2
RR''
R' OHVO(acac)2, CHP
CH2Cl2, mol sieves,-10°C
11
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Effects of a Stereocenter on SOS Reaction
SePh
VO(acac)2, CHP, CH 2Cl2
4 Å mol. sieves -10 °C, 60%
PhOH
1.1:1 d.r.
Ph PhOH
1.2:1 d.r.Se
O2N
O2N
VO(acac)2, CHP, CH 2Cl2
4 Å mol. sieves -10 °C, 71%
12
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Conclusion from Racemic SOS Reaction
• Conditions optimized for racemic series of Vanadium-catalyzed SOS reaction.
• System works on a wide variety of substrates.
• Good yields, short reaction times.
• Stereocenter does not effect SOS reaction.
13
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Fujita’s Asymmetric Oxidation of Sulfides with Salen-VO(acac)2
Nokijima, K.; Kojima, M.; Fujita, J. Chem. Lett. 1986, 1433.
N N
OH HO
X X
1 X = OMe2 X = OEt3 X = t-Bu
SCH3
VO(acac)2, 1 - 3
CHP, -20°C, CH2Cl2, 2h SCH3
O
up to 41% e.e.
96%
14
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Bolm’s Ligand-Based for Asymmetric Oxidation of Sulfides
Bolm, C.; Bienwald, F. Angew. Chem. Int. Ed. Engl. 1995, 34, 2640.
S
SPh
VO(acac)2 (1 mol %), ligand
H2O2, CH2Cl2, r.t. 16h, 84%
S
SPh
O
t-Bu
OHt-Bu
N
HO
85% e.e.
ligand
15
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Two Chiral Events Occurring in SOS Reaction
RSe
[O]R"
RSe
R"O
OH
R"
SeO
R"
RSe-O
cleavageRSe
R"O
Oxidation of selenide to chiral selenoxide:
Rearrangement of chiral selenoxide to alcohol:
16
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Endo vs. Exo Pathways
• Endo pathway appears to be favored by calculations and experimental results
Reich, H. J. et. al. J. Am. Chem. Soc. 1983, 105, 2503.
SeR
R'Ar
O
H
H
exoHO
R
R'
H
H
SeR'
R
H
HO
Ar
endo
R
R'H
HOH
17
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Davis’ Oxidation of Selenides
oxaziridine
Davis, F. A.; Reddy, T. R. J. Org. Chem. 1992, 57, 2599.
ClCl
O
N SO2Ph
0°C
oxaziridine
90-95% e.e.
Se SeO
(S)
18
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Davis’ Work in SOS Reaction
• Chiral induction from selenoxide to selenenate only 70-80% efficient.
• (Z)-Olefin geometry gives higher selectivity.
• Stereochemical outcome consistent with an endo transition state.
Davis, F. A.; Reddy, T. R. J. Org. Chem. 1992, 57, 2599.
Cl
ClN
OSO2
oxaziridine
Se
R1
Oxaziridine, CDCl3, -60°C, Ph
OHR2
R1 = H, R2 = Ph 54% (40% e.e.) R
R1 = Ph, R2 = H 46% (60% e.e.) S
19
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Vanadium-Catalyzed ASOS Reaction: Ligand-BasedApproach
20
SeNO2
VO(acac)2, CHPligand
CH2Cl2, 4 Å mol. sieves-30°C
ArN OH
t-Bu PhPh
N NAr Ar
t-Bu
t-Bu
OHAr =
OH
< 2% e.e.< 2% e.e.
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Selected Examples of Ligand-Based ASOS Reaction
21
SeNO2
VO(acac)2, CHPligand
CH2Cl2, 4 Å mol. sieves-30°C
ArN OH
RR'R
N NAr Ar
t-Bu
t-Bu
OHAr =
OH
10% e.e.< 2% e.e.
R = t-Bu, R' = HR = Ph, R' = HR = i-Pr, R' = HR = CH3, R' = PhR = Ph, R' = H
R'
R = R' = PhR = R' = -(CH2)4
N OHAr
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Problems with Ligand-Based System
L* = Chiral Schiff base ligandLB* = Chiral Auxiliary containing a Lewis Base
Se
R
VO(acac)2, CHP Chiral ligand
CH2Cl2, 4 Å mol. sieves
NO2R
OHR
VO
O
t-Bu
O
L*n
H
SeAr
R'
R'
R'
Se
R
VO(acac)2, CHP
CH2Cl2, 4 Å mol. sieves
LB*R
OH
Se
LB*
R
VO O
O
t-Bu
R' R'
R'
Ln
22
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Auxiliary-Based System Used to Understand Ligand-Based Systems
Auxiliary Approach:
Ligand Approach:
N O
Bn
O
R
OR''
R'
R'
R''
O
N O
O
RBn
EtAlCl2
98 % d.e.
N O
O
R
O
Cu(OTf)2, (2-10 mol %),
O N O
OH
RH
94 % e.e.O
N
O
Nt-Bu t-Bu
Evans, D. A.; et. al. J. Am. Chem. Soc. 1999, 121, 686. 23
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Williams Use of Auxiliary for Asymmetric Oxidation of Sulfides
S N
O
Me R
R'
S N
O
Me RO
R'
See Table
THBP, CH2Cl2-20°C
Entry R R’ Metal Time d.e.
a i-Pr H VO(acac)2 24 h 70%
b CH2OH Ph VO(acac)2 3 h 74%
c CH2OH Ph Ti(Oi-Pr)4 4 h 94%
Williams, J. M. J.; et. al. J. Chem. Soc. Perkin Trans. 1 1996, 331. 24
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Examples of Auxiliaries Utilized in ASOS Reactions
R' SeR m-CPBA
R"
R" OH
R'
OHN
OMe
Me
H
NMe2
Fe
Ts
68% (32% d.e.) 81% (66% d.e.)60% (89% d.e.) 88% (66% d.e.)
R =
R' = PhR" = H
R' = PhR" = H
R' = PhR" = H
CH2CH2CH CMe2R' = R " = Me
Reich, H. J.; Yelm, K. E. J.
Org. Chem. 1991, 56, 5672
Fujita, K.; et. al. Synlett 1998,
987.
Uemura, S.; et. al.
J. Org. Chem. 1995,
60, 4114.
Koizumi, N.; et. al.
Tetrahedron1997, 53,
12115 25
(t-BuOCl instead of m-CPBA)
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Synthesis of Monodentate Auxiliaries Applied to Vanadium-Catalyzed ASOS Reaction
Br
Br
N
O
H
O
N
OHH2N
R1
OH
R1
SOCl2, CH2Cl2
R1
Se
O
N R1
Ph
Br
COCl
Et3N, CH2Cl2, 0°C to r.t.
t-BuLi, THF, 78°C;Se powder then
Cinnamyl bromide
50-74%
50-74%
61-73% 26
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ASOS Reaction with Mondentate Auxiliaries
VO(acac)2, TBHPCH2Cl2, mol. sieves, -50°C;
PBu3
SeO
Ar
Ph
O
N
Se Ph
O
N
SeV(O)Ln
OOt-Bu
H
OH
Ph
R
R
H
endo
27
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Results From Monodentate ASOS Reaction
Entry R R' Yield d.e.
1 Bn H 78% 10% (R)
2 H i-Pr 56% 22% (S)
3 t-Bu H 52% 40% (R)
VO(acac)2, TBHPCH2Cl2, mol. sieves, -50°C;
PBu3
O
NR'
Se Ph
OHR
1
4
69
28
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Camphor Based Monodentate Oxazoles
ON
exo
Se
Ph
OH
6% d.e.
OH
14% d.e.endo
NO
Se Ph
VO(acac)2, TBHPmol. sieves, CH2Cl2, -35°C;
PBu3, 50%
VO(acac)2, TBHPmol. sieves, CH2Cl2, -40°C;
PBu3, 57%
29
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Monodentate Auxillary with m-CPBA
O
N
Se Ph m-CPBA, CH2Cl2mol. sieves, -50°C;
PBu3, 41%
OH
Only 4% d.e.
O
N
Se Ph VO(acac)2, TBHPCH2Cl2, mol. sieves, -50°C;
PBu3, 52%
OH
40% d.e.
30
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Williams Use of Auxiliary for Asymmetric Oxidation of Sulfides
S N
O
Me R
R'
S N
O
Me RO
R'
See Table
THBP, CH2Cl2-20°C
Entry R R’ Metal Time d.e.
a i-Pr H VO(acac)2 24 h 70%
b CH2OH Ph VO(acac)2 3 h 74%
c CH2OH Ph Ti(Oi-Pr)4 4 h 94%
Williams, J. M. J.; et. al. J. Chem. Soc. Perkin Trans. 1 1996, 331. 31
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Synthesis of Bidentate Auxiliary System
Se
O
NOSiR3
Ph
TBAF, THF, AcOH
Se
O
NOH
Ph
t-BuLi, THF, -78°C;Se powder then
Cinnamyl bromide, 70-72%
Br
O
NOSiR3
76-94%
32
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ASOS Reaction with Bidentate Auxiliary
Se
O
N
PhVO(acac)2, TBHP,
CH2Cl2, mol. sieves, -50°C;
PBu3
OH
OR
R Yield d.e. (configuration)
TIPS 52% < 2 %
H 63% 60 % (S)
33
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Methylated Serine-based Auxillary ASOS Reaction
Se
O
N
Ph
NaH, MeI,0°C82%
R = HR = OMe
OH
< 5% d.e.
OR
VO(acac)2, TBHP,CH2Cl2, mol. sieves, -50°C;
PBu3, 50%
34
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Bidentate Auxillary ASOS Reaction with Different Metal Catalysts
Se
O
N
Ph See Table, TBHP,
CH2Cl2, mol. sieves;PBu3
OH
OH
Entry Metal Temp Yield d.e.
a
b
c
d
e
f
g
Ti(Oi-Pr)4 (10 mol %)
Ti(Oi-Pr)4 (100 mol %)
MoO2(acac)2 (10 mol%)
Zr(acac)2 (10 mol %)
Mn(acac)2 (10 mol %)
m-CPBA (100 mol %)
VO(acac)2 (10 mol %)
-50 to -25°C
-50°C
-50°C
-50°C
-50°C
-50°C
-50°C
47%
60%
58%
35%
19%
63%
63%
30%
30%
25%
35%
34%
26%
60%35
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Threonine-Based Auxillary ASOS Reaction
Se Ph
O
N
X
HVO(acac)2, TBHP,
CH2Cl2, mol. sieves,
-50°C; PBu3
OH
Y
X Y Yield d.e. (configuration)
OTIPS H 69% 15% (R)
OH H 74% 50% (S)
H OH 74% 66% (S)
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Synthesis of Epimeric Selenides
BrHN
OOMe
O
OH
1) DAST, K2CO3, CH2Cl2, -78°C, 91%
2) i-PrMgCl, THF,-78°C, 49%
Br
O
N O
NaBH4, MeOH, r.t.
Br
O
N OH
Br
O
N OHH H
58% 42%
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Synthesis of Iso-Propyl Selenides
Br
O
NHH
OTBS
Se
O
NHH
OTBS
Ph
Se
O
NHH
OH
Ph
TBAF, AcOHCH2Cl2, r.t.
t-BuLi, THF, 78°C;Se powder then
Cinnamyl bromide
Br
O
NHH
OH TBSOTf, 2,6-lutidine,CH2Cl2, 0°C
62%
75%
60%
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ASOS Reaction with Iso-propyl Selenides
Se
O
NYH
X
Ph
VO(acac)2, CH2Cl2,mol. sieves, TBHP,
-50°C; PBu3
OH
X Y Yield d.e. (configuration)
OH H 61% 62% (R)
H OH 71% 70% (R)
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Possible Explanation of Stereochemistry
40
SeH
O
N
Se Ph
SeN
OH
O
VO
O
t-Bu
O
MeH
OH
MeH
Ph
OH SeOO
N
H
OVO
Ln
Ph
H
endo
Me
H
SOO
N
H
OVO
Ln
exo
Me
H
Ph
H
Ph
OH
R
Ln
Ph
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Conclusion
Racemic SOS reaction:• Developed the first catalytic, metal-based method.
• Requires only 10 mol% VO(acac)2 and applicable to a wide range of substrates.
Vanadium-catalyzed, Auxiliary-Based ASOS reaction:•Achieved up to 70% diastereomeric excess (d.e.) with an oxazole-based auxiliary.
• Laid the foundation for the development of a ligand- based ASOS reaction system.
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Acknowledgements
Committee Members
Dr. Rich CarterDr. Mitch AveryDr. Dan Mattern
Lab Group
Wei ZhangDavid WeldonMelissa Gronemeyer
Chrissy CastrichiniDr. and Mrs. Walter BourlandRachel GravesThe Graves ClanStacy JonesQun ZhuG-Flo and Big SergeDr. Ismail AhmedDr. Linda SpargoThe University of Mississippi
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