Vanadium-Catalyzed Selenide Oxidation with in situ [2,3] Sigmatropic Rearrangement: Scope and...
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Transcript of Vanadium-Catalyzed Selenide Oxidation with in situ [2,3] Sigmatropic Rearrangement: Scope and...
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
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
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
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
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
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
Selenoxide vs. Sulfoxide
Se
R
S
RO
R OS
R OSe
O
7Reich, H. J. et. al. J. Am. Chem. Soc. 1983, 105, 2503.
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
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
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
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
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
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
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
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
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
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
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
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
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.
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
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
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
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
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)
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
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
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
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
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
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
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
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
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
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
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)
36
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%
37
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%
38
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)
39
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
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.
41
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
42