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Dioxiranes and Sulfonium Ylides Catalytic Asymmetric ... · Catalytic Asymmetric Epoxidation via...
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Catalytic Asymmetric Epoxidation via Chiral Oxaziridines Dioxiranes and Sulfonium Ylides Teresa Beeson MacMillan Group Meeting July 6, 2004
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Catalytic Asymmetric Epoxidation via Chiral OxaziridinesDioxiranes and Sulfonium Ylides
Teresa Beeson
MacMillan Group Meeting
July 6, 2004
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
1967 Henbest reports first asymmetric epoxidation:
COOH
OOH
O
(+)-Peroxycamphoric acid
O
Ewins, R. C.; Henbest, H.B.; McKarvey, M.A. J. Chem. Soc., Chem. Commun. 1967, 1085.
4.4% ee
1984 Curci provides the first catalytic dioxirane-promoted epoxidation:
O
92% yield 12% ee
Me
OO
H
Ph
Me
O
68% yield11.2% ee
O
O
Me
H
Curci et. al., J. Chem. Soc., Chem. Commun., 1984,155.
50 mol%
20 mol%
KHSO5
KHSO5
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Yang et. al., J. Amer. Chem. Soc., 1996, 491.
1996 Shi provides the first general enantioseletive dioxirane epoxidation of trans-olefins:
oxone OO
O
O
OO
O
73% yield>95%ee
OTBSOTBS
O
80% yield93%ee
O
73% yield92%ee
3 eq.
Ketone decomposed under reaction conditions
Reactions were stopped before complete conversion to limit ee reduction
pH7-8
oxone
pH7-8
oxone
pH7-8
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
pH study allows catalytic asymmetric epoxidation:
Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Amer. Chem. Soc., 1997, 11224.
Wang, Z.; Tu, Y.; Frohn, M.; Shi, Y. J. Org. Chem., 1997, 2328.
Plot of the conversion of trans-methylstyrene against pHusing ketone (0.2 eq.) as catalyst in two solvent systems, H2O-CH3CN (1:1.5 v/v) (A) and H2O-CH3CN-DMM (2:1:2 v/v) (B)
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Shi Epoxidation catalytic cycle:
Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Amer. Chem. Soc., 1997, 11224.
Wang, Z.; Tu, Y.; Frohn, M.; Shi, Y. J. Org. Chem., 1997, 2328.
Baeyer-Villiger suppressed at higher pH
Reactions become catalytic in ketone at 30 mol%
O
OO
OO
OO
O
OO
OO
OO-
O
OO
OO
OOH
R1
R2
R3
O
R1
R2
R3
HSO5-
B.V.
O SO3-
OH-
O SO3-
SO42-
O
O
OO
O
O O
O
O
OO
O
O
O
HydrolysisO
achiral ketone
O OO
OO
O
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Yang et. al., J. Amer. Chem. Soc., 1996, 491.
1996 Yang shows electronic effect on ketone catalysts:
oxone
R R
OO
R Reaction Time (min)
Me
CF3
CH2Cl
CH2OAc
300
<4
18
30
Discovery leads to design of C2-symmetric catalyst:
O
80% yield87% ee
Ph
Ph
Ph
Ph
O
O
O
O
O
10 mol%
oxone
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Yang et. al., J. Amer. Chem. Soc., 1998, 5949.
18O labelling provides evidence for dioxirane intermediate:
OO
O O
O
ratio 1:1
16/18
OO
O O
OO
O O
OO OO16 16 16 18
ratio 1:1
Ph
PhPh
PhO
Ph
PhO16 18
3:1 theoretical ratio
23% experimentally obtained
oxone
pH7-8
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Possible Dioxirane Geometries:
O
O Me
Me
H
R1
H
R2
Spiro-trans
O
O Me
Me
H
HR1
R2
Spiro-cis
O
O
Me
Me
H R2
HR1
Planar-trans
O
O
Me
Me
R1 R2
HH
Planar-cis
Spiro calculated by Houk to be lower in energy
Cis-olefins epoxidize 7-9 times faster; only the spiro geometery explains this observation
Molecular Orbital Considerations:
O
O
Me
Me
oxygen lone-pairattacks olefin !*-orbital
O
O
Me
Me
olefin !-orbitalsattack oxygen "*-orbital
No overlap in planar geometery
Comprehensive Asymmetric Catalysis, Vol II. Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. Eds; Springer: Berlin 1999
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Stereochemical Considerations:
O
O R3
R4
H
R1
H
R2
Spiro-trans
O
O R4
R3
H
R1
H
R2
Spiro-trans
O
O R3
R4
H
R2
H
R1
Spiro-trans
O
O R4
R3
H
R2
H
R1
Spiro-trans
Design of asymmetric catalyst must be able to differentiate between possible dioxirane orientations
OO
OO
OOOO
OO
OO
vs
Yang et. al., J. Amer. Chem. Soc., 1998, 5943.
Two possible orientations when R1=R2
Distant stereocenter less affective with small or long-chain aliphatic R groups
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Shi's non-C2-symmetric catalyst proved more effective for other functionalities:
O
O
O
OO
OO
O
O
O
OO
OO
PhPh
Ph
Ph
vs
Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J. Shi, Y. J. Amer. Chem. Soc., 1997, 11224.
O
O
O
OO
OO
O
O
O
OO
OO
R1R2
R2
R1
vs
R3
favored disfavored
R3
favored disfavored
Attack underneath prevented by acetal; olefin approach directed by anomeric acetal
Quaternary center ! to carbonyl minimizes epimerization of stereogenic centers
Stereogenicity in close proximity to reacting centers enhances stereocontrol
Effective for trans or tri-substituted olefins, but not cis or terminal olefins
R
R1
R2
24-35% ee
32-61% ee
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Tian, H.; She, X.; Yu, H.; Shu, L.; Shi, Y. J. Org. Chem. 2002, 2435.
2002 Shi reports catalyst for enantioselective epoxidation of terminal and cis-olefins:
R1
oxone O
R1
O
O
O
NBocO
O
58-88% yield83-97%ee
15-30 mol%
pH10.5R2 R2
oxone
pH10.5
O
93% yield71%ee
2004 Shi reports catalyst for enantioselective epoxidation of styrenes:
oxoneO
O
O
NBocO
O
56-84% yield89-93%ee
20 mol%
pH10.5R R
Hickey, M.; Goeddel, D.; Crane, Z.; Shi, Y. Proc. Natl. Acad. Sci. 2004, xxx.
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Hickey, M.; Goeddel, D.; Crane, Z.; Shi, Y. Proc. Natl. Acad. Sci. 2004, xxx.
Electronic Considerations:
O
O
O
OO
OO
R3
R2
R1
Spiro AFavored Sterically
O
O
O
OO
OO
Planar B
R2
R1
R3
O
O
O
NRO
OO
R!
R
Spiro CFavored Electronically
O
O
O
NRO
OO
R
R!
Spiro D
O
O
O
OO
OO
Planar EDisfavored Sterically
R!
R
(R,R)76-98% ee
(S,S) (S,R)(R,S)87-97% ee
(R,S)
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Hickey, M.; Goeddel, D.; Crane, Z.; Shi, Y. Proc. Natl. Acad. Sci. 2004, xxx.
Electronic Considerations:
O
O
O
NRO
OO
R!
H
Spiro FFavored Electronically
O
O
O
NRO
OO
H
R!
Spiro G
O
O
O
OO
OO
Planar H
R!
H
(R)30-85% ee
(S)
O
O
NRO
OO
R!
H
Spiro JFavored Electronically
O
O
NRO
OO
H
R!
Spiro K
(R)89-93% ee
(S)
Nonbonding orbital of dioxirane oxygen raised
Secondary overlap increased
Spiro even more favored over planar
O
O
O
OO
OO
Planar I
R!
H
(S)(R)
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Hickey, M.; Goeddel, D.; Crane, Z.; Shi, Y. Proc. Natl. Acad. Sci. 2004, xxx.
Electronic Considerations:
O
O
O
NO
OO
Spiro L
O
O
O
NO
OO
Planar MFavored Electronically
Ph
Boc Boc
Ph
O
Ph
39% ee(S,S)
O
O
NO
OO
Spiro NFavored Electronically
O
O
NO
OO
Planar O
Ph
Boc Boc
PhO
Ph
40% ee(R,R)
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
1986 Davis further increases epoxidation enantioselectivity:
O
N
O
SN
OO
Davis et. al., Tet. Lett., 1986, 5079.
Bn
Me
Ph
H
Ar
65% ee
1983 Davis demonstrates enantioselective epoxidation using chiral oxaziridines:
O
40% ee
N
O
SO
O
Ar
H
Br
O
16% ee
Davis et. al., J. Amer, Chem. Soc., 1983, 3123.
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
1988 Lusinchi finds oxaziridinium salts to be efficient oxygen transfer agents:
N
O
BF4-
O
96% yield
Hanquet, G.; Lusinchi, X.; Milliet, P. Tet. Lett. 1988, 3941.
1993 Lusinchi reports first catalytic epoxidation with oxaziridium salts:
Hanquet, G.; Lusinchi, X.; Milliet, P. Tetrahedron 1993, 423.
NBF4
-
85% yield
mCPBA
10 mol%
OO
O
1996 Aggarwal reports a catalytic asymmetric epoxidation with oxaziridinium salts:
80% yield71% ee
oxone
Aggarwal, et. al. Chem. Commun. 1996, 191.
N
BF4-
Ph Ph
O
10 mol%
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Recent reports show minor improvements in enantioselectivity:
oxone
Page, P. C. B. et. al. Org. Lett. 2004, 1543.
N
BF4-
5 mol%
R1
R2
Ph
R1
R2
PhO
58-70% yield17-95% ee
O
O
Ph
NBF4
-O
78% yield73% ee
10 mol%
oxone
Page, et. al. J. Org. Chem. 1998, 2774.
oxoneR1
R2
Ph
R1
R2
PhO
51-100% yield17-65% ee
N
AcO
HN
O
CO3-
10 mol%
Wong, M. et. al. Org. Lett. 2001, 2587.
Page, et. al. J. Org. Chem. 2001, 6926.
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Stereochemical Considerations:
NR*
X-
oxone
NR*
OOSO3-
NR*
OOSO3-
_ SO42- _ SO4
2-
NR*
O
NR*
O
R2 R1
Ph
R2 R1
Ph
R2 R1
PhO
R2 R1
PhO
Two diastereomeric oxaziridines may be formed
Each oxaziridine may lead to the same product enantiomer, but will have different selectivities
N
O
H
PhR1
R2
Spiro A
N
O
H
PhR1
R2
Spiro B
O
N
Me
Me
Ph R2
R2R1
Planar A
O
N
Me
Me
R1 R2
HPh
Planar B
Spiro calculated by Houk to be lower in energy by 4.1 kcal/mol
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Stereochemical Considerations:
Washington, I.; Houk, K. N. J. Amer. Chem. Soc. 2000, 2948.
N
O
H
PhR1
R2
Spiro
2.5Å
Early transition state predicted, allowing flexibility unlike dioxiranes
N
O
HPh
R1
R2
Twisted-Spiro
2.5Å
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
1965 Corey demonstrates epoxidation of aldehydes and ketones with sulfur ylides:
Corey, E. et. al. J. Amer. Chem. Soc. 1965, 1356.
Furukawa, N. et. al. J. Org. Chem. 1989, 4222.
R1 R2
O
R1
OR2
SCH2
75-97% Yield
1989 Furukawa achieves enantioselectivity and some turnover via sulfide alkylation/deprotonation:
1996 Dai improves enantioselectivity and turnover for this system:
H
O
O
SMe
OHPhCH2Br
KOH
230% Yield (based on sulfide)31% ee
H
O
O
OHPhCH2Br
KOH
SMe
20 mol%97% Yield42% ee
Dai, L. et. al. J. Org. Chem. 1996, 489.
2001 Metzner's C2 symmetric catalyst achieves best results to date:
H
O
OPhCH2Br
NaOH, n-Bu4NI
10 mol%90% Yield92% ee85% de
Zanardi, J.; Leriverend, C.; Aubert, K.; Metzner, P. J. Org. Chem. 2001, 5620.
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Reactions limited to aromatic aldehydes and benzyl bromides
PhCHO
PhR
OPhCH2I
OH-
S
S
S
Ph
I-
S
Ph
PhCH2Br
n-Bu4NI
organicaqueous
2004 Goodman achieves methylene transfer stoichiometrically:
H
OO
Et2Zn
2 eq.48-96% Yield34-76% ee
Bellenie, B.; Goodman, J. Chem Commun. 2004, 1076.
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
S
O
O O
OPh Ph
CH2IClR R
H
OO
Et2Zn
57% convsyn:anti 12:1
S
O
O O
OPh Ph
CH2ICl
H
OO
Et2Zn
45% convsyn:anti 3:1
S
O
O O
OPh Ph
CH2ICl
Bn2N
Bn2N
Ph
Ph
Bn2N
Bn2N
Ph
Ph
OBn2N
Ph
OBn2N
Ph
1994 Aggarwal uses diazo compounds to generate sulfur ylide catalyst in situ:
Aggarwal, V. et. al. J. Amer. Chem. Soc. 1994, 5973.
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Rh2(OAc)4Me2S
Ph
PhO
1 mol%20 mol%
74% Yield76% de (trans)
H
O
slow addition
Slow addition of diazo compound to minimize dimerization
N2CHPh
R H
O
R
R'O
N2CHPh
N2
R2S CHR'
Rh CHR'SR2
Rh2(OAc)4
1996 Aggarwal achieves good diastereoselectivity and enantioselectivity:
Aggarwal, V. et. al. J. Amer. Chem. Soc. 1996, 7004.
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Rh2(OAc)4
64-73% Yield92-93% ee>96% de (trans)
H
O
N2CHPhO
S
20 mol%
R
O
R
Rh2(OAc)4
73% Yield89% ee>96% de (trans)
H
O
N2CHPhO
S
20 mol%
O
PhPh
Rh2(OAc)4
32% Yield90% ee40% de (trans)
H
O
N2CHPhO
S
20 mol%
O
Stereochemical Considerations:
Aggarwal, V. et. al. Acc. Chem. Res. 2004, ASAP.
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Diastereoselectivity:
SR2R1
PhPh H
O
Ph H
O
H
SR2Ph
PhPh
O
anti betaine
H Ph
O
H
SR2Ph
syn betaine
Ph
O
Ph
k1
k-1
k-4
k4
Ph H
O
S
PhH
R2R1
H Ph
O
S
PhH
R2R1
k2 k3
k5 k6
anti betaine: small barreir of rotation. k2 > k-1
syn betaine: large barrier of rotation. k5 < k-4
Aliphatics have lower k5, making syn betaine more pronounced
Stereochemical Considerations:
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Enantioselectivity:
Sulfur lone pair and filled orbital on ylide carbon calculated to be orthogonal
OS
H
PhHH
Favored
OS
Ph
HHH
Disfavored
Ylide formation could give mixture of only two diastereomers
SR
R
H
SR
R
H
H
Favored Disfavored
H
Comprehensive Asymmetric Catalysis, Vol II. Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. Eds; Springer: Berlin 1999
Stereochemical Considerations:
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Enantioselectivity:
Facial selectivity determined by catalyst
OS Me
H
PhHH
SH
H
HR
Comprehensive Asymmetric Catalysis, Vol II. Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. Eds; Springer: Berlin 1999
S
HH
A CB
O
H
R
RCHO
RCHO
RCHO
Concerted pathway or anti-addition?
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Kawashima, T. et. al. J. Amer. Chem. Soc. 1996, 12455.
Lindvall, M.; Koskinen, A. J. Org. Chem. 1999, 4596.
Kawashima reports oxirane formation with retention of configuration
Koskinen calculates anti-addition to be lower in energy by atleast 10 kcal/mol
S
O
OO
Ph
R2
R1
F3CCF3
OR2 Ph
R1S
O
CF3F3C
O
R2R1
O
R2R1
O
O S
R1 HR2H
S
R2
HO
HR1
Conclusions:
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
PhPh
O O
Ph
O
PhPh
O
Ph
Pr OH
OEt
O
TBSO
Jacobsenc
Shid
Yangd
Pagee
Metznerf
Goodmanf
Aggarwalf
75% yield97% ee
80% yield
90% eea
99% yield47% ee
78% yield73% ee
97% yield
93% eeb
61% yield48% ee
87% yield94% ee
97% yield92% ee
88% yield86% ee
63% yield90% ee
87% yield91% ee
54% yield97% ee
85% yield93% ee
60% yield78% ee
82% yield81% ee
43% yield54% ee
a >92% de
36% yield86% ee
b 88% de
c metal Salen
d dioxirane
e oxaziridine
f sulfur ylide
Conclusions:
Epoxidation With Chiral Oxaziridines, Dioxiranes and Sulfonium Ylides
Improvements in yield and enantioselectivity are needed for the following substrates:
Aliphatic epoxides
Terminal epoxides
Styrenes
Cis-epoxides
Tetra-substituted epoxides
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