CHM-6315
Cours 12 - 1
1
Epoxidation of Olefins: The Reagents
O
O
Cl
O
H
O
O
Cl
O H
O
O
Cl
O H
O H
A. THE PERACIDS: Unfunctionalized olefins, allylic alcohols.
Most common: MCPBA (m-chloroperoxybenzoic acid)
Electrophilic reagent
In the case of an allylic alcohol, an
additional hydrogen bond is present
(directing effect):
Mechanism:
Nucleophilic substrate
CHM-6315
Cours 12 - 2
2
Metal-catalyzed epoxidations
O
O
M
R
O
O
M
R
M-OR
O
O
O
M
R
M O
M
O
O
R
M
O
O
Type I: Peroxide based Catalysts
R = H, alkyl, etc.
+
+
Some metals are capable of being "directed" by hydroxy groups: Ti, V, Mo, Zr , Hf, Nb, Ta
Type II: Oxo-based catalysts
dihydroxylation (ex: OsO4)
Epoxidation of
unfunctionalized olefins
(Cytochrome P-450: Fe=O)
A metal complex is mixed with an oxidizing agent:
CHM-6315
Cours 12 - 3
3
Organic Dioxiranes
Adam Acc. Chem. Res. 1989, 22, 205-211.
Murray Chem. Rev. 1989, 89, 1187-1201.
Adam Eur. J. Org. Chem. 1998, 349-354.
Adam J. Org. Chem. 1996, 61, 3506-3510.
H3C
CH3
O
O
H3C
CF3
O
O
F3C
CF3
O
O
CHM-6315
Cours 12 - 4
4
Epoxidation of Olefins: Chiral Substrates
O
O
H
O
OH
OH
O
OAc
MCPBA
MCPBA
HO
O
O
OAc
O
Corey, E. J.; Niwa, H.; Falck, J. R. J. Am. Chem. Soc. 1979, 101, 1586-1587.
See also: Rebek, J. McCready, R. J. Am. Chem. Soc. 1980, 102, 5602-5605.
10 : 1
but...
4 : 1
Reading: Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993, 93, 1307-1370. (epoxidation: 1314-1330)
CHM-6315
Cours 12 - 5
5
R
R
R
OH
R
R
R
O
H
O
O
H
O
Ar
R
R
R
OH
O
OH
Me
OH
Me
O
>20 : 1
Me
HO
OH
Me
HO
OH
O
1 isomer
Me
OH
Me
OH
O
1 isomer
OH
OH
O
1 isomer
MCPBA
MCPBA
MCPBA
MCPBA
CHM-6315
Cours 12 - 6
6
Directed Epoxidation: Directing Groups
HN
HO
HO
Me
O
RCO3H
PGO
PGO
PGO
PGO
O
HN
HO
HO
Me
O
O
PGO
PGO
O
HO
Me
Bz
Me
TBS
RCO3H
MCPBA
HO
Me
O
1 isomer
1 isomer
O'Brien Tetrahedron Lett. 1999, 40, 391-392.
+
A mixture of oxone/trifluoroacetone is sometimes better
PG
Oxone/CF3COCH3
56:44
98:2
TES
39:61
98:2
75:25
94:6
80:20
81:19
trans
cis
trans:cis
CHM-6315
Cours 12 - 7
7
Relative Rates for Epoxidation of Cyclohexenol
OH
OAc
OH
pe