Page 1115 - Advanced Organic Chemistry Part B - Reactions & Synthesis

chemoselectivity for the 4,5-double bond in a dienoate ester. This case also illustrates 1091
the occurrence of isomerization during the epoxidation. Entry 4 is a step in the
enantioselective synthesis of CDP840, a phosphodiesterase inhibitor. The reaction in SECTION 12.2
Entry 5 provided a starting material for the synthesis of the DNA-alkylating antitumor Addition of Oxygen at
Carbon-Carbon Double
agent CC-1065. Bonds

12.2.2. Epoxides from Alkenes and Peroxidic Reagents

12.2.2.1. Epoxidation by Peroxy Acids and Related Reagents. The most general
reagents for conversion of simple alkenes to epoxides are peroxycarboxylic acids. 67
m-Chloroperoxybenzoic acid 68 (MCPBA) is a particularly convenient reagent. The
magnesium salt of monoperoxyphthalic acid is an alternative. 69 Potassium hydrogen
®
peroxysulfate, which is sold commercially as Oxone , is a convenient reagent for
70
epoxidations that can be done in aqueous methanol. Peroxyacetic acid, peroxybenzoic
acid, and peroxytrifluoroacetic acid have also been used frequently for epoxidation.
All of the peroxycarboxylic acids are potentially hazardous materials and require
appropriate precautions.
It has been demonstrated that ionic intermediates are not involved in the epoxi-
71
dation reaction. The reaction rate is not very sensitive to solvent polarity. Stereospe-
cific syn addition is consistently observed. The oxidation is therefore believed to be a
concerted process. A representation of the transition structure is shown below.

R″
O O
H
O O HOC R″ +
R′ R′ O
R′ R′
R R R R

The rate of epoxidation of alkenes is increased by alkyl groups and other
ERG substituents and the reactivity of the peroxy acids is increased by EWG
72
substituents. These structure-reactivity relationships demonstrate that the peroxyacid
acts as an electrophile in the reaction. Decreased reactivity is exhibited by double bonds
that are conjugated with strongly electron-attracting substituents, and more reactive
peroxyacids, such as trifluoroperoxyacetic acid, are required for oxidation of such
compounds. 73 Electron-poor alkenes can also be epoxidized by alkaline solutions of

67 D. Swern, Organic Peroxides, Vol. II, Wiley-Interscience, New York, 1971, pp. 355–533; B. Plesnicar,
in Oxidation in Organic Chemistry, Part C, W. Trahanovsky, ed., Academic Press, New York, 1978,
pp. 211–253.
68
R. N. McDonald, R. N. Steppel, and J. E. Dorsey, Org. Synth., 50, 15 (1970).
69 P. Brougham, M. S. Cooper, D. A. Cummerson, H. Heaney, and N. Thompson, Synthesis, 1015 (1987).
70
R. Bloch, J. Abecassis, and D. Hassan, J. Org. Chem., 50, 1544 (1985).
71
N. N. Schwartz and J. N. Blumbergs, J. Org. Chem., 29, 1976 (1964).
72 B. M. Lynch and K. H. Pausacker, J. Chem. Soc., 1525 (1955).
73
W. D. Emmons and A. S. Pagano, J. Am. Chem. Soc., 77, 89 (1955).