Page 1159 - Advanced Organic Chemistry Part B - Reactions & Synthesis

The concerted O−O heterolysis-migration is usually the rate-determining step. 225 The 1135
reaction is catalyzed by protic and Lewis acids, 226 including Sc O SCF 227 and
3 3 3 SECTION 12.5
Bi O SCF . 228
3 3
3
Oxidation of Ketones
When the reaction involves an unsymmetrical ketone, the structure of the and Aldehydes
product depends on which group migrates. A number of studies have been directed
at ascertaining the basis of migratory preference in the Baeyer-Villiger oxidation,
and a general order of likelihood of migration has been established: tert-alkyl,
sec-alkyl>benzyl, phenyl>pri-alkyl>cyclopropyl>methyl. 229 Thus, methyl ketones
uniformly give acetate esters resulting from migration of the larger group. 230 A
major factor in determining which group migrates is the ability to accommodate
partial positive charge. In para-substituted phenyl groups, ERG substituents favor
migration. 231 Similarly, silyl substituents enhance migratory aptitude of alkyl groups. 232
As is generally true of migration to an electron-deficient center, the configuration of
the migrating group is retained in Baeyer-Villiger oxidations.
Steric and conformational factors are also important, especially in cyclic
systems. 233 There is a preference for the migration of the group that is antiperiplanar
with respect to the peroxide bond. In relatively rigid systems, this effect can outweigh
the normal preference for the migration of the more branched group. 234

OH O O
O
O O
CH 2 CO H
2
H O
CO 3

This stereoelectronic effect also explains the contrasting regioselectivity of cis- and
trans-2-fluoro-4-t-butylcyclohexanone. 235 As a result of a balance between its polar
effect and hyperconjugation, the net effect of a fluoro substituent in acyclic systems is
small. However, in 2-fluorocyclohexanones an unfavorable dipole-dipole interaction
comes into play for the cis isomer and preferential migration of the fluoro-substituted
carbon is observed.

225
Y. Ogata and Y. Sawaki, J. Org. Chem., 37, 2953 (1972).
226 G. Stukul, Angew. Chem. Intl. Ed. Engl., 37, 1199 (1998).
227 H. Kotsuki, K. Arimura, T. Araki, and T. Shinohara, Synlett, 462 (1999).
228
M. M. Alam, R. Varala, and S. R. Adapa, Synth. Commun., 33, 3035 (2003).
229 H. O. House, Modern Synthetic Reactions, 2nd Edition, W. A. Benjamin, Menlo Park, CA, 1972, p. 325.
230
P. A. S. Smith, in Molecular Rearrangements, P. de Mayo, ed., Interscience, New York, 1963,
pp. 457–591.
231 W. E. Doering and L. Speers, J. Am. Chem. Soc., 72, 5515 (1950).
232
P. F. Hudrlik, A. M. Hudrlik, G. Nagendrappa, T. Yimenu, E. T. Zellers, and E. Chin, J. Am. Chem.
Soc., 102, 6894 (1980).
233
M. F. Hawthorne, W. D. Emmons, and K. S. McCallum, J. Am. Chem. Soc., 80, 6393 (1958); J. Meinwald
and E. Frauenglass, J. Am. Chem. Soc., 82, 5235 (1960); P. M. Goodman and Y. Kishi, J. Am. Chem.
Soc., 120, 9392 (1998).
234 S. Chandrasekhar and C. D. Roy, J. Chem. Soc., Perkin Trans. 2, 2141 (1994).
235
C. M. Crudden, A. C. Chen, and L. A. Calhoun, Angew. Chem. Int. Ed. Engl., 39, 2852 (2000).