PALLADIUM-CATALYZED ISOMERIZATION OF ARYL-SUBSTITUTED EPOXIDES - A SELECTIVE SYNTHESIS OF SUBSTITUTED BENZYLIC ALDEHYDES AND KETONES

Aryl-substituted epoxides bearing multiple methyl substituents on the epoxide ring isomerize in the presence of 5 mol % Pd(OAc)(2)PR3 (R = n -Bu, Ph) to form the corresponding benzylic aldehyde or ketone, with c omplete regioselectivity for the carbonyl compound formed via cleavage of the benzylic C-O bond. No allylic alcohols or products arising fro m alkyl migration are observed. Rapid reaction rates and nearly quanti tative yields are obtained, even with highly sterically hindered epoxi des, using tri-n-butylphosphine as ligand and tert-butyl alcohol as so lvent. 2-Aryl-substituted epoxides with two methyl substituents on C3 are completely unreactive, consistent with an oxidative addition/beta- hydride elimination mechanism. Catalyst variation studies show that bo th Pd(OAc)(2) and PR3 are essential for optimal activity and that pall adium catalysts formed in this manner are superior to other Pd(O) cata lysts (e.g., Pd(PPh3)(4)). The reactivity of catalytic Pd(OAc)(2)/PR3 toward multiply-substituted epoxides is compared to traditional Lewis acid catalysts; the former is found to be much more selective for isom erization without skeletal rearrangement. A mechanistic rationale invo lving turnover-limiting S(N)2-like attack of Pd(O) at the benzylic car bon is proposed.