Aerobic Oxidative Heck/Dehydrogenatioe Reactions of Cyclohexenones: Efficient Access to meta-Substituted Phenols

摘要

Phenol derivatives are common and important structural motifs in bioactive natural products and pharmaceuticals, and the selective synthesis of substituted phenols is facilated by the strong ortho/para-dixecting effect of the hydroxy group. The same directing effect, however, limits access to analogous meto-substituted derivatives. In recent years, considerable efforts have targeted C—H functionalization reactions which enable preparation of meto-substituted arenes by steric or directing-group control over the site selectivity. The overall efficiency of these methods is often limited by functional-group interconversions or installation and removal of directing groups needed to access the final product. Moreover, in molecules with more than one electronically or sterically active substituent, competition between the directing groups can lead to product mixtures. Following our recent development of palladium-catalyzed aerobic dehydrogenation reactions of ketones, we envisioned that meto-substituted phenols could be accessed efficiently by an aerobic oxidative Heck/dehydrogenation sequence with cyclohexenone (Scheme 1).