Asymmetric permanganate dihydroxylation of enoates: substrate scope, mechanistic insights and application in bicalutamide synthesis

Asymmetric dihydroxylation (AD) of alkenes without using osmium reagents is highly desirable and under intensive research. Permanganate dihydroxylation catalysed by a chiral cation under phase-transfer conditions offers a green approach with potential practicality. In this paper, we systematically investigated the substrate scope of chiral cinchoninium catalysed permanganate dihydroxylation of enoates with different substitution types. Generally, moderate to good yields of chiral vicinal diols were obtained in up to 98% ee. Tetrasubstituted enoates were oxidized smoothly, providing vicinal tertiary diols with moderate yields and high enantioselectivities, which has not been achieved by other catalytic AD systems. The yield of the dihydroxylated product is determined not only by the reaction conditions and substrate but also by the structure of the chiral cation catalyst. If efficient chiral cation catalysts would be identified, asymmetric permanganate dihydroxylation might provide competitive approaches to chiral vicinal diols with excellent yields. Preliminary mechanistic studies were performed and a catalytic cycle was proposed. A chiral intermediate for the synthesis of (R)-bicalutamide was obtained efficiently from dihydroxylation of a readily available methacrylic acid derivative. Chiral cinchoninium catalysed permanganate dihydroxylation of enoates with different substitution types, including challenging tetrasubstituted ones, provides good yields of chiral vicinal diols in up to 98% ee.