Construction of Chiral Quaternary Carbons via Enzymatic Epoxidation of Tertiary Allylic Alcohols.

A chemoenzymatic strategy to construct aryl-substituted chiral quaternary carbon centers has been established. Directed evolution of P450BM3 enables highly enantioselective epoxidation of tertiary allylic alcohols (up to 99% ee), which is a formidable challenge in chemical synthesis. The resulting chiral epoxides undergo acid-catalyzed semipinacol rearrangement with retention of chirality, affording enantioenriched cyclic ketones. This approach is applied to the total synthesis of (-)-sinoracutine, demonstrating the possibility of divergent synthesis of complex molecules.