Asymmetric Hydroxymethylative Etherification of 1,3-Dienes with Isatins and Alcohols via Pd(0)-π-Lewis Base Catalysis

Abstract

Although the asymmetric hydroalkoxylation of 1,3dienes has been achieved recently, the development of a modular and mechanistically distinct strategy for concurrently introducing an alkoxyl group and another chiral moiety into 1,3-dienes remains to be disclosed. Presented herein is a palladium(0)-π-Lewis basecatalyzed asymmetric hydroxymethylative etherification reaction of 1,3-dienes, isatins, and aliphatic alcohols, proceeding through a cascade vinylogous addition and allylic etherification sequence. This three-component reaction exhibits a broad substrate scope and good functionality tolerance under mild catalytic conditions, generally furnishing structurally diverse chiral 1,3-diol derivatives bearing two stereogenic centers with moderate-to-high levels of diastereo-and enantioselectivity, which can be further converted to valuable frameworks with higher molecular complexity. In addition, a few control experiments were conducted to elucidate the reaction process.