Diastereodivergent Aldol‐Type Coupling of Alkoxyallenes with Pentafluorophenyl Esters Enabled by Synergistic Palladium/Chiral Lewis Base Catalysis

摘要

Abstract As a fundamental and synthetically useful C?C bond formation reaction, the aldol reaction is one of the most versatile transformations in organic synthesis. However, despite extensive research on asymmetric versions of the reaction, a unified method for stereoselective access to the complementary syn and anti diastereomeric products remains to be developed. In this study, we developed a synergistic palladium/chiral Lewis base system that overcomes the inherent diastereoselectivity bias of aldol reactions and, as a result, allowed us to achieve the first diastereodivergent coupling reactions of alkoxyallenes with pentafluorophenol esters. Computational studies suggest a mechanism involving an intermolecular protonative hydropalladation pathway rather than a palladium‐hydride migratory insertion pathway. The origin of the stereochemistry for this synergistic catalysis system is rationalized by DFT calculations.