Palladium‐Catalyzed Enantioselective Heck Carbonylation with a Monodentate Phosphoramidite Ligand: Asymmetric Synthesis of (+)‐Physostigmine, (+)‐Physovenine, and (+)‐Folicanthine

Abstract

AbstractReported herein is the development of the first enantioselective monodentate ligand assisted Pd‐catalyzed domino Heck carbonylation reaction with CO. The highly enantioselective domino Heck carbonylation of N‐aryl acrylamides and various nucleophiles, including arylboronic acids, anilines, and alcohols, in the presence of CO was achieved. A novel monodentate phosphoramidite ligand, Xida‐Phos, has been developed for this reaction and it displays excellent reactivity and enantioselectivity. The reaction employs readily available starting materials, tolerates a wide range of functional groups, and provides straightforward access to a diverse array of enantioenriched oxindoles having β‐carbonyl‐substituted all‐carbon quaternary stereocenters, thus providing a facile and complementary method for the asymmetric synthesis of bioactive hexahydropyrroloindole and its dimeric alkaloids.