Diastereoselective synthesis of 10b-substituted hexahydropyrroloisoquinolines from l-tartaric acid. Creation of a quaternary carbon stereocentre via N-acyliminium ion cyclization

Abstract

A simple, three-step synthesis of 10b -substituted-hexahydropyrroloisoquinolines 12– 17 starting from an L-tartaric acid derived imide is described. The methodology presented employs the addition of a Grignard reagent to the imide carbonyl group, followed by a one-pot acetylation–cyclization sequence. The crucial step, an acid-catalyzed carbon–carbon bond forming reaction via an N-acyliminium ion offers moderate to high stereoselectivity, which has been shown to be strongly dependent on the size of the R-substituent. The mixtures of pyrroloisoquinolines obtained can be separated as enantiomerically pure 2-silyloxy-derivatives.