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

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. (C) 2004 Elsevier Ltd. All rights reserved.