10b-Substituted hexahydropyrrolo-isoquinolines: studies on diastereoselective formation of a quaternary carbon stereocenter via N-acyliminium ion cyclization

Abstract

The stereoselective synthesis of hexahydro-pyrroloisoquinolines with a quaternary carbon stereocenter is described. The presented methodology employs the addition of a Grignard reagent to the carbonyl group of imide 1 , derived from l-tartaric acid, followed by acetylation and BF 3·Et 2O induced cyclization. The acetylation–cyclization sequence can be run either as a one-pot process, or stepwise in a selected solvents. The crucial step, an acid-catalyzed carbon–carbon bond-forming reaction via an N-acyliminium ion offers high stereoselectivity, which has been shown to be strongly dependent on the size of the R 1 substituents and the reaction conditions, that is, choice of solvent, amount of a Lewis acid, temperature, and concentration of the substrate. Based on the results observed, participation of solvent in the cyclization, via an N-acyliminium cation is proposed.