Enantiospecific synthesis of (+)-(R)-6,7-dimethoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline from (+)-(S)-2-methylamino-1-phenylethanol (halostachine)

Abstract

Acid-promoted cyclisation of (+)-(R)-N-(3,4-dimethoxybenzyl)halostachine tricarbonylchromium at –20 °C is highly stereoselective, proceeding with retention of configuration, to yield, after removal of the tricarbonylchromium unit, homochiral (+)-(R)-6,7-dimethoxy-2-methyl-4-phenyl-1,2,3,4tetrahydroisoquinoline. In contrast, cyclisation of (–)-(R)-N-(3,4-dimethoxybenzyl)halostachine under acidic conditions at –20 °C showed poor stereoselectivity giving predominantly the tetrahydroisoquinoline product corresponding to inversion of configuration, (+)-(R)-6,7-dimethoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline, with an e.e. of 54%.