Tetrahydroisoquinolines. Part 4. Enantioselective conversion of (+)-amphetamine into (+)-(1R,3S,4S)- and (–)-(1S,3S,4R)-1,2,3,4-tetramethyl-1,2,3,4-tetrahydroisoquinoline via tricarbonyl(arene)chromium methodology

Abstract

Co-ordination of the tricarbonylchromium moiety to the diastereotopic faces of (+)-(3S)-2,3-dimethyl-1,2,3,4-tetrahydroisoquinoline (9) occurs preferentially to the least hindered face. The mixture of tricarbonyl [exo-(3S)-2,3-dimethyl-1,2,3,4-tetrahydroisoquinoline]chromium (11) and tricarbonyl-[endo-(3S)-2,3-dimethyl-1,2,3,4-tetrahydroisoquinoline]chromium (12) thus generated may undergo regio- and stereo-selective exo-1,4-dimethylation by sequential treatment with BuLi–Mel and Bu^tLi–Mel to give (+)-[tricarbonyl-(1R,3S,4R)-1,2,3,4-tetramethyl-1,2,3,4-tetrahydroisoquinoline]chromium (15) and (+)-[tricarbonyl-(1S,3S,4S)-1,2,3,4-tetramethyl-1,2,3,4-tetrahydroisoquinoline]chromium (16). The relative and absolute stereochemistry of (15) is assigned on the basis of differential n.O.e. experiments and confirmed by single crystal X-ray structure determination. Oxidative decomplexation gives (1R,3S,4S)-and (1S,3S,4R)-(–)-1,2,3,4-tetramethyl-1,2,3,4-tetrahydroisoquinolines (17) and (18).