Stereoselective synthesis of cis-1,3-dimethyltetrahydroisoquinolines: formal synthesis of naphthylisoquinoline alkaloids

Abstract

Starting from tricyclic lactam 2, which is easily accessible by cyclocondensation of -oxoester 1 with (R)-phenylglycinol, a three-step synthetic route to enantiopure 1-substituted tetrahydroisoquinolines, including 1-alkyl-, 1-aryl-, and 1-benzyl- tetrahydroisoquinoline alkaloids as well as the tricyclic alkaloid (-)-crispine A, has been developed. The key step is a stereoselective -amidoalkylation reaction using the appropriate Grignard reagent.