A general methodology for the enantioselective synthesis of 1-substituted tetrahydroisoquinoline alkaloids

Abstract

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