Synthesis of the Phthalide Isoquinoline Alkaloids (−)-Egenine, (−)-Corytensine, and (−)-Bicuculline by Asymmetric Carbonyl Addition of Chiral Dipole-Stabilized Organometallics

Abstract

The asymmetric addition of metalated [(methylenedioxy)isoquinolyl]oxazolines is 100% selective for the erythro (α-hydroxybenzyl)isoquinoline diastereomers, with 2:1 selectivity of the two possible erythro stereoisomers. Enrichment to 100% ee after removal of the auxiliary and conversion to (−)-bicuculline and (+)-bicuculline diol establish the absolute configuration of the major addition product. Inversion of the C-9 hydroxyl affords entry into the threo series as well. The asymmetric carbonyl addition was used to synthesize, for the first time, the phthalide-isoquinoline hemiacetals corytensine and egenine, confirming the previously assigned structures and absolute configurations, and establishing the identity of egenine with decumbensine and of corytensine with epi-α-decumbensine. © 1991, American Chemical Society. All rights reserved.