SYNTHESIS OF THE PHTHALIDE ISOQUINOLINE ALKALOIDS (-)-EGENINE, (-)-CORYTENSINE, AND (-)-BICUCULLINE BY ASYMMETRIC CARBONYL ADDITION OF CHIRAL DIPOLE-STABILIZED ORGANOMETALLICS

The asymmetric addition of metalated [(methylenedioxy)isoquinolyl]oxazolines is 100% selective for the erythro (alpha-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-alpha-decumbensine.