Studies on the asymmetric Birch reductive alkylation to access spiroimines

The asymmetric Birch reductive alkylation has been investigated to synthesize spiroimine analogs of the neurophycotoxin (?)-gymnodimine A 1. Two types of chiral aromatic substrates, an acyclic benzamide 2 and a benzoxazepinone 3 were studied. We found that the chiral auxiliary of benzoxazepinone could be easily removed in a three step procedure to afford β-ketoester 14 that was converted into spiroimines 23–24 possessing antagonist effects on nicotinic acetylcholine receptors (nAChRs).