A simple total synthesis of the isoindolobenzazepine alkaloids lennoxamine and chilenamine

Abstract

Lennoxamine(8) and chilenamine (9) have been synthesized from 3-(3,4-methylenedioxybenzylidene)-6,7-dimethoxyphthalide (1) in four and five high-yielding steps, respectively. The key step of the process is the cyclization, by intramolecular alkylation, of 3-(3,4-methylenedioxybenzyl)-6,7-dimethoxyphthalimidin-2-ylacetaldehyde dimethyl acetal (3) to 13,13a-dihydro-3,4-dimethoxy-10,11-methytenedioxyisoindolo[1,2-b][3]benzazepin-5-one (7). Attempts to prepare (3) by base-catalysed cyclization of 3,4-dimethoxy-3′,4′-methylenedioxystilbene-2-(2,2-dimethoxyethyl)carboxamide (15) were unsuccessful.