Benzyne reaction. Part I. Total syntheses of (±)-cryptaustoline and (±)-cryptowoline by the benzyne reaction

Abstract

Cyclisation of 1-(2-bromo-4,5-dimethoxybenzyl)-(XVII) and 1-(2-chloro-4,5-methylenedioxybenzyl)-7-benzyloxy-1,2,3,4-tetrahydro-6-methoxyisoquinoline (XVIII) with sodamide in liquid ammonia afforded the dibenzindolizine derivatives, (XII) and (XIII), whose methylation with methyl iodide, followed by hydrolysis with acid, gave the corresponding methochlorides (V; X = Cl) and (VI; X = Cl). Treatment of these compounds with potassium iodide or hydriodic acid gave the iodides of (±)-cryptaustoline (V) and (±)-cryptowoline (VI), respectively. The same treatment of the 1-(4-benzyloxy-3-bromobenzyl)-isoquinoline (XIX) also afforded the expected indolizine (XV), and therefore this cyclisation is through the benzyne reaction.