Examination of Diels–Alder/Tsuji–Trost Route towards Kopsia Alkaloids

Abstract

A reaction sequence of Diels-Alder cycloaddition and Tsuji-Trost allylation was examined in terms of its application to synthesis of kopsinine and the related Kopsia alkaloids. Results of the studies in two synthetic directions are presented herein: 1) synthesis of the properly substituted diene, required for the Diels-Alder step; 2) model studies and optimization of the key reaction sequence in the absence of side-chain. Details on the challenging introduction of the side-chain into tetrahydrocarboline ketone and its silylation, resulting in rare but unproductive vinylogous Claisen cyclization, and the successful Mannich/Mukaiyama aldol sequence are disclosed for the first direction. For the second direction endo-selective Diels-Alder reaction with allyl acrylate and Tsuji-Trost allylation providing incorrect stereochemistry are discovered. Interaction of both dienes with an alkyne provides carbazoles via Alder-Rickert reaction.