Enantioselective total synthesis of (S)-(+)-lennoxamine through asymmetric hydrogenation mediated by L-proline-tetrazole ruthenium catalyst

Abstract

A novel asymmetric synthetic strategy to prepare isoindolobenzazepine based lennoxamine alkaloid has been achieved in high ee% starting from 2-(benzo[d][1,3]dioxol-5-yl)ethanamine and 1-(chloromethyl)-2,3-dimethoxybenzene in 5 steps and with a 34% overall yield. The potentiality of this route involved the Bischler-Napieralsky cyclization that leads to tetracyclic indolinium skeleton, generation of chiral center through asymmetric hydrogen-transfer reaction employing L-proline-tetrazole as chiral ligand with Ru/Ir/Rh, and anodic oxidation as the key steps in the synthesis. (C) 2012 Elsevier Ltd. All rights reserved.