Phosgenation of benzyltetrahydroisoquinolines: A new method of berbines and berbin-8-ones synthesis

Abstract

A novel synthesis of the berbine ring skeleton by the way of the berbin-8-ones is reported. Treatment of 1-benzyl-1,2,3,4-tetrahydroisoquinolines 1a-d with phosgene gas gave a new series of N-chloroformyl derivatives 2a-d. Intramolecular ring closure of these compounds in presence of a Lewis acid catalyst afforded berbin-8-ones 3a-d in good yield. The choice of the cyclization catalyst is discussed. Reduction of products 3a-d with lithium aluminium hydride gave the berbines 4a-d. Hydrolysis of berbines 4b, c gave the new 3-hydroxyberbines 4e, f. Preparation of new starting benzyltetrahydroisoquinolines 1b, c are described.