A Novel Synthesis of Berbines¹-Synthesis of 2,3-Dimethoxy-10,11-Methylenedioxyberbine by Use of Palladium Catalyzed Insertion of Carbon Monoxide

Abstract

Palladium catalyzed amidation has recently been reported for the synthesis of benzolactams². We wish to report a simple and efficient method for the synthesis of berbines by the Palladium catalyzed insertion of carbon monoxide under mild reaction conditions such as an atmospheric pressure of carbon monoxide at 95° by use of a catalytic amount of Pd(OAc)₂ and PPh₃ in presence of a tertiary amine. The approach has wider applicability in the berbine synthesis³ as examplified by the synthesis of 2,3-dimethoxy-10,11-methylene-dioxyberbine 7. The bromo-1-benzyl tetrahydroisoquinoline derivative 5 ⁴, the key precursor, was prepared from the known reaction sequence involving an Schotten-Baumann condensation⁵ and B.N. reaction followed by sodium borohydride reduction.