Short Stereoselective Synthesis of (+)-Monocerin via a Palladium-Catalysed Intramolecular Alkoxycarbonylation

Abstract

A concise stereoselective total synthesis of (+)-monocerin has been accomplished using cross metathesis, tandem dihydroxylation-SN2 cyclisation and intramolecular alkoxycarbonylation as key steps. Cross-metathesis of 2-iodo-3,4,5-trimethoxyvinylbenzene and ( R)-hepten-4-ol, followed by tandem dihydroxylation-SN2 cyclisation generated a tri-substituted tetrahydrofuran ring. Finally, the dihydroisocoumarin was obtained by an intramolecular alkoxycarbonylation. In this paper, we have developed an expedient operationally simple Pd(OAc)2/bathocuproine catalysed alkoxycarbonylation under atmospheric pressure of carbon monoxide. The catalytic system developed here can be useful for the synthesis of various dihydroisocoumarins and phthalides.