Construction of bicyclic tetrahydroisoquinolinones by combination of an IMDAF-ring cleavage reaction of <i>N</i>-allyl-2-furan-2-yl-acetamides

Abstract

The intramolecular Diels-Alder reaction of furanyl amides derived from 2-furylacetic acid has been examined. Substrates containing either an imide or tertiary amide linkage between the furan and the dienophile underwent smooth cycloaddition upon thermolysis. By varying the reaction conditions, either the primary cycloadduct or the ring-opened and acetylated product could be isolated in excellent yield. The stereochemical outcome of the IMDAF cycloaddition has the side arm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. Semi-empirical AM1 calculations show that the exo-cycloadduct is 11 kcal lower in energy than the corresponding endo adduct and, presumably, some of this energy difference is reflected in the transition state for the cycloaddition. The IMDAF reaction of N-allyl-[2-(3,4-dimethoxyphenethyl)]-2-furanyl-2-yl-acetamide proceeded in 90% yield upon heating in xylene. The 4+2-cycloadduct undergoes ring-opening on treatment with base and the resulting alcohol was converted into the corresponding benzyl ether. Raney nickel reduction followed by Bischler-Napieralski cyclization furnished the tetracyclic skeleton of the berberine alkaloids.Key words: intramolecular, cycloaddition, Diels-Alder, furanylamide, heterocycle.