Stereoselective synthesis of the basic skeleton of aphidicolan-type diterpenes via intramolecular Diels–Alder cyclisation. Synthetic approach to aphidicoline

Abstract

The basic tetracyclic skeleton of aphidicolan-type diterpenes has been synthesised by an intramolecular Diels–Alder reaction of 1-(1-cyano-5-methoxy-3-methylbenzocyclobuten-1-yl)hept-6-en-3-one (9). The cyclised product (10) was converted into the tetracyclic compound (11) by treatment with base followed by acid hydrolysis. The stereochemistry of (11) was easily determined from the n.m.r. spectral data, in which one of the aromatic protons was observed to be deshielded by the five-membered ketone moiety. Thus benzocyclobutene thermolysis again proved to be a powerful method for the construction of a complex molecule.