Molecular complexity from aromatics. Cycloaddition of spiroepoxycyclohexa-2,4-dienones and intramolecular Diels-Alder reaction: a stereoselective entry into tetracyclic core of atisane diterpenoids

A stereoselective approach to tetracyclic core of atisane diterpenoids is described. Oxidative dearomatization, intermolecular cycloaddition of spiroepoxycyclohexa-2,4-dieone with ethyl acrylate, and intramolecular inverse demand pi(4)s+pi(2)s cycloaddition are the key features of our design. Oxidation of appropriately appended o-hydroxymethyl phenols to corresponding 6,6-spiroepoxycyclohexadienones followed by cycloaddition with ethyl acrylate furnished bridged bicyclo[2.2.2]octanes disposed with appropriate functionality. Regioselective manipulation of functional groups led to highly embellished bicyclic systems endowed with appendages containing diene and dienophilic moieties that upon inverse electron demand intramolecular cycloaddition provide the tetracyclic framework of atisanes in stereoselective fashion. A remarkable effect of a remote functional group on intramolecular Diels-Alder reaction has also been described. (C) 2012 Elsevier Ltd. All rights reserved