Stereoselective construction of vicinal stereogenic quaternary carbon atoms. Enantiospecific approaches to (+)-valerane†

Abstract

Two enantiospecific routes to (+)-valerane starting from (R)-carvone, using a combination of Claisen rearrangement and intramolecular diazo ketone cyclopropanation reactions for the stereoselective generation of the vicinal stereogenic quaternary carbon atoms, are described. Thus, orthoester Claisen rearrangement of 3-methylcarveol 6 furnishes the ester 9 containing the first quaternary carbon atom. Intramolecular cyclopropanation of the diazo ketone 10 derived from the ester 9, followed by regioselective reductive cyclopropane cleavage, generates the hydrindanone 11 containing all stereocentres of valerane. Ring expansion of the hydrindanone to tetralone and further reductions transform 11 into (+)-valerane 2. In another direction, homologation of the acid 5 followed by intramolecular cyclopropanation of the diazo ketone 24 and regioselective cyclopropane ring cleavage lead to valerenone 25, which is transformed into (+)-valerane.