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

Two enantiospecific routes to (+)-valerane starting from (R)-carvone, using a combination of Claisen rearrangement and intramolecular diazo ketone cyc lopropanation reactions for the stereoselective generation of the vicinal s tereogenic quaternary carbon atoms, are described. Thus, orthoester Claisen rearrangement of 3-methylcarveol 6 furnishes the ester 9 containing the fi rst quaternary carbon atom. Intramolecular cyclopropanation of the diazo ke tone 10 derived from the ester 9, followed by regioselective reductive cycl opropane cleavage, generates the hydrindanone 11 containing all stereocentr es of valerane. Ring expansion of the hydrindanone to tetralone and further reductions transform 11 into (+)-valerane 2. In another direction, homolog ation of the acid 5 followed by intramolecular cyclopropanation of the diaz o ketone 24 and regioselective cyclopropane ring cleavage lead to valerenon e 25, which is transformed into (+)-valerane.