Asymmetric synthesis of (-)-trichodiene. Generation of vicinal stereogenic quaternary centers via the thio-Claisen rearrangement

The use of chiral bicyclic lactams, in their thiocarbonyl form 9, has been shown to serve as important intermediates for producing alpha-quaternary alkyl derivatives 8, which were readily transformed into the title compound (-)-1. The reversibility of the thio-Claisen rearrangement, 15 reversible arrow 8, was clearly demonstrated and appears to be unprecedented. Solvent effects to alter the equilibrium position were studied and found to have only a moderate, but beneficial effect. The title compound was obtained in 14% overall yield in 10 steps from bicyclic lactam, 9.