STEREOSELECTIVE SYNTHESIS OF HIGHLY SUBSTITUTED GAMMA-LACTONES BY DIASTEREOSELECTIVE ALKYLATION OF ALPHA-(BENZENESULFONYL) DERIVATIVES WITHUNUSUAL FACIAL SELECTIVITY

The oxidation of alpha-(phenylthio) gamma-lactones obtained by the bas e-induced cyclization of enantiomerically enriched gamma-[(phenylthio) acyl]-alpha,beta-unsaturated esters to sulfones in those cases where the a-carbon has an available proton and further basic alkylation led to an unexpected facial selectivity. The reaction proceeded smoothly w ith alkylating agents and unsaturated carbonyl compounds, but was unsu ccessful when an addition to carbonyl derivatives was attempted. The a lkylation reaction was performed over a wide range of substituted subs trates in order to investigate the scope and limitations of the method and to have information about the possible origin of the selectivity. The application of the alkylation reaction was extended to the synthe sis of bicyclic systems, including a cyclobutane with total stereochem ical control. The presence of the alpha-(benzenesulfonyl) group is sho wn to be essential to achieve the facial selection. In order to ration alize the stereochemical results, extensive semiempirical calculations were performed. The use of MNDO and AM1 permits rationalization of th e fact that the alpha-(benzenesulfonyl) group encumbers a diastereofac e of the enolate generated in the ring, leading to the observed stereo chemistry.