ENANTIOSELECTIVE SYNTHESIS OF 2-METHYL-2-HYDROXY-GAMMA-BUTYROLACTONE AND ITS APPLICATION IN THE ASYMMETRIC-SYNTHESIS OF FRONTALIN AND MEVALONOLACTONE

The asymmetric hydroxylation of the enolates of fully substituted acyc lic ester 8 and lactone 10 with (camphorylsulfonyl)oxaziridines 1a-c w as studied. The stereoselectivities of the tertiary alpha-hydroxy carb onyl products were highly dependent on the enolate structure, the oxid izing reagents, and the reaction conditions. While high diastereoselec tivity (up to 94%) was obtained for enolates of fully substituted ment hol ester 8 with substoichiometric amounts of oxaziridine 1a, the yiel ds were unsatisfactory. On the other hand, the enantioselective alpha- hydroxylation of the sodium enolate of 2-methyl-gamma-butyrolactone (1 0) with [(8,8-dimethoxycamphoryl)sulfonyl]oxaziridine (1c) afforded al pha-hydroxy lactone 11a in 70% yield and 84% ee. The enantiomeric exce ss was improved to > 93% ee by crystallization of the corresponding be nzoyl ester 11c. The utility of both enantiomers of 11c were demonstra ted in the formal asymmetric syntheses of the pheromone, (1S,5R)-(-)-f rontalin (13) and in the asymmetric synthesis of (R)-(-)-mevalonolacto ne (20).