ENZYME-CATALYZED ADDITION OF HYDROCYANIC ACID TO SUBSTITUTED PIVALALDEHYDES - A NOVEL SYNTHESIS OF (R)-PANTOLACTONE

(R)-Cyanohydrins (R)2b-h are obtained in good optical yields by (R)-oxynitrilase catalyzed enantioselective addition of HCN to beta-substituted pivalaldehydes 1b-h. Under optimized reaction conditions with highly purified (R)-oxynitrilase, hydroxypivalaldehyde (1a) is converted to (R)-2a in satisfactory chemical and optical yields. By acid-catalyzed hydrolysis the cyanohydrins (R)-2a-h cyclize directly to give crude (R)-pantolactone (R)-3 with ee-values of 56-95% which, after recrystallization, go up to greater than or equal to 98%ee in all cases.