HIGHLY STEREOSELECTIVE ACCESS TO NOVEL 2,2,4-TRISUBSTITUTED TETRAHYDROFURANS BY HALOCYCLIZATION - PRACTICAL CHEMOENZYMATIC SYNTHESIS OF SCH-51048, A BROAD-SPECTRUM ORALLY-ACTIVE ANTIFUNGAL AGENT

A convenient synthesis of (-)-(2R)-cis-tosylate 2 is reported via ster eoselective 5-exo iodocyclization of the optically active 2,2-disubsti tuted olefin 9a. Enzymatic desymmetrization of the homoallylic diol 4 with Novo SP435 allowed optimal pro-(S) selectivity to provide the des ired (-)-(S)-monoacetate 9a. Under the irreversible reaction condition s, the presence of a bulky aryl substituent on the 2,2-disubstituted o lefin seems to determine stereochemical outcome of these halocyclizati ons.