HIGHLY STEREOSELECTIVE SYNTHESIS OF SPIRO-ALPHA-METHYLENE-GAMMA-BUTYRO-LACTONES - THE ROLE OF ALPHA-HYDROXY SUBSTITUTION

An alpha-alkoxy substituent provides acceleration and greater diastere oselectivity in organometallic additions to chiral ketones. We find th at alpha-hydroxy substitution also plays a similar role. Whereas the a ddition of a Reformatsky reagent to unsubstituted steroidal ketones do es not yield the desired products, alpha-hydroxy substitution provides the alpha-methylene-gamma-butyrolactone steroid in good yields and ve ry high diastereoselectivity. The alpha-methylene-gamma-butyrolactone moiety has been synthesized at several positions on the steroid nucleu s. The stereochemistry can be explained through a chelated transition state, while the enhancement in the rate may be due to both the electr on-withdrawing nature of the Reformatsky reagent and the neighbouring group effect.