A convenient stereoselective synthesis of β-lactams from β-hydroxy-α-thioalkylesters prepared from Michael/aldol tandem reaction or stereoselective addition of thiols to the Baylis–Hillman adducts

Abstract A convenient stereoselective synthesis of β-lactams from thio-Michael/aldol tandem adduct is described. syn -Selective tandem reaction followed by amidation and intramolecular S N 2 reaction provided β-lactams in diastereomerically pure form. The tandem reaction with aliphatic aldehydes, on the other hand, afforded a mixture of diastereomers of corresponding tandem adducts in about 3:1 ratio so that the conversion to β-lactams afforded a diastereomeric mixture. As an alternative approach to prepare the tandem adducts, the stereoselective Michael addition of aliphatic thiols to Baylis–Hillman adduct was developed. The stereoselectivity was sensitive to the protective group at the hydroxyl group and TBS protection brought the most successful syn -selective formation of the tandem adducts. The procedure could be applied to the ketone derivatives of the Baylis–Hillman adduct but no selectivity was observed for the nitrile-Baylis–Hillman adducts. A similar conversion of the adduct provided desired β-lactams stereoselectively.