A facile synthesis of the key intermediate for penems, carbapenems, and related beta-lactam antibiotics

Michael addition of the hydroxylamine 14 to the N-acryloyl-1, 3-benzoxazinone 13 followed by the titanium enolate-mediated aldol reaction with acetaldehyde gave syn-aldol 16 in a high yield with excellent diastereoselectivity. Silylation of 16 followed by treatment with BnOLi and acetylation gave benzyl ester 19 together with the recovered chiral auxiliary 12 both in high yields. Mild hydrogenolysis of 19 furnished the beta-amino acid derivative 20 which was transformed into acetoxyazetidinone 3, the key intermediate of penems 1 and carbapenems 2. Copyright (C) 1996 Elsevier Science Ltd