Stereocontrolled formation of cephams from 1,3-O-ethylidene-L-erythritol

[2+2]Cycloaddition of chlorosulfonyl isocyanate to (Z)-1,3-O-ethylidene-2-0-propenyl-4-0-trityl-L-erythritol proceeds with excellent stereoselectivity to afford the corresponding (R)-4'-alkoxy-azetidin-2-one which can be transformed into 5-oxa-cepham by intramolecular alkylation of the p-lactam nitrogen atom. Cepham having the alternative (S) configuration at the bridgehead carbon atom can be achieved by another methodology based on alkylation of the nitrogen atom in 4-vinyloxy-aze-tidin-2-one by the suitably protected 1,3-ethylidene-L-erythritol followed by intramolecular displacement of the vinyloxy group. (C) 2001 Elsevier Science Ltd. All rights reserved.