Strategies for the formation of 1-dethia-1-oxa-cephams

The paper describes three possible routes for the formation of 1-dethia-1-o xa-cephams. The first two routes: (a) [2+2]cycloaddition to chiral vinyl et hers and (b) condensation of 4-acetoxyazetidin-2-one to chiral alcohols, ar e followed by the ring closure step involving N-alkylation. The third route (c) consists of N-alkylation prior to the cyclization step. In order to co mpare routes (a), (b) and (c), diastereomeric 1-dethia-3-(4-methoxybenzylox y)-1-oxacephams were synthesized using three possible strategies. While the comparison of stereoselectivities of the [2+2]cycloaddition method (a) and the condensation (b) shows unequivocally the advantage of the former, the route (c) leads to the reverse direction of asymmetric induction relative t o the first two steps and offers the highest asymmetric induction. (C) 2000 Elsevier Science Ltd. All rights reserved.