Asymmetric synthesis of 34- [formula omitted]-substituted β-lactams via chiral norephedrine-derived oxazolidines.

Abstract

A diastereo- and enantioselective approach to functionalized 3,4- cis -β-lactams 9 and 16 was developed based on the use of chiral norephedrine-derived oxazolidines. The key-steps in the synthesis of 9 (Scheme 1) are the potassium hypochlorite epoxidation of aldehyde 1 and the lithium dimethylcuprate addition to acid 2, both steps proceed regio- and stereoselectively (98%) and in high yield. Standard synthetic methods and the Miller hydroxamate procedure for NC cyclization were used to complete the synthesis of the target cis -β-lactwn 9 (98% enantiomeric excess). In the synthesis of cis -substituted 3-amino-2-azetidinone 16 (Scheme 4) the key-step is the aqueous ammonia opening of epoxy acid 2 which proceeds regio- and stereoselectively (98%). The Miller-type cyclization of hydroxamate 15a under Mitsunobu conditions failed to give 16a in a yield higher than 35%.