Regioselective chlorination of valine derivatives

Abstract

Reaction of N-benzoylvaline methyl ester (5a) with sulphuryl chloride gave the β-chlorovaline derivative (6a) and lesser amounts of diastereoisomers of the γ-chlorovaline derivative (7a). A similar mixture of products was obtained through photolysis of the N-chloroamide (13). The reactions of the valine derivatives (5a) and (13) involve regioselective intermolecular transfer of the β-valinyl hydrogen. There is no evidence for reaction at the α-position. The β-chloroalanine derivative (23) was produced through reaction of N-benzoylalanine methyl ester (17a) with sulphuryl chloride and by photolysis of the N-chloroamide (22). Chlorination of the azetidinone (16a) gave (16b) in modest yield. These reactions establish the chemical validity of a regiospecific hydrogen-atom abstraction proposed in penicillin biosynthesis.