Formation of bicyclic beta-lactams from dichloro-1,4-oxathiane-3-carboxanilides: Nucleophilic substitution of nitrogen on anomeric carbon

Abstract

Transformation of dichloro-1,4-oxathiane anilides (2) to bicyclic beta-lactam (5) is described. In the presence of sodium hydride, an intramolecular nucleophilic substitution of nitrogen to anomeric carbon of 2 gave (1R*, 6R*)-1-chloro-6-methyl-7-phenyl-5-oxa-2-thia-7-azabicyclo[4,2,0]octan-8-ones (5). The reason for facile displacement at C-2 is attributable to neighboring group participation of sulfur and C-2 is anomeric. Plausible mechanisms for the formation of 2-chloromethyl-5,6-dihydro-N-phenyl-1,4-oxathiin-3-carboxyamide (4) under the neutral conditions, or 2,3-dihydroxy-2-methyl-N-phenyl-1,4-oxathiane-3-carboxyamide (9) in aqueous solution, or bicyclic beta-lactam (5) in the presence of sodium hydride were proposed.