Three-component synthesis of β-phostams

Abstract

Reaction of ethyl diarylmethylphosphonochloridates, cinnamaldehydes, and lithium hexamethyldisilylamide (LiHMDS) directly accesses β-phostams in satisfactory to excellent yields with moderate to good diastereoselectivities. The reaction is a tandem sequence of the imine formation of cinnamaldehydes with LiHMDS and subsequent [2 + 2] annulation of the imines with phosphonochloridates. The reaction features readily available starting materials, high atom-economy, no catalyst, mild conditions, and separable diastereomers. β-Phostams are highly potential antibiotic and enzyme inhibitor candidates.