β-Lactam Synthesis through Diodomethane Addition to Amide Dianions

Abstract

We present a novel route for the quick and easy synthesis of a broad range of β-lactams. The synthesis involves a [3+1] cyclization of amide dianions with diiodomethane. In contrast to the seminal work of Hirai et al. from 1979, the reaction proved to be a general and efficient approach towards azetidinones. The ease of the process was confirmed by DFT calculations and its power demonstrated by a diversity-oriented synthesis of β-lactams with four points of diversity determined by the choice of Ugi adducts as starting materials.

Keywords: Ugi reactions; amides; diiodomethane; diversity-oriented synthesis; β-lactams.