Synthesis of chiral lactams by asymmetric nitrogen insertion

This is the authors' abstract. We don't add key points for this paper.

Asymmetric nitrogen insertion into prochiral and meso cycloalkanones is achieved using diphenylphosphinyl hydroxylamine (DPPH) as the nitrogen source. A combination of Brønsted acid catalyst and Lewis acid promoter enables high yields and selectivity in the syntheses of a range of 5- to 7-membered lactams (19 examples, up to 97 : 3 er). Mechanistically, the sequence follows a Beckmann pathway involving an asymmetric condensation followed by a stereospecific rearrangement. The utility of the method is showcased by the syntheses of the drugs phenotropil, rolipram, pregabalin, and baclofen.