Work

Synthesis of chiral lactams by asymmetric nitrogen insertion

Year: 2025

Type: article

Abstract: 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.

Source: Chemical Science

DOI: 10.1039/d5sc08417b

Authors: Jasmin Hammes, Clara Mañas, Abhilash Pedada, Marlene Arnold, Johannes M. Wahl

Institution: Johannes Gutenberg University Mainz

Language: English

Topic: Asymmetric Synthesis and Catalysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: diamond

Funders: Boehringer Ingelheim, Deutsche Forschungsgemeinschaft, Johannes Gutenberg-Universität Mainz, H2020 European Research Council

Awards: G3797312198, SFB 1552: Defekte und Defektkontrolle in weicher Materie