Reductive N-Alkylation of Amines with Ketones Using Heterogeneous Polysilane-Palladium Catalysts under Continuous-Flow Conditions

Org Lett. 2024 Apr 26. doi: 10.1021/acs.orglett.4c00876. Online ahead of print.

Abstract

This work reports a continuous-flow reductive N-alkylation of amines with ketones using molecular hydrogen. The reaction, performed with highly active polysilane-modified heterogeneous palladium catalysts, enables the efficient synthesis of diversely substituted amines under mild flow conditions. The developed catalyst exhibits sustained activity for 5 days (turnover number of >2400). Moreover, the utility of the method is demonstrated by the synthesis of a key intermediate of the active pharmaceutical ingredient teneligliptin.