Metal-Free Difunctionalization of Pyridines: Selective Construction of N-CF2H and N-CHO Dihydropyridines

Sen Zhou; Ze-Ying Sun; Kongying Zhu; Wentao Zhao; Xiangyang Tang; Minjie Guo; Guangwei Wang

doi:10.1021/acs.orglett.1c00352

Metal-Free Difunctionalization of Pyridines: Selective Construction of N-CF₂H and N-CHO Dihydropyridines

Org Lett. 2021 Mar 19;23(6):2205-2211. doi: 10.1021/acs.orglett.1c00352. Epub 2021 Feb 26.

Authors

Sen Zhou¹, Ze-Ying Sun¹, Kongying Zhu², Wentao Zhao¹, Xiangyang Tang¹, Minjie Guo³, Guangwei Wang¹

Affiliations

¹ Tianjin Key Laboratory of Molecular Optoelectronic Science, Department of Chemistry, School of Science, Tianjin University, Tianjin 300072, P. R. China.
² Nuclear Magnetic Resonance Testing Center, Tianjin University, Tianjin 300072, P. R. China.
³ Institute for Molecular Design and Synthesis, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, P. R. China.

PMID: 33635677
DOI: 10.1021/acs.orglett.1c00352

Abstract

The reactivity of N-difluoromethylpyridinium salts is seldom explored because of their instability and low availability. Here we present a novel nucleophilic addition of N-difluoromethylpyridinium salts with nitroalkanes to synthesize N-CF₂H-dihydropyridines and N-CHO-dihydropyridines in a highly efficient and regioselective pathway. This protocol exhibits good functional group tolerance and good to excellent yields.

Publication types

Research Support, Non-U.S. Gov't