Nickel-Catalyzed Cascade C–H Alkynylation/Hydroamination of Free Benzylamines for the Synthesis of Substituted 1H-Isoindoles Using a Transient Directing Group Strategy

Xinghao Cai; Wei Lu; Chen Ma; Ying Kang; Yuqiang Ren; Xue Meng; David J. Craik; Shiming Fan; Lai Yue Chan; Shouxin Liu

doi:10.1002/cjoc.70222

Chinese Journal of Chemistry ›› 2025, Vol. 43 ›› Issue (23) :3171 -3177. DOI: 10.1002/cjoc.70222

Concise Report

Nickel-Catalyzed Cascade C–H Alkynylation/Hydroamination of Free Benzylamines for the Synthesis of Substituted 1H-Isoindoles Using a Transient Directing Group Strategy

Author information +

History +

PDF

Abstract

A nickel-catalyzed cascade C(sp²)–H alkynylation/hydroamination of unprotected α-substituted benzylamines is achieved using a transient directing group (TDG). The combination of a TDG with a nickel catalyst significantly improves the overall step- and atom-economy. Studies have shown that the p-trifluoromethylbenzoic acid ligand is critical for achieving C(sp²)–H alkynylation and subsequent intramolecular hydroamination. This protocol provides a straightforward and efficient route for synthesizing substituted 1H-isoindoles, featuring good substrate compatibility.

Keywords

Nickel / Transient directing group / Cascade / Alkynylation / Hydroamination / 1H-Isoindoles / 3d transition metals / C–H activation / N-Heterocycles

Cite this article

Download citation ▾

Xinghao Cai, Wei Lu, Chen Ma, Ying Kang, Yuqiang Ren, Xue Meng, David J. Craik, Shiming Fan, Lai Yue Chan, Shouxin Liu. Nickel-Catalyzed Cascade C–H Alkynylation/Hydroamination of Free Benzylamines for the Synthesis of Substituted 1H-Isoindoles Using a Transient Directing Group Strategy. Chinese Journal of Chemistry, 2025, 43(23): 3171-3177 DOI:10.1002/cjoc.70222