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Copper-catalyzed C-N cross-coupling of (hetero)aryl bromides with N-Boc hydrazine
Zanjie Xu1, Ting Liu1, Mingming Liu1
1Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China. weihuizhong@zjut.edu.cn.
Abstract:
The selective synthesis of arylhydrazines remains a significant challenge, particularly for sterically hindered substrates. Herein, we report an efficient CuI/6-hydroxypicolinohydrazide catalytic system for the highly monoarylation-selective C-N cross-coupling of (hetero)aryl bromides with N-Boc hydrazine. This practical protocol features a broad substrate scope and smoothly accommodates challenging ortho-substituted arenes, effectively overcoming the limitations of previous cross-coupling methods. The synthetic utility and potential impact of this approach are further demonstrated by gram-scale synthesis and straightforward downstream derivatization into valuable bioactive molecular scaffolds, including precursors for NMDA receptor antagonists and tryptamine derivatives.
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