Bimetallic Relay Catalysis for Radical Hydrofunctionalization of Alkenes with Diverse Nucleophiles
The radical hydrofunctionalization of alkenes with nucleophiles has been established as a reliable method for constructing organic molecules in organic synthesis. Despite recent efforts, the reaction selectivity and efficiency toward a broad spectrum of nucleophiles remain highly challenging. Herein, we disclose a mechanistically distinct cobalt/copper bimetallic relay catalytic system, which enables radical hydrofunctionalization of alkenes with an unprecedented nucleophile scope. Different kinds of nucleophiles, ranging from amines, alcohols, and phosphonates to alkynes, TMSN<sub>3</sub>, TMSCN, and NH<sub>4</sub>SCN, all demonstrate excellent reactivity, delivering the target products in moderate to good yields (up to 94%) under mild conditions. The protocol accommodates a broad range of nucleophilic partners through the synergistic interplay between cobalt and copper centers. Mechanistic studies, including radical clock and EPR experiments, Stern-Volmer quenching studies, and DFT calculations, demonstrate a synergistic cobalt/copper bimetallic radical relay process. Furthermore, its synthetic versatility is highlighted by the successful development of an enantioselective hydroamination variant using a commercially available chiral MebBox ligand (L2), giving rise to a rich library of structurally diverse chiral amine building blocks with up to 92% ee (>99% ee after recrystallization).
Authors
- Jin Xie (ORCID: https://orcid.org/0000-0003-2600-6139)
- Zhong Tao (ORCID: https://orcid.org/0000-0003-2117-2162)
- Jun Huang (ORCID: https://orcid.org/0000-0003-1861-2390)
- Chengjian Zhu (ORCID: https://orcid.org/0000-0003-4465-9408)
- Yaohang Cheng
- Peicheng Luo
- Hongliang Chen (ORCID: https://orcid.org/0000-0002-4442-7984)
- Weipeng Li (ORCID: https://orcid.org/0000-0001-8305-2479)
- Yulong Fu (ORCID: https://orcid.org/0009-0009-8936-9800)
Institutions
- Nanjing University (CN)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2025-11-14
- DOI
- https://doi.org/10.1021/jacs.5c15985
- Citations
- 3
- Primary Topic
- Radical Photochemical Reactions
- Type
- article
- Field-Weighted Citation Impact
- 2.81