期刊
NATURE CHEMISTRY
卷 12, 期 5, 页码 459-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41557-020-0436-1
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资金
- National Institute of General Medical Sciences (NIGMS), the NIH [R01 GM078201-05]
- Princeton University, E. Taylor and the Taylor family
The introduction of a trifluoromethyl (CF3) group can dramatically improve a compound's biological properties. Despite the well-established importance of trifluoromethylated compounds, general methods for the trifluoromethylation of alkyl C-H bonds remain elusive. Here we report the development of a dual-catalytic C(sp(3))-H trifluoromethylation through the merger of light-driven, decatungstate-catalysed hydrogen atom transfer and copper catalysis. This metallaphotoredox methodology enables the direct conversion of both strong aliphatic and benzylic C-H bonds into the corresponding C(sp(3))-CF3 products in a single step using a bench-stable, commercially available trifluoromethylation reagent. The reaction requires only a single equivalent of substrate and proceeds with excellent selectivity for positions distal to unprotected amines. To demonstrate the utility of this new methodology for late-stage functionalization, we have directly derivatized a broad range of approved drugs and natural products to generate valuable trifluoromethylated analogues. Preliminary mechanistic experiments reveal that a 'Cu-CF3' species is formed during this process and the critical C(sp(3))-CF3 bond-forming step involves the copper catalyst.
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