551936-59-5Relevant articles and documents
The merger of decatungstate and copper catalysis to enable aliphatic C(sp 3)–H trifluoromethylation
Sarver, Patrick J.,Bacauanu, Vlad,Schultz, Danielle M.,DiRocco, Daniel A.,Lam, Yu-hong,Sherer, Edward C.,MacMillan, David W. C.
, p. 459 - 467 (2020/03/23)
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(sp3)–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(sp3)–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(sp3)–CF3 bond-forming step involves the copper catalyst. [Figure not available: see fulltext.].
