The merger of decatungstate and copper catalysis to enable aliphatic C(sp3)-H trifluoromethylation.
Nat Chem
; 12(5): 459-467, 2020 05.
Article
en En
| MEDLINE
| ID: mdl-32203440
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cobre
/
Complejos de Coordinación
/
Hidrocarburos Fluorados
Idioma:
En
Revista:
Nat Chem
Asunto de la revista:
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos