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Copper-Mediated Cyanodifluoromethylation of (Hetero)aryl Iodides and Activated (Hetero)aryl Bromides with TMSCF2CN.
Nicolai, Jeremy; Fantoni, Tommaso; Butcher, Trevor W; Arlow, Sophie I; Ryabukhin, Serhiy V; Volochnyuk, Dmytro M; Hartwig, John F.
Afiliación
  • Nicolai J; Department of Chemistry, University of California, Berkeley, California 94720, United States.
  • Fantoni T; Department of Chemistry, University of California, Berkeley, California 94720, United States.
  • Butcher TW; Department of Chemistry, University of California, Berkeley, California 94720, United States.
  • Arlow SI; Department of Chemistry, University of California, Berkeley, California 94720, United States.
  • Ryabukhin SV; The Institute of High Technologies, Taras Shevchenko National University of Kyiv, Kyiv 03022, Ukraine.
  • Volochnyuk DM; Enamine Ltd, Kyiv 02094, Ukraine.
  • Hartwig JF; Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv 02000, Ukraine.
J Am Chem Soc ; 146(22): 15464-15472, 2024 06 05.
Article en En | MEDLINE | ID: mdl-38780539
ABSTRACT
Molecules bearing fluorine are increasingly prevalent in pharmaceuticals, agrochemicals, and functional materials. The cyanodifluoromethyl group is unique because its size is closer than that of any other substituted difluoromethyl group to the size of the trifluoromethyl group, but its electronic properties are distinct from those of the trifluoromethyl group. In addition, the presence of the cyano group provides synthetic entry to a wide range of substituted difluoromethyl groups. However, the synthesis of cyanodifluoromethyl compounds requires multiple steps, highly reactive reagents (such as DAST, NSFI, or IF5), or specialized starting materials (such as α,α-dichloroacetonitriles or α-mercaptoacetonitriles). Herein, we report a copper-mediated cyanodifluoromethylation of aryl and heteroaryl iodides and activated aryl and heteroaryl bromides with TMSCF2CN. This cyanodifluoromethylation tolerates an array of functional groups, is applicable to late-stage functionalization of complex molecules, yields analogues of FDA-approved pharmaceuticals and fine chemicals, and enables the synthesis of a range of complex molecules bearing a difluoromethylene unit by transformations of the electron-poor CN unit. Calculations of selected steps of the reaction mechanism by Density Functional Theory indicate that the barriers for both the oxidative addition of iodobenzene to [(DMF)CuCF2CN] and the reductive elimination of the fluoroalkyl product from the fluoroalkyl copper intermediate lie in between those of [(DMF)CuCF3] and [(DMF)CuCF2C(O)NMe2].

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: J Am Chem Soc Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: J Am Chem Soc Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos