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Dual electrocatalysis enables enantioselective hydrocyanation of conjugated alkenes.
Song, Lu; Fu, Niankai; Ernst, Brian G; Lee, Wai Hang; Frederick, Michael O; DiStasio, Robert A; Lin, Song.
Afiliación
  • Song L; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.
  • Fu N; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.
  • Ernst BG; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.
  • Lee WH; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.
  • Frederick MO; Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, IN, USA.
  • DiStasio RA; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA. distasio@cornell.edu.
  • Lin S; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA. songlin@cornell.edu.
Nat Chem ; 12(8): 747-754, 2020 08.
Article en En | MEDLINE | ID: mdl-32601407
Chiral nitriles and their derivatives are prevalent in pharmaceuticals and bioactive compounds. Enantioselective alkene hydrocyanation represents a convenient and efficient approach for synthesizing these molecules. However, a generally applicable method featuring a broad substrate scope and high functional group tolerance remains elusive. Here, we address this long-standing synthetic problem using dual electrocatalysis. Using this strategy, we leverage electrochemistry to seamlessly combine two canonical radical reactions-cobalt-mediated hydrogen-atom transfer and copper-promoted radical cyanation-to accomplish highly enantioselective hydrocyanation without the need for stoichiometric oxidants. We also harness electrochemistry's unique feature of precise potential control to optimize the chemoselectivity of challenging substrates. Computational analysis uncovers the origin of enantio-induction, for which the chiral catalyst imparts a combination of attractive and repulsive non-covalent interactions to direct the enantio-determining C-CN bond formation. This work demonstrates the power of electrochemistry in accessing new chemical space and providing solutions to pertinent challenges in synthetic chemistry.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Alquenos / Nitrilos Idioma: En Revista: Nat Chem Asunto de la revista: QUIMICA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Alquenos / Nitrilos Idioma: En Revista: Nat Chem Asunto de la revista: QUIMICA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido