Enantioselective Copper-Catalyzed Cyanation of Remote C(sp3)-H Bonds Enabled by 1,5-Hydrogen Atom Transfer
Cheng-Yu Wang,
Zi-Yang Qin,
Yu-Ling Huang,
Ruo-Xing Jin,
Quan Lan,
Xi-Sheng Wang
Affiliations
Cheng-Yu Wang
Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, Center for Excellence in Molecular Synthesis of CAS, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, P. R. China
Zi-Yang Qin
Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, Center for Excellence in Molecular Synthesis of CAS, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, P. R. China
Yu-Ling Huang
Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, Center for Excellence in Molecular Synthesis of CAS, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, P. R. China
Ruo-Xing Jin
Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, Center for Excellence in Molecular Synthesis of CAS, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, P. R. China
Quan Lan
Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, Center for Excellence in Molecular Synthesis of CAS, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, P. R. China
Xi-Sheng Wang
Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, Center for Excellence in Molecular Synthesis of CAS, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, P. R. China; Corresponding author
Summary: The direct functionalization of C(sp3)-H bonds has led to the development of methods to access molecules or intermediates from basic chemicals in an atom- and step-economic fashion. Nevertheless, achieving high levels of chemo-, regio-, and enantioselectivity in these reactions remains challenging due to the ubiquity and low reactivity of C(sp3)-H bonds. Herein, we report an unprecedented protocol for enantioselective cyanation of remote C(sp3)-H bonds. With chiral Box-Cu complex as the catalyst, the reaction of N-fluorosulfonamide furnishes the corresponding products in excellent yields and high enantiomeric excess (ee) under mild reaction conditions. A radical relay pathway involving 1,5-hydrogen atom transfer (1,5-HAT) of N-center radicals followed by enantioselective cyanation of the in situ-formed benzyl radicals is proposed. This enantioselective copper-catalyzed cyanation thus offers insights into an efficient way for the synthesis of bioactive molecules for drug discovery. : Catalysis; Organic Synthesis; Stereochemistry Subject Areas: Catalysis, Organic Synthesis, Stereochemistry
