Enantioselective Copper-Catalyzed Cyanation of Remote C(sp3)-H Bonds Enabled by 1,5-Hydrogen Atom Transfer

• Published in: iScience Vol. 21; pp. 490 - 498
• Main Authors: Wang, Cheng-Yu, Qin, Zi-Yang, Huang, Yu-Ling, Jin, Ruo-Xing, Lan, Quan, Wang, Xi-Sheng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.11.2019; Elsevier
• Subjects: Catalysis; Organic Synthesis; Stereochemistry; Organic Synthesis; Catalysis; Stereochemistry
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2019.10.048

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. [Display omitted] •Remote C-H functionalization•Enantioselective cyanation•High ee and excellent yields•Low catalysts loading Catalysis; Organic Synthesis; Stereochemistry