Wang Cheng-Yu, Qin Zi-Yang, Huang Yu-Ling, Jin Ruo-Xing, Lan Quan, Wang Xi-Sheng
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.
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.
iScience. 2019 Nov 22;21:490-498. doi: 10.1016/j.isci.2019.10.048. Epub 2019 Oct 26.
The direct functionalization of C(sp)-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(sp)-H bonds. Herein, we report an unprecedented protocol for enantioselective cyanation of remote C(sp)-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.
C(sp)−H键的直接官能团化已促使人们开发出以原子经济性和步骤经济性的方式从基础化学品制备分子或中间体的方法。然而，由于C(sp)−H键无处不在且反应活性低，在这些反应中实现高水平的化学选择性、区域选择性和对映选择性仍然具有挑战性。在此，我们报道了一种前所未有的远程C(sp)−H键对映选择性氰化反应方法。以手性Box-Cu配合物为催化剂，N-氟磺酰胺的反应在温和的反应条件下以优异的产率和高对映体过量（ee）提供相应产物。我们提出了一种自由基接力途径，该途径涉及N中心自由基的1,5-氢原子转移（1,5-HAT），随后对原位形成的苄基自由基进行对映选择性氰化。因此，这种对映选择性铜催化的氰化反应为药物发现中生物活性分子的合成提供了一种有效方法。
