中科院上海有机化学研究所张国柱团队报道了光诱导铜催化环胺分子内1,5-氢原子转移的不对称C(sp3)-H炔化反应。相关研究成果于2022年6月25日发表在《德国应用化学》。
开发一种温和且通用的环胺C（sp3）–H功能化方法一直是一个挑战。
该文中，研究人员描述了在光照下通过分子内1,5-氢原子转移（HAT），铜催化的未活化环2-碘代苯甲酰胺的对映选择性C（sp3）H炔化反应。新的双恶唑啉二苯胺配体与1,1’-双-2-萘酚结合使用，显著提高了铜络合物的还原电位，这是该化学成功的关键。
机理和计算研究表明，新的铜配合物具有光氧化还原和偶联催化剂的双重作用，反应经历了自由基过程，分子内1,5-HAT过程参与了限速步骤。除了广泛的底物范围，包括前所未有的苯并环胺外，该方法还通过底物控制对2-单取代环胺表现出优异的非对映选择性。
附：英文原文
Title: Photoinduced Copper-Catalyzed Asymmetric C(sp3)-H Alkynylation of Cyclic Amines by Intramolecular 1,5-Hydrogen Atom Transfer
Author: Rui Guo, Haijing Xiao, Sijia Li, Yixin Luo, Jiahui Bai, Mengzhen Zhang, Xiaotian Qi, Yinlong Guo, Guozhu Zhang
Issue&Volume: 2022-06-25
Abstract: The development of a mild and general method for C(sp3)–H functionalization of cyclic amines has been an ongoing challenge. In this work, we described the copper-catalyzed enantioselective C(sp3)H alkynylation of unactivated cyclic 2-iodo-benzamide under photo-irradiation by intramolecular 1,5-hydrogen atom transfer (HAT). The employment of a new bisoxazoline diphenylamine ligand, in conjunction with 1,1'-bi-2-naphthol, which significantly improved the reduction potential of the copper complex, was the key to success of this chemistry. Mechanistic and computational studies supported that the new copper complex served dual role as a photoredox and coupling catalyst, the reaction went through a radical process, and the intramolecular 1,5-HAT process was involved in the rate-limiting step. Apart from broad substrate scope including unprecedented benzocyclic amines, this method also showed excellent diastereoselectivity in 2-monosubstituted cyclic amines via substrate control.
DOI: 10.1002/anie.202208232
Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202208232
