Yu Zhang-Long, Cheng Yong-Feng, Liu Ji-Ren, Yang Wu, Xu Dan-Tong, Tian Yu, Bian Jun-Qian, Li Zhong-Liang, Fan Li-Wen, Luan Cheng, Gao Ang, Gu Qiang-Shuai, Liu Xin-Yuan
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China.
Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.
J Am Chem Soc. 2023 Mar 22;145(11):6535-6545. doi: 10.1021/jacs.3c00671. Epub 2023 Mar 13.
Transition-metal-catalyzed enantioselective functionalization of acyl radicals has so far not been realized, probably due to their relatively high reactivity, which renders the chemo- and stereocontrol challenging. Herein, we describe Cu(I)-catalyzed enantioselective desymmetrizing C-O bond coupling of acyl radicals. This reaction is compatible with (hetero)aryl and alkyl aldehydes and, more importantly, displays a very broad scope of challenging alcohol substrates, such as 2,2-disubstituted 1,3-diols, 2-substituted-2-chloro-1,3-diols, 2-substituted 1,2,3-triols, 2-substituted serinols, and meso primary 1,4-diols, providing enantioenriched esters characterized by challenging acyclic tetrasubstituted carbon stereocenters. Partnered by one- or two-step follow-up transformations, this reaction provides a convenient and practical strategy for the rapid preparation of chiral C3 building blocks from readily available alcohols, particularly the industrially relevant glycerol. Mechanistic studies supported the proposed C-O bond coupling of acyl radicals.
到目前为止，过渡金属催化的酰基自由基对映选择性官能化尚未实现，这可能是由于它们相对较高的反应活性，使得化学和立体控制具有挑战性。在此，我们描述了铜（I）催化的酰基自由基对映选择性去对称化C-O键偶联反应。该反应与（杂）芳基和烷基醛兼容，更重要的是，它对多种具有挑战性的醇底物具有广泛的适用性，如2,2-二取代的1,3-二醇、2-取代-2-氯-1,3-二醇、2-取代的1,2,3-三醇、2-取代的丝氨醇和内消旋伯1,4-二醇，能提供具有挑战性的无环四取代碳立体中心的对映体富集酯。通过一步或两步后续转化，该反应为从易得的醇，特别是工业上相关的甘油快速制备手性C3结构单元提供了一种方便实用的策略。机理研究支持了所提出的酰基自由基的C-O键偶联反应。
