Yuan Pengfei, Chen Jiean, Zhao Jing, Huang Yong
State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University, Shenzhen Graduate School, Shenzhen, 518055, China.
State Key Laboratory of Coordination Chemistry, Institute of Chemistry and BioMedical Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, China.
Angew Chem Int Ed Engl. 2018 Jul 9;57(28):8503-8507. doi: 10.1002/anie.201803556. Epub 2018 May 14.
An enantioselective synthesis of β-chiral amides through asymmetric and redox-neutral hydroamidation of enals is reported. In this reaction, a chiral N-heterocyclic carbene (NHC) catalyst reacts with enals to generate the homoenolate intermediate. Upon highly enantioselective β-protonation through proton-shuttle catalysis, the resulting azolium intermediate reacts with imidazole to yield the key β-chiral acyl species. This transient intermediate provides access to diversified β-chiral carbonyl derivatives, such as amides, hydrazides, acids, esters, and thioesters. In particular, β-chiral amides can be prepared in excellent yield and ee (40 chiral amides, up to 95 % yield and 99 % ee). This modular strategy overcomes the challenge of disruption of the highly selective proton-shuttling process by basic amines.
报道了一种通过烯醛的不对称氧化还原中性氢酰胺化反应对β-手性酰胺进行对映选择性合成的方法。在该反应中，手性N-杂环卡宾（NHC）催化剂与烯醛反应生成均烯醇盐中间体。通过质子穿梭催化进行高度对映选择性的β-质子化后，生成的唑鎓中间体与咪唑反应生成关键的β-手性酰基物种。这种瞬态中间体可用于制备多种β-手性羰基衍生物，如酰胺、酰肼、酸、酯和硫酯。特别地，β-手性酰胺可以以优异的产率和对映体过量值（ee）制备（40种手性酰胺，产率高达95%，ee高达99%）。这种模块化策略克服了碱性胺破坏高选择性质子穿梭过程的挑战。
