Yuan Yang, Zhang Youcan, Li Wenbo, Zhao Yanying, Wu Xiao-Feng
Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, Liaoning, China.
School of Chemistry and Chemical Engineering, Key Laboratory of Surface & Interface Science of Polymer Materials of Zhejiang Province, Zhejiang Sci-Tech University, Hangzhou, 310018, China.
Angew Chem Int Ed Engl. 2023 Oct 2;62(40):e202309993. doi: 10.1002/anie.202309993. Epub 2023 Aug 28.
Given the prevalence of amide backbones in marketed pharmaceuticals and their ubiquity as critical binding units in natural peptides and proteins, it remains important to develop novel methods to construct amide bonds. We report here a general method for the anti-Markovnikov hydroaminocarbonylation of unactivated alkenes under mild conditions, using copper catalysis in combination with hydroxylamine electrophile reagents and poly(methylhydrosiloxane) (PMHS) as a cheap and environmentally friendly hydride source. The reaction tolerates a variety of functional groups and efficiently converts unactivated terminal alkenes, 1,1-disubstituted alkenes, and cyclic alkenes to the corresponding amides with exclusive anti-Markovnikov selectivity (and high enantioselectivities/diastereoselectivities). Additionally, with minimal modification of the reaction conditions, alkynes can also undergo tandem hydrogenation-hydroaminocarbonylation to alkyl amides.
鉴于酰胺骨架在市售药品中的普遍性，以及它们作为天然肽和蛋白质中关键结合单元的无处不在，开发构建酰胺键的新方法仍然很重要。我们在此报告一种在温和条件下对未活化烯烃进行反马氏氢胺羰基化的通用方法，该方法使用铜催化，结合羟胺亲电试剂和聚甲基氢硅氧烷（PMHS）作为廉价且环保的氢化物源。该反应能耐受多种官能团，并能将未活化的末端烯烃、1,1 - 二取代烯烃和环状烯烃高效地转化为相应的酰胺，具有唯一的反马氏选择性（以及高对映选择性/非对映选择性）。此外，只需对反应条件进行最小程度的修改，炔烃也能进行串联氢化 - 氢胺羰基化反应生成烷基酰胺。
