Ag_(2)O/squaramide cocatalyzed asymmetric interrupted Barton-Zard reaction of 8-nitroimidazo[1,2-a]pyridines  

氧化银/方酰胺共催化8-硝基咪唑并[1,2-a]吡啶的不对称中断Barton-Zard反应

作　　者：Qian Wan Chao Zheng Yao-Feng Yuan Shu-Li You 万倩;郑超;袁耀锋;游书力(State Key Laboratory of Organometallic Chemistry,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032,China;College of Chemistry,Fuzhou University,Fuzhou 350108,China)

机构地区：[1]State Key Laboratory of Organometallic Chemistry,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032,China [2]College of Chemistry,Fuzhou University,Fuzhou 350108,China

出　　处：《Science Bulletin》2022年第16期1688-1695,M0004,共9页科学通报（英文版）

基　　金：supported by the National Key R&D Program of China(2021YFA1500100);the National Natural Science Foundation of China(21821002,22031012,and 22171282);the Science and Technology Commission of Shanghai Municipality(19590750400 and 21520780100)。

摘　　要：Imidazo[1,2-a]pyridines are present in numerous biologically active compounds as the core structural motif.Herein,we report an asymmetric interrupted Barton-Zard reaction of electron-deficient imidazo[1,2-a]pyridines withα-substituted isocyanoacetates.The reaction enables the dearomatization of 8-nitroimidazo[1,2-a]pyridines and hence offers straightforward access to an array of optically active highly functionalized imidazo[1,2-a]pyridine derivatives that possess three contiguous stereogenic centers in good yields(up to 98%)with high stereoselectivities(>19:1 dr,>99%ee).It is worth noting that the catalytic system consisting of a chiral squaramide and silver oxide displays remarkable reactivity and stereoselectivity,and a gram-scale reaction is compatible with the catalyst loading of 0.5 mol%.In addition,the synthetic potential of this method was showcased by versatile transformations of the product.咪唑并[1,2-a]吡啶是一类独特的杂芳环骨架,广泛存在于生物活性分子中.本文实现了缺电子咪唑并[1,2-a]吡啶与α-取代异氰基乙酸酯的不对称中断Barton-Zard反应,以优秀的收率和立体选择性获得一系列具有3个连续立体中心的咪唑并[1,2-a]吡啶衍生物.由氧化银和手性方酰胺组成的催化体系表现出显著的催化活性和立体选择性.反应可以放大至克级规模,催化剂用量可以降低至0.5%(摩尔百分比).此外,反应产物可以进行多样化的转化.这一工作为合成手性咪唑并[1,2-a]吡啶类衍生物提供了新的策略.

关 键 词：Asymmetric catalysis DEAROMATIZATION Interrupted Barton-Zard reaction Imidazo[1 2-a]pyridine Isocyanoacetates 

分 类 号：O626[理学—有机化学]