Park Sang Yeon, Liu Yidong, Oh Joong Suk, Kweon Yoo Kyung, Jeong Yong Bok, Duan Mengying, Tan Yu, Lee Ji-Woong, Yan Hailong, Song Choong Eui
Department of Chemistry, Sungkyunkwan University, Suwon, 440-746, Korea.
Innovative Drug Research Centre, Chongqing University, Chongqing, 401331, China.
Chemistry. 2018 Jan 24;24(5):1020-1025. doi: 10.1002/chem.201703800. Epub 2017 Dec 5.
Asymmetric cation-binding catalysis, in principle, can generate "chiral" anionic nucleophiles, where the counter cations are coordinated within chiral environments. Nitrogen nucleophiles are intrinsically basic, therefore, its use as nucleophiles is often challenging and limiting the scope of the reaction. Particularly, a formation of configurationally labile aminal centers with alkyl substituents has been a formidable challenge due to the enamine/imine equilibrium of electrophilic substrates. Herein, we report enantioselective nucleophilic addition reactions of potassium phthalimides to Boc-protected alkyl- and aryl-substituted α-amido sulfones. In situ generated imines smoothly reacted with the nitrogen nucleophiles to corresponding aminals with good to excellent enantioselectivitiy under mild reaction conditions. In addition, transformation of aminal products gave biologically relevant pyrrolidinone-fused hexahydropyrimidine scaffold with excellent stereoselectivity and good yield.
原则上，不对称阳离子结合催化可以产生“手性”阴离子亲核试剂，其中抗衡阳离子在手性环境中配位。氮亲核试剂本质上是碱性的，因此，将其用作亲核试剂往往具有挑战性，并限制了反应的范围。特别是，由于亲电底物的烯胺/亚胺平衡，具有烷基取代基的构型不稳定氨基中心的形成一直是一个巨大的挑战。在此，我们报道了邻苯二甲酰亚胺钾与Boc保护的烷基和芳基取代的α-酰胺基砜的对映选择性亲核加成反应。原位生成的亚胺在温和的反应条件下与氮亲核试剂顺利反应，生成对映选择性良好至优异的相应氨基化合物。此外，氨基产物的转化以优异的立体选择性和良好的产率得到了与生物相关的吡咯烷酮稠合六氢嘧啶骨架。
