Zhang Hai-Jun, Xie Yan-Cheng, Yin Liang
CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
Nat Commun. 2019 Apr 12;10(1):1699. doi: 10.1038/s41467-019-09750-5.
Chiral aziridines are structure units found in many biologically active compounds and are important building blocks in organic synthesis. Herein, by merging nucleophilic generation through copper(I)-catalyzed decarboxylation and activation of poorly electrophilic 2H-azirines through protonation with carboxylic acids, an asymmetric decarboxylative Mannich reaction between α,α-disubstituted cyanoacetic acids and 2H-azirines is uncovered, which leads to generation of chiral aziridines containing vicinal tetrasubstituted and acyclic quaternary stereogenic carbon centers in good to excellent diastereo- and enantioselectivities. At last, transformations of the produced chiral aziridine are successfully carried out to deliver synthetically useful compounds.
手性氮杂环丙烷是许多生物活性化合物中的结构单元，也是有机合成中重要的构建模块。在此，通过铜（I）催化脱羧产生亲核试剂，并利用羧酸质子化来活化亲电性较弱的2H-氮杂环丙烯，发现了α,α-二取代氰基乙酸与2H-氮杂环丙烯之间的不对称脱羧曼尼希反应，该反应能以良好至优异的非对映选择性和对映选择性生成含有邻位四取代和无环季碳立体中心的手性氮杂环丙烷。最后，成功实现了所制备的手性氮杂环丙烷的转化，得到了具有合成用途的化合物。
