Qian Siran, Lazarus Tanya M, Nicewicz David A
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, United States.
J Am Chem Soc. 2023 Aug 23;145(33):18247-18252. doi: 10.1021/jacs.3c06936. Epub 2023 Aug 14.
The β-amino nitrile moiety and its derivatives frequently appear in natural product synthesis, in drug design, and as ligands in asymmetric catalysis. Herein, we describe a direct route to these complex motifs through the amino- and oxycyanation of olefins utilizing an acridinium photooxidant in conjunction with copper catalysis. The transformation can be rendered asymmetric by using a serine-derived bisoxazoline ligand. Mechanistic studies implicate olefin-first oxidation. The scope of amines for the aminocyanation reaction has been greatly expanded by undergoing a cation radical intermediate as opposed to previous -centered radical-initiated aminocyanations. Furthermore, alkyl carboxylic acids were included as nucleophiles in this type of transformation for the first time without any decarboxylative side reactions.
β-氨基腈部分及其衍生物经常出现在天然产物合成、药物设计以及不对称催化中的配体中。在此,我们描述了一种通过使用吖啶鎓光氧化剂与铜催化相结合,对烯烃进行氨基氰化和氧氰化反应来直接合成这些复杂结构单元的方法。通过使用丝氨酸衍生的双恶唑啉配体,该转化反应可以实现不对称性。机理研究表明烯烃首先发生氧化反应。与之前以碳为中心的自由基引发的氨基氰化反应不同,通过阳离子自由基中间体,氨基氰化反应中胺的适用范围得到了极大的扩展。此外,首次将烷基羧酸作为亲核试剂纳入此类转化反应中,且没有任何脱羧副反应。