Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Jiangsu National Synergetic Innovation Center for Advanced Materials, Nanjing Tech University, Nanjing 211816, China.
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
Org Lett. 2021 May 21;23(10):4018-4022. doi: 10.1021/acs.orglett.1c01232. Epub 2021 May 10.
Herein, we disclose a transition-metal-free reaction system that enables α-cyanation of sulfonamides through C-H bond cleavage for the preparation of α-amino nitriles, including difficult-to-access all-alkyl α-tertiary scaffolds. More than 50 substrate examples prove a wide functional group tolerance. Additionally, its synthetic practicality is highlighted by gram-scalability and the late-stage modification of natural compounds. Mechanistic experiments suggest that this process involves in situ formation of an imine intermediate via base-promoted elimination of HF.
在这里,我们揭示了一种无过渡金属的反应体系,通过 C-H 键断裂实现磺酰胺的α-氰化反应,从而制备包括难以获得的全烷基α-叔碳骨架在内的α-氨基酸腈。超过 50 个底物实例证明了该方法具有广泛的官能团容忍性。此外,通过克级规模放大实验和对天然化合物的后期修饰,突出了其合成实用性。机理实验表明,该过程涉及通过碱促进 HF 消除原位形成亚胺中间体。