Xie Ting, Wang Guo-Qiang, Wang Ya-Wen, Rao Weidong, Xu Haiyan, Li Shuhua, Shen Zhi-Liang, Chu Xue-Qiang
Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China.
Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
iScience. 2020 Jul 24;23(7):101259. doi: 10.1016/j.isci.2020.101259. Epub 2020 Jun 11.
The significance of organofluorine compounds has inspired the establishment of numerous methods for the functionalization of rather inert C-F bonds. Despite advances achieved in the manipulation of C(sp)-F bonds by employing transition-metal catalysts, such as Pd, Rh, Cu, Ni, Ru, and Ir, strategies that address the paucity of effective pathways for selective activation of multiple C(sp)-F bonds remained challenging. In this context, we present an unprecedented coupling-aromatization-cyclization reaction of polyfluorinated ketones with diverse N- and S-nucleophiles that forms regiodefined perfluoroalkylated naphtho[1,2-b]furan/benzofuran derivatives by harnessing Co-promoted distinctive quadruple C(sp)-F bonds cleavage relay. This chemistry involving controlled and successive selective defluorination at heteronuclear centers would greatly contribute to the preparation of drug-like heterocycles as well as the late-stage elaboration of biorelevant compounds. Controlled experiments and DFT theoretical studies revealed that the combination of cheap cobalt salt with CsCO enable expeditious C-F functionalization.
有机氟化合物的重要性促使人们建立了许多用于惰性C-F键官能化的方法。尽管在通过使用过渡金属催化剂（如Pd、Rh、Cu、Ni、Ru和Ir）来操纵C(sp)-F键方面取得了进展，但解决多个C(sp)-F键选择性活化有效途径匮乏问题的策略仍然具有挑战性。在此背景下，我们报道了多氟代酮与各种N-和S-亲核试剂之间前所未有的偶联-芳构化-环化反应，该反应通过利用钴促进的独特四重C(sp)-F键裂解接力，形成区域选择性定义的全氟烷基化萘并[1,2-b]呋喃/苯并呋喃衍生物。这种涉及在异核中心进行可控且连续选择性脱氟的化学方法，将极大地有助于制备类药物杂环以及生物相关化合物的后期修饰。对照实验和DFT理论研究表明，廉价钴盐与CsCO的组合能够实现快速的C-F官能化。
