Selective Quadruple C(sp³)-F Functionalization of Polyfluoroalkyl Ketones

Ting Xie,^1# Guo-Qiang Wang,^2# Ya-Wen Wang,¹ Weidong Rao,³ Haiyan Xu,⁴ Shuhua Li,²* Zhi-Liang Shen,¹* and Xue-Qiang Chu¹*

¹Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China.

²Key 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.

³Jiangsu Provincial Key Lab for the Chemistry and Utilization of Agro-Forest Biomass, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China.

⁴School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212003, China.

^#Contribute equally.

Summary: The significance of organofluorine compounds have inspired the establishment of numerous methods for the functionalization of rather inert C-F bonds. Despite advances achieved in the manipulation of C(sp²)-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(sp³)-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 regio-defined perfluoroalkylated naphtho[1,2-b]furan/benzofuran derivatives by harnessing Co-promoted distinctive quadruple C(sp³)-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 Cs₂CO₃ enable expeditious C-F functionalization.

iScience 2020, 23, 101259. (Impact factor: 4.447).

论文链接：https://www.cell.com/iscience/fulltext/S2589-0042(20)30445-4