Selective Quadruple C(sp3)-F Functionalization of Polyfluoroalkyl Ketones
Ting Xie,
Guo-Qiang Wang,
Ya-Wen Wang,
Weidong Rao,
Haiyan Xu,
Shuhua Li,
Zhi-Liang Shen,
Xue-Qiang Chu
Affiliations
Ting Xie
Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China
Guo-Qiang Wang
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
Ya-Wen Wang
Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China
Weidong Rao
Jiangsu Provincial Key Lab for the Chemistry and Utilization of Agro-Forest Biomass, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China
Haiyan Xu
School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212003, China
Shuhua Li
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; Corresponding author
Zhi-Liang Shen
Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China; Corresponding author
Xue-Qiang Chu
Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China; Corresponding author
Summary: 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(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 regiodefined 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.
