Synthesis of polycyclic furan and chromene derivatives via cascade reactions enabled by cleavage of multiple C(sp³)-F bonds

Ting Xie,^a Chen Zhang,^a Si-Xuan Zhang,^a Weidong Rao,^b Haiyan Xu,^c Zhi-Liang Shen,*^a and Xue-Qiang Chu*^a

^a Technical Institute of Fluorochemistry (TIF), Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, People’s Republic of China.

^b Jiangsu Provincial Key Lab for the Chemistry and Utilization of Agro-Forest Biomass, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, People’s Republic of China.

^c School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212003, People’s Republic of China.

Abstract: The strong and unreactive C-F bond makes polyfluorocarbons extremely long-lived and potentially toxic. A successive selective and controllable C(sp³)-F functionalization of polyfluoroalkylated ketones with S- and O-nucleophiles to enable efficient synthesis of pharmaceutically important fluorine- and sulfur-containing polycyclic furan and chromene derivatives under transition metal-free conditions is demonstrated here. The combination of C-S/C-O coupling, aromatization, and cyclization cascade contribute to the accurate four/five C(sp³)-F bond cleavage at two different sites of perfluoroalkyl chain. The formation of reactive quinoid intermediates and the necessity of using TBAB (tetrabutylammonium bromide) as additive and Cs₂CO₃ as base were identified by detailed mechanistic studies.

Adv. Synth. Catal. 2020, 362, DOI: 10.1002/adsc.202000660 (Impact factor: 5.851).

论文链接：https://onlinelibrary.wiley.com/doi/abs/10.1002/adsc.202000660