Iron(III)-Catalyzed Difluoroalkylation of Aryl Alkyne with Difluoroenol Silyl Ether in the Presence of Trimethylsilyl Chloride

M.-M. Guo,^#a X.-D. Song,^#a X. Liu,^a Y.-W. Zheng,^a X.-Q. Chu,*^a W. Rao,^b Z.-L. Shen*^a

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

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

Abstract: The reaction of non-fluorinated silyl enol ether with alkyne is useful for the synthesis of β,γ-unsaturated carbonyl compounds. However, most of the existing methods for realizing such organic transformation usually employ stoichiometric amounts of relatively expensive Lewis acids/metallic salts. Herein, an iron(III)-catalyzed difluoroalkylation of aryl alkynes with difluoroenol silyl ether was developed. The reactions proceeded smoothly in the presence of a catalytic amount of iron(III) chloride, stoichiometric amounts of trimethylsilyl chloride, and 4 Å molecular sieves in dichloroethane (DCE) to afford the corresponding α-alkenyl-α,α-difluoroketones in modest to good yields. Remarkably, among the various metallic salts screened, cheap and less-toxic iron(III) salt was found to be the most efficient Lewis acid catalyst for the present reaction. In addition, in the absence of iron(III) chloride or trimethylsilyl chloride, either no reaction occurred or considerably reduced reaction performance was observed. Moreover, the use of Brønsted acid to replace iron(III) chloride as reaction catalyst failed to promote the reaction. The reaction could be scaled up and the obtained difluoroalkylated carbonyl compound serves as a versatile building block which could be subjected to late-stage diversification to be converted into useful organic molecules containing CF₂H and CF₂CF₂ moieties. Deuterated experiments showed that the proton in the generated alkene product should originate from trace amounts of water present in the reaction system.

Adv. Synth. Catal. 2022, 364, 2454–2460, DOI: 10.1002/adsc.202200277. (Impact factor: 5.981, ^#Equal contribution)

论文链接：https://doi.org/10.1002/adsc.202200277