Palladium‐Catalyzed Decarbonylative Trifluoromethylation of Acid Fluorides

Abstract

While acid fluorides can readily be made from widely available or biomass-feedstock-derived carboxylic acids,t heir use as functional groups in metal-catalyzed crosscoupling reactions is rare.T his report presents the first demonstration of Pd-catalyzed decarbonylative functionalization of acid fluorides to yield trifluoromethyl arenes (ArCF 3 ). The strategy relies on aP d/Xantphos catalytic system and the supply of fluoride for transmetalation through intramolecular redistribution to the the Pd center.This strategy eliminated the need for exogenous and detrimental fluoride additives and allows Xantphos to be used in catalytic trifluoromethylations for the first time.O ur experimental and computational mechanistic data support asequence in which transmetalation by R 3 SiCF 3 occurs prior to decarbonylation.

Coupling of Alternating Current to Transition-Metal Catalysis: Examples of Nickel-Catalyzed Cross-Coupling

“…The spectra data matched with values reported in the literature. 31 Rf (hexane)—0.53. 1 H NMR (400 MHz, CDCl 3 ): δ 7.74 (d, J = 8.6 Hz, 4H), 7.70 (d, J = 8.6 Hz, 4H).…”

Pd-catalyzed fluoro-carbonylation of aryl, vinyl, and heteroaryl iodides using 2-(difluoromethoxy)-5-nitropyridine

“…Based on these experiments, additional 19 F NMR experiments, and mass spectroscopy analyses (for details, see Supplementary Figs. [26][27][28] as well as information from the literature 60 , we would like to propose a plausible reaction mechanism (Fig. 6).…”

“…Due to the inertness of the C-F bond, the properties and reactivity of R-COFs are very different from those of other acyl halides and their equivalents. R-COFs are robust and multiple synthetic tools have been developed that allow easy and convenient access to a wide range of high-value organic compounds based on acyl coupling reactions that use R-COFs as an "Ar-CO" source [21][22][23][24][25][26] , on decarbonylative coupling reactions that use R-COFs as an "Ar" source [27][28][29][30][31][32][33] , and on fluorination reactions that use R-COFs as an "F" source [34][35][36][37] (Fig. 1a).…”

“…1a). Although the development of new applications for R-COFs and reactions that involve R-COFs have recently gained attention [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] , especially in the context of transition-metal catalysis, strategies for the synthesis of R-COFs remain somewhat limited [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] . Currently, the synthetic routes to R-COFs are categorized into two groups.…”

Organocatalyzed Fluoride Metathesis

“…23,24 They are also useful building blocks for the synthesis of partially fluorinated arenes relevant to drug discovery through a further hydrodefluorination step. [25][26][27] Acyl fluorides are versatile fluorinating agents for a variety of reactions including: oxidative addition to transition metals; 27,28 the enantioselective ring-opening fluorination of epoxides, 29 and the hydrofluorination of alkynes. 30 A series of experiments and calculations were undertaken to interrogate the proposed mechanism of fluoride metathesis.…”