Palladium-Catalyzed Decarbonylative Trifluoromethylation of Acid Fluorides

Abstract

While acid fluorides can readily be made from widely available or biomass-feedstock-derived carboxylic acids, their use as functional groups in metal-catalyzed cross-coupling reactions is rare. This report presents the first demonstration of Pd-catalyzed decarbonylative functionalization of acid fluorides to yield trifluoromethyl arenes (ArCF₃ ). The strategy relies on a Pd/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. Our experimental and computational mechanistic data support a sequence in which transmetalation by R₃ SiCF₃ occurs prior to decarbonylation.

Keywords: carboxylic acids; catalysis; density functional calculations; palladium; trifluoromethylation.

Figure 1

Overview of challenges in Pd^0/Pd^II‐catalyzed trifluoromethylation (top) and our work (bottom).

Figure 2

Mechanistic possibilities for ArCOF to ArCF₃ conversion (top) and computed activation free energy barriers at the CPCM (toluene) M06L/ def2TZVP// ωB97XD/6‐31G(d)+SDD level of theory at 160 °C [ΔG ^≠ given in kcal mol⁻¹]. Bottom: illustration of computed decarbonylation transition states.

Scheme 1

Temperature‐dependent ArCF₃ 2 a versus ArCOCF₃ 4 a formation.