CF₃–Ph Reductive Elimination from [(Xantphos)Pd(CF₃)(Ph)]

Abstract

CF3–Ph reductive elimination from [(Xantphos)Pd(Ph)(CF3)] (1) and [(i-Pr-Xantphos)Pd(Ph)(CF3)] (2) has been studied by experimental and computational methods. Complex 1 is cis in the solid state and predominantly cis in solution, undergoing degenerate cis–cis isomerization (ΔG ≠ exp = 13.4 kcal mol–1; ΔG ≠ calc = 12.8 kcal mol–1 in toluene) and slower cis–trans isomerization (ΔG calc = +0.9 kcal mol–1; ΔG ≠ calc = 21.9 kcal mol–1). In contrast, 2 is only trans in both solution and the solid state with trans-2 computed to be 10.2 kcal mol–1 lower in energy than cis-2. Kinetic and computational studies of the previously communicated (J. Am. Chem. Soc. 2006, 128, 12644), remarkably facile CF3–Ph reductive elimination from 1 suggest that the process does not require P–Pd bond dissociation but rather occurs directly from cis-1. The experimentally determined activation parameters (ΔH ≠ = 25.9 ± 2.6 kcal mol–1; ΔS ≠ = 6.4 ± 7.8 e.u.) are in excellent agreement with the computed data (ΔH ≠ calc = 24.8 kcal mol–1; ΔG ≠ calc = 25.0 kcal mol–1). ΔG ≠ calc for CF3–Ph reductive elimination from cis-2 is only 24.0 kcal mol–1; however, the overall barrier relative to trans-2 is much higher (ΔG ≠ calc = 34.2 kcal mol–1) due to the need to include the energetic cost of trans–cis isomerization. This is consistent with the higher thermal stability of 2 that decomposes to PhCF3 only at 100 °C and even then only in a sluggish and less selective manner. The presence of excess Xantphos has a minor decelerating effect on the decomposition of 1. A steady slight decrease in k obs in the presence of 1 and 2 equiv of Xantphos then plateaus at [Xantphos]:1 = 5, 10, and 20. Specific molecular interactions between 1 and Xantphos are not involved in this kinetic effect (NMR, T 1 measurements). A deduced kinetic scheme accounting for the influence of extra Xantphos involves the formation of cis-[(η1-Xantphos)2Pd(Ph)(CF3)] that, by computation, is predicted to access reductive elimination of CF3–Ph with ΔG ≠ calc = 22.8 kcal mol–1.

Rh–POP Pincer Xantphos Complexes for C–S and C–H Activation. Implications for Carbothiolation Catalysis

“…The structure demonstrates the κ 3 -mer geometry of the final product, in which the thiomethyl and aryl groups sit mutually Exchange between isomers of Xantphos, in which the phosphines adopt a cis or trans geometry, has been noted previously, and in some cases this is reversible. 10,42,43 For the system fac/mer-[Rh(κ 3 -P,O,P -Xantphos)(PCyp 3 )(H 2 )][BAr F 4 ], equilibrium measurements indicate that the fac isomer is preferred and that although enthalpically there is little difference between the isomers, entropic considerations determine the final position of the equilibrium (ΔS is positive for the generation of the fac isomer). 10 On heating mer-8 (373 K, C 6 D 5 CD 3 ), we saw no evidence, to the detection limit of 31 P NMR spectroscopy, for fac-8.…”

Investigations into Transition-Metal-Catalyzed Arene Trifluoromethylation Reactions

“…2). 4a More recently, Buchwald has shown that (Brettphos)Pd II (aryl)(CF 3 ) (Brettphos = dicyclohexyl(2′-isopropyl-3,6-dimethoxy-4′,6′-dipropyl-[1,1′-biphenyl]-2-yl)phosphine) also undergoes aryl–CF 3 bond-forming reductive elimination under mild conditions (80 °C, ~30 min). 7 …”

“…2). 4 This was the first reported example of selective aryl–CF 3 coupling from a Pd center. The properties of the Xantphos ligand (particularly its large bite angle) were hypothesized to play an important role in this novel transformation.…”

ChemInform Abstract: Synthesis of α,α‐Difluoromethylene Alkynes by Palladium‐Catalyzed gem‐Difluoropropargylation of Aryl and Alkenyl Boron Reagents.

“…Furthermore, the intrinsic limitations of these nucleophilic substitution reactions, such as a requirement for strong nucleophiles and their incompatibility with base-or nucleophile-sensitive functional groups, restrict their wide application in organic synthesis. However, other ligands were inferior to L1; even the bisphosphine ligand XantPhos, which was previously demonstrated to be a suitable ligand for reductive elimination from fluoroalkyl palladium complexes, [12] afforded 3 a in only 9 % yield (entry 8). In continuation of our interest in transitionmetal-catalyzed fluoroalkylation reactions, [9] we herein describe the first palladium-catalyzed gem-difluoropropargylation of organoboron species, which proceeds with high efficiency (Scheme 1 c).…”