The trifluoromethyl group can dramatically influence the properties of organic molecules, thereby increasing their applicability as pharmaceuticals, agrochemicals, or building blocks for organic materials. Despite the importance of this substituent, no general method exists for its installment onto functionalized aromatic substrates. Current methods either require the use of harsh reaction conditions or suffer from a limited substrate scope. Herein, we report the palladium-catalyzed trifluoromethylation of aryl chlorides under mild conditions, allowing the transformation of a wide range of substrates, including heterocycles, in excellent yields. The process tolerates functional groups such as esters, amides, ethers, acetals, nitriles, and tertiary amines and therefore should be applicable to late-stage modifications of advanced intermediates. We also have prepared all the putative intermediates in the catalytic cycle and demonstrated their viability in the process.

Boronic acids which quickly deboronate under basic conditions, such as polyfluorophenylboronic acid and five-membered 2-heteroaromatic boronic acids, are especially challenging coupling partners for Suzuki-Miyaura reactions. Nevertheless, being able to use these substrates is highly desirable for a number of applications. Having found that monodentate biarylphosphine ligands can promote these coupling processes, we developed a precatalyst that forms the catalytically active species under conditions where boronic acid decomposition is slow. With this precatalyst, Suzuki-Miyaura reactions of a wide range of (hetero)aryl chlorides, bromides, and triflates with polyfluorophenyl, 2-furan, 2-thiophene and 2-pyrroleboronic acids and their analogs proceed at room temperature or 40 °C in short reaction times to give the desired products in excellent yields.The Suzuki-Miyaura cross-coupling (SMC) reaction is arguably the most important and widely used method for the construction of sp 2 -sp 2 carbon-carbon bonds.1 However, since SMCs are typically performed at elevated temperatures and require several hours reaction time, the scope of usable boronic acids is limited to those that do not significantly decompose under standard conditions. Consequently, the SMCs of quickly deboronating2 2,6-difluorophenylboronic acid (1) and analog 2 as well as the SMCs of five-membered 2-heterocyclic boronic acids 3-8 (Chart 1) are problematic.3 , 4 , 5 , 6 Being able to couple these boronic acids with functionalized aryl and heteroaryl substrates would be of great interest for the synthesis of pharmaceutical and agrochemical candidates, natural products, and materials.One viable solution to this problem is the masking of the boronic acids as MIDA boronates, 7 cyclic triolborates,8 or trifluoroborate salts9 , 10 which slowly hydrolyze11 to the free boronic acid under the reaction conditions. The ratio of the concentration of catalyst and the boronic acid is relatively high and, as a result, transmetalation is favored over protodeboronation. Nevertheless, these surrogates are typically prepared from the free boronic acids, and often, high palladium loadings and/or long reaction times are required for Herein, we report the fast and efficient SMC of the free boronic acids 1-8 at room temperature or 40 °C in short reaction times of 30 minutes to 2 hours. Key to the success was the development of a new precatalyst that generates the catalytically active LPd(0) species quickly under mild conditions under which the deboronation of the boronic acid is significantly slowed down.In the course of mechanistic investigations, we prepared complex SPhosPdPhCl (9) that results from oxidative addition of SPhosPd(0) with chlorobenzene,14 and treated it with 1 in the presence of aqueous K 3 PO 4 (Scheme 1). Rapid formation of product 10 demonstrated that transmetalation and reductive elimination occur with 1 at room temperature.15Using 2 mol% of 9 as precatalyst, 4-chloroanisole was coupled with 1 to give the desired product in 93% yield in less than ...

Despite increasing pharmaceutical importance, fluorinated aromatic organic molecules remain difficult to synthesize. Present methods require either harsh reaction conditions or highly specialized reagents, making the preparation of complex fluoroarenes challenging. Thus, the development of new and general methods for their preparation that overcome the limitations of those techniques currently in use is of great interest. We have prepared [LPd(II)Ar(F)] complexes where L is a biaryl monophosphine ligand and Ar is an aryl group, and identified conditions under which reductive elimination occurs to form an Ar-F bond. Based on these results, we have developed a catalytic process that converts aryl bromides and aryl triflates into the corresponding fluorinated arenes using simple fluoride salts. We expect this method to allow the introduction of fluorine atoms into advanced, highly functionalized intermediates.

The subtle trans-gauche equilibrium in the ethanol molecule is affected by hydrogen bonding. The resulting conformational complexity in ethanol dimer manifests itself in three hydrogen-bonded OH stretching bands of comparable infrared intensity in supersonic helium expansions. Admixture of argon or nitrogen promotes collisional relaxation and is shown to enhance the lowest frequency transition. Global and local harmonic frequency shift calculations at MP2 level indicate that this transition is due to a gauche-gauche dimer, but the predictions are sensitive to basis set and correlation level. Energetically, the homochiral gauche-gauche dimer is predicted to be the most stable ethanol dimer conformation. The harmonic MP2 predictions are corroborated by perturbative anharmonicity contributions and CCSD(T) energies. Thus, a consistent picture of the subtle hydrogen bond energetics and vibrational dynamics of the ethanol dimer is starting to emerge for the first time.

A mechanistic investigation of the Pd-catalyzed conversion of aryl triflates to fluorides is presented. Studies reveal that C—F reductive elimination from an LPd(II)(aryl) fluoride complex (L = t-BuBrettPhos (2), RockPhos (3)) does not occur when the aryl group is electron rich. Evidence is presented that a modified phosphine, generated in-situ, serves as the actual supporting ligand during catalysis with such substrates. A preliminary study of the reactivity of an LPd(II)(aryl) fluoride complex based on this modified ligand is reported.