Ligand-controlled Regioselective Cu-Catalyzed Trifluoromethylation to Generate Trifluoromethylallenes

“Cu–CF3” species have been used historically for a broad spectrum of nucleophilic trifluoromethylation reactions. Although recent advancements have employed ligands to stabilize and harness the reactivity of this key organometallic intermediate, the ability of a ligand to differentiate a regiochemical outcome of a Cu–CF3-mediated or -catalyzed reaction has not been previously reported. Herein, we report the first example of a Cu-catalyzed trifluoromethylation reaction in which a ligand controls the regiochemical outcome. More specifically, we demonstrate the ability of bipyridyl-derived ligands to control the regioselectivity of the Cu-catalyzed nucleophilic trifluoromethylation reactions of propargyl electrophiles to generate trifluoromethylallenes. This method provides a variety of di-, tri- and tetra-substituted trifluoromethylallenes, which can be further modified to generate complex fluorinated substructures

Copper-Mediated Perfluoroalkylation of Heteroaryl Bromides with (phen)CuR F

[Image: see text] The attachment of perfluoroalkyl groups onto organic compounds has been a major synthetic goal over the past several decades. Previously, our group reported phenanthroline-ligated perfluoroalkyl copper reagents, (phen)CuR(F), which react with aryl iodides and aryl boronates to form the corresponding benzotrifluorides. Herein the perfluoroalkylation of a series of heteroaryl bromides with (phen)CuCF(3) and (phen)CuCF(2)CF(3) is reported. The mild reaction conditions allow the process to tolerate many common functional groups. Perfluoroethylation with (phen)CuCF(2)CF(3) occurs in somewhat higher yields than trifluoromethylation with (phen)CuCF(3), creating a method to generate fluoroalkyl heteroarenes that are less accessible from trifluoroacetic acid derivatives

The Palladium-Catalyzed Trifluoromethylation of Vinyl Sulfonates

A method for the palladium-catalyzed trifluoromethylation of cyclohexenyl sulfonates has been developed. Various cyclohexenyl triflates and nonaflates underwent trifluoromethylation under mild reaction conditions using a catalyst system composed of Pd(dba)[subscript 2] or [(allyl)PdCl][subscript 2] and the monodentate biaryl phosphine ligand [superscript t]BuXPhos. The trifluoromethyl anion (CF[– over 3]) or its equivalent for the process was generated in situ from TMSCF[subscript 3] in combination with KF or TESCF[subscript 3] in combination with RbF.National Institutes of Health (U.S.) (Grant GM46059

Stable and Storable N(CF 3

Fluorinated groups are essential for drug design, agrochemicals, and materials science. The bis(trifluoromethyl)amino group is an example of a stable group that has a high potential. While the number of molecules containing perfluoroalkyl, perfluoroalkoxy, and other fluorinated groups is steadily increasing, examples with the N(CF$_{3}$)$_{2}$ group are rare. One reason is that transfer reagents are scarce and metal-based storable reagents are unknown. Herein, a set of Cu$^{I}$ and Ag$^{I}$ bis(trifluoromethyl)amido complexes stabilized by N- and P-donor ligands with unprecedented stability are presented. The complexes are stable solids that can even be manipulated in air for a short time. They are bis(trifluoromethyl)amination reagents as shown by nucleophilic substitution and Sandmeyer reactions. In addition to a series of benzylbis(trifluoromethyl)amines, 2-bis(trifluoromethyl)amino acetate was obtained, which, upon hydrolysis, gives the fluorinated amino acid N,N-bis(trifluoromethyl)glycine

Copper-Catalyzed Oxytrifluoromethylation of Unactivated Alkenes

A mild, versatile and convenient method for the efficient oxytrifluoromethylation of unactivated alkenes has been developed based on a copper-catalyzed oxidative difunctionalization strategy. This methodology provides access to a variety of classes of synthetically useful CF(3)-containing building blocks from simple starting materials