CF3 Complexes Research Articles

The Tetrel Bonds of Hypervalent Halogen Compounds.

The tetrel bond between PhXF2Y(TF3) (T = C and Si; X = Cl, Br, and I; Y = F and Cl) and the electron donor MCN (M = Li and Na) was investigated at the M06-2X/aug-cc-pVDZ level of theory. As the electronegativity of the halogen atom X increases, the strength of the tetrel bond also increases, but as the electronegativity of the halogen atom Y increases, the strength of the tetrel bond decreases. The magnitude of the interaction energy in most -CF3 complexes was found to be less than 10 kcal/mol, but to exceed 11 kcal/mol for PhClF2Cl(CF3)⋯NCNa. The tetrel bond is greatly enhanced when the -SiF3 group interacts with LiCN or NaCN, with the largest interaction energy approaching 100 kcal/mol and displaying a covalent Si⋯N interaction. Along with this enhancement, the Si⋯N distance was found to be less than the X-Si bond length, the -SiF3 group to be closer to the N atom, and in most -SiF3 systems, the X-Si-F angle to be less than 90°; the -SiF3 group therefore undergoes inversion and complete transfer in some systems.

Catalytic C-H Trifluoromethylation of Arenes and Heteroarenes via Visible Light Photoexcitation of a Co(III)-CF3 Complex.

A cobalt photocatalyst for direct trifluoromethylation of (hetero)arene C(sp2)-H bonds is described and shown to operate via visible light activation of a Co-CF3 intermediate, which functions as a combined chromophore and organometallic reaction center. Chemical oxidations of previously reported (OCO)Co complexes containing a redox-active [OCO] pincer ligand afford a Co-CF3 complex two oxidation states above Co(II). Computational and spectroscopic studies are consistent with formulation of the product as [(OCO•)CoIII(CF3)(THF)(OTf)] (II) containing an open-shell [OCO•]1- radical ligand bound to a S = 0 Co(III) center. II is thermodynamically stable, but exposure to blue (440 nm) light induces Co-CF3 bond homolysis and release of •CF3, which is trapped by radical acceptors including TEMPO•, (hetero)arenes, or the radical [OCO•] ligand in II. The latter comprises a competitive degradation pathway, which is overcome under catalytic conditions by using excess substrate. Accordingly, generation of II from the reaction of [(OCO)CoIIL] (III) (L = THF, MeCN) with Umemoto's dibenzothiophenium trifluoromethylating reagent (1) followed by photolytic Co-CF3 bond activation completes a photoredox catalytic cycle for C-H (hetero)arene trifluoromethylation utilizing visible light. Electronic structure and photophysical studies, including time-dependent density functional theory (TDDFT) calculations, suggest that Co-CF3 bond homolysis at II occurs via an ligand-to-metal charge-transfer (LMCT) (OCO0)CoII(CF3) state, revealing ligand redox activity as a critical design feature and establishing design principles for the use of base metal chromophores for selectivity in photoredox bond activations occurring via free radical intermediates.

High-valent Cu(III)-CF3 compound-mediated esterification reaction.

Cu(III)-CF3 compounds are reported herein as novel coupling reagents to mediate ester synthesis from carboxyl acids and alcohols/phenols. Carboxylic acids are transformed to trifluoromethyl ester and acyl fluoride activated species that interact with each other. The broad substrate scope and late-stage application of this method are demonstrated. This study opens up new opportunities to develop interesting reactions using Cu(III)-CF3 compounds without transferring a CF3 group to the products.

Copper-Catalyzed Ring-Opening Radical Trifluoromethylation of Cycloalkanone Oximes.

The copper-catalyzed ring-opening C-trifluoromethylation of cycloalkanone oximes with Zn(CF3)2 complexes is described. The reaction proceeds in dichloromethane under mild conditions, providing an efficient and general entry to γ- or δ-CF3-substituted nitriles via tandem N-O and C(sp2)-C(sp3) bond cleavage and C(sp3)-CF3 bond formation. The protocol exhibits a broad substrate scope and wide functional group compatibility. A radical mechanism involving the CF3 transfer from Cu(II)-CF3 complexes to alkyl radicals is proposed.

Copper-Catalyzed Remote C(sp3 )-H Trifluoromethylation of Carboxamides and Sulfonamides.

Reported herein is an unprecedented protocol for trifluoromethylation of unactivated aliphatic C(sp3 )-H bonds. With Cu(OTf)2 as the catalyst, the reaction of N-fluoro-substituted carboxamides (or sulfonamides) with Zn(CF3 )2 complexes provides the corresponding δ-trifluoromethylated carboxamides (or sulfonamides) in satisfactory yields under mild reaction conditions. A radical mechanism involving 1,5-hydrogen atom transfer of N-radicals followed by CF3 -transfer from CuII -CF3 complexes to the thus formed alkyl radicals is proposed.

Copper‐Catalyzed Remote C(sp3)−H Trifluoromethylation of Carboxamides and Sulfonamides

AbstractReported herein is an unprecedented protocol for trifluoromethylation of unactivated aliphatic C(sp3)−H bonds. With Cu(OTf)2 as the catalyst, the reaction of N‐fluoro‐substituted carboxamides (or sulfonamides) with Zn(CF3)2 complexes provides the corresponding δ‐trifluoromethylated carboxamides (or sulfonamides) in satisfactory yields under mild reaction conditions. A radical mechanism involving 1,5‐hydrogen atom transfer of N‐radicals followed by CF3‐transfer from CuII−CF3 complexes to the thus formed alkyl radicals is proposed.

Synthesis and Reactivity of Mn–CF3 Complexes

The synthesis, characterization and reactivity of several bi- and tridentate, N-ligated manganese carbonyl trifluoromethyl complexes are presented. These complexes exhibit elongated Mn–CCF3 bonds (versus Mn(CF3)(CO)5), suggesting a lability that could be utilized for the transfer or insertion of the CF3 functional group into organic substrates. Unlike their Mn–X congeners (X = Cl, Br), these Mn–CF3 complexes exhibit a preference for hard donor ancillary ligands, thus enabling the synthesis of 4 N-ligated Mn–CF3 complexes including a mixed-donor tridentate complex using an NNS Schiff base ([2-(methylthio)-N-(1-(pyridin-2-yl)ethylidene)aniline]). Although we have not yet identified efficient CF3 transfer reactions, fluoride abstraction from the Mn–CF3 complexes using trimethylsilyl triflate affords the first stable Mn fluorocarbenes as evidenced by 19F NMR spectroscopy.

General and selective syn-carboxylation-trifluoromethylation of terminal alkynes: application to the late-stage modification of dehydrocholic acid.

A general and selective method is developed that allows difunctionalization of terminal alkynes by a Cu(iii)-CF3 complex and a carboxylic acid regioselectively and with unusual syn-stereochemistry. This method is broadly applicable to various carboxylic acids and terminal alkynes, producing a range of biologically active trifluoromethyl enol carboxylic esters. The synthetic potential of this method is further demonstrated by the late-stage functionalization of a complex pharmaceutical compound dehydrocholic acid.

Regio‐ and Stereoselective Vicinal syn‐Arylation‐Trifluoromethylation of Terminal Arylacetylenes

AbstractOne‐pot three‐component syn‐arylation‐trifluoromethylation of terminal arylalkynes is developed by using an isolated (phen)Cu(III)(CF3)3 complex (phen: phenanthroline) and aryl boronic acids. This reaction is chemoselective that can suppress the competing trifluoromethylation of alkyne C−H and aryl boronic acids. It is also regioselective to install an aryl group on Cα and a CF3 group on Cβ of arylalkynes. Finally, unusual syn‐difunctionalization chemistry is achieved that is complementary to the general anti‐stereochemistry for difunctionalization of alkynes involving trifluoromethylation. The use of a Cu(III)−CF3 complex is crucial to the success that not only acts as a reactive CF3 precursor, but is also responsible for the unusual syn‐stereochemistry. This study allows ready access to vicinal arylated‐trifluoromethylated olefins, which is a widely existing structural motif in many biologically active compounds.

Synthesis of Trifluoromethylated B12 Derivative and Photolysis of Cobalt(III)–Trifluoromethyl Bond

A vitamin B12 derivative with a trifluoromethyl group as an axial ligand, heptamethyl trifluoromethylaquacobyrinate perchlorate, [[(CF3)(H2O)Cob(III)7C1ester]ClO4], is prepared and characterized by elemental analysis, 1H NMR, 19F NMR, ESI-MS, UV-vis absorption, and cyclic voltammetry. The Co–CF3 complex shows homolysis of the Co(III)–CF3 bond under visible light irradiation, which releases a CF3 radical that can be detected by a radical trapping experiment.

Cu(III)–CF3 Complex Enabled Unusual (Z)-Selective Hydro-trifluoromethylation of Terminal Alkynes

An efficient and selective hydro-trifluoromethylation of terminal alkynes is developed to enable the synthesis of 1,2-disubstituted trifluoromethylated Z-alkenes from terminal alkynes, a silane and a Cu(III)-CF3 complex in DMF. The unusual Z-selectivity and the compatibility of various functional groups make this reaction complementary to previous vinyl-CF3 bond-forming methods producing dominantly E-products or a mixture of E, Z-isomers. Extensive mechanistic studies indicate that this reaction may involve a key step of migratory insertion of initially formed Ar-C≡C-CF3 into LCu(I)-H intermediate and subsequent hydrogenation of the vinyl-copper species to give finally the Z-trifluoromethylated styrenes. Deuterium labeling experiments show that DMF acts not merely as the solvent but also as the source of α-H in the Z-trifluoromethylated styrene products. Given the novel syn-difunctionalization of alkynes using Cu(III)-CF3 complexes/a nucleophilic reagent we developed recently that are also in contrast to the previous anti-difunctionalization chemistry, Cu(III)-CF3 complexes are demonstrated to show distinct reactivity properties compared to conventional CF3 reagents (Togni's reagents and Umemoto-type reagents) and may thus enable the development of other interesting reactions.

Perfluoroalkyl Cobaloximes: Preparation Using Hypervalent Iodine Reagents, Molecular Structures, Thermal and Photochemical Reactivity

Treatment of cobaloximes(II), [Co(Hdmg)2(L)2] (Hdmg = dimethylglyoximate, L = neutral ligand), with perfluoroalkyl iodane reagents leads to the formation of perfluoroalkyl cobaloximes(III), [CoRF(Hdmg)2(L)] (RF = CF3, C2F5, n-C3F7, CF2CF2Ph; L = Py, NH3, MeNH2, PhNH2, MeOH). The synthetic protocol can be significantly simplified to a one-pot procedure starting from cobalt(II) acetate–tetrahydrate. The products have been fully characterized by NMR, IR, and UV/vis spectroscopy as well as single-crystal X-ray diffraction, and the thermal and photochemical reactivity has been studied. According to the Co–L distances in the crystal, the trans influence of the RF– ligands can be rated as C2F5– ≈ n-C3F7– < CF2CF2Ph– ≈ CF3– < CH3–. The thermal decomposition of the complexes is different from that of nonfluorinated analogues, probably including perfluoroalkylation of an Hdmg– ligand as the initial step. In the CF3 complexes, the Co–C bond is very resistant against photolysis, but the ligand L is readily exchanged ...

Diverse copper(iii) trifluoromethyl complexes with mono-, bi- and tridentate ligands and their versatile reactivity.

Cu(iii) trifluoromethyl complexes are proposed as essential intermediates for many copper-promoted trifluoromethylation reactions, but remain elusive and scarcely explored. We report herein the isolation and spectroscopic and X-ray crystallographic characterization of diverse CuIII-CF3 complexes (6-10) with varied coordinating motifs (mono-, bi- or tridentate) and formal charges (neutral or monoanionic) for the ligand L (L is pyridine, 2,4,6-trimethylpyridine, quinol-8-yloxide or 2,6-bis(2'-pyridyl)pyridine). Square planar complexes 6, 7 and 9 show rapid dynamic behavior in solution possibly due to the weak Cu-CF3 bonds that can quickly dissociate and recombine with the CF3 radical. In contrast, 10, with octahedral geometry, is more rigid. Reactivity studies show that except for ion-pair complex 8, they are highly reactive for the trifluoromethylation of arylboronic acids and the C-H bond of terminal alkynes. Furthermore, syn-fluoro- and -oxy-trifluoromethylation across the triple bond of alkynes can be achieved using 6 and CsF or NaOPh. These results greatly expand the scope of isolated and well-characterized Cu(iii)-CF3 complexes, and establish their versatile reactivity that may be widely involved in copper-mediated trifluoromethylation reactions, thus substantiating the essential yet undeveloped aspects of trifluoromethylation chemistry.

Syn-Fluoro- and -Oxy-trifluoromethylation of Arylacetylenes.

One-step concurrent fluoro-trifluoromethylation across the triple bond of arylacetylenes in a syn mode is enabled by the collaboration of (phen)CuIII(CF3)3 and CsF that produces chemo-, regio-, and stereoselectively (Z)-α-fluoro-β-CF3 styrenes. This method can be extended to achieve syn-oxy-trifluoromethylation and syn-aryl-trifluoromethylation of alkynes using phenoxides, alkoxides, or phenylboronic acid in place of CsF. It opens up new opportunities for preparing various functionalized trifluoromethylated Z-alkenes and demonstrates the potential of Cu(III)-CF3 complexes in organic synthesis.

C-H Bond Trifluoromethylation of Arenes Enabled by a Robust, High-Valent Nickel(IV) Complex.

The robust, high-valent NiIV complex [(Py)2 NiIV F2 (CF3 )2 ] (Py=pyridine) was synthesized and fully characterized by NMR spectroscopy, X-ray diffraction, and elemental analysis. It reacts with aromatic compounds at 25 °C to form the corresponding benzotrifluorides in nearly quantitative yield. The monomeric and dimeric NiIII CF3 complexes 2⋅Py and 2 were identified as key intermediates, and their structures were unambiguously determined by EPR spectroscopy and X-ray diffraction. Preliminary kinetic studies in combination with the isolation of reaction intermediates confirmed that the C-H bond-breaking/C-CF3 bond-forming sequence can occur both at NiIV CF3 and NiIII CF3 centers.

An Organometalllic NiIV Complex That Participates in Competing Transmetalation and C(sp2)–O Bond-Forming Reductive Elimination Reactions

This communication describes the synthesis of an organometallic NiIV complex bearing a labile trifluoroacetate (OTFA) ligand via the oxidation of a NiII precursor with PhI(OTFA)2. Intramolecular C(sp2)–O bond-forming reductive elimination from this NiIV complex is relatively slow, requiring 6 h at 70 °C to reach completion. In contrast, transmetalation with TMSCF3 occurs within just 1 h at room temperature to generate a NiIV–CF3 complex. These studies show that intermolecular reactions such as transmetalation can be competitive with intramolecular reductive elimination processes at NiIV centers.

Isolation and characterization of copper(iii) trifluoromethyl complexes and reactivity studies of aerobic trifluoromethylation of arylboronic acids

Novel phenCuIII–CF3 complexes, isolated purely and fully characterized, are highly reactive for aerobic trifluoromethylation of arylboronic acids.

The cyclometalated nickel complex [(Phbpy)NiBr] (Phbpy− = 2,2′-bipyridine-6-phen-2-yl) – Synthesis, spectroscopic and electrochemical studies

The new organometallic nickel complex [(Phbpy)NiBr] containing the anionic tridentate N,N,C ligand 6-(phen-2-yl)-2,2′-bipyridine (Phbpy−) was synthesised from PhbpyBr and [Ni(COD)2] in excellent yields and was fully characterised (MS, NMR, single crystal XRD). [(Phbpy)NiBr] was reacted with (CF3)SiMe3 giving the CF3 complex [(Phbpy)Ni(CF3)]. Both new complexes were studied in detail by electrochemical (CV) and spectroelectrochemical (UV/vis/NIR absorption) methods. For both complexes the first one-electron reduction and the first oxidation of the Br complex occur fully reversible in the CV, while spectroelectrochemistry shows decomposition reactions. The CF3 complex is unstable in solution producing 2-CF3-Phbpy. Reactivity patterns for these reactions were discussed, also in comparison with the non-cyclometalated complex [(bpy)Ni(Mes)Br].

Fluoro and Trifluoromethyl Derivatives of POCOP-Type Pincer Complexes of Nickel: Preparation and Reactivities in SN2 Fluorination and Direct Benzylation of Unactivated Arenes

This report describes the synthesis, characterization, and reactivities of the pincer-type complexes κP,κC,κP-(R-POCOP)NiX (R-POCOP = 2,6-(i-Pr2PO)2,4-R-C6H3; R = H, X = F (2a), CF3 (3a); R = OMe, X = F (2b), X = CF3 (3b)). These complexes were prepared by treating their Ni–Br analogues with excess AgF at rt (2a and 2b) or excess AgF and Me3SiCF3 (3a and 3b) at 45 °C. The Ni–F derivative 2a was shown to be an intermediate for the formation of the Ni–CF3 derivative 3a. Complexes 2a, 3a, and 3b were fully characterized by multinuclear NMR spectroscopy, cyclic voltammetry, and X-ray diffraction analysis. Variable temperature, multinuclear NMR analysis of 2a helped elucidate interaction of the fluoride ligand with hydrofluoric acid present in the reaction medium. The bromo complexes 1a or 1b catalyzed fluorination of benzyl halides at 90 °C in the presence of excess AgF, whereas the Ni–CF3 complexes 3 failed to promote trifluoromethylation of benzyl bromide, leading instead to a direct benzylation of the aromatic reaction solvent (benzene, toluene, xylene, or bromobenzene). Possible mechanisms for this benzylation reaction have been probed and discussed.

Iminosemiquinone radical ligands enable access to a well-defined redox-active Cu(II)-CF₃ complex.

The reaction of a copper complex bearing iminosemiquinone ligands with a CF3(+) source provides an unprecedented Cu(II)-CF3 complex through ligand-based oxidation. Reactivity of this complex leads to nucleophilic trifluoromethylation of the ligand, suggesting an electronic interplay that results in a formal umpolung of the initial CF3(+).