RESUMO
First evidence for the existence of free trifluoromethyl anion CF3 (-) has been obtained. The 3D-caged potassium cation in [K(crypt-222)](+) is inaccessible to CF3 (-) , thus rendering it uncoordinated ("naked"). Ionic [K(crypt-222)](+) CF3 (-) has been characterized by single-crystal X-ray diffraction, solution NMR spectroscopy, DFT calculations, and reactivity toward electrophiles.
RESUMO
The first π-coordination-catalyzed nucleophilic fluorination of unactivated aryl halides has been demonstrated. Chlorobenzene reacts with alkali metal fluorides (CsF, KF) in the presence of a Cp*Ru catalyst at 120-180 °C to give fluorobenzene.
Assuntos
Benzeno/química , Flúor/química , Rutênio/química , Catálise , HalogenaçãoRESUMO
[(Ph3P)3Ru(L)(H)2] (where L = H2 (1) in the presence of styrene, Ph3P (3), and N2 (4)) cleave the Ph-X bond (X = Cl, Br, I) at RT to give [(Ph3P)3RuH(X)] (2) and PhH. A combined experimental and DFT study points to [(Ph3P)3Ru(H)2] as the reactive species generated upon spontaneous loss of L from 3 and 4. The reaction of 3 with excess PhI displays striking kinetics which initially appears zeroth order in Ru. However mechanistic studies reveal that this is due to autocatalysis comprising two factors: 1)â complex 2, originating from the initial PhI activation with 3, is roughly as reactive toward PhI as 3 itself; and 2)â the Ph-I bond cleavage with the just-produced 2 gives rise to [(Ph3P)2RuI2], which quickly comproportionates with the still-present 3 to recover 2. Both the initial and onward activation reactions involve PPh3 dissociation, PhI coordination to Ru through I, rearrangement to a η(2)-PhI intermediate, and Ph-I oxidative addition.
RESUMO
Four new well-defined Cu(I) complexes bearing a C2 F5 ligand have been prepared and fully characterized: [(Ph3 P)2 CuC2 F5 ] (2), [(bpy)CuC2 F5 ] (3), [(Ph3 P)Cu(phen)C2 F5 ] (4), and [(IPr*)CuC2 F5 ] (5). X-ray structures of all four have been determined, showing that the C2 F5 -ligated Cu atom can be di- (5), tri- (2 and 3), and tetracoordinate (4). The mixed phen-PPh3 complex 4 is a highly efficient fluoroalkylating agent for a broad variety of acid chlorides. This high-yielding transformation represents the first general method for the synthesis of RCOC2 F5 from the corresponding RCOCl.
Assuntos
Cloretos/química , Complexos de Coordenação/química , Cobre/química , Flúor/química , Cristalografia por Raios X , Cetonas/síntese química , Cetonas/química , Conformação Molecular , Fenantrolinas/químicaRESUMO
CuCl or pre-generated CuCF3 reacts with CF3 SiMe3 /KF in DMF in air to give [Cu(CF3 )4 ](-) quantitatively. [PPN](+) , [Me4 N](+) , [Bu4 N](+) , [PhCH2 NEt3 ](+) , and [Ph4 P](+) salts of [Cu(CF3 )4 ](-) were prepared and isolated spectroscopically and analytically pure in 82-99% yield. X-ray structures of the [PPN](+) , [Me4 N](+) , [Bu4 N](+) , and [Ph4 P](+) salts were determined. A new synthetic strategy with [Cu(CF3 )4 ](-) was demonstrated, involving the removal of one CF3 (-) from the Cu atom in the presence of an incoming ligand. A novel Cu(III) complex [(bpy)Cu(CF3 )3 ] was thus prepared and fully characterized, including by single-crystal X-ray diffraction. The bpy complex is highly fluxional in solution, the barrier to degenerate isomerization being only 2.3 kcal mol(-1) . An NPA study reveals a huge difference in the charge on the Cu atom in [Cu(CR3 )4 ](-) for R=F (+0.19) and R=H (+0.46), suggesting a higher electron density on Cu in the fluorinated complex.
RESUMO
The fluoride [(bpy)CuF2(H2O)]·2H2O (1) reacts with CF3SiMe3 and PhB(OH)2 in DMF at rt to give PhCF3 in >95% yield within 15 min. Although 1 is a Cu(II) complex, this reaction occurs only in air; no Ph-CF3 coupling takes place under anaerobic conditions. A distinct mechanism is operational in this transformation. First, 1 is trifluoromethylated with TMSCF3 to give "[(bpy)Cu(CF3)2]" that spontaneously disproportionates to two Cu(III) ([Cu(CF3)4](-) and [(bpy)Cu(CF3)3]) and two Cu(I) ([(bpy)Cu(CF3)] and [Cu(CF3)2](-)) complexes. In contrast with the Chan-Evans-Lam reaction, where the Cu(III) products of the Cu(II) disproprotionation effect the coupling, those formed in the 1-TMSCF3 system, [Cu(CF3)4](-) and [(bpy)Cu(CF3)3], are stable and unreactive, remaining dead-end spectators throughout the coupling process. Consequently, the trifluoromethylation of PhB(OH)2 with 1-CF3SiMe3 does not and cannot occur in the absence of O2. Only by air oxidation of the Cu(I) disproportionation product, [(bpy)Cu(CF3)] in equilibrium with [Cu(CF3)2](-), is the reactive species generated, serving as a catalyst for the Ph-CF3 bond formation even if 1 is used in stoichiometric quantities.
RESUMO
A combined experimental (radical clock, kinetic, Hammett) and computational (DFT, MM) study of the trifluoromethylation reaction of aryl halides with CuCF3 reveals a nonradical mechanism involving Ar-X oxidative addition to the Cu(I) center as the rate determining step. The reaction is second order, first order in each reactant with ΔG(⧧) ≈ 24 kcal/mol for PhI (computed ΔG(⧧) = 21.9 kcal/mol). An abrupt change in the gradient on the Hammett plot of log(kR/kH) versus σp for 11 p-RC6H4I substrates produces two correlations (ρ = +0.69 and +1.83), which is temptingly suggestive of two different reaction pathways. Only one mechanism is operational, however, as advocated by a single linear correlation with σp(-) (ρ = +0.91), analysis of the experimental ρ values, close similarity of the transition states varying in R and displaying clear signs of -M interactions, and excellent reproduction of the plot by DFT. The long-known yet previously uncomprehended ortho effect has been quantified, for the first time, using the reaction of CuCF3 with a series of o-RC6H4Br: R(kR/kH) = H (1) < Me (3.5) < MeO (4) < CN (20) < CHO (250) < CO2Me (850) < NO2 (4300) < Ac (7300) < CO2H (150 000). With minor contributions from electronic factors, the ortho effect is largely determined by (i) the stabilizing coordination of the o-substituent to Cu in the transition state with the Cu···O distance varying directly with the barrier and (ii) the steric bulk of the o-substituent that raises the ground state free energy of the haloarene (G(o)ortho - G(o)H or G(o)ortho - G(o)para) by inflicting molecular strain and consequently weakening the Ar-X bond.
RESUMO
A new protocol has been developed for trifluoromethylation of arenediazonium salts with moisture-sensitive CuCF3 (from fluoroform) in aqueous media. The reaction is governed by a radical mechanism, tolerates a broad variety of functional groups, and is applicable to the synthesis of complex, polyfunctionalized molecules.
Assuntos
Clorofluorcarbonetos de Metano/química , Cobre/química , Compostos de Diazônio/química , Água/química , Cristalografia por Raios X , MetilaçãoRESUMO
Exceedingly facile (23 °C) and chemoselective H-CF3 activation with [(dppp)Pd(Ph)(OH)] in the presence of a Lewis base promoter such as n-Bu3P leads to Pd-CF3 bond formation in nearly quantitative yield. A combined experimental and computational study points to a new mechanism that involves H-bonding Pd-O(H)···H-CF3 and nucleophilic attack of the promoter on the metal, followed by a push-pull-type collapse of the resultant five-coordinate Pd(II) intermediate via a polar transition state.
RESUMO
Just a spectator or a key player? The alkali-metal counterion (K(+) ) plays a remarkable key role in the recently discovered cupration reaction of fluoroform with dialkoxycuprates. A total of eight Lewis acid and Lewis base centers synergistically interacting with one another arrange in a stable transition state, providing a low-energy pathway for this unique transformation.
RESUMO
Fluoroform-derived CuCF3 recently discovered in our group exhibits remarkably high reactivity toward aryl and heteroaryl halides, performing best in the absence of extra ligands. A broad variety of iodoarenes undergo smooth trifluoromethylation with the "ligandless" CuCF3 at 23-50 °C to give the corresponding benzotrifluorides in nearly quantitative yield. A number of much less reactive aromatic bromides also have been trifluoromethylated, including pyridine, pyrimidine, pyrazine, and thiazole derivatives as well as aryl bromides bearing electron-withdrawing groups and/or ortho substituents. Only the most electrophilic chloroarenes can be trifluoromethylated, e.g., 2-chloronicotinic acid. Exceptionally high chemoselectivity of the reactions (no side-formation of arenes, biaryls, and C2F5 derivatives) has allowed for the isolation of a large number of trifluoromethylated products in high yield on a gram scale (up to 20 mmol). The CuCF3 reagent is destabilized by CuX coproduced in the reaction, the magnitude of the effect paralleling the Lewis acidity of CuX: CuCl > CuBr > CuI. While S(N)Ar and S(RN)1 mechanisms are not operational, there is a well-pronounced ortho effect, i.e., the enhanced reactivity of ortho-substituted aryl halides 2-RC6H4X toward CuCF3. Intriguingly, this ortho-effect is observed for R = NO2, COOH, CHO, COOEt, COCH3, OCH3, and even CH3, but not for R = CN. The fluoroform-derived CuCF3 reagent and its reactions with haloarenes provide an unmatched combination of reactivity, selectivity, and low cost.
Assuntos
Clorofluorcarbonetos de Metano/química , Cobre/química , Hidrocarbonetos Halogenados/química , Hidrocarbonetos Halogenados/síntese química , Compostos Organometálicos/química , Modelos Moleculares , Estrutura MolecularRESUMO
Pentafluoroethane, C2F5H (HFC-125), is smoothly cuprated with preisolated or in situ-generated [K(DMF)][(t-BuO)2Cu] to give [K(DMF)2][(t-BuO)Cu(C2F5)] (1) in nearly quantitative yield. Complex 1 has been isolated, structurally characterized, and demonstrated to be an exceedingly versatile pentafluoroethylating reagent for a variety of substrates, including unactivated aryl bromides.
Assuntos
Cobre/química , Fluorocarbonos/química , Hidrocarbonetos Bromados/química , Compostos Organometálicos , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Compostos Organometálicos/isolamento & purificaçãoRESUMO
The C-X bond (X = Br, Cl) of α-haloketones is smoothly trifluoromethylated with the fluoroform-derived CuCF(3) reagent recently developed in our laboratories. This is the first nucleophilic α-trifluoromethylation reaction of carbonyl compounds and a rare example of CF(3)-C(sp(3)) coupling. The transformation employs only low-cost chemicals and cleanly occurs in up to 99% yield at room temperature, thereby providing an unprecedentedly easy entry to valuable 2,2,2-trifluoroethylketones.
Assuntos
Clorofluorcarbonetos de Metano/química , Halogênios/química , Cetonas/química , Estereoisomerismo , Especificidade por Substrato , TemperaturaRESUMO
Catalytic asymmetric transfer hydrogenation of rac-furoin and furil produces hydrofuroin with up to 99% ee and 9:1 dr. This reaction provides an exceptionally easy access to optically active hydrofuroins in two straightforward steps from biomass-derived furfural (global production 200,000-300,000 t annually) using benzoin condensation.
Assuntos
Furaldeído/química , Catálise , Hidrogenação , Estrutura Molecular , EstereoisomerismoRESUMO
Easy does it: Aryl boronic acids undergo smooth and selective trifluoromethylation with low-cost fluoroform-derived CuCF(3) in DMF in non-dried air. The reaction occurs under mild conditions (1â atm, room temperature), exhibits unprecedented functional-group tolerance, and affords trifluoromethylated aromatic compounds in up to 99 % yield.
Assuntos
Ácidos Borônicos/química , Hidrocarbonetos Fluorados/síntese química , Compostos Organometálicos/química , Ar , Hidrocarbonetos Fluorados/química , Estrutura Molecular , EstereoisomerismoRESUMO
We have found the first reaction of direct cupration of fluoroform, the most attractive CF(3) source for the introduction of the trifluoromethyl group into organic molecules. Treatment of CuX (X = Cl, Br, I) with 2 equiv of MOR (M = K, Na) in DMF or NMP produces novel alkoxycuprates that readily react with CF(3)H at room temperature and atmospheric pressure to give CuCF(3) derivatives. The CuCl and t-BuOK (1:2) combination provides best results, furnishing the CuCF(3) product within seconds in nearly quantitative yield. As demonstrated, neither CF(3)(-) nor CF(2) mediate the Cu-CF(3) bond formation, which accounts for its remarkably high selectivity. The fluoroform-derived CuCF(3) solutions can be efficiently stabilized with TREAT HF to produce CuCF(3) reagents that readily trifluoromethylate organic and inorganic electrophiles in the absence of additional ligands such as phenanthroline. A series of novel Cu(I) complexes have been structurally characterized, including K(DMF)[Cu(OBu-t)(2)] (1), Na(DMF)(2)[Cu(OBu-t)(2)] (2), [K(8)Cu(6)(OBu-t)(12)(DMF)(8)(I)](+) I(-) (3), and [Cu(4)(CF(3))(2)(C(OBu-t)(2))(2)(µ(3)-OBu-t)(2)] (7).
Assuntos
Clorofluorcarbonetos de Metano/química , Cobre/química , Compostos Organometálicos/química , Estrutura MolecularRESUMO
Rational catalysis design on the basis of a detailed mechanistic understanding has been used to successfully develop the first efficient general Pd-catalyzed aromatic cyanation reaction under the highly sought after practicable conditions: (i) MCN (M = Na or K) as a cyanide source; (ii) low-boiling recyclable solvents; and (iii) minimal quantities of inexpensive, nontoxic promoters. The developed catalytic reaction converts aromatic bromides to the corresponding nitriles in 88-99% isolated yield with NaCN and 0.5-1.0 mol % of a t-Bu(3)P-monoligated Pd catalyst in MeCN-THF within 2 h at 70 °C. The process exhibits high functional group tolerance.