Palladium and Iron Cocatalyzed Aerobic Alkene Aminoboration.

Aminoboration of simple alkenes with nitrogen nucleophiles remains an unsolved problem in synthetic chemistry; this transformation can be catalyzed by palladium via aminopalladation followed by transmetalation with a diboron reagent. However, this catalytic process faces inherent challenges with instability of the alkylpalladium(II) intermediate toward ß-hydride elimination. Herein, we report a palladium/iron cocatalyzed aminoboration, which enables this transformation. We demonstrate these conditions on a variety of alkenes and norbornenes with an array of common nitrogen nucleophiles. In the developed strategy, the iron cocatalyst is crucial to achieving the desired reactivity by serving as a halophilic Lewis acid to release the transmetalation-active cationic alkylpalladium intermediate. Furthermore, it serves as a redox shuttle in the regeneration of the Pd(II) catalyst by reactivation of nanoparticulate palladium.

Computational Investigation of the Preferred Binding Modes of N2O in Group 8 Metal Complexes.

Nitrous oxide (N2O) is a potentially important oxidant for green chemistry applications but thus far has shown limited examples as a ligand for transition metal complexes. Given the lack of reported N2O complexes, density functional theory was utilized to study the potential binding effects in multiple group 8 metal complexes. N2O is found to be a very weakly π-accepting ligand (approximately 1/3 as effective as CO). With the weak π-accepting character, the N2O is predicted to be bound through the nitrogen atom in a linear geometry. In all calculated ruthenium and osmium complexes, the nitrogen bound mode of binding is preferred. Only by introduction of a very weak π-donor metal (such as iron) can the N2O be found to slightly prefer binding through the oxygen atom in a purely σ-donor fashion.

Experimental and Computational Investigation of the Aerobic Oxidation of a Late Transition Metal-Hydride.

The rational development of homogeneous catalytic systems for selective aerobic oxidations of organics has been hampered by the limited available knowledge of how oxygen reacts with important organometallic intermediates. Recently, several mechanisms for oxygen insertion into late transition metal-hydride bonds have been described. Contributing to this nascent understanding of how oxygen reacts with metal-hydrides, a detailed mechanistic study of the reaction of oxygen with the IrIII hydride complex (dmPhebox)Ir(OAc)(H) (1) in the presence of acetic acid, which proceeds to form the IrIII complex (dmPhebox)Ir(OAc)2(OH2) (2), is described. The evidence supports a multifaceted mechanism wherein a small amount of an initially formed metal hydroperoxide proceeds to generate a metal-oxyl species that then initiates a radical chain reaction to rapidly convert the remaining IrIII-H. Insight into the initiation step was gained through kinetic and mechanistic studies of the radical chain inhibition by BHT (butylated hydroxytoluene). Computational studies were employed to contribute to a further understanding of initiation and propagation in this system.

Mechanistic Studies of Single-Step Styrene Production Using a Rhodium(I) Catalyst.

The direct and single-step conversion of benzene, ethylene, and a Cu(II) oxidant to styrene using the Rh(I) catalyst (FlDAB)Rh(TFA)(η2-C2H4) [FlDAB = N,N'-bis(pentafluorophenyl)-2,3-dimethyl-1,4-diaza-1,3-butadiene; TFA = trifluoroacetate] has been reported to give quantitative yields (with Cu(II) as the limiting reagent) and selectivity combined with turnover numbers >800. This report details mechanistic studies of this catalytic process using a combined experimental and computational approach. Examining catalysis with the complex (FlDAB)Rh(OAc)(η2-C2H4) shows that the reaction rate has a dependence on catalyst concentration between first- and half-order that varies with both temperature and ethylene concentration, a first-order dependence on ethylene concentration with saturation at higher concentrations of ethylene, and a zero-order dependence on the concentration of Cu(II) oxidant. The kinetic isotope effect was found to vary linearly with the order in (FlDAB)Rh(OAc)(η2-C2H4), exhibiting no KIE when [Rh] was in the half-order regime, and a kH/kD value of 6.7(6) when [Rh] was in the first-order regime. From these combined experimental and computational studies, competing pathways, which involve all monomeric Rh intermediates and a binuclear Rh intermediate in the other case, are proposed.

High-valent copper in biomimetic and biological oxidations.

A long-standing debate in the Cu-O2 field has revolved around the relevance of the Cu(III) oxidation state in biological redox processes. The proposal of Cu(III) in biology is generally challenged as no spectroscopic or structural evidence exists currently for its presence. The reaction of synthetic Cu(I) complexes with O2 at low temperature in aprotic solvents provides the opportunity to investigate and define the chemical landscape of Cu-O2 species at a small-molecule level of detail; eight different types are characterized structurally, three of which contain at least one Cu(III) center. Simple imidazole or histamine ligands are competent in these oxygenation reactions to form Cu(III) complexes. The combination of synthetic structural and reactivity data suggests (1) that Cu(I) should be considered as either a one or two electron reductant reacting with O2, (2) that Cu(III) reduction potentials of these formed complexes are modest and well within the limits of a protein matrix and (3) that primary amine and imidazole ligands are surprisingly good at stabilizing Cu(III) centers. These Cu(III) complexes are efficient oxidants for hydroxylating phenolate substrates with reaction hallmarks similar to that performed in biological systems. The remarkable ligation similarity of the synthetic and biological systems makes it difficult to continue to exclude Cu(III) from biological discussions.

An Uncanny Dehydrogenation Mechanism: Polar Bond Control over Stepwise or Concerted Transition States.

The mechanism of the dehydrogenation of N-heterocycles with the recently established bifunctional catalyst (iPrPNP)Fe(CO)(H) was investigated through experiments and density functional theory calculations (iPrPNP = iPr2PCH2CH2NCH2CH2PiPr2). In this system, the saturated N-heterocyclic substrates are completely dehydrogenated to the aromatic products. Calculations indicate that dehydrogenation barriers of the C-C bonds are very high in energy (ΔG‡ = 37.4-42.2 kcal/mol), and thus dehydrogenation only occurs at the C-N bond (ΔG‡ = 9.6-22.2 kcal/mol). Interestingly, substrates like piperidine with relatively unpolarized C-N bonds are dehydrogenated through a concerted proton/hydride transfer bifunctional transition state involving the nitrogen on the PNP ligand. However, substrates with polarized C-N bonds entail stepwise (proton then hydride) bifunctional dehydrogenation.

Direct Copper(III) Formation from O2 and Copper(I) with Histamine Ligation.

Histamine chelation of copper(I) by a terminal histidine residue in copper hydroxylating enzymes activates dioxygen to form unknown oxidants, generally assumed as copper(II) species. The direct formation of copper(III)-containing products from the oxygenation of histamine-ligated copper(I) complexes is demonstrated here, indicating that copper(III) is a viable oxidation state in such products from both kinetic and thermodynamic perspectives. At low temperatures, both trinuclear Cu(II)2Cu(III)O2 and dinuclear Cu(III)2O2 predominate, with the distribution dependent on the histamine ligand structure and oxygenation conditions. Kinetics studies suggest the bifurcation point to these two products is an unobserved peroxide-level dimer intermediate. The hydrogen atom reactivity difference between the trinuclear and binuclear complexes at parity of histamine ligand is striking. This behavior is best attributed to the accessibility of the bridging oxide ligands to exogenous substrates rather than a difference in oxidizing abilities of the clusters.

Chemical Plausibility of Cu(III) with Biological Ligation in pMMO.

The mechanisms of dioxygen activation and methane C-H oxidation in particulate methane monooxygenase (pMMO) are currently unknown. Recent studies support a binuclear copper site as the catalytic center. We report the low-temperature assembly of a high-valent dicopper(III) bis(µ-oxide) complex bearing marked structural fidelity to the proposed active site of pMMO. This unprecedented dioxygen-bonded Cu(III) species with exclusive biological ligation directly informs on the chemical plausibility and thermodynamic stability of the bis(µ-oxide) structure in such dicopper sites and foretells unusual optical signatures of an oxygenation product in pMMO. Though the ultimate pMMO active oxidant is still debated, C-H oxidation of exogenous substrates is observed with the reported Cu(III) complexes. The assembly of a high valent species both narrows the search for relevant pMMO intermediates and provides evidence to substantiate the role of Cu(III) in biological redox processes.

Carbon(sp(3))-fluorine bond-forming reductive elimination from palladium(IV) complexes.

Pd(IV)-fluoride complexes, some of which are remarkably insensitive to water, have been synthesized and used in the title reaction, which proceeds with high selectivity to give the product of the C(sp(3))-F coupling. Preliminary mechanistic studies implicate a pathway involving dissociation of pyridine followed by direct C-F coupling at the Pd center.

Mechanistic and computational studies of oxidatively-induced aryl-CF3 bond-formation at Pd: rational design of room temperature aryl trifluoromethylation.

This article describes the rational design of first generation systems for oxidatively induced Aryl-CF(3) bond-forming reductive elimination from Pd(II). Treatment of (dtbpy)Pd(II)(Aryl)(CF(3)) (dtbpy = di-tert-butylbipyridine) with NFTPT (N-fluoro-1,3,5-trimethylpyridinium triflate) afforded the isolable Pd(IV) intermediate (dtbpy)Pd(IV)(Aryl)(CF(3))(F)(OTf). Thermolysis of this complex at 80 °C resulted in Aryl-CF(3) bond-formation. Detailed experimental and computational mechanistic studies have been conducted to gain insights into the key reductive elimination step. Reductive elimination from this Pd(IV) species proceeds via pre-equilibrium dissociation of TfO(-) followed by Aryl-CF(3) coupling. DFT calculations reveal that the transition state for Aryl-CF(3) bond formation involves the CF(3) acting as an electrophile with the Aryl ligand serving as a nucleophilic coupling partner. These mechanistic considerations along with DFT calculations have facilitated the design of a second generation system utilizing the tmeda (N,N,N',N'-tetramethylethylenediamine) ligand in place of dtbpy. The tmeda complexes undergo oxidative trifluoromethylation at room temperature.

Synthetic, mechanistic, and computational investigations of nitrile-alkyne cross-metathesis.

The terminal nitride complexes NW(OC(CF 3) 2Me) 3(DME) ( 1-DME), [Li(DME) 2][NW(OC(CF 3) 2Me) 4] ( 2), and [NW(OCMe 2CF 3) 3] 3 ( 3) were prepared in good yield by salt elimination from [NWCl 3] 4. X-ray structures revealed that 1-DME and 2 are monomeric in the solid state. All three complexes catalyze the cross-metathesis of 3-hexyne with assorted nitriles to form propionitrile and the corresponding alkyne. Propylidyne and substituted benzylidyne complexes RCW(OC(CF 3) 2Me) 3 were isolated in good yield upon reaction of 1-DME with 3-hexyne or 1-aryl-1-butyne. The corresponding reactions failed for 3. Instead, EtCW(OC(CF 3)Me 2) 3 ( 6) was prepared via the reaction of W 2(OC(CF 3)Me 2) 6 with 3-hexyne at 95 degrees C. Benzylidyne complexes of the form ArCW(OC(CF 3)Me 2) 3 (Ar = aryl) then were prepared by treatment of 6 with the appropriate symmetrical alkyne ArCCAr. Three coupled cycles for the interconversion of 1-DME with the corresponding propylidyne and benzylidyne complexes via [2 + 2] cycloaddition-cycloreversion were examined for reversibility. Stoichiometric reactions revealed that both nitrile-alkyne cross-metathesis (NACM) cycles as well as the alkyne cross-metathesis (ACM) cycle operated reversibly in this system. With catalyst 3, depending on the aryl group used, at least one step in one of the NACM cycles was irreversible. In general, catalyst 1-DME afforded more rapid reaction than did 3 under comparable conditions. However, 3 displayed a slightly improved tolerance of polar functional groups than did 1-DME. For both 1-DME and 3, ACM is more rapid than NACM under typical conditions. Alkyne polymerization (AP) is a competing reaction with both 1-DME and 3. It can be suppressed but not entirely eliminated via manipulation of the catalyst concentration. As AP selectively removes 3-hexyne from the system, tandem NACM-ACM-AP can be used to prepare symmetrically substituted alkynes with good selectivity, including an arylene-ethynylene macrocycle. Alternatively, unsymmetrical alkynes of the form EtCCR (R variable) can be prepared with good selectivity via the reaction of RCN with excess 3-hexyne under conditions that suppress AP. DFT calculations support a [2 + 2] cycloaddition-cycloreversion mechanism analogous to that of alkyne metathesis. The barrier to azametalacyclobutadiene ring formation/breakup is greater than that for the corresponding metalacyclobutadiene. Two distinct high-energy azametalacyclobutadiene intermediates were found. These adopted a distorted square pyramidal geometry with significant bond localization.

H2 addition to (Me4PCP)Ir(CO): studies of the isomerization mechanism.

Reduced steric demand of the Me4PCP pincer ligand (PCP = κ3-C6H4-1,3-[CH2PR2]2, R = Me), allows for a more open metal center. This is evident through structure and reactivity comparisons between (Me4PCP)Ir derivatives and other (R4PCP)Ir complexes (R = tBu, iPr, CF3). In particular, isomerization from cis-(R4PCP)Ir(H)2(CO) to trans-(R4PCP)Ir(H)2(CO) is more facile when R = Me than when R = iPr. Deuterium incorporation in the hydride ligands from solvent C6D6 was observed during this isomerization when R = Me. This deuterium exchange has not been observed for other analogous R4PCP iridium complexes. A kinetic study of the cis/trans isomerization combined with computational studies suggests that the cis/trans isomerization proceeds through a migratory-insertion pathway involving a formyl intermediate.