Supermetal: SbF5-mediated methane oxidation occurs by C-H activation and isobutane oxidation occurs by hydride transfer.

SbVF5 is generally assumed to oxidize methane through a methanium-to-methyl cation mechanism. However, experimentally no H2 is observed, and the mechanism of methane oxidation has remained unsolved for several decades. To solve this problem, density functional theory calculations with multiple chemical models (mononuclear and dinuclear) were used to examine methane oxidation by SbVF5 in the presence of CO leading to the methyl acylium cation ([CH3CO]+). While there is a low barrier for methane protonation by [SbVF6]-[H]+ (the combination of SbVF5 and HF) to give the [SbVF5]-[CH5]+ ion pair, H2 dissociation is a relatively high energy process, even with CO assistance, and so this protonation pathway is reversible. While Sb-mediated hydride transfer has a reasonable barrier, the C-H activation/σ-bond metathesis mechanism with the formation of an SbV-Me intermediate is lower in energy. This pathway leads to the acylium cation by functionalization of the SbV-Me intermediate with CO and is consistent with no observation of H2. Because this C-H activation/metal-alkyl functionalization pathway is higher in energy than methane protonation, it is also consistent with the experimentally observed methane hydrogen-to-deuterium exchange. This is the first time that evidence is presented demonstrating that SbVF5 acts beyond a Bronsted superacid and involves C-H activation with an organometallic intermediate. In contrast to methane, due to the much lower carbocation hydride affinity, isobutane significantly favors hydride transfer to give the tert-butyl carbocation with concomitant SbV to SbIII reduction. In this mechanism, the resulting highly acidic SbV-H intermediate provides a route to H2 through protonation of isobutane, which is consistent with experiments and resolves the longstanding enigma of different experimental results for methane versus isobutane.

Selective C-H Functionalization of Methane and Ethane by a Molecular SbV Complex.

Owing to the strong nonpolar bonds involved, selective C-H functionalization of methane and ethane to esters remains a challenge for molecular homogeneous chemistry. We report that the computationally predicted main-group p-block SbV (TFA)5 complex selectively functionalizes the C-H bonds of methane and ethane to the corresponding mono and/or diol trifluoroacetate esters at 110-180 °C with yields for ethane of up to 60 % with over 90 % selectivity. Experimental and computational studies support a unique mechanism that involves SbV -mediated C-H activation followed by functionalization of a SbV -alkyl intermediate.

Selective CH functionalization of methane, ethane, and propane by a perfluoroarene iodine(III) complex.

Direct partial oxidation of methane, ethane, and propane to their respective trifluoroacetate esters is achieved by a homogeneous hypervalent iodine(III) complex in non-superacidic (trifluoroacetic acid) solvent. The reaction is highly selective for ester formation (>99%). In the case of ethane, greater than 0.5 M EtTFA can be achieved. Preliminary kinetic analysis and density functional calculations support a nonradical electrophilic CH activation and iodine alkyl functionalization mechanism.

A mechanistic change results in 100 times faster CH functionalization for ethane versus methane by a homogeneous Pt catalyst.

The selective, oxidative functionalization of ethane, a significant component of shale gas, to products such as ethylene or ethanol at low temperatures and pressures remains a significant challenge. Herein we report that ethane is efficiently and selectively functionalized to the ethanol ester of H2SO4, ethyl bisulfate (EtOSO3H) as the initial product, with the Pt(II) "Periana-Catalytica" catalyst in 98% sulfuric acid. A subsequent organic reaction selectively generates isethionic acid bisulfate ester (HO3S-CH2-CH2-OSO3H, ITA). In contrast to the modest 3-5 times faster rate typically observed in electrophilic CH activation of higher alkanes, ethane CH functionalization was found to be ~100 times faster than that of methane. Experiment and quantum-mechanical calculations reveal that this unexpectedly large increase in rate is the result of a fundamentally different catalytic cycle in which ethane CH activation (and not platinum oxidation as for methane) is now turnover limiting. Facile Pt(II)-Et functionalization was determined to occur via a low energy ß-hydride elimination pathway (which is not available for methane) to generate ethylene and a Pt(II)-hydride, which is then rapidly oxidized by H2SO4 to regenerate Pt(II)-X2. A rapid, non-Pt-catalyzed reaction of formed ethylene with the hot, concentrated H2SO4 solvent cleanly generate EtOSO3H as the initial product, which further reacts with the H2SO4 solvent to generate ITA.

Selective monooxidation of light alkanes using chloride and iodate.

We describe an efficient system for the direct partial oxidation of methane, ethane, and propane using iodate salts with catalytic amounts of chloride in protic solvents. In HTFA (TFA = trifluoroacetate), >20% methane conversion with >85% selectivity for MeTFA have been achieved. The addition of substoichiometric amounts of chloride is essential, and for methane the conversion increases from <1% in the absence of chloride to >20%. The reaction also proceeds in aqueous HTFA as well as acetic acid to afford methyl acetate. (13)C labeling experiments showed that less than 2% of methane is overoxidized to (13)CO2 at 15% conversion of (13)CH4. The system is selective for higher alkanes: 30% ethane conversion with 98% selectivity for EtTFA and 19% propane conversion that is selective for mixtures of the mono- and difunctionalized TFA esters. Studies of methane conversion using a series of iodine-based reagents [I2, ICl, ICl3, I(TFA)3, I2O4, I2O5, (IO2)2S2O7, (IO)2SO4] indicated that the chloride enhancement is not limited to iodate.

Main-group compounds selectively oxidize mixtures of methane, ethane, and propane to alcohol esters.

Much of the recent research on homogeneous alkane oxidation has focused on the use of transition metal catalysts. Here, we report that the electrophilic main-group cations thallium(III) and lead(IV) stoichiometrically oxidize methane, ethane, and propane, separately or as a one-pot mixture, to corresponding alcohol esters in trifluoroacetic acid solvent. Esters of methanol, ethanol, ethylene glycol, isopropanol, and propylene glycol are obtained with greater than 95% selectivity in concentrations up to 1.48 molar within 3 hours at 180°C. Experiment and theory support a mechanism involving electrophilic carbon-hydrogen bond activation to generate metal alkyl intermediates. We posit that the comparatively high reactivity of these d(10) main-group cations relative to transition metals stems from facile alkane coordination at vacant sites, enabled by the overall lability of the ligand sphere and the absence of ligand field stabilization energies in systems with filled d-orbitals.

Using reduced catalysts for oxidation reactions: mechanistic studies of the "Periana-Catalytica" system for CH4 oxidation.

Designing oxidation catalysts based on CH activation with reduced, low oxidation state species is a seeming dilemma given the proclivity for catalyst deactivation by overoxidation. This dilemma has been recognized in the Shilov system where reduced Pt(II) is used to catalyze methane functionalization. Thus, it is generally accepted that key to replacing Pt(IV) in that system with more practical oxidants is ensuring that the oxidant does not over-oxidize the reduced Pt(II) species. The "Periana-Catalytica" system, which utilizes (bpym)Pt(II)Cl2 in concentrated sulfuric acid solvent at 200 °C, is a highly stable catalyst for the selective, high yield oxy-functionalization of methane. In lieu of the over-oxidation dilemma, the high stability and observed rapid oxidation of (bpym)Pt(II)Cl2 to Pt(IV) in the absence of methane would seem to contradict the originally proposed mechanism involving CH activation by a reduced Pt(II) species. Mechanistic studies show that the originally proposed mechanism is incomplete and that while CH activation does proceed with Pt(II) there is a solution to the over-oxidation dilemma. Importantly, contrary to the accepted view to minimize Pt(II) overoxidation, these studies also show that increasing that rate could increase the rate of catalysis and catalyst stability. The mechanistic basis for this counterintuitive prediction could help to guide the design of new catalysts for alkane oxidation that operate by CH activation.

Designing catalysts for functionalization of unactivated C-H bonds based on the CH activation reaction.

In an effort to augment or displace petroleum as a source of liquid fuels and chemicals, researchers are seeking lower cost technologies that convert natural gas (largely methane) to products such as methanol. Current methane to methanol technologies based on highly optimized, indirect, high-temperature chemistry (>800 °C) are prohibitively expensive. A new generation of catalysts is needed to rapidly convert methane and O(2) (ideally as air) directly to methanol (or other liquid hydrocarbons) at lower temperatures (~250 °C) and with high selectivity. Our approach is based on the reaction between CH bonds of hydrocarbons (RH) and transition metal complexes, L(n)M-X, to generate activated L(n)M-R intermediates while avoiding the formation of free radicals or carbocations. We have focused on the incorporation of this reaction into catalytic cycles by integrating the activation of the CH bond with the functionalization of L(n)M-R to generate the desired product and regenerate the L(n)M-X complex. To avoid free-radical reactions possible with the direct use of O(2), our approach is based on the use of air-recyclable oxidants. In addition, the solvent serves several roles including protection of the product, generation of highly active catalysts, and in some cases, as the air-regenerable oxidant. We postulate that there could be three distinct classes of catalyst/oxidant/solvent systems. The established electrophilic class combines electron-poor catalysts in acidic solvents that conceptually react by net removal of electrons from the bonding orbitals of the CH bond. The solvent protects the CH(3)OH by conversion to more electron-poor [CH(3)OH(2)](+) or the ester and also increases the electrophilicity of the catalyst by ligand protonation. The nucleophilic class matches electron-rich catalysts with basic solvents and conceptually reacts by net donation of electrons to the antibonding orbitals of the CH bond. In this case, the solvent could protect the CH(3)OH by deprotonation to the more electron-rich [CH(3)O](-) and increases the nucleophilicity of the catalysts by ligand deprotonation. The third grouping involves ambiphilic catalysts that can conceptually react with both the HOMO and LUMO of the CH bond and would typically involve neutral reaction solvents. We call this continuum base- or acid-modulated (BAM) catalysis. In this Account, we describe our efforts to design catalysts following these general principles. We have had the most success with designing electrophilic systems, but unfortunately, the essential role of the acidic solvent also led to catalyst inhibition by CH(3)OH above ~1 M. The ambiphilic catalysts reduced this product inhibition but were too slow and inefficient. To date, we have designed new base-assisted CH activation and L(n)M-R fuctionalization reactions and are working to integrate these into a complete, working catalytic cycle. Although we have yet to design a system that could supplant commercial processes, continued exploration of the BAM catalysis continuum may lead to new systems that will succeed in addressing this valuable goal.

Reaction of molecular oxygen with a Pd(II)-hydride to produce a Pd(II)-hydroperoxide: experimental evidence for an HX-reductive-elimination pathway.

The reaction of molecular oxygen with a Pd(II)-hydride species to form a Pd(II)-hydroperoxide represents one of the proposed catalyst reoxidation pathways in Pd-catalyzed aerobic oxidation reactions, but well-defined examples of this reaction were discovered only recently. Here, we present a mechanistic study of the reaction of O2 with trans-(IMes) 2Pd(H)(OBz), 1 (IMes = 1,3-dimesitylimidazol-2-ylidene), which yields trans-(IMes) 2Pd(OOH)(OBz), 2. The reaction was monitored by (1)H NMR spectroscopy in benzene-d6, and kinetic studies reveal a two-term rate law, rate = k1[1] + k2[1][BzOH], and a small deuterium kinetic isotope effect, k(Pd-H)/k(Pd-D) = 1.3(1). The rate is independent of the oxygen pressure. The data support a stepwise mechanism for the conversion of 1 into 2 consisting of rate-limiting reductive elimination of BzOH from 1 followed by rapid reaction of molecular oxygen with (IMes) 2Pd(0) and protonolysis of a Pd-O bond of the eta(2)-peroxo complex (IMes) 2Pd(O2). Benzoic acid and other protic additives (H2O, ArOH) catalyze the oxygenation reaction, probably by stabilizing the transition state for reductive elimination of BzOH from 1. This study provides the first experimental validation of the mechanism traditionally proposed for aerobic oxidation of Pd-hydride species.

Characterization of peroxo and hydroperoxo intermediates in the aerobic oxidation of N-heterocyclic-carbene-coordinated palladium(0).

An eta2-peroxopalladium(II) complex, derived from dioxygen addition to Pd(IMes)2 (IMes = bis-1,3-di(2,4,6-trimethylphenyl)imidazoline-2-ylidene), has been isolated and characterized. Subsequent addition of HOAc to (IMes)2Pd(O2) yields the first example of a hydroperoxopalladium species derived from molecular oxygen. The characterization and reactivity studies of these complexes provide the most detailed insights to date into the proposed mechanism for palladium(0) oxidation by molecular oxygen.

Antitrypanosomal activities of tryptanthrins.

New drugs and molecular targets are needed against Trypanosoma brucei, the protozoan that causes African sleeping sickness. Tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione), a traditional antifungal agent, and 11 analogs were tested against T. brucei in vitro. The greatest activity was conferred by electron-withdrawing groups in the 8 position of the tryptanthrin ring system; the most potent compound had a 50% effective concentration of 0.40 microM.