One of the remaining "grand challenges" in chemistry is the development of a next generation, less expensive, cleaner process that can allow the vast reserves of methane from natural gas to augment or replace oil as the source of fuels and chemicals. Homogeneous (gas/liquid) systems that convert methane to functionalized products with emphasis on reports after 1995 are reviewed. Gas/solid, bioinorganic, biological, and reaction systems that do not specifically involve methane functionalization are excluded. The various reports are grouped under the main element involved in the direct reactions with methane. Central to the review is classification of the various reports into 12 categories based on both practical considerations and the mechanisms of the elementary reactions with methane. Practical considerations are based on whether or not the system reported can directly or indirectly utilize O as the only net coreactant based only on thermodynamic potentials. Mechanistic classifications are based on whether the elementary reactions with methane proceed by chain or nonchain reactions and with stoichiometric reagents or catalytic species. The nonchain reactions are further classified as CH activation (CHA) or CH oxidation (CHO). The bases for these various classifications are defined. In particular, CHA reactions are defined as elementary reactions with methane that result in a discrete methyl intermediate where the formal oxidation state (FOS) on the carbon remains unchanged at -IV relative to that in methane. In contrast, CHO reactions are defined as elementary reactions with methane where the carbon atom of the product is oxidized and has a FOS less negative than -IV. This review reveals that the bulk of the work in the field is relatively evenly distributed across most of the various areas classified. However, a few areas are only marginally examined, or not examined at all. This review also shows that, while significant scientific progress has been made, greater advances, particularly in developing systems that can utilize O, will be required to develop a practical process that can replace the current energy and capital intensive natural gas conversion process. We believe that this classification scheme will provide the reader with a rapid way to identify systems of interest while providing a deeper appreciation and understanding, both practical and fundamental, of the extensive literature on methane functionalization. The hope is that this could accelerate progress toward meeting this "grand challenge."

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 ...

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.

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 PtII is used to catalyze methane functionalization. Thus, it is generally accepted that key to replacing PtIV in that system with more practical oxidants is ensuring that the oxidant does not over-oxidize the reduced PtII species. The “Periana-Catalytica” system, which utilizes (bpym)PtIICl2 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)PtIICl2 to PtIV in the absence of methane would seem to contradict the originally proposed mechanism involving CH activation by a reduced PtII species. Mechanistic studies show that the originally proposed mechanism is incomplete and that while CH activation does proceed with PtII there is a solution to the over-oxidation dilemma. Importantly, contrary to the accepted view to minimize PtII 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.

Computational design of molecular homogeneous organometallic catalysts followed by experimental realization remains a significant challenge. Here, we report the development and use of a density functional theory transition-state model that provided quantitative prediction of molecular Cr catalysts for controllable selective ethylene trimerization and tetramerization. This computational model identified a general class of phosphine monocyclic imine (P,N)-ligand Cr catalysts where changes in the ligand structure control 1-hexene versus 1-octene selectivity. Experimental ligand and catalyst synthesis as well as reaction testing quantitatively confirmed predictions.

Chelate-assisted and internal electrophilic substitution type transition states were studied using a DFTbased energy decomposition method. Interaction energies for benzene and methane C-H bond activation by (acac-O,O) 2 Ir(X) complexes (X ) CH 3 COO and OH) were evaluated using the absolutely localized molecular orbital energy decomposition analysis (ALMO-EDA). A ratio of ∼1.5:1 for forward to reverse charge-transfer between (acac-O,O) 2 Ir(X) and benzene or methane transition state fragments confirms "ambiphilic" bonding, the result of an interplay between the electrophilic iridium center and the internal base component. This analysis also revealed that polarization effects account for a significant amount of transition state stabilization. The energy penalty to deform reactants into their transition state geometry, distortion energy, was also used to understand the large activation energy difference between six-membered and four-membered acetate-assisted transition states and help explain why these complexes do not activate the methane C-H bond.

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 β-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.

S2General Procedures: All manipulations were carried out using an argon filled MBraun glovebox and standard Schlenk techniques using over dried glassware (>1 h at 110 °C under vacuum,. THF was HPLC grade from EMD and distilled over Na/Benzophenone and then degassed under argon before use. H 2 O was degassed and stored under argon before use.Pentane was HPLC grade from EMD and distilled over NaH prior to use. Reagent-grade chemicals and solvents were purchased from Sigma Aldrich, Alfa Aesar, or EMD and used as is unless otherwise specified. Deuterated solvents were purchased from Cambridge Isotope Inc. and degassed and stored under argon before use. Re 2 O 7 was obtained from Strem or Alfa and stored in the glovebox freezer (-30 °C) before use. H 2 18 O 2 was obtained from Sigma Aldrich. H 2 18 O was obtained from Cambridge Isotopes Inc. Elemental analyses were performed by Columbia Analytical Services; Tucson, Arizona. Electrospray Ionization (ESI) mass spectroscopy was performed at the University of Florida Mass Spec Facility; Gainesville, Florida. Liquid phase organic products were analyzed with a Shimadzu GC-MS QP2010S equipped with cross-linked methyl silicone gum capillary column, RTX-5. Gas measurements were performed using an Agilent GasPro column. The retention times of the products were confirmed by known standards. NMR spectra were obtained on a Bruker Digital Avance III 400 (400.132 MHz for 1 H and 100.623 MHz for 13 C) spectrometer. Chemical shifts are given in ppm relative to residual solvent proton resonances or to a stated internal or external standard. The rhenium phenyl, tolyl,pentafluoro, and mesityl trioxides have been previously prepared and characterization data of these compounds compared with that of previous reports. 1 The phenyl and pentafluoro diarylzincs were purchased from Strem Inc. The tolyl 2 and mesityl 3 diaryl-zincs were prepared as previously described.