Steven M. Bischof

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.

Main-Group Compounds Selectively Oxidize Mixtures of Methane, Ethane, and Propane to Alcohol Esters

Light Alkanes, Heavy Metals Hydraulic fracturing, or fracking, has rapidly increased the supply of natural gas and has motivated methods to convert its constituents into commodity chemicals. Hashiguchi et al. (p. 1232) have found that lead and thallium salts are both efficient and selective oxidants, not only for methane, but for ethane and propane as well. In trifluoroacetic acid solvent, the alkanes are cleanly oxidized to the trifluoroacetate esters of their respective alcohols and 1,2-diols. Building on earlier discoveries, this work paves the way to developing methods that reduce our dependence on petroleum for industrial feedstocks. Lead and thallium salts are surprisingly selective and efficient oxidants of the constituents of natural gas. 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 d10 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.

Mechanism of efficient anti-Markovnikov olefin hydroarylation catalyzed by homogeneous Ir(III) complexes

The mechanism of the hydroarylation reaction between unactivated olefins (ethylene, propylene, and styrene) and benzene catalyzed by [(R)Ir(μ-acac-O,O,C3)-(acac-O,O)2]2 and [R-Ir(acac-O,O)2(L)] (R = acetylacetonato, CH3, CH2CH3, Ph, or CH2CH2Ph, and L = H2O or pyridine) Ir(III) complexes was studied by experimental methods. The system is selective for generating the anti-Markovnikov product of linear alkylarenes (61:39 for benzene + propylene and 98:2 for benzene + styrene). The reaction mechanism was found to follow a rate law with first-order dependence on benzene and catalyst, but a non-linear dependence on olefin. 13C-labelling studies with CH313CH2-Ir-Py showed that reversible β-hydride elimination is facile, but unproductive, giving exclusively saturated alkylarene products. The migration of the 13C-label from the α to β-positions was found to be slower than the C–H activation of benzene (and thus formation of ethane and Ph-d5-Ir-Py). Kinetic analysis under steady state conditions gave a ratio of the rate constants for CH activation and β-hydride elimination (kCH: kβ) of ∼0.5. The comparable magnitude of these rates suggests a common rate determining transition state/intermediate, which has been shown previously with B3LYP density functional theory (DFT) calculations. Overall, the mechanism of hydroarylation proceeds through a series of pre-equilibrium dissociative steps involving rupture of the dinuclear species or the loss of L from Ph-Ir-L to the solvento, 16-electron species, Ph-Ir(acac-O,O)2-Sol (where Sol refers to coordinated solvent). This species then undergoes trans to cisisomerization of the acetylacetonato ligand to yield the pseudo octahedral species cis-Ph-Ir-Sol, which is followed by olefin insertion (the regioselective and rate determining step), and then activation of the C–H bond of an incoming benzene to generate the product and regenerate the catalyst.

Oxy-Functionalization of Nucleophilic Rhenium(I) Metal Carbon Bonds Catalyzed by Selenium(IV)

We report that SeO2 catalyzes the facile oxy-functionalization of (CO)5Re(I)-Me(delta-) with IO4(-) to generate methanol. Mechanistic studies and DFT calculations reveal that catalysis involves methyl group transfer from Re to the electrophilic Se center followed by oxidation and subsequent reductive functionalization of the resulting CH3Se(VI) species. Furthermore, (CO)3Re(I)(Bpy)-R (R = ethyl, n-propyl, and aryl) complexes show analogous transfer to SeO2 to generate the primary alcohols. This represents a new strategy for the oxy-functionalization of M-R(delta-) polarized bonds.

The para-substituent effect and pH-dependence of the organometallic Baeyer-Villiger oxidation of rhenium-carbon bonds

We studied the Baeyer-Villiger (BV) type oxidation of phenylrhenium trioxide (PTO) by H(2)O(2) in the aqueous phase using Quantum Mechanics (density functional theory with the M06 functional) focusing on how the solution pH and the para-substituent affect the Gibbs free energy surfaces. For both PTO and MTO (methylrhenium trioxide) cases, we find that for pH > 1 the BV pathway having OH(-) as the leaving group is lower in energy than the one involving simultaneous protonation of hydroxide. We also find that during this organometallic BV oxidation, the migrating phenyl is a nucleophile so that substituting functional groups in the para-position of phenyl with increased electron-donating character lowers the migration barrier, just as in organic BV reactions. However, this substituent effect also pushes electron density to Re, impeding HOO(-) coordination and slowing down the reaction. This is in direct contrast to the organic analog, in which para-substitution has an insignificant influence on 1,2-addition of peracids. Due to the competition of the two opposing effects and the dependence of the resting state on pH and concentration, the reaction rate of the organometallic BV oxidation is surprisingly unaffected by para-substitution.

Synthesis and Reactivity of a Neutral, Three‐Coordinate Platinum(II) Complex Featuring Terminal Amido Ligation

A crystallographically characterized three-coordinate, formally 14 electron Pt(II) complex 1 featuring terminal amido ligation is reported. Computational analysis revealed relatively weak π donation from the amide lone pair to platinum and supports a 14-electron assignment for 1. Stoichiometric reactivity studies confirmed the viability of net O-H and C-H addition across, as well as isonitrile insertion into, the terminal platinum-amido linkage of 1.

Designing Molecular Catalysts for Selective CH Functionalization

The design of molecular catalysts for the selective hydroxylation of hydrocarbons is an important challenge. Designing systems that couple the CH activation reaction with oxy-functionalization of the resulting M–R intermediates has emerged as a promising strategy to meeting this goal. A large number of well-defined CH activation systems have been reported, but relatively few have been utilized as efficient hydroxylation catalysts. The primary reason for this observation is that most efficient CH activation catalysts are incompatible with the conditions required for oxy-functionalization of M–R. Significantly, the reported systems for CH hydroxylation suffer from a combination of challenges related to product protection, poor reaction selectivity, low catalytic activity, stability, and/or expensive product separation which have prevented further development. The design of next generation systems that are more active for both the CH activation and M–R functionalization steps will be directly dependent on improving reaction selectivity and stability of the catalyst systems. Herein, we outline the requirements for meeting these goals in regard to developing new oxy-functionalization catalysts and describe our efforts in this area.

Iridium(III) catalyzed trifluoroacetoxylation of aromatic hydrocarbons

A tridentate, NNC-tb (where NNC-tb = 2-(pyridin-2-yl)benzo[h]quinoline) ligated IrIII complex (NNC-tb)Ir(Ph)(4-MePy)(TFA), 11 along with analogues are very active for CH activation as evidenced by rapid catalytic H/D exchange between benzene and trifluoroacetic acid – d1 (DTFA). The complexes were examined with a variety of oxidants for the catalytic conversion of benzene to phenyltrifluoroacetate. Herein, the synthesis and characterization of (NNC-tb)Ir complexes is described along with the reactivity of these complexes towards arenes and alkanes.

Dehydrogenative B−H/C(sp3)−H Benzylic Borylation within the Coordination Sphere of Platinum(II)

The first examples of stoichiometric dehydrogenative B-H/C(sp3 )-H benzylic borylation reactions, which are of relevance to catalytic methylarene (di)borylation, are reported. These unusual transformations involving a (κ2 -P,N)Pt(η3 -benzyl) complex, and either pinacolborane or catecholborane, proceed cleanly at room temperature. Density functional calculations suggest that borylation occurs via successive σ-bond metathesis steps, whereby a PtII -H intermediate engages in C(sp3 )-H bond activation-induced dehydrogenation.

Correction: Iridium(III) catalyzed trifluoroacetoxylation of aromatic hydrocarbons

Correction for ‘Iridium(III) catalyzed trifluoroacetoxylation of aromatic hydrocarbons’ by Steven M. Bischof et al., RSC Adv., 2014, 4, 35639–35648.