Pd(II) and Rh(I) Catalytic Precursors for Arene Alkenylation: Comparative Evaluation of Reactivity and Mechanism Based on Experimental and Computational Studies.

We combine experimental and computational investigations to compare and understand catalytic arene alkenylation using the Pd(II) and Rh(I) precursors Pd(OAc)2 and [(η2-C2H4)2Rh(µ-OAc)]2 with arene, olefin, and Cu(II) carboxylate at elevated temperatures (>120 °C). Under specific conditions, previous computational and experimental efforts have identified heterotrimetallic cyclic PdCu2(η2-C2H4)3(µ-OPiv)6 and [(η2-C2H4)2Rh(µ-OPiv)2]2(µ-Cu) (OPiv = pivalate) species as likely active catalysts for these processes. Further studies of catalyst speciation suggest a complicated equilibrium between Cu(II)-containing complexes containing one Rh or Pd atom with complexes containing two Rh or Pd atoms. At 120 °C, Rh catalysis produces styrene >20-fold more rapidly than Pd. Also, at 120 °C, Rh is ∼98% selective for styrene formation, while Pd is ∼82% selective. Our studies indicate that Pd catalysis has a higher predilection toward olefin functionalization to form undesired vinyl ester, while Rh catalysis is more selective for arene/olefin coupling. However, at elevated temperatures, Pd converts vinyl ester and arene to vinyl arene, which is proposed to occur through low-valent Pd(0) clusters that are formed in situ. Regardless of arene functionality, the regioselectivity for alkenylation of mono-substituted arenes with the Rh catalyst gives an approximate 2:1 meta/para ratio with minimal ortho C-H activation. In contrast, Pd selectivity is significantly influenced by arene electronics, with electron-rich arenes giving an approximate 1:2:2 ortho/meta/para ratio, while the electron-deficient (α,α,α)-trifluorotoluene gives a 3:1 meta/para ratio with minimal ortho functionalization. Kinetic intermolecular arene ethenylation competition experiments find that Rh reacts most rapidly with benzene, and the rate of mono-substituted arene alkenylation does not correlate with arene electronics. In contrast, with Pd catalysis, electron-rich arenes react more rapidly than benzene, while electron-deficient arenes react less rapidly than benzene. These experimental findings, in combination with computational results, are consistent with the arene C-H activation step for Pd catalysis involving significant η1-arenium character due to Pd-mediated electrophilic aromatic substitution character. In contrast, the mechanism for Rh catalysis is not sensitive to arene-substituent electronics, which we propose indicates less electrophilic aromatic substitution character for the Rh-mediated arene C-H activation.

Ethylene Dimerization and Oligomerization Using Bis(phosphino)boryl Supported Ni Complexes.

We report the dimerization and oligomerization of ethylene using bis(phosphino)boryl supported Ni(II) complexes as catalyst precursors. By using alkylaluminum(III) compounds or other Lewis acid additives, Ni(II) complexes of the type (RPBP)NiBr (R = tBu or Ph) show activity for the production of butenes and higher olefins. Optimized turnover frequencies of 640 molethylene·molNi-1·s-1 for the formation of butenes with 41(1)% selectivity for 1-butene using (PhPBP)NiBr, and 68 molethylene·molNi-1·s-1 for butenes production with 87.2(3)% selectivity for 1-butene using (tBuPBP)NiBr, have been demonstrated. With methylaluminoxane as a co-catalyst and (tBuPBP)NiBr as the precatalyst, ethylene oligomerization to form C4 through C20 products was achieved, while the use of (PhPBP)NiBr as the pre-catalyst retained selectivity for C4 products. Our studies suggest that the ethylene dimerization is not initiated by Ni hydride or alkyl intermediates. Rather, our studies point to a mechanism that involves a cooperative B/Ni activation of ethylene to form a key 6-membered borametallacycle intermediate. Thus, a cooperative activation of ethylene by the Ni-B unit of the (RPBP)Ni catalysts is proposed as a key element of the Ni catalysis.

Cleavage of Carbon Dioxide C=O Bond Promoted by Nickel-Boron Cooperativity in a PBP-Ni Complex.

The synthesis and characterization of (tBu PBP)Ni(OAc) (5) by insertion of carbon dioxide into the Ni-C bond of (tBu PBP)NiMe (1) is presented. An unexpected CO2 cleavage process involving the formation of new B-O and Ni-CO bonds leads to the generation of a butterfly-structured tetra-nickel cluster (tBu PBOP)2 Ni4 (µ-CO)2 (6). Mechanistic investigation of this reaction indicates a reductive scission of CO2 by O-atom transfer to the boron atom via a cooperative nickel-boron mechanism. The CO2 activation reaction produces a three-coordinate (tBu P2 BO)Ni-acyl intermediate (A) that leads to a (tBu P2 BO)-NiI complex (B) via a likely radical pathway. The NiI species is trapped by treatment with the radical trap (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) to give (tBu P2 BO)NiII (η2 -TEMPO) (7). Additionally, 13 C and 1 H NMR spectroscopy analysis using 13 C-enriched CO2 provides information about the species involved in the CO2 activation process.

Aerobic Partial Oxidation of Alkanes Using Photodriven Iron Catalysis.

Photodriven oxidations of alkanes in trifluoroacetic acid using commercial and synthesized Fe(III) sources as catalyst precursors and dioxygen (O2) as the terminal oxidant are reported. The reactions produce alkyl esters and occur at ambient temperature in the presence of air, and catalytic turnover is observed for the oxidation of methane in a pure O2 atmosphere. Under optimized conditions, approximately 17% conversion of methane to methyl trifluoroacetate at more than 50% selectivity is observed. It is demonstrated that methyl trifluoroacetate is stable under catalytic conditions, and thus overoxidized products are not formed through secondary oxidation of methyl trifluoroacetate.

Advances in Group 10 Transition-Metal-Catalyzed Arene Alkylation and Alkenylation.

On a large scale, the dominant method to produce alkyl arenes has been arene alkylation from arenes and olefins using acid-based catalysis. The addition of arene C-H bonds across olefin C═C bonds catalyzed by transition-metal complexes through C-H activation and olefin insertion into metal-aryl bonds provides an alternative approach with potential advantages. This Perspective presents recent developments of olefin hydroarylation and oxidative olefin hydroarylation catalyzed by molecular complexes based on group 10 transition metals (Ni, Pd, Pt). Emphasis is placed on comparisons between Pt catalysts and other group 10 metal catalysts as well as Ru, Ir, and Rh catalysts.

Reductive C-C Coupling from Molecular Au(I) Hydrocarbyl Complexes: A Mechanistic Study.

Organometallic gold complexes are used in a range of catalytic reactions, and they often serve as catalyst precursors that mediate C-C bond formation. In this study, we investigate C-C coupling to form ethane from various phosphine-ligated gem-digold(I) methyl complexes including [Au2(µ-CH3)(PMe2Ar')2][NTf2], [Au2(µ-CH3)(XPhos)2][NTf2], and [Au2(µ-CH3)(tBuXPhos)2][NTf2] {Ar' = C6H3-2,6-(C6H3-2,6-Me)2, C6H3-2,6-(C6H2-2,4,6-Me)2, C6H3-2,6-(C6H3-2,6-iPr)2, or C6H3-2,6-(C6H2-2,4,6-iPr)2; XPhos = 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl; tBuXPhos = 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl; NTf2 = bis(trifluoromethyl sulfonylimide)}. The gem-digold methyl complexes are synthesized through reaction between Au(CH3)L and Au(L)(NTf2) {L = phosphines listed above}. For [Au2(µ-CH3)(XPhos)2][NTf2] and [Au2(µ-CH3)(tBuXPhos)2][NTf2], solid-state X-ray structures have been elucidated. The rate of ethane formation from [Au2(µ-CH3)(PMe2Ar')2][NTf2] increases as the steric bulk of the phosphine substituent Ar' decreases. Monitoring the rate of ethane elimination reactions by multinuclear NMR spectroscopy provides evidence for a second-order dependence on the gem-digold methyl complexes. Using experimental and computational evidence, it is proposed that the mechanism of C-C coupling likely involves (1) cleavage of [Au2(µ-CH3)(PMe2Ar')2][NTf2] to form Au(PR2Ar')(NTf2) and Au(CH3)(PMe2Ar'), (2) phosphine migration from a second equivalent of [Au2(µ-CH3)(PMe2Ar')2][NTf2] aided by binding of the Lewis acidic [Au(PMe2Ar')]+, formed in step 1, to produce [Au2(CH3)(PMe2Ar')][NTf2] and [Au2(PMe2Ar')]+, and (3) recombination of [Au2(CH3)(PMe2Ar')][NTf2] and Au(CH3)(PMe2Ar') to eliminate ethane.

Advances in Rhodium-Catalyzed Oxidative Arene Alkenylation.

ConspectusAlkyl and alkenyl arenes are of substantial value in both large-scale and fine chemical processes. Billions of pounds of alkyl and alkenyl arenes are produced annually. Historically, the dominant method for synthesis of alkyl arenes is acid-catalyzed arene alkylation, and alkenyl arenes are often synthesized in a subsequent dehydrogenation step. But these methods have limitations that result from the catalytic mechanism including (1) common polyalkylation, which requires an energy intensive transalkylation process, (2) quantitative selectivity for Markovnikov products for arene alkylation using α-olefins, (3) for substituted arenes, regioselectivity that is dictated by the electronic character of the arene substituents, (4) inability to form alkenyl arenes in a single process, and (5) commonly observed slow reactivity with electron-deficient arenes. Transition-metal-catalyzed aryl-carbon coupling reactions can produce alkyl or alkenyl arenes from aryl halides. However, these reactions often generate halogenated waste and typically require a stoichiometric amount of metal-containing transmetalation reagent. Transition-metal-catalyzed arene alkylation or alkenylation that involves arene C-H activation and olefin insertion into metal-aryl bonds provides a potential alternative method to prepare alkyl or alkenylation arenes. Such reactions can circumvent carbocationic intermediates and, as a result, can overcome some of the limitations mentioned above. In particular, controlling the regioselectivity of the insertion of α-olefins into metal-aryl bonds provides a strategy to selectively synthesize anti-Markovnikov products. But, previously reported catalysts often show limited longevity and low selectivity for anti-Markovnikov products.In this Account, we present recent developments in single-step arene alkenylation using Rh catalyst precursors. The reactions are successful for unactivated hydrocarbons and exhibit unique selectivity. The catalytic production of alkenyl arenes operates via Rh-mediated aromatic C-H activation, which likely occurs by a concerted metalation-deprotonation mechanism, olefin insertion into a Rh-aryl bond, ß-hydride elimination from the resulting Rh-hydrocarbon product, and net dissociation of alkenyl arene with formation of a Rh hydride. Reaction of the Rh hydride with Cu(II) oxidant completes the catalytic cycle. Although Rh nanoparticles can be formed under some conditions, mechanistic studies have revealed that soluble Rh species are likely responsible for the catalysis. These Rh catalyst precursors achieve high turnovers with >10,000 catalytic turnovers observed in some cases. Under anaerobic conditions, Cu(II) carboxylates are used as the oxidant. In some cases, aerobic recycling of Cu(II) oxidant has been demonstrated. Hence, the Rh arene alkenylation catalysis bears some similarities to Pd-catalyzed olefin oxidation (i.e., the Wacker-Hoechst process). The Rh-catalyzed arene alkenylation is compatible with some electron-deficient arenes, and they are selective for anti-Markovnikov products when using substituted olefins. Finally, when using monosubstituted arenes, consistent with a metal-mediated C-H activation process, Rh-catalyzed alkenylation of substituted arenes shows selectivity for meta- and para-alkenylation products.

Synthesis of Stilbenes by Rhodium-Catalyzed Aerobic Alkenylation of Arenes via C-H Activation.

Arene alkenylation is commonly achieved by late transition metal-mediated C(sp2)-C(sp2) cross-coupling, but this strategy typically requires prefunctionalized substrates (e.g., with halides or pseudohalides) and/or the presence of a directing group on the arene. Transition metal-mediated arene C-H activation and alkenylation offers an alternative method to functionalize arene substrates. Herein, we report a rhodium-catalyzed oxidative arene alkenylation from arenes and styrenes to prepare stilbene and stilbene derivatives. The reaction is successful with several functional groups on both the arene and the olefin including fluoride, chloride, trifluoromethyl, ester, nitro, acetate, cyanide, and ether groups. Reactions of monosubstituted arenes are selective for alkenylation at the meta and para positions, generally with approximately 2:1 selectivity, respectively. Resveratrol and (E)-1,2,3-trimethoxy-5-(4-methoxystyryl)benzene (DMU-212) are synthesized by this single-step approach in high yield. Comparison with palladium catalysis showed that rhodium catalysis is more selective for meta-functionalization for monosubstituted arenes and that the Rh catalysis has better tolerance of halogen groups.

Generalized Synthetic Strategy for Transition-Metal-Doped Brookite-Phase TiO2 Nanorods.

We report a generalized wet-chemical methodology for the synthesis of transition-metal (M)-doped brookite-phase TiO2 nanorods (NRs) with unprecedented wide-range tunability in dopant composition (M = V, Cr, Mn, Fe, Co, Ni, Cu, Mo, etc.). These quadrangular NRs can selectively expose {210} surface facets, which is induced by their strong affinity for oleylamine stabilizer. This structure is well preserved with variable dopant compositions and concentrations, leading to a diverse library of TiO2 NRs wherein the dopants in single-atom form are homogeneously distributed in a brookite-phase solid lattice. This synthetic method allows tuning of dopant-dependent properties of TiO2 nanomaterials for new opportunities in catalysis applications.

Catalytic Synthesis of Superlinear Alkenyl Arenes Using a Rh(I) Catalyst Supported by a "Capping Arene" Ligand: Access to Aerobic Catalysis.

Alkyl and alkenyl arenes are used in a wide range of products. However, the synthesis of 1-phenylalkanes or their alkenyl variants from arenes and alkenes is not accessible with current commercial acid-based catalytic processes. Here, it is reported that an air-stable Rh(I) complex, (5-FP)Rh(TFA)(η2-C2H4) (5-FP = 1,2-bis( N-7-azaindolyl)benzene; TFA = trifluoroacetate), serves as a catalyst precursor for the oxidative conversion of arenes and alkenes to alkenyl arenes that are precursors to 1-phenylalkanes upon hydrogenation. It has been demonstrated that coordination of the 5-FP ligand enhances catalyst longevity compared to unligated Rh(I) catalyst precursors, and the 5-FP-ligated catalyst permits in situ recycling of the Cu(II) oxidant using air. The 5-FP ligand provides a Rh catalyst that can maintain activity for arene alkenylation over at least 2 weeks in reactions at 150 °C that involve multiple Cu(II) regeneration steps using air. Conditions to achieve >13 000 catalytic turnovers with an 8:1 linear:branched (L:B) ratio have been demonstrated. In addition, the catalyst is active under aerobic conditions using air as the sole oxidant. At 80 °C, an 18:1 L:B ratio of alkenyl arenes has been observed, but the reaction rate is substantially reduced compared to 150 °C. Quantum mechanics (QM) calculations compare two predicted reaction pathways with the experimental data, showing that an oxidative addition/reductive elimination pathway is energetically favored over a pathway that involves C-H activation by concerted metalation-deprotonation. In addition, our QM computations are consistent with the observed selectivity (11:1) for linear alkenyl arene products.

Catalytic Synthesis of "Super" Linear Alkenyl Arenes Using an Easily Prepared Rh(I) Catalyst.

Linear alkyl benzenes (LAB) are global chemicals that are produced by acid-catalyzed reactions that involve the formation of carbocationic intermediates. One outcome of the acid-based catalysis is that 1-phenylalkanes cannot be produced. Herein, it is reported that [Rh(µ-OAc)(η2-C2H4)2]2 catalyzes production of 1-phenyl substituted alkene products via oxidative arene vinylation. Since C═C bonds can be used for many chemical transformations, the formation of unsaturated products provides a potential advantage over current processes that produce saturated alkyl arenes. Conditions that provide up to a 10:1 linear:branched ratio have been achieved, and catalytic turnovers >1470 have been demonstrated. In addition, electron-deficient and electron-rich substituted benzenes are successfully alkylated. The Rh catalysis provides ortho:meta:para selectivity that is opposite to traditional acid-based catalysis.

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.

Organometallic Complexes Anchored to Conductive Carbon for Electrocatalytic Oxidation of Methane at Low Temperature.

Low-temperature direct methane fuel cells (DMEFCs) offer the opportunity to substantially improve the efficiency of energy production from natural gas. This study focuses on the development of well-defined platinum organometallic complexes covalently anchored to ordered mesoporous carbon (OMC) for electrochemical oxidation of methane in a proton exchange membrane fuel cell at 80 °C. A maximum normalized power of 403 µW/mg Pt was obtained, which was 5 times higher than the power obtained from a modern commercial catalyst and 2 orders of magnitude greater than that from a Pt black catalyst. The observed differences in catalytic activities for oxidation of methane are linked to the chemistry of the tethered catalysts, determined by X-ray photoelectron spectroscopy. The chemistry/activity relationships demonstrate a tangible path for the design of electrocatalytic systems for C-H bond activation that afford superior performance in DMEFC for potential commercial applications.

Rhodium bis(quinolinyl)benzene complexes for methane activation and functionalization.

A series of rhodium(III) bis(quinolinyl)benzene (bisq(x)) complexes was studied as candidates for the homogeneous partial oxidation of methane. Density functional theory (DFT) (M06 with Poisson continuum solvation) was used to investigate a variety of (bisq(x)) ligand candidates involving different functional groups to determine the impact on Rh(III)(bisq(x))-catalyzed methane functionalization. The free energy activation barriers for methane C-H activation and Rh-methyl functionalization at 298 K and 498 K were determined. DFT studies predict that the best candidate for catalytic methane functionalization is Rh(III) coordinated to unsubstituted bis(quinolinyl)benzene (bisq). Support is also found for the prediction that the η(2)-benzene coordination mode of (bisq(x)) ligands on Rh encourages methyl group functionalization by serving as an effective leaving group for SN2 and SR2 attack.

Long-range C-H bond activation by Rh(III)-carboxylates.

Traditional C-H bond activation by a concerted metalation-deprotonation (CMD) mechanism involves precoordination of the C-H bond followed by deprotonation from an internal base. Reported herein is a "through-arene" activation of an uncoordinated benzylic C-H bond that is 6 bonds away from a Rh(III) ion. The mechanism, which was investigated by experimental and DFT studies, proceeds through a dearomatized xylene intermediate. This intermediate was observed spectroscopically upon addition of a pyridine base to provide a thermodynamic trap.

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.

Density functional theory study of oxygen-atom insertion into metal-methyl bonds of iron(II), ruthenium(II), and osmium(II) complexes: study of metal-mediated C-O bond formation.

Metal-mediated C-O bond formation is a key step in hydrocarbon oxygenation catalytic cycles; however, few examples of this reaction have been reported for low-oxidation-state complexes. Oxygen insertion into a metal-carbon bond of Cp*M(CO)(OPy)R (Cp* = η(5)-pentamethylcyclopentadienyl; R = Me, Ph; OPy = pyridine-N-oxide; M = Fe, Ru, Os) was analyzed via density functional theory calculations. Oxygen-atom insertions through a concerted single-step organometallic Baeyer-Villiger pathway and a two-step pathway via a metal-oxo intermediate were studied; calculations predict that the former pathway was lower in energy. The results indicated that functionalization of M-R to M-OR (R = Me, Ph) is plausible using iron(II) complexes. Starting from Cp*Fe(CO)(OPy)Ph, the intermediate Fe-oxo showed oxyl character and, thus, is best considered an Fe(III)O(•-) complex. Oxidation of the π-acid ancillary ligand CO was facile. Substitutions of CO with dimethylamide and NH3 were calculated to lower the activation barrier by ∼1-2 kcal/mol for formation of the Fe(III)O(•-) intermediate, whereas a chloride ligand raised the activation barrier to 26 kcal/mol from 22.9 kcal/mol.

C-H activation of pyrazolyl ligands by Ru(II).

Previously, hydridotris(pyrazolyl)borate (Tp) Ru(II) alkyl and aryl complexes of the type TpRu(L)(NCMe)R (R = methyl or aryl; L = charge-neutral two-electron donating ligand) were demonstrated to activate aromatic C-H bonds. To determine the impact of replacing the anionic Tp ligand with charge-neutral poly(pyrazolyl)alkane ligands, [(C(pz)4)Ru(P(OCH2)3CEt)(NCMe)Me][BAr'4] (pz = pyrazolyl, BAr'4 = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate) was prepared. Heating a C6D6 solution of [(C(pz)4)Ru(P(OCH2)3CEt)(NCMe)Me][BAr'4] with 1 equiv of NCMe resulted in C-H activation of the 5-position of a pyrazolyl ring to yield [(κ(3)-(N,C(5),N)C(pz)4)Ru(P(OCH2)3CEt)(NCMe)2][BAr'4] and CH4. Intramolecular C-H activation of the 5-position of a pyrazolyl ring also occurred when (η(6)-p-cymene)Ru(P(OCH2)3CEt)(Br)Ph was heated in the presence of C(pz)4 to yield [(κ(3)-N,C(5),N)C(pz)4]Ru(P(OCH2)3CEt)(NCMe)Br and C6H6. Density functional theory calculations revealed that the different reactivities of TpRu(P(OCH2)3CEt)(NCMe)R and [(C(pz)4)Ru(P(OCH2)3CEt)(NCMe)Me][BAr'4] result from the stronger binding of the Tp pyrazolyl rings to Ru(II) compared to that of C(pz)4.

1,2-Addition of dihydrogen across rhodium(III)-OMe bonds.

The Rh(III) complexes [((t)bpy)2Rh(OMe)(L)][X]n ((t)bpy = 4,4'-di-tert-butyl-2,2'-bipyridyl; L = MeOH, n = 2, X = OTf (OTf = trifluoromethanesulfonate), TFA (TFA = trifluoroacetate); L = TFA, n = 1, X = OTf) have been shown to activate dihydrogen via net 1,2-addition of the H-H bond across the Rh(III)-OMe bond. The bis(methoxide) complex [((t)bpy)2Rh(OMe)2][OTf] was synthesized by addition of CsOH·H2O in methanol to [((t)bpy)2Rh(OTf)2][OTf] in CH3CN. The addition of HTFA to [((t)bpy)2Rh(OMe)2][OTf] leads to the formation of [((t)bpy)2Rh(OMe)(MeOH)][OTf][TFA], which exists in equilibrium with [((t)bpy)2Rh(OMe)(TFA)][OTf]. The mixture of [((t)bpy)2Rh(OMe)(MeOH)][OTf][TFA] and [((t)bpy)2Rh(OMe)(TFA)][OTf] activates dihydrogen at 68 °C to give methanol and [((t)bpy)2Rh(H)(TFA)][OTf]. Studies indicate that the activation of dihydrogen has a first-order dependence on the Rh(III) methoxide complex and a dependence on hydrogen that is between zero and first order. Combined experimental and computational studies have led to a proposed mechanism for hydrogen activation by [((t)bpy)2Rh(OMe)(MeOH)][OTf][TFA] that involves dissociation of MeOH, coordination of hydrogen, and 1,2-addition of hydrogen across the Rh-OMe bond. DFT calculations indicate that there is a substantial energy penalty for MeOH dissociation and a relatively flat energy surface for subsequent hydrogen coordination and activation.

Polymers for the stabilization and delivery of proteins topically and per os to the insect hemocoel through conjugation with aliphatic polyethylene glycol.

Co-feeding of aliphatic polyethylene glycol (PEG), phospholipase A2, anionic and ionic detergents, and amphipathic glycoside with bovine serum albumin (BSA) as a model protein to fourth stadium tobacco budworms, Heliothis virescens, did not affect the levels of BSA in the hemolymph. Covalent conjugation of small proteins like the decapeptide trypsin modulating oostatic factor (TMOF) to polyethylene glycol was previously shown to protect the peptide from protease attack and enhance its accumulation in the insect hemocoel. Whether this polymer chemistry could do the same for larger proteins was examined. The chemistry for the synthesis of polydispersed aliphatic PEG350-insulin and monodispersed aliphatic PEG333-insulin are described herein. Insulin was used for this synthesis and not BSA to better control conjugation among the available free amine groups. When PEGylated insulin or free insulin were fed in artificial diet to fifth stadium budworms, greater concentrations of insulin using the PEGylated variants were found in the hemolymph than when free insulin was used (a 6.7 and 7.3-fold increase for the PEG350 and PEG333 conjugates, respectively). When insulin is topically applied to the dorsum of H. virescens, no insulin is found in the hemolymph. However, after topical application of the PEGylated insulins, PEG350-insulin and PEG333-insulin were detected in the hemolymph. After injections of insulin into the hemocoel of fourth stadium H. virescens, insulin is completely cleared from the hemolymph in 120min. In comparison, PEG350-insulin and PEG333-insulin were present in the hemolymph for 300 and 240min after injection, respectively, translating to a 3.3 and 2.7-fold increase in the length of time insulin remains in the hemolymph after injection.