Nitrous oxide activation by picoline-derived Ni-CNP hydrides.

Oxygen atom transfer (OAT) from N2O to the Ni-H bond of proton-responsive picoline-derived CNP nickel complexes has been investigated both experimentally and theoretically. These Ni-CNP complexes efficiently catalyse the reduction of N2O with pinacolborane (HBpin) under mild conditions.

Catalytic Nitrous Oxide Reduction with H2 Mediated by Pincer Ir Complexes.

Reduction of nitrous oxide (N2O) with H2 to N2 and water is an attractive process for the decomposition of this greenhouse gas to environmentally benign species. Herein, a series of iridium complexes based on proton-responsive pincer ligands (1-4) are shown to catalyze the hydrogenation of N2O under mild conditions (2 bar H2/N2O (1:1), 30 °C). Among the tested catalysts, the Ir complex 4, based on a lutidine-derived CNP pincer ligand having nonequivalent phosphine and N-heterocyclic carbene (NHC) side donors, gave rise to the highest catalytic activity (turnover frequency (TOF) = 11.9 h-1 at 30 °C, and 16.4 h-1 at 55 °C). Insights into the reaction mechanism with 4 have been obtained through NMR spectroscopy. Thus, reaction of 4 with N2O in tetrahydrofuran-d8 (THF-d8) initially produces deprotonated (at the NHC arm) species 5NHC, which readily reacts with H2 to regenerate the trihydride complex 4. However, prolonged exposure of 4 to N2O for 6 h yields the dinitrogen Ir(I) complex 7P, having a deprotonated (at the P-arm) pincer ligand. Complex 7P is a poor catalytic precursor in the N2O hydrogenation, pointing out to the formation of 7P as a catalyst deactivation pathway. Moreover, when the reaction of 4 with N2O is carried out in wet THF-d8, formation of a new species, which has been assigned to the hydroxo species 8, is observed. Finally, taking into account the experimental results, density functional theory (DFT) calculations were performed to get information on the catalytic cycle steps. Calculations are in agreement with 4 as the TOF-determining intermediate (TDI) and the transfer of an apical hydrido ligand to the terminal nitrogen atom of N2O as the TOF-determining transition state (TDTS), with very similar reaction rates for the mechanisms involving either the NHC- or the P-CH2 pincer methylene linkers.

Prophylactic thoracic duct obliteration and resection during esophagectomy: What is the impact on perioperative risks and long-term survival? A systematic review and meta-analysis.

There is no agreement whether prophylactic thoracic duct ligation (TDL), with or without resection, during esophagectomy for patients with cancer is beneficial. The effects of these procedures on postoperative complications and overall survival remain unclear. This systematic review included 16 articles. TDL did not influence short- and long-term outcomes. However, thoracic duct resection increased postoperative chylothorax and overall complications, with no improvement in survival.

Ammonia-Borane Dehydrogenation Catalyzed by Dual-Mode Proton-Responsive Ir-CNNH Complexes.

Metal complexes incorporating proton-responsive ligands have been proved to be superior catalysts in reactions involving the H2 molecule. In this contribution, a series of IrIII complexes based on lutidine-derived CNNH pincers containing N-heterocyclic carbene and secondary amino NHR [R = Ph (4a), tBu (4b), benzyl (4c)] donors as flanking groups have been synthesized and tested in the dehydrogenation of ammonia-borane (NH3BH3, AB) in the presence of substoichiometric amounts (2.5 equiv) of tBuOK. These preactivated derivatives are efficient catalysts in AB dehydrogenation in THF at room temperature, albeit significantly different reaction rates were observed. Thus, by using 0.4 mol % of 4a, 1.0 equiv of H2 per mole of AB was released in 8.5 min (turnover frequency (TOF50%) = 1875 h-1), while complexes 4b and 4c (0.8 mol %) exhibited lower catalytic activities (TOF50% = 55-60 h-1). 4a is currently the best performing IrIII homogeneous catalyst for AB dehydrogenation. Kinetic rate measurements show a zero-order dependence with respect to AB, and first order with the catalyst in the dehydrogenation with 4a (-d[AB]/dt = k[4a]). Conversely, the reaction with 4b is second order in AB and first order in the catalyst (-d[AB]/dt = k[4b][AB]2). Moreover, the reactions of the derivatives 4a and 4b with an excess of tBuOK (2.5 equiv) have been analyzed through NMR spectroscopy. For the former precursor, formation of the iridate 5 was observed as a result of a double deprotonation at the amine and the NHC pincer arm. In marked contrast, in the case of 4b, a monodeprotonated (at the pincer NHC-arm) species 6 is observed upon reaction with tBuOK. Complex 6 is capable of activating H2 reversibly to yield the trihydride derivative 7. Finally, DFT calculations of the first AB dehydrogenation step catalyzed by 5 has been performed at the DFT//MN15 level of theory in order to get information on the predominant metal-ligand cooperation mode.

Hydrogenation/dehydrogenation of N-heterocycles catalyzed by ruthenium complexes based on multimodal proton-responsive CNN(H) pincer ligands.

Ru complexes based on lutidine-derived pincer CNN(H) ligands having secondary amine side donors are efficient precatalysts in the hydrogenation and dehydrogenation of N-heterocycles. Reaction of a Ru-CNN(H) complex with an excess of base produces the formation of a Ru(0) derivative, which is observed under catalytic conditions.

Reaction of [TpRh(C2 H4 )2 ] with Dimethyl Acetylenedicarboxylate: Identification of Intermediates of the [2+2+2] Alkyne and Alkyne-Ethylene Cyclo(co)trimerizations.

The reaction between the bis(ethylene) complex [TpRh(C2 H4 )2 ], 1, (Tp=hydrotris(pyrazolyl)borate), and dimethyl acetylenedicarboxylate (DMAD) has been studied under different experimental conditions. A mixture of products was formed, in which TpRh(I) species were prevalent, whereas the presence of trapping agents, like water or acetonitrile, allowed for the stabilization and isolation of octahedral TpRh(III) compounds. An excess of DMAD gave rise to a small amount of the [2+2+2] cyclotrimerization product hexamethyl mellitate (6). Although no catalytic application of 1 was achieved, mechanistic insights shed light on the formation of stable rhodium species representing the resting state of the catalytic cycle of rhodium-mediated [2+2+2] cyclo(co)trimerization reactions. Metallacyclopentene intermediate species, generated from the activation of one alkyne and one ethylene molecule from 1, and metallacyclopentadiene species, formed by oxidative coupling of two alkynes to the rhodium centre, are crucial steps in the pathways leading to the final organometallic and organic products.

(Butane-1,4-di-yl)(trimethyl-phosphane-κP)[tris-(3,5-dimethyl-pyrazol-1-yl-κN (2))hydro-borato]iridium(III).

In the mononuclear title iridium(III) complex, [Ir(C4H8)(C15H22BN6)(C3H9P)], which is based on the [tris-(3,5-dimethyl-pyrazol-1-yl)hydro-borato]iridium moiety, Ir[Tp(Me2)], the Ir(III) atom is coordinated by a chelating butane-1,4-diyl fragment and a trimethyl-phosphane ligand in a modestly distorted octa-hedral coordination environment formed by three facial N, two C and one P atom. The iridium-butane-1,4-diyl ring has an envelope conformation. This ring is disordered because alternately the second or the third C atom of the butane-1,4-diyl fragment function as an envelope flap atom (the occupancy ratio is 1:1). In the crystal, mol-ecules are organized into densely packed columns extending along [101]. Coherence between the mol-ecules is essentially based on van der Waals inter-actions.

Chlorido[1-(2-oxidophen-yl)ethyl-idene][tris-(3,5-dimethyl-pyrazol-1-yl)hydro-borato]iridium(III) chloro-form monosolvate.

In the title compound, [Ir(C15H22BN6)(C8H7O)Cl]·CHCl3, the Ir atom is formally trivalent and is coordinated in a slightly distorted octa-hedral geometry by three facial N atoms, one C atom, one O atom and one Cl atom. The Ir=Ccarbene bond is strong and short and exerts a notable effect on the trans-Ir-N bond, which is about 0.10 Šlonger than the two other Ir-N bonds. The chloro-form solvent mol-ecule is anchored via a weak C-H⋯Cl hydrogen bond to the Cl atom of the Ir complex mol-ecule. In the crystal, the constituents adopt a layer-like arrangement parallel to (010) and are held together by weak inter-molecular C-H⋯Cl hydrogen bonds, as well as weak Cl⋯Cl [3.498 (2) Å] and Cl⋯π [3.360 (4) Å] inter-actions. A weak intra-molecular C-H⋯O hydrogen bond is also observed.

C-H bond activation reactions of ethers that generate iridium carbenes.

Two important objectives in organometallic chemistry are to understand C-H bond activation reactions mediated by transition metal compounds and then to develop efficient ways of functionalizing the resulting products. A particularly ambitious goal is the generation of metal carbenes from simple organic molecules; the synthetic chemist can then take advantage of the almost unlimited reactivity of this metal-organic functionality. This goal remains very difficult indeed with saturated hydrocarbons, but it is considerably more facile for molecules that possess a heteroatom (such as ethers), because coordination of the heteroatom to the metal renders the ensuing C-H activation an intramolecular reaction. In this Account, we focus on the activation reaction of different types of unstrained ethers, both aliphatic and hemiaromatic, by (mostly) iridium compounds. We emphasize our recent results with the Tp(Me2)Ir(C(6)H(5))(2)(N(2)) (1.N(2)) complex (where Tp(Me2) denotes hydrotris(3,5-dimethylpyrazolyl)borate). Most of the reactivity observed with this system, and with related electronically unsaturated iridium species, starts with a C-H activation reaction, which is then followed by reversible alpha-hydrogen elimination. An alpha-C-H bond is, in every instance, broken first; when there is a choice, cleavage of the stronger terminal C(sp(3))-H bonds is always preferred over the weaker internal C(sp(3))-H (methylene) bonds of the ether. Nevertheless, competitive reactions of the unsaturated [Tp(Me2)Ir(C(6)H(5))(2)] iridium intermediate with ethers that contain C(sp(3))-H and C(sp(2))-H bonds are also discussed. We present theoretical evidence for a sigma-complex-assisted metathesis mechanism (sigma-CAM), although for other systems oxidative addition and reductive elimination events can be effective reaction pathways. We also show that additional unusual chemical transformations may occur, depending on the nature of the ether, and can result in C-O and C-C bond-breaking and bond-forming reactions, leading to the formation of more elaborate molecules. Although the possibility of extending these results to saturated hydrocarbons appears to be limited for this iridium system, the findings described in this Account are of fundamental importance for various facets of C-H bond activation chemistry, and with suitable modifications of the ancillary ligands, they could be even broader in scope. We further discuss experimental and theoretical studies on unusual alkene-to-alkylidene equilibria for some of the products obtained in the reactions of iridium complex 1.N(2) with alkyl aryl ethers. The rearrangement involves reversible alpha- and beta-hydrogen eliminations, with a rate-determining metal inversion step (supported by theoretical calculations); the alkylidene is always favored thermodynamically over the alkene. This startling result contrasts with the energetically unfavorable isomerization of free ethene to ethylidene (by about 80 kcal mol(-1)), showing that the tautomerism equilibrium can be directed toward one product or the other by a judicious choice of the transition metal complex.

Experimental and computational studies on the iridium activation of aliphatic and aromatic C-H bonds of alkyl aryl ethers and related molecules.

Reaction of the Ir(III) complex [(Tp(Me2))Ir(C(6)H(5))(2)(N(2))] (1N(2)) with ortho-cresol (2-methylphenol) occurs with cleavage of the O-H and two C(sp(3))-H bonds of the phenol and formation of the electrophilic hydride alkylidene derivative [(Tp(Me2))Ir(H){=C(H)C(6)H(4)-o-O}] (2). The analogous reaction of 2-ethylphenol gives a related product 3. Both 2 and 3 have been shown to be identical to the minor, unidentified products of the already reported reactions of 1 with anisole and phenetole, respectively. Thus, in addition to the route that leads to the known heteroatom-stabilized hydride carbene [(Tp(Me2))Ir(H){=C(H)OC(6)H(4)-o-}] (B), anisole can react with 1 with cleavage of the O-CH(3) bond and formation of a new carbon-carbon bond. In contrast, only C-H bond-activation products with structures akin to B result from 1N(2) and 3,5-dimethylanisole (complex 8) or 4-fluoroanisole (9). Using anisole as a model, a computational study of the triple C-H bond activation (two aliphatic C-H bonds plus an ortho-metalation reaction) that is responsible for the formation of these heteroatom-stabilized hydride carbenes has been undertaken.

Synthetic, mechanistic, and theoretical studies on the generation of iridium hydride alkylidene and iridium hydride alkene isomers.

Experimental and theoretical studies on equilibria between iridium hydride alkylidene structures, [(Tp(Me2))Ir(H){=C(CH(2)R)ArO}] (Tp(Me2) = hydrotris(3,5-dimethylpyrazolyl)borate; R = H, Me; Ar = substituted C(6)H(4) group), and their corresponding hydride olefin isomers, [(Tp(Me2))Ir(H){R(H)C=C(H)OAr}], have been carried out. Compounds of these types are obtained either by reaction of the unsaturated fragment [(Tp(Me2))Ir(C(6)H(5))(2)] with o-C(6)H(4)(OH)CH(2)R, or with the substituted anisoles 2,6-Me(2)C(6)H(3)OMe, 2,4,6-Me(3)C(6)H(2)OMe, and 4-Br-2,6-Me(2)C(6)H(2)OMe. The reactions with the substituted anisoles require not only multiple C-H bond activation but also cleavage of the Me-OAr bond and the reversible formation of a C-C bond (as revealed by (13)C labeling studies). Equilibria between the two tautomeric structures of these complexes were achieved by prolonged heating at temperatures between 100 and 140 degrees C, with interconversion of isomeric complexes requiring inversion of the metal configuration, as well as the expected migratory insertion and hydrogen-elimination reactions. This proposal is supported by a detailed computational exploration of the mechanism at the quantum mechanics (QM) level in the real system. For all compounds investigated, the equilibria favor the alkylidene structure over the olefinic isomer by a factor of between approximately 1 and 25. Calculations demonstrate that the main reason for this preference is the strong Ir-carbene interactions in the carbene isomers, rather than steric destabilization of the olefinic tautomers.

Multisite solid catalyst for cascade reactions: the direct synthesis of benzodiazepines from nitro compounds.

Substituted 1,5-benzodiazepines are selectively synthesized in one pot from substituted nitroaromatics and ketones. The reaction is performed in the presence of hydrogen and in the absence of solvent by using a bifunctional solid catalyst with a chemoselective hydrogenation functional group capable of reducing the nitro group to a diamino group and an acid functional group, which catalyzes the cyclocondensation of the amino group with the ketone.

Chemoselective synthesis of substituted imines, secondary amines, and beta-amino carbonyl compounds from nitroaromatics through cascade reactions on gold catalysts.

Substituted imines, alpha,beta-unsaturated imines, substituted secondary amines, and beta-amino carbonyl compounds have been synthesized by means of new cascade reactions with mono- or bifunctional gold-based solid catalysts under mild reaction conditions. The related synthetic route involves the hydrogenation of a nitroaromatic compound in the presence of a second reactant such as an aldehyde, alpha,beta-unsaturated carbonyl compound, or alkyne, which circumvents an ex situ reduction process for producing the aromatic amine. The process is shown to be highly selective towards other competing groups, such as double bonds, carbonyls, halogens, nitriles, or cinnamates, and thereby allows the synthesis of different substituted nitrogenated compounds. For the preparation of imines, substituted anilines are formed and condensed in situ with aldehydes to provide the final product through two tandem reactions. High chemoselectivity is observed, for instance, when double bonds or halides are present within the reactants. In addition, we show that the Au/TiO2 system is also able to catalyze the chemoselective hydrogenation of imines, so that secondary amines can be prepared directly through a three-step cascade reaction by starting from nitroaromatic compounds and aldehydes. On the other hand, Au/TiO2 can also be used as a bifunctional catalyst to obtain substituted beta-amino carbonyl compounds from nitroaromatics and alpha,beta-unsaturated carbonyl compounds. Whereas gold sites promote the in situ formation of anilines, the intrinsic acidity of Ti species on the support surface accelerates the subsequent Michael addition. Finally, two gold-catalyzed reactions, that is, the hydrogenation of nitro groups and a hydroamination, have been coupled to synthesize additional substituted imines from nitroaromatic compounds and alkynes.

Formation and cleavage of C-H, C-C, and C-O bonds of ortho-methyl-substituted anisoles by late transition metals.

2,6-Dimethyl-substituted anisoles can be converted into the corresponding 2-ethyl-6-methylphenols in a several-step reaction mediated by a TpMe2Ir(III) complex; use of the 13C-enriched anisoles, ArO13CH3, shows that the 13C label distributes across the two ethyl sites with a preference for the terminal position.

Iridium solutes effect C-H bond activation and C-C bond forming reactions of C6H6-MeOCH2CH2OMe solvent mixtures.

The in situ generated [Tp(Me2)Ir(C(6)H(5))(2)] fragment induces both aromatic and aliphatic C-H bond activation reactions, along with C-C bond formation, when heated with benzene and 1,2-dimethoxyethane.

Coupling of internal alkynes in tp(me2)ir derivatives: selective oxidation of a noncoordinated double bond of the resulting iridacycloheptatrienes.

The reaction of different Tp(Me2)Ir derivatives and dimethylacetylene dicarboxylate (DMAD) allows the preparation of three different metallacycloheptatriene complexes and an unusual allyl-terminated metallacycle. The C atoms of distant C=C bonds in the metallacycles, including aromatic ones, can be converted selectively to the corresponding keto functionality under mild conditions.