A DFT Comparison of C-C Reductive Coupling from Terminal Cyanido and Cyaphido Complexes of Nickel.

The density functional theory study of the thermal C-C reductive coupling from terminal cyanido and hypothetical cyaphido complexes of [Ni(dmpe)] (dmpe = 1,2-bis(dimethylphosphino)ethane) revealed the key reaction intermediate in the reductive C-CP coupling being a σ-CC complex unlike an η2-aryl complex in the Ni C-CN system, as already observed in our previous studies. The reaction in THF is endothermic by 4.9 kcal/mol for cyanido with a 32.0 kcal/mol activation barrier and exothermic by 28.5 kcal/mol for cyaphido with an 11.3 kcal/mol activation barrier. To compare our results with the existing experimental data, we chose mesityl as the aryl group and also studied the CP reaction with [Pt(dmpe)] and [Pt(dmpm)] (dmpe = 1,2-bis(dimethylphosphino)methane) fragments. Our findings are consistent with the thermodynamically uphill photolytic C-CP bond activation in phosphaalkynes with Pt and a faster thermal back-reaction with [Pt(dmpe)] compared to that of [Pt(dmpm)]. Based on the natural population analysis, when the polarity of the C-C bond is inverted, the sign of ΔG° is also inverted.

ortho-Fluoro or ortho Effect? Oxidative Addition of Zerovalent Nickel into the C-CN Bond of Substituted Benzonitriles.

A recent study of the oxidative addition of zerovalent Ni to the C-CN bond of F-substituted benzonitriles showed significantly increased stabilization of the C-CN oxidative addition products with o-F groups (-6.6 kcal/mol per o-F) compared to m-F groups (-1.8 kcal/mol per m-F). To answer the question of whether this is an o-F effect or an ortho effect, in this study the effect of CF3 and CH3 groups on the oxidative addition of the [Ni(dmpe)] fragment [dmpe = 1,2-bis(dimethylphosphino)ethane] to the C-CN bond of benzonitriles has been studied. A density functional theory study of the reaction pathway between η2-CN complexes and the C-CN oxidative addition products shows stabilization of the C-CN oxidative addition product with the electron-withdrawing CF3 group and destabilization with the electron-donating CH3 group in both tetrahydrofuran and toluene. There is a slightly larger ortho effect with CF3 (-7.4 kcal/mol) than with F. However, due to steric crowding, two o-CF3 groups did not show considerably more stabilization than one o-CF3 group. There is a linear relationship between ΔG° and the number of meta groups (2.0 kcal/mol stabilization per m-CF3 and 0.8 kcal/mol destabilization per m-CH3). On the basis of natural population analysis, as the C-CN bond becomes more polarized, the stability of the C-CN oxidative addition products with respect to the η2-CN complexes increases.

Photochemical C(sp)-C(sp2) Bond Activation in Phosphaalkynes: A New Route to Reactive Terminal Cyaphido Complexes LnM-C≡P.

The photochemical activation of the C(sp)-C(sp2) bond in Pt(0)-η2-aryl-phosphaalkyne complexes leads selectively to coordination compounds of the type LnPt(aryl)(C≡P). The oxidative addition reaction is a novel, clean, and atom-economic route for the synthesis of reactive terminal Pt(II)-cyaphido complexes, which can undergo [3 + 2] cycloaddition reactions with organic azides, yielding the corresponding Pt(II)-triazaphospholato complexes. The C-C bond cleavage reaction is thermodynamically uphill. Upon heating, the reverse and quantitative reductive elimination toward the Pt(0)-phosphaalkyne-π-complex is observed.

The fate of the left subclavian artery in TEVAR for aortic arch pathology.

BACKGROUND AND AIM OF STUDY: The origin of the vertebral artery (VA) from the left subclavian (LSA) is variable and must be considered when proximal ligation or embolization is performed post thoracic endovascular aortic repair (TEVAR) and extra-anatomical bypass (EAB). A retrospective study was conducted to understand the patency of the LSA and VAs after TEVAR and the relationship of the EAB to the LSA. METHODS: Fifty-six patients underwent TEVAR where the LSA origin was occluded. A comparison was performed between the length of the proximal LSA from the arch of the aorta to the origin of the VA. Patient outcomes included posterior or anterior circulation cerebrovascular accident, spinal cord ischemia (SCI), and symptoms and signs of left arm ischemia (LAI). Thirty one underwent EAB with 8 undergoing occlusion of the LSA proximal to the origin of the left VA. A further 25 underwent TEVAR with no EAB performed. The mean (standard deviation) of origin of the VA from the origin at the arch was 37.0 (12.9) mm compared to 34.0 (13.7) mm in those where no bypass was performed (p 0.45). Four patients underwent intraluminal plug occlusion and four had external ligation of the proximal LSA in those undergoing EAB. CONCLUSIONS: Careful evaluation of the LSA is needed when planning TEVAR as occlusion techniques may be dependent on a minimum length of the VA from the aortic arch. The mean length of the VA from the aorta has high heterogeneity which may dictate the optimum occlusion method for LSA.

Reversible Concerted Metalation-Deprotonation C-H Bond Activation by [Cp*RhCl2]2.

The reversibility of the concerted metalation-deprotonation exchange of eight para-substituted phenylpyridines is examined with the parent Cp*RhCl(κ-C,N-NC5H4-C6H4). Equilibrium constants are determined, and the free energies are used to extract the most important parameters that control the thermodynamics. Keq values are found to correlate best with heterolytic C-H bond strengths but in a way that is not obvious considering the electrophilic nature of these activations.

Coordination or Oxidative Addition? Activation of N-H with [Tp'Rh(PMe3)].

A thermal reaction of amines, anilines, and amides with Tp'Rh(PMe3)(CH3)H (1, Tp' = tris(3,5-dimethyl-pyrazolyl)borate) is described in this report. No N-H bond cleavage was observed for reactions between ammonia or unsubstituted aliphatic amines with the reactive fragment [Tp'Rh(PMe3)]. Instead, amine coordination products (κ2-Tp')Rh(PMe3)(NHR1R2) (R1 = H, R2 = H, nPr, iPr, octyl; R1 = R2 = Et; R1, R2: pyrrolidine) were observed, and the crystal structure of (κ2-Tp')Rh(PMe3)(NH2 iPr) is reported. No coordination products were observed when 1 was reacted with 1,1,1,3,3,3-hexafluoropropan-2-amine, anilines, and amides. Instead, the oxidative addition products (κ3-Tp')Rh(PMe3)(NHR)H (R = CH(CF3)2, C6H5, 3,5-dimethylbenzyl, C6F5, C(O)CH3, C(O)CF3) were observed. Both RhI-N coordination products (κ2-Tp')Rh(PMe3)(NH2CH2CF3) and RhIII N-H addition products (κ3-Tp')Rh(PMe3)(NHCH2CF3)H were generated when 1 was reacted with 2,2,2-trifluoroethylamine. Coordination products dissociate ammonia and amines in benzene much faster than oxidative addition products eliminate anilines and amides. The relative metal-nitrogen bond energies were studied using established kinetic techniques. Analysis of the relationship between the relative M-N bond strengths and N-H bond strengths showed a linear correlation with a slope = RM-N/N-H of 0.91 (10), indicating that the Rh-N bond strength varies in direct proportion to the N-H bond strength.

Probing the Carbon-Hydrogen Activation of Alkanes Following Photolysis of Tp'Rh(CNR)(carbodiimide): A Computational and Time-Resolved Infrared Spectroscopic Study.

Carbon-hydrogen bond activation of alkanes by Tp'Rh(CNR) (Tp' = Tp = trispyrazolylborate or Tp* = tris(3,5-dimethylpyrazolyl)borate) were followed by time-resolved infrared spectroscopy (TRIR) in the υ(CNR) and υ(B-H) spectral regions on Tp*Rh(CNCH2CMe3), and their reaction mechanisms were modeled by density functional theory (DFT) on TpRh(CNMe). The major intermediate species were: κ3-η1-alkane complex (1); κ2-η2-alkane complex (2); and κ3-alkyl hydride (3). Calculations predict that the barrier between 1 and 2 arises from a triplet-singlet crossing and intermediate 2 proceeds over the rate-determining C-H activation barrier to give the final product 3. The activation lifetimes measured for the Tp*Rh(CNR) and Tp*Rh(CO) fragments with n-heptane and four cycloalkanes (C5H10, C6H12, C7H14, and C8H16) increase with alkanes size and show a dramatic increase between C6H12 and C7H14. A similar step-like behavior was observed previously with CpRh(CO) and Cp*Rh(CO) fragments and is attributed to the wider difference in C-H bonds that appear at C7H14. However, Tp'Rh(CNR) and Tp'Rh(CO) fragments have much longer absolute lifetimes compared to those of CpRh(CO) and Cp*Rh(CO) fragments, because the reduced electron density in dechelated κ2-η2-alkane Tp' complexes stabilizes the d8 Rh(I) in a square-planar geometry and weakens the metal's ability for oxidative addition of the C-H bond. Further, the Tp'Rh(CNR) fragment has significantly slower rates of C-H activation in comparison to the Tp'Rh(CO) fragment for the larger cycloalkanes, because the steric bulk of the neopentyl isocyanide ligand hinders the rechelation in κ2-Tp'Rh(CNR)(cycloalkane) species and results in the C-H activation without the assistance of the rechelation.

Reversible catalytic dehydrogenation of alcohols for energy storage.

Reversibility of a dehydrogenation/hydrogenation catalytic reaction has been an elusive target for homogeneous catalysis. In this report, reversible acceptorless dehydrogenation of secondary alcohols and diols on iron pincer complexes and reversible oxidative dehydrogenation of primary alcohols/reduction of aldehydes with separate transfer of protons and electrons on iridium complexes are shown. This reactivity suggests a strategy for the development of reversible fuel cell electrocatalysts for partial oxidation (dehydrogenation) of hydroxyl-containing fuels.

Catalytic Dehydrogenative C-C Coupling by a Pincer-Ligated Iridium Complex.

The pincer-iridium fragment (iPrPCP)Ir (RPCP = κ3-2,6-C6H3(CH2PR2)2) has been found to catalyze the dehydrogenative coupling of vinyl arenes to afford predominantly (E,E)-1,4-diaryl-1,3-butadienes. The eliminated hydrogen can undergo addition to another molecule of vinyl arene, resulting in an overall disproportionation reaction with 1 equiv of ethyl arene formed for each equivalent of diarylbutadiene produced. Alternatively, sacrificial hydrogen acceptors (e.g., tert-butylethylene) can be added to the solution for this purpose. Diarylbutadienes are isolated in moderate to good yields, up to ca. 90% based on the disproportionation reaction. The results of DFT calculations and experiments with substituted styrenes indicate that the coupling proceeds via double C-H addition of a styrene molecule, at ß-vinyl and ortho-aryl positions, to give an iridium(III) metalloindene intermediate; this intermediate then adds a ß-vinyl C-H bond of a second styrene molecule before reductively eliminating product. Several metalloindene complexes have been isolated and crystallographically characterized. In accord with the proposed mechanism, substitution at the ortho-aryl positions of the styrene precludes dehydrogenative homocoupling. In the case of 2,4,6-trimethylstyrene, dehydrogenative coupling of ß-vinyl and ortho-methyl C-H bonds affords dimethylindene, demonstrating that the dehydrogenative coupling is not limited to C(sp2)-H bonds.

An Uncanny Dehydrogenation Mechanism: Polar Bond Control over Stepwise or Concerted Transition States.

The mechanism of the dehydrogenation of N-heterocycles with the recently established bifunctional catalyst (iPrPNP)Fe(CO)(H) was investigated through experiments and density functional theory calculations (iPrPNP = iPr2PCH2CH2NCH2CH2PiPr2). In this system, the saturated N-heterocyclic substrates are completely dehydrogenated to the aromatic products. Calculations indicate that dehydrogenation barriers of the C-C bonds are very high in energy (ΔG‡ = 37.4-42.2 kcal/mol), and thus dehydrogenation only occurs at the C-N bond (ΔG‡ = 9.6-22.2 kcal/mol). Interestingly, substrates like piperidine with relatively unpolarized C-N bonds are dehydrogenated through a concerted proton/hydride transfer bifunctional transition state involving the nitrogen on the PNP ligand. However, substrates with polarized C-N bonds entail stepwise (proton then hydride) bifunctional dehydrogenation.

Determination of Rhodium-Alkoxide Bond Strengths in Tp'Rh(PMe3)(OR)H.

The active fragment [Tp'Rh(PMe3)], generated from a thermal precursor Tp'Rh(PMe3)(CH3)H, underwent oxidative addition of water and alcohols to give O-H adducts of the type Tp'Rh(PMe3)(OR)H (R = H, Me, Et, (n)Pr, (n)Bu, CH2Ph, (i)Pr, c-pentyl, CH2CF3, CH2CH2OH) at ambient temperature. These activation products eliminate water or alcohols in benzene, which allows determination of the relative metal-oxygen bond energies by using previously established kinetics techniques. Analysis of the relationship between the relative M-O bond strengths and O-H bond strengths showed a linear correlation with RM-O/O-H of 0.97 (3) for aliphatic alcohols. The two extraordinary substrates (R = CH2CF3, CH2CH2OH) both have stronger M-O bonds than would be predicted from this trend, suggesting the stabilization of the M-O bond when an electron-withdrawing substituent is present as previously seen in M-C bond strengths. In addition, the O-H activation products of aliphatic alcohols are thermally unstable at 80 °C, as rearrangement to form Tp'Rh(PMe3)H2 from ß-elimination is observed after 1 or 2 d. Benzyl alcohol and 2,2,2-trifluoroethanol activation products were stable. For benzyl alcohol, although the O-H activation product was kinetically favored, the C-H activation products of the benzene ring were thermodynamically preferred.

Highly Selective Formation of n-Butanol from Ethanol through the Guerbet Process: A Tandem Catalytic Approach.

A highly selective (>99%) tandem catalytic system for the conversion of ethanol (up to 37%) to n-butanol, through the Guerbet process, has been developed using a bifunctional iridium catalyst coupled with bulky nickel or copper hydroxides. These sterically crowded nickel and copper hydroxides catalyze the key aldol coupling reaction of acetaldehyde to exclusively yield the C4 coupling product, crotonaldehyde. Iridium-mediated dehydrogenation of ethanol to acetaldehyde has led to the development of an ethanol-to-butanol process operated at a lower temperature.

Activation of B-H, Si-H, and C-F bonds with Tp'Rh(PMe3) complexes: kinetics, mechanism, and selectivity.

The photochemical reactions of Tp'Rh(PMe3)H2 (1) and thermal reactions of Tp'Rh(PMe3)(CH3)H (1a, Tp' = tris(3,5-dimethylpyrazolyl)borate) with substrates containing B-H, Si-H, C-F, and C-H bonds are reported. Complexes 1 and 1a are known activators of C-H bonds, including those of alkanes. Kinetic studies of reactions with HBpin and PhSiH3 show that photodissociation of H2 from 1 occurs prior to substrate attack, whereas thermal reaction of 1a proceeds by bimolecular reaction with the substrate. Complete intramolecular selectivity for B-H over C-H activation of HBpin (pin = pinacolate) leading to Tp'Rh(PMe3)(Bpin)H is observed. Similarly, the reaction with Et2SiH2 shows a strong preference for Si-H over C-H activation, generating Tp'Rh(PMe3)(SiEt2H)H. The Rh(Bpin)H and Rh(SiEt2H)H products were stable to heating in benzene in accord with DFT calculations that showed that reaction with benzene is endoergic. The intramolecular competition with PhSiH3 yields a ∼1:4 mixture of Tp'Rh(PMe3)(C6H4SiH3)H and Tp'Rh(PMe3)(SiPhH2)H, respectively. Reaction with pentafluoropyridine generates Tp'Rh(PMe3)(C5NF4)F, while reaction with 2,3,5,6-tetrafluoropyridine yields a mixture of C-H and C-F activated products. Hexafluorobenzene proves unreactive. Crystal structures are reported for B-H, Si-H, and C-F activated products, but in the latter case a bifluoride complex Tp'Rh(PMe3)(C5NF4)(FHF) was crystallized. Intermolecular competition reactions were studied by photoreaction of 1 in C6F6 with benzene and another substrate (HBpin, PhSiH3, or pentafluoropyridine) employing in situ laser photolysis in the NMR probe, resulting in a wide-ranging map of kinetic selectivities. The mechanisms of intramolecular and intermolecular selection are analyzed.

A molecular iron catalyst for the acceptorless dehydrogenation and hydrogenation of N-heterocycles.

A well-defined iron complex (3) supported by a bis(phosphino)amine pincer ligand efficiently catalyzes both acceptorless dehydrogenation and hydrogenation of N-heterocycles. The products from these reactions are isolated in good yields. Complex 3, the active catalytic species in the dehydrogenation reaction, is independently synthesized and characterized, and its structure is confirmed by X-ray crystallography. A trans-dihydride intermediate (4) is proposed to be involved in the hydrogenation reaction, and its existence is verified by NMR and trapping experiments.

Mechanistic studies of transition metal-mediated C-C bond activation.

Organometallic compounds have been found to be of use in cleaving C-C bonds, as strong metal-carbon bonds can be formed to replace the bond that is broken. Studies of the mechanism of C-C cleavage can provide insight into how these bonds can be cleaved, and can give valuable information that can be used to develop new strategies for breaking C-C bonds and using the products in catalysis. In this chapter, we will examine a number of systems where mechanistic information has been obtained in C-C cleavage.

Kinetic and thermodynamic selectivity of intermolecular C-H activation at [Tp'Rh(PMe3)]. How does the ancillary ligand affect the metal-carbon bond strength?

Tp'Rh(PMe3)(CH3)H was synthesized as a precursor to produce the coordinatively unsaturated fragment [Tp'Rh(PMe3)], which reacts with benzene, mesitylene, 3,3-dimethyl-1-butene, 2-methoxy-2-methylpropane, 2-butyne, acetone, pentane, cyclopentane, trifluoroethane, fluoromethane, dimethyl ether, and difluoromethane at ambient temperature to give only one product in almost quantitative yield in each case. All of the complexes Tp'Rh(PMe3)(R)H were characterized by NMR spectroscopy, and their halogenated derivatives were fully characterized by NMR spectroscopy, elemental analysis, and X-ray crystallography. The active species [Tp'Rh(PMe3)] was also able to activate the alkynyl C-H bond of terminal alkynes to give activation products of the type Tp'Rh(PMe3)(C≡CR)H (R = t-Bu, SiMe3, hexyl, CF3, Ph, p-MeOC6H4, and p-CF3C6H4). The measured relative rhodium-carbon bond strengths display two linear correlations with the corresponding carbon-hydrogen bond strengths, giving a slope of 1.54 for α-unsubstituted hydrocarbons and a slope of 1.71 for substrates with α-substitution. Similar trends of energy correlations were established by DFT calculated metal-carbon bond strengths for the same groups of substrates.

Rhodium-carbon bond energies in Tp'Rh(CNneopentyl)(CH2X)H: quantifying stabilization effects in M-C bonds.

A series of substituted methyl derivatives of the type Tp'Rh(CNneopentyl)(CH2X)H (CH2X = CH2C(═O)CH3, CH2C≡CCH3, CH2O-t-Bu, CH2CF3, CH2F, CHF2) was synthesized either by photolysis of Tp'Rh(CNneopentyl)(PhNCNneopentyl) in neat CH3X or by exchange with the labile hydrocarbon in Tp'Rh(CNneopentyl)(n-pentyl)H or Tp'Rh(CNneopentyl)(CH3)H. Only a single product was observed in each case. Clean reductive elimination was observed for all compounds in C6D6. Structures of these complexes and their corresponding chlorinated derivatives have been characterized by NMR spectroscopy, elemental analysis, and X-ray crystallography. Relative Rh-C bond energies are calculated using previously established kinetic techniques, and two separate linear correlations are observed versus known C-H bond strengths, one for the parent hydrocarbons, and one for the substituted hydrocarbons. Both correlations have slopes of 1.4, and are separated vertically by 7.5 kcal mol(-1) (-CH2X above -CxHy). In addition, it is now clear that preferences for linear vs branched olefin insertion products in substituted derivatives can be predicted on the basis of the strengths of the ß-C-H bonds. The DFT calculations of the metal-carbon bond strengths in these Rh-CH2X derivatives with α-substitution show a trend that is in good agreement with the experimental results.

A tris(pyrazolyl)borate rhodium phosphite complex that undergoes an Arbusov-like rearrangement.

Tp'Rh[P(OMe)3](Me)H, loses methane in pentane solution containing CH2F2 to give the scorpionate complex bis(µ-dimethyl phosphito)-κ(2)P:O;κ(2)O:P-bis{methyl[tris(3,5-dimethyl-1H-pyrazol-1-yl-κN(2))borato]rhodium(III)}, [Rh2(CH3)2(C2H6O3P)2(C15H22BN6)2], in which the phosphine O-Me bond is cleaved. The product is dimeric and resembles the Arbusov-type rearrangement product known to form from trimethyl phosphite.

Reduced GS Domain Serine/Threonine Requirements of Fibrodysplasia Ossificans Progressiva Mutant Type I BMP Receptor ACVR1 in the Zebrafish.

Fibrodysplasia ossificans progressiva (FOP) is a rare human genetic condition characterized by altered skeletal development and extraskeletal bone formation. All cases of FOP are caused by mutations in the type I bone morphogenetic protein (BMP) receptor gene ACVR1 that result in overactivation of the BMP signaling pathway. Activation of the wild-type ACVR1 kinase requires assembly of a tetrameric type I and II BMP receptor complex followed by phosphorylation of the ACVR1 GS domain by type II BMP receptors. Previous studies showed that the FOP-mutant ACVR1-R206H required type II BMP receptors and presumptive glycine/serine-rich (GS) domain phosphorylation for overactive signaling. Structural modeling of the ACVR1-R206H mutant kinase domain supports the idea that FOP mutations alter the conformation of the GS domain, but it is unclear how this leads to overactive signaling. Here we show, using a developing zebrafish embryo BMP signaling assay, that the FOP-mutant receptors ACVR1-R206H and -G328R have reduced requirements for GS domain phosphorylatable sites to signal compared to wild-type ACVR1. Further, ligand-independent and ligand-dependent signaling through the FOP-mutant ACVR1 receptors have distinct GS domain phosphorylatable site requirements. ACVR1-G328R showed increased GS domain serine/threonine requirements for ligand-independent signaling compared to ACVR1-R206H, whereas it exhibited reduced serine/threonine requirements for ligand-dependent signaling. Remarkably, while ACVR1-R206H does not require the type I BMP receptor partner, Bmpr1, to signal, a ligand-dependent GS domain mutant of ACVR1-R206H could signal independently of Bmpr1 only when Bmp7 ligand was overexpressed. Of note, unlike human ACVR1-R206H, the zebrafish paralog Acvr1l-R203H does not show increased signaling activity. However, in domain-swapping studies, the human kinase domain, but not the human GS domain, was sufficient to confer overactive signaling to the Acvr1l-R203H receptor. Together these results reflect the importance of GS domain activation and kinase domain functions in regulating ACVR1 signaling and identify mechanisms of reduced regulatory constraints conferred by FOP mutations. © 2023 American Society for Bone and Mineral Research (ASBMR).