Computational studies on carboxylate-assisted C–H activation and functionalization at group 8–10 transition metal centers are reviewed. This Review is organized by metal and will cover work published ...from late 2009 until mid-2016. A brief overview of computational work prior to 2010 is also provided, and this outlines the understanding of carboxylate-assisted C–H activation in terms of the “ambiphilic metal–ligand assistance” (AMLA) and “concerted metalation deprotonation” (CMD) concepts. Computational studies are then surveyed in terms of the nature of the C–H bond being activated (C(sp2)–H or C(sp3)–H), the nature of the process involved (intramolecular with a directing group or intermolecular), and the context (stoichiometric C–H activation or within a variety of catalytic processes). This Review aims to emphasize the connection between computation and experiment and to highlight the contribution of computational chemistry to our understanding of catalytic C–H functionalization based on carboxylate-assisted C–H activation. Some opportunities where the interplay between computation and experiment may contribute further to the areas of catalytic C–H functionalization and applied computational chemistry are identified.
Gene-based tests such as versatile gene-based association study (VEGAS) are commonly used following per-single nucleotide polymorphism (SNP) GWAS (genome-wide association studies) analysis. Two ...limitations of VEGAS were that the HapMap2 reference set was used to model the correlation between SNPs and only autosomal genes were considered. HapMap2 has now been superseded by the 1,000 Genomes reference set, and whereas early GWASs frequently ignored the X chromosome, it is now commonly included. Here we have developed VEGAS2, an extension that uses 1,000 Genomes data to model SNP correlations across the autosomes and chromosome X. VEGAS2 allows greater flexibility when defining gene boundaries. VEGAS2 offers both a user-friendly, web-based front end and a command line Linux version. The online version of VEGAS2 can be accessed through https://vegas2.qimrberghofer.edu.au/. The command line version can be downloaded from https://vegas2.qimrberghofer.edu.au/zVEGAS2offline.tgz. The command line version is developed in Perl, R and shell scripting languages; source code is available for further development.
Cp*‐free cobalt‐catalyzed alkyne annulations by C−H/N−H functionalizations were accomplished with molecular O2 as the sole oxidant. The user‐friendly oxidase strategy proved viable with various ...internal and terminal alkynes through kinetically relevant C−H cobaltation, providing among others step‐economical access to the anticancer topoisomerase‐I inhibitor 21,22‐dimethoxyrosettacin. DFT calculations suggest that electronic effects control the regioselectivity of the alkyne insertion step.
Mit O2: Co(OAc)2 enabled the aerobic C−H/N−H functionalization with O2 as the sole oxidant under Cp*‐free conditions, which enabled step‐economical access to anticancer isoquinolones by highly selective C−H activation (see scheme, Cp*=pentamethylcyclopentadienyl).
The reactions of substituted 1-phenylpyrazoles (phpyz-H) at MCl2Cp*2 dimers (M = Rh, Ir; Cp* = C5Me5) in the presence of NaOAc to form cyclometalated Cp*M(phpyz)Cl were studied experimentally and ...with density functional theory (DFT) calculations. At room temperature, time-course and H/D exchange experiments indicate that product formation can be reversible or irreversible depending on the metal, the substituents, and the reaction conditions. Competition experiments with both para- and meta-substituted ligands show that the kinetic selectivity favors electron-donating substituents and correlates well with the Hammett parameter giving a negative slope consistent with a cationic transition state. However, surprisingly, the thermodynamic selectivity is completely opposite, with substrates with electron-withdrawing groups being favored. These trends are reproduced with DFT calculations that show C–H activation proceeds by an AMLA/CMD mechanism. H/D exchange experiments with the meta-substituted ligands show ortho-C–H activation to be surprising facile, although (with the exception of F substituents) this does not generally lead to ortho-cyclometalated products. Calculations suggest that this can be attributed to the difficulty of HOAc loss after the C–H activation step due to steric effects in the 16e intermediate that would be formed. Our study highlights that the use of substituent effects to assign the mechanism of C–H activation in either stoichiometric or catalytic reactions may be misleading, unless the energetics of the C–H cleavage step and any subsequent reactions are properly taken into account. The broader implications of our study for the assignment of C–H activation mechanisms are discussed.
CF bond borylation: A 16‐electron rhodium(I)–boryl complex was synthesized by borylation of a rhodium(I)–fluorine complex. The former reacts with benzene or 2,3,5,6‐tetrafluoropyridine by CH ...activation. A catalytic CF borylation reaction of pentafluoropyridine was also developed, which uses Rh(Bpin)(PEt3)3 as a catalyst and Me3SiSiMe3 as a solvent. pin=pinacol.
A range of novel heterocyclic cations have been synthesized by the Rh(III)-catalyzed oxidative C–N and C–C coupling of 1-phenylpyrazole, 2-phenylpyridine, and 2-vinylpyridine with alkynes (4-octyne ...and diphenylacetylene). The reactions proceed via initial C–H activation, alkyne insertion, and reductive coupling, and all three of these steps are sensitive to the substrates involved and the reaction conditions. Density functional theory (DFT) calculations show that C–H activation can proceed via a heteroatom-directed process that involves displacement of acetate by the neutral substrate to form charged intermediates. This step (which leads to cationic C–N coupled products) is therefore favored by more polar solvents. An alternative non-directed C–H activation is also possible that does not involve acetate displacement and so becomes favored in low polarity solvents, leading to C–C coupled products. Alkyne insertion is generally more favorable for diphenylacetylene over 4-octyne, but the reverse is true of the reductive coupling step. The diphenylacetylene moiety can also stabilize unsaturated seven-membered rhodacycle intermediates through extra interaction with one of the Ph substituents. With 1-phenylpyrazole this effect is sufficient to suppress the final C–N reductive coupling. A comparison of a series of seven-membered rhodacycles indicates the barrier to coupling is highly sensitive to the two groups involved and follows the trend C–N+ > C–N > C–C (i.e., involving the formation of cationic C–N, neutral C–N, and neutral C–C coupled products, respectively).
In this Account, we describe the transition metal-mediated cleavage of C−F and C−H bonds in fluoroaromatic and fluoroheteroaromatic molecules. The simplest reactions of perfluoroarenes result in C−F ...oxida tive addition, but C−H activation competes with C−F activation for partially fluorinated molecules. We first consider the reactivity of the fluoroaromatics toward nickel and platinum complexes, but extend to rhenium and rhodium where they give special insight. Sections on spectroscopy and molecular structure are followed by discussions of energetics and mechanism that incorporate experimental and computational results. We highlight special characteristics of the metal−fluorine bond and the influence of the fluorine substituents on energetics and mechanism. Fluoroaromatics reacting at an ML2 center initially yield η2-arene complexes, followed usually by oxidative addition to generate MF(ArF)(L)2 or MH(ArF)(L)2 (M is Ni, Pd, or Pt; L is trialkylphosphine). The outcome of competition between C−F and C−H bond activation is strongly metal dependent and regioselective. When C−H bonds of fluoroaromatics are activated, there is a preference for the remaining C−F bonds to lie ortho to the metal. An unusual feature of metal−fluorine bonds is their response to replacement of nickel by platinum. The Pt−F bonds are weaker than their nickel counterparts; the opposite is true for M−H bonds. Metal−fluorine bonds are sufficiently polar to form M−F···H−X hydrogen bonds and M−F···I−C6F5 halogen bonds. In the competition between C−F and C−H activation, the thermodynamic product is always the metal fluoride, but marked differences emerge between metals in the energetics of C−H activation. In metal−fluoroaryl bonds, ortho-fluorine substituents generally control regioselectivity and make C−H activation more energetically favorable. The role of fluorine substituents in directing C−H activation is traced to their effect on bond energies. Correlations between M−C and H−C bond energies demonstrate that M−C bond energies increase far more on ortho-fluorine substitution than do H−C bonds. Conventional oxidative addition reactions involve a three-center triangular transition state between the carbon, metal, and X, where X is hydrogen or fluorine, but M(d)−F(2p) repulsion raises the activation energies when X is fluorine. Platinum complexes exhibit an alternative set of reactions involving rearrangement of the phosphine and the fluoroaromatics to a metal(alkyl)(fluorophosphine), M(R)(ArF)(PR3)(PR2F). In these phosphine-assisted C−F activation reactions, the phosphine is no spectator but rather is intimately involved as a fluorine acceptor. Addition of the C−F bond across the M−PR3 bond leads to a metallophosphorane four-center transition state; subsequent transfer of the R group to the metal generates the fluorophosphine product. We find evidence that a phosphine-assisted pathway may even be significant in some apparently simple oxidative addition reactions. While transition metal catalysis has revolutionized hydrocarbon chemistry, its impact on fluorocarbon chemistry has been more limited. Recent developments have changed the outlook as catalytic reactions involving C−F or C−H bond activation of fluorocarbons have emerged. The principles established here have several implications for catalysis, including the regioselectivity of C−H activation and the unfavorable energetics of C−F reductive elimination. Palladium-catalyzed C−H arylation is analyzed to illustrate how ortho-fluorine substituents influence thermodynamics, kinetics, and regioselectivity.
An iron catalyst has been developed for the transfer hydrogenation of carbon–carbon multiple bonds. Using a well-defined β-diketiminate iron(II) precatalyst, a sacrificial amine and a borane, even ...simple, unactivated alkenes such as 1-hexene undergo hydrogenation within 1 h at room temperature. Tuning the reagent stoichiometry allows for semi- and complete hydrogenation of terminal alkynes. It is also possible to hydrogenate aminoalkenes and aminoalkynes without poisoning the catalyst through competitive amine ligation. Furthermore, by exploiting the separate protic and hydridic nature of the reagents, it is possible to regioselectively prepare monoisotopically labeled products. DFT calculations define a mechanism for the transfer hydrogenation of propene with n BuNH2 and HBpin that involves the initial formation of an iron(II)-hydride active species, 1,2-insertion of propene, and rate-limiting protonolysis of the resultant alkyl by the amine N–H bond. This mechanism is fully consistent with the selective deuteration studies, although the calculations also highlight alkene hydroboration and amine–borane dehydrocoupling as competitive processes. This was resolved by reassessing the nature of the active transfer hydrogenation agent: experimentally, a gel is observed in catalysis, and calculations suggest this can be formulated as an oligomeric species comprising H-bonded amine–borane adducts. Gel formation serves to reduce the effective concentrations of free HBpin and n BuNH2 and so disfavors both hydroboration and dehydrocoupling while allowing alkene migratory insertion (and hence transfer hydrogenation) to dominate.
We report mechanistic studies on the reactivity of different α-substituted C(sp3)–H bonds, −CH n R (R = H, Me, CO2Me, CONMe2, OMe, and Ph, as well as the cyclopropyl and isopropyl derivatives ...−CH(CH2)2 and −CHMe2) in the context of Pd0-catalyzed C(sp3)–H arylation. Primary kinetic isotope effects, k H/k D, were determined experimentally for R = H (3.2) and Me (3.5), and these, along with the determination of reaction orders and computational studies, indicate rate-limiting C–H activation for all substituents except when R = CO2Me. This last result was confirmed experimentally (k H/k D ∼ 1). A reactivity scale for C(sp3)–H activation was then determined: CH 2CO2Me > CH(CH2)2 ≥ CH 2CONMe2 > CH 3 ≫ CH 2Ph > CH 2Me > CH 2OMe ≫ CHMe2. C–H activation involves AMLA/CMD transition states featuring intramolecular O → H–C H-bonding assisted by C–H → Pd agostic bonding. The “AMLA coefficient”, χ, is introduced to quantify the energies associated with these interactions via natural bond orbital 2nd order perturbation theory analysis. Higher barriers correlate with lower χ values, which in turn signal a greater agostic interaction in the transition state. We believe that this reactivity scale and the underlying factors that determine this will be of use for future studies in transition-metal-catalyzed C(sp3)–H activation proceeding via the AMLA/CMD mechanism.
Bridges and Vertices in Heteroboranes Macgregor, Stuart A; Welch, Alan J
Molecules (Basel, Switzerland),
12/2022, Letnik:
28, Številka:
1
Journal Article
Recenzirano
Odprti dostop
A number of (hetero)boranes are known in which a main group atom
'bridges' a B-B connectivity in the open face, and in such species
has previously been described as simply a bridge or, alternatively, ...as a vertex in a larger cluster. In this study we describe an approach to distinguish between these options based on identifying the best fit of the experimental {B
} cluster fragment with alternate exemplar {B
} fragments derived from DFT-optimized B
H
models. In most of the examples studied atom
is found to be better regarded as a vertex, having 'a 'verticity' of ca. 60-65%. Consideration of our results leads to the suggestion that the radial electron contribution from
to the overall skeletal electron count is more significant than the tangential contribution.
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