C–H bond activation in the total syntheses of natural products

The transition metal-mediated C–H bond activation has emerged as a powerful and ideal method for the total syntheses of natural products and pharmaceuticals, and has had a significant impact on synthetic planning and strategy in complex natural products.In this review, we describe selected recent examples of the transition metal-mediated C–H bond activation strategies for the rapid syntheses of natural products.     

Do amines react with protonated peptides in the gas phase via transacylation reactions to induce peptide bond cleavage?

The proposal that protonated peptides react with NH(3) in the gas phase via transacylation reactions (Tabet et al., Spectros. Int. J. 5: 253 1987) has been investigated by studying the reactions of the fixed charge derivatives [RC(O)NMe(2)CH(2)CO(2)H](+) (R=Me and Ph) with pyridine and triethylamine and the reactions of protonated glycine oligomers and leucine enkenphalin with butylamine. Under the near thermal conditions of the quadrupole ion trap, both the fixed charge derivatives as well as the protonated peptides react with the amines via either proton transfer or proton bound dimer formation. Collision induced dissociation of protonated peptides in the presence of butylamine yields b(n) and y(n) sequence ions as well as [b(n) + BuNH(2)](+) and [y(n) + BuNH(2)](+) ions. MS(3) experiments reveal that a major route to these [b(n) + BuNH(2)](+) and [y(n) + BuNH(2)](+) ions involves ion-molecule reactions between the b(n) and y(n) sequence ions and butylamine. MS(4) experiments, carried out to determine the nature of the [b(n) + BuNH(2)](+) ions, reveal that they correspond to a mixture of hydrogen bonded (i.e. proton bound dimer) and covalent amide bond structures.     

Recent advances in radical-mediated fluorination through C–H and C–C bond cleavage

The C–H and C–C bonds are abundant in organic compounds, yet generally inert in chemical transformations. Therefore, direct functionalization of inert chemical bonds remains challenging. The fluorine-containing compounds are of special interest for their uses in medicinal chemistry. Direct fluorination of C–H and C–C bonds undoubtedly represents one of the most ideal and attractive approaches to incorporate fluorine atom into complex molecules. Herein, we summarize the recent advances in radical-mediated C–H and C–C bond fluorination. Three types of transformations are discussed: (1) direct C–H abstraction/fluorination of alkanes; (2) decarboxylative fluorination of alkyl carboxylic acids; (3) ring-opening fluorination.     

Vinylation of trialkylamines with acyl- and cyanoacetylenes via C–N bond cleavage in the presence of water

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Termolecular ion-molecule reactions in Titan’s atmosphere. II: The structure of the association adducts of HCNH+ with C2H2 and C2H4

The ion-molecule reactivity of the products formed in the association reactions of HCNH+ with C2H2 (C3H4N+) and C2H4 (C3H6N+) has been investigated to provide information on the structures of the adducts thus formed. The C3H4N+ and C3H6N+ adducts were formed in the reaction flow tube of a flowing afterglow sourced-selected ion flow tube (FA-SIFT) and their reactivity with a neutral molecular "probe" examined. The reactivity of possible known structural isomers for the C3H4N+ and C3H6N+ ions was investigated in both the FA-SIFT and an ion cyclotron resonance spectrometer (ICR). Ab initio investigations of the potential energy surfaces for both structures at the G2(MP2) level have also been performed and structures corresponding to local minima on both surfaces have been identified and evaluated. The results of these experimental and theoretical studies show that at room temperature, the C3H4N+ adduct ion contains two isomers; a less reactive one that is likely to be a four-membered cyclic covalent isomer (approximately 70%) and a faster reacting component that is probably an electrostatic complex (approximately 30%). The C3H6N+ adduct ion formed from HCNH+ + C2H4 at room temperature is a single isomer that is likely to be the four-membered covalently bound cyclic CH2CH2CHNH+ species.     

Disruptive influence of the host cage C60 on the guest He–H+ bond and bonding in H3+

Although a helium atom prefers to stay at the centre of a fullerene (C₆₀) cage and a proton binds with one of the carbon atoms from inside, DFT(MN15)/cc-pVTZ and DLPNO-MP2/def2-TZVP calculations show that the helium atom and the proton in HeH⁺ prefer to stay away from the centre of the cage, weakening the He–H⁺ covalent bond considerably. Both the helium atom and the proton exhibit noncovalent interactions with the carbon atoms of two pentagons at the opposite ends of the fullerene cage. Our calculations also show that a linear arrangement of H₃⁺ (inside C₆₀), pointing towards the centres of two pentagons opposite to each other, with the proton breaking away from H_2, is energetically more favored over the equilateral triangle geometry of free H₃⁺.     

Sequential methyl-fluorine exchange reactions of siloxide ions in the gas phase

Exchange Me for a fluorine: Trimethylsiloxide ions in the presence of NF(3) in the gas?phase undergo an unusual and sequential metathesis-type reaction wherein methyl groups are exchanged for fluorine. Theoretical calculations suggest that the reaction proceeds by a three-step internal-nucleophilic-displacement mechanism which features a pentacoordinated siliconate species as a transition state rather than as an intermediate.     

Recent advance in transition-metal-catalyzed oxidant-free 4+1 annulation through C–H bond activation

4+1 annulation based reaction offers a versatile tool for the synthesis of 5-membered carbo/heterocycles. Recent advances of 4+1 annulation through transition-metal-catalyzed C–H bond activation have provided straightforward and widely applicable alternatives to the traditional methods. In particular, the redox-neutral strategies emerged in the past 5?years overcome the inherent disadvantages caused by the external oxidant which are generally required in the early protocols to regenerate the active catalyst, such as limited substrate scope, harsh reaction conditions and generation of stoichiometric by-products. Progress in oxidant-free 4+1 annulations through transition-metal-catalyzed C–H bond activation are discussed in this review until September 2017.     

Cation-π effects in the complexation of Na+ and K+ with Phe, Tyr, and Trp in the gas phase

Na⁺ and K⁺ gas-phase affinities of the three aromatic amino acids Phe, Tyr, and Trp were measured by the kinetic method. Na⁺ binds these amino acids much more strongly than K⁺, and for both metal ions the binding strength was found to follow the order Phe ≤ Tyr < Trp. Quantum chemical calculations by density functional theory (DFT) gave the same qualitative ordering, but suggested a somewhat larger Phe/Trp increment. These results are in acceptable agreement with predictions based on the binding of Na⁺ and K⁺ to the side chain model molecules benzene, phenol, and indole, and are also in reasonable agreement with the predictions from purely electrostatic calculations of the side-chain binding effects. The binding energies were compared with those to the aliphatic amino acids glycine and alanine. Binding to the aromatic amino acids was found to be stronger both experimentally and computationally, but the DFT calculations indicate substantially larger increments relative to alanine than shown by the experiments. Possible reasons for this difference are discussed. The metal ion binding energies show the same trends as the proton affinities.     

C–H bond addition and copolymerization reactions of N-arylmaleimides: Fundamentals of coagent-assisted polymer cross-linking

Solid-state rheometry and model compound reactions are used to investigate free radical reactions of N-arylmaleimide coagents with saturated and unsaturated polymers. N,N′-m-phenylene dimaleimide (BMI) is shown to provide superior cross-link densities over diacrylate and diallyl coagents for all of the polymers studied, including linear low density polyethylene (LLDPE), poly(ethylene oxide) (PEO), cis-poly(butadiene) (PBD) and cis-poly(isoprene) (PIP). Studies of the N-phenylmaleimide (NPM) + cis-cyclooctane system show that C–H bond addition to yield N-aryl-2-alkylsuccimide grafts is the predominant reaction pathway, as opposed to maleimide homopolymerization. In contrast, peroxide-initiated reactions of cis-cyclooctene with small NPM concentrations generate highly alternating poly(cycloctene-alt-N-phenylmaleimide) in high yield, indicating that unsaturated mers in materials such as PBD engage maleimides in an efficient alternating copolymerization between electron-rich and electron-deficient monomer pairs. Factors that affect the reactivity of different polymers in these C–H bond additions and alternating copolymerizations are discussed.     

Can transacylation reactions occur via S(N)2 pathways in the gas phase? Insights via ion-molecule reactions of N-acylpyridinium ions and ab initio calculations

[reaction: see text]The gas-phase identity exchange reactions of N-acylpyridinium ions with pyridine have been examined experimentally in an ion trap mass spectrometer through the use of isotope labeling experiments. The nature of the acyl group plays a crucial role, with the bimolecular rates following the order acetyl > benzoyl > N,N-dimethylaminocarbamyl. The experimental results correlate with ab initio calculations on the simple model system RC(O)NH3+ + NH3, which also demonstrates that these are "SN2 like" processes.     

Homolytic dissociation in hydrogen-bonding liquids: energetics of the phenol O–H bond in methanol and the water O–H bond in water

The energetics of the phenol O–H bond in methanol and the water O–H bond in liquid water were investigated by microsolvation modelling and statistical mechanics Monte Carlo simulations. The microsolvation approach was based on density functional theory calculations. Optimised structures for clusters of phenol and the phenoxy radical with one and two methanol molecules are reported. By analysing the differential solvation of phenol and the phenoxy radical in methanol, we predict that the phenol O–H homolytic bond dissociation enthalpy in solution is 24.3±11 kJ/mol above the gas-phase value. The analysis of the water O–H bond dissociation by microsolvation was based on optimised structures of OH–(H₂O)_1–6 and –(H₂O)_1–7 clusters. Microsolvation modelling and statistical mechanics simulations predict that the HO–H bond dissociation enthalpies in the gas phase and in liquid water are very similar. Our results stress the importance of estimating the differences between the solvation enthalpies of the radical species and the parent molecule and the limitations of local models based on microsolvation.Proceedings of the 11th International Congress of Quantum Chemistry satellite meeting in honor of Jean-Louis Rivail     

Recent advances in Palladium(II)-catalyzed activation of aromatic ring C–H bonds

Palladium is a precious metal, which has been widely used for various organic transformations in the past decades. Currently, the palladium-catalyzed direct activation of the aromatic ring C–H bonds is one of the frontier areas in organic chemistry, and the progress of research in this field is very rapid. Compared with other transition metals, palladium has the advantages of high catalytic activity and strong selectivity. Combining the domestic and foreign scholars' research on this aspect, this paper summarizes the research progress of the palladium-catalyzed activation of aromatic ring C–H bonds in the past ten years.     

Reduction-induced o-C–H bond activation of pyridine with decamethylzirconocene dichloride

Treatment of decamethylzirconocene dichloride (η⁵-Cp^∗)₂ZrCl₂ with amalgamated magnesium in pyridine results in formation of the o-C–H bond activation product [η⁵-C₅Me₅]₂ZrH[η²-κC,N-C₅H₄N] (1). X-ray diffraction analysis (solid state) and NMR spectroscopy data (solutions) reveal the lateral positioning of the nitrogen atom in 1. At elevated temperatures, complex 1 smoothly rearranges into its isomer 2 with medial positioning of the N-atom. The parameters of equilibrium between 1 and 2 were measured at different temperatures. A reaction of 1 or a mixture of 1 and 2 (ca. 1:10) with CDCl₃ smoothly and under mild conditions leads to one and the same η²-pyridyl chloride complex [η⁵-C₅Me₅]₂ZrCl[η²-κC,N-C₅H₄N] (3) with medial positioning of the N-atom. The thermodynamic and mechanistic concepts of the paper are discussed with application of the DFT computational data.     

Iodine and Brønsted acid catalyzed C–C bond cleavage of 1,3-diketones for the acylation of amines

Abstract

A metal-free N-acylation method of anilines with 1,3-diketones has been developed, by using iodine and p-toluene sulfonic acid as the co-catalysts. The reaction can proceed in 1,4-dioxane at elevated temperature to produce the corresponding amides with 48–89% yields. Further, the gram-scale experiment was carried out under the standard conditions and the possible mechanism was proposed.     

Copper and zinc co-catalyzed synthesis of imidazoles via the activation of sp C–H and N–H bonds

An efficient and facile approach to synthesize imidazoles from amidines and arylketone via oxidative coupling of sp³ C–H bond and N–H bond is reported. This strategy exhibits high performance in terms of regioselectivity with moderate to high yields by using easily available materials, and provides an alternative method to synthesize multi-substituted imidazole skeletons.     

Carbon–hydrogen (C–H) bond activation at PdIV: a Frontier in C–H functionalization catalysis

The direct functionalization of carbon–hydrogen (C–H) bonds has emerged as a versatile strategy for the synthesis and derivatization of organic molecules. Among the methods for C–H bond activation, catalytic processes that utilize a Pd^II/Pd^IV redox cycle are increasingly common. The C–H activation step in most of these catalytic cycles is thought to occur at a Pd^II centre. However, a number of recent reports have suggested the feasibility of C–H cleavage occurring at Pd^IV complexes. Importantly, these latter processes often result in complementary reactivity and selectivity relative to analogous transformations at Pd^II. This mini review highlights proposed examples of C–H activation at Pd^IV centres. Applications of this transformation in catalysis as well as mechanistic details obtained from stoichiometric model studies are discussed. Furthermore, challenges and future perspectives for the field are reviewed.     

A theoretical study of H?H σ bond activation catalyzed by VO2+ in gas phase

The mechanism of H? H σ bond activation catalyzed by VO(¹A₁/³A′) has been investigated by using density functional theory at the B3LYP/6‐311G(2d, p) level and the single‐point energy calculations were done at the CCSD/6‐311G (2d, p)//B3LYP/6‐311G(2d, p) level of theory using the geometries along the minimum energy pathway. According to our calculation results, the different reaction mechanisms were found for the singlet and triplet potential energy surfaces (PESs). Specially, the crossing points (CPs) between the different PESs have been located by means of the intrinsic reaction coordinate approach used by Yoshizawa et al, and corresponding minimum energy CPs that we obtained by the mathematical algorithm proposed by Harvey et al. has also been employed. In addition, the orbital interaction for ion‐molecule complexes ¹IM1 and ³IM1 have been examined by fragment molecular orbital analysis. Finally, the frontier molecular orbital interaction analysis about ³TS1 and ³TS2 were used to gain useful information about the H? H σ bond activation by VO. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012     

Catalytic transformation of cellulose and its derived carbohydrates into chemicals involving C–C bond cleavage

The catalytic transformation of cellulose, the major component of abundant and renewable lignocellulosic biomass, into building-block chemicals is a key to establishing sustainable chemical processes. Cellulose is a polymer of glucose and a lot research effort has been devoted to the conversion of cellulose to six-carbon platform compounds such as glucose and glucose derivatives through C–O bond activation. There also exist considerable studies on the catalytic cleavage of C–C bonds in biomass for the production of high-value chemicals, in particular polyols and organic acids such as ethylene glycol and lactic acid. This review article highlights recent advances in the development of new catalytic systems and new strategies for the selective cleavage of C–C bonds in cellulose and its derived carbohydrates under inert, reductive and oxidative atmospheres to produce C1–C5polyols and organic acids. The key factors that influence the catalytic performance will be clarified to provide insights for the design of more efficient catalysts for the transformation of cellulose with precise cleavage of C–C bonds to high-value chemicals. The reaction mechanisms will also be discussed to understand deeply how the selective cleavage of C–C bonds can be achieved in biomass.