Aromatic Carbon-hydrogen Research Articles

2022’s synthesis showstoppers

Evolved enzymes built biaryl bonds Chemists use biaryl molecules, which feature aryl groups tethered to one another by a single bond, as chiral ligands, materials building blocks, and pharmaceuticals. But making the biaryl motif with metal-catalyzed reactions, such as Suzuki and Negishi cross-couplings, typically requires several synthetic steps to make the coupling partners. What’s more, these metal-catalyzed reactions falter when making bulky biaryls. Inspired by enzymes’ ability to catalyze reactions, a team led by the University of Michigan’s Alison R. H. Narayan used directed evolution to create a cytochrome P450 enzyme that builds a biaryl molecule via oxidative coupling of aromatic carbon-hydrogen bonds. The enzyme weds aromatic molecules to create one stereoisomer around a bond with hindered rotation (shown). The researchers think this biocatalytic approach could become a bread-and-butter transformation for making biaryl bonds ( Nature 2022, DOI: 10.1038/s41586-021-04365-7 ). Recipe for tertiary amines relied on a little salt Mixing

Recent Advances in the Synthesis of Isocoumarins and Polyaromatic Hydrocarbons for Photoactive Materials

The discovery of transition metal-catalyzed selective activation of aromatic carbon–hydrogen bonds in 1993 has opened a new era in the synthesis of carbo- and heterocyclic compounds. This review covers the applications of oxidative annulations of aromatic compounds with alkynes involving CH activation for the synthesis of isocoumarins and polyaromatic hydrocarbons (PAHs). The limitations, advantages, and mechanical aspects of this approach as well as the current tendencies in the application of the reaction products for photoactive materials are discussed.

A radical approach for the selective C-H borylation of azines.

Boron functional groups are often introduced in place of aromatic carbon-hydrogen bonds to expedite small-molecule diversification through coupling of molecular fragments1-3. Current approaches based on transition-metal-catalysed activation of carbon-hydrogen bonds are effective for the borylation of many (hetero)aromatic derivatives4,5 but show narrow applicability to azines (nitrogen-containing aromatic heterocycles), which are key components of many pharmaceutical and agrochemical products6. Here we report an azine borylation strategy using stable and inexpensive amine-borane7 reagents. Photocatalysis converts these low-molecular-weight materials into highly reactive boryl radicals8 that undergo efficient addition to azine building blocks. This reactivity provides a mechanistically alternative tactic for sp2 carbon-boron bond assembly, where the elementary steps of transition-metal-mediated carbon-hydrogen bond activation and reductive elimination from azine-organometallic intermediates are replaced by a direct, Minisci9-style, radical addition. The strongly nucleophilic character of the amine-boryl radicals enables predictable and site-selective carbon-boron bond formation by targeting the azine's most activated position, including the challenging sites adjacent to the basic nitrogen atom. This approach enables access to aromatic sites that elude current strategies based on carbon-hydrogen bond activation, and has led to borylated materials that would otherwise be difficult to prepare. We have applied this process to the introduction of amine-borane functionalities to complex and industrially relevant products. The diversification of the borylated azine products by mainstream cross-coupling technologies establishes aromatic amino-boranes as a powerful class of building blocks for chemical synthesis.

Surface Chemical Heterogeneity of Low Rank Coal Characterized by Micro-FTIR and Its Correlation with Hydrophobicity

Micro-Fourier transform infrared (micro-FTIR) spectroscopy was used to correlate the surface chemistry of low rank coal with hydrophobicity. Six square areas without mineral impurities on low rank coal surfaces were selected as testing areas. A specially-designed methodology was applied to conduct micro-FTIR measurements and contact angle tests on the same testing area. A series of semi-quantitative functional group ratios derived from micro-FTIR spectra were correlated with contact angles, and the determination coefficients of linear regression were calculated and compared in order to identify the structure of the functional group ratios. Finally, two semi-quantitative ratios composed of aliphatic carbon hydrogen, aromatic carbon hydrogen and two different types of carbonyl groups were proposed as indicators of low rank coal hydrophobicity. This work provided a rapid way to predict low rank coal hydrophobicity through its functional group composition and helped us understand the hydrophobicity heterogeneity of low rank coal from the perspective of its surface chemistry.

Palladium-catalysed electrophilic aromatic C-H fluorination.

Aryl fluorides are widely used in the pharmaceutical and agrochemical industries, and recent advances have enabled their synthesis through the conversion of various functional groups. However, there is a lack of general methods for direct aromatic carbon-hydrogen (C-H) fluorination. Conventional methods require the use of either strong fluorinating reagents, which are often unselective and difficult to handle, such as elemental fluorine, or less reactive reagents that attack only the most activated arenes, which reduces the substrate scope. A method for the direct fluorination of aromatic C-H bonds could facilitate access to fluorinated derivatives of functional molecules that would otherwise be difficult to produce. For example, drug candidates with improved properties, such as increased metabolic stability or better blood-brain-barrier penetration, may become available. Here we describe an approach to catalysis and the resulting development of an undirected, palladium-catalysed method for aromatic C-H fluorination using mild electrophilic fluorinating reagents. The reaction involves a mode of catalysis that is unusual in aromatic C-H functionalization because no organometallic intermediate is formed; instead, a reactive transition-metal-fluoride electrophile is generated catalytically for the fluorination of arenes that do not otherwise react with mild fluorinating reagents. The scope and functional-group tolerance of this reaction could provide access to functional fluorinated molecules in pharmaceutical and agrochemical development that would otherwise not be readily accessible.

Amorphous carbon nitride thin films for electrochemical electrode: Effect of molecular structure and substrate materials

We report on the effect of molecular structure and substrate material on amorphous carbon nitride (a-CN:H) electrode properties including film adhesion to the substrate and electrochemical properties. Films were prepared by neutral beam enhanced chemical vapor deposition on different substrate materials (p-type Si, Cu, Ti, and Pt) below room temperature. When depositing on Si, doping nitrogen into carbon improved the electrochemical properties despite weak adhesion to the substrate. Nitrogen in a-CN:H formed two different bonding configurations: incorporation into aromatic carbon rings and hydrogen nitride by infrared (IR) spectroscopy. Therefore, delocalization of π bonds by incorporation of nitrogen affected the electrochemical improvement of the a-CN:H electrode. For samples deposited on a different metal substrate, the adhesion to substrate increased as a function of decreasing oxygen concentration on the metal substrate surface; the Pt substrate performed well with no delamination in our evaluation. The electrochemical properties were improved only in the case of deposition on Pt. Moreover, Pt surface modification by hydrogen beam was also effective; consequently, the electrochemical property of the a-CN:H electrode was superior to the graphite electrode with high temperature annealing. The observed increases in IR spectra of aromatic clusters were in line with the electrochemical improvements of a-CN:H.

Palladium-Catalyzed Regioselective Homocoupling of Arenes Using Anodic Oxidation: Formal Electrolysis of Aromatic Carbon–Hydrogen Bonds

Palladium-catalyzed regioselective homocoupling of arylpyridines under anodic oxidation conditions was achieved in the presence of I2. The dimerization of meta-substituted arylpyridines proceeded selectively at less-sterically congested ortho-positions, and the selectivity is different from that reported for the palladium-catalyzed dimerization using Oxone as an oxidant. The dimerization also proceeds using catalytic amounts of both Pd(OAc)2 and I2 under the electrochemical reaction conditions.

Metal-free oxidation of aromatic carbon–hydrogen bonds through a reverse-rebound mechanism

Methods for carbon-hydrogen (C-H) bond oxidation have a fundamental role in synthetic organic chemistry, providing functionality that is required in the final target molecule or facilitating subsequent chemical transformations. Several approaches to oxidizing aliphatic C-H bonds have been described, drastically simplifying the synthesis of complex molecules. However, the selective oxidation of aromatic C-H bonds under mild conditions, especially in the context of substituted arenes with diverse functional groups, remains a challenge. The direct hydroxylation of arenes was initially achieved through the use of strong Brønsted or Lewis acids to mediate electrophilic aromatic substitution reactions with super-stoichiometric equivalents of oxidants, significantly limiting the scope of the reaction. Because the products of these reactions are more reactive than the starting materials, over-oxidation is frequently a competitive process. Transition-metal-catalysed C-H oxidation of arenes with or without directing groups has been developed, improving on the acid-mediated process; however, precious metals are required. Here we demonstrate that phthaloyl peroxide functions as a selective oxidant for the transformation of arenes to phenols under mild conditions. Although the reaction proceeds through a radical mechanism, aromatic C-H bonds are selectively oxidized in preference to activated Csp3-H bonds. Notably, a wide array of functional groups are compatible with this reaction, and this method is therefore well suited for late-stage transformations of advanced synthetic intermediates. Quantum mechanical calculations indicate that this transformation proceeds through a novel addition-abstraction mechanism, a kind of 'reverse-rebound' mechanism as distinct from the common oxygen-rebound mechanism observed for metal-oxo oxidants. These calculations also identify the origins of the experimentally observed aryl selectivity.

A Meta-Selective Copper-Catalyzed C–H Bond Arylation

For over a century, chemical transformations of benzene derivatives have been guided by the high selectivity for electrophilic attack at the ortho/para positions in electron-rich substrates and at the meta position in electron-deficient molecules. We have developed a copper-catalyzed arylation reaction that, in contrast, selectively substitutes phenyl electrophiles at the aromatic carbon-hydrogen sites meta to an amido substituent. This previously elusive class of transformation is applicable to a broad range of aromatic compounds.

Characterization of heavy petroleum feedstocks

Characterization of key heavy petroleum feedstock properties is important for optimizing the production of clean transportation fuels. A correlation-based method has been developed to accurately estimate the aromatic carbon and total hydrogen content of heavy petroleum feedstocks. The new characterization methodology is significantly superior to existing methods in that it is applicable to all types of heavy petroleum feedstocks, uses only two (most) commonly measured bulk petroleum properties and is more accurate. The new method has been validated via analysis of an unprecedented number (three hundred and fifty four) of heavy petroleum feedstocks with an extremely broad range of properties.

Reactivity of Silylene Complexes

The metal–silicon bond in silylene complexes is highly polarized in a Mδ−–Siδ+ manner. Accordingly, silylene complexes show high reactivities toward nucleophiles, such as water, alcohols, ketones, isocyanates, and phosphorus ylides. The metal–silicon double bond can also activate aromatic carbon–hydrogen bonds. Among the various silylene complexes, silyl(silylene) complexes occupy a unique position; these complexes undergo intramolecular 1,3-migration, which is postulated as a key step in the metal-mediated redistribution of substituents on organosilicon compounds. Alkyl(silylene) complexes are not stable and undergo 1,2-alkyl migration to yield alkylsilyl complexes.

Reactivity of silylene complexes

The metal–silicon bond in silylene complexes is highly polarized in a Mδ−–Siδ+ manner. Accordingly, silylene complexes show high reactivities toward nucleophiles, such as water, alcohols, ketones, isocyanates, and phosphorus ylides. The metal–silicon double bond can also activate aromatic carbon–hydrogen bonds. Among the various silylene complexes, silyl(silylene) complexes occupy a unique position; these complexes undergo intramolecular 1,3-migration, which is postulated as a key step in the metal-mediated redistribution of substituents on organosilicon compounds. Alkyl(silylene) complexes are not stable and undergo 1,2-alkyl migration to yield alkylsilyl complexes.

ChemInform Abstract: Ruthenium‐Catalyzed Coupling of Aromatic Carbon—Hydrogen Bonds in Aromatic Imidates with Olefins.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Ruthenium-Catalyzed Coupling of Aromatic Carbon-Hydrogen Bonds in Aromatic Imidates with Olefins

Abstract Catalytic C-H/olefin coupling can be directed by N,O-heterocyclic substituents. The Ru3(CO)12-catalyzed reaction of 4,4-dimethyl-2-(2-methylphenyl)-5,6-dihydro-4H-1,3-oxazine (1) with triethoxyvinylsilane gave a mixture of the corresponding 1:1 addition product (3a) and its olefinic analogue (3b) in good yields in ca. a 1:1 ratio. In the case of the reaction of 4,4-dimethyl-2-(2-methylphenyl)-4,5-dihydro-1,3-oxazole (7), the olefinic analogue (8b) of the coupling product (8a) was obtained as the major product. The existence of a new reaction pathway is discussed.

Selective aliphatic and aromatic carbon-hydrogen bond activation catalysed by mutants of cytochrome p450 cam

The substrate range of the haem monooxygenase cytochrome P450 cam (CYP101) has been broadened by site-directed mutagenesis. The hydroxylation selectivity of five mutants at the 96 position towards a range of substrates has been used to investigate P450 cam -substrate molecular recognition. The substrates contained aromatic and activated and unactivated aliphatic CH bonds, as well as reactive functional groups. Diphenylmethane, diphenylether, diphenylamine, and 1,1-di-phenylethylene were all hydroxylated regiospecifically at the para position, with no attack at the amine or the olefinic double bond. With benzylcyclohexane the activated benzylic and tertiary CH bonds were not attacked, and the reactions catalysed by the Y96G and Y96A mutants were highly diastereoselective, with 4- trans-benzylcyclohexanol constituting 90% of the products. 1-Phenyl-1-cyclohexylethylene was oxidised predominantly at the 4-position of the cyclohexane ring without attack at the olefinic double bond, and approximately equal amounts of cis- and trans-4-phenylethenylcyclohexanol were formed. These results show that P450 cam can be engineered to oxidise CH bonds without attacking more reactive functional groups.

Catalytic Addition of Aromatic Carbon–Hydrogen Bonds to Olefins with the Aid of Ruthenium Complexes

Abstract Ruthenium complexes, e.g., Ru(H)2(CO)(PPh3)3, have been found to catalyze the addition of ortho C–H bonds of aromatic ketones to olefins with a high degree of efficiency and selectivity. 2′-Methylacetophenone reacts with various types of terminal olefins to give 1 : 1 coupling products in good to excellent yields. The C–C bond formation takes place exclusively at the terminal carbon atom of olefins except for styrene which affords a mixture of two regioisomers. Acetylnaphthalenes, cyclic aromatic ketones, and heteroaromatic ketones also react with triethoxyvinylsilane to give 1 : 1 addition products in virtually quantitative yields. From 2′-acetonaphthone or 3-acetylthiophene, in which two different reaction sites are available, only one out of four possible regioisomers is obtained. The importance of the coordination of the oxygen atom of the ketone to ruthenium and the intervention of a cyclometallation intermediate are suggested. A deuterium labeling experiment using acetophenone-d5 and triethoxyvinylsilane shows that an H/D exchange between the aromatic and olefinic positions takes place to some extent, even prior to the formation of the product. This implies that the rate-determining step is not the C–H bond cleavage step, but the product forming step.

Ruthenium catalyzed regioselective copolymerization of anthrone, fluorenone, or xanthone with ?,?-dienes

This paper reports a novel ruthenium catalyzed regioselective copolymerization reaction between anthrone, fluorenone or xanthone and α,ω-dienes such as 1,3-divinyltetramethyldisiloxane and 3,3,6,6-tetramethyl-3,6-disila-1,7-octadiene. This reaction involves the ruthenium catalyzed regioselective Anti-Markovnikov insertion of the carbon-carbon double bonds of the α,ω-dienes into the aromatic carbon-hydrogen bonds which are ortho to the carbonyl group of anthrone, fluorenone or xanthone. Similar ruthenium catalyzed copolymerization reactions between acetophenone and α,ω-dienes [1] have been recently reported as have reactions between acetophenone and alkenes to yield monomeric ortho-alkyl substituted acetophenones [2].

Ligand Effects in the Rhodium(II)-Catalyzed Reactions of .alpha.-Diazoamides. Oxindole Formation is Promoted by the Use of Rhodium(II) Perfluorocarboxamide Catalysts

An improved procedure for the preparation of ethyl 2-diazomalonyl chloride was developed which involves the reaction of ethyl diazoacetate with triphosgene. Using this diazo acid chloride, it was possible to prepare a variety of diazoamides from substituted amines. The rhodium(II)-catalyzed decomposition of these diazoamides was studied in order to probe the chemoselectivity of the carbenoid intermediates in intramolecular insertion reactions. Rhodium(II) acetate decomposition of N-benzyl-2-diazo-N-phenylmalonamic acid ethyl ester resulted in intramolecular C-H insertion to give ethyl 1,4-diphenyl-2-oxoazetidine-3-carboxylate. By changing the catalyst ligand to trifluoroacetamide, β-lactam formation was completely suppressed in favor of the aromatic C-H insertion which produces an oxindole as the only detectable product. The competition between aliphatic and aromatic carbon-hydrogen insertion of 2-diazo-N-isobutyl-N-phenylmalonamic acid ethyl ester provides another example of ligand effectiveness in controlling chemoselectivity in dirhodium (II)-catalyzed metal carbene reactions. Thus, treatment of the N-isobutyldiazoanilide with rhodium(II) acetate results in exclusive aliphatic C-H insertion giving 4,4-dimethyl-2-oxo-1-phenylpyrrolidine-3-carboxylic acid ethyl ester, while the perfluorobutyramide ligand promotes oxindole formation by aromatic C-H insertion. Several other rhodium(II)-catalyzed reactions were studied and were studied and were found to be highly catalyst dependent, rhodium (II) perfluorocarboxamides promoting aromatic C-H insertion, and hence oxindole formation, over O-H insertion, cyclization onto adjacent triple bonds, or cyclization to generate 1,3-dipolar intermediates

Efficient catalytic addition of aromatic carbon-hydrogen bonds to olefins

The selective cleavage of carbon–hydrogen bonds in organic compounds is a critical step in many organic syntheses, and is particularly important in the conversion of hydrocarbons to useful organic compounds. An organometallic ruthenium complex can cleave C–H bonds in a variety of aromatic systems, leading to addition to alkenes by C–C bond formation. The catalyst operates with a degree of efficiency, selectivity and generality that will make it extremely valuable in organic synthesis.

N.m.r. determination of aromatic carbon balances and hydrogen utilization in direct coal liquefaction

Solid- and liquid-state 13C n.m.r. measurements were made on a suite of samples obtained from different stages of a coal liquefaction run at the Wilsonville Two-Stage Advanced Coal Liquefaction Research and Development Facility. The n.m.r. measurements were combined with elemental analysis and mass balance data to measure aromatic carbon balances and hydrogen utilization for Wilsonville coal liquefaction run 259G. This was a catalytic/catalytic integrated two-stage liquefaction run on a deeply cleaned, Pittsburgh seam, high volatile bituminous (hvAb) coal from the Ireland mine in West Virginia, USA. The n.m.r. measurements showed that on the basis of the feed coal, about 58% of the aromatic carbons in Pittsburgh coal were hydrogenated during two-stage liquefaction, and 55% of the hydrogenation occurred during the second stage. A net of 68.1 mol of hydrogen per 100 mol of coal carbon was consumed during the first stage of Wilsonville run 259G. This amounted to 69% of the total overall two-stage hydrogen consumption. Matrix cleavage and hydrogenation reactions accounted for 31% and 27%, respectively, of the total first-stage hydrogen consumption. Hydrogenation reactions accounted for most (69%) of the hydrogen consumed during the second stage, and accounted for 40% of the overall two-stage total hydrogen consumption. Most of the total hydrogen consumed for hydrocarbon gas generation (70%), and for heteroatom removal and heterogas production (71%) occurred in the first stage. Overall hydrogen consumption was 14% for hydrocarbon gas production and 27% for heteroatom removal and heterogas production.