Aryl Carbonyl Research Articles

Stoichiometry Dependence in the Consecutive, Competing Reduction, Halogenation, or Deoxygenation of Aryl Carbonyls.

Six fundamental chemical transformations of aryl carbonyls are achieved by properly adjusting the stoichiometry of the borane-amine and titanium tetrachloride reagent system. This set of reagents acts collectively as a hydride donor, Lewis acid catalyst, and halogen source for the reduction of carbonyls to alcohols, reductive halogenation of carbonyls to halides, deoxygenation of carbonyls to alkanes, dehydroxyhalogenation of alcohols to halides, deoxygenation of alcohols to alkanes, and hydrodehalogenation of halides to alkanes. While the carbonyl reduction is broadly applicable to both aromatic and aliphatic substrates, the remaining reactions are dependent on the stability of the proposed carbocationic intermediates, enabling highly selective reactions at the substrates' benzylic position. This unique selectivity allows benzylic dehalogenation in the presence of aryl and alkyl halides in addition to highly selective dehydroxyhalogenation of alcohols even for tertiary versus secondary aliphatic and secondary versus primary benzylic substrates using only titanium tetrachloride as the chlorinating agent.

Organic Room Temperature Phosphorescence from BN‐Substituted Xanthene Derivatives

AbstractEmissive organic materials are predominantly fluorescent and there is significant interest in realizing and understanding examples that defy this paradigm and exhibit phosphorescence under ambient conditions. Organic room temperature phosphorescence (ORTP) offers the long‐lived excited states and bathochromically‐shifted emission maxima of phosphorescence without the use of potentially toxic and expensive transition metals. Most ORTP materials rely on well‐studied structural motifs that include aryl carbonyls, sulfones, and heavy main group elements. We report the unexpected ORTP of a series of heavy atom‐free BN‐substituted xanthene derivatives. The creation of heteroatom‐rich scaffolds, combined with stabilizing C−H⋅⋅⋅F interactions in the solid‐state, resulted in oxygen‐tolerant heavy atom‐free organic phosphorescence without relying on the use of cryogenic temperatures, polymer matrices, or host–guest interactions. The observation of ORTP in these simple systems sets a blueprint for the further development of heavy atom‐free organic phosphors.

Organic Room Temperature Phosphorescence from BN-Substituted Xanthene Derivatives.

Emissive organic materials are predominantly fluorescent and there is significant interest in realizing and understanding examples that defy this paradigm and exhibit phosphorescence under ambient conditions. Organic room temperature phosphorescence (ORTP) offers the long-lived excited states and bathochromically-shifted emission maxima of phosphorescence without the use of potentially toxic and expensive transition metals. Most ORTP materials rely on well-studied structural motifs that include aryl carbonyls, sulfones, and heavy main group elements. We report the unexpected ORTP of a series of heavy atom-free BN-substituted xanthene derivatives. The creation of heteroatom-rich scaffolds, combined with stabilizing C-H···F interactions in the solid-state, resulted in oxygen-tolerant heavy atom-free organic phosphorescence without relying on the use of cryogenic temperatures, polymer matrices, or host-guest interactions. The observation of ORTP in these simple systems sets a blueprint for the further development of heavy atom-free organic phosphors.

Aryl carbonyls and carbinols as proelectrophiles for Friedel-Crafts benzylation and alkylation.

Friedel-Crafts benzylation/alkylation using benzylic, tertiary, and homobenzylic alcohols; aryl aldehydes, aryl ketones, and the highly challenging aryl carboxylic acids and esters as proelectrophiles has been achieved using borane-ammonia and TiCl4, greatly broadening the scope of useable substrates. Incorporation of deactivated aromatic proelectrophiles and specificity for substitution at the benzylic position are demonstrated in the synthesis of various di- and triarylalkane products. Dual protocols allow for the use of standard nucleophilic solvents (benzene, toluene, etc.) or for stoichiometric addition of more valuable nucleophiles including furans, thiophenes, and benzodioxoles.

Three derivatives of phenacyldiphenylphosphine oxide: influence of aromatic and alkyl substituents on the luminescence sensitization of four Ln(NO3)3 salts.

A series of four β-carbonylphosphine oxide compounds have been synthesized, and their complexes with the nitrate salts of Sm3+, Eu3+, Tb3+ and Dy3+ have been characterized in solution and in the solid state. Analysis of the complexes using IR and NMR suggests that metal-ligand binding occurs mainly through the phosphine oxide group of the ligand, with some involvement of the carbonyl group. All 16 complexes luminesce in solutions of acetonitrile, albeit with varying degrees of intensity. The highest quantum yield values obtained for this series are those where the ligand contains an aryl carbonyl group paired with an electron rich phosphine oxide group (29.8 and 11% for the Tb3+ and Eu3+ complexes, respectively). In contrast, the longest emission lifetime values were found for complexes where the ligand contains a bulky substituent on the carbonyl group paired with an electron rich phosphine oxide (1.86, 1.402, 0.045 ms for the Tb3+, Eu3+ and Sm3+ complexes, respectively).

Directing group assisted rhodium-catalyzed formal C–H arylation and carbonylative arylation of arenes with aryl halides in the presence of CO

A controllable rhodium-catalyzed formal C–H arylation and carbonylative arylation of a variety of readily accessible arenes bearing N-containing heterocycles-directing groups and aryl halides under 1 atm of carbon monoxide (CO) was developed. Good to excellent yields of various bi(hetero)aryls and 7-aroyl indolines were obtained using different substrates. Preliminary mechanistic studies support that a proposed carbonylation/decarbonylation reaction sequence might be involved in the formal C–H arylation. This approach features high efficiency, good functional group tolerance, excellent chemoselectivity, and offers a powerful strategy to access various biaryls, 7-aroyl indolines and 7-aroyl indoles as well.

Balancing Lewis Acidity and Carbocation Stability for the Selective Deoxyhalogenation of Aryl Carbonyls and Carbinols.

Deoxyhalogenation of aryl aldehydes, ketones, carboxylic acids, and esters has been achieved utilizing an appropriate metal halide Lewis acid acting as a carbonyl activator and halogen carrier in combination with borane-ammonia as the reductant. Selectivity is accomplished by matching the stability of the carbocation intermediate with the effective acidity of the Lewis acid. Substituents and substitution patterns significantly influence the requisite solvent/Lewis acid combination. Logical combinations of these factors have also been applied for the regioselective conversion of alcohols to alkyl halides.

Palladium-Catalyzed Benzylic C(sp3 )-H Carbonylative Arylation with Aryl Bromides.

A novel, selective and high-yielding palladium-catalyzed carbonylative arylation of a variety of weakly acidic (pKa 25-35 in DMSO) benzylic and heterobenzylic C(sp3 )-H bonds with aryl bromides has been achieved. This system is applicable to a range of pro-nucleophiles for access to sterically and electronically diverse α-aryl or α,α-diaryl ketones, which are ubiquitous substructures in biologically active compounds. The Josiphos SL-J001-1-based palladium catalyst was identified as the most efficient and selective, enabling carbonylative arylation with aryl bromides under 1 atm CO to provide the ketone products without the formation of direct coupling byproducts. Additionally, (Josiphos)Pd(CO)2 was identified as the catalyst resting state. A kinetic study suggests that the oxidative addition of aryl bromides is the turnover-limiting step. Key catalytic intermediates were also isolated.

Palladium‐Catalyzed Benzylic C(sp3)−H Carbonylative Arylation with Aryl Bromides

AbstractA novel, selective and high‐yielding palladium‐catalyzed carbonylative arylation of a variety of weakly acidic (pKa 25–35 in DMSO) benzylic and heterobenzylic C(sp3)−H bonds with aryl bromides has been achieved. This system is applicable to a range of pro‐nucleophiles for access to sterically and electronically diverse α‐aryl or α,α‐diaryl ketones, which are ubiquitous substructures in biologically active compounds. The Josiphos SL‐J001‐1‐based palladium catalyst was identified as the most efficient and selective, enabling carbonylative arylation with aryl bromides under 1 atm CO to provide the ketone products without the formation of direct coupling byproducts. Additionally, (Josiphos)Pd(CO)2 was identified as the catalyst resting state. A kinetic study suggests that the oxidative addition of aryl bromides is the turnover‐limiting step. Key catalytic intermediates were also isolated.

Synthesis of Fluorenones and Xanthones through Intramolecular C–F Arylation

Abstract Facile methods to synthesize fluorenones and xanthones through C–F cleavages are disclosed. Transition-metal-catalyzed coupling reactions of 2-halogenated benzotrifluorides with arylboronic acids and phenols and following intramolecular carbonylative arylation of trifluoromethyl group afforded fluorenones and xanthones. A wide variety of cyclic ketones can be prepared by the cross-coupling/C–F arylation approach since electron-withdrawing trifluoromethyl groups facilitated deprotonated transformations at neighboring moieties realizing an efficient synthesis of 2-halogenated benzotrifluorides.

Comparative Evaluation of Liquid–Liquid Phase Equilibria for Aqueous Mixtures of Acetic Acid with Structurally Related Aryl Carbonyl Compounds at 298.2 and 308.2 K

Experimental solubility curves and tie-line compositions were comparatively investigated for the aqueous mixtures of acetic acid with three structurally similar aryl carbonyl compounds (propiophenone, acetophenone, and methyl benzoate) at (298.2 and 308.2) K and 101 kPa. The studied ternary mixtures display type-1 phase behavior. The correlation of the measured tie lines was performed by the NRTL and UNIQUAC models. The model binary interaction parameters were obtained by measured tie-line values and minimizing an objective function. The consistency of the NRTL parameters was validated through topological analysis connected to the Gibbs tangent principle and stability test. Evaluation of the capacity of each solvent was performed using the calculation of distribution coefficients and separation factors. Distribution coefficient (constant) and selectivity (separation factor) values were evaluated over the immiscibility region using the experimental equilibrium data. The influence of extraction temperature on the immiscibility region was found to be minor.

Nanohybrid Photocatalyst for the Synthesis of Aryl Carbonyl Compounds and Benzimidazoles

Key words cobalt catalysis - carbon nitride - titanium dioxide - photocatalysis - oxidation - benzimidazoles

Pd-Catalyzed Enantioselective Hydroamidocarbonylation of α-Substituted Acrylamides to Chiral Succinimides.

With the aid of an innate amide group, an intramolecular Pd-catalyzed enantioselective hydroamidocarbonylation reaction of α-substituted acrylamides was developed, and a series of chiral 2-substituted succinimides were obtained in moderate to high yields and enantioselectivities. The generality of this approach was demonstrated by the carbonylation of both aryl- and alkyl-substituted acrylamides containing numerous functional groups.

Revisiting the Mg/TMSCl/Dipolar Solvent System for Dearomatic Silylation of Aryl Carbonyl Compounds: Substrate Scope, Transformations, and Mechanistic Studies.

Dearomatic silylation of arene derivatives is an intriguing synthetic target, which represents an elegant extension of Birch reduction and produces silylated cyclohexene derivatives with great potential of further transformation. Herein, we report a systematic study on dearomatic silylation of aryl carbonyl compounds with Mg and the TMSCl/NMP adduct. The protocol displays a wide range of substrate scope, including alkyl aryl ketones, aromatic amides, benzonitriles, tert-butyl benzoates, and even 2,2'-bipyridines. Synthetic utility is demonstrated using the products as versatile substrate in various transformations. The detailed mechanism is presented with both control experimental analyses and theoretical calculations. An unusual five-coordinated silicon dianion intermediate is first proposed and described here. The selectivity is influenced by the relative rates of single electron reductions (the TMSCl/NMP adduct versus the substrate) and the steric effects.

Chemoselective and Tandem Reduction of Arenes Using a Metal-Organic Framework-Supported Single-Site Cobalt Catalyst.

The development of heterogeneous, chemoselective, and tandem catalytic systems using abundant metals is vital for the sustainable synthesis of fine and commodity chemicals. We report a robust and recyclable single-site cobalt-hydride catalyst based on a porous aluminum metal-organic framework (DUT-5 MOF) for chemoselective hydrogenation of arenes. The DUT-5 node-supported cobalt(II) hydride (DUT-5-CoH) is a versatile solid catalyst for chemoselective hydrogenation of a range of nonpolar and polar arenes, including heteroarenes such as pyridines, quinolines, isoquinolines, indoles, and furans to afford cycloalkanes and saturated heterocycles in excellent yields. DUT-5-CoH exhibited excellent functional group tolerance and could be reusable at least five times without decreased activity. The same MOF-Co catalyst was also efficient for tandem hydrogenation-hydrodeoxygenation of aryl carbonyl compounds, including biomass-derived platform molecules such as furfural and hydroxymethylfurfural to cycloalkanes. In the case of hydrogenation of cumene, our spectroscopic, kinetic, and density functional theory (DFT) studies suggest the insertion of a trisubstituted alkene intermediate into the Co-H bond occurring in the turnover limiting step. Our work highlights the potential of MOF-supported single-site base-metal catalysts for sustainable and environment-friendly industrial production of chemicals and biofuels.

Highly γ‐Selective Arylation and Carbonylative Arylation of 3‐Bromo‐3,3‐difluoropropene via Nickel Catalysis

AbstractA nickel‐catalyzed highly γ‐regioselective arylation and carbonylative arylation of 3‐bromo‐3,3‐difluoropropene has been developed. The reaction proceeds under mild reaction conditions, providing the gem‐difluoroalkenes with high efficiency and good functional group tolerance. The resulting gem‐difluoroalkenes can serve as versatile building blocks for diversified synthesis. Preliminary mechanistic studies and density functional theory calculations reveal that both non‐radical and radical pathways are possible for the reaction, and the radical pathway is more likely. The high γ‐regioselectivity results from the β‐bromide elimination of alkylnickel(II) species or from the reductive elimination of nickel(III) species [(aryl)(CF2=CHCH2)NiIII(Ln)X]. The γ‐selective carbonylation of 3‐bromo‐3,3‐difluoropropene under 1 atm CO gas also provides a new way for nickel‐catalyzed carbonylation.

Highly γ-Selective Arylation and Carbonylative Arylation of 3-Bromo-3,3-difluoropropene via Nickel Catalysis.

A nickel-catalyzed highly γ-regioselective arylation and carbonylative arylation of 3-bromo-3,3-difluoropropene has been developed. The reaction proceeds under mild reaction conditions, providing the gem-difluoroalkenes with high efficiency and good functional group tolerance. The resulting gem-difluoroalkenes can serve as versatile building blocks for diversified synthesis. Preliminary mechanistic studies and density functional theory calculations reveal that both non-radical and radical pathways are possible for the reaction, and the radical pathway is more likely. The high γ-regioselectivity results from the β-bromide elimination of alkylnickel(II) species or from the reductive elimination of nickel(III) species [(aryl)(CF2 =CHCH2 )NiIII (Ln )X]. The γ-selective carbonylation of 3-bromo-3,3-difluoropropene under 1 atm CO gas also provides a new way for nickel-catalyzed carbonylation.

Photo-redox coupled Co-pincer complexes for efficient decarbonylation of aryl carbonyls: A quantum chemical investigation

Abstract Catalytic decarbonylation of aryl carbonyls is a challenging task. Although some precious metal based catalysts have been developed, Earth abundant transition metal based decarbonylating catalysts are yet to be realized. Very recently, Co(I) pincer complex has been utilized for one step decarbonylation of aromatic and aliphatic aldehydes, however, the reactions do not proceed for the next step catalytic cycle. To address this issue, we here present the thermodynamic and mechanistic aspects of the reactions and on the basis of first principles calculations, we shed some light for further developing the catalyst. We demonstrate that it is the thermodynamic factor that inhibits the catalytic activity due to very strong metal-carbonyl interactions. However, a similar Co(II) complex shows much less regeneration energy but fails to initiate the reaction. We propose that if a suitable Ru(II)/Ir(III) photo sensitizer is used, the resultant photoredox catalytic system coupled with the Co(II) pincer complex might be very efficient for the decarbonylation process.

Co2(CO)8 as a Solid CO (g) Source for the Amino Carbonylation of (Hetero)aryl Halides with Highly Deactivated (Hetero)arylamines.

Carbonylation of (hetero)aryl iodides/bromides with highly deactivated 2-aminopyridines using Pd-Co(CO)4 bimetallic catalysis is accomplished. The use of Co2(CO)8 as a solid CO(g) source enhanced reaction rates observed when compared to CO(g), and excellent yields highlight the versatility of the developed protocol. A wide range of electronically and sterically demanding heterocyclic amines and (hetero)aryl iodides/bromides employed for this study resulted in excellent yields of amino carbonylated products. The developed methodology was further extended to synthesize Trypanosome brucie and luciferase inhibitors.

Reductive electrophilic C-H alkylation of quinolines by a reusable iridium nanocatalyst.

The incorporation of a coupling step into the reduction of unsaturated systems offers a desirable way for diverse synthesis of functional molecules, but it remains to date a challenge due to the difficulty in controlling the chemoselectivity. Herein, by developing a new heterogeneous iridium catalyst composed of Ir-species (Irδ+) and N-doped SiO2/TiO2 support (Ir/N-SiO2/TiO2), we describe its application in reductive electrophilic mono and dialkylations of quinolines with various 2- or 4-functionalized aryl carbonyls or benzyl alcohols by utilizing renewable formic acid as the reductant. This catalytic transformation offers a practical platform for direct access to a vast range of alkyl THQs, proceeding with excellent step and atom-efficiency, good substrate scope and functional group tolerance, a reusable catalyst and abundantly available feedstocks, and generation of water and carbon dioxide as by-products. The work opens a door to further develop more useful organic transformations under heterogeneous reductive catalysis.