Benzyl Ketones Research Articles

Nickel-catalyzed enantioselective reductive amination of benzylic ketones in alcohols

Nickel-catalyzed enantioselective reductive amination of benzylic ketones in alcohols

Boosting Solvent-Free Aerobic Oxidation of Benzylic Compounds into Ketones over Au-Pd Nanoparticles Supported by Porous Carbon

The exploitation of highly efficient solvent-free catalytic systems for the selective aerobic oxidation of benzylic compounds to produce corresponding ketones with molecular oxygen under mild conditions remains a great challenge in the chemical industry. In this work, Au-Pd nanoparticles supported on porous carbon catalysts were fabricated by the borax-mediated hydrothermal carbonization method and the chemical reduction method. The physicochemical properties of Au-Pd bimetallic samples were examined by XRD, N2 sorption, SEM, TEM, and XPS techniques. The Au-Pd nanoparticles have successfully immobilized on the spherical carbon support with a porous structure and large surface area. A solvent-free catalytic oxidation system was constructed to selectively convert indane into indanone with Au-Pd nanocatalysts and O2. In contrast with a monometallic Au or Pd catalyst, the resulting bimetallic Au-Pd catalyst could effectively activate O2 and exhibit improved catalytic activity in the controlled oxidation of indane into indanone under 1 bar O2. A total of 78% conversion and >99% selectivity toward indanone can be achieved under optimized conditions. The synergistic effect of Au and Pd and porous carbon support contributed to the high catalytic activity for aerobic benzylic compound oxidation. This work offers a promising application prospect of efficient and recyclable Au-Pd nanocatalysts in functional benzylic ketone production.

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ3-iodanes.

We present N-heterocycle-stabilized iodanes (NHIs) as suitable reagents for the mild oxidation of activated alcohols. Two different protocols, both involving activation by chloride additives, were used to synthesize benzylic ketones and aldehydes without overoxidation in up to 97% yield. Based on MS experiments an activated hydroxy(chloro)iodane is proposed as the reactive intermediate.

Selective Electrochemical Oxidation of Benzylic C-H to Benzylic Alcohols with the Aid of Imidazolium Radical Mediators.

Selective oxidation of benzylic C-H to benzylic alcohols is a well-known challenge in the chemical community since benzylic C-H is more prone to be overoxidized to benzylic ketones. In this work, we report the highly selective electro-oxidation of benzylic C-H to benzylic alcohols in an undivided cell in ionic liquid-based solution. As an example, the selectivity toward xanthydrol could be as high as 95.7% at complete conversion of xanthene, a typical benzylic C-H compound, on gram-scale in imidazolium bromide/H2O/DMF. Mechanism investigation reveals that the imidazolium radical generated in situ participants in a proton-coupled electron transfer process and low-barrier hydrogen bonds stabilize the reaction intermediates, together steering the redox equilibrium, favoring benzylic alcohols over benzylic ketones.

Borrowing hydrogen and dehydrogenative/oxidative cyclization reactions catalyzed by a CCC-NHC pincer Re complex: An air stable catalyst for the synthesis of α-alkylated ketones and quinolines

Successful catalytic activity of the CCC-NHC pincer Re(I) complex was achieved for the borrowing hydrogen coupling reaction between primary and secondary benzylic alcohols. An expansive scope of 17 aromatic and 2 aliphatic substrates were investigated and isolated yields from 40% to 91% were collected. The aliphatic substrates yielded complex aldol self-condensation by-products. The catalytic activity of the CCC-NHC pincer Re(I) complex was also evaluated for the formation of quinolines via the dehydrogenative/oxidative cyclization of 2-aminobenzyl alcohols with benzylic ketones or secondary benzylic alcohols. Isolated yields from 68% to 87% were obtained for 12 examples. All products and by-products were fully characterized by 1H &13C NMR and mass spectroscopies. Control studies such as dehydrogenative and hydrogen transfer reaction were carried out, and the results from these experiments supported a proposed mechanism of a borrowing hydrogen coupling reaction catalyzed by the CCC-NHC pincer Re(I) complex.

Plasma Electrochemistry for Carbon-Carbon Bond Formation via Pinacol Coupling.

The formation of carbon-carbon bonds by pinacol coupling of aldehydes and ketones requires a large negative reduction potential, often realized with a stoichiometric reducing reagent. Here, we use solvated electrons generated via a plasma-liquid process. Parametric studies with methyl-4-formylbenzoate reveal that selectivity over the competing reduction to the alcohol requires careful control over mass transport. The generality is demonstrated with benzaldehydes, benzyl ketones, and furfural. A reaction-diffusion model explains the observed kinetics, and ab initio calculations provide insight into the mechanism. This study opens the possibility of a metal-free, electrically-powered, sustainable method for reductive organic reactions.

Catalytic cascade synthesis of cyanohydrin esters via water/O2-induced cyanide transfer from K3Fe(CN)6.

The copper-catalyzed α-oxygenation of aryl benzyl ketones is merged with a unique water/O2-induced release of cyanide ions from K3Fe(CN)6 and a benzil-cyanide reaction. This strategy gives expedient access to cyanohydrin esters starting directly from broadly accessible aryl benzyl ketones. The cyanide release strategy was further integrated with a copper catalyzed oxygenation-decarbonylation sequence to produce cyanohydrin esters from 1,3-diketones.

Synthesis of a CCC‐NHC pincer Re complex: An air stable catalyst for coupling ketones with primary alcohols via borrowing hydrogen

To date, no CCC‐NHC pincer complexes of Re have been reported in the literature. The first CCC‐NHC pincer complex of Re is reported. It was fully characterized by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, mass spectroscopy, elemental analysis, and X‐ray crystallographic methods to determine the molecular structure. It was synthesized via transmetallation from an isolated Zr precursor and was found to be air stable. The catalytic activity of the CCC‐NHC Re(I) pincer complex was demonstrated for the borrowing hydrogen coupling reaction between benzylic ketones and primary alcohols to generate a new C–C bond in an environmentally friendly catalysis requiring no activating groups for the alcohol functionality. This borrowing hydrogen coupling reaction produced a stoichiometric amount of water as the only by‐product and did not require the conversion of the primary alcohol to a leaving group. A broad range of substrates was examined, and isolated yields from 53% to 92% were obtained. A catalytic cycle for the CCC‐NHC Re(I) pincer complex catalyzed borrowing hydrogen coupling reaction is proposed.

Domino Nitro Reduction-Friedländer Heterocyclization for the Preparation of Quinolines.

The Friedländer synthesis offers efficient access to substituted quinolines from 2-aminobenzaldehydes and activated ketones in the presence of a base. The disadvantage of this procedure lies in the fact that relatively few 2-aminobenzaldehyde derivatives are readily available. To overcome this problem, we report a modification of this process involving the in situ reduction of 2-nitrobenzaldehydes with Fe/AcOH in the presence of active methylene compounds (AMCs) to produce substituted quinolines in high yields. The conditions are mild enough to tolerate a wide range of functionality in both reacting partners and promote reactions not only with phenyl and benzyl ketones, but also with β-keto-esters, β-keto-nitriles, β-keto-sulfones and β-diketones. The reaction of 2-nitroaromatic ketones with unsymmetrical AMCs is less reliable, giving a competitive formation of substituted quinolin-2(1H)-ones from the cyclization of the Z Knoevenagel intermediate which appears to be favored when certain large groups are adjacent to the AMC ketone carbonyl.

Asymmetric Transfer Hydrogenative Amination of Benzylic Ketones Catalyzed by Cp*Ir(III) Complexes Bearing a Chiral N-(2-Picolyl)sulfonamidato Ligand

A convenient asymmetric reductive amination of benzylic ketones (α-arylated ketones) catalyzed by newly designed Cp*Ir complexes bearing a chiral N-(2-picolyl)sulfonamidato ligand was developed. Using readily available β-amino alcohols as chiral aminating agents, a range of benzo-fused and acyclic ketones were successfully reduced with formic acid in methanol at 40 °C to afford amines with favorable chemo- and diastereoselectivities. The amino alcohol-derived chiral auxiliary was easily removed by mild periodic oxidants, leading to optically active primary β-arylamines without erosion of the optical purity (up to 97% ee). The excellent catalytic performance was retained even upon lowering the amount of catalyst to a substrate/catalyst (S/C) ratio of 20,000, and the amination could be performed on a large scale exceeding 100 g. The precise hydride transfer to iminium species generated from the ketonic substrate and the chiral amine counterpart was suggested by the mechanistic studies on stoichiometric reactions of isolable hydridoiridium complexes and model intermediates such as N,O-acetal, enamine, and iminium compounds.

Dual Carbene and Photoredox Catalysis Permits Tandem Cyclization to Cyclic Benzylic Ketones

Dual Carbene and Photoredox Catalysis Permits Tandem Cyclization to Cyclic Benzylic Ketones

Synthesis of Cyclohexanones by a Tandem Photocatalyzed Annulation.

The rapid synthesis of cyclic scaffolds is of high importance to the chemistry community. Strategies for the convergent synthesis of substituted carbocycles and heterocycles remain underexplored despite the plethora of applications that these cyclic motifs have in the pharmaceutical and materials industries. Reported herein is a tandem carbene and photoredox-catalyzed process for the convergent synthesis of substituted cycloalkanones via a formal [5 + 1] cycloaddition. Featuring two distinct photoredox cycles and a novel α-oxidation of benzylic ketones, this reaction offers a mild approach to construct two contiguous C-C bonds and eliminates the need for strong bases or expensive metal catalysts. The utility of this method is highlighted through various product diversification reactions that allow access to a range of important cyclic scaffolds.

TBAI-Catalyzed Oxidative Coupling of Benzyl Ketones to Synthesize 2,3-Diaryl-1,4-Diketones in Water.

An efficient and green route of C–C bond formation was disclosed to construct 2,3-diaryl-1,4-diketones from α-methylene ketones by the catalysis of tetrabutylammonium iodide (TBAI) with tert-butyl hydroperoxide (TBHP) as an oxidant in water. This reaction affords the desired products in good to excellent yields from readily available materials, with a broad substrate scope, good functional group tolerance, and mild reaction conditions. Furthermore, tetrasubstituted furan and pyrrole were smoothly constructed from α-methylene ketones in one pot with 96 and 90% yields, respectively.

Selective upgrading of biomass-derived benzylic ketones by (formic acid)–Pd/HPC–NH2 system with high efficiency under ambient conditions

Selective upgrading of biomass-derived benzylic ketones by (formic acid)–Pd/HPC–NH2 system with high efficiency under ambient conditions

Synthesis of 1-Benzyl-, 1-Alkoxyl-, and 1-Aminoisoquinolines via Rhodium(III)-Catalyzed Aryl C-H Activation and Alkyne Annulation.

One-pot syntheses of 1-benzyl-, 1-alkoxyl-, and 1-alkylamino- isoquinolines through automatic directing group (DGauto)-assisted, rhodium(III)-catalyzed aryl C-H activation and annulation with internal alkynes were developed. The reactions affording 1-benzylisoquinolines involve a cascade oximation of diarylacetylenes with hydroxylamine, forming aryl benzyl ketone oxime, and oxime-assisted rhodium(III)-catalyzed aryl C-H activation and followed annulation with another molecule of diarylacetylene in a one-pot manner. The formation of 1-alkoxyl/amino isoquinolines includes the addition of nucleophilic alcohols or amines to aryl nitriles, imine-assisted rhodium-catalyzed aryl C-H activation, and subsequent alkyne annulation.

Benzylic C\u2212H acylation by cooperative NHC and photoredox catalysis

Methods that enable site selective acylation of sp3 C-H bonds in complex organic molecules are not well explored, particularly if compared with analogous transformations of aromatic and vinylic sp2 C-H bonds. We report herein a direct acylation of benzylic C-H bonds by merging N-heterocyclic carbene (NHC) and photoredox catalysis. The method allows the preparation of a diverse range of benzylic ketones with good functional group tolerance under mild conditions. The reaction can be used to install acyl groups on highly functionalized natural product derived compounds and the C-H functionalization works with excellent site selectivity. The combination of NHC and photoredox catalysis offers options in preparing benzyl aryl ketones.

NHC‐Catalyzed Oxidative Annulation of α,β‐unsaturated Aldehydes with Benzyl Ketones: Direct Access to 4,5,6‐Trisubstituted Dihydropyranones

AbstractA novel and efficient access to polysubstituted dihydropyranones was developed by N‐heterocyclic carbene catalyzed annulation reaction of α,β‐unsaturated aldehydes and benzyl ketones under oxidative conditions. Various α,β‐unsaturated aldehydes with long‐chain aliphatic and aromatic substitution groups were compatible in this transformation, giving the corresponding products in good to excellent yields under mild conditions. This strategy features simple and readily available materials and mild reaction conditions and provides a green and practical method for the rapid synthesis of functionalized dihydropyranones.

Site-selective unidirectional benzylic sp3 C–H oxidation of dodecahydrotriphenylene with RuCl3–NaIO4: formation of benzylic ketones

Dodecahydrotriphenylene, a higher homologue of trindane chemoselectively undergoes unidirectional benzylic sp3 C–H oxidation and the central benzene ring remains intact unlike that in trindane under similar reaction conditions. RuO4 which generally attacks sp2 C–H to form oxidative products is found to give benzylic ketones via sp3 C–H oxidation. Density functional theory (DFT) calculations have also been performed to analyse the potential energy, energy barrier and HOMO–LUMO energy gap of the products.

Synthesis of Benzylic Ketones through Electrochemical Oxidation of Aryl Alkenes

Synthesis of Benzylic Ketones through Electrochemical Oxidation of Aryl Alkenes

Representative model compounds for understanding the pyrolytic behavior of pre-oxidized β-ether-type lignin

To achieve a better understanding of the pyrolysis behavior of pre-oxidized β-ether-type lignin, three Cα=O type dimers with different substituent groups on the aromatic ring were synthesized and analyzed by a simultaneous thermal analysis instrument (STA), in-situ Fourier transform infrared spectroscopy (in-situ FTIR), and pyrolysis-gas chromatography/ mass spectrometry (Py-GC/MS). The results showed that major primary pyrolysis reactions of Cα=O type models normally occurred at 200 to 400 °C, and connecting bridge structures of models were completely destroyed, causing the emission of abundant volatiles. Substituent groups of aromatic rings played direct roles in thermal stability of models, volatiles emission, product characteristics, and secondary reaction pathways of major primary products. Particularly, the aryl–OCH3 group clearly enhanced the reactivity of intramolecular linkages and was an important active functional group for secondary reactions. As major primary products and intermediates, guaiacol and 2-methoxy-benzaldehyde were formed via the cleavage of Cα–O and Cα–Cβ bonds and could also be converted into phenol, benzaldehyde, and 2-methylphenol via rearrangement of aryl–OCH3 into an aryl–CH3 group or –OCH3 group removal. Oxidization of benzylic alcohol to benzylic ketone not only simplified depolymerization pathways, but also resulted in better selectivity of phenolic monomers and a predictable product distribution.