Acyclic Ketones Research Articles

1,4-Reduction of α,β-Unsaturated Ketones through Rhodium(III)-Catalyzed Transfer Hydrogenation

AbstractA rhodium(III)-catalyzed transfer hydrogenation of unsaturated ketones was developed. The simple catalytic system could be used for the 1,4-reduction of unsaturated cyclic, acyclic ketones, diketones, as well as β-ketoester, and a variety of functional groups were well-tolerated, affording products in moderate to excellent yields.

Reaction of α-Diazopyrroles with Enamines: Synthesis of Pyrrolo[2,1-c][1,2,4]triazines and α-(1,2,5-Triazapenta-1,3-dienyl)pyrroles.

α-Diazopyrroles selectively react with enamines at room temperature to give either (4+2)-cycloaddition-dehydroamination cascade products, pyrrolo[2,1-c][1,2,4]triazines, or azo coupling products. The reaction was used for the synthesis of functionalized ortho-fused heterocycles with new tetrahydrobenzo[e]pyrrolo[2,1-c][1,2,4]triazine and tetrahydro-6H-cyclohepta[e]pyrrolo[2,1-c][1,2,4]triazine frameworks. Unstable azo compounds, 2-[(2-aminovinyl)diazenyl]pyrroles, were obtained from enamines of tetralone or acyclic ketones. According to the density functional theory calculations, (4+2)-cycloaddition of α-diazopyrroles with enamines proceeds in a nonconcerted manner via the zwitterionic intermediate, which undergoes cyclization to pyrrolotriazine or a competitive 1,5-prototropic shift leading to the formation of azo coupling product.

MARIGOLD BIOPESTICIDE AS AN ALTERNATIVE TO CONVENTIONAL CHEMICAL PESTICIDES

Marigold (Tagetes spp) which is considered to be a traditional medicinal plant, has significant therapeutic value and is used in treatment of a number of ailments. This review mainly emphasizes on the role of Tagetes as biopesticides especially as insecticide, mosquitocide, nematicide, bactericide and fungicide. The essential oils obtained from the aerial part of Tagetes mainly contain monoterpene hydrocarbons (ocimenes, limonene, terpinene etc) and acyclic monoterpene ketones (tagetones, dihydrotagetone and tagetenone) in addition to lower amount of sesquiterpene and oxygenated compounds. These components are mainly responsible for insecticidal, larvicidal and mosquitocidal property. On the other hand species of Tagetes also show strong nematicidal effect .Thus they can be used to suppress nematode species in the field by different techniques such as crop rotation or intercropping system or by exterting allelopahic effect. Tagetes can show a remarkable biochemical interaction known as allelopathy by producing a potentially bioactive component α-therthienyl that is mainly responsible for nematicidal action. This sulphur containing compound has nematicidal, insecticidal, fungicidal, antiviral and cytotoxic effect. The essential oil of Tagetes also shows strong bactericidal and fungicidal effect against a number of plant pathogenic bacteria and fungi. This review not only discusses the role of marigold as biopesticides especially as insecticides, mosquitocides, nematicides, bactericides and fungicide but also elucidates its ecofriendly potential to be used in the agricultural field as an alternative to chemical synthetic pesticides.

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.

Syntheses of N-acylhydrazones of 2-hydroxy-3,5-dinitrobenzohydrazide, and their Conversion into 3-Acetyl-2,3-dihydro-1,3,4-oxadiazole

N-Acylhydrazones 11-17 were prepared via reaction of 2-hydroxy-3,5-dinitrobenzohydrazide 3 with aromatic aldehydes 4-6 or with aromatic ketone 7 or aliphatic acyclic ketone 8 and cyclic aliphatic ketones 9-10 under reflux in ethanol. Conversion of hydrazide hydrazone 17 into N-acetyl-1,3,4-oxadiazole derivative 19 was achieved via reaction with acetic anhydride 18. The products were characterized by MS, 1H-NMR and 13C-NMR. The structure of 19 was confirmed by X-ray analysis. Compound 19 was evaluated for in vitro antibacterial activity against two microorganisms (S. aureus and E. coli ). The obtained results showed that this compound has good inhibition against the tested bacterial pathogens by micro-dilution method with MIC 15.1 μg.

Conformationally Biased Ketones React Diastereoselectively with Allylmagnesium Halides.

The addition of the highly reactive reagent allylmagnesium halide to α-substituted acyclic chiral ketones proceeded with high stereoselectivity. The stereoselectivity cannot be analyzed by conventional stereochemical models because these reactions do not conform to the requirements of those models. Instead, the stereoselectivity arises from the approach of the nucleophile to the most accessible diastereofaces of the lowest-energy conformations of the ketones. High stereoselectivity is expected, and the stereochemical outcome can be predicted, with conformationally biased ketones that have sterically distinguishable diastereofaces wherein only one face is accessible for nucleophilic addition. The conformations of the ketones can be determined by a combination of computational modeling and, in some cases, structure determination by X-ray crystallography.

Titanium-Mediated Domino Cross-Coupling/Cyclodehydration and Aldol-Addition/Cyclocondensation: Concise and Regioselective Synthesis of Polysubstituted and Fused Furans.

Titanium enolates, in situ-generated from readily available ketones and titanium tetraisopropoxide, undergo domino cross-coupling/cyclodehydration or domino Aldol-addition/cyclocondensation with α-chloroketones to provide synthetically valuable furan derivatives. The domino process tolerates a variety of cyclic and acyclic ketones and chloroketones, producing polysubstituted furans and bi-, tri-, and tetracyclic fused furans.

Asymmetric Catalytic Rearrangements with α-Diazocarbonyl Compounds.

α-Diazocarbonyl compounds serve as nucleophiles, dipoles, carbene precursors, and rare electrophiles, enabling a vast array of organic transformations under the influence of metal catalysts. Among them, rearrangement processes are attractive and provide straightforward and efficient accesses to one-carbon extension adducts or heteroatom-containing molecules. The reactions occur upon the release of dinitrogen after nucleophilic addition or before ylide formation. Although significant progress has been made for these two types of rearrangement reactions, the issue of enantiocontrol is challenging because the final optically enriched products are generated via multistep transformations and the inherent spacial arrangement of the intermediates has more or less influence on the regio- and enantioselectivity.In this Account, we collected several rearrangements of α-diazocarbonyl compounds, showcasing the efficient catalysts and tailored strategies for tackling enantioselective varieties of these two types of rearrangement reactions. Our research group initiated the catalytic asymmetric reactions of α-diazocarbonyl compounds during the development of chiral Feng N,N'-dioxide-metal complex catalysts and others. As a kind of useful chiral Lewis acid catalyst chiral N,N'-dioxide-metal complexes are favorable for the activation of various carbonyl compounds, accelerating the diastereo- and enantioselective nucleophilic addition of α-diazoesters and the sequential rearrangements in either an intermolecular or intramolecular manner. Aldehydes, acyclic and cyclic ketone derivatives, and α,β-unsaturated ketones could participate in efficient asymmetric homologation reactions, and an obvious ligand-acceleration effect is observed in these processes. For example, the Roskamp-Feng reaction of aldehydes gives optically active β-ketoesters through a H-shift, overwhelming the aryl group shift or oxygen attack. The shift preference and enantiocontrol in the homologation of acyclic and cyclic ketone derivatives could be under excellent control of the chiral catalysts. An unusual electrophilic α-amination of aryl/alkyl ketones and even a complicated homologation/dyotropic rearrangement/interconversion/[3 + 2] cycloaddition cascade used to construct dimeric polycyclic compounds were discovered as a result of the selection of chiral ligands and additives. On the basis of the understanding of the interaction of the functional group with N,N'-dioxide-metal complexes in catalysis and the key enantio-determining issues in ylide-based rearrangements, we designed new α-diazocarbonyl compounds by introducing a pyrazole-1-carboxyl group as the acceptor unit, which could benefit the formation of both carbenoid species and the chiral catalyst-bound ylides to deliver stereoselectivity. Taking advantage of Ni(II) or Co(II) complexes of Feng N,N'-dioxide ligands, we realized several kinds of enantioselective [2,3]-sigmatropic rearrangements, such as the Doyle-Kirmse reaction with allylic sulfides or selenides, [2,3]-Stevens rearrangements of vinyl-substituted α-diazo pyrazoleamides with thioacetates, Sommelet-Hauser rearrangements of aryl-substituted α-diazo pyrazoleamides with thioamides, and thio-Claisen rearrangements of 2-thio-indoles as well. Moreover, this strategy was shown to be applicable to highly γ-selective and enantioselective insertion into N-H bonds of secondary amines with vinyl-substituted α-diazo pyrazoleamides.

Volatile Composition and Biological Activities of Tagetes (Marigold): An Overview

Tagetes commonly known as wild marigold is a plant belonging to family Asteraceae. Tagetes minuta L., commonly known as African marigold, is reputed as a source of ‘Tagetes oil’ of trade that finds an extensive use in food, flavoring, pharmaceutical, perfumery and cosmetic industry. The plant is valued for its essential oil, which is present almost in every part of the plant with little percentage in the stem and roots. The plant is native to South America and has been introduced to many countries since the time of Spanish conquest. Many species of this genus, such as T. minuta, T. erecta, T. patula, and T. tenuifolia, are cultivated as ornamental plants and studied for their medicinal properties based on the basis of their use in folk medicine. Different parts of the Tagetes species are used as remedies to treat various health problems, including dental, stomach, intestinal, emotional, and nervous disorders and muscular pain, across the world. Furthermore, these plants are studied in the field of agriculture for their fungicidal, bactericidal, and insecticidal activities. The plant occurs in temperate forests and mountain regions of the world. Himachal Pradesh, Uttrakhand and Jammu & Kashmir are the main sources of “Tagetes oil” in India where it occurs at an altitude of 1000 to 2500m AMSL. The major constituents (90-95%) of Tagetes minuta essential oil are Z-ß-ocimene, limonene (hydrocarbons) and acyclic unsaturated monoterpenes ketones, dihydrotagetone, tagetones (E, Z) and ocimenones (E, Z). The plant possess pharmacological, phytotoxic effect, antibacterial and antifungal effect, insecticidal properties, nematicidal properties, antiviral and antimicrobial activity and also find use in perfume and flavour industry. Its oil has a great demand, so the species holds a lot of potential for undertaking its large-scale cultivation.

Enantioselective Ni/N-Heterocyclic Carbene-Catalyzed Redox-Economical Coupling of Aldehydes, Alkynes, and Enones for Rapid Construction of Acyclic All-Carbon Quaternary Stereocenters.

Acyclic quaternary carbon stereocenters exist widely in natural products and bioactive molecules, but their enantioselective construction remains a prominent challenge. In particular, multicomponent enantioselective couplings of simple precursors to acyclic all-carbon quaternary stereocenters are very rare. We describe herein an N-heterocyclic carbene (NHC)-Ni catalyzed redox-economical three-component reaction of aldehydes, alkynes, and enones that proceeds in a highly chemo-, regio-, and enantioselective manner. A wide variety of valuable acyclic α-quaternary chiral ketones were synthesized in a single step with 100% atom economy. This reaction proceeds through the formation of a transient cyclic enolate followed by an aldol reaction/ring-opening sequence. The strategy is expected to inspire new and efficient approaches to generate other acyclic quaternary stereocenters.

Visible-Light Photoredox-Catalyzed Dicarbofunctionalization of Styrenes with Oxime Esters and CO2: Multicomponent Reactions toward Cyanocarboxylic Acids and γ-Keto Acids.

A photoredox-catalyzed dicarbofunctionalization of styrenes with oxime esters and CO2 has been achieved. Notably, a series of four-, five-, or six-membered cyclic ketone oximes worked well to furnish a wide range of ε-, ζ-, and η-cyanocarboxylic acids in good yields. Furthermore, a series of γ-keto acids also could be obtained by employing acyclic ketone oxime esters as the carbonyl radical precursor. It provides convergent access to diverse biologically important cyanocarboxylic and γ-keto acids.

Asymmetric construction of acyclic quaternary stereocenters via direct enantioselective additions of \u03b1-alkynyl ketones to allenamides

Acyclic quaternary stereocenters are widely present in a series of biologically active natural products and pharmaceuticals. However, development of highly efficient asymmetric catalytic methods for the construction of these privileged motifs represents a longstanding challenge in organic synthesis. Herein, an efficient chiral phosphoric acid catalyzed direct asymmetric addition of α-alkynyl acyclic ketones with allenamides has been developed, furnishing the acyclic all-carbon quaternary stereocenters with excellent regioselectivities and high enantioselectivities. Extensive and detailed experimental mechanistic studies were performed to investigate the mechanism of this reaction. Despite a novel covalent allyl phosphate intermediate was found in these reactions, further studies indicated that a SN2-type mechanism with the ketone nucleophiles is not very possible. Instead, a more plausible mechanism involving the elimination of the allyl phosphate to give the α,β-unsaturated iminium intermediate, which underwent the asymmetric conjugate addition with the enol form of ketone nucleophiles under chiral anion catalysis, was proposed. In virtue of the fruitful functional groups bearing in the chiral products, the diverse derivatizations of the chiral products provided access to a wide array of chiral scaffolds with quaternary stereocenters.

Recent Advances in Transition-Metal-Catalyzed C–H Addition to Nitriles

AbstractTransition-metal-catalyzed C–H bond addition to nitriles has emerged as a powerful synthetic approach for the construction of C–C bonds in organic synthesis. Due to the merits of atom- and step-economy, as well the easy availability of the starting materials, these transformations not only deliver acyclic aryl ketone products with nitriles­ as C-building blocks, but can also be utilized for the highly efficient­ assembly of azaheterocyclic skeletons using nitriles as C–N building blocks. This short review summarizes recent progress on transition-metal-catalyzed C–C bond-forming reactions based on C(sp2)–H and C(sp3)–H additions to nitriles.1 Introduction2 Palladium-Catalyzed C–H Addition to Nitriles2.1 Palladium-Catalyzed C–H Addition to Nitriles for the Preparation of Ketone (Imine) Products2.2 Palladium-Catalyzed C–H Addition to Nitriles for the Preparation of Azaheterocycles2.3 Palladium-Catalyzed C–H Addition to Nitriles/1,2-Rearangement3 Other Transition-Metal-Catalyzed C–H Additions to Nitriles4 Summary and Outlook

Development and Mechanistic Studies of the Iridium-Catalyzed C-H Alkenylation of Enamides with Vinyl Acetates: A Versatile Approach for Ketone Functionalization.

Ketone functionalization is a cornerstone of organic synthesis. Herein, we describe the development of an intermolecular C-H alkenylation of enamides with the feedstock chemical vinyl acetate to access diverse functionalized ketones. Enamides derived from various cyclic and acyclic ketones reacted efficiently, and a number of sensitive functional groups were tolerated. In this iridium-catalyzed transformation, two structurally and electronically similar alkenes-enamide and vinyl acetate-underwent selective cross-coupling through C-H activation. No reaction partner was used in large excess. The reaction is also pH- and redox-neutral with HOAc as the only stoichiometric by-product. Detailed experimental and computational studies revealed a reaction mechanism involving 1,2-Ir-C migratory insertion followed by syn-β-acetoxy elimination, which is different from that of previous vinyl acetate mediated C-H activation reactions. Finally, the alkenylation product can serve as a versatile intermediate to deliver a variety of structurally modified ketones.

Development and Mechanistic Studies of the Iridium‐Catalyzed C−H Alkenylation of Enamides with Vinyl Acetates: A Versatile Approach for Ketone Functionalization

AbstractKetone functionalization is a cornerstone of organic synthesis. Herein, we describe the development of an intermolecular C−H alkenylation of enamides with the feedstock chemical vinyl acetate to access diverse functionalized ketones. Enamides derived from various cyclic and acyclic ketones reacted efficiently, and a number of sensitive functional groups were tolerated. In this iridium‐catalyzed transformation, two structurally and electronically similar alkenes—enamide and vinyl acetate—underwent selective cross‐coupling through C−H activation. No reaction partner was used in large excess. The reaction is also pH‐ and redox‐neutral with HOAc as the only stoichiometric by‐product. Detailed experimental and computational studies revealed a reaction mechanism involving 1,2‐Ir‐C migratory insertion followed by syn‐β‐acetoxy elimination, which is different from that of previous vinyl acetate mediated C−H activation reactions. Finally, the alkenylation product can serve as a versatile intermediate to deliver a variety of structurally modified ketones.

Constructing Tertiary Alcohols with Vicinal Stereocenters: Highly Diastereo- and Enantioselective Cyanosilylation of α-Branched Acyclic Ketones and Their Kinetic Resolution

We report the first highly diastereo- and enantioselective C–C bond-forming reaction of racemic α-branched ketones to construct tertiary alcohols with adjacent stereocenters. Accordingly, a highly ...

Nickel-Catalyzed Regioselective Alkenylarylation of γ,δ-Alkenyl Ketones via Carbonyl Coordination.

We disclose a nickel-catalyzed reaction, which enabled us to difunctionalize unactivated γ,δ-alkenes in ketones with alkenyl triflates and arylboronic esters. The reaction was made feasible by the use of 5-chloro-8-hydroxyquinoline as a ligand along with NiBr2 ⋅DME as a catalyst and LiOtBu as base. The reaction proceeded with a wide range of cyclic, acyclic, endocyclic and exocyclic alkenyl ketones, and electron-rich and electron-deficient arylboronate esters. The reaction also worked with both cyclic and acyclic alkenyl triflates. Control experiments indicate that carbonyl coordination is required for the reaction to proceed.

Nickel‐Catalyzed Regioselective Alkenylarylation of γ,δ‐Alkenyl Ketones via Carbonyl Coordination

AbstractWe disclose a nickel‐catalyzed reaction, which enabled us to difunctionalize unactivated γ,δ‐alkenes in ketones with alkenyl triflates and arylboronic esters. The reaction was made feasible by the use of 5‐chloro‐8‐hydroxyquinoline as a ligand along with NiBr2⋅DME as a catalyst and LiOtBu as base. The reaction proceeded with a wide range of cyclic, acyclic, endocyclic and exocyclic alkenyl ketones, and electron‐rich and electron‐deficient arylboronate esters. The reaction also worked with both cyclic and acyclic alkenyl triflates. Control experiments indicate that carbonyl coordination is required for the reaction to proceed.

Interrupted Curtius Rearrangements of Quaternary Proline Derivatives: A Flow Route to Acyclic Ketones and Unsaturated Pyrrolidines.

Conversion of N-Boc-protected quaternary proline derivatives under thermal Curtius rearrangement conditions was found to afford a series of ring-opened ketone and unsaturated pyrrolidine products instead of the expected carbamate species. The nature of the substituent on the quaternary carbon thereby governs the product outcome due to the stability of a postulated N-acyliminium species. A continuous flow process with in-line scavenging was furthermore developed to streamline this transformation and safely create products on a gram scale.

Propargylic Amination Enabled the Access to Enantioenriched Acyclic α-Quaternary α-Amino Ketones.

A propargylic amination approach toward chiral acyclic α-quaternary α-amino ketones is described. This Cu-catalyzed procedure could be performed open to air using commercially available amines as nucleophiles. The key to success is the use of rationally designed propargylic cyclic carbonates as substrates, which can generate a Cu-bonded enolate zwitterionic intermediate upon decarboxylation. This protocol features wide functional group tolerance and high asymmetric induction, with typical ee value higher than 93%, and thus advances a great step forward in the challenging synthesis of acyclic chiral α-quaternary α-amino ketones.