Alkenyl Ketones Research Articles

Photocatalytic Cross-Coupling of Aldehydes and Alkenes for Aryl Vinyl Ketones by a Single Catalyst.

Herein is the first example of photocatalytic cross-coupling of alkenes with aldehydes by a single catalyst without an external photosensitizer and any additives. Irradiation of the aromatic aldehyde and cobaloxime catalyst results in the formation of an acyl radical, which undergoes radical addition with alkene or indole and subsequently β-H elimination to afford alkenyl ketone. The reaction features cheap and readily available raw materials, a broad substrate scope, and mild conditions, even for late-stage derivatization of bioactive compounds.

Diphosphine Ligand‐Enabled Nickel‐Catalyzed Chelate‐Assisted Inner‐Selective Migratory Hydroarylation of Alkenes

AbstractThe precise control of the regioselectivity in the transition metal‐catalyzed migratory hydrofunctionalization of alkenes remains a big challenge. With a transient ketimine directing group, the nickel‐catalyzed migratory β‐selective hydroarylation and hydroalkenylation of alkenyl ketones has been realized with aryl boronic acids using alkyl halide as the mild hydride source for the first time. The key to this success is the use of a diphosphine ligand, which is capable of the generation of a Ni(II)‐H species in the presence of alkyl bromide, and enabling the efficient migratory insertion of alkene into Ni(II)‐H species and the sequent rapid chain walking process. The present approach diminishes organosilanes reductant, tolerates a wide array of complex functionalities with excellent regioselective control. Moreover, this catalytic system could also be applied to the migratory hydroarylation of alkenyl azahetereoarenes, thus providing a general approach for the preparation of 1,2‐aryl heteroaryl motifs with wide potential applications in pharmaceutical discovery.

Diphosphine Ligand-Enabled Nickel-Catalyzed Chelate-Assisted Inner-Selective Migratory Hydroarylation of Alkenes.

The precise control of the regioselectivity in the transition metal-catalyzed migratory hydrofunctionalization of alkenes remains a big challenge. With a transient ketimine directing group, the nickel-catalyzed migratory β-selective hydroarylation and hydroalkenylation of alkenyl ketones has been realized with aryl boronic acids using alkyl halide as the mild hydride source for the first time. The key to this success is the use of a diphosphine ligand, which is capable of the generation of a Ni(II)-H species in the presence of alkyl bromide, and enabling the efficient migratory insertion of alkene into Ni(II)-H species and the sequent rapid chain walking process. The present approach diminishes organosilanes reductant, tolerates a wide array of complex functionalities with excellent regioselective control. Moreover, this catalytic system could also be applied to the migratory hydroarylation of alkenyl azahetereoarenes, thus providing a general approach for the preparation of 1,2-aryl heteroaryl motifs with wide potential applications in pharmaceutical discovery.

Visible-Light-Induced Difunctionalization of Alkenyl Ketones with α-Carbonyl Alkyl Bromide: Concomitant Installation of C-C Bonds.

The visible-light-promoted difunctionalization of alkenyl ketones has been developed for easy access of various tetralones, cyclopropane, or alkenyl migration compounds. With fac-[Ir(ppy)3] as the photocatalyst, alkenyl ketones captured the α-carbonyl alkyl radical and evolved through intramolecular cyclization and the elimination of a proton to give the difunctionalized products. This strategy is characterized by good yields, mild reaction conditions, and outstanding functional group tolerance.

Construction of C(sp2)-Si Bonds via Ligand-Promoted C-C Bonds Cleavage of Unstrained Ketones.

Herein, we report an efficient palladium-catalyzed silylation of aryl and alkenyl ketones via C-C bond cleavage and C-Si bond formation. This protocol features high efficiency and broad substrate scope. Further applications in the late-stage diversification of biologically important molecules demonstrate the synthetic utility of this method.

RuH‐Catalyzed Synthesis of 1,3‐Diaryl Ketones via Cross‐Coupling of Aromatic Enones with Aromatic Aldehydes and Mechanistic Insights

AbstractRuHCl(CO)(PPh3)3‐catalyzed cross‐coupling of alkenyl ketones with aldehydes has been extended to the synthesis of 1,3‐diaryl 1,3‐diketones. The reaction has been successfully applied to the synthesis of PPT (propyl pyrazole triol), a selective estrogen receptor modulator compound. A study of the stoichiometric reaction of phenyl vinyl ketone with RuHCl(CO)(PPh3)3 has revealed that the β‐ruthenium ketone PhCOCH2CH2RuCl(CO)(PPh3)2, a five‐membered ruthenacycle is formed with liberation of one molecule of PPh3. The observed catalytic activity of this ruthenacycle in the presence of PPh3 suggests that it serves as a resting state, in equilibrium with an oxa‐π‐allyl ruthenium species, which is the key coupling partner with aldehyde substrates.magnified image

Photoredox/nickel dual catalyzed stereospecific synthesis of distal alkenyl ketones.

The selective C-C bond deconstruction/refunctionalization via a photoredox/nickel dual-catalyzed hydroalkylation of alkynes is developed under mild reaction conditions. In this protocol, a broad range of alkyl- and aryl-alkynes could react smoothly with cycloalkanols, affording the corresponding distal and site-specific vinyl-substituted ketones with high yields and excellent regioselectivities. Moreover, DFT calculations verified that the electron-rich behavior of aromatics and weak Brønsted bases have a common effect on the photocatalytic oxidant ring-opening of cyclobutanols.

From selective transfer hydrogenation to selective hydrogen auto-transfer process: An efficient method for the synthesis of alkenyl ketones via iridium-catalyzed α-alkylation of ketones with alkenyl alcohols

A strategy for the synthesis of alkenyl ketones via the α-alkylation of ketones with alkenyl ketones has proposed and accomplished. In the presence of a metal–ligand bifunctional catalyst [Cp*Ir(2,2′-bpyO)(H2O)], a series of desirable products were obtained in high yields. Mechanistic investigation revealed that functional groups in the ligand are crucial for the activity of catalyst and selective transfer hydrogenation is the determining step of the formation of alkenyl ketones as products. Notably, the present research exhibited also the unique potential of metal–ligand bifunctional catalysts for the activation of unsaturated alcohols as electrophiles for hydrogen auto-transfer process.

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.

Ni-Catalyzed 1,2-Diarylation of Alkenyl Ketones: A Comparative Study of Carbonyl-Directed Reaction Systems.

A nickel-catalyzed 1,2-diarylation of alkenyl ketones with aryl iodides and arylboronic esters is reported. Ketones with a variety of substituents serve as effective directing groups, offering high levels of regiocontrol. A representative product is diversified into a wide range of useful products that are not readily accessible via existing 1,2-diarylation reactions. Preliminary mechanistic studies shed light on the binding mode of the substrate, and Hammett analysis reveals the effect of electronic factors on initial rates.

Origin of diastereoselectivity and catalytic efficiency on Isothiourea-mediated cyclization of carboxylic acid with alkenyl ketone

Asymmetric synthesis plays an important role in organic chemistry. To this end, a theoretical study of the possible mechanisms, origin of diastereoselectivity, and efficiency of catalysts on isothiourea-catalyzed asymmetric cyclization of carboxylic acids and alkenyl ketones was performed by using density functional theory (DFT). The calculated results show that the diastereoselectivity can be induced in the CC bond formation step involved in the [4 + 2] cycloaddition. The atoms-in-molecules (AIM) analysis shows that bonding interaction and hydrogen bonds contribute significantly for the favorability of SS-configured product. The catalytic efficiency of isothioureas was explored and predicted by nucleophilic atom energy Ea-.

Iron-Catalyzed Decarboxylative Olefination of Unstrained Carbon-Carbon Bonds Relying on Alkoxyl Radical Induced Cascade.

An iron-catalyzed decarboxylative olefination of unstrained carbon-carbon bonds via alkoxyl radical induced C-C bond cleavage is presented. This protocol features mild conditions (room temperature, redox-neutral), good substrate scope and functional group compatibility, as well as excellent stereoselectivity, thus providing a facile access to the distal alkenyl ketones.

ChemInform Abstract: Copper(I)‐Catalyzed Diastereoselective Borylative exo‐Cyclization of Alkenyl Aryl Ketones.

Copper(I)-catalyzed diastereoselective borylative exo-cyclization of alkenyl ketones with bis(pinacolato)diboron is reported. The reaction of alkenyl aryl ketones under a CuCl/Xantphos catalyst system provides four- or five-membered-ring syn-2-(borylmethyl)cycloalkanol derivatives in good yields with high syn selectivities. The utility of this method is demonstrated by further transformations of the cyclic products.

ChemInform Abstract: Synthesis of Functionalized Pyrazoles via Vanadium‐Catalyzed C—N Dehydrogenative Cross‐Coupling and Fluorescence Switch‐On Sensing of BSA Protein.

AbstractAlkenyl hydrazones are generated in‐situ from alkenyl ketones and arylhydrazines and give pyrazoles using commercially available, nontoxic, and recyclable VOSO4 as the catalyst and air as the oxidant.

Copper(I)-Catalyzed Diastereoselective Borylative Exo-Cyclization of Alkenyl Aryl Ketones

Copper(I)-catalyzed diastereoselective borylative <i>exo</i>-cyclization of alkenyl ketones with bis(pinacolato)diboron is reported. The reaction of alkenyl aryl ketones under a CuCl/Xantphos catalyst system provides four- or five-membered-ring <i>syn</i>-2-(borylmethyl)cycloalkanol derivatives in good yields with high <i>syn</i> selectivities. The utility of this method is demonstrated by further transformations of the cyclic products.

Synthesis and reactivity of di- and tri-metallic complexes containing the TpRu(PPh3) fragment

Treatment of the TpRu complex Tp(PPh3)2RuCl (Tp = HB(pz)3, pz = pyrazolyl) (1) with ethynylferrocene in MeOH gave the trimetallic alkenyl ketone complex Tp(PPh3)Ru{C(Fc) = CHC(O)CH2(Fc)} (Fc=(η5-C5H4)Fe(η5-C5H5)) (2). Intriguingly, a similar reaction was performed in the presence of NaOMe afforded the dimetallic acetylide complex Tp(PPh3)2Ru–CC-Fc (3). A number of new cationic vinylidene complexes [Tp(PPh3)2Ru{ = CC(Fc)CH2R}]+ [4a, R = CN; 4b, R = HCCH2; 4c, R = CHC(CH3)2; 4d, R = Ph] have been prepared by electrophilic addition of organic halides to complex 3. The substitution reaction of 4a with pyrazole is followed by an intramolecular nucleophilic addition of the nitrogen atom at the α-carbon atom and removal of HI to afford the metallacyclic complex, Tp(PPh3)Ru(C3H3NN)CC(Fc) CH2CN (5a). All of the complexes are identified by spectroscopic methods as well as elementary analysis. The structure of 2 has been determined by X-ray diffraction analysis. Pathways for the synthesis of these compounds are proposed.

ChemInform Abstract: A Novel Efficient Route for Acid‐Catalyzed Synthesis of α,β‐Alkynyl/Alkenyl Ketones.

AbstractAlthough aliphatic alkynes form alkynyl ketones using AgOTf/TfOH as the catalyst, no alkenyl ketones are observed with catalytic amounts of TfOH.

A Novel Efficient Route for Acid-Catalyzed Synthesis of α,β-Alkynyl/Alkenyl Ketones

Herein, we have developed a simple and efficient synthesis of α,β-alkynyl/alkenyl ketone derivatives by acid-catalyzed reactions of 2,6-dimethyl-<i>N</i>-(4-methylbenzylidene)aniline and alkynes. This methodology provides a novel pathway for the synthesis of α,β-alkynyl/alkenyl ketones via acid-catalyzed coupling reactions and subsequent silica gel catalyzed hydrolysis. Characterized by wide substrate scope, mild reaction conditions, and good to excellent yields this protocol may aid the further development of the C–C coupling reactions.

Protonation‐Triggered Generation of Acylcobalt Species from Alkyne–[Co2(CO)6] Complexes and Their Reaction with Alkenes

An efficient protocol for the generation of acylcobalt species from alkyne-[Co(2)(CO)(6)] complexes is realized by treatment of the complexes with AcOH and pyridine. The generated acylcobalt species smoothly underwent addition reactions with various alkenes to give alkyl alkenyl ketones in good yield.