Aryl Vinyl 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.

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction.

We describe the use of bismuth(III) triflate as an efficient and environmentally friendly catalyst for the Nazarov reaction of aryl vinyl ketones, leading to the synthesis of 3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones. By changing the temperature and reaction time, it was possible to modulate the reactivity, allowing the synthesis of two distinct product classes (3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones) in good to excellent yield. The reaction did not require additives and was insensitive to both air and moisture. Preliminary biological evaluation of some indanones showed a promising profile against some human cancer line cells.

Efficient Approach for the Synthesis of Aryl Vinyl Ketones and Its Synthetic Application to Mimosifoliol with DFT and Autodocking Studies.

An efficient and elegant method was developed for the preparation of substituted phenyl vinyl ketones using low-cost and commercially available ethyl chloroformate and diisopropylethylamine as reagents. This methodology was also applied to the synthesis of natural products such as mimosifoliol and quinolines. Frontier molecular orbital (FMO) studies on mimosifoliol were carried out to understand its chemical reactivity. Electron localization function (ELF) and localized orbital locator (LOL) analysis gave information about localized and delocalized electrons. Reduced density gradient (RDG) analysis gave information on steric, van der Waals, and hydrogen-bonding interactions. Molecular electrostatic potential (MEP) and Fukui functions gave information about nucleophilic and electrophilic attack. Nonlinear optical (NLO) analysis represented the mimosifoliol good NLO material. Molecular docking showed that the mimosifoliol compound had effectively inhibited the aspulvinone dimethylallyltransferase enzyme.

Experimental Investigation of Microwave-Specific Effect on Nazarov Cyclization

Abstract A copper-catalyzed Nazarov cyclization using an aryl vinyl ketone derivative containing a 1,3-dicarbonyl moiety was carried out under microwave irradiation conditions. The Nazarov cyclization was dramatically accelerated and the kinetic rate of the microwave irradiation was 5.8 times faster than that by conventional heating conditions. A theoretical interpretation of the microwave-specific effect as physical phenomena of the molecules based on chemical kinetics and dynamics was attempted. The microwave-specific effect in terms of the pre-exponential factor in the Arrhenius equation is discussed, thus a hypothesis of the conformational equilibrium activation by microwaves is theoretically supported. To further investigate the microwave-specific effect, a catalytic asymmetric Nazarov cyclization was finally performed. As the enantioselectivity is defined as the function of the reaction temperature, observation of the same enantioselectivity implies the same reaction temperature. Interestingly, when the asymmetric Nazarov cyclization was conducted using a chiral copper catalyst, the Nazarov reaction was subsequently enhanced by the microwave irradiation without any loss of the enantioselectivity. It is suggested that the drastic enhancement with the retention of the enantioselectivity was caused not by a thermal effect, but by a microwave-specific effect on the enantioselective reaction.

Magnesium-Promoted Reductive Carboxylation of Aryl Vinyl Ketones: Synthesis of γ-Keto Carboxylic Acids.

Direct reductive carboxylation of easily prepared aryl vinyl ketones under the atmosphere of carbon dioxide led to the selective formation of γ-keto carboxylic acids in 38-86% yields. The reaction is characterized by the carbon-carbon bond formation of carbon dioxide at the β-position of enone, with the use of magnesium turnings that can be easily handled as the reducing agent and the eco-friendly reaction conditions such as no pressuring, no lower or higher reaction temperature, and short reaction time. This protocol showed a wide substrate scope and provided a useful and convenient alternative to access biologically important γ-keto carboxylic acids.

The role of terphenyl-containing carboxylic acid in the oligomerization of aryl vinyl ketone.

The molecular structure of 8-((4''-((1R,4S)-4-butylcyclohexyl)-2'-chloro-[1,1',4',1''-terphenyl]-4-yl)oxy)oct-1-en-3-one (TERPh-VK) and 6-((4''-((1R,4S)-4-butylcyclohexyl)-2'-chloro-[1,1':4',1''-terphenyl]-4-yl)oxy) hexanoic acid (TERPh-COOH) is analyzed by FTIR spectroscopy. Vinyl ketone isolated from solution forms a thermodynamically unstable cis conformation due to probable peculiarities of the crystal structure formation. The heating of this substance above 100 °C results in the cis-trans transformation with the simultaneous opening of the vinyl double bond. The mixing of the above terphenyls in solution followed by the isolation of the solid product results in the formation of the TERPh-VK/TERPH-COOH associated species due to the H-bonding between ketone and carboxylic groups. The thermal transformation of the H-bond associated species resulted in the formation of the oligo (TERPh-VK)/TERPh-COOH associated species.

A Facile Approach to Access Multi‐Substituted Indenes via Nazarov Cyclisation of Aryl, Vinyl, and Alkyl/Aryl Carbinols

AbstractA divergent approach to highly substituted functionalized indenes has been developed. The two‐step reaction involving nucleophilic addition reaction of aryl vinyl ketone, an ideal intermediate with aryl or alkyl nucleophilic reagent, followed by electrocyclic reaction (Nazarov cyclization) in the presence of Lewis acid catalyst afforded indene derivatives in good to excellent yield.

Rhodium-Catalyzed Reductive trans-Alkylacylation of Internal Alkynes via a Formal Carborhodation/C-H Carbonylation Cascade.

A rhodium-catalyzed reductive annulation cascade reaction that consists of a formal anti-carborhodation of a C≡C bond and an aromatic C-H carbonylation cascade for producing cyclopenta[de]quinoline-2,5(1H,3H)-diones is described. This method uses the Mn reductant to reductively regenerate the active rhodium species, hence obviating the need for prefunctionalization, and represents a new route to the carbonylation of aromatic C-H bonds with alkynes leading to aryl vinyl ketone frameworks.

Domino Synthesis of 3‐Alkyliden‐2,3‐Dihydro‐4‐Quinolones

AbstractThe synthesis of 3‐alkyliden‐2,3‐dihydro‐4‐quinolones has been accomplished in a domino fashion through a three‐step sequence that comprised an initial aza‐Baylis‐Hillman reaction, followed by a 1,3‐rearrangement and an intramolecular amination. Starting from readily available aryl vinyl ketones and N‐tosyl imines, the reaction with PPh3, CsOAc and CuI in CH3CN gave rise, in good overall yields, to final 3‐alkyliden‐4‐quinolone derivatives, valuable scaffolds in medicinal chemistry. The simultaneous addition of two bases, PPh3 and CsOAc, was found to be crucial for the success of the process. While PPh3 promoted the reversible aza‐Baylis‐Hillman reaction, CsOAc triggered the subsequent 1,3‐rearrangement, which shifted the initial equilibrium and allowed to complete the synthetic sequence upon the addition of CuI.magnified image

N-Heterocyclic Carbene-Catalyzed Olefination of Aldehydes with Vinyliodonium Salts To Generate α,β-Unsaturated Ketones

An organocatalyzed metal-free, direct olefination of aldehydes with vinyliodonium salts has been achieved by an N-heterocyclic carbene-promoted C-H bond activation. The reaction proceeds under very mild conditions, delivering a range of (hetero)aryl-vinyl ketones in good yields. The retention of the double bond configuration is uniformly observed, and the application of 2-methoxyphenyl auxiliary group in iodonium salts secures a complete selectivity of the vinyl transfer.

Catalytic Efficient Nazarov Reaction of Unactivated Aryl Vinyl Ketones via a Bidentate Diiron Lewis Acid Activation Strategy

AbstractA catalytic highly efficient Nazarov reaction of unactivated aryl vinyl ketones has been accomplished by employing aryl boric acid/Fe(OTf)3. Significant progress was obtained in utilizing an extremely broad substrate scope, giving indanones in high yields with high regioselectivities and diastereoselectivities. The mechanistic investigation supports a bidentate diiron Lewis acid catalysis, and the strong double electrophilic activation of aryl vinyl ketones via simultaneous coordination plays a key role in achieving a high reaction efficiency.magnified image

Multistereocenter-Containing Cyclopentanoids from Ynamides via Oxazolidinone-Controlled Nazarov Cyclization.

Achieving ready-enantioselective access to multistereocenter-containing cyclopentyl rings is an area of great significance to organic synthesis. In this work, we describe a general protocol for accessing multistereocenter-containing cyclopentanoids from simple N-alkynyloxazolidinones (Ox-ynamides). This protocol involves conversion of Ox-ynamides into Ox-activated divinyl and aryl vinyl ketones that undergo facile Nazarov cyclization with excellent chemo-, regio-, and stereocontrol. The Ox auxiliary directs all aspects of reactivity and selectivity, both in the electrocyclization and in the subsequent transformations of the resulting oxyallyl intermediate. Stereoinduction in the electrocyclization results from a "coupled-torque" mechanism in which rotation of the Ox group, driven by increasing orbital overlap of the nitrogen lone pair with the incipient oxyallyl cation, is coupled with the rotation of the termini of the pentadienyl cation, favoring a particular direction of conrotatory ring closure (torquoselectivity). The associated lone-pair stabilization of the transition state by Ox promotes cyclization of traditionally resistant substrates, broadening the scope of this asymmetric Nazarov cyclization. The Ox group also facilitates the stereo- and regioselective incorporation of nucleophiles (Nu) and dienes, giving more complex, multistereocenter containing cyclopentanoids. Finally, the Ox group is readily removed and recovered or can be converted into other amine functionalities.

Lewis Acid Mediated Nazarov Cyclization as a Convergent and Enantioselective Entry to C-nor-D-homo-Steroids.

A straightforward synthesis of C-nor-D-homo steroids starting from (+)-Wieland-Miescher ketone is reported. This convergent synthetic strategy utilizes ascalable diastereoselective Nazarov cyclization of functionalized chiral aryl vinyl ketones, allowing for further functionalization. The ability to conduct this key transformation on a multi-gram scale paves the way for the synthesis of a variety of completely new C-nor-D-homo steroids, without the need of a classic steran steroid rearrangement or achiral linear reaction sequences.

Construction of Carbazoles by Palladium-Catalyzed Direct Cross-Coupling of Indoles with in situ Generated Aryl Vinyl Ketones

The synthesis of carbazoles via Pd-catalyzed direct cross-coupling of indoles with in situ generated aryl vinyl ketones by using statured ketones as the olefins source is described. This protocol obviates the need for additional preparation steps of aryl vinyl ketones and therefore opens up a new door to synthesis of carbazoles in an atom-and step-economical fashion.

Planar chiral [2.2]paracyclophane-based phosphine-phenol catalysts: application to the aza-Morita-Baylis-Hillman reaction of N-sulfonated imines with various vinyl ketones

Several planar chiral [2.2]paracyclophane-based phosphine-phenol catalysts were prepared and applied to the aza-Morita-Baylis-Hillman reaction of aldimines with vinyl ketones. The pseudo-ortho-substituted aryl[2.2]paracyclophanol, in which the phosphino group was located at the meta-position of the aryl group, showed an exceptionally high reactivity and good enantioselectivity for the reaction of N-tosylated aldimines with various alkyl or aryl vinyl ketones.

Quinine-derived thiourea and squaramide catalyzed conjugate addition of α-nitrophosphonates to enones: asymmetric synthesis of quaternary α-aminophosphonates.

Conjugate addition of α-nitrophosphonates to enones was carried out in the presence of two sets of organocatalysts, viz. a quinine-thiourea and a quinine-squaramide. The quinine-thiourea provided the products possessing an α-quaternary chiral center in high enantioselectivities only in the case of electron rich enones. On the other hand, the quinine-squaramide was more efficient in that a wide variety of electron rich and electron poor enones underwent Michael addition of nitrophosphonates to afford the quaternary α-nitrophosphonates in excellent yields and enantioselectivities. The hydrogen bonding donor ability of the bifunctional catalyst, as shown in the proposed transition states, appears primarily responsible for the observed selectivity. However, a favorable π-stacking between the aryl groups of thiourea/squaramide and aryl vinyl ketone also appeared favorable. The reaction was amenable to scale up, and the enantioenriched quaternary α-nitrophosphonates could be easily transformed to synthetically and biologically useful quaternary α-aminophosphonates and other multifunctional molecules.

The photo-Nazarov reaction: scope and application.

The reaction conditions and scope of the photo-Nazarov reaction of aryl vinyl ketones were investigated. In contrast to the conventional acid-catalyzed methods, this photolytic electrocyclization proceeds in the neutral or basic conditions. Irradiating substrates bearing various aromatic rings, acid-sensitive groups, cyclohexenyl, cycloheptenyl, and unsaturated pyran with UV-light (254 nm) smoothly yielded hexahydrofluorenones and related structures. This photo-Nazarov reaction could also be applicable to the substrates carrying β-alkyl groups on the enone, which gave corresponding polycyclic rings containing quaternary centers. These photo-electrocyclized products may prove useful for synthesizing a variety of natural products and their derivatives. Further application of this mild photo-Nazarov reaction in the synthesis of taiwaniaquinol B was achieved.

Cationic cyclizations and rearrangements promoted by a heterogeneous gold catalyst.

A heterogeneous gold catalyst with remarkable activity for promoting the electrophilic reactions of aryl vinyl ketones and aryl dienyl ketones is described. The catalyst is easy to prepare, is robust, and can be recycled. Low loadings are effective for different types of cationic reactions, including Nazarov cyclizations, lactonizations, and [1,2] shifts.

Catalytic asymmetric Diels-Alder reactions involving aryl vinyl ketones.

A catalytic asymmetric Diels-Alder reaction of an aryl vinyl ketone with 1,3-dienylcarbamate has been developed. Cyclohexenes bearing vicinal amino and aroyl groups in a cis-configuration were prepared in excellent ee (>99%) and endo (single diastereomer) selectivity. The absolute configuration of one DA product was unambiguously confirmed using XRD analysis. The transition state structure was proposed on the basis of DFT calculations.

ChemInform Abstract: Efficient Synthesis of Trifluoromethylated Dihydrochalcones, Aryl Vinyl Ketones and Indanones by Superelectrophilic Activation of 4,4,4‐Trifluoro/3‐(trifluoromethyl)crotonic Acids.

AbstractA novel and efficient direct synthetic route to trifluoromethylated dihydrochalcones (III), aryl vinyl ketones (V), and indanones like (VIII) is based on Friedel—Crafts reactions under superacidic conditions.