Ethynyl Ketones Research Articles

One-Pot Synthesis of Dihydrobenzo[a]fluorenes via Cascade C-H Annulation of Thiobenzamide with Alkynes.

We herein disclose a highly efficient one-pot synthetic strategy for dihydrobenzo[a]fluorenes via cascade rhodium(III)-catalyzed ortho-C-H activation/annulation of thiobenzamides with aryl ethynyl ketones and subsequently copper(II)-promoted intramolecular C-H/C-H cross-coupling reactions. Mechanistic investigations suggest that Cu(II) plays two crucial roles by serving as a sulfide scavenger to regenerate the Rh(III) catalyst and promoting the intramolecular C-H/C-H cross-coupling reaction. This protocol greatly streamlines accesses to a variety of appealing tetracyclic benzo[a]fluorene skeletons, which may have potential biological activity and medicinal properties.

Novel Stereo‐Induction Pattern in Pudovik Addition/Phospha‐Brook Rearrangement Towards Chiral Trisubstituted Allenes

AbstractDespite the significance of chiral allene skeletons in catalysis, organic synthesis and medicinal chemistry et al., there is a scarcity of reports on axially chiral allenyl phosphorus compounds. Here, we disclosed an efficient and straightforward cascade reaction between ethynyl ketones and phosphine oxides, resulting in a broad array of trisubstituted allenes incorporating a phosphorus moiety in high yields with excellent stereoselectivities facilitated by peptide‐mimic phosphonium salt (PPS) catalysis, Additionally, comprehensive series of mechanistic experiments have been conducted to elucidate that this cascade reaction proceeds via an asymmetric Pudovik addition reaction followed by a subsequent phospha‐Brook rearrangement that occurs concomitantly with kinetic resolution, representing a stereospecific rearrangement and protonation process facilitating central‐to‐axial chirality transfer in a cascade manner. We anticipate that our research will pave the way for a promising exploration of novel stereo‐induction pattern in the Pudovik addition/phospha‐Brook rearrangement cascade reaction.

Novel Stereo-Induction Pattern in Pudovik Addition/Phospha-Brook Rearrangement Towards Chiral Trisubstituted Allenes.

Despite the significance of chiral allene skeletons in catalysis, organic synthesis and medicinal chemistry et al., there is a scarcity of reports on axially chiral allenyl phosphorus compounds. Here, we disclosed an efficient and straightforward cascade reaction between ethynyl ketones and phosphine oxides, resulting in a broad array of trisubstituted allenes incorporating a phosphorus moiety in high yields with excellent stereoselectivities facilitated by peptide-mimic phosphonium salt (PPS) catalysis, Additionally, comprehensive series of mechanistic experiments have been conducted to elucidate that this cascade reaction proceeds via an asymmetric Pudovik addition reaction followed by a subsequent phospha-Brook rearrangement that occurs concomitantly with kinetic resolution, representing a stereospecific rearrangement and protonation process facilitating central-to-axial chirality transfer in a cascade manner. We anticipate that our research will pave the way for a promising exploration of novel stereo-induction pattern in the Pudovik addition/phospha-Brook rearrangement cascade reaction.

Further Developments on the Regioselective Synthesis of 3-Aroylindole Derivatives from <i>C</i>-Nitrosoaromatics and Alkynones: A Novel Synthetic Approach to Pravadoline, JWH-073, Indothiazinone Analogues and Related Compounds

An uncatalyzed and easily accessible synthetic approach for the preparation of 3-aroylindoles was investigated using nitrosoarenes and aromatic terminal ethynyl ketones. Indole derivatives were produced in good yields and excellent regioselectivity. Functionalizations of the indole products were carried out affording highly valuable and versatile compounds. The indolization protocol was studied as a fundamental step for the preparation of pravadoline and 1-butyl-3-(1-naphthoyl)indole (JWH-073), bioactive molecules showing antinociceptic properties.

Elemental Chalcogen (Se, S) in PEG-400 to the Synthesis of Seleno- and Thioflavones from 2-Chlorophenyl Ethynyl Ketone and Nucleophilic Species of Chalcogen

An alternative green method was developed for the synthesis of thio- and selenoflavones by the ring closure of 2-chlorophenyl ethynyl ketone with NaHY (Y = S, Se). These nucleophilic chalcogen species were generated in situ using NaBH4 to reduce the elemental chalcogen in the presence of polyethylene glycol-400 (PEG-400). The efficiency of this reaction is strongly dependent on the PEG-400 solvent, acting like a crown ether, complexing with the sodium atom of NaHY species, making the chalcogen nucleophile more active. The synthetic protocol proceeded efficiently at 100 °C under argon, using a range of 2-chlorophenyl ethynyl ketone containing alkyl, aryl, or vinyl groups and the sulfur and selenium chalcogen. By this efficient and simple approach, 18 chalcogenoflavones were obtained in good to excellent yields after 2 h.

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones.

We introduced a regioselective and atom-economical procedure for the synthesis of 3-substituted indoles by annulation of nitrosoarenes with ethynyl ketones. The reactions were carried out achieving indoles without any catalyst and with excellent regioselectivity. No traces of 2-aroylindole products were detected. Working with 4-nitronitrosobenzene as starting material, the 3-aroyl-N-hydroxy-5-nitroindole products precipitated from the reaction mixtures and were isolated by filtration without any further purification technique. Differently from the corresponding N-hydroxy-3-aryl indoles that, spontaneously in solution, give dehydrodimerization products, the N-hydroxy-3-aroyl indoles are stable and no dimerization compounds were observed.

Domino reactions of vinyl ethynyl ketones with 1-aryl-3,4-dihydroisoquinolines — Search for selectivity

We report an efficient domino reaction for synthesizing new pyrrolo[2,1-a]isoquinolines from 1-aryl-3,4-dihydroisoquinolines and vinyl ethynyl ketones. We also address the chemical selectivity of vinyl ethynyl ketones; i.e., adduct formation by the double or triple bond. The reaction outcome depends on the solvent, temperature, microwave irradiation, and catalyst. Donor substituents in the initial isoquinolines provide a regioselective addition to double or triple bonds.

ChemInform Abstract: Microwave‐Assisted Bohlmann—Rahtz Synthesis of Highly Substituted 2‐Aminonicotinates.

Microwave irradiation of 2-carbethoxyacetamidine and an ethynyl ketone under acidic or basic conditions in ethanol at 150 °C for 1.5 hours facilitated Bohlmann–Rahtz pyridine synthesis to give highly substituted ethyl 2-aminonicotinates with total regiocontrol and in reasonable to excellent yield, following purification by immobilization upon an acidic resin.

Microwave-Assisted Bohlmann–Rahtz Synthesis of Highly Substituted 2-Aminonicotinates

Microwave irradiation of 2-carbethoxyacetamidine and an ethynyl ketone under acidic or basic conditions in ethanol at 150 °C for 1.5 hours facilitated Bohlmann–Rahtz pyridine synthesis to give highly substituted ethyl 2-aminonicotinates with total regiocontrol and in reasonable to excellent yield, following purification by immobilization upon an acidic resin.

ChemInform Abstract: Synthesis of Novel Pyrimidine Derivatives Containing the Vinylsulfanyl Group by Regio‐ and Stereoselective Addition of Thiouracils to Ethynyl Ketones.

A regio- and stereoselective method for preparation of novel functionalized pyrimidine derivatives containing the vinylsulfanyl group has been developed based on addition reactions of 2-thiouracils with phenylethynyl ketones. Reactions with ketones containing the disubstituted triple bond afford adducts of Z-stereochemistry, whereas addition to ketone with the terminal triple bond gives preferentially products of E-configuration.

Synthesis and antimitotic activity of alkoxy-substituted 1-aryl-3-(arylamino)alkenones

Alkoxy-substituted 1-aryl-3-(arylamino)prop-2-en-1-ones and 1-aryl-3-(arylamino)but-2en-1-ones were synthesized by the addition of anilines to 1,3-dioxo derivatives or aryl ethynyl ketones. The cis-trans isomerism of these compounds was studied. Biological tests on a sea urchin embryo model showed that 1-aryl-3-(arylamino)prop-2-en-1-ones exhibit an antimitotic effect both via microtubule destabilization and through the action on other cellular targets. The antiproliferative activity of these compounds increases with an increase in the number of alkoxy substituents in 1-aryl ring, whereas the presence of one methoxy group in the para position proved to be optimal for the arylamino moiety.

Cu(OAc)2/FOXAP complex catalyzed construction of 2,5-dihydropyrrole derivatives via asymmetric 1,3-dipolar cycloaddition of azomethine ylides to ethynyl ketones

Cu(OAc)2/FOXAP catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides to ethynyl ketones, affording 2,5-dihydropyrroles in good to excellent yields and excellent enantioselectivities.

Synthesis of Novel Pyrimidine Derivatives Containing the Vinylsulfanyl Group by Regio- and Stereoselective Addition of Thiouracils to Ethynyl Ketones

A regio- and stereoselective method for preparation of novel functionalized pyrimidine derivatives containing the vinylsulfanyl group has been developed based on addition reactions of 2-thiouracils with phenylethynyl ketones. Reactions with ketones containing the disubstituted triple bond afford adducts of Z-stereochemistry, whereas addition to ketone with the terminal triple bond gives preferentially products of E-configuration.

Gold-catalyzed reaction of oxabicyclic alkenes with electron-deficient terminal alkynes to produce acrylate derivatives

Oxabicyclic alkenes can react with electron-deficient terminal alkynes in the presence of a gold catalyst under mild conditions, affording the corresponding addition products in moderate yields. When using alkynyl esters as substrates, the (Z)-acrylate derivatives are obtained. Using but-3-yn-2-one (ethynyl ketone) as a substrate, the corresponding addition product is obtained with (E)-configuration. The proposed mechanism of these reactions is also discussed.

ChemInform Abstract: Synthesis and Biological Activities of Triazole Derivatives as Inhibitors of InhA and Antituberculosis Agents.

Abstractα‐Ketotriazoles (V) are obtained in a one‐pot cycloaddition reaction between ethynyl ketones (III) and azides (IV) mediated by Cu(II) without prior deprotection.

Concise Synthesis of β,β-Diaryl Esters and Ketones from Ethynylcarbonyl Compounds by Rhodium-catalyzed Double Arylation with Arylboroxins

Abstract 3,3-Diarylpropanoate esters were prepared from tert-butyl propiolate and arylboroxins in high yields through the rhodium-catalyzed double arylation of β-alkoxyacrylate, which was generated in situ from tert-butyl propiolate and 2,2,2-trifluoroethanol. The present method was also successfully applied to the double arylation of ethynyl ketones.

Reactions of a 16-electron Cp*Co half-sandwich complex containing a chelating 1,2-dicarba-closo-dodecaborane-1,2-dithiolate ligand with alkynones HC≡C-C(O)R (R = OMe, Me, Ph)

The reaction of the 16e half-sandwich complex Cp*Co(S2C2B10H10) (1) (Cp* = pentamethylcyclopentadienyl) with excess methyl acetylene monocarboxylate, HC≡C-CO2Me, affords the 18e complexes 2–6. Compound 2 bears a B-CH2 unit in which B-substitution occurs in the B(3)/B(6) position of the ortho-carborane cage. Complexes 3–6 are geometrical isomers, in which the alkyne is twofold inserted into one of the Co-S bonds in all the four possible ways. Treatment of 1 with excess 3-butyn-2-one or phenyl ethynyl ketone, HC≡C-C(O)R (R = Me, Ph), at ambient temperature leads to the 18e complexes 7–10, respectively, with two alkynes inserted into one of the Co-S bonds. All the new complexes were fully characterized by spectroscopic techniques and elemental analysis. The solid-state structures of 2, 3, 5, 7, 8, 9 and 10 were further characterized by X-ray structural analysis.

ChemInform Abstract: Preparation and Photolysis of Diaryl Esters of Acetylenedicarboxylic Acid.

Abstract Two diaryl acetylenedicarboxylates 1 a,b have been prepared in moderate yields by direct reaction of acetylenedicarboxylic acid with the corresponding phenols catalyzed by sulfuric or p -toluenesulfonic acids and also through acetylenedicarbonyl chloride. The accompanying by-products have been characterized. Attempted esterification using N,N′-dicyclohexylcarbodiimide as condensing agent gives an asymmetric ester amide 11a and a substituted uracil 12a . Photolysis of the aryl esters 1 a,b in benzene solution affords the benzocoumaran-3-ones 14a,b . In the case of 1b , minor amounts of a polycyclic condensed 4-chromanone 17b have also been observed. These results shows that the nature of the substituent attached at the β-position of the C  C triple bond plays an important role in the cyclization of o -hydroxyaryl ethynyl ketones.

Reactions of sodium selenide with ethynyl and bromoethynyl ketones: Stereo- and regioselective synthesis of functionalized divinyl selenides and 1,3-diselenetanes

A method for the preparation of 2,4-dimethylene-1,3-diselenetanes based on the novel reaction of sodium selenide with bromoethynyl ketones has been developed. New functionalized divinyl selenides have been obtained by regio- and stereoselective addition of sodium selenide to ethynyl ketones.

1-ベンゾテルロピリリウム塩の化学：合成、構造および反応

The three main parts; i.e., the preparations, structures and reactions of the 1-benzotelluropyrylium salts are described. The synthetic workup has been achieved by transformation from the tellurochromones, which were simply prepared by the reaction of the o-bromophenyl ethynyl ketones with sodium hydrogen telluride (NaHTe). The synthetic method for the preparation of the tellurochromones is based on the intramolecular ring closure of a tellurol moiety into a triple bond. The study shows that these salts, although being stable compounds, are highly reactive with various nucleophiles including OMe-, diethylamine, CN-, an active methylene compound and Grignard reagents, and also hydrogenation and hydrolysis to afford the successful corresponding 2- or 4-substituted tellurochromene derivatives. The chemistry of the 1-benzoselenopyrylium salts is also described. The thermolysis of the 2-azidoselenochromenes, which were easily obtained by the reaction of the selenopyrylium salts with sodium azide, resulted in a ring expansion to produce the novel stable 1,3-benzoselenazepines. X-ray structural analyses of the tert-butyltelluro- and selenopyrylium salts are also reported.