Aryl Alkynes Research Articles

Cu2O Nanocatalysts Immobilized on p(SBMA) for Synergistic CO2 Activation to Afford Esters and Heterocycles at Ambient Pressure

Herein, we report a chemoselective insertion of CO2 into unsaturated alkyne substrates under ambient conditions, which is achieved over poly (sulfobetain methacrylate) (p(SBMA)) supported Cu2O nanocatalyst (Cu2O/p(SBMA)) and a series of 3a,4-dihydronaphtho[2,3-c]furan-1(3H)-ones, can be obtained in excellent yields. Cu2O/p(SBMA) presents high performance for environment pressure activation and interpolation of CO2 into unsaturated alkyne substrates. This provides an attainable and competent catalyst for interpolation of CO2 into aryl alkynes, and binding allylic chlorides through SN2 mechanism in order to produce efficient ester and lactone heterocycles that are supposed to have favorable utilizations. All in all, these findings signify practical methods of hybrid catalyst development for detailed alterations, including CO2 employment in a green and sustainable manner.

Short-Chained Platinum Complex Catalyzed Hydrosilylation under Thermomorphic Conditions: Heterogeneous Phase Separation at Ice Temperature.

Homogeneous catalysts PtCl2[5,5′-bis-(n-ClCF2(CF2)3CH2OCH2)-2,2′-bpy] (2A) and PtCl2[5,5′-bis-(n-HCF2(CF2)3CH2OCH2)-2,2′-bpy] (2B), which contained short fluorous chains, were synthesized and used in catalysis of hydrosilylation of alkynes. In these reactions the thermomorphic mode was effectively used to recover these catalysts from the reaction mixture up to eight cycles by taking advantage of heterogeneous phase separation at ice temperature. This kind of catalysis had previously been observed in fluorous catalysts of platinum containing about 50% F-content, but in this work the percentage of F-content is decreased to only about 30%, by which we termed them as “very light fluorous”. Our new type of catalyst with limited number of F-content is considered as the important discovery in the fluorous technology field as the reduced number of fluorine atoms will help to be able to comply the EPA 8-carbon rule. The metal leaching after the reaction has been examined by ICP-MS, and the testing results show the leaching of residual metal to be minimal. Additionally, comparing these results to our previous work, fluorous chain assisted selectivity has been observed when different fluorous chain lengths of the catalysts are used. It has been found that there exists fluorous chain assisted better selectivity towards β-(E) form in the Pt-catalyzed hydrosilylation of non-symmetric terminal alkyne when the Pt catalyst contains short fluorous chain (i.e., 4 Cs). Phenyl acetylenes showed the opposite regioselectivity due to pi-pi interaction while using the same catalyst via Markovnikov’s addition to form terminal vinyl silane, which is then a major product for Pt-catalyzed hydrosilylation of terminal aryl acetylene with triethylsilane. Finally, the kinetic studies indicate that the insertion of alkyne into the Pt-H bond is the rate-determining step.

An environmentally benign regioselective synthesis of 2-benzyl-4-arylquinoline derivatives using aryl amines, styrene oxides and aryl acetylenes.

A novel and an expedient metal- and solvent-free synthesis of a wide variety of 2-benzyl-4-arylquinoline derivatives is described from readily available aryl amines, styrene oxides and aryl acetylenes in the presence of 10 mol% molecular iodine. This domino reaction occurs under metal- and solvent-free conditions at 120 °C, which avoids the usage of metal catalyst and as a consequence generation of metal waste. The salient features of this methodology are the use of simple starting materials, ease of handling, high regioselectivity, shorter reaction time, atom-economical, step-economical, the formation of one C-N and two C-C bonds and a wide range of functional groups tolerance.

Markovnikov-addition of H-phosphonates to terminal alkynes under metal- and solvent-free conditions.

An addition of H-phosphonates to aryl alkynes was realized under solvent- and metal-free conditions, affording Markovnikov-selective α-vinylphosphonates in moderate to good yields. A wide range of aryl alkynes could be applied for the reaction. A tentative mechanism of addition–substitution was proposed based on in situ31P {1H} NMR studies.

Mechanistic understanding of the Cu(i)-catalyzed domino reaction constructing 1-aryl-1,2,3-triazole from electron-rich aryl bromide, alkyne, and sodium azide: a DFT study

The mechanism of the Cu(i)-catalyzed domino reaction furnishing 1-aryl-1,2,3-triazole assisted by CuI and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is explored with density functional theory (DFT) calculations.

Manganese-Catalyzed Chlorosulfonylation of Terminal Alkene/Yne <i>Via</i> Convergent Paired Electrolysis

Convergent paired electrolysis is an energy-efficient model in organic synthesis. Whereas the main obstacle is the matching properties of intermediates generated in two electrodes. Herein, we develop a manganese-catalyzed atom-transfer radical addition of terminal aryl alkenes and alkynes with sulfonyl chlorides, where manganese salt plays the role of chlorine atom-transfer catalyst as well as redox mediator. This method generates analogues of chlorosulfonylated products in high regio- and stereoselectivity, which are derivatives of pharmaceutical drug and natural products.

Formal metal-free γ-arylation of 1,3-dicarbonyl compounds via an isomerisation/1,4-addition/[3,3]-sigmatropic rearrangement sequence

A metal-free redox arylation of alkynes with sulfoxides has been developed to provide unconventional access to diverse γ-arylated 1,3-dicarbonyl compounds in an atom-economical manner.

Reductive Ni-catalysis for stereoselective carboarylation of terminal aryl alkynes.

Stereoselective dicarbofunctionalization of terminal aryl alkynes has been achieved through reductive Ni-catalysis. The exclusive regioselective and anti-addition selective alkylarylation of terminal alkynes is accomplished using alkyl iodide and aryl iodide as electrophilic coupling partners in the presence of NiBr2 as the catalyst and Mn as an inexpensive reductant.

Rhodium-Catalyzed One-Pot Access to N-Polycyclic Aromatic Hydrocarbons from Aryl Ketones through Triple C-H Bond Activations.

A Rh-catalyzed pot and step economic synthesis of aza-polycyclic aromatic hydrocarbons (N-PAHs) from readily available aryl ketones and alkynes has been disclosed. Additionally, a novel synthetic application of the well-known aminating reagent hydroxylamine-O-sulfonic acid (HOSA) has been explored as an in situ redox-neutral directing group for the formation of N-PAHs via isoquinoline. Multiple bond formation in a single operation through a cascade of triple C-H bond activations is the beauty of this protocol. The challenging annulations of two different alkynes in a regioselective fashion have been demonstrated effectively. Mechanistic studies reveal that 3,4-diphenyl-1-methylisoquinoline is an active intermediate for this one-pot transformation.

Regioselective Synthesis of Chromones via Cyclocarbonylative Sonogashira Coupling Catalyzed by Highly Active Bridged-Bis(N-Heterocyclic Carbene)Palladium(II) Complexes

The one-pot regioselective and catalytic synthesis of bioactive chromones and flavones was achieved via phosphine-free cyclocarbonylative Sonogashira coupling reactions of 2-iodophenols with aryl alkynes, alkyl alkynes, and dialkynes. The reactions are catalyzed by new dibromidobis(NHC)palladium(II) complexes. The new bridged N,N′-substituted benzimidazolium salts (L1, L2, and L3) and their palladium complexes C1, C2, and C3 were designed, prepared, and fully characterized using different physical and spectroscopic techniques. The molecular structures of complexes C1 and C3 were determined by single-crystal X-ray diffraction analysis. They showed a distorted square planar geometry, where the Pd(II) ion is bonded to the carbon atoms of two cis NHC carbene ligands and two cis bromido anions. These complexes displayed a high catalytic activity in cyclocarbonylative Sonogashira coupling reactions with low catalyst loadings. The regioselectivity of these reactions was controlled by using diethylamine as the base and DMF as the solvent.

Hybrides of Alkaloid Lappaconitine with Pyrimidine Motif on the Anthranilic Acid Moiety: Design, Synthesis, and Investigation of Antinociceptive Potency.

Convenient and efficient routes to construct hybrid molecules containing diterpene alkaloid lappaconitine and pyrimidine fragments are reported. One route takes place via first converting of lappaconitine to 1-ethynyl-lappaconitine, followed by the Sonogashira cross-coupling-cyclocondensation sequences. The other involves the palladium-catalyzed carbonylative Sonogashira reaction of 5′-iodolappaconitine with aryl acetylene and Mo (CO)6 as the CO source in acetonitrile and subsequent cyclocondensation reaction of the generated alkynone with amidines. The reaction proceeded cleanly in the presence of the PdCl2-(1-Ad)2PBn∙HBr catalytic system. The protocol provides mild reaction conditions, high yields, and high atom and step-economy. Pharmacological screening of lappaconitine-pyrimidine hybrids for antinociceptive activity in vivo revealed that these compounds possessed high activity in experimental pain models, which was dependent on the nature of the substituent in the 2 and 6 positions of the pyrimidine nucleus. Docking studies were undertaken to gain insight into the possible binding mode of these compounds with the voltage-gated sodium channel 1.7. The moderate toxicity of the leading compound 12 (50% lethal dose (LD50) value was more than 600 mg/kg in vivo) and cytotoxicity to cancer cell lines in vitro encouraged the further design of therapeutically relevant analogues based on this novel type of lappaconitine–pyrimidine hybrids.

Copper‐Catalyzed Asymmetric Coupling of Allenyl Radicals with Terminal Alkynes to Access Tetrasubstituted Allenes

AbstractIn contrast to the wealth of asymmetric transformations for generating central chirality from alkyl radicals, the enantiocontrol over the allenyl radicals for forging axial chirality represents an uncharted domain. The challenge arises from the unique elongated linear configuration of the allenyl radicals that necessitates the stereo‐differentiation of remote motifs away from the radical reaction site. We herein describe a copper‐catalyzed asymmetric radical 1,4‐carboalkynylation of 1,3‐enynes via the coupling of allenyl radicals with terminal alkynes, providing diverse synthetically challenging tetrasubstituted chiral allenes. A chiral N,N,P‐ligand is crucial for both the reaction initiation and the enantiocontrol over the highly reactive allenyl radicals. The reaction features a broad substrate scope, covering a variety of (hetero)aryl and alkyl alkynes and 1,3‐enynes as well as radical precursors with excellent functional group tolerance.

Copper-Catalyzed Asymmetric Coupling of Allenyl Radicals with Terminal Alkynes to Access Tetrasubstituted Allenes.

In contrast to the wealth of asymmetric transformations for generating central chirality from alkyl radicals, the enantiocontrol over the allenyl radicals for forging axial chirality represents an uncharted domain. The challenge arises from the unique elongated linear configuration of the allenyl radicals that necessitates the stereo-differentiation of remote motifs away from the radical reaction site. We herein describe a copper-catalyzed asymmetric radical 1,4-carboalkynylation of 1,3-enynes via the coupling of allenyl radicals with terminal alkynes, providing diverse synthetically challenging tetrasubstituted chiral allenes. A chiral N,N,P-ligand is crucial for both the reaction initiation and the enantiocontrol over the highly reactive allenyl radicals. The reaction features a broad substrate scope, covering a variety of (hetero)aryl and alkyl alkynes and 1,3-enynes as well as radical precursors with excellent functional group tolerance.

Mechanistic insight into ligand‐promoted C–H alkenylation of arenes with alkynes: A computational study

AbstractThe ligand‐promoted palladium‐catalyzed arylation of alkynes with arenes without directing group is able to furnish alkenyl chlorides via a 1,4‐chlorine migration or trisubstituted alkenes. This reaction is challenging due to bidentate N, N ligand and electron‐neutral arenes have rarely been reported to afford good yields. Intrigued by the novel strategy, we carried out density functional theory calculations to unravel the ligand effects and origins of substituent‐controlled chemoselectivity of the C–H functionalization reactions. For the n‐propyl‐substituted alkyne system, CMD process is identified as the rate‐determining step. And the chemoselectivity is controlled by oxidative addition with the C–Cl bond cleavage and protonation process. While for 3,5‐dimethylphenyl‐substituented alkyne system, the dominant pathway turns to the protonation process. The electrostatic attractions, repulsive force and aryl substituent effects jointly result in reverse chemoselectivity. Compared with the L2 ligand, the bidentate ligand L1 reacts with palladium acetate to form a different stable square‐planer species. The steric repulsion are found to be mainly responsible for the absence of products using the L2 ligand, which is different from previous reports.

DFNS/α-CD/Au as a Nanocatalyst for Interpolation of CO2 into Aryl Alkynes Followed by SN2 Coupling with Allylic Chlorides

In the present study, to effectively carbonylate cinnamyl chloride and phenylacetylene with CO2, α-cyclodextrin doping dendritic fibrous nanosilica (DFNS) supported nanoparticles of gold was used as a catalyst (DFNS/α-CD/Au NPs). In the catalyst, the nanoparticles of Au were in situ reduced on the surfaces of DFNS. Transmission electron microscopy (TEM), scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and X-ray energy dispersive spectroscopy (EDS) were utilized for characterizing the nanostructures DFNS/α-CD/Au. It was found that the nanostructures of DFNS/α-CD/Au can be nominated due to their effective and novel catalytic behaviour during the synthesis of 3a,4-dihydronaphtho[2,3-c] furan-1(3H)-ones from cinnamyl chloride, phenylacetylene, and CO2.

Donor-Acceptor Bicyclopropyls as 1,6-Zwitterionic Intermediates: Synthesis and Reactions with 4-Phenyl-1,2,4-triazoline-3,5-dione and Terminal Acetylenes.

The bicyclopropyl system activated by incorporation of donor and acceptor groups in the presence of Lewis acids was used as a synthetic equivalent of 1,6-zwitterions. Opening of both cyclopropane rings in 2'-aryl-1,1'-bicyclopropyl-2,2-dicarboxylates (D-A bicyclopropyl, ABCDs) in the presence of GaI3 + Bu4N+GaI4- results in 5-iodo-5-arylpent-2-enylmalonates as products of HI formal 1,6-addition to the bicyclopropyl system. The use of GaCl3 or GaBr3 as a Lewis acid and terminal aryl or alkyl acetylenes as 1,6-zwitterion interceptors allows the alkyl substituent to be grown to give the corresponding acyclic 7-chloro(bromo)-hepta-2,6-dienylmalonates. The reaction of ABCDs with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) catalyzed by Yb(OTf)3 also results in the opening of both cyclopropane rings. The reaction products are tetrahydropyridazine derivatives - (7,9-dioxo-1,6,8-triazabicyclo[4.3.0]non-3-en-2-ylmethyl)malonates - containing one more PTAD moiety in the malonyl group.

Copper-Catalyzed Formal Transfer Hydrogenation/Deuteration of Aryl Alkynes.

A copper-catalyzed reduction of alkynes to alkanes and deuterated alkanes is described under transfer hydrogenation and transfer deuteration conditions. Commercially available alcohols and silanes are used interchangeably with their deuterated analogues as the hydrogen or deuterium sources. Transfer deuteration of terminal and internal aryl alkynes occurs with high levels of deuterium incorporation. Alkyne-containing complex natural product analogues undergo transfer hydrogenation and transfer deuteration selectively, in high yield. Mechanistic experiments support the reaction occurring through a cis-alkene intermediate and demonstrate the possibility for a regioselective alkyne transfer hydrodeuteration reaction.

Ruthenium(II)‐Catalyzed Synthesis of Indolo[2,1‐a]isoquinolines through Double Oxidative Annulation Reaction of Phenyl Isocyanates with Di(hetero)aryl Alkynes

AbstractIndole‐containing polycyclic hetero aromatic compounds are synthesized by multistep process, which have wide application in biological activities and organic semi‐conductor materials. Herein we report the one‐pot method for the synthesis of polysubstituted indolo[2,1‐a]isoquinolines by Ru(II) catalyzed double aryl/hetero aryl C(sp2)−H activation through in‐situ installed carbamide of phenyl isocyanate and di(hetero)aryl substituted alkynes in the presence of Cu(OAc)2.H2O as an oxidant and CsOAc as an additive at 120 °C for 3 h in good to excellent yields.magnified image

Use of Hypervalent Iodine Reagents in Visible Light-Promoted α-Ketoacylations of Sulfoximines with Aryl Alkynes.

In visible light, sulfoximidoyl-containing hypervalent iodine reagents react with aryl alkynes to give N-α-ketoacylated sulfoximines in good to high yields. The process is metal- and base-free, providing the diketonic products without the use of highly oxygenated reagents such as peroxides. Results from mechanistic investigations suggest the intermediacy of radicals and reveal the importance of molecular oxygen.

Photoinduced Deaminative Coupling of Alkylpyridium Salts with Terminal Arylalkynes.

A novel and simple Z-alkene synthesis by the photocatalyzed coupling reactions of alkylpyridium salts, which were prepared from primary amines, with terminal aryl alkynes at room temperature is reported here. A wide range of primary amines, which contain different functional groups, were tolerated under these conditions. The mild reaction conditions, broad substrate scope, functional group tolerance, and operational simplicity make this deaminative coupling reaction a valuable method in organic syntheses.