Internal Aryl Alkynes Research Articles

Visible-Light-Induced Oxidative α-keto-Dichlorination of Arylalkynes by CuCl2 at Room Temperature.

A visible light-induced oxidative α-keto-dichlorination of terminal and internal aryl alkynes was developed to form dichloroacetophenones (DCAPs) and dichlorophenyl-acetophenones (DCPAPs), respectively, by using CuCl2 as a photoredox catalyst in the presence of air at room temperature (without using any exogenous photocatalyst). Here, photoexcited CuCl2 underwent ligand-to-metal charge transfer to generate a Cl radical, which readily added to the alkynes to form DCAPs or DCPAPs in the presence of O2 . This α-keto-dichlorination reaction is a green and mild protocol as it produced water as the only by-product. Moreover, the evaluation of green chemistry metrics indicated that the E-factor (mass of wastes/mass of products) of the current α-keto-chlorination method is around 10.1 times lower than that of a literature-reported photochemical method. The Eco Scale value (score 55, which on a scale of 0-100 indicates an acceptable synthesis) signifies that this process is simple, highly efficient, eco-friendly, and cost-effective.

Copper-catalyzed regioselective trans-silaboration of internal arylalkynes with stereochemical switch to cis-addition mode.

Copper-catalyzed silafunctionalization of alkynes using a silylboronic ester as a silicon source has recently progressed rapidly. Generally, the reaction affords a product with cis-stereoselectivity. We herein describe trans-selective 1,2-addition of silylboronic esters to internal arylalkynes, which was promoted efficiently by the CuOt-Bu/RCy2P/NaOt-Bu catalysts. Moreover, we report a stereochemical switch to cis-addition in the reactions of Me2(i-PrO)Si-B(pin) in hydrocarbon solvents including cyclohexane.

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.

Divergent functionalization of terminal alkynes enabled alkynylative [5+1] benzannulation of 3-acetoxy-1,4-enynes.

We here describe an alkynylative [5+1] benzannulation of 3-acetoxy-1,4-enynes with terminal alkynes, which enables both the construction of a benzene ring skeleton and intermolecular incorporation of an alkynyl group in a single reaction using Pd and Cu cooperative catalysts. The method represents efficient access to internal aryl alkynes through divergent functionalization of two terminal alkyne components: one alkyne serves as the one-carbon unit to realize the [5+1] benzannulation and the other alkyne as a nucleophile terminates the reaction.

Synthesis of Aryl Alkynes via Copper Catalyzed Decarboxylative Alkynylation of 2-Nitrobenzoic Acids.

An efficient protocol for the synthesis of internal aryl alkynes was achieved via Cu-catalyzed decarboxylative cross-coupling reactions, and to the best of our knowledge, this is the first example of a Cu-catalyzed decarboxylative alkynylation of benzoic acids with terminal alkynes. This approach utilizes simple Cu salt as catalyst and O2, an abundant, clean, and green material, as the oxidant. The reaction tolerates various functional groups, and a variety of internal aryl alkynes were synthesized in 46-83% yields.

Gold‐Catalyzed Highly Regioselective Coupling Reaction between Alkynes and Aldehydes for the Synthesis of Conjugated Enones

AbstractAn efficient AuCl3/AgSbF6‐catalysed enone synthesis from coupling of alkynes and aldehydes has been presented. The present reaction is very effective, simple and mild and has wide range of substrate scope. Both aryl (electron rich and electron deficient) and aliphatic aldehydes and terminal and internal arylalkynes participated smoothly in the reaction and provided exclusively trans product. This simple reaction can be coupled with other gold catalysed transformations which involve enones as substrates for further development.

PtO2/PTSA system catalyzed regioselective hydration of internal arylalkynes bearing electron withdrawing groups

A highly efficient PtO2/PTSA catalyst system for the hydration of a wide array of alkynes was developed. This method proved to be compatible with a large range of functional groups and the ketone products were obtained in high yields. The scope of this methodology was also extended to the synthesis of 3-aryl-isochromenones, -indoles and -benzofurans.

Cesium Hydroxide-mediated Regio- and Stereoselective Hydroamidation of Internal Aryl Alkynes with Primary Amides

A cesium hydroxide-mediated hydroamidation of internal aryl alkynes with primary amides has been developed. The reaction proceeds with high anti-selectivity to deliver the corresponding stereodefined (Z)-enamides in good yields. The alkali base-promoted system is also compatible with unsymmetrical aryl alkyl alkynes, and the hydroamidated products are obtained with high regioselectivity as well as stereoselectivity.

Stereoselective Photoredox-Catalyzed Chlorotrifluoromethylation of Alkynes: Synthesis of Tetrasubstituted Alkenes.

A new photoredox-catalyzed chlorotrifluoromethylation reaction of internal arylalkynes under mild conditions using visible light has been developed. The reactions proceed with high levels of regio- and stereoselectivity and utilize commercially available CF3SO2Cl as both the CF3 and Cl source. In the mechanistic pathway for this process, generation of the CF3 radical and chloride ion occurs by Ir(ppy)3-photocatalyzed reductive decomposition of CF3SO2Cl. The synthetically important trifluoromethyl-substituted vinyl chlorides produced in this process can be readily transformed to 1,1-bis-arylalkenes by using Suzuki coupling.

Selective hydration of asymmetric internal aryl alkynes without directing groups to α-aryl ketones over Cu-based catalyst

The catalyst enlarges the uniqueness of the electron population on the two triple-bond carbon atoms, resulting in highly regioselective hydration.

CuH-catalysed hydroamination of arylalkynes with hydroxylamine esters - a computational scrutiny of rival mechanistic pathways.

An in-depth computational mechanistic probe of the CuH-mediated hydroamination of internal arylalkynes with an archetype hydroxylamine ester and hydrosilane by a (Xantphos)CuH catalyst (Xantphos ≡ {P^P} ≡ 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) is presented. This first comprehensive computational study of the CuH-mediated electrophilic alkyne hydroamination has identified the most accessible pathway for the rival avenues for direct and reductive hydroamination. The mechanistic picture derived from smooth energy profiles obtained by employing a reliable computational protocol applied to a realistic catalyst model conforms to all available experimental data. The crucial vinyl- and alkylcopper intermediates were found to display a distinct chemodivergence in their reactivity towards amine electrophile and alcohol, which ensures the successful formation of α-branched alkylamines together with (E)-enamines. On the one hand, the vinylcopper is somewhat preferably approached by the alcohol, thereby rendering the reductive hydroamination avenue favourable in the presence of both amine electrophile and alcohol. In contrast, the greater kinetic demands for protonation versus electrophilic amination predicted for the alkylcopper prevents the reductive hydroamination avenue to become non-productive. Electronically modified hydroxylamine esters are found to influence the chemoselectivity in reactivity towards amine electrophile and alcohol achievable for the vinyl- and alkylcopper, thereby offering an opportunity for process improvement.

Synthesis of Substituted Benzils from Diarylalkyne Oxidation

In this review, the oxidation of diarylalkynes leading to functionalized benzils [di(het)aryl 1,2-diketones] is summarized. Some synthetic one-pot transformations of internal arylalkynes leading to the construction of heterocycles are presented. 1 Introduction 2 Oxidation Using Inorganic Reagents 2.1 I2, I+, and NIS 2.2 Potassium Permanganate (KMnO4) 2.3 Sulfur Trioxide (SO3) 2.4 Potassium Peroxymonosulfate (Oxone) 2.5 O2, hν, MgBr2·Et2O 2.6 Cerium Ammonium Nitrate (CAN) 2.7 Overview of Inorganic Reagents 3 Metal-Catalyzed Oxidation of Diarylalkynes 3.1 Palladium Catalysts 3.2 Copper Catalysts 3.3 Iron Catalysts 3.4 Ruthenium Catalysts 3.5 Gold Catalysts 3.6 Mercury Catalysts 3.7 Overview of Metal Catalysts 4 Sequential Hydration–Oxidation of Diarylalkynes 5 Applications to the Synthesis of Heterocycles 5.1 One-Pot Access to Heterocycles 5.2 Access to Various Heterocycles 6 Conclusions

Directed ortho-C–H Silylation Coupled with trans-Selective Hydrogenation of Arylalkynes Catalyzed by Ruthenium Complexes of a Xanthene-Based Si,O,Si-Chelate Ligand, “Xantsil”

Ruthenium complexes bearing a xanthene-based bis(silyl) chelate ligand, “xantsil” ((9,9-dimethylxanthene-4,5-diyl)bis(dimethylsilyl)), Ru{κ3(Si,O,Si)-xantsil}(CO)(PR3) (1-Cy: R = Cy (cyclohexyl), 1-Cyp: R = Cyp (cyclopentyl)), were found to catalyze the reactions of internal arylalkynes with tertiary silanes (1–1.3 equiv) at a moderate temperature (room temperature to 70 °C) to give (E)-alkenes having an ortho-silylated aryl group, i.e., (E)-R1C(H)═C(H)(C6H3-o-SiR33-p-R2). These catalytic reactions involve a unique ortho-selective C–H silylation of an aryl group in arylalkynes accompanied by hydrogenation of their C–C triple bonds (ortho-C–H silylation/hydrogenation). Importantly, in these reactions, the alkynyl moiety of arylalkynes serves as both a directing group and a hydrogen acceptor. The substrate scope of this ortho-C–H silylation/hydrogenation was explored by use of eight combinations of arylalkynes and tertiary silanes. In cases using bulky substrates, the catalytic performance of 1-Cyp with a r...

ChemInform Abstract: Metal‐Free [4 + 2] Annulation of Arylalkynes with tert‐Butyl Nitrite Through C(sp2)—H Oxidation to Assemble Benzo[e][1,2]oxazin‐4‐ones.

AbstractA metal‐free radical‐mediated [4+2] annulation of internal arylalkynes with tert‐butyl nitrite is presented for the synthesis of benzoxazinones through the addition of t‐BuONO across the CC triple bond, hydration, isomerization, and aromatic C(sp2)—H oxidation cascades.

Metal-Free [4+2] Annulation of Arylalkynes withtert-Butyl Nitrite through C(sp2)H Oxidation to Assemble Benzo[e][1,2]oxazin-4-ones

A metal-free radical-mediated [4+2] annulation of internal arylalkynes with tert-butyl nitrite (t-BuONO) is presented for the synthesis of benzo[e][1,2]oxazin-4-ones through the addition of t-BuONO across the C C triple bond, hydration, isomerization and aromatic C(sp(2)) H oxidation cascades. The O-18-labeling experiment shows that two oxygen atoms in the product system are from water.

Origin of Regioselectivity in the Copper-Catalyzed Borylation Reactions of Internal Aryl Alkynes with Bis(pinacolato)diboron

The detailed reaction mechanism for the borylation of internal aryl alkynes catalyzed by copper(I) boryl complexes was studied by experiments and density functional theory (DFT) calculations. The calculated results indicate that the Cu(I)-catalyzed borylation occurs through Ph–C≡C–R insertion into the Cu–B bond to give the α- and β-borylalkyl intermediates. Among the various substituent groups (Me, Et, i-Pr, t-Bu, 1,1-Et2Pr, and Cum) at the R position, internal aryl alkynes having substituent groups less bulky than an aryl group converted to β-borylated products, whereas those having substituent groups bulkier than an aryl group converted to α-borylated products with high regio- and stereoselectivity.

Unimolecular tetrakis-piperidine-4-ol: an efficient ligand for copper and amine free Sonogashira coupling

Unimolecular tetrakis-4-hydroxypiperidine catalysed Cu and amine free Sonogashira coupling of various aryliodides/bromides and alkyl or aryl terminal alkynes giving access to internal arylalkynes is reported.

ChemInform Abstract: Highly Selective Synthesis of Tetra‐Substituted Furans and Cyclopropenes: Copper(I)‐Catalyzed Formal Cycloadditions of Internal Aryl Alkynes and Diazoacetates.

A convenient Cu(I)-catalyzed cycloaddition of electron rich internal aryl alkynes and diazoacetates was discovered for the chemoselective and regioselective synthesis of tetra-substituted furans and cyclopropenes in moderate isolated yields (18–67%), and alkyne conversion (29–73%).

ChemInform Abstract: ortho‐Amide‐Directed Oxidation of Internal Aryl Alkynes Mediated by Cerium(IV) Ammonium Nitrate.

AbstractThe optimized conditions produce diketone structures, subunits of pharmaceutical drugs, in a selective manner.

Ortho-Amide-Directed Oxidation of Internal Aryl Alkynes Mediated by Cerium(IV) Ammonium Nitrate

A fascinating oxidation of alkynes mediated by CAN directed by the amide group to synthesize <i>N</i>-[2-(2-oxo-2-phenylacetyl)phenyl]benzamide derivatives under mild conditions is reported. Excellent yields were obtained with various substituents by this method.