Internal Alkynes Research Articles

Development of Controllable Hetero-Pauson-Khand Polymerization to Functional Stimuli-Responsive Poly(γ-lactam)s.

Polymers containing lactam structures play a crucial role in both natural biological systems and human life, and their synthesis, functions and applications are of utmost importance for biomimetics and the creation of new materials. In this study, we developed an efficient heterogeneous Pauson-Khand polymerization (h-PKP) method for the controlled synthesis of main-chain poly(γ-lactam)s containing α, β-unsaturated γ-lactam functionalities using readily available internal alkynes and imines. The molecular weights of the resulting poly(N-Ts/γ-lactam)s can be precisely controlled by adjusting the ratio of phenyl formate and nickel. These polymers exhibit high solid-state luminescence and demonstrate rapid and sensitive dual responsiveness to light and acid stimuli. They further demonstrate strong reactive oxygen species (ROS) generation capability. The unique dual-emission peaks observed in poly(N-H/γ-lactam)s obtained through post-treatment under acidic conditions demonstrate a mechanism of aggregation-induced intermolecular excited-state proton transfer specific to lactam structures. The efficient one-pot synthetic method for poly(γ-lactam) provides a novel strategy for constructing polymers with γ-lactam structures in the main chain and the simple and efficient post-modification method offer a versatile toolbox for functionalizing poly(γ-lactam)s to expand their potential applications.

Ru-Catalyzed Redox-Neutral Coupling of N-Chlorobenzamides with Unsymmetrical Alkynes in Water.

In water, Ru-catalyzed annulation of N-chlorobenzamides with unsymmetrical internal alkynes bearing aryl, hydroxy, ester, and sulfonyl functionalities has been accomplished to afford isoquinolone scaffolds under external oxidant-free conditions at room temperature. Use of water as reaction medium, redox-neutral conditions, regioselectivity, and substrate scope are important practical features.

Experimental and computational studies of steric factors in the isomerization of internal alkynes within the coordination environment of half-sandwich metal complexes.

The isomerization of internal alkynes Ar1C≡CAr2 within the coordination environment of low-valent half-sandwich [Ru(dppe)Cp]+ complexes via a 1,2-migration process affords vinylidene species [Ru{=C=C(Ar1)Ar2}(dppe)Cp]+. The rearrangement reactions of symmetrically and asymmetrically substituted substrates featuring different electron-donating and -withdrawing groups and of varying steric bulk were modelled using density functional theory (DFT), and the conclusions supported by experimental observations. Examination of the reaction pathway and associated activation barriers reveal a high solvent dependency for the generation of the key intermediate species [Ru(dppe)Cp]+ from [RuCl(dppe)Cp] by Na+ induced halide abstraction , with the lattice enthalpy of the NaCl by-product playing a critical role in the overall thermochemical balance of the reaction. The activation barriers associated with the reaction of [Ru(dppe)Cp]+ with Ar1C≡CAr2, and the relative energies of the alkyne complexes [Ru(h2-Ar1C≡CAr2)(dppe)Cp]+, are sensitive to the electron density of the alkyne and conformational changes associated with the 'bend-back' of the substrate. The latter differs by up to 66.1 kJ/mol, which in turn impacts the barrier height of the subsequent 1,2-migration step . The relative importance of these factors is evinced by the successful rearrangement of the very sterically congested 1(9-anthryl)-2(9-phenanthryl) acetylene into the fully characterized diaryl vinylidene complex, which was isolated in 89% yield.

Rare-Earth Metal-Catalyzed Regioselective Hydrosilylation of Internal Alkenes and Alkynes

A highly regioselective hydrosilylation reaction of internal alkenes was achieved by commercially available La(HMDS)3. Notably, the Z or E configuration of internal alkenes displays negligible influence on the reactivity and regioselectivity. In addition, internal alkynes were applicable, affording the mono di-hydrosilylation product in the presence of La(HMDS)3 or mono-hydrosilylation product with Y(HMDS)3 as the promoter.

Stereodivergent Hydrohalogenation of SCF3 Alkynes and Cross- Coupling Reactions.

SCF3-substituted internal alkynes undergo regio- and stereoselective hydrohalogenation to provide the corresponding β-halo-α-SCF3-alkenes. The regioselectivity is ensured by the strong polarization of the C≡C triple bond in SCF3-alkynes, while the stereoselectivity is governed by the strength of the proton donor and/or by the solvent polarity. The potential of β-iodo-α-SCF3-alkenes was illustrated in several cross-coupling, protodeiodination, and cyanation reactions.

Hydrosilylation of Alkynes Catalyzed by an Iron(II) PCP Pincer Alkyl Complex

Vinylsilanes are very useful building blocks in organic synthesis and have widespread applications in life sciences and materials chemistry. Here we describe the potential of complex cis‐[Fe(PCP‐iPr)(CH2CH2CH3)(CO)2] as an effective catalyst for the hydrosilylation of both terminal and internal alkynes with SiPhH3 to give vinylsilanes. The reactions were typically performed with a catalyst loading of 1 mol% for 24 h at 70oC. The catalytic reaction is initiated by migratory insertion of a CO ligand into the Fe‐alkyl bond to yield an acyl intermediate which reacts with silanes to form the 16e‐ Fe(II) silyl catalyst [Fe(PCP‐iPr)(SiPhH2)(CO)]. In the case of aliphatic terminal alkynes good regioselectivity (anti‐Markovnikov addition) towards the thermodynamically more stable β‐(E)‐vinylsilanes in ratios of up to 10:90 was achieved, while for aromatic alkynes the selectivities were poor with ratios of β‐(Z)‐ to β‐(E)‐vinylsilanes of about 40:60. With internal unsymmetrical alkynes, the two possible regioisomers of the syn‐addition of SiPhH3 were obtained in different ratios with no clear trend towards one regioisomer. Internal symmetrical alkynes yielded exclusively the respective syn‐products in high yields. Mechanistic investigations including deuterium labelling studies were undertaken to provide a reasonable reaction mechanism.

Palladium-Catalyzed Double Decarboxylative [3 + 2] Annulation of Naphthalic Anhydrides with Internal Alkynes.

A palladium-catalyzed [3 + 2] annulation of naphthalic anhydrides with internal alkynes has been developed. The present protocol offers an efficient and convenient route to access a series of 1,2-disubstituted acenaphthylenes with excellent functional group compatibility. The reaction is proposed to proceed through a double decarboxylation sequence. The reported synthetic protocols can be extended to napthalene- and perylenedicarboximide-containing substrates. The molecular structures, photophysical properties, and frontier molecular orbitals of the obtained adducts were investigated by X-ray crystallography, UV-vis and fluorescence spectroscopy, and DFT calculations.

Semi-reduction of alkynes catalyzed by a tri-palladium complex

Upon activation by ammonia-borane, a tri-palladium complex [(bpnp)2Pd3Cl2]Cl2 (Pd3) was found to be catalytically active for hydrogenation of alkynes to render the corresponding cis-olefins. Typically, a mixture of diphenylacetylene (0.80 mmol), Pd3 (0.2 mol %), and NH3.BH3 (10 mol%) in THF/H2O (10:1, 1 mL) was stirred at 30 °C under H2 (1 atm) for 2 h, giving (Z)-stilbene in 95 % yield with a turnover frequency (TOF) ∼240 h−1. This catalyst is applicable to both internal and terminal alkynes with aryl or alkyl substituents.

Hydromethylthiolation of alkynes via nucleophilic addition of dimethyl disulfide in DMSO

A hydromethylthiolation method for various alkynes has been developed using dimethyl disulfide as a source of the nucleophilic methylthiolate anion in a DMSO/EtOH or DMSO/H2O solvent system, with KOH as the base. For terminal aromatic alkynes, the reactions predominantly yield (Z)-anti-Markovnikov hydromethylthiolation products. The ratio of anti-Markovnikov to Markovnikov products typically exceeds 10:1, while the ratio of (Z)- to (E)-anti-Markovnikov products usually surpasses 7:1. In contrast, terminal aliphatic alkynes primarily produce Markovnikov hydromethylthiolation products. Reactions of internal aromatic alkynes also successfully produce the corresponding hydromethylthiolation products, whereas internal aliphatic alkynes do not exhibit reactivity in this system. The proposed mechanism suggests that in a basic DMSO solvent system, each equivalent of dimethyl disulfide is converted into two equivalents of methylthiolate anion. This anion then undergoes nucleophilic addition to the alkyne substrates, yielding hydromethylthiolation products. The regioselectivity and stereoselectivity of the hydromethylthiolation are influenced by the stability of the vinyl carbanion intermediate. Additionally, this method is also applicable to the hydrothiolation of alkynes using other disulfides.

Ru(II)-Catalyzed Skeletal Editing of Oxindole with Internal Alkyne To Synthesize C7-Alkylated Indole Derivatives.

A Ru(II)-catalyzed skeletal editing of oxindole scaffolds was established to afford C7-alkyl acetate indole derivatives using internal alkyne and alkyl alcohol. The developed method is simple, efficient, and straightforward. The reaction was extended to substrates having wide chemoselective profiles. When unsymmetrical alkynes were used, promising regioselectivity was realized. A preliminary mechanistic study revealed that the reaction pathway proceeded by Ru(II)/Ag(I)-catalyzed amide cleavage and subsequent oxidative annulation.

Unconventional Insertions of Internal Alkynes into a Mixed-Valent Silaiminyl-Silylene.

The reactivity of a mixed-valent silaiminyl-silylene [LSi-Si(NDipp)L] (L = PhC(NtBu)2, Dipp = 2,6-iPr-C6H3) toward various substituted internal alkynes was investigated. In contrast to previous reports that primarily yield [Si(μ-C2)Si]-modified rings via 1,2-addition of two silylenes in the center of the molecule, our study reveals a novel reaction pathway. The introduction of [R1-C≡C-R2] (R1 = Ph or SiMe3, R2 = Ph or C≡CSiMe3) gave unconventional insertion into one of the amidinate ligands, followed by migration of the {NtBu} group to bridge two Si atoms. This results in the formation of diverse expanded silacycles.

Catalytic Cycloaddition Reactions of Ynol and Thioynol Ethers

Comprehensive SummaryElectron‐rich alkynes, such as ynol and thioynol ethers, have proven to be versatile and appealing partners in catalytic cycloaddition reactions, and thus have raised considerable attentions owing to the practical application in the modular assembly of valuable carbo‐ and heterocycles. The past decades have witnessed inspiring advances in this emerging field, and an increasing number of related discoveries have been exploited. Divided into two main sections on the basis of substrate type, in each section this comprehensive review will initially summarize their synthetic preparations and subsequently examine their reactivity in every sort of catalytic cycloaddition with emphasis on the methodology development, aimed at providing an access to this burgeoning area and encouraging further innovations in the near future. Key ScientistsFor the cycloaddition of ynol ethers, in 2004, Kozmin et al. firstly developed a silver‐catalyzed [2 + 2] cycloaddition of siloxy alkynes with electron‐poor olefins. In 2012, Hiyama et al. realized a palladium‐catalyzed formal [4 + 2] annulation of alkynyl aryl ethers with internal alkynes. In the same year, Sun et al. discovered an efficient [6 + 2] cyclization between siloxy alkynes and 2‐(oxetan‐3‐yl)benzaldehydes by applying HNTf2 as catalyst. In 2017, Wender et al. first utilized vinylcyclopropanes (VCPs) as coupling partners in the [5 + 2] annulation of ynol ethers. In 2018 and 2020, Ye et al. reported zinc‐catalyzed formal [3 + 2] and [4 + 3] cycloaddition, respectively. For the cycloaddition of thioynol ethers, in 2004, Hilt et al. realized a [4 + 2] cycloaddition by employing the alkynyl sulfides and acyclic 1,3‐dienes. In 2006, a ruthenium‐catalyzed [2 + 2] cycloaddition of thioynol ethers with bicyclic alkenes was accomplished by Tam. In 2014, Sun et al. reported an elegant iridium‐catalyzed click reaction of thioalkynes with azides.

Ligand-Controlled Regiodivergent Ring Expansion of Benzosilacyclobutenes with Alkynes en Route to Axially Chiral Silacyclohexenyl Arenes.

A ligand-controlled regiodivergent and enantioselective ring expansion of benzosilacyclobutenes with internal naphthyl alkynes has been achieved by adjusting the ligand cavity size. The ligand (S)-8H-binaphthyl phosphoramidite, featuring small methyl groups on its arms, provides a spacious cavity that favors sterically demanding Si-Csp3 ring expansion, predominantly yielding axially chiral (S)-1-silacyclohexenyl arenes. In contrast, the ligand (R)-spiro phosphoramidite, with bulky t-Bu groups on its arms, offers a compact cavity that facilitates less sterically demanding Si-Csp2 ring expansion, leading primarily to axially chiral (S)-2-silacyclohexenyl arenes. Density functional theory calculations delineate distinct mechanistic pathways for each ring expansion route and elucidate their regio- and enantioselectivity.

Metal-free radical selenothiocyanation of terminal and internal alkynes.

We report herein a synthetic strategy for the generation of direct selenothiocyanation from both terminal and internal alkynes via a radical process. Alkynes derived from bioactive molecules, such as L(-)-borneol and L-menthol, are suitable for selenothiocyanation reaction. This method features metal-free conditions and readily available reagents.

Mechanism of Iron‐Catalyzed C—H Alkenylation of Pivalophenone Derivatives With Unsymmetric Internal Alkynes

ABSTRACTThe mechanism of an iron‐catalyzed C—H alkenylation of pivalophenone derivatives with unsymmetric internal alkynes is investigated in details by means of density functional theory calculations. It is shown that the reaction begins with two consecutive ligand exchanges, followed by a fast and reversible oxidative addition C—H activation step. Next, an alkyne insertion into the Fe—H bond, two isomerization steps, and a reductive elimination afford the final product. The reductive elimination is the turnover‐limiting step of the process, and also determines the regiochemical outcome of the reaction. The origin of the regioselectivity is proposed to be the steric repulsion between the bulky trimethylsilyl group and the aromatic fragment in the reductive elimination step leading to the not observed regioisomer.

Ir(III)-Catalyzed Tandem Annulation of Aromatic Amides with 1,6-Diynes via Dual C-H Bond Activation.

An Ir(III)-catalyzed annulation of aryl amides with 1,6-diynes via ortho- as well as meta-dual C-H bond activation reaction is reported. The scope of the annulation reaction was examined with various substituted aryl amides, as well as 1,6-diynes. In this protocol, 1,6-diynes exhibit diverse reactivity compared with internal alkynes. It is important to note that the three C-C bond formation takes place consecutively via ortho followed by meta-dual C-H bond annulation by using a weak chelating group in one pot. A possible catalytic reaction mechanism was proposed to account for the annulation reaction.

Gold Trifluoromethyl Complexes as Efficient Regioselective Catalysts in Alkyne Hydration.

Gold(III) complexes containing trifluoromethyl ligands are efficient catalysts in the hydration of alkynes, operating at low catalyst loadings, without additives, using environmentally friendly solvents and at mild conditions (60 °C). Hydration of terminal and internal alkynes provides the corresponding ketones in quantitative yields without special precautions as dry solvents or inert atmospheres. Remarkably, hydration of asymmetric internal alkynes proceeds with moderate to notable regioselectivities, providing mixtures of the two possible isomers with ratios up to 90 : 10.

Palladium‐Catalyzed Denitrogenative Coupling of Aryldiazonium Salts with Terminal Alkynes for the Assembly of Internal Alkynes

AbstractAn N‐heterocyclic carbene palladium (NHC‐palladium)‐catalyzed denitrogenative coupling of aryldiazonium salts with terminal alkynes in ionic liquids has been accomplished. This catalytic strategy provides an effective and green synthetic protocol for the assembly of structurally diverse internal alkynes with excellent functional group compatibility and mild conditions. In the presence of 1 mol % of IMes‐Pd‐Im‐Cl2 as the catalyst, a wide range of terminal alkynes and aryldiazonium salts could be excellently tolerated. Basic ionic liquid plays a crucial role in this catalytic system, which not only acts as the green solvent, but also provides basic environment for the carbon‐carbon bond formation process. Notably, this catalytic system could be recycled up to six times and reused without significant loss of catalytic activity.

Development of Controllable Hetero‐Pauson‐Khand Polymerization to Functional Stimuli‐Responsive Poly(γ‐lactam)s

Polymers containing lactam structures play a crucial role in both natural biological systems and human life, and their synthesis, functions and applications are of utmost importance for biomimetics and the creation of new materials. In this study, we developed an efficient heterogeneous Pauson‐Khand polymerization (h‐PKP) method for the controlled synthesis of main‐chain poly(γ‐lactam)s containing α, β‐unsaturated γ‐lactam functionalities using readily available internal alkynes and imines. The molecular weights of the resulting poly(N‐Ts/γ‐lactam)s can be precisely controlled by adjusting the ratio of phenyl formate and nickel. These polymers exhibit high solid‐state luminescence and demonstrate rapid and sensitive dual responsiveness to light and acid stimuli. They further demonstrate strong reactive oxygen species (ROS) generation capability. The unique dual‐emission peaks observed in poly(N‐H/γ‐lactam)s obtained through post‐treatment under acidic conditions demonstrate a mechanism of aggregation‐induced intermolecular excited‐state proton transfer specific to lactam structures. The efficient one‐pot synthetic method for poly(γ‐lactam) provides a novel strategy for constructing polymers with γ‐lactam structures in the main chain and the simple and efficient post‐modification method offer a versatile toolbox for functionalizing poly(γ‐lactam)s to expand their potential applications.

Revealing the Role of Solvent in anti-Oxypalladation-Triggered Regiocontrolled Domino Reactions for the Synthesis of Benzazepine- and Tetrahydroquinoline-Containing Scaffolds: A Combined Computational and Experimental Study.

Palladium-catalyzed regiocontrolled intramolecular oxypalladation-initiated cascades of multifunctional internal alkyne bearing an N-tosyl tether deliver functionalized benzazepine as an exclusive product via 6-endo-dig pathway in 1,4-dioxane solvent and tetrahydroquinoline scaffold as a major product via the 5-exo-dig pathway in the DMSO solvent. The role of the solvent in controlling the regioselectivity is still unknown which can be a major hurdle for further reaction development. Moreover, the reaction in DMSO suffered from having a mixture of products, and no exclusive formation of tetrahydroquinoline was achieved. Herein, we report a concerted computational and experimental study, revealing the role of the solvent in controlling the reaction outcome. DFT study revealed that the formation of the σ-vinylpalladium intermediate is reversible for the 5-exo-dig pathway while it is irreversible for the 6-endo-dig mechanism in 1,4-dioxane and consequently, the 5-exo-dig pathway is difficult to proceed. In contrast, both the 5-exo-dig and 6-endo-dig pathways are irreversible in DMSO. We predicted an exclusive formation of isobenzofuranone-fused chromane via the 5-exo-dig pathway when the N-tosyl tether is replaced by the O-tether in the internal alkyne in DMSO. The experimental study confirms the theoretical hypothesis and provides a highly chemo-divergent approach for the synthesis of biologically significant chromane with a large substrate scope and up to 95% yield at room temperature.