Unsymmetrical Alkynes Research Articles

Doubly Regioselective C-H Hydroarylation of Unsymmetrical Alkynes Using Carboxylates as Deciduous Directing Groups.

A catalyst system composed of [(C6Me6)RuCl2]2, potassium carbonate/guanidine carbonate, and mesitoic acid efficiently promotes the doubly regioselective C-H hydroarylation of unsymmetrical alkynes. The process involves carboxylate-directed ortho-C-H bond activation followed by regioselective addition to the alkyne C-C triple bond with concerted decarboxylation. This action of the carboxylate as a deciduous directing group ensures exclusive monovinylation with high selectivity for the (E)-1,2-diarylalkene.

Ruthenium-Catalyzed Alkyne trans-Hydrometalation: Mechanistic Insights and Preparative Implications.

[Cp*RuCl]4 (1) has previously been shown to be the precatalyst of choice for stereochemically unorthodox trans-hydrometalations of internal alkynes. Experimental and computational data now prove that the alkyne primarily acts as a four-electron donor ligand to the catalytically active metal fragment [Cp*RuCl] but switches to adopt a two-electron donor character once the reagent R3MH (M = Si, Ge, Sn) enters the ligand sphere. In the stereodetermining step the resulting loaded complex evolves via an inner-sphere mechanism into a ruthenacyclopropene which swiftly transforms into the product. In accord with the low computed barriers, spectral and preparative data show that the reaction is not only possible but sometimes even favored at low temperatures. Importantly, such trans-hydrometalations are distinguished by excellent levels of regioselectivity when unsymmetrical alkynes are used that carry an -OH or -NHR group in vicinity of the triple bond. A nascent hydrogen bridge between the protic substituent and the polarized [Ru-Cl] unit imposes directionality onto the ligand sphere of the relevant intermediates, which ultimately accounts for the selective delivery of the R3M- group to the acetylene C-atom proximal to the steering substituent. The interligand hydrogen bonding also allows site-selectivity to be harnessed in reactions of polyunsaturated compounds, since propargylic substrates bind more tightly than ordinary alkynes; even the electronically coupled triple bonds of conjugated 1,3-diynes can be faithfully discriminated as long as one of them is propargylic. Finally, properly positioned protic sites lead to a substantially increased substrate scope in that they render even 1,3-enynes, arylalkynes, and electron-rich alkynylated heterocycles amenable to trans-hydrometalation which are otherwise catalyst poisons.

Ru(ii)-Catalyzed annulation of benzamidines and alkynes by C-H/N-H activation: a facile synthesis of 1-aminoisoquinolines.

An inexpensive Ru(ii) complex catalyzes the oxidative annulation reaction of disubstituted alkynes with benzamidines to provide highly valuable 1-aminoisoquinolines in high yields. The reaction also features excellent regioselectivity with some unsymmetrical alkynes.

Pd(NHC)PEPPSI-diazonium salts: an efficient blend for the decarboxylative Sonogashira cross coupling reaction

Pd(NHC) complexes catalyzed the synthesis of symmetrical and unsymmetrical internal alkynes with a broad spectrum of substrates that includes aromatic and heteroaromatic diazonium salts.

Synthesis of Unsymmetrical Aromatic Acetylenes by Diphenyl Chlorophosphate-Promoted Condensation Reaction of Aromatic Aldehydes and Sulfones

Synthesis of Unsymmetrical Aromatic Acetylenes by Diphenyl Chlorophosphate-Promoted Condensation Reaction of Aromatic Aldehydes and Sulfones

Ru-Catalyzed One-Pot Diannulation of Heteroaryls: Direct Access to π-Conjugated Polycyclic Amides.

A novel Ru-catalyzed oxidative double annulation of heteroarenes with symmetrical and unsymmetrical alkynes is reported. A general method for the unsymmetrical annulation of heteroarenes with two distinct alkynes is showcased for the first time. Methylphenyl sulfoximine (MPS) plays an important role in the annulations of heteroarenes and allows the construction of structurally complex π-conjugated heteroarene-fused polycyclic amide skeletons via the formation of multiple C-C and C-N bonds in a single operation. The reaction exhibits excellent substrate scope and tolerates a wide range of functional groups.

ChemInform Abstract: Ir‐Catalyzed Regio‐ and Stereoselective Hydrosilylation of Internal Thioalkynes: A Combined Experimental and Computational Study.

Iridium complexes are known catalysts for a range of silylation reactions. However, the exploitation for selective hydrosilylation of unsymmetrical internal alkynes has been limitedly known. Described here is a new example of this type. Specifically, [(cod)IrCl]2 catalyzes the efficient and mild hydrosilylation of thioalkynes by various silanes with excellent regio- and stereoselectivity. DFT studies suggested a new mechanism involving Ir(I) hydride as the key intermediate.

ChemInform Abstract: Selective Rhodium‐Catalyzed Hydroformylation of Alkynes to α,β‐Unsaturated Aldehydes with a Tetraphosphoramidite Ligand.

AbstractThe reaction tolerates diaryl as well as dialkyl substituted alkynes.

Titanium-Promoted Cross-Coupling for the Selective Synthesis of Polysubstituted, Conjugated Amides.

α,β-Unsaturated amides are important building blocks and are key structural elements in a number of biologically active natural products. Despite their importance and prevalence, few methods exist to prepare conjugated amides directly and modularly. To address this gap, a titanium-promoted coupling of alkynes and isocyanates has been developed. The method is highly stereoselective, producing only the E isomer with good chemoselectivity and regioselectivity (>95/5), for unsymmetrical internal alkynes that contain a steric bias. The reactive titanacyclopentene intermediate formed from the coupling of the alkyne and isocyanate was additionally reacted with various electrophiles to access tetrasubstituted enamides.

New Regio- and Stereoselective Cascades via Unstabilized Azomethine Ylide Cycloadditions for the Synthesis of Highly Substituted Tropane and Indolizidine Frameworks.

Multisubstituted tropanes and indolizidines have been prepared with high regio- and stereoselectivity by the [3+2] cycloaddition of unstabilized azomethine ylides generated from readily prepared trimethylsilyl-substituted 1,2-dihydropyridines via protonation or alkylation followed by desilylation. Starting from 1,2-dihydropyridines bearing a ring trimethylsilyl substituent at the 6-position, an intermolecular alkylation/desilylation provides endocyclic unstabilized ylides that successfully undergo cycloaddition with a range of symmetrical and unsymmetrical alkyne and alkene dipolarophiles to afford densely substituted tropanes incorporating quaternary carbons in good yields and with high regio- and stereoselectivity. Additionally, an intramolecular alkylation/desilylation/cycloaddition sequence provides convenient and rapid entry to bridged tricyclic tropane skeletons, allowing for five contiguous carbon stereocenters to be set in a single experimental operation and under mild conditions. Starting from 1,2-dihydropyridines with trimethylsilylmethyl groups on nitrogen, protonation followed by desilylation generates exocyclic unstabilized ylides that undergo cycloaddition with unsymmetrical alkynes to give indolizidines with good regio- and stereoselectivity. N-Trimethylsilylmethyl-1,2-dihydropyridines can also be alkylated and subsequently desilylated to give endocyclic unstabilized ylides that undergo intermolecular cycloadditions with carbonyl compounds to give bicyclic oxazolidine products in good overall yields. Moreover, an intramolecular alkylation/desilylation/cycloaddition sequence with the N-trimethylsilylmethyl-1,2-dihydropyridines affords tricyclic indolizidines that incorporate quaternary carbons and up to five stereocenters with good to excellent regio- and diastereoselectivity.

Copper(I)‐catalyzed reaction of unsymmetrical alkyne with HB(pin): a density functional theory study

AbstractWith the aid of density functional theory calculations, we have investigated the mechanism of copper(I)‐catalyzed reaction between unsymmetrical alkyne 1‐phenyl‐1‐butyne and HB(pin). The results of the density functional theory calculations show that the reaction mechanism involves syn‐addition of catalyst ([NHC]CuH) (NHC = N‐heterocyclic carbene) to 1‐phenyl‐1‐butyne to form the alkenyl copper intermediates 2a and 5a, and then intermediates 2a and 5a react with HB(pin) to give intermediates 3 (3a, 3b) and 6 (6a, 6b), and finally elimination of catalyst completes the catalytic cycle and yields the α‐product P1 and β‐product P2. We found that α‐product should be more favored than β‐product. The calculated results are consistent with the experimental findings. The present paper may provide a useful guide for understanding other analogous copper‐catalyzed hydroboration of unsymmetrical alkynes.

Regio- and Stereoselective Hydrosilylation of Unsymmetrical Alkynes Catalyzed by a Well-Defined, Low-Valent Cobalt Catalyst.

Herein, the use of a well-defined low-valent cobalt(I) catalyst [HCo(PMe3)4] capable of performing the highly regio- and stereoselective hydrosilylation of internal alkynes is reported. The reaction can be applied to a variety of hydrosilanes, symmetrical and unsymmetrical alkynes, giving in many cases a single hydrosilylation isomer. Experimental and theoretical studies suggest the key step to be a hydro-cobaltation and that the reaction proceeds through a classical Chalk-Harrod mechanism.

Chemo- and Regioselective Rhodium(I)-Catalyzed [2+2+2] Cycloaddition of Allenynes with Alkynes.

A highly chemo- and regioselective partially intramolecular rhodium(I)-catalyzed [2+2+2] cycloaddition of allenynes with alkynes is described. A range of diverse polysubstituted benzene derivatives could be synthesized in good to excellent yields, in which the allenynes served as synthetic equivalent to the diynes. A high regioselectivity could be observed when allenynes were treated with unsymmetrical alkynes.

Acceleration of metallacycle-mediated alkyne–alkyne cross-coupling with TMSCl

Investigation of titanium-centered metallacycle-mediated cross-coupling between unsymmetrical internal alkynes has led to the discovery that TMSCl significantly accelerates the CC bond forming event. We report a collection of results that compare the efficiency of this reaction employing Ti(Oi-Pr)4/2n-BuLi in PhMe with and without TMSCl, demonstrating in every case that the presence of TMSCl has a profound impact on efficiency. While relevant in the context of developing this fundamental bond-forming process as an entry to more complex organometallic transformations, these modified reaction conditions allow coupling processes to be run at >10 times the concentrations previously possible [in 2.4M n-BuLi (hexanes)], without the requirement of additional solvent. Finally, we demonstrate the effectiveness of these modified reaction conditions for the annulative cross-coupling between TMS-alkynes and 1,6-enynes leading to the formation of angularly substituted hydrindanes with, now well appreciated, high levels of regio- and stereoselection.

Selective Rhodium-Catalyzed Hydroformylation of Alkynes to α,β-Unsaturated Aldehydes with a Tetraphosphoramidite Ligand.

A tetraphosphoramidite ligand was successfully applied to a Rh-catalyzed hydroformylation of various symmetrical and unsymmetrical alkynes to afford corresponding α,β-unsaturated aldehyde products in good to excellent yields (up to 97% yield). Excellent chemo- and regioselectivities and high activities (up to 20 000 TON) were achieved. The corresponding α,β-unsaturated aldehyde products can be transformed into many useful and important organic molecules, such as indenamine derivatives and lukianol pyrroles. This great performance makes the hydroformylation of alkynes highly practical with great potential.

Ir-Catalyzed Regio- and Stereoselective Hydrosilylation of Internal Thioalkynes: A Combined Experimental and Computational Study.

Iridium complexes are known catalysts for a range of silylation reactions. However, the exploitation for selective hydrosilylation of unsymmetrical internal alkynes has been limitedly known. Described here is a new example of this type. Specifically, [(cod)IrCl]2 catalyzes the efficient and mild hydrosilylation of thioalkynes by various silanes with excellent regio- and stereoselectivity. DFT studies suggested a new mechanism involving Ir(I) hydride as the key intermediate.

Synthesis of Vinyl Carboxylic Acids using Carbon Dioxide as a Carbon Source by Iron‐Catalyzed Hydromagnesiation

AbstractAn iron‐catalyzed synthesis of α,β‐unsaturated carboxylic acids from alkynes and carbon dioxide was developed. This reaction proceeds through hydromagnesiation of alkynes followed by carbon dioxide insertion under atmospheric pressure and ambient temperature in the presence of iron and a Grignard reagent as a catalyst and hydride source, respectively. Several symmetrical and unsymmetrical alkynes were transformed into the corresponding acids in good to excellent yields. The methodology provides an efficient route to the synthesis of vinyl carboxylic acids.

ChemInform Abstract: Selective Double Carbomagnesiation of Internal Alkynes Catalyzed by Iron‐N‐Heterocyclic Carbene Complexes: A Convenient Method to Highly Substituted 1,3‐Dienyl Magnesium Reagents.

AbstractAn iron(II)‐N‐heterocyclic carbene (NHC) complex is found to be effective as precatalyst for double carbometalation of unsymmetrical internal alkynes with Grignard‐reagents.

Rhodium catalyzed regioselective arene homologation of aryl urea via double C–H bond activation and migratory insertion of alkyne

A convenient rhodium catalyzed oxidative arene homologation of aniline derivatives with symmetrical or unsymmetrical alkynes using Cu(OAc)2 as oxidant is described. Urea group is shown to be effective as a directing group for initial ortho C–H activation. Two migratory insertion events of alkyne into Rh–C bond occur successively, both with complete regioselectivity. This method is particularly useful for synthesis of polyarenes with different substituents, which has not been reported with conventional protocol. A mechanism has been proposed to explain the observed data.

Nickel(0)-Catalyzed Denitrogenative Transannulation of Benzotriazinones with Alkynes: Mechanistic Insights of Chemical Reactivity and Regio- and Enantioselectivity from Density Functional Theory and Experiment

The mechanism of Ni(0)-catalyzed denitrogenative transannulation of 1,2,3-benzotriazin-4(3H)-ones with alkynes to access isoquinolones has been comprehensively studied by a density functional theory (DFT) calculation and control experimental investigation. The results indicate that the transformations proceed via a sequential nitrogen extrusion, carbometalation, Ni–C bond insertion, and reductive elimination process. A frontier molecular orbital (FMO) theory and natural bond orbital (NBO) analysis reveals that the advantages of substituents on chemical reactivity and regioselectivity exist for multiple reasons: (1) Phenyl groups on the N atom of benzotriazinone and/or unsymmetrical alkynes mainly account for the high reactivity and regioselectivity via its electronic effect. (2) The π···π interaction between the phenyl substituent on the alkyne and triazole ring might partially contribute to the high regioselectivity when unsymmetrical alkynes were employed as the substrates. Furthermore, DFT calculations...