Simple Alkynes Research Articles

Synthesis of Functionalized 4‐Fluoropyridazines

AbstractA route to 4‐fluoropyridazines by a [2+1]/[3+2] cycloaddition sequence between an acetylenic derivative, a difluorocarbene source, and a diazo compound is reported. This approach is highly modular and compatible with a broad range of functional groups. The protocol does not require the isolation of any reactive intermediates and, thus, allows for access to a wide range of 4‐fluoropyridazines in a single synthetic step from simple alkynes. Furthermore, these fluorinated compounds can be easily diversified by nucleophilic aromatic substitution (SNAr) to displace the fluoro group to give a wider range of 3,4,6‐trisubstituted pyridazines. As a result of increasing interest in functionalized pyridazines as well as fluorinated derivatives, this efficient and concise approach to 4‐fluoropyridazines should be of value to medicinal chemists.

A modular route to boron doped PAHs by combining borylative cyclisation and electrophilic C-H borylation.

Heteroatom doping into polyaromatic hydrocarbons (PAHs) is a powerful approach for modifying key physical properties, however, there are extremely few modular routes that enable facile formation of B-, B2- and B,N-(specifically not containing direct B-N bonds) doped PAHs despite the growing importance of these materials. Sequential, one pot borylative cyclisation/intramolecular electrophilic C-H borylation of naphthyl-alkynes provides a simple new route to access novel B-, B,N- and B2-doped (PAHs). The initial products, dihydronaphthalene/dihydroquinoline B-mesityl PAHs, were reacted with [Ph3C][BF4]/pyridyl base to form the oxidised B-, and B,N-doped PAHs. However, for B-triisopropylphenyl (Trip) PAH congeners oxidation has to be performed prior to Trip installation due to preferential oxidation of an isopropylaryl moiety to the styrene. This alternative sequence enables access to Trip-B-PAHs and to structurally constrained B and B2-PAHs. Analysis of the solid state structures and optoelectronic properties of these PAHs confirm that frontier orbital energies, extended packing structures, Stokes shift and quantum yields all can be rationally modified using this methodology. The simplicity of this synthetic approach makes it a powerful tool for rapidly generating novel bench stable boron doped PAHs, which is important for facilitating further structure-property relationship studies and the wider utilisation of these materials in optoelectronic applications.

BCl3‐Induced Annulative Oxo‐ and Thioboration for the Formation of C3‐Borylated Benzofurans and Benzothiophenes

AbstractBCl3‐induced borylative cyclization of aryl‐alkynes possessing ortho‐EMe (E=S, O) groups represents a simple, metal‐free method for the formation of C3‐borylated benzothiophenes and benzofurans. The dichloro(heteroaryl)borane primary products can be protected to form synthetically ubiquitous pinacol boronate esters or used in situ in Suzuki–Miyaura cross couplings to generate 2,3‐disubstituted heteroarenes from simple alkyne precursors in one pot. In a number of cases alkyne trans‐haloboration occurs alongside, or instead of, borylative cyclization and the factors controlling the reaction outcome are determined.

BCl3 -Induced Annulative Oxo- and Thioboration for the Formation of C3-Borylated Benzofurans and Benzothiophenes.

BCl3‐induced borylative cyclization of aryl‐alkynes possessing ortho‐EMe (E=S, O) groups represents a simple, metal‐free method for the formation of C3‐borylated benzothiophenes and benzofurans. The dichloro(heteroaryl)borane primary products can be protected to form synthetically ubiquitous pinacol boronate esters or used in situ in Suzuki–Miyaura cross couplings to generate 2,3‐disubstituted heteroarenes from simple alkyne precursors in one pot. In a number of cases alkyne trans‐haloboration occurs alongside, or instead of, borylative cyclization and the factors controlling the reaction outcome are determined.

Multicomponent Coupling Approach to Cross-Conjugated Polymers from Vanillin-Based Monomers

We describe the use of vanillin-based monomers as a renewable feedstock for the synthesis of cross-conjugated polymers. This transformation exploits a catechyl-substituted phosphonite mediated multicomponent polymerization to convert vanillin-derived diimines, commercial diacid chlorides, and simple alkynes or alkenes into conjugated pyrrole-based polymers. The flexibility of the multicomponent polymerization has allowed for the efficient formation of families of vanillin-derived fluorescent polymers with tunable properties. This includes coupling vanillin with furan-based acid chlorides as the first cross-conjugated polymer composed of both components of lignocellulosic biomass.

Selenide-Catalyzed Stereoselective Construction of Tetrasubstituted Trifluoromethylthiolated Alkenes with Alkynes.

The efficient regio- and stereoselective construction of tetrasubstituted alkenes is challenging and very important. For this purpose, we have developed an efficient approach to synthesize tetrasubstituted trifluoromethylthiolated alkenes from simple alkynes in excellent regio- and stereoselectivities by selenide-catalyzed multicomponent coupling. Using this method, trifluoromethylthiolated alkenyl triflates and arenes were achieved. In particular, the triflates could be further converted into carbofunctionalized alkenes by palladium-catalyzed cross-coupling reactions. Our method provides a new pathway for the construction of trifluoromethylthiolated tricarboalkenes. This work presents the first example of selenide-catalyzed trifluoromethylthiolation of alkynes and enables the challenging functionalizations of alkynes.

Copper Nitrate Mediated Regio- and Stereoselective Difunctionalization of Alkynes: A Direct Approach to α-Chloro-β-nitroolefins.

An efficient copper nitrate mediated chloronitration reaction was developed for the direct synthesis of α-chloro-β-nitroolefins with high regio- and stereoselectivity from simple alkynes and low toxic stannous chloride. This protocol provides a direct access to polysubstituted alkenes with operational simplicity, good functional group tolerance, and a wide substrate scope. Various applications of given products allowed the straightforward assembly of molecular complexity and indicated them as promising and valuable building blocks in organic synthesis.

Atom-economic catalytic amide synthesis from amines and carboxylic acids activated in situ with acetylenes.

Amide bond-forming reactions are of tremendous significance in synthetic chemistry. Methodological research has, in the past, focused on efficiency and selectivity, and these have reached impressive levels. However, the unacceptable amounts of waste produced have led the ACS GCI Roundtable to label ‘amide bond formation avoiding poor atom economy' as the most pressing target for sustainable synthetic method development. In response to this acute demand, we herein disclose an efficient one-pot amide coupling protocol that is based on simple alkynes as coupling reagents: in the presence of a dichloro[(2,6,10-dodecatriene)-1,12-diyl]ruthenium catalyst, carboxylate salts of primary or secondary amines react with acetylene or ethoxyacetylene to vinyl ester intermediates, which undergo aminolysis to give the corresponding amides along only with volatile acetaldehyde or ethyl acetate, respectively. The new amide synthesis is broadly applicable to the synthesis of structurally diverse amides, including dipeptides.

Reaction Dynamics of O((3)P) + Propyne: I. Primary Products, Branching Ratios, and Role of Intersystem Crossing from Crossed Molecular Beam Experiments.

We performed synergic experimental/theoretical studies on the mechanism of the O((3)P) + propyne reaction by combining crossed molecular beams experiments with mass-spectrometric detection and time-of-flight analysis at 9.2 kcal/mol collision energy (Ec) with ab initio electronic structure calculations at a high level of theory of the relevant triplet and singlet potential energy surfaces (PESs) and statistical calculations of branching ratios (BRs) taking into account intersystem crossing (ISC). In this paper (I) we report the results of the experimental investigation, while the accompanying paper (II) shows results of the theoretical investigation with comparison to experimental results. By exploiting soft electron ionization detection to suppress/mitigate the effects of the dissociative ionization of reactants, products, and background gases, product angular and velocity distributions at different charge-to-mass ratios were measured. From the laboratory data angular and translational energy distributions in the center-of-mass system were obtained for the five competing most important product channels, and product BRs were derived. The reactive interaction of O((3)P) with propyne under single collision conditions is mainly leading to the rupture of the three-carbon atom chain, with production of the radical products methylketenyl + atomic hydrogen (BR = 0.04), methyl + ketenyl (BR = 0.10), and vinyl + formyl (BR = 0.11) and the molecular products ethylidene/ethylene + carbon monoxide (BR = 0.74) and propandienal + molecular hydrogen (BR = 0.01). Because some of the products can only be formed via ISC from the entrance triplet to the low-lying singlet PES, we infer from their BRs an amount of ISC larger than 80%. This value is dramatically large when compared to the negligible ISC reported for the O((3)P) reaction with the simplest alkyne, acetylene. At the same time, it is much larger than that (∼20%) recently observed in the related reaction of the three-carbon atom alkene, O((3)P) + propene at a comparable Ec. This poses the question of how important it is to consider nonadiabatic effects and their dependence on molecular structure for this kind of combustion reactions. The prevalence of the CH3 over the H displacement channels is not explained by invoking a preference for the addition on the methyl-substituted acetylenic carbon atom, but rather it is believed to be due to the different tendencies of the two addition triplet intermediates CH3CCHO (preferentially leading to H elimination) and CH3COCH (preferentially leading to CH3 elimination) to undergo ISC to the underlying singlet PES. It is concluded that the main coproduct of the CO forming channel is singlet ethylidene ((1)CH3CH) rather than ground-state ethylene. By comparing the derived BRs with those very recently derived from kinetics studies at room temperature and 4 Torr we obtained information on how BRs vary with collision energy. The extent of ISC is estimated to remain essentially constant (∼85%) with increasing Ec from ∼1 to ∼10 kcal/mol. The present experimental results shed light on the mechanism of the title reaction at energies comparable to those involved in combustion and, when compared with the results from the statistical calculations on the ab initio coupled PESs (see accompanying paper II), lead to an in-depth understanding of the rather complex reaction mechanism of O + propyne. The overall results are expected to contribute to the development of more refined models of hydrocarbon combustion.

ChemInform Abstract: Cu‐Catalyzed Transformation of Alkynes and Alkenes with Azide and Dimethyl Sulfoxide Reagents

Abstractas a facile route for the synthesis of 1‐((alkylthio)methyl)‐1H‐1,2,3‐triazoles

Calcium Carbide: A Unique Reagent for Organic Synthesis and Nanotechnology.

Acetylene, HC≡CH, is one of the primary building blocks in synthetic organic and industrial chemistry. Several highly valuable processes have been developed based on this simplest alkyne and the development of acetylene chemistry has had a paramount impact on chemical science over the last few decades. However, in spite of numerous useful possible reactions, the application of gaseous acetylene in everyday research practice is rather limited. Moreover, the practical implementation of high-pressure acetylene chemistry can be very challenging, owing to the risk of explosion and the requirement for complex equipment; special safety precautions need to be taken to store and handle acetylene under high pressure, which limit its routine use in a standard laboratory setup. Amazingly, recent studies have revealed that calcium carbide, CaC2 , can be used as an easy-to-handle and efficient source of acetylene for in situ chemical transformations. Thus, calcium carbide is a stable and inexpensive acetylene precursor that is available on the ton scale and it can be handled with standard laboratory equipment. The application of calcium carbide in organic synthesis will bring a new dimension to the powerful acetylene chemistry.

Cu-Catalyzed Transformation of Alkynes and Alkenes with Azide and Dimethyl Sulfoxide Reagents.

A novel and efficient Cu-catalyzed nitrogenation of alkynes and alkenes for the direct synthesis of sulfur-containing triazoles is described. Simple and readily available sulfoxides and azides are employed as the S- and N-source to prepare highly value N-,S-containing compounds from simple alkynes and alkenes.

ChemInform Abstract: Copper‐Catalyzed Synthesis of 1,1‐Diborylalkanes Through Regioselective Dihydroboration of Terminal Alkynes.

The copper-catalyzed sequential hydroboration of terminal alkynes with pinacolborane to prepare 1,1-diborylalkanes directly from alkynes was studied. Protected propargyl amines, propargyl alcohol derivatives, and simple alkynes regioselectively produced the desired 1,1-diborylalkanes in good yields with a copper/xantphos catalyst.

Photoredox-Catalyzed Stereoselective Conversion of Alkynes into Tetrasubstituted Trifluoromethylated Alkenes.

A regio- and stereoselective synthesis of trifluoromethylated alkenes bearing four different substituents has been developed. Stereocontrolled sulfonyloxytrifluoromethylation of unsymmetric internal alkynes with an electrophilic CF3 reagent, namely the triflate salt of the Yagupol'skii-Umemoto reagent, in the presence of an Ir photoredox catalyst under visible-light irradiation afforded trifluoromethylalkenyl triflates with well-predictable stereochemistry resulting from anti addition of the trifluoromethyl and triflate groups. Subsequent palladium-catalyzed cross-couplings led to tetrasubstituted trifluoromethylated alkenes in a highly stereoselective manner. The present method is the first example of a facile one-pot synthesis of tetrasubstituted trifluoromethylated alkenes from simple alkynes.

Photoredox‐Catalyzed Stereoselective Conversion of Alkynes into Tetrasubstituted Trifluoromethylated Alkenes

AbstractA regio‐ and stereoselective synthesis of trifluoromethylated alkenes bearing four different substituents has been developed. Stereocontrolled sulfonyloxytrifluoromethylation of unsymmetric internal alkynes with an electrophilic CF3 reagent, namely the triflate salt of the Yagupol’skii–Umemoto reagent, in the presence of an Ir photoredox catalyst under visible‐light irradiation afforded trifluoromethylalkenyl triflates with well‐predictable stereochemistry resulting from anti addition of the trifluoromethyl and triflate groups. Subsequent palladium‐catalyzed cross‐couplings led to tetrasubstituted trifluoromethylated alkenes in a highly stereoselective manner. The present method is the first example of a facile one‐pot synthesis of tetrasubstituted trifluoromethylated alkenes from simple alkynes.

Ligand- and Acid-Free Gold(I) Chloride Catalyzed Hydration of Terminal Alkynes

Our work shows that simple alkynes can be hydrated by the AuCl/MeOH catalyst system to afford the corresponding methyl ketones in moderate to high yields without any additive, ligand, or acid promoter. This methodology is simpler, milder, and operationally easier than those reported before. The reaction media significantly affects the reaction, and methanol is found to be the best solvent. Both aliphatic and aromatic terminal alkynes were able to undergo hydration, affording moderate to excellent yields under the reaction conditions used in the present work, and excellent functional-group tolerance was also observed. A plausible mechanism for the hydration reaction was proposed.

Forming Stereogenic Centers in Acyclic Systems from Alkynes

The combined carbometalation/zinc homologation followed by reactions with α-heterosubstituted aldehydes and imines proceed through a chair-like transition structure with the substituent of the incoming aldehyde residue preferentially occupying a pseudo-axial position to avoid the two gauche interactions. The heteroatom in the axial position produces a chelated intermediate (and not a Cornforth-Evans transition structure for α-chloro aldehydes and imines) leading to a face differentiation in the allylation reaction. This method provides access to functionalized products in which three new carbon-carbon bonds and two to three stereogenic centers, including a quaternary one, were created in acyclic systems in a single-pot operation from simple alkynes.

Forming Stereogenic Centers in Acyclic Systems from Alkynes

AbstractThe combined carbometalation/zinc homologation followed by reactions with α‐heterosubstituted aldehydes and imines proceed through a chair‐like transition structure with the substituent of the incoming aldehyde residue preferentially occupying a pseudo‐axial position to avoid the two gauche interactions. The heteroatom in the axial position produces a chelated intermediate (and not a Cornforth–Evans transition structure for α‐chloro aldehydes and imines) leading to a face differentiation in the allylation reaction. This method provides access to functionalized products in which three new carbon–carbon bonds and two to three stereogenic centers, including a quaternary one, were created in acyclic systems in a single‐pot operation from simple alkynes.

Copper-catalyzed direct transformation of simple alkynes to alkenyl nitriles via aerobic oxidative N-incorporation.

A novel direct transformation of aliphatic terminal alkynes to alkenyl nitriles through the incorporation of a nitrogen atom into the simple hydrocarbons has been reported. The usage of inexpensive copper catalyst, O2 as the sole oxidant, broad substrate scope as well as feasibility for "late-stage modification" make this protocol very promising. Mechanistic studies including DFT calculation demonstrate a novel 1,2-hydride shift process for this novel nitrogenation reaction.

ChemInform Abstract: Nickel‐Catalyzed [2 + 2] Cycloaddition Reaction of Bulky Enones with Simple Alkynes. The Effect of Bulkiness of Substituent Attached at β‐Carbon.

AbstractTitle reaction of enones (I) bearing bulky substituents affords cyclobutenes (III) or (V) and (VI), resp., rather than cyclohexenes or cyclohexadienes.