Copper(I)‐Catalyzed Regioselective Addition of Nucleophilic Silicon Across Terminal and Internal Carbon–Carbon Triple Bonds

The copper(I) alkoxide‐catalyzed release of a silicon‐based cuprate reagent from a silicon–boron pronucleophile is applied to the addition across carbon–carbon triple bonds. Commercially available CuBr?Me₂S was found to be a general precatalyst that secures high regiocontrol for both aryl‐ and alkyl‐substituted terminal as well as internal alkynes. The solvent greatly influences the regioisomeric ratio, favoring the linear regioisomer with terminal acceptors. This facile protocol even allows for the transformation of internal acceptors with remarkable levels of regio‐ and diastereocontrol.     

Iron‐Induced Regio‐ and Stereoselective Addition of Sulfenyl Chlorides to Alkynes by a Radical Pathway

The radical addition of the Cl? S σ‐bond in sulfenyl chlorides to various C? C triple bonds has been achieved with excellent regio‐ and stereoselectivity in the presence of a catalytic amount of a common iron salt. The reaction is compatible with a variety of functional groups and can be scaled up to the gram‐scale with no loss in yield. As well as terminal alkynes, internal alkynes underwent stereodefined chlorothiolation to provide tetrasubstituted alkynes. Preliminary mechanistic investigations revealed a plausible radical process involving a sulfur‐centered radical intermediate via iron‐mediated homolysis of the Cl? S bond. The resulting chlorothiolation adducts can be readily transformed to the structurally complex alkenyl sulfides by cross‐coupling reactions. The present reaction can also be applied to the complementary synthesis of the potentially useful bis‐sulfoxide ligands for transition‐metal‐catalyzed reactions.     

One-pot three-component synthesis of pyrazoles through a tandem coupling-cyclocondensation sequence

An efficient and general one-pot procedure for the synthesis of pyrazoles from acid chlorides, terminal alkynes and hydrazines was described via a coupling and cyclocondensation sequence. Acid chlorides coupled with terminal alkynes to give α,β-unsaturated ynones, and in situ converted into pyrazoles by the cycloaddition of hydrazines. The desired pyrazoles were obtained with 15-85% isolated yields.     

Migratory Hydrogenation of Terminal Alkynes by Base/Cobalt Relay Catalysis

Migratory functionalization of alkenes has emerged as a powerful strategy to achieve functionalization at a distal position to the original reactive site on a hydrocarbon chain. However, an analogous protocol for alkyne substrates is yet to be developed. Herein, a base and cobalt relay catalytic process for the selective synthesis of (Z)‐2‐alkenes and conjugated E alkenes by migratory hydrogenation of terminal alkynes is disclosed. Mechanistic studies support a relay catalytic process involving a sequential base‐catalyzed isomerization of terminal alkynes and cobalt‐catalyzed hydrogenation of either 2‐alkynes or conjugated diene intermediates. Notably, this practical non‐noble metal catalytic system enables efficient control of the chemo‐, regio‐, and stereoselectivity of this transformation.     

Palladium‐Catalyzed Regio‐ and Stereoselective Chlorothiolation of Terminal Alkynes with Sulfenyl Chlorides

Chlorothiolation of terminal alkynes with sulfenyl chlorides yields anti‐adducts without transition‐metal catalysts. In sharp contrast, transition‐metal‐catalyzed chlorothiolation has not been developed to date, possibly because organosulfur compounds can poison catalyst. Herein, the regio‐ and stereoselective palladium‐catalyzed chlorothiolation of terminal alkynes with sulfenyl chlorides is described. syn‐Chlorothiolation offers a complementary synthetic route to chloroalkenyl sulfides. 2‐Chloroalkenyl sulfides can easily be transformed into various sulfur‐containing products, most of which are often found in natural products and pharmaceuticals.     

Stereo‐ and Regioselective Alkyne Hydrometallation with Gold(III) Hydrides

The hydroauration of internal and terminal alkynes by gold(III) hydride complexes [(C^N^C)AuH] was found to be mediated by radicals and proceeds by an unexpected binuclear outer‐sphere mechanism to cleanly form trans‐insertion products. Radical precursors such as azobisisobutyronitrile lead to a drastic rate enhancement. DFT calculations support the proposed radical mechanism, with very low activation barriers, and rule out mononuclear mechanistic alternatives. These alkyne hydroaurations are highly regio‐ and stereospecific for the formation of Z‐vinyl isomers, with Z/E ratios of >99:1 in most cases.     

Stereoselective Synthesis of Trisubstituted Alkenes through Sequential Iron‐Catalyzed Reductive anti‐Carbozincation of Terminal Alkynes and Base‐Metal‐Catalyzed Negishi Cross‐Coupling

The stereoselective synthesis of trisubstituted alkenes is challenging. Here, we show that an iron‐catalyzed anti‐selective carbozincation of terminal alkynes can be combined with a base‐metal‐catalyzed cross‐coupling to prepare trisubstituted alkenes in a one‐pot reaction and with high regio‐ and stereocontrol. Cu‐, Ni‐, and Co‐based catalytic systems are developed for the coupling of sp‐, sp²‐, and sp³‐hybridized carbon electrophiles, respectively. The method encompasses a large substrate scope, as various alkynyl, aryl, alkenyl, acyl, and alkyl halides are suitable coupling partners. Compared with conventional carbometalation reactions of alkynes, the current method avoids pre‐made organometallic reagents and has a distinct stereoselectivity.     

A Highly Efficient Dimeric Manganese‐Catalyzed Selective Hydroarylation of Internal Alkynes

We have developed a general and site‐predictable manganese‐catalyzed hydroarylation of internal alkynes in the presence of water, under an air atmosphere without the involvement of ligand. The unique catalytic feature of this reaction is highlighted by comparison with other widely used transition metal catalysts including palladium, rhodium, nickel, or copper. The simple operation, high efficiency and excellent functional group compatibility make this protocol practical for more than 90 structurally diverse internal alkynes, overcoming the influence of both electronic and steric effect of alkynes. Its exclusive regio‐ and chemoselectivity originates from the unique reactivity of the manganese‐based catalyst towards an inherent double controlled strategy of sterically hindered propargyl alcohols without the installing of external directing groups. Its synthetic robustness and practicality have been illustrated by the concise synthesis of bervastatin, a hypolipidemic drug, and late‐stage modification of complex alkynes with precise regioselectivity.     

Regio‐ and Stereoselective Chlorocyanation of Alkynes

A variety of terminal and internal alkynes were converted regio‐ and stereoselectively into (Z )‐3‐chloroacrylonitriles by treatment with BCl₃ in the presence of stoichiometric amounts of imidazolium thiocyanates. These products could be readily functionalized to provide useful building blocks, thus demonstrating the synthetic value of the method. Preliminary mechanistic studies suggest initial activation of the cationic thiocyanate by the Lewis acid, followed by electrophilic attack of the alkyne. The syn addition of a chloride to the vinyl cation intermediate and final elimination of the thiourea unit afford the desired chloroacrylonitriles.     

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.     

A novel one-pot method for the preparation of pyrazoles by 1,3-dipolar cycloadditions of diazo compounds generated in situ

A convenient one-pot procedure for the preparation of pyrazoles by 1,3-dipolar cycloaddition of diazo compounds generated in situ has been developed. Diazo compounds derived from aldehydes were reacted with terminal alkynes to furnish regioselectively 3,5-disubstituted pyrazoles. Furthermore, the reaction of N-vinylimidazole and diazo compounds derived from aldehydes gave exclusively 3-substituted pyrazoles in a one-pot process.     

1,3‐Dipolar Cycloadditions of Ethyl 2‐Diazo‐3,3,3‐trifluoropropanoate to Alkynes and [1,5] Sigmatropic Rearrangements of the Resulting 3H‐Pyrazoles: Synthesis of Mono‐, Bis‐ and Tris(trifluoromethyl)‐Substituted Pyrazoles

The 1,3‐dipolar cycloadditions of ethyl 2‐diazo‐3,3,3‐trifluoropropanoate with electron‐rich and electron‐deficient alkynes, as well as the van Alphen? Hüttel rearrangements of the resulting 3H‐pyrazoles were investigated. These reactions led to a series of CF₃‐substituted pyrazoles in good overall yields. Phenyl‐ and diphenylacetylene proved to be unreactive, but, at high temperature, the diazoalkane and phenylacetylene furnished a cyclopropene derivative. As expected, the 1,3‐dipolar cycloaddition to the ynamine occurred much faster than those to electron‐deficient alkynes. With one exception, all cycloadditions proceeded with excellent regioselectivities. The [1,5] sigmatropic rearrangement of the primary 3H‐pyrazoles provided products with shifted acyl groups; products resulting from the migration of a CF₃ group were not detected. In agreement with literature reports, this rearrangement occurs faster with 3H‐pyrazoles bearing electron‐withdrawing substituents.     

Fluorobenziodoxole−BF3 Reagent for Iodo(III)etherification of Alkynes in Ethereal Solvent

A combination of fluorobenziodoxole (FBX) and BF₃ ? OEt₂ in cyclopentyl methyl ether promotes regio‐ and stereoselective addition of benziodoxole and methoxy groups to alkynes. This difunctionalization reaction tolerates a variety of functionalized internal and terminal alkynes to afford trans‐β‐alkoxyvinylbenziodoxoles, which represent versatile precursors to stereochemically well‐defined multisubstituted vinyl ethers. The reaction is proposed to involve cleavage of the I?F bond of FBX by BF₃, followed by electrophilic activation of the alkyne by the resulting cationic I^III species that triggers the nucleophilic addition of the ethereal oxygen.     

In Situ Generation of Silylzinc by Si−B Bond Activation Enabling Silylzincation and Silaboration of Terminal Alkynes

A new protocol has been designed for the in situ generation of unstable Si?Zn species through the reaction of dialkylzinc, phosphine, and silylborane (Si?B). Successive reactions with various terminal alkynes using this protocol enabled highly controllable regio‐/stereo‐/chemoselective silylzincation and silaboration on demand without the need for a transition‐metal catalyst.     

Syngas‐Free Highly Regioselective Rhodium‐Catalyzed Transfer Hydroformylation of Alkynes to α,β‐Unsaturated Aldehydes

The hydroformylation of alkynes is a fundamental and important reaction in both academic research and industry. Conventional methods focus on the conversion of alkynes, CO, and H₂ into α,β‐unsaturated aldehydes, but they often suffer from problems associated with operation, regioselectivity, and chemoselectivity. Herein, we disclose an operationally simple, mild, and syngas‐free rhodium‐catalyzed reaction for the hydroformylation of alkynes via formyl and hydride transfer from an alkyl aldehyde. This synthetic method uses inexpensive and easy‐to‐handle n‐butyraldehyde to overcome the challenge posed by the use of syngas in traditional approaches and employs a commercially available catalyst and ligand to transform a broad range of internal alkynes, especially alkynyl‐containing complex molecules, into versatile stereodefined α,β‐unsaturated aldehydes with excellent chemo‐, regio‐, and stereoselectivity.     

Synthesis of Chiral Pyrazoles: A 1,3‐Dipolar Cycloaddition/[1,5] Sigmatropic Rearrangement with Stereoretentive Migration of a Stereogenic Group

The reactions between terminal alkynes and α‐chiral tosylhydrazones lead to the obtention of chiral pyrazoles with a stereogenic group directly attached at a nitrogen atom. The cascade reaction includes decomposition of the hydrazone into a diazocompound, 1,3‐dipolar cycloaddition of the diazo compound with the alkyne, and [1,5] sigmatropic rearrangement with migration of the stereogenic group. This strategy has been successfully applied to the synthesis of structurally diverse chiral pyrazoles through α‐chiral tosylhydrazones, obtained from α‐phenylpropionic acid, α‐amino acids, and 2‐methoxycyclohexanone. Notably, the stereoretention of the [1,5] sigmatropic rearrangements represent very rare examples of this stereospecific transformation.     

Intramolecular trans‐Dicarbofunctionalization of Alkynes by a Formal anti‐Carbopalladation/Stille Cascade

An intramolecular Pd‐catalyzed trans‐dicarbofunctionalization of internal alkynes using aryl bromides and aryl stannanes is presented. Tetrasubstituted double bonds embedded in an oligocyclic ring system are obtained in a regio‐ and diastereoselective fashion. The transformation features a broad substrate scope and functional‐group tolerance.     

Palladium‐Catalyzed Vicinal Amino Alcohols Synthesis from Allyl Amines by In Situ Tether Formation and Carboetherification

Vicinal amino alcohols are important structural motifs of bioactive compounds. Reported herein is an efficient method for their synthesis based on the palladium‐catalyzed oxy‐alkynylation, oxy‐arylation, or oxy‐vinylation of allylic amines. High regio‐ and stereoselectivity were ensured through the in situ formation of a hemiaminal tether using the cheap commercially available trifluoroacetaldehyde in its hemiacetal form. The obtained compounds are important building blocks, which can be orthogonally deprotected to give either free alcohols, amines, or terminal alkynes.     

A Convergent Synthesis of Functionalized Alkenyl Halides through Cobalt(III)‐Catalyzed Three‐Component C−H Bond Addition

A Co^III‐catalyzed three‐component coupling of C(sp²)−H bonds, alkynes, and halogenating agents to give alkenyl halides is reported. This transformation proceeds with high regio‐ and diastereoselectivity, and is effective for a broad range of aryl and alkyl terminal alkynes. Diverse C−H bond partners also exhibit good reactivity for a range of heteroaryl and aryl systems as well as synthetically useful secondary and tertiary amide, urea, and pyrazole directing groups. This multicomponent transformation is also compatible with allenes in place of alkynes to furnish tetrasubstituted alkenyl halides, showcasing the first halo‐arylation of allenes.     

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.