Alkynyl Bromides Research Articles

Enantioconvergent Reductive C(sp)-C(sp3 ) Cross-Coupling to Access Chiral α-Alkynyl Phosphonates Under Dual Nickel/Photoredox Catalysis.

Transition-metal-catalyzed asymmetric carbon-carbon bond formation to forge phosphonates with an α-chiral carbon center through C(sp3 )-C(sp3 ) and C(sp2 )-C(sp3 ) couplings has been successful. However, the enantioselective C(sp)-C(sp3 ) coupling has not yet been disclosed. Reported herein is an unprecedented enantioconvergent cross-coupling of alkynyl bromides and α-bromo phosphonates to deliver chiral α-alkynyl phosphonates.

Synthesis of β-graphdiyne-like film with terminal alkynyl bromine groups

β-Graphdiyne (β-GDY), as a classical two-dimensional carbon material with zero band gap, has become a prevailing topic within the field of carbon nanomaterials due to the potential applications in energy storage, organic electronics, etc. Thus, the explorations to synthesize high-performance β-GDY-based materials and to reveal the relationship between their structures and properties are of great significance. In this work, we proposed a new strategy to prepare large-area β-GDY-like film on copper foil via the dehalogenative homocoupling reaction of a new monomer tetra(bromomethynyl)ethene (TBE). Due to the higher selectivity of the terminal alkynyl bromide functional groups, the reaction can proceed high-efficiently at room temperature. The configurations and nanostructures of as-synthesized film was well characterized by using SEM, TEM, Raman, FT-IR and XPS. Their hydrogen/oxygen evolution reaction (HER/OER) catalytic performances have been demonstrated.

Transition-Metal-Catalyzed C–C Bond Macrocyclization via Intramolecular C–H Bond Activation

Macrocycles are commonly synthesized via late-stage macrolactamization and macrolactonization. Strategies involving C–C bond macrocyclization have been reported, and examples include the transition-metal-catalyzed ring-closing metathesis and coupling reactions. In this mini-review, we summarize the recent progress in the direct synthesis of polyketide and polypeptide macrocycles using a transition-metal-catalyzed C–H bond activation strategy. In the first part, rhodium-catalyzed alkene–alkene ring-closing coupling for polyketide synthesis is described. The second part summarizes the synthesis of polypeptide macrocycles. The activation of indolyl and aryl C(sp2)–H bonds followed by coupling with various coupling partners such as aryl halides, arylates, and alkynyl bromide is then documented. Moreover, transition-metal-catalyzed C–C bond macrocyclization reactions via alkyl C(sp3)–H bond activation are also included. We hope that this mini-review will inspire more researchers to explore new and broadly applicable strategies for C–C bond macrocyclization via intramolecular C–H activation.

Visible-Light-Mediated Deacylated Alkynylation of Unstrained Ketone.

Deconstructive alkynylation of an unstrained ketone catalyzed by an organic photocatalyst under blue light irradiation is reported for the first time. A broad substrate scope with up to 63 examples, excellent functional group tolerance, and gram scale reaction demonstrated the practicality of this novel alkynylation method. The dihydroquinazolinone derivative of trifluoroacetophenone had been proved to have potential as a novel trifluoromethylation reagent after working well for the trifluoromethylation reaction with various alkynyl bromides.

Regio- and stereocontrolled synthesis of borylated E-enynes, Z-enediynes and derivatives from alkenyl-1,2-bis-(boronates).

An efficient stereo-controlled synthesis of enyne and enediyne derivatives, via sequential Suzuki-Miyaura coupling reactions from easily prepared 1-alkene-1,2-diboronic esters and alkynyl bromides, is reported. The resulting enyne boronic esters were subjected to Borono-Mannich and Suzuki coupling reactions independently to obtain α,β-unsaturated aminoester and tri-substituted olefin derivatives, respectively. Additionally, divergent syntheses of triazole and cyclopropylboronate derivatives are also reported.

Synthesis of graphdiyne on a copper substrate via a self-coupling reaction.

A new strategy is proposed to prepare graphdiyne via the self-coupling reaction of hexakis(bromoethynyl)benzene (hBEP) with alkynyl bromide groups. Prominently, the reaction can proceed moderately in 12 h at room temperature. The as-synthesized film displays a porous structure, excellent chemical characteristics, and an admirable catalytic performance for the hydrogen/oxygen evolution reaction (HER/OER).

Visible-light-induced decarboxylative alkynylation of carboxylic acids in batch and continuous flow

A green efficient photoredox-catalyzed decarboxylative alkynylation of carboxylic acids with alkynyl bromides has been developed. This broadly applicable protocol is presented wherein α-amino, aliphatic and α-oxy acids are converted into useful alkynylation products. The commercially-available organic photocatalyst 4CzIPN is used as the photocatalyst, organic base DBU is utilized as the base, and DMSO serves as solvent. This strategy features mild conditions, is metal-free, and is environmentally friendly. The batch and continuous-flow protocols described were applied to obtain a broader substrate scope of functionalization (more than 50 examples). Furthermore, we demonstrate that the use of microflow technology enhanced and intensified the reaction process, achieving significantly reduced reaction times (i.e., 10 ​min of residence time).

Modular Synthesis of Multifunctionalized CF3-Allenes through Selective Activation of Saturated Hydrocarbons

Catalytic 1,4-dicarbofunctionalization of 1,3-enynes is a powerful strategy for the synthesis of polysubstituted allenes. Despite impressive progress, such a strategy is still restricted to the use of alkyl-metallic reagents or pre-activated radical precursors, thus limiting its functional group compatibility and atom economy. Herein, we report that through the combination of decatungstate photo-hydrogen atom transfer and nickel catalysis, a three-component 1,4-dicarbofunctionalization of 2-trifluoromethyl-1,3-enynes is achieved. This strategy allows the modular synthesis of tetrasubstituted CF3-allenes under exceptionally mild conditions. A variety of electrophiles such as aryl bromides, alkenyl bromides, acyl chlorides, and alkynyl bromides were successfully employed as traps to lead to the desired products. Another significant advantage is that the most abundant hydrocarbons are used as feedstocks, and a wide range of synthetically versatile functional groups and complex drug-like structures can be easily incorporated. Based on experimental and density functional theories, a possible catalytic cycle involving 1,3-nickel rearrangement is proposed.

Visible-Light-Driven α-Aminoalkyl Radical-Mediated C(sp3)-C(sp) Cross-Coupling of Iodoalkanes and Alkynyl Bromides.

We herein report a simple protocol for metal-free cross-coupling between unactivated alkyl iodides and terminal alkynyl bromides promoted by visible light. The salient features of this transformation are the utilization of an organic photocatalyst and commercially available tri-n-butylamine as a reductant. This protocol couples a variety of unactivated iodoalkanes containing different functional groups and with a variety of terminal alkynyl bromides under mild reaction conditions to afford the substituted alkynes in good yields.

Reductive Cross‐Coupling of α‐Oxy Halides Enabled by Thermal Catalysis, Photocatalysis, Electrocatalysis, or Mechanochemistry

AbstractHerein, we report a reductive cross‐coupling reaction of α‐oxy halides, simply generated from aldehydes, with a series of C(sp2)‐ and C(sp)‐electrophiles. A wide range of aryl and heteroatom aryl halides, vinyl bromides, alkynyl bromides, and acyl chlorides react with unhindered and hindered aldehyde‐derived α‐oxy halides by providing protected alcohols as well as α‐hydroxy ketones. Noteworthy, the reductive couplings are achieved not only through thermal catalysis with the use of metal reductants but also by photocatalysis, electrochemistry, and mechanochemistry. The unrestricted interchange of the four strategies indicates their underlying mechanistic similarities. The generation of NiI intermediate is proposed to be the key point for ketyl radical formation via a single‐electron transfer (SET) event, which was rationalized by an array of control experiments and density functional theory (DFT) calculations.

Reductive Cross-Coupling of α-Oxy Halides Enabled by Thermal Catalysis, Photocatalysis, Electrocatalysis, or Mechanochemistry.

Herein, we report a reductive cross-coupling reaction of α-oxy halides, simply generated from aldehydes, with a series of C(sp2 )- and C(sp)-electrophiles. A wide range of aryl and heteroatom aryl halides, vinyl bromides, alkynyl bromides, and acyl chlorides react with unhindered and hindered aldehyde-derived α-oxy halides by providing protected alcohols as well as α-hydroxy ketones. Noteworthy, the reductive couplings are achieved not only through thermal catalysis with the use of metal reductants but also by photocatalysis, electrochemistry, and mechanochemistry. The unrestricted interchange of the four strategies indicates their underlying mechanistic similarities. The generation of NiI intermediate is proposed to be the key point for ketyl radical formation via a single-electron transfer (SET) event, which was rationalized by an array of control experiments and density functional theory (DFT) calculations.

Copper-Catalyzed Stereospecific Transformations of Alkylboronic Esters.

Copper-catalyzed stereospecific cross-couplings of boronic esters are reported. Boron "ate" complexes derived from pinacol boronic esters and tert-butyl lithium undergo stereospecific transmetalation to copper cyanide, followed by coupling with alkynyl bromides, allyl halides, propargylic halides, β-haloenones, hydroxylamine esters, and acyl chlorides. Through this simple transformation, commercially available inexpensive compounds can be employed to convert primary and secondary alkylboronic esters to a wide array of synthetically useful compounds.

Catalytic C(sp)–Si cross-coupling silylation of alkynyl bromides with hydrosilanes by palladium catalysis

An unprecedented and convenient Si–C(sp) bond-forming cross-coupling of alkynyl bromides with hydrosilanes has been established for the facile synthesis of alkynylsilanes in good yields and with excellent chemoselectivity.

Double 1,2-Migration of Bromine and Silicon in Directed C–H Alkynylation Reactions with Silyl-Substituted Alkynyl Bromides through an Iridium Vinylidene Intermediate

The iridium(III)-catalyzed C–H alkynylation of 2-acylimidazoles with alkynyl bromides, which was recently developed by our group, provides an efficient strategy for the construction of both C(sp)–C(sp2) and C(sp)–C(sp3) bonds. The mechanism for this reaction was extensively studied using density functional theory (DFT) calculations. The computed catalytic cycle is initiated by C–H activation, and the formed iridacycle undergoes a strain-controlled regioselective migratory insertion of an alkynyl bromide. The resulting α-bromovinyl iridium species is rapidly converted into a more stable iridium vinylidene intermediate by a 1,2-bromine migration, and the adjacent silyl group subsequently migrates to furnish a C–H-alkynylated product. The origin of the unique difference in reactivity with respect to the substituent on the alkynyl bromide is the 1,2-migration step, in which a silyl group can highly stabilize the transition state by the β-silicon effect.

Synthesis of C-Alkynyl Glycosides by Photoredox-Catalyzed Reductive Coupling of Alkynyl Bromides with Glycosyl Bromides.

A general, convenient, and highly α stereoselective approach to access C-alkynyl glycosides via the photoredox-catalyzed reductive coupling of alkynyl bromides and glycoside bromides has been developed. Cheap and small-load eosin Y is used as the photocatalyst, and organic base N,N-diisopropylethylamine serves as the reducing reagent. This strategy features readily available starting materials, diverse substrates, mild conditions, and high α stereoselectivity. Moreover, a glycoconjugated peptide could also be achieved using this strategy.

Redox‐Neutral Vicinal Difunctionalization of Five‐Membered Heteroarenes with Dual Electrophiles

AbstractA new reaction mode of palladium/norbornene (Pd/NBE) cooperative catalysis is reported involving the selective coupling of two different carbon‐based electrophiles for vicinal double C‐H functionalization of five‐membered heteroarenes in a site‐selective and redox‐neutral manner. The key is to use alkynyl bromides as the second electrophile, which allows vicinal difunctionalization of a wide range of heteroarenes including pyrroles, thiophenes and furans at their C4 and C5 positions. One‐ or two‐step tetrafunctionalizations of simple pyrrole and thiophene have also been realized. The C2‐substituted NBEs prove most effective in these reactions, and the mechanistic exploration discloses the origin of the high selectivity of this transformation. Synthetic utility of this method has been exemplified in the concise preparations of thiophene‐containing organic materials and a protein kinase inhibitor analogue. Preliminary success has also been achieved in a direct annulation event, using a tethered ketone as the second electrophile.

Redox‐Neutral Vicinal Difunctionalization of Five‐Membered Heteroarenes with Dual Electrophiles

A new reaction mode of palladium/norbornene (Pd/NBE) cooperative catalysis is reported involving the selective coupling of two different carbon-based electrophiles for vicinal double C-H functionalization of five-membered heteroarenes in a site-selective and redox-neutral manner. The key is to use alkynyl bromides as the second electrophile, which allows vicinal difunctionalization of a wide range of heteroarenes including pyrroles, thiophenes and furans at their C4 and C5 positions. One- or two-step tetrafunctionalizations of simple pyrrole and thiophene have also been realized. The C2-substituted NBEs prove most effective in these reactions, and the mechanistic exploration discloses the origin of the high selectivity of this transformation. Synthetic utility of this method has been exemplified in the concise preparations of thiophene-containing organic materials and a protein kinase inhibitor analogue. Preliminary success has also been achieved in a direct annulation event, using a tethered ketone as the second electrophile.

Palladium-Catalyzed Intermolecular 1,1-Carbobromination of Alkenes with Alkynyl Bromides

Palladium-Catalyzed Intermolecular 1,1-Carbobromination of Alkenes with Alkynyl Bromides

Coupling of Bis(perfluoroalkyl)zinc with Alkynyl Bromides

Coupling of Bis(perfluoroalkyl)zinc with Alkynyl Bromides

Nickel-Catalyzed Difunctionalization of Alkynyl Bromides with Thiosulfonates and N-Arylthio Succinimides: A Convenient Synthesis of 1,2-Thiosulfonylethenes and 1,1-Dithioethenes

AbstractAn efficient nickel-catalyzed vicinal thiosulfonylation of 1-bromoalkynes with thiosulfonates in the presence of cesium carbonate is described. An operationally simple and highly regioselective atom transfer radical addition (ATRA) of alkynyl bromides provides a wide range of (E)-1,2-thiosulfonylethenes (α-aryl-β-thioarylvinyl sulfones) in moderate to high yields. The extensive substrate scope of both alkynyl bromides and thiosulfonates is explored with a broad range of functional groups. Indole-derived 1,1-bromoalkenes were also successfully explored in this 1,2-thiosulfonylation process. Moreover, the nickel-catalyzed geminal-dithiolation of alkynyl bromides with N-arylthio succinimides provides 1,1-dithioalkenes in high yields. The present protocol is reliable on gram scale, and a sequential one-pot bromination and thiosulfonylation of phenylacetylene is achieved in a scale-up synthesis. Following control experiments, a plausible mechanism is proposed to rationalize the experimental outcome and the vicinal thio­sulfonylation.