Alkynyl Bromides Research Articles

Photoredox-Catalyzed Alkynylation of C(sp3)-H Bonds Adjacent to a Nitrogen Atom of Tertiary Amines with Alkynyl Bromides.

A novel and robust alkynylation of C(sp3)-H bonds adjacent to a nitrogen atom of tertiary amines with alkynyl bromides as radical alkynylating reagents has been realized under visible-light irradiation. A range variety of tertiary amines including N-arylamines and N-alkylamine have been coupled with both aromatic and aliphatic alkynyl bromides to furnish 51 examples of propargylamines in moderate to excellent yields (31-80% yields). The possible mechanism was a radical addition-elimination process based on preliminary mechanistic studies.

Redox-Active α-Amino-CF3 Reagents: Developing and Applications in Ni-Catalyzed Reductive Cross-Coupling.

α-Amino-CF3 compounds are widely employed in bio- and pharmaceutical chemistry for improved stability and bioactivities. Traditional methods often face challenges with functional group tolerance and lack a general approach for late-stage functionalization. Herein, we report a new type of redox-active α-amino-CF3 reagents, easily prepared from trifluoro acetaldehyde hydrates. These α-amino-CF3 reagents can serve as versatile building blocks for coupling with alkynyl bromides, aryl bromides, and enol triflates under nickel catalysis.

Visible Light Catalyzed Reductive Cross‐Coupling of α‐CF3‐alkyl Bromide and Alkynyl Bromide†

Comprehensive SummaryTraditional reduction coupling reactions of two bromides typically rely on transition metal catalysis. Here, we introduce the development of a visible‐light catalytic direct reduction coupling reaction between α‐CF3‐alkyl bromides and alkynyl bromides to access valuable organic frameworks. Our research confirms the excellent compatibility of this reaction with various functional groups, which could be used to modify the substrate with biologically active molecular fragments. Mechanistic investigations, including control experiments, fluorescence quenching studies, and light‐switching experiments, have provided insights into the reaction mechanism. This study paves the way for the application of visible‐light catalysis in diverse synthetic transformations, offering a sustainable and efficient approach to organic synthesis.

Palladium‐Catalyzed Direct Alkynylation of Carbazoles with Alkynyl Bromides

Carbazole derivatives are vital in medicinal and materials chemistry, yet accessing diverse substitutions remains challenging. Here, we introduce a regioselective approach for C1 and C8 alkynylation of carbazoles via palladium‐catalyzed C‒H activation. This method provides a direct route to mono‐ and di‐alkynylated derivatives, addressing the scarcity of alkynylated carbazole‐based materials. Our study broadens the synthetic toolbox for carbazole functionalization, offering potential applications in optoelectronics, bio‐imaging, and beyond, while contributing to developing sustainable C‒H activation methodologies.

Palladium-catalyzed Cross-coupling of 2-Benzo[b]thiophene or 2- Benzo[b]furan Aluminum with Heteroaryl or Alkynyl Bromides for the Synthesis of 2-Hetroaryl or Alkynyl Benzo[b]thiophene or Benzo[b]furan Derivatives

Abstract: An alternative method for the synthesis of 2-heteroaryl or alkynyl benzo[b]thiophene or furan derivatives via direct palladium-catalyzed cross-coupling of 2-benzo[b]thiophene or furan aluminum with heteroaryl or alkynyl bromides, respectively, has been successfully developed. This case is remarkable as the same catalytic system could simultaneously produce either 2-substituted benzo[ b]thiophene or furan derivatives.

The synthesis of isoxazolines and dihydrooxazines by Pd-catalyzed oxyalkynylation alkenyl oximes with alkynyl bromides

Synthesis of isoxazolines and dihydrooxazines bearing an alkyne group by Pd-catalyzed oxyalkynylation of alkenyl oximes with alkynyl bromides. This new approach has a broad substrate scope and good functional tolerance.

Pd-catalysed C-H alkynylation of benzophospholes.

A palladium-catalysed C2-H alkynylation of benzophospholes with alkynyl bromides has been developed to afford the corresponding phosphole-alkyne conjugations in good to high yields. The C-C triple bond as well as terminal alkyne C-H bond in the obtained products is a good synthetic handle for further manipulations, thus giving the versatile π-conjugated benzophosphole derivatives. The optoelectronic properties of the newly synthesized conjugated benzophospholes are also described.

Aromatization-driven deconstructive functionalization of spiro dihydroquinazolinones via dual photoredox/nickel catalysis.

Aromatization-driven deconstruction and functionalization of spiro dihydroquinazolinones via dual photoredox/nickel catalysis is developed. The aromatization effect was introduced to synergistically drive unstrained cyclic C-C bond cleavage, with the aim of overcoming the ring-size limitation of nitrogen-centered radical induced deconstruction of carbocycles. Herein, we demonstrate the synergistic photoredox/nickel catalyzed deconstructive cross-coupling of spiro dihydroquinazolinones with organic halides. Remarkably, structurally diverse organic halides including aryl, alkenyl, alkynyl, and alkyl bromides were compatible for the coupling. In addition, this protocol is also characterized by its mild and redox-neutral conditions, excellent functional group compatibility, high atom economy, and easy scalability. A telescoped procedure involving condensation and ring-opening/coupling was found to be accessible. This work provides a complementary strategy to the existing radical-mediated C-C bond cleavage of unstrained carbocycles.

Cobalt-catalyzed reductive alkynylation to construct C(sp)-C(sp3) and C(sp)-C(sp2) bonds

Transition-metal-catalyzed cross-electrophile coupling has emerged as a reliable method for constructing carbon–carbon bonds. Herein, we report a general method, cobalt-catalyzed reductive alkynylation, to construct C(sp)-C(sp3) and C(sp)-C(sp2) bonds. This presented reaction has a broad substrate scope, enabling the efficient cross-electrophile coupling between alkynyl bromides with alkyl halides and aryl or alkenyl (pseudo)halides. This presented reaction is conducted under mild conditions, tolerating many functional groups, thus suitable for the modification and synthesis of biologically active molecules.

Visible-Light-Enabled Radical Alkynylborylation of Activated Alkenes

AbstractA photoredox-catalyzed protocol for performing radical difunctionalization of alkenes using N-heterocyclic carbene (NHC) boranes and alkynyl bromines is described. The alkynylborylation difunctionalization reaction involves photoredox generation of boryl radical, with subsequent radical addition to the double bond followed by the capture of alkynyl bromide to form a C–C bond. This method features mild reaction conditions, remarkable chemoselectivity, broad substrate scope and good to excellent yields (up to 89%). The modification of coumarin derivatives indicates that this approach can provide a useful route for the synthesis of complex alkynylborylated products.

Merging Visible Light Photocatalysis and P(III)‐Directed C−H Activation by a Single Catalyst: Modular Assembly of P‐Alkyne Hybrid Ligands

AbstractMetal‐catalyzed C−H activation strategies provide an efficient approach for synthesis by minimizing atom, step, and redox economy. Developing milder, greener, and more effective protocols for these strategies is always highly desirable to the scientific community. In this study, the utilization of a single rhodium complex enabled the visible‐light‐induced late‐stage C−H activation of biaryl‐type phosphines with alkynyl bromides, employing inherent phosphorus atoms as directing groups. This chemistry combines P(III)‐directed C−H activation with visible light photocatalysis, under exogenous photosensitizer‐free conditions, offering a unique platform for ligand design and preparation. Furthermore, this study also explores the asymmetric catalysis and coordination chemistry of the resulting P‐alkyne hybrid ligands with specific transition metals. Experimental results and density functional theory calculations demonstrate the mechanistic intricacies of this transformation.

Merging Visible Light Photocatalysis and P(III)-Directed C-H Activation by a Single Catalyst: Modular Assembly of P-Alkyne Hybrid Ligands.

Metal-catalyzed C-H activation strategies provide an efficient approach for synthesis by minimizing atom, step, and redox economy. Developing milder, greener, and more effective protocols for these strategies is always highly desirable to the scientific community. In this study, the utilization of a single rhodium complex enabled the visible-light-induced late-stage C-H activation of biaryl-type phosphines with alkynyl bromides, employing inherent phosphorus atoms as directing groups. This chemistry combines P(III)-directed C-H activation with visible light photocatalysis, under exogenous photosensitizer-free conditions, offering a unique platform for ligand design and preparation. Furthermore, this study also explores the asymmetric catalysis and coordination chemistry of the resulting P-alkyne hybrid ligands with specific transition metals. Experimental results and density functional theory calculations demonstrate the mechanistic intricacies of this transformation.

Construction of Conjugated 1,3-Enynes via Pd-Catalyzed Cascade Alkynylation of Aryl Phenol-Tethered Alkynes with Alkynyl Bromides.

An efficient Pd-catalyzed cascade alkynylation of aryl phenol-tethered alkynes with alkynyl bromides is described. This protocol could provide various conjugated 1,3-enynes possessing a polysubstituted spirocyclohexadienone, as well as an all-carbon tetrasubstituted alkene moiety. The products could also undergo ring-expansion and cyclization transformations under different conditions to convert to diverse fused cyclic scaffolds.

Enantioselective Hydroalkenylation and Hydroalkynylation of Alkenes Enabled by a Transient Directing Group: Catalyst Generality through Rigidification.

The catalytic enantioselective synthesis of α-chiral alkenes and alkynes represents a powerful strategy for rapid generation of molecular complexity. Herein, we report a transient directing group (TDG) strategy to facilitate site-selective palladium-catalyzed reductive Heck-type hydroalkenylation and hydroalkynylation of alkenylaldehyes using alkenyl and alkynyl bromides, respectively, allowing for construction of a stereocenter at the δ-position with respect to the aldehyde. Computational studies reveal the dual beneficial roles of rigid TDGs, such as L-tert-leucine, in promoting TDG binding and inducing high levels of enantioselectivity in alkene insertion with a variety of migrating groups.

Enantioselective Hydroalkenylation and Hydroalkynylation of Alkenes Enabled by a Transient Directing Group: Catalyst Generality through Rigidification**

AbstractThe catalytic enantioselective synthesis of α‐chiral alkenes and alkynes represents a powerful strategy for rapid generation of molecular complexity. Herein, we report a transient directing group (TDG) strategy to facilitate site‐selective palladium‐catalyzed reductive Heck‐type hydroalkenylation and hydroalkynylation of alkenylaldehyes using alkenyl and alkynyl bromides, respectively, allowing for construction of a stereocenter at the δ‐position with respect to the aldehyde. Computational studies reveal the dual beneficial roles of rigid TDGs, such as L‐tert‐leucine, in promoting TDG binding and inducing high levels of enantioselectivity in alkene insertion with a variety of migrating groups.

Functionalization of Olefinic C−H Bonds by an Aryl‐to‐Vinyl 1,4‐Nickel Migration/Reductive Coupling Sequence

AbstractAn attractive approach to selective functionalization of remote C−H bonds is a metal/hydride shift/cross‐coupling reaction sequence. Complimentary to the heavily exploited 1,2‐nickel/hydride shift along an sp3 chain, a chain‐walking process, the 1,4‐nickel/hydride shift along an sp2 chain is more complex. Here we report an unprecedented aryl‐to‐vinyl 1,4‐nickel/hydride shift reaction, in which the migratory alkenylnickel species generated in situ is selectively trapped by one of various coupling partners, such as isocyanates, alkyl bromides, aryl chlorides or alkynyl bromides, allowing regio‐ and stereoselective access to trisubstituted alkenes. In contrast to the well‐reported ipso‐aryl coupling reactions, this strategy provides remote alkenyl C−H functionalized products with good yield and with excellent chemo‐, regio‐ and E/Z‐selectivity.

Functionalization of Olefinic C-H Bonds by an Aryl-to-Vinyl 1,4-Nickel Migration/Reductive Coupling Sequence.

An attractive approach to selective functionalization of remote C-H bonds is a metal/hydride shift/cross-coupling reaction sequence. Complimentary to the heavily exploited 1,2-nickel/hydride shift along an sp3 chain, a chain-walking process, the 1,4-nickel/hydride shift along an sp2 chain is more complex. Here we report an unprecedented aryl-to-vinyl 1,4-nickel/hydride shift reaction, in which the migratory alkenylnickel species generated in situ is selectively trapped by one of various coupling partners, such as isocyanates, alkyl bromides, aryl chlorides or alkynyl bromides, allowing regio- and stereoselective access to trisubstituted alkenes. In contrast to the well-reported ipso-aryl coupling reactions, this strategy provides remote alkenyl C-H functionalized products with good yield and with excellent chemo-, regio- and E/Z-selectivity.

Nickel/Photoredox-Catalyzed Enantioconvergent Reductive Cross-Coupling of α-Bromo Phosphonates

Key words alkynyl bromides - nickel catalysis - phosphonates - photoredox catalysis - reductive cross-coupling

Palladium-Catalyzed 1,1-Alkynyloxygenation of 2-Vinylbenzoates with Alkynyl Bromides

The palladium-catalyzed reaction of alkyl 2-vinylbenzoates with silyl-protected alkynyl bromides leads to the selective production of 3-alkynylated isochroman-1-ones. The use of an alkyl ester group as an effective oxygen nucleophile is crucial for the efficient 1,1-alkynyloxygenation of alkenes.

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

AbstractTransition‐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.