Coupling Of Alkynes Research Articles

Cobalt-Catalyzed Enantioselective Reductive Coupling of Imines and Internal Alkynes.

Chiral allylamines are important structural components in natural products, pharmaceuticals, and chiral catalysts. Herein, we report a cobalt-catalyzed enantioselective reductive coupling of imines with internal alkynes to synthesize chiral allyl amines. The reaction is catalyzed by a cobalt complex derived from commercially available bisphosphine ligand utilizing zinc as the electron donor.The substrate scope is extensive. Symmetric and asymmetric alkyl and aryl alkynes have been successfully coupled with various imines derived from aryl and alkyl aldehydes. Tri- and tetra-substituted allyl amines were isolated in high yields exceeding 89%, with enantiomeric excess surpassing >99.9% and regioselectivities exceeding >20:1. These chiral allylamines can serve as versatile platformsfor subsequent transformations while preserving their stereochemical integrity. Extensive experimental and computational mechanistic studies were performed to elucidate the mechanism. These investigations have indicated that an in situ cobalt(I) catalyst enables the oxidative cyclization of alkynes and imines, and a spin crossover occurs during the enantio-determining step. Zinc plays a pivotal role in facilitating the transmetallation of the resulting azacobaltacycle. The observed enantioselectivity was interpreted by the stabilization of the transition state through higher stabilization interaction energy from high negative polarization, dispersion, and C-H•••π interactions.

Cobalt‐Catalyzed Enantioselective Reductive Coupling of Imines and Internal Alkynes

Cobalt‐Catalyzed Enantioselective Reductive Coupling of Imines and Internal Alkynes

Advances in the Synthesis of Isoquinolines Using an Alkyne Coupling Partner via Transition‐Metal‐Catalyzed C─H Activation

AbstractIsoquinoline is a privileged structural motif and has extensive applications in asymmetric catalysis, photochemistry, and pharmaceutical use. Naturally, isoquinoline is a popular synthetic target for many research groups worldwide, who, as a result, have developed numerous methodologies to afford a wide variety of derivatives. The synthesis of isoquinoline in recent years has flourished, employing C─H activation strategies using various transition metal catalysts: rhodium (Rh), ruthenium (Ru), nickel (Ni), manganese (Mn), and cobalt (Co). To summarize this diverse area of study, this review comprehensively assimilates the literature where isoquinolines are synthesized using alkynes (both internal and terminal) as coupling partners. Wherever possible, the mechanistic details associated with the reported reactions are provided.

Chemodivergent, enantio- and regioselective couplings of alkynes, aldehydes and silanes enabled by nickel/N-heterocyclic carbene catalysis

Chemodivergent, enantio- and regioselective couplings of alkynes, aldehydes and silanes enabled by nickel/N-heterocyclic carbene catalysis

Reductive coupling of allenyl/allyl carbonate with alkyne under dual cobalt-photoredox catalysis

Skipped dienes are among the most prevalent motifs in a vast array of natural products, medicinal compounds, and fatty acids. Herein, we disclose a straightforward one-step reductive protocol under Co/PC for the synthesis of diverse 1,4-dienes with excellent regio- and stereoselectivity. The protocol employs allenyl or allyl carbonate as π-allyl source, allowing for the direct synthesis of skipped diene with a broad range of alkynes including terminal alkynes, propargylic alcohols, and internal alkynes. The method also demonstrated the biomimetic homologation of natural terpenols into synthetic counterparts via iterative allylation of three-carbon allyl units, employing propargylic alcohol as a readily available alkyne source. Experimental studies, control experiments, and DFT calculations suggest the dual catalytic process generates 1,3-diene from allenyl carbonate, followed by proton and electron transfer leading to Co(II)-π-allyl species prior to the alkyne coupling. The catalytic cycle transitions through Co(II), Co(I), and Co(III).

Generation of Bis(pentafluorophenyl)boron Enolates from Alkynes and Their Catalyst‐Free Alkyne Coupling

Carbon‐carbon bond forming reactions are powerful synthetic tools for constructing organic molecular frameworks. In this study, strongly Lewis acidic bis(pentafluorophenyl)boron enolates were generated from alkynes through oxygen transfer from 2,6‐dibromopyridine N‐oxide using tris(pentafluorophenyl)borane [B(C6F5)3]. Boron enolates were highly reactive owing to the strong acidity of the boron centers, and thus immediately coupled with alkynes. N‐Ethynylphthalimide reacted as an alkyne with 2,6‐dibromopyridine N‐oxide and B(C6F5)3 to form a semi‐stable bis(pentafluorophenyl)boron enolate through the coordination of the carbonyl group to the boron center. This enolate underwent coupling with another alkyne.

Insights Into the Magnesium‐Catalyzed C−C Coupling of Terminal Alkynes with Carbodiimides

AbstractThe bis‐guanidinate anion stabilized amido magnesium (II) compound [LMgN(SiMe3)2; L={(ArHN)(ArN)−C=N−C=(NAr)(NHAr); Ar=2,6‐Et2−C6H3}] (Mg‐1) has been synthesized and characterized. It has been successfully employed as a pre‐catalyst for the catalytic C−C coupling of terminal alkynes with carbodiimides, producing propiolamidine products with moderate to good yields. The active catalyst bis‐guanidinate magnesium acetylide [LMgC≡C−Ph]2 (Mg‐2) and the intermediate magnesium propiolamidinate [LMg{(NiPr)2C}C≡C−Ph] (Mg‐3) involved in the catalytic reaction were isolated and thoroughly characterized through multinuclear NMR and mass spectral analyses, as well as single crystal X‐ray diffraction studies. Based on the above findings, a plausible mechanistic cycle has been proposed. Additionally, a new example of bis‐guanidinate supported structurally characterized magnesium propiolamidate compound [LMg{(4−CH3−C6H4)N−(C−C≡C−Ph)=O]2 (Mg‐4) has been described via the reaction between Mg‐2 and isocyanate.

Generation of Bis(pentafluorophenyl)boron Enolates from Alkynes and Their Catalyst-Free Alkyne Coupling.

Carbon-carbon bond forming reactions are powerful synthetic tools for constructing organic molecular frameworks. In this study, strongly Lewis acidic bis(pentafluorophenyl)boron enolates were generated from alkynes through oxygen transfer from 2,6-dibromopyridine N-oxide using tris(pentafluorophenyl)borane [B(C6F5)3]. Boron enolates were highly reactive owing to the strong Lewis acidity of the boron centers, and thus immediately coupled with alkynes. N-Ethynylphthalimide reacted as an alkyne with 2,6-dibromopyridine N-oxide and B(C6F5)3 to form a semi-stable bis(pentafluorophenyl)boron enolate through the coordination of the carbonyl group to the boron center. This enolate underwent coupling with another alkyne.

Copper Catalysts Anchored on Cysteine-Functionalized Polydopamine-Coated Magnetite Particles: A Versatile Platform for Enhanced Coupling Reactions.

Cysteine plays a crucial role in the development of an efficient copper-catalyst system, where its thiol group serves as a strong anchoring site for metal coordination. By immobilizing copper onto cysteine-modified, polydopamine-coated magnetite particles, this advanced catalytic platform exhibits exceptional stability and catalytic activity. Chemical modification of the polydopamine (PDA) surface with cysteine enhances copper salt immobilization, leading to the formation of the Fe3O4@PDA-Cys@Cu platform. This system was evaluated in palladium-free, copper-catalyzed Sonogashira coupling reactions, effectively catalyzing the coupling of terminal acetylenes with aryl halides. Additionally, the Fe3O4@PDA-Cys@Cu platform was employed in click reactions, confirming the enhanced catalytic efficiency due to increased copper content. The reusability of the platform was further investigated, demonstrating improved performance, especially in recyclability tests in click reaction, making it a promising candidate for sustainable heterogeneous catalysis.

AgOTf-catalyzed three-component coupling for the synthesis of C-alkynyl iminosugars

A3 coupling of tosylribose, primary amine and alkyne has been accomplished for the synthesis of C-alkynyl iminosugars using a catalytic amount of AgOTf under extremely mild conditions. This method is compatible with acid sensitive acetonide and cyclohexylidene and also TBS and PMB ethers The reaction proceeds through a cyclic iminium ion, which is formed from tosylribose and a primary amine followed by the attack of alkyne resulting in the formation of C-alkynyl iminosugar, which is a key intermediate of many biologically important natural products.

Rhodium Catalysts Based on Phenyl Substituted Cp Ligands for Indole Synthesis via Oxidative Coupling of Acetanilides and Alkynes

AbstractRhodium‐catalyzed oxidative coupling of acetanilides and alkynes via C−H activation is the most powerful synthetic tool for producing the indole motif from commercially available precursors. However, this reaction usually requires large catalyst loadings (5 mol% of rhodium). In this study, a 1,2‐diphenylcyclopentadienyl ligand‐based catalyst was developed that works well at 1 mol% loading of rhodium. DFT calculations of the C−H activation step provided insight into its high catalytic activity. The catalyst efficiency was also demonstrated in the synthesis of naturally occurring isocoumarins, such as polygonolide, tubakialactone B and penicimarine F. The developed catalytic protocols tolerate a wide range of functional groups, for example, halide, nitro, hydroxy, and alkoxy.

Copper on charcoal: copper nanoparticles catalyzed for highly efficient aerobic oxidative coupling of terminal alkynes

Copper on charcoal: copper nanoparticles catalyzed for highly efficient aerobic oxidative coupling of terminal alkynes

Synergistic Homogeneous Asymmetric Cu Catalysis with Pd Nanoparticle Catalysis in Stereoselective Coupling of Alkynes with Aldimine Esters.

Understanding the nature of a transition-metal-catalyzed process, including catalyst evolution and the real active species, is rather challenging yet of great importance for the rational design and development of novel catalysts, and this is even more difficult for a bimetallic catalytic system. Pd(0)/carboxylic acid combined system-catalyzed allylic alkylation reaction of alkynes has been used as an atom-economical protocol for the synthesis of allylic products. However, the asymmetric version of this reaction is still rather limited, and the in-depth understanding of the nature of active Pd species is still elusive. Herein we report an enantioselective coupling between readily available aldimine esters and alkynes using a synergistic Cu/Pd catalyst system, affording a diverse set of α-quaternary allyl amino ester derivatives in good yields with excellent enantioselectivities. Mechanistic studies indicated that it is most likely a synergistic asymmetric molecular Cu catalysis with Pd nanoparticle catalysis. The Pd catalyst precursor is transformed to soluble Pd nanoparticles in situ, which are responsible for activating the alkyne to an electrophilic allylic Pd intermediate, while the chiral Cu complex of the aldimine ester enolate provides chiral induction and works in synergy with the Pd nanoparticles.

Regiocontrollable B(2/3)-H Alkenylation of nido-Carboranes.

Anionic nido-carboranes, as open-cage analogues of closo-carboranes with strong hydrophilicity and higher potential in the development of biomedicines, have been notably more challenging because of their strong interaction with transition metals. While the exo-cage B-H activation reactions of nido-carboranes have been widely studied, there are few reports on the direct functionalization of B-H bonds located on a closed polyhedral sphere. Here, we report an efficient palladium-catalyzed regioselective B(2/3)-H alkenylation of nido-carboranes with various alkenes and alkyne coupling partners, enabled by 3-methylpyridine directing groups, to achieve a regiocontrollable functionalization of B(2/3)-H vertices over highly reactive exo-cage B11-H vertex in nido-carboranes.

TBHP Promotes Cross-Dehydrogenative Coupling of SF4 Alkynes with Tetrahydroisoquinolines under Copper Catalysis.

We present a viable approach for the cross-dehydrogenative coupling of Het-SF4-alkynes with tetrahydroisoquinolines under oxidative conditions, using TBHP and copper catalysts. These newly developed conditions boast enhanced yields and a more extensive range of substrates, demonstrating tolerance to various functional groups and addressing the limitations of earlier reports. Consequently, this method should increase opportunities for the exploration of SF4-containing compounds and their potential applications in drug discovery, materials science, and as alternatives to PFAS.

Water-catalyzed iron-molybdenum carbyne formation in bimetallic acetylene transformation

Transition metal carbyne complexes are of fundamental importance in carbon-carbon bond formation, alkyne metathesis, and alkyne coupling reactions. Most reported iron carbyne complexes are stabilized by incorporating heteroatoms. Here we show the synthesis of bioinspired FeMo heterobimetallic carbyne complexes by the conversion of C2H2 through a diverse series of intermediates. Key reactions discovered include the reduction of a μ-η2:η2-C2H2 ligand with a hydride to produce a vinyl ligand (μ-η1:η2-CH = CH2), tautomerization of the vinyl ligand to a carbyne (μ-CCH3), and protonation of either the vinyl or the carbyne compound to form a hydrido carbyne heterobimetallic complex. Mechanistic studies unveil the pivotal role of H2O as a proton shuttle, facilitating the proton transfer that converts the vinyl group to a bridging carbyne.

Photo-catalyzed dearomative coupling of benzylmalonates and alkynes with CO2 leading to spiro-1,4-cyclohexadiene carboxylic acids

A dearomative coupling reaction of benzylmalonates and alkynes with CO2via visible-light catalysis is developed, leading to a series of spiro-1,4-cyclohexadiene carboxylic acids. This three-component transformation achieves sequential dearomatization, alkenylation, and carboxylation of non-activated bezene ring, building spiro architecture and installing two functional groups in one reaction step. The strategy has the advantages of mild conditions, broad substrate scope, low loading of photocatalyst, redox neutral, excellent yield and high selectivity. Gram-scale reaction and product derivatizations indicate promising application prospects. Mechanistic studies reveal that the reaction might proceed through tandem radical addition, dearomatization and nucleophilic addition.

Cobalt‐Catalyzed Regioselective Methylative Coupling of Internal Alkynes with Aldehydes/Aldimines

Comprehensive SummaryCatalytic methylative coupling of internal alkynes and aldehydes/aldimines through regioselective oxidative cyclization promoted by a phosphine–Co complex is presented. Such process constitutes an unprecedented and unique approach for Co‐catalyzed generation of metallacycles that reversed inherent regiochemical biases to furnish a wide range of allylic alcohols and allylic amides bearing a tetrasubstituted alkene in up to 98% yield with high regioselectivity, representing a novel and general strategy for reversal of substrate‐controlled regioselectivity in metal‐catalyzed oxidative cyclization.

Design of efficient benzimidazole-derived N-heterocyclic carbene Ag(I) catalysts for aldehyde–amine–alkyne coupling

A mild catalytic protocol for aldehyde, amine, and alkyne coupling (A3-coupling) allows for the selective synthesis of propargyl amines using 5,6-dimethylbenzimidazole-derived N-heterocyclic carbene (BNHC) silver(I) catalysts. A series of BNHC Ag(Ⅰ) halide complexes were synthesized and their structures have been elucidated through the use of multinuclear NMR and FT-IR spectroscopy. Furthermore, the pseudo-linear geometry of two different compounds was substantiated by single-crystal X-ray diffraction. Silver-based A3-coupling was achieved for both acyclic and cyclic secondary amines using a diverse set of alkynes to afford propargyl amines with yields of up to 95 %. The present approach is environmentally benign and water is generated as the sole byproduct.

Nickel-Catalyzed Multicomponent Assembly of Alkynes toward α-CF3-Alkenes.

We disclose an efficient nickel catalytic system for expediting the coupling of alkynes with fluoroalkyl hydrazones and boronic acids, thus facilitating the synthesis of stereospecific α-fluoroalkyl-alkene derivatives. 3H-Pyrazoles might be involved as key intermediates through a nitrogen-releasing process, enabling subsequent coupling with boronic acids to afford 1,2-difunctional alkenes in a highly efficient and step-economical fashion. This tandem platform demonstrates broad functional group tolerance, including complex natural products and drug-like molecules.