Coupling Of Alkynes Research Articles

Carpet Beater Molecules: Synthesis and Characterization of Functional Hexa‐peri‐benzocoronene–Alkyne Coupling Products

AbstractWithin the scope of this paper, nine π‐expanded mono‐substituted 5,8,11,14,17‐pentakis‐(tert‐butyl)‐hexa‐peri‐hexabenzocoronenes (HBC) are introduced. 2‐Iodo‐5,8,11,14,17‐pentakis‐(tert‐butyl)‐hexa‐peri‐hexabenzocoronene served as precursor and was reacted with ethynyltrimethylsilane in a Sonogashira coupling reaction. The acetylene unit is used as a linker and can undergo another Sonogashira coupling reaction combining different phenyl coupling partners with the HBC core. The electron‐withdrawing groups such as nitrile, pyridine and carbonyl species (aldehyde, methylester, carboxylic acid) as well as the three quinoxaline based species (diphenylquinoxaline, dibenzo[a,c]phenazine, phenanthro[4’,5’‐a,b,c]phenazine) serve as substitution moieties. Their influence on the optoelectronic properties were investigated by UV/Vis absorption spectroscopy demonstrating a maximum redshift of 7 nm compared to starting compound 2‐Iodo‐5,8,11,14,17‐pentakis‐(tert‐butyl) HBC. As for the phenanthro[4’,5’‐a,b,c]phenazine substituted HBC a dramatic decrease in the intensity of the absorption of the UV/Vis spectrum was observed. The fluorescence spectroscopy pointed out that the dibenzo[a,c]phenazine and phenanthro[4’,5’‐a,b,c]phenazine substitution changed the spectra to one broad peak departing from the characteristic HBC‐like emission pattern.

Silver-mediated Room Temperature Reactions for the Synthesis of N-α-Ketoacyl Sulfoximines and N-α,β-Unsaturated Acyl Sulfoximines.

Here, we report a silver-mediated coupling of acetylenes with sulfoximines to synthesize N-α-ketoacyl sulfoximines and N-α,β-unsaturated acyl sulfoximines. The reactions are performed under an open atmosphere using the oxidant K2S2O8 and the ligand 2,2-bipyridyl. However, the fate of the product formation is controlled by the type of substrate used. The coupling between aryl acetylenes and sulfoximines afforded the N-α-ketoacylsulfoximines, while the alkyl acetylenes provided the N-α,β-unsaturated acyl sulfoximines. Controlled experiments reveal the differential reactivity patterns of substrates. The labeling 18O experiments showed that water is the source of the incoming oxygen atom for the keto group of N-α-ketoacyl sulfoximines and N-α,β-unsaturated acyl sulfoximines.

Palladium-Catalyzed Cyclization Coupling with Cyclobutanone-Derived N-Tosylhydrazones: Synthesis of Benzofuran-3-Cyclobutylidenes and Spirocyclobutanes

A palladium-catalyzed cyclization coupling of iodoarene-tethered alkynes with cyclobutanone-derived N-tosylhydrazones is reported, providing a convenient and efficient approach to benzofuran-3-cyclobutylidenes. On this basis, spirocyclobutanes can be generated smoothly in an efficient cascade manner by the addition of dienophiles. Good yields and scalability are demonstrated. Sequential intramolecular carbopalladation, palladium-carbene migratory insertion, δ-hydride elimination, and cycloaddition processes are involved.

Stereoselective Synthesis of Functionalized 1,3‐Enynes through Recyclable Copper(I)‐Catalyzed Three‐Component Reaction of Terminal Alkynes, Diazoesters and Aldehydes

AbstractA highly efficient heterogeneous copper(I)‐catalyzed three‐component coupling of terminal alkynes, diazoesters and aldehydes has been achieved by using 10 mol% of copper(I) iodide complex [N,N‐CuI‐MCM‐41] anchored on 2‐aminoethylamino‐modified mesoporous material MCM‐41 as the catalyst under mild conditions, delivering a wide variety of 2‐alkoxycarbonyl‐substituted (E)‐1,3‐enynes in mostly good to high yields with excellent stereoselectivity. The heterogenized copper(I) complex can be facilely prepared from inexpensive reagents by using a simple procedure and exhibits a remarkably higher catalytic activity than CuI, and can be recycled more than ten times without a significant drop in its catalytic efficiency. This protocol represents the first example of heterogeneous copper‐catalyzed stereoselective construction of functionalized 1,3‐enynes from simple and commercially available starting materials.

Ni-catalyzed arylation of alkynes with organoboronic acids and aldehydes to access stereodefined allylic alcohols.

A new, efficient and practical method for the three-component arylative coupling of aldehydes, alkynes and arylboronic acids has been developed through nickel catalysis. This transformation provides diverse Z-selective tetrasubstituted allylic alcohols without the use of any aggressive oragnometallic nucleophiles or reductants. Moreover, benzylalcohols are viable coupling partners via oxidation state manipulation and arylative coupling in one single catalytic cycle. This reaction features a direct and flexible approach for the preparation of stereodefined arylated allylic alcohols with broad substrate scope under mild conditions. The utility of this protocol is demonstrated through the synthesis of diverse biologically active molecular derivatives.

Electrochemical synthesis of 2-alkyl-4-phenylalkan-2-ols via cathodic reductive coupling of alkynes with unactivated aliphatic ketones.

Herein, we present an efficient electrochemical method for synthesizing 2-alkyl-4-phenylalkan-2-ols through an electrochemically driven cathodic reductive coupling of the terminal and internal acetylenes with unactivated aliphatic ketones under mild conditions. The process proceeds through a ketyl radical, which then activates the aryl acetylene and causes complete reduction of the triple bond of the acetylene moiety. This strategy is environmentally benign and exhibits a broad substrate scope with ubiquitously available starting materials.

Cobalt-Catalyzed Electrochemical Reductive Coupling of Alkynes and Alkenes

Cobalt-Catalyzed Electrochemical Reductive Coupling of Alkynes and Alkenes

Cu/SaBox-Catalyzed Photoinduced Coupling of Acylsilanes with Alkynes.

The transition metal-catalyzed cross-coupling reaction with Fischer metal carbene intermediates bearing an electron-rich alkoxyl or siloxyl group remains a big challenge due to the lack of readily available corresponding carbene precursors. Herein, we report the coupling of alkynes with the Fischer-type copper carbene species bearing a α-siloxyl group, which could be in situ generated from acylsilanes catalytically under photoirradiation and redox-neutral conditions. The side-arm modified bisoxazoline (SaBox) ligands prove to be crucial for this coupling reaction, which provides the corresponding alkynyl alcohol in high yields with remarkable heterocycle tolerance and broad substrate scope.

Cu/SaBox‐Catalyzed Photoinduced Coupling of Acylsilanes with Alkynes

AbstractThe transition metal‐catalyzed cross‐coupling reaction with Fischer metal carbene intermediates bearing an electron‐rich alkoxyl or siloxyl group remains a big challenge due to the lack of readily available corresponding carbene precursors. Herein, we report the coupling of alkynes with the Fischer‐type copper carbene species bearing aα‐siloxyl group, which could be in situ generated from acylsilanes catalytically under photoirradiation and redox‐neutral conditions. The side‐arm modified bisoxazoline (SaBox) ligands prove to be crucial for this coupling reaction, which provides the corresponding alkynyl alcohol in high yields with remarkable heterocycle tolerance and broad substrate scope.

A Copper‐Catalyzed [5+1] Cycloaddition of Terminal Alkynes with Diazo Esters through a Tandem 1,5‐H‐Shift Cyclization

Comprehensive SummaryA copper‐catalyzed [5+1] cycloaddition reaction of terminal alkynes with diazo esters for the rapid construction of protected naphthalen‐1(2H)‐one derivatives in moderate to good yields has been disclosed along with good functional group compatibility and a broad substrate scope. The mechanistic investigations reveal that this tandem cyclization process proceeds through a Cu(I)‐catalyzed coupling of terminal alkyne with diazoacetate, a 1,5‐H shift process and a thermally induced pericyclic reaction via an allene intermediate. The synthetic utility and the further transformations of the obtained cycloadduct to naphthalenone, naphthol and dihydronaphthol have been also presented in this paper.

Synthesis and crystal structures of copper complexes with N,N,N-tridentate chelating ligands containing o-phenanthroline-appended benz-fused polyazoles and their catalytic application in A3 coupling reaction

Design of two new N-enriched N,N,N-tridentate chelating ligands comprising of benz-fused polyazole-based heterocyclic scaffolds in combination with 1,10-phenanthroline motif, has been presented in this work for exploring their Cu-complexes as structurally well-defined precatalysts for A3 coupling reactions. With the two different tridentate N-donor ligands L1 and L2, two monomeric Cu(II) complexes, [Cu(L1)2(OClO3)][ClO4] (Cu-1) and [Cu(L2)(OClO3)(OH2)2][ClO4] (Cu-2) have been synthesized in good yield and characterized well with spectroscopic and crystallographic techniques. In spite of similar type of ligands, structures of the complexes are quite different which can be attributed to the electronic effect of the ligands. Crystal structure of Cu-1 reveals that the central copper ion is in octahedral geometry where one ligand is ligated in tridentate mode and the other is coordinated in a bidentate mode. In case of complex Cu-2, it is observed that only one ligand has been coordinated in tridentate mode. The N-heterocyclic backbone possesses key electronic properties such as good π-accepting/σ-donating property, and efficient charge sinks due to the presence of the extended π-conjugation, Accordingly, both the complexes have been found to be efficient precatalysts in A3 coupling of aldehydes, amines, and alkynes for the synthesis of propargylamines.

Microwave‐Assisted Tandem Copper‐Catalyzed Three‐Component Reaction for Synthesis of 2‐Iminopyrans

AbstractThe iminopyrans were synthesized by the CuAAC‐MCR approach, the coupling of enaminones, phenyl acetylenes, and sulfonyl, under microwave treatment. The mechanism of the formation of iminopyrans along with amidine has been studied in detail. Experiments to minimize amidine formation were explored, and unfortunately, these experiments were unsuccessful. Molar equivalents of enaminones, phenyl acetylenes, and sulfonyl were optimized to increase the yield of iminopyran. Fluorescent properties of iminopyrans were characterized using Frontier molecular orbital analysis, UV absorption, and emission studies.

Regio- and Stereoselective Reductive Coupling of Alkynes and Crotononitrile.

A new regio- and stereoselective reductive coupling of alkynes and crotononitrile has been developed via visible light organophotoredox cobalt dual catalysis. A variety of enantioenriched homoallylic nitriles bearing a stereodefined trisubstituted alkene have been easily synthesized with good to excellent regio- (up to >20:1 rr), stereo- (>20:1 E/Z), and enantioselectivity (up to 98% ee) control under mild conditions. The corresponding nitrile products were smoothly converted into various chiral building blocks. Remarkably, a simple organic base together with water have been utilized as hydrogen sources in this photoinduced reductive reaction.

On-DNA Alkyne Iodination and Acetylenic Coupling as a Useful Tool for DEL Synthesis.

1-Iodoalkynes and 1,3-diynes are versatile chemical intermediates and pharmaceutically valuable ingredients. In this study, copper mediated on-DNA alkyne iodination and Cadiot-Chodkiewicz coupling are developed for the first time. This generates diverse, systematic, and unprecedented topographic structural features, which could be invaluable as molecular recognition agents for drug discovery in DEL screening.

Convenient and efficient reaction system for the oxidative coupling of terminal alkynes over Cu+-containing layered double hydroxides

An efficient and convenient catalytic procedure has been developed for the aerobic oxidative coupling of terminal alkynes to produce 1,3-conjugated diynes over CuCoFe-LDH (Layered double hydroxide) in the absence of base additive. The heterogeneous catalytic system could tolerate various arylacetylenes in good to excellent yields. The results indicated that Cu+ species in CuCoFe-LDH should play the predominant role in the transformation, and dual functions of the catalyst were observed. The CuCoFe-LDH also showed good structural and catalytical stability during the reactions.

Selective Reductive Coupling of Vinyl Azaarenes and Alkynes via Photoredox Cobalt Dual Catalysis.

A visible light-induced Co-catalyzed highly regio- and stereoselective reductive coupling of vinyl azaarenes and alkynes has been developed. Notably, Hünig's base together with simple ethanol has been successfully applied as the hydrogen sources instead of commonly used Hantzsch esters in this catalytic photoredox reaction. This approach has considerable advantages for the straightforward synthesis of stereodefined multiple substituted alkenes bearing an azaarene motif, such as excellent regioselectivity (>20 : 1 for >30 examples) and stereoselectivity (>20 : 1 E/Z), broad substrate scope and good functional group compatibility under mild reaction conditions, which has been utilized in the concise synthesis of natural product monomorine I. A reasonable catalytic reaction pathway involving protolysis of the cobaltacyclopentene intermediate has been proposed based on the mechanistic studies.

Selective Reductive Coupling of Vinyl Azaarenes and Alkynes via Photoredox Cobalt Dual Catalysis

AbstractA visible light‐induced Co‐catalyzed highly regio‐ and stereoselective reductive coupling of vinyl azaarenes and alkynes has been developed. Notably, Hünig's base together with simple ethanol has been successfully applied as the hydrogen sources instead of commonly used Hantzsch esters in this catalytic photoredox reaction. This approach has considerable advantages for the straightforward synthesis of stereodefined multiple substituted alkenes bearing an azaarene motif, such as excellent regioselectivity (>20 : 1 for >30 examples) and stereoselectivity (>20 : 1 E/Z), broad substrate scope and good functional group compatibility under mild reaction conditions, which has been utilized in the concise synthesis of natural product monomorine I. A reasonable catalytic reaction pathway involving protolysis of the cobaltacyclopentene intermediate has been proposed based on the mechanistic studies.

Palladium Nanoparticles from Desulfovibrio alaskensis G20 Catalyze Biocompatible Sonogashira and Biohydrogenation Cascades.

Transition-metal nanoparticles produced by living bacteria are emerging as novel catalysts for sustainable synthesis. However, the scope of their catalytic activity and their ability to be integrated within metabolic pathways for the bioproduction of non-natural small molecules has been underexplored. Herein we report that Pd nanoparticles synthesized by the sulfate-reducing bacterium Desulfovibrio alaskensis G20 (DaPdNPs) catalyze the Sonogashira coupling of phenyl acetylenes and aryl iodides, and the subsequent one-pot hydrogenation to bibenzyl derivatives using hydrogen gas generated from d-glucose by engineered Escherichia coli DD-2. The formal hydroarylation reaction is biocompatible, occurs in aqueous media at ambient temperature, and affords products in 70-99% overall yield. This is the first reported microbial nanoparticle to catalyze the Sonogashira reaction and the first demonstration that these biogenic catalysts can be interfaced with the products of engineered metabolism for small molecule synthesis.

Ni-catalyzed, enantioselective three-component radical relayed reductive coupling of alkynes: Synthesis of axially chiral styrenes

Axially chiral styrenes are of great interest because they could serve as a class of novel chiral ligands in enantioselective synthesis. However, only recently have strategies been developed for their enantioselective preparation. Herein, we have developed a Ni-catalyzed, enantioselective, three-component radical relayed reductive coupling to rapidly construct axially chiral styrene. This three-component radical relayed reductive coupling strategy utilizes a chiral nickel/pyridine-oxazoline system to facilitate the challenging three-component, enantioselective difunctionalization of alkynes with high efficiency and excellent enantioselectivity. The mild conditions allow for broad substrate scopes as well as good functional-group toleration. We performed computational mechanistic studies to gain insights into the mechanism and origin of the chemo- and enantioselectivity. Furthermore, the reaction could be scaled up, and the resulting axially chiral styrenes could be easily transformed into 1-(1-phenylvinyl)naphthalene phosphine ( ( s )-SJTU-PHOS-1 ) with high stereoselectivities, which showed great promise as a new type of styrene ligand. • Three-component radical relayed reductive coupling to construct axial chiral styrene • Broad substrate scope with excellent enantioselectivity and regioselectivity • Axially chiral styrenes transformed into chiral ligand • Computational studies to gain insights into the chemo- and enantioselectivity Axially chiral styrene has recently attracted considerable attention from chemists because of its widespread use in biological active compounds, chiral catalysts, and ligands. In this article, we develop a radical relayed reductive coupling to construct axially chiral styrene with high efficiency and excellent enantioselectivity via highly active sp 2 center radicals. The resulting axially chiral styrenes could be easily transformed into a new type of potential styrene ligand. Mechanistically, we conducted detailed computational mechanistic studies to understand the chemo- and enantioselectivity of this reaction. We anticipate that this enantioselective three-component radical relayed reductive coupling protocol will have important implications for the construction of axially chiral styrene. Zhang and co-workers have developed a novel radical relayed reductive coupling to construct axial chiral styrene with high efficiency. A weak coordination effect, found to be crucial in nickel-catalyzed three-component cross-coupling reactions, is not required in this system. The authors performed computational studies to gain insights into the chemo- and enantioselectivity. Furthermore, the reaction could be scaled up, and the resulting axially chiral styrenes could be transformed into chiral ligand ( s )-SJTU-PHOS-1 , which showed great promise as a new styrene ligand.

C – C coupling of alkynes to the CH2 group in a 1-phosphonioethenyl ligand in a zwitterionic dirhenium carbonyl complex

Reactions of the zwitterionic dirhenium complex Re2(CO)8[μ-η2-1-C(CH2)(PMePh2)], 3 with the terminal alkynes, HCC(OEt) and HCCPh, have yielded two new isomeric ethoxy-substituted dirhenium complexes, Re2(CO)7[µ-η3-C(H)C(OCH2CH3)CH2C(PMePh2)], 5 and Re2(CO)7[µ-η3-C(OCH2CH3)C(H)CH2C(PMePh2)], 6 and one phenyl-substituted dirhenium complex Re2(CO)7[µ-η3-C(H)CPhCH2C(PMePh2)], 7, respectively, with each containing a bridging, substituted 1-phosphonio-3,4-butenyl ligand formed by loss of CO and the addition and coupling of one alkyne to the CH2 group of the 1-phosphonioethenyl ligand in 3. The bridging 1-phosphonio-3,4-butenyl ligand in compound 6 exhibits a dynamical “flip-flop” exchange for the phosphonio-3,4-butenyl ligand between the two rhenium atoms that leads to an averaging of the inequivalent protons on its methylene group that is rapid on the NMR timescale. When heated to 70oC, compound 5 was converted to two new compounds: Re2(CO)6(µ-H)[µ-η4-C(H)C(OCH2CH3)CHC(PMePh2)], 8, by loss of a CO ligand and a CH activation at the CH2 group in its C(H)C(OCH2CH3)CH2C(+PMePh2) ligand and an isomer Re2(CO)6(PMePh2)[µ-η4-C(H)C(OCH2CH3)CHCH], 9. Compound 9 was also obtained from 8 by heating to 80 °C for 5 days by shifting the PMePh2 group from its phosphonium carbon atom in 8 to one of the rhenium atoms to become a PMePh2 ligand in 9 and then shifting the hydrido ligand back to the same carbon atom to form a bridging η4-2-ethoxybutadiendiyl, [C(H)C(OCH2CH3)CHCH], ligand. All new products were characterized structurally by single-crystal X-ray diffraction analyses.