Sonogashira Cross-coupling Reaction Research Articles

Palladium Catalyzed Synthesis of Phenylquinoxaline-Alkyne Derivatives via Sonogashira Cross Coupling Reaction

Transition metals mediated cross coupling methodologies provide an extremely powerful versatile pathway in organic syntheses undoubtedly, a facile route for syntheses and derivatization of biologically important heterocycles from easily available precursors. Sonogashira coupling reaction, a leading method to Csp-Csp2 bond formation is one of the most important and rapid pathways to couple aryl/vinyl halides with terminal alkynes. Current research study deals with the synthesis of alkyne substituted quinoxaline derivatives. The quinoxalines class of aromatic heterocycles exhibits a wide variety of important biological potencies. Palladium catalyzed cross coupling process provided an effective synthetic practice for the synthesis of alkyne derivatives of quinoxaline. Vareity of terminal alkynes were coupled with 2-(4-bromophenyl)quinoxaline under optimized conditions for Sonogashira reaction, affording alkyne substituted quinoxaline derivatives in high yields. The optimized reaction conditions for coupling of range of terminal alkyne with quinoxaline basic core render this process significant for designing of medicinally interesting precursors.

Palladium Catalyzed Synthesis of Phenylquinoxaline-Alkyne Derivatives via Sonogashira Cross Coupling Reaction

Transition metals mediated cross coupling methodologies provide an extremely powerful versatile pathway in organic syntheses undoubtedly, a facile route for syntheses and derivatization of biologically important heterocycles from easily available precursors. Sonogashira coupling reaction, a leading method to Csp-Csp2 bond formation is one of the most important and rapid pathways to couple aryl/vinyl halides with terminal alkynes. Current research study deals with the synthesis of alkyne substituted quinoxaline derivatives. The quinoxalines class of aromatic heterocycles exhibits a wide variety of important biological potencies. Palladium catalyzed cross coupling process provided an effective synthetic practice for the synthesis of alkyne derivatives of quinoxaline. Vareity of terminal alkynes were coupled with 2-(4-bromophenyl)quinoxaline under optimized conditions for Sonogashira reaction, affording alkyne substituted quinoxaline derivatives in high yields. The optimized reaction conditions for coupling of range of terminal alkyne with quinoxaline basic core render this process significant for designing of medicinally interesting precursors.

Palladium Catalyzed Synthesis of Phenylquinoxaline-Alkyne Derivatives via Sonogashira Cross Coupling Reaction

Transition metals mediated cross coupling methodologies provide an extremely powerful versatile pathway in organic syntheses undoubtedly, a facile route for syntheses and derivatization of biologically important heterocycles from easily available precursors. Sonogashira coupling reaction, a leading method to Csp-Csp2 bond formation is one of the most important and rapid pathways to couple aryl/vinyl halides with terminal alkynes. Current research study deals with the synthesis of alkyne substituted quinoxaline derivatives. The quinoxalines class of aromatic heterocycles exhibits a wide variety of important biological potencies. Palladium catalyzed cross coupling process provided an effective synthetic practice for the synthesis of alkyne derivatives of quinoxaline. Vareity of terminal alkynes were coupled with 2-(4-bromophenyl)quinoxaline under optimized conditions for Sonogashira reaction, affording alkyne substituted quinoxaline derivatives in high yields. The optimized reaction conditions for coupling of range of terminal alkyne with quinoxaline basic core render this process significant for designing of medicinally interesting precursors.

Synthesis of anthradithiophene containing conjugated polymers via a cross-coupling strategy.

New conjugated polymers that incorporate dihexylanthradithiophene (DHADT) in the main chain were prepared by Stille, Sonogashira, and Yamamoto cross-coupling polymerization reactions. The polymerization chemistry is enabled by a soluble 5,11-dibromodihexylanthradithiophene monomer that is capable of cross-coupling reactions. Five readily soluble DHADT containing polymers were prepared and characterized experimentally and computationally. These polymers possess HOMO energies of −5.18 eV to −5.43 eV and LUMO energies of −3.0 eV to −2.82 eV. The notable optical features include broad absorption and band gaps ranging from 1.62 eV to 2.15 eV. Polymers were tested in organic field effect transistors and were found to operate in the p-type regime.

Copper-free Sonogashira cross-coupling reactions: an overview.

The Sonogashira reaction is a cross-coupling reaction of a vinyl or aryl halide with a terminal alkyne to form a C–C bond. In its original form, the Sonogashira reaction is performed with a palladium species as a catalyst while co-catalyzed by a copper species and a phosphine or amine. The reaction is conducted under mild conditions, i.e., room temperature, aqueous solutions, and the presence of mild bases. Undeniably, the Sonogashira reaction is among the most competent and efficient reactions widely used in organic synthesis. This named reaction has proved useful in many organic synthesis areas, including the synthesis of pharmaceuticals, heterocycles, natural products, organic compounds, complex molecules having biological activities, nanomaterials, and many more materials that we use in our daily lives. The presence of transition metals as a catalyst was indeed essential in the Sonogashira reaction. However, recently, the reaction has been successfully conducted without copper as a co-catalyst and phosphines or amines as bases. In this critical review, we have focused on developments in the Sonogashira reaction successfully performed in the absence of copper complexes, phosphines or amines, which could be of particular advantage in implementing green chemistry principles and making the reactions more achievable from an economic viewpoint.

Fluorinated Iron(ii) clathrochelate units in metalorganic based copolymers: improved porosity, iodine uptake, and dye adsorption properties.

We report the synthesis of metalorganic copolymers made from the palladium catalyzed Sonogashira cross-coupling reaction between various iron(ii) clathrochelate building blocks with diethynyl–triptycene and fluorene derivatives. The target copolymers CCP1–5 were isolated in excellent yield and characterized by various instrumental analysis techniques. Interestingly, investigation of the copolymers' porosity properties discloses BET surface areas up to 337 m2 g−1 for the target compounds bearing fluorinated iron(ii) clathrochelate units CCP2,5. Moreover, the fluorinated copolymers display an outstanding uptake capacity of iodine with a maximum adsorption of 200 wt%. The target metalorganic copolymers CCP1–5 reveal very good adsorption of organic dyes, namely, methyl blue and methylene blue, from aqueous media.

Triazine-wingtips accelerated NHC-Pd catalysed carbonylative Sonogashira cross-coupling reaction

The transmetalation as the rate-limiting step was effectively accelerated by newly designed N-heterocyclic carbenes with triazine wingtips (T-NHC).

Sonogashira cross-coupling reactions of 5-(benzothiazol-2-yl)-1-(4-iodophenyl)-3-phenyl-6-vinyl(phenyl)verdazyls: synthetic and theoretical aspects

New ethynyl derivatives were synthesized from 5-(benzothiazol-2-yl)-1-(4-iodophenyl)-3-phenyl-6-vinyl(phenyl)verdazyls using Sonogashira cross-coupling reactions carried out in two stages. The resulted radicals were characterized using EPR, IR, UV/Vis spectroscopy, mass spectrometry, and cyclic voltammetry. Electronic structure calculations using quantum chemistry methods were performed to analyze some experimental results.

Design and synthesis of 1,8-naphthalimide functionalized benzothiadiazoles

Push-pull derivatives BTD2–BTD5 were designed and synthesized via Pd-catalyzed Sonogashira cross-coupling reaction followed by [2+2] cycloaddition–electrocyclic ring-opening reaction.

Chalice-Type Tridentate Silicon Lewis Acids of C3 Symmetry in a Single Step Starting from Hexadehydrotribenzo[12]annulene.

Tridentate Lewis acids with aligned functions were synthesized based on the rigid framework hexadehydrotribenzo[12]annulene. The backbone and its fluorinated analogue were synthesised in one‐pot syntheses, with alkyne deprotection and Sonogashira cross coupling reaction being carried out in one step. Hydrosilylation of the annulene with chlorohydrosilanes proceeded highly selectively and afforded rigid poly‐Lewis acids with three SiCl3 or SiCl2Me substituents perfectly oriented to one side of the molecule in a single step. The progress of hydrosilylation was investigated by time‐correlated NMR spectroscopic studies. The crystal structures show that the framework is symmetrically functionalised and the silyl substituents are aligned in one direction. To increase the acidity of the Lewis acids the chlorosilyl substituents were fluorinated with SbF3. Further investigation of hydrometallation reactions (M=B, Al, Ga, Sn) did not lead to corresponding structures.

Diorganyl Diselenides and Iron(III) Chloride Drive the Regio- and Stereoselectivity in the Selenation of Ynamides.

We report here our results on the application of ynamides as substrates in the reactions with diorganyl dichalcogenides and iron(III) chloride to give selectively three different types of compounds: E-α-chloro-β-(organoselenyl)enamides, 4-(organochalcogenyl)oxazolones, and vinyl tosylates. The results reveal that the selectivity in the formation of products was obtained by controlling the functional groups directly bonded to the nitrogen atom of the ynamides. Thus, α-chloro-β-(organoselenyl) enamide derivatives were exclusively obtained when the TsN- and MsN-ynamides were treated with a mixture of diorganyl diselenides (1.0 equiv) and FeCl3 (3.0 equiv) in dichloroethane (DCE, 3 mL), at room temperature. The 4-(organochalcogenyl)oxazolones were selectively obtained with ynamides having an ester group, directly bonded to the nitrogen atom, upon treatment with a solution of FeCl3 (1.5 equiv) and diorganyl dichalcogenides (1.0 equiv) in dichloromethane (3 mL) at room temperature. Finally, vinyl tosylates were obtained from ynamides having an ester group, directly bonded to the nitrogen atom, by reaction with p-toluenesulfonic acid. We also studied the application of the prepared compounds as substrates for Suzuki and Sonogashira cross-coupling reactions.

Synthesis and reactivity of 3-(1-alkynyl)chromones

For the first time, the literature data on the methods of synthesis and reactivity of 3-(1-alkynyl)chromones are summarized and systematized. The main method for obtaining these compounds is the Sonogashira cross-coupling reaction of 3-halochromones with terminal acetylenes, and their most important chemical properties include the transformation into furans, reactions with dinucleophiles, ambiphilic [4+2]- and [4+3]-cyclizations, and also dimerization and mixed condensation of 2-methyl-3-(1-alkynyl)chromones due to the vinylogous methyl group. Except for the oxacyclization to furans, chemical transformations of 3-(1-alkynyl)chromones are accompanied by pyrone ring transformation, in which not only the carbonyl group but also the triple bond can participate. This significantly increases the synthetic value of these compounds and ensures the production of more complex heterocyclic systems based on them. The mechanisms of the reactions are discussed, the conditions for their implementation and the yields of the resulting products are indicated.The bibliography includes 80 references.

Tuning the Cell Uptake and Subcellular Distribution in BODIPY–Carboranyl Dyads: An Experimental and Theoretical Study

A set of BODIPY-carboranyl dyads synthesized by a Sonogashira cross-coupling reaction, where different C-substituted ortho- and meta-carboranyl fragments have been linked to a BODIPY fluorophore is described. Chemical, photophysical and physicochemical analyses are presented, including NMR and single XRD experiments, optical absorption/emission studies and partition coefficient (log P) measurements. These studies, supported by DFT computations (M06-2X/6-31G**), provide an explanation to the largely divergent cell income that these fluorescent carboranyl-based fluorophores display, for which a structural or physicochemical explanation remains elusive. By studying the cell uptake efficiency and subcellular localization for our set of dyads on living HeLa cells, we tracked the origins of these differences to significant variations in their static dipole moments and partition coefficients, which tune their ability to interact with lipophilic microenvironments in cells. Remarkably, m-carboranyl-BODIPY derivatives with a higher lipophilicity are much better internalised by cells than their homologous with o-carborane, suggesting that m-isomers are potentially better theranostic agents for in vitro bioimaging and boron carriers for boron neutron capture therapy.

Formation of Highly Efficient, Long-Lived Charge Separated States in Star-Shaped Ferrocene-Diketopyrrolopyrrole-Triphenylamine Donor-Acceptor-Donor Conjugates.

The significance of multiple number of donor-acceptor entities on a central electron donor in a star-shaped molecular system in improving light energy harvesting ability is reported. For this, donor-acceptor-donor type conjugates comprised up to three entities ferrocenyl (Fc)-diketopyrrolopyrrole (DPP) onto a central triphenylamine (TPA), (4-6) by the Pd-catalyzed Sonogashira cross-coupling reactions have been newly synthesized and characterized. Donor-acceptor conjugates possessing diketopyrrolopyrrole (1 to 3 entities) onto the central triphenylamine, (1-3) served as reference dyads while monomeric DPP and Fc-DPP served as control compounds. Both DPP and Fc-DPP carrying conjugates exhibited red-shifted absorption compared to their respective control compounds revealing existence of ground state interactions. Furthermore, DPP fluorescence in 4-6 was found to be quantitatively quenched while for 1-3, this property varied between 73-65 % suggesting occurrence moderate amounts of excited state events. The electrochemical investigations exhibited an additional low potential oxidation in the case of Fc-DPP-TPA based derivatives (4-6) owing to the presence of ferrocene unit(s). This was in addition to DPP and TPA redox peaks. Using spectral, electrochemical and computational studies, Gibbs free-energy calculations were performed to visualize excited state charge separation (ΔGCS ) in these donor-acceptor conjugates as a function of different number of Fc-DPP entities. Formation of Fc+ -DPP.- -TPA charge separated states (CSS) in the case of 4-6 was evident. Using spectroelectrochemical studies, spectrum of CSS was deduced. Finally, femtosecond transient absorption spectral studies were performed to gather information on excited state charge separation. Increasing the number of Fc-DPP entities in 4-6 improved charge separation rates. Surprisingly, lifetime of the charge separated state, Fc+ -DPP.- -TPA was found to persist longer with an increase in the number of Fc-DPP entities in 4-6 as compared to Fc-DPP-control and simple DPP derived donor-acceptor conjugates in literature. This unprecedented result has been attributed to subtle changes in ΔGCS and ΔGCR and the associated electron coupling between different entities.

Copper (I)–Organic Frameworks for Catalysis: Networking Metal Clusters with Dynamic Covalent Chemistry

Metal clusters exhibit diverse structures, emerging functions, and applications; thus, incorporating clusters into metal–organic frameworks (MOFs) brings tremendous merits. Although the constructio...

Copper(I) complexes with N-(2-quinolinylmethylene)-1, 5-dimethyl- 2-phenyl-1-pyrazole-3-(2H)-one and phosphine as ligands: Effective catalyst for Sonogashira cross-coupling reaction

A new series of copper(I) complexes of the type [Cu( L )(PPh 3 ) 2 ]X( 1a-c ) and [Cu( L )(dppe)]X ( 2a-c ) have been prepared by the reaction of Cu(MeCN) 4 ]X (Where X = ClO 4 - , BF 4 - and PF 6 - ) with N-(2-quinolinylmethylene)-1,5-dimethyl-2-phenyl-1-pyrazole-3-(2H)-one ( L ) in presence of triphenyl- phosphine (PPh 3 ) or 1,2-bis(diphenylphosphino)ethane (dppe) as an ancillary ligand. The UV–Visible spectra indicate that the ancillary phosphine ligands significantly perturb the MLCT state of copper(I) complexes. The thermally stable 1a-c and 2a-c complexes exhibit quasireversible redox behaviour corresponding to Cu(I)/Cu(II) couple. All complexes were tested as catalyst for Sonogashira cross-coupling of phenylacetylene with aryl iodide. The results showed that all complexes worked as an effective catalyst at low temperature yielded substituted aryl alkynes as a product. The nature of phosphine ligands and size of counter anions shows marked effect on their catalytic properties of all the complexes .

Ni(acac)2/2,6-bis(diphenylphosphino)pyridine/CuI: A highly efficient palladium-free homogeneous catalyst for the Sonogashira cross-coupling reaction

A highly efficient palladium-free homogeneous catalyst involving Ni(acac)2/2,6-bis(diphenylphosphino)pyridine ((Ph2P)2py)/CuI components was used for the Sonogashira cross-coupling reaction. The Sonogashira reaction was investigated between phenylacetylene and various bromo- and chloroarenes containing electron-neutral, electron-rich, electron-poor, electron-deficient, and sterically hindered aryl fragments. The aryl alkynes coupling products were obtained with good to excellent yields at the optimized conditions using Ni(acac)2 (0.3 mol%)/(Ph2P)2py (0.6 mol%)/CuI (0.03 mol%) as the catalyst, tetrabutylammonium bromide (TBAB) as the additive, Et3N as the base in DMF at 100 °C under N2 atmosphere.

Stereocomplementary and Parallel Syntheses of Multi-Substituted (E)-, (Z)-Stereodefined α,β-Unsaturated Esters: Application to Drug Syntheses.

Ubiquitous α,β-unsaturated esters are well recognized as key structural olefin scaffolds in organic chemistry. (E)- and (Z)-steroselectivity is the most critical issue in their synthesis, however, (E)- and (Z)- stereocomplementary synthetic methods remain quite limited. The present account discloses general (E)-, (Z)-stereocomplementary syntheses of a variety of α,β-unsaturated esters from highly accessible (E)-, (Z)-stereodefined enol tosylates derived from β-ketoesters and α-formyl esters. Step 1 toward the stereocomplementary preparation of (E)-, (Z)-stereodefined enol tosylates is implemented by using inexpensive reagents under mild reaction conditions. Step 2 toward the highly stereoretentive synthesis of (E)- and (Z)-stereodefined α,β-unsaturated esters involves Suzuki-Miyaura, Negishi, Sonogashira, Iron-catalyzed, Mizoroki-Heck, and Buchwald-Hartwig cross-coupling reactions. Notably, this strategy was successfully applied for parallel drug syntheses of (E)- and (Z)-zimelidine, (E)- and (Z)-tamoxifen, and Merck's cyclopropane pharmacophore. Representative successful utilizations by other groups are also introduced.

Decorated palladium nanoparticles on mesoporous organosilicate as an efficient catalyst for Sonogashira coupling reaction

Reforming mesoporous silica was provided by the reaction of SBA‐15 with (3-aminopropyl)triethoxysilane, the product of which was treated with furfural to give SBA-propyl-imine-furan. In the next step, palladium chloride was attached to the functionalized SBA‐15, so Pd nanoparticles immobilized on the mentioned catalyst for providing an applicable catalyst to use in the Sonogashira cross-coupling reaction. The high stability and performance of functionalized heterogeneous hybrid catalyst of Pd@SBA-Pr-imine-furan in overall were highly essential. The nano-structured Pd@SBA-Pr-imine-furan catalyst was studied for Sonogashira cross-coupling reaction by phenylacetylene and various aryl halides under reflux conditions with a small amount of catalyst. In comparison with the earlier reports, this paper offered several benefits such as short reaction times, high yields of products, catalyst stability, quick recovery, and catalytic activity for at least seven continuous runs.

Palladium(II) phthalocyanines efficiently promote phosphine-free Sonogashira cross-coupling reaction at room temperature

Herein we report that exceptionally simple and inexpensive Pd(II) complexes of phthalocyanines efficiently catalyze direct formation of diphenylacetylenes at ambient conditions with low loading of catalyst (0.5 mol%). Results of this study demonstrate that terminal alkynes reacted mildly with p-substituted aryl bromides at room temperature under Pd and Cu-cocatalysis to give the corresponding phenylacetylenes in yields up to 98%. Also we have examined this catalyst in Sonogashira cross-coupling with aryl chlorides and it was very effective and this reaction at room temperature that there is no examples in recent articles. This protocol represents the first use of palladium phthalocyanine as homogeneous catalyst in the Pd/Cu-promoted Sonogashira reaction. The palladium(II) phthalocyanine complex is significantly more active in Sonogashira cross-coupling between aryl halides and terminal alkynes as compared with traditional catalysts because of absence of palladium black formation through agglomeration of metal particles and deactivation of catalyst.