Sequential Sonogashira Coupling Research Articles

A Highly Selective Synthesis of (E)‐11‐Arylidenebenzo [4′,5′] thieno [2′,3′ : 4,5] Pyrimido [2,1‐a] Isoindol‐13(1H)‐ones via Copper‐Catalyzed Sonogashira Coupling and Hydroamination

AbstractAn efficient and highly selective reaction of 2‐(2‐bromophenyl)‐5,6,7,8‐tetrahydrobenzo [4,5] thieno[2,3‐d]pyrimidin‐4(3H)‐one and terminal alkyne has been developed under palladium‐free conditions by CuI‐catalyzed sequential Sonogashira coupling reaction and 5‐exo‐dig hydroamination reaction. A series of 11‐arylidene‐2,3,4,11‐tetrahydrobenzo [4′,5′]thieno [2′,3′ : 4,5]pyrimido [2,1‐a]isoindol‐13(1H)‐one derivatives with only the (E)‐configuration were obtained.

Heterobimetallic Pd/Mn and Pd/Co complexes as efficient and stereoselective catalysts for sequential Cu-free Sonogashira coupling-alkyne semi-hydrogenation reactions.

A series of heterobimetallic PdII/MII complexes (MII = Mn, Co) were synthesised and tested as precatalysts for sequential Sonogashira coupling-alkyne semi-hydrogenation reactions to form Z-aryl alkenes. The carbometalated heterobimetallic PdII/CoII complex CoPdL3' demonstrated an apparent cooperative effect compared to the corresponding monometallic counterparts. This compound was identified as a potent single-molecule catalyst for the one-pot Cu-free Sonogashira coupling of aryl bromides with terminal alkynes followed by chemo- and stereoselective semi-hydrogenation of the alkyne intermediate using NH3·BH3 as a hydrogen source. Furthermore, different aromatic substrates have been tested to show the generality of the reaction for the synthesis of Z-alkenes, including biologically active combretastatin A-4. In addition, the homogeneous nature of the catalytically active species was demonstrated.

A facile approach to 6-amino-2H-pyrano[2,3-g]isoquinolin-2-ones via a sequential Sonogashira coupling of 6-cyanoumbelliferone triflate and annulations with amines

Palladium-catalyzed synthesis of 2H-pyrano[2,3-g]isoquinolinones have been described from easily accessible precursor 6-cyanoumbelliferone triflate via sequential of Sonogashira coupling and the following annulations with several primary alkylamines under basic conditions The so obtained 6-propargylamino-2H-pyrano[2,3-g]isoquinolinones were involved in the CuAAC reaction with 2-azidobenzoic acid for obtaining 2H-pyrano[2,3-g]isoquinoline-benzoic acid hybrid compounds containing a 1,2,3-triazole linker.

One-pot regioselective synthesis of substituted pyrazoles and isoxazoles in PEG-400/water medium by Cu-free nano-Pd catalyzed sequential acyl Sonogashira coupling–intramolecular cyclization

Catalyst efficacy of in situ generated Pd-nanoparticles in the regioselective one-pot synthesis of substituted pyrazoles and isoxazoles via sequential coupling-cyclization methodology in environmentally benign medium is described.

One‐Pot Synthesis of Naphtho[1′,2′:4,5]imidazo[1,2‐a]pyridin‐5‐yl(aryl)methanones through Sequential Sonogashira Coupling/Alkyne–Carbonyl Metathesis

An efficient one‐pot route for the construction of naphtho[1′,2′:4,5]imidazo[1,2‐a]pyridin‐5‐yl(aryl)methanones and 5‐phenylnaphtho[1′,2′:4,5]imidazo[1,2‐a]pyridines by sequential Sonogashira coupling reaction followed by trifluoroacetic acid promoted alkyne‐carbonyl metathesis (ACM) has been developed. 2‐(2‐Bromophenyl)imidazo[1,2‐a]pyridine‐3‐carbaldehyde preferentially underwent ACM with phenyl acetylenes, whereas intramolecular hydroarylation reaction was the common pathway in the absence of a carbonyl moiety at the C‐3 position under similar conditions. This protocol is compatible with a wide variety of functional groups and delivered corresponding naphtho[1′,2′:4,5]imidazo[1,2‐a]pyridines in good to excellent yields.

Regio- and Stereoselective Synthesis of Triarylalkene-Capped Rotaxanes via Palladium-Catalyzed Tandem Sonogashira/Hydroaryl Reaction of Terminal Alkynes.

Triarylalkene-capped conjugated rotaxanes were synthesized via a palladium-catalyzed tandem Sonogashira/hydroaryl reaction between aryl halides and terminal alkynes bearing two permethylated α-cyclodextrins (PM α-CDs) with high regioselectivity because of the insulation effect of the PM α-CDs. Moreover, sequential Sonogashira coupling and hydroarylation reactions using different aryl substrates afforded a regio- and stereoselective trisubstituted alkene as a single product. This new class of rotaxane-forming reactions can be used to increase the diversity of rotaxane skeletons, and thereby the material functionalities of rotaxanes.

Hexafluorosilicic Acid as a Novel Reagent for the Desilylation of Silylacetylenes: Application in Sequential Sonogashira Coupling and Click Reaction

Hexafluorosilicic acid was utilized as a novel, cheap, readily available, and environmentally benign alternative reagent for the desilylation of 1-trimethylsilylacetylenes. The applicability of the aqueous solution of the hexafluorosilicic acid was demonstrated in the sequential coupling of aryl halides and ethynyltrimethylsilane to afford internal acetylenes, benzofurans, and triazoles in one-pot Sonogashira–Sonogashira­ and Sonogashira–CuAAC reactions.

A one-pot synthesis of 2,2'-disubstituted diindolylmethanes (DIMs) via a sequential Sonogashira coupling and cycloisomerization/C3-functionalization of 2-iodoanilines.

A Pd(ii)-Ag(i) catalyzed highly efficient synthesis of diindolylmethane has been developed. This transformation consists of a one-pot sequential Sonogashira coupling (and desilylation) followed by cycloisomerization/C3-functionalization of 2-iodoanilines. Six new bonds (four C-C and two C-N) are formed in a one-pot fashion. A variety of diindolylmethanes were obtained in excellent yields (up to 94%) under mild reaction conditions and this strategy is amenable to gram scale synthesis also. The products were transformed into various synthetically useful compounds.

ChemInform Abstract: Sequential Sonogashira and Glaser Coupling Reactions: Facile Access to 1,4‐Disubstituted 1,3‐Butadiynes from Arylbromide.

Abstract1‐Aryl‐2‐trimethylsilylethynes, prepared in situ via Sonogashira coupling, undergo base promoted homocoupling to form 1,3‐butadiynes in moderate yields.

Sequential Sonogashira and Glaser coupling reactions: facile access to 1,4-disubstituted 1,3-butadiynes from arylbromide

A simplified synthesis of symmetrical 1,4-disubstitued 1,3-butadiynes was developed using a sequential two-step process combining a typical Sonogashira coupling with a Glaser coupling. The Sonogashira reaction coupled arylbromide and trimethylsilylacetylene. In the second step, a Glaser coupling reaction was performed using the crude trimethyl(arylethynyl)silane product from the previous Sonogashira coupling in a basic solvent; the Glaser coupling proceeded to completion without the addition of extra Pd or Cu catalysts. The catalytic amount of metal (Cu and Pd) in the second step was substantially less than that used in a typical Glaser coupling reaction.

Pd catalyzed facile synthesis of cyclopenta[b]quinolin-1-one via sequential Sonogashira coupling and annulation. An unusual mode of ring closure, using sulphur as a soft nucleophile

Pd mediated one pot sequential Sonogashira coupling followed by annulation using o-alkynyl aldehyde is reported.

Double Sonogashira reactions on dihalogenated aminopyridines for the assembly of an array of 7-azaindoles bearing triazole and quinoxaline substituents at C-5: Inhibitory bioactivity against Giardia duodenalis trophozoites

The synthesis of 2,3,5-trisubstituted 7-azaindoles as well as 2,5-disubstituted 7-azaindoles from 3,5-dihalogenated 2-aminopyridines is outlined. Using a double Sonogashira coupling reaction on 2-amino-3,5-diiodopyridine followed by the Cacchi reaction the synthesis of 2,3,5-trisubstituted 7-azaindoles was accomplished. In addition, using two sequential Sonogashira coupling reactions on 2-amino-5-bromo-3-iodopyridine and a potassium t-butoxide mediated ring closure reaction resulted in the assembly of 2,5-disubstituted 7-azaindoles. The 5-alkynyl substituent of the azaindole was easily converted into both quinoxaline and triazole substituents, the latter utilizing an alkyne–azide cycloaddition reaction. Some of these azaindole derivatives showed very promising biological activity against the gastrointestinal protozoal parasite Giardia duodenalis.

Total synthesis of calothrixin B via sequential Sonogashira coupling/copper-catalyzed oxidative cyclization

A total synthesis of the antimalarial indolo[3,2-j]phenanthridine alkaloid calothrixin B is reported. The key intermediate, ketoester 11, was assembled using sequential Sonogashira coupling and intra/intermolecular fashioned copper-catalyzed oxidative cyclization reactions.

ChemInform Abstract: Palladium‐Catalyzed One‐Pot Synthesis of Benzo[b][1,6]naphthyridines via Sonogashira Coupling and Annulation Reactions from 2‐Chloroquinoline‐3‐carbonitriles.

AbstractA one‐pot sequential Sonogashira coupling and intramolecular cyclization of 2‐chloroquinoline‐3‐carbonitriles is reported.

ChemInform Abstract: Synthesis of Indoles with a Polyfluorinated Benzene Ring.

AbstractPolyfluorinated 2‐iodoanilines are found to undergo a sequential Sonogashira coupling followed by KOH‐promoted cyclization of the 2‐alkynylaniline intermediates to yield 2‐substituted indoles.

Synthesis of Polycyclic Isoindoline Derivatives via Tandem Pd-Catalyzed Coupling, Propargyl–Allenyl Isomerization, [4 + 2] Cycloaddition and Aromatization Reaction

We report in this paper an interesting sequential reaction involving sequential Sonogashira coupling, propargyl-allenyl isomerization, [4 + 2] cycloaddition and aromatization reaction, which provides a facile method for the synthesis of a variety of polycyclic isoindoline derivatives from easily accessible starting materials.

Synthesis and second-order nonlinear optical properties of push-pull BODIPY derivatives

A series of boron dipyrromethene derivatives bearing an electron-donating 4-(dimethylamino)phenylethynyl group and an electron-withdrawing 4-nitrophenylethynyl group in the opposite 2- and 6-positions have been synthesized by Knoevenagel condensation followed by sequential Sonogashira coupling reactions. The compounds have been fully characterized with various spectroscopic methods. Their electrochemical properties have also been studied by cyclic voltammetry in CH2Cl2. It has been found that expansion of the π systems by introduction of the 4-dodecyloxystyryl or 4-(dimethylamino)phenylethynyl group results in lowering of the first oxidation potential, while the first reduction potential remains relatively unaffected. The second-order nonlinear optical properties of these compounds have also been studied by electric-field-induced second-harmonic generation method in CHCl3. The values of the dot product μ·β are in the range from 94×10−48 to 330×10−48esu at 1907nm, depending the substituents at the 3- and 5-positions.

Practical Synthesis of Unsymmetrical Diarylacetylenes from Propiolic Acid and Two Different Aryl Bromides

AbstractA palladium catalyst that mediates the one‐pot sequential Sonogashira and decarboxylative coupling of propiolic acid with two different aryl bromides has been developed. Selective coupling of the first aryl bromide was achieved in the presence of a copper‐free, monometallic catalyst generated in situ from allylpalladium chloride dimer and SPhos with tetra‐n‐butylammonium fluoride as the base in an N‐methyl‐2‐pyrrolidone/water solvent mixture. Upon addition of another aryl bromide and raising the temperature from 50 to 80 °C, the intermediate arylpropiolic acid underwent decarboxylative coupling to give the corresponding diarylacetylene. Thus, the new system permits a one‐pot three‐component synthesis of unsymmetrical diarylacetylenes from widely available aryl bromides, rather than expensive aryl iodides, and propiolic acid, rather than (trimethylsilyl)acetylene, as an inexpensive and easy‐to‐handle acetylene synthon. The process is highly selective, modular, and gives access to a wide range of unsymmetrical diarylacetylenes in good yields.

ChemInform Abstract: One‐Pot Regioselective Synthesis of 3‐Benzylthiazolo[3,2‐a]indoles by Sequential Sonogashira Coupling Followed by Triethylamine‐Induced Cyclization.

AbstractA regioselective method for the synthesis of the title compounds such as (III) and (V) is developed.

One-Pot Regioselective Synthesis of 3-Benzylthiazolo[3,2-a]indoles by Sequential Sonogashira Coupling Followed by Triethylamine-Induced Cyclization

A number of 2-(prop-2-ynylthio)-1H-indoles have been utilized for the synthesis of 3-benzylthiazolo[3,2-a]indoles by Sonogashira­ acetylide-coupling followed by triethylamine-induced regioselective cyclization in a one-pot operation. The cyclization is dependent on the nature of the substituents on the phenyl ring of the substrates.