3-Iodo-4-chalcogen-2H-benzopyran as a convenient precursor for the sonogashira cross-coupling: synthesis of 3-alkynyl-4-chalcogen-2H-benzopyrans

3-Iodo-4-chalcogen-2H-benzopyran derivatives underwent a direct Sonogashira cross-coupling reaction with several terminal alkynes in the presence of a catalytic amount of Pd(PPh₃)₂Cl₂ with CuI as a co-catalyst, using Et₃N as base and solvent. This cross-coupling reaction proceeded cleanly under mild conditions and was performed with propargylic alcohols, propargylic ethers, as well as alkyl and aryl alkynes, furnishing the correspondent 3-alkynyl-4-chalcogen-2H-benzopyrans in good yields.     

Palladium-catalyzed deacetonative coupling of aryl propargylic alcohols with aryl chlorides in water

A highly efficient and green process for palladium-catalyzed deacetonative coupling of aryl propargylic alcohols with aryl chlorides has been developed. The reaction occurs smoothly in neat water with 2?mol% PdCl₂ as catalyst, and various synthetically useful functional groups, including ether, aldehyde, ketone, and heterocyclics, are well tolerated. Moreover, the reaction could proceed through a consecutive Sonogashira/deacetonative process using 2-methyl-3-butyn-2-ol and aryl chlorides as coupling partners, affording the symmetric alkynes in good yields.     

Reaction of sulfene and dichloroketene with N,N-disubstituted 5-aminomethylene-1,5,6,7-tetrahydro-2-methyl-1-phenylindol-4-ones. Synthesis of 1,2-oxathiino[6,5-E] indole and of pyrano[2,3-e] indole derivatives

The 1,4-cycloaddition of sulfene to N,N-disubstituted 5-aminomethylene-1,5,6,7-tetrahydro-2-methyl-1-phenylindol-4-ones afforded N,N-disubstituted 3,4,5,6-tetrahydro-8-methyl-7-phenyl-7H-1,2-oxathiino[6,5-e]indol-4-amine 2,2-dioxides only in the case of aliphatic N-substitution. The 1,4-cycloaddition of dichloroketene occurred normally only in the case of 1,5,6,7-tetrahydro-2-methyl-1-phenyl-5-piperidinomethyleneindol-4-one to give 3,3-dichloro-3,4,5,6-tetrahydro-8-methyl-7-phenyl-4-piperidino-7H-pyrano[2,3-e]indol-4-one. Attempted recrystallisation, dehydro-chlorination or treatment with palladium on carbon of this adduct, as well as reaction of similar enaminoketones with dichloroketene, gave instead the same product, namely 3-chloro-8-methyl-7-phenyl-7H-pyrano[2,3-e]indol-4-one, as a result of dehydrochlorination, dehydrogenation and subsequent hydrogenolysis of the C-NR₂ bond in the primary adduct.     

Trisoxazoline/Cu(II)-promoted Kinugasa reaction. Enantioselective synthesis of beta-lactams

The reactions of nitrones with terminal alkynes, catalyzed by chiral (i)Pr-trisoxazoline 2a/Cu(ClO4)2.6H2O under air atmosphere, afforded beta-lactams in moderate to good yields with up to 85% ee. The diastereoselectivity depends on the alkyne. Propiolate gives the trans-isomer as a major product, while the other alkynes afford cis-disubstituted lactams predominantly. Copper(II) salt proved to be an efficient catalyst precursor for the first time in the Kinugasa reaction, and this allowed the reaction to be performed under a practical and convenient condition. An appropriate base used in this reaction was essential to control both diastereoselectivity and enantioselectivity. Compared with primary and tertiary amines, secondary amines gave higher enantioselectivities. The reaction scope and limitation as well as the mechanism were also studied.     

Cryptand-22 as an efficient ligand for the copper-catalyzed cross-coupling reaction of diorgano dichalcogenides with terminal alkynes leading to the synthesis of alkynyl chalcogenides

A general and efficient method for the cross-coupling reaction of diorgano dichalcogenides with terminal alkynes using copper iodide/cryptand-22 (CuI/C22) has been developed. This protocol gave alkynyl chalcogenides in moderate to excellent yields in the presence of K₃PO₄ as the base under aerobic conditions.     

Tandem versus single C-C bond forming reaction under palladium-copper catalysis: regioselective synthesis of α-pyrones fused with thiophene

We herein report a highly convenient protocol for rapid construction of α-pyrone fused with thiophene. This includes one-pot and regioselective synthesis of 4,5-disubstituted and 5-substituted thieno[2,3-c]pyran-7-ones, 6,7-disubstituted and 6-substituted thieno[3,2-c]pyran-4-ones. The synthesis of thieno[2,3-c]pyran-7-ones involves palladium mediated cross coupling of 3-iodothiophene-2-carboxylic acid with terminal alkynes in a simple synthetic operation. The coupling-cyclization reaction was initially studied in the presence of Pd(PPh₃)₂Cl₂ and CuI in a variety of solvents. 5-Substituted 4-alkynylthieno[2,3-c]pyran-7-ones were isolated in good yields when the reaction was performed in DMF. Similarly, 6-substituted 7-alkynylthieno[3,2-c]pyran-4-ones were synthesized via palladium-catalyzed cross coupling of 2-bromothiophene-3-carboxylic acid with terminal alkynes. A tandem C-C bond forming reaction in the presence of palladium catalyst rationalizes the formation of coupled product in this apparently three-component reaction. The cyclization step of this coupling-cyclization-coupling process occurs in a regioselective fashion to furnish products containing six-membered ring only. This sequential C-C bond forming reaction however, can be restricted to the formation of single C-C bond by using 10% Pd/C-Et₃N-CuI-PPh₃ as catalyst system in the cross coupling reaction. 5-Substituted thieno[2,3-c]pyran-7-ones were obtained in good yields when the coupling reaction was performed under this condition. Some of the compounds synthesized were tested in vitro for their anticancer activities.     

Synthesis and application of a new selenoplatinum catalyst

The reaction of 4-methyl-5-ethoxycarbonyl-1,2,3-selenadiazole with (PPh₃)₄Pt leads to the formation of a new platinum-containing heterocyclic system. It was found that the selenoplatinum complex is a selective catalyst for the hydrosilylation of terminal alkynes to yield β-(Z)- and β-(E)-silylethylenes.     

The dramatic effect of thiophenol on the reaction pathway of ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with thiophenolates: ring expansion versus nucleophilic substitution

Ethyl 4-methyl-2-oxo-7-phenylthio-2,3,6,7-tetrahydro-1H-1,3-diazepine-5-carboxylate and/or ethyl 6-methyl-2-oxo-4-(phenylthiomethyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate were obtained in the reaction of ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with PhSNa or PhSK with or without PhSH, depending on the reagent ratio, reaction time, or temperature, as a result of ring expansion and/or nucleophilic substitution. The reaction pathway was affected strongly by the basicity-nucleophilicity of the reaction media. The results obtained were confirmed by reactions of 4-mesyloxymethyl-6-methyl-5-tosyltetrahydropyrimidin-2-one with PhSNa/PhSH and ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with NaCN/HCN or NaCH(COOEt)₂/CH₂(COOEt)₂.     

A selective and convenient synthesis of β, β-dialkyl-substituted alkenylbroanes and alkenylzirconiums via carboalumination of alkynes1

Treatment of (E)-2-methyl-1=-alkenylalanes ($\text{1}$), readily obtainable via Zr-cata-lyzed reaction of Me₃Al with 1=alkynes, with β-methoxydialkylboranes producers the corresponding alkenylboranes, while sequential treatment of $\text{1}$ with n-Buli and X₂ZrCp₂ (X = Cl or I) provides the desired monoalkenylzirconium derivatives, the product yields for both reactions beig 85-100%.     

A highly effective synthesis of 2-alkynyl-7-azaindoles: Pd/C-mediated alkynylation of heteroaryl halides in water

The reaction of 4-chloro-2-iodo-7-azaindole with terminal alkynes was investigated using 10% Pd/C-PPh₃-CuI as a catalyst system in water. This study afforded a new, mild and selective process for the preparation of 2-alkynyl-4-chloro-7-azaindole in good yields via C-C bond forming reaction. The resulting chloro derivative can be functionalized further via another Pd-mediated C-C bond forming reaction with arylboronic acid.     

Synthesis of 3-substituted benzo[g]isoquinoline-5,10-diones: a convenient one-pot Sonogashira coupling/iminoannulation procedure

A series of 3-substituted 5,10-dimethoxybenzo[g]isoquinolines were prepared by coupling of terminal alkynes with the tert-butylimine of 3-bromo-1,4-dimethoxy-2-naphthaldehyde in the presence of a Pd-catalyst and subsequent Cu-catalyzed cyclization of the intermediate 3-alkynyl-2-naphthylcarbaldehyde. A CAN-mediated oxidative demethylation yielded the corresponding 2-azaanthraquinones in excellent yields. Since this methodology proved to be limited to alkynes bearing aromatic groups, an alternative and more general Pd-catalyzed coupling procedure was developed, starting from 3-bromo-1,4-dimethoxy-2-naphthaldehyde. For more acidic terminal alkynes, like phenylacetylene, a combination of Pd(OAc)₂/P(t-Bu)₃/CuI (2/6/1) with potassium carbonate in DMF gave a complete conversion within 24 h. For less acidic acetylenes, 2 equiv of alkyne and caesium carbonate as a base were required in order to obtain complete conversion of the starting material within 24 h. These altered Sonogashira conditions also allowed the isolation of a benzo[f]indenone as an interesting side product in case Bu₄NCl was added to the reaction mixture. The 3-alkynyl-1,4-dimethoxy-2-naphthaldehyde acquired after completion of the Pd-catalyzed coupling could be cyclized by adding a solution of ethanolic ammonia and an extra equivalent of potassium carbonate to the reaction mixture. As such, this consecutive one-pot coupling/iminoannulation procedure was a convenient alternative to the Larock isoquinoline procedure, enabling the isolation of a series of 3-substituted 5,10-dimethoxybenzo[g]isoquinolines.     

Enyne synthesis through a modified Sonogashira cross-coupling reaction catalyzed by cyclopalladated complexes

A series of conjugated enynes were successfully synthesized by the palladacycle-catalyzed modified Sonogashira cross-coupling reaction of β-bromostyrene and terminal alkynes. The reaction proceeds smoothly in DMSO at 40 °C to give the corresponding products in moderate to excellent yields. This catalytic system is tolerant to a broad range of functional groups on the substrates. Moreover, the products were furnished as specific E isomers. We also found that the product of the reaction between (E)-β-bromostyrene and 2-methyl-3-butyn-2-ol is diarylated enyne in the presence of excess Cs₂CO₃.     

Pd/C mediated synthesis of 2-substituted benzo[b]furans/nitrobenzo[b]furans in water

An efficient synthesis of 2-alkyl/aryl substituted benzo[b]furans/nitrobenzo[b]furans in water has been accomplished via Pd/C catalyzed reaction of o-iodophenols with terminal alkynes in the presence of PPh₃, CuI and prolinol. This method can tolerate a variety of functional groups present in the alkynes as well as base labile nitro group in the o-iodophenols. The protocol does not require the use of a phase transfer catalyst or water-soluble phosphine ligands and is free from the use of any organic co-solvent.     

Palladium-catalyzed reaction of methyl 5-amino-4-chloro-2-methylthiopyrrolo[2,3-<Emphasis Type="Italic">d</Emphasis>]-pyrimidine-6-carboxylate with arylboronic acids. Synthesis of 1,3,4,6-tetraazadibenzo[<Emphasis Type="Italic">cd,f</Emphasis>]-azulene heterocyclic system

Densely substituted methyl 5-amino-4-aryl-7-methyl-2-methylthio-7H-pyrrolo[2,3-d]pyrimidine-6-carboxy- lates were synthesized by the palladium-catalyzed cross-coupling reaction of methyl 5-amino-4-chloro-7-methyl-2-methylthio-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate with arylboronic acids using Pd(OAc)₂/dicyclohexyl(2-biphenyl)phosphine/K₃PO₄ as a catalyst system. Reaction of methyl 5-amino-4-chloro-7-methyl-2-methylthio-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate with 2-formylphenyl- boronic acid led to a novel heterocyclic system – 1,3,4,6-tetraazadibenzo[cd,f]azulene.     

Nitroimidazoles. V . Synthesis of 1-methyl-2-(2-methyl-4-thiazolyl)nitroimidazoles

Reaction of readily available 2-methyl-4-formylthiazole ( 1 ) with glyoxal and ammonia gave 2-(2-methyl-4-thiazolyl)imidazole ( 2 ). Nitration of 2 with a mixture of nitric acid-sulfuric acid at 100° yielded 2-(2-methyl-4-thiazolyl)-4,5-dinitroimidazole ( 3 ) as the sole reaction product, while nitration at 65° afforded 2-(2-methyl-4-thiazolyl)-4-(or 5)-nitroimidazole ( 4 ). N-Methylation of compound 4 in the presence of base gave 1-methyl-2-(2-methyl-4-thiazolyl)4-nitroimidazole ( 6 ), whereas N-methylation with diazomethane afforded 1-methyl-2-(2-methyl-4-thiazolyl)-5-nitroimidazole ( 5 ). N-Methylation of compound 3 yielded 1-methyl-2-(2-methyl-4-thiazolyl)-3,5-dinitroimidazole ( 7 ) in high yield.     

Crystal Structure and Spectral Characterization of a Rare Example of a Salen-Type Zinc Complex with Neutral Monodentate Oxygen Donor Ligands Coordination

Summary. The new zinc complex of the N,N′-bis(salicylidene)-4-methyl-1,3-phenylenediamine ligand as a product of the [2 + 1] Schiff base condensation process was synthesized in the one-step metal-promoted reaction between salicylaldehyde and 4-methyl-1,3-phenylenediamine in ethanol in the presence of zinc chloride. The two potentially tetradentate N₂O₂ Schiff bases function as neutral monodentate ligands involving only one oxygen atom in coordination. This rare coordination pattern of a mononuclear salen-type zinc complex was revealed by X-ray crystallography and correlated with spectroscopic characterization.     

A Total Synthesis of Isosolanone

Nitroaldol reaction of acetone with nitromethane in the presence of base to give a nitroalcohol 3, followed by acetylation, and subsequent reduction of the resultant acetate 4 with NaBH₄ gave 2-methyl-1-nitropropane 5. Michael reaction of 5 in base with acrylonitrile to give nitronitrile 6, and Nef conversion of the nitro group resulted in the corresponding ketonic nitrile 7. Wittig olefination of the ketonic nitrile with 3-methyl-2-butenyl triphenylphosphonium bromide 8 gave dienenitrile 9, which upon treatment with MeLi, followed by acidic work up, provided isosolanone 2.     

Cu(OTf)2-catalyzed arylmethylation of terminal alkynes with benzylic alcohols under ligand-, base-, and additive-free reaction conditions

An effective, convenient, and mild coupling reaction of benzylic alcohols with terminal alkynes has been developed. As an effective Lewis acid, Cu(OTf)₂-catalyzed arylmethylation of terminal alkynes with benzylic alcohols generated the corresponding products in BrCH₂CH₂Br with good yields in the absence of ligand, base, and additive.     

Crystal Structure and Spectral Characterization of a Rare Example of a Salen-Type Zinc Complex with Neutral Monodentate Oxygen Donor Ligands Coordination

The new zinc complex of the N,N′-bis(salicylidene)-4-methyl-1,3-phenylenediamine ligand as a product of the [2 + 1] Schiff base condensation process was synthesized in the one-step metal-promoted reaction between salicylaldehyde and 4-methyl-1,3-phenylenediamine in ethanol in the presence of zinc chloride. The two potentially tetradentate N₂O₂ Schiff bases function as neutral monodentate ligands involving only one oxygen atom in coordination. This rare coordination pattern of a mononuclear salen-type zinc complex was revealed by X-ray crystallography and correlated with spectroscopic characterization.     

Stereochemistry of the Horner-Emmons reaction of 3-functionalized 2-methyl-2-propenylphosphonates with aliphatic aldehydes 5. Effects of base anion,temperature, solvent,and addition of a crown ether

Taking the reaction of diethyl 3-ethoxycarbonyl-2-methyl-2-propenylphosphonate with 3-methylbutanal as an example, it has been shown that the composition of the equilibrium mixture of the E- and Z-isomers of the starting phosphonate formed in the presence of bases is independent of the base anion (KOH or K₂CO₃) and the solvent (benzene or DMSO). In the mixture of 2E,4E- and 2Z,4E-isomers of ethyl 3, 7-dimethyl-2, 4-octadienoate formed in this reaction, the proportion of the 2E, 4E-ester falls as the temperature is reduced from +40 to –40C; the proportion of the 2E, 4E-ester in the heterophase system base/aprotic solvent increases with increasing polarity; and in the presence of 10 mole % of 18-crown-6 ether the proportion of the 2E, 4E-isomer is increased, being greater than 50% in all solvents. These findings indicate that the stereochemical outcome of the reaction depends on the balance between the phase systems and the chemical equilibria, including the formation, dissociation, and reactions of the intermediate products.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2544–2550, November, 1990.