Reactions of zinc enolates derived from 1-aryl-2-bromo-alkanones and 1-aryl-2-bromo-2-phenylethanone with 3-aroyl-6-bromochromen-2-ones and 2-benzoylbenzo[f]chromen-3-one

3-Aroyl-6-bromochromen-2-ones and 2-benzoylbenzo[f]chromen-3-one reacted with zinc enolates derived from 1-aryl-2-bromoalkanones and 1-aryl-2-bromo-2-phenylethanone to give, respectively, 4-(1-alkyl-2-aryl-2-oxoethyl)-3-aroyl-6-bromochroman-2-ones and 1-(2-aroyl-1-methyl-2-oxoethyl)-2-benzoyl-1,2-dihydrobenzo[f]chromen-3-ones as a single stereoisomer. Treatment with acetic anhydride of the intermediate product obtained from 3-benzoyl-6-bromochromen-2-one and [1-(4-chlorophenyl)-2-phenylethen-1-yloxy]-zinc(II) bromide resulted in the formation of 3-(1-acetoxy-1-phenylmethylidene)-6-bromo-4-[2-(4-chlorophenyl)-2-oxo-1-phenylethyl]chroman-2-one.     

Synthesis of fluorescent fluorene–isoindole-containing mono- and oligomers

Novel fluorene–isoindole-containing light-emitting mono- and oligomers were prepared. The synthesis of the monomers N-(4-bromo-phenyl)-2-(7-bromo-9,9-diethylfluoren-2-yl)-isoindole-1-carboxamide, N-(7-bromo-9,9-dibutylfluoren-2-yl)-2-(7-bromo-9,9-dibutylfluoren-2-yl)-isoindole-1-carboxamide, and N-[7-bromo-9,9-bis(2-ethylhexyl)-fluoren-2-yl]-2-[7-bromo-9,9-bis(2-ethylhexyl)-fluoren-2-yl]-isoindole -1-carboxamide was carried out by a three-component reaction of ortho-phthalaldehyde with the corresponding amine and isocyanide partners. The Ni(0) mediated polymerization reactions of the obtained monomers gave the corresponding mixture of oligomers from two up to twelve repeat units. The optical properties were also studied and it was found that the phenylene-containing oligomer emitted green light in dichloromethane solution, while both difluorene-containing oligomers, under the same conditions, proved to be blue light-emitters with good quantum efficiency.     

Efficient synthesis of 3,3′,5,5′-tetra(p-X-phenylethynyl)biphenyl (X: NMe2; OMe) by homocoupling of 1-bromo-3,5-di(p-X-phenylethynyl)benzene or by heterocoupling of 3,3′,5,5′-tetraethynylbiphenyl with p-X-phenylbromobenzene with nickel or palladium complexes, respectively

The conjugated 3,3′,5,5′-tetra(p-X-phenylethynyl)biphenyl derivatives were efficiently obtained by homocoupling of 1-bromo-3,5-di(p-X-phenylethynyl)benzene mediated by zero-valent nickel complexes.The 1-bromo-3,5-di(p-X-phenylethynyl)benzene was previously prepared by heterocoupling between 1-bromo-3,5-di(ethynyl)benzene and p-X-iodobenzene (X: NMe₂; OMe) catalysed by the palladium/copper system in good yield. The necessary 1-bromo-3,5-di(ethynyl)benzene was obtained by heterocoupling between 1,3,5-tribromobenzene and 2-methyl-3-butyn-2-ol catalysed by palladium and successive treatment with sodium hydroxide in dry toluene, in good yield.The same 3,3′,5,5′-tetra(p-X-phenylethynyl)biphenyl (X: NMe₂; OMe) derivatives were alternatively synthesised in highest yield by heterocoupling between 3,3′,5,5′-tetra(ethynyl)biphenyl and p-X-bromobenzene (X: NMe₂; OMe) catalysed by palladium in excellent yields. Previously, 3,3′,5,5′-tetra(ethynyl)biphenyl was obtained in practically quantitative yield by homocoupling of 1-bromo-3,5-di[4-(2-methyl-3-butyn-2-ol)] benzene mediated by the zero-valent nickel complex to the 3,3′,5,5′-tetra{di[4-(2-methyl-3-butyn-2-ol)]}biphenyl followed the treatment with sodium hydroxide.     

A highly enantioselective chemoenzymatic synthesis of syn-3-amino-2-hydroxy esters: key intermediates for taxol side chain and phenylnorstatine

Starting from the bromination of α-ketoesters to obtain 3-bromo-2-oxoalkanoates and bioreduction with Saccharomyces cerevisiae entrapped in calcium alginate pellets with double gel layers, syn-(2R,3S)-β-bromo-α-hydroxy esters were obtained regioselectively in high yields and high ee. These chiral bromohydrins were cyclized to epoxides that were transformed into oxazolidines and finally opened by acidic hydrolysis to give syn-(2S,3S)-β-amino-α-hydroxy esters in high overall yields and high ee. The enantiomeric excesses of all the intermediates were maintained during the reaction sequence.     

Microwave synthesis,characterization and antimicrobial study of new pyrazolyl-oxopropyl-quinazolin-4(3H)-one derivatives

Heterocyclic compounds containing pyrazolyl-oxopropyl-quinazolin-4(3H)-one are reported to possess significant biological activity. Syntheses of 6-bromo-2-(3-chloro-2-oxopropyl)-3-(4-fluorophenyl)quinazolin-4(3H)-one 2 6-bromo-3-(4-fluorophenyl)-2-(3-hydrazinyl-2-oxopropyl)quinazolin-4(3H)-one 3 and 6-bromo-2-(3-(3-(4-(1-(2-chlorophenyl)-3-methyl-1H-pyrazol-5(4H)-ylideneamino)phenyl)-5-(substituted phenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxopropyl)-3-(4-fluorophenyl)quinazolin-4(3H)-one 5a–j using microwave irradiation have been described. These compounds have been characterized on the basis of the UV, IR, ¹H NMR, ¹³C NMR, Mass and elemental analysis. Compounds have been evaluated for their antimicrobial activity.     

Preparation of the four stereoisomers of 3-bromo-2-butanol or their acetates via lipase-catalysed resolutions of the racemates derived from dl- or meso-2,3-butanediol

The four stereoisomeric 3-bromo-2-butanols and/or their acetates were prepared via lipase-catalysed kinetic resolution by hydrolyses of the acetates of the (±)-syn- and (±)-anti-3-bromo-2-butanols, or via esterifications of the alcohols. The diastereomeric bromoacetates were obtained by syntheses from the dl- and meso-2,3-butanediols, respectively. On a preparative scale, the four stereoisomers, either as the free alcohols or as their acetates, were obtained in >95% ee, and in 35–40% yield (based on the starting racemates).     

Reactions of dialkyl 4-bromo-2,2-dimethyl-3-oxohexane-1,6-dioates,-heptane-1,7-dioates with zinc and aromatic aldehydes

Zinc enolates generated from dimethyl 4-bromo-2,2-dimethyl-3-oxohexane-1,6-dioate and zinc reacted with aromatic aldehydes giving methyl 2,2-dimethyl-3-oxo-3-(5-oxo-2-aryltetrahydrofuran-3-yl)propanoates. The reaction of zinc enolates obtained from dimethyl 4-bromo-2,2-dimethyl-3-oxoheptane-1,7-dioate and zinc with aromatic aldehydes depending on the synthesis conditions led to the formation either methyl 2,2-dimethyl-3-oxo-3-(6-oxo-2-aryltetrahydropyran-3-yl)propanoates or 3-(5,5-dimethyl-4,6-dioxo-2-aryltetrahydropyran-3-yl)propanoates. The compounds synthesized formed as a single diastereomer of E-configuration.     

Synthesis of 2-(5-halogeno-2-f uryl)-2,3-dihydroperimidines

By boiling naphthylene-1,8-diamine with 5-halogeno- and 5-nitrofurfural in benzene or xylene, 90–95% yields of the corresponding 2-(5-halogeno-2-furyl)- and 2-(5-nitro-2-furyl)-2, 3-dihydroperimidines have been obtained. The dehydrogenation of 2-(5-bromo-2-furyl)-2, 3-dihydroperimidine with palladium on carbon has given 2-(5-bromo-2-furyl)perimidine. The compounds obtained have been characterized by their UV and IR spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1001–1003, July, 1973.     

Synthesis of 2-(hetero)arylthieno[2,3-b] or [3,2-b]pyridines from 2,3-dihalopyridines, (hetero)arylalkynes,and Na2S. Further functionalizations

A simple and efficient three-step methodology is described for the first time for the synthesis of 2-(hetero)arylthieno[2,3-b] or [3,2-b]pyridines. The first step is a Sonogashira coupling from 3-bromo-2-chloropyridine or 2-bromo-3-chloropyridine with several (hetero)arylalkynes to obtain the corresponding 2- or 3-chloro(hetero)arylethynylpyridines. These were cyclized by treatment with Na₂S affording the expected 2-(hetero)arylthienopyridines. As an improvement, these reactions were also performed in one-pot, without the isolation of the Sonogashira product, giving the thienopyridines in similar or better yields, reducing significantly the reaction time after the addition of Na₂S. Further functionalizations were achieved in the thienopyridine system either by bromination in the thiophene ring or chlorination in the pyridine ring via a N-oxide intermediate, allowing metal-catalyzed coupling reactions and/or nucleophilic substitutions. The functionalization of some substituents is also possible and as an example a 1,3-diarylurea was obtained from the reaction of an aniline derivative with an arylisocyanate.     

Synthesis of 4,6-diaryl-1-benzyl-6-hydroxy-5,5-dimethyl-2-oxopiperidine-3-carbonitriles and their analogs via a modified Reformatsky reaction

Organozinc compounds obtained from 1-aryl-2-bromo-2-methylpropanone and zinc react with N-benzyl-3-aryl-2-cyanoacrylamides or N-[6-(2-cyano-1-oxo-3-phenylprop-2-enylamino)hexyl]-2-cyano-3-phenylacrylamide to give 4,6-diaryl-1-benzyl-6-hydroxy-5,5-dimethyl-2-oxopiperidine-3-carbonitriles or 1,6-bis(6-aryl-3-cyano-6-hydroxy-5,5-dimethyl-2-oxo-4-phenylpiperidyl)hexanes as a single isomer with trans-located piperidine hydrogen atoms.     

Regioselective synthesis of cytotoxic 4-(1-alkynyl)-substituted 2-(5H)-furanones

4-(1-Alkynyl)-3-bromo- and 4-(1-alkynyl)-3-chloro-2(5H)-furanones have been regioselectively synthesized in moderate to good yields by a new version of the Pd/Cu-catalyzed Sonogashira reaction involving treatment of 1-alkynes with 3,4-dibromo- and 3,4-dichloro-2(5H)-furanone, respectively, in the presence of KF as a base. 4-(1-Alkynyl)-3-bromo-2(5H)-furanones have been found to be able to undergo Stille-type and Suzuki-type reactions with aryl(tributyl)tins and arylboronic acids, respectively, to give 4-(1-alkynyl)-3-aryl-2(5H)-furanones in modest to satisfactory yields. Some 4-(1-alkynyl)-substituted 2(5H)-furanones so prepared have been found to exhibit significant cytotoxic activities, especially against human leukemia cell lines.     

Efficient synthesis of new 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrol-2(5H)-ones

The synthesis of 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrol-2(5H)-ones 5, 6a-d from 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 3, 4a-d is reported. The 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 3, 4a-d were obtained from regiospecific bromination of 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 1, 2a-d with molecular bromine. The NMR and X-ray diffraction data showed that 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones were brominated at 4-position in the pyrrolidin-2-one ring.     

Chemoenzymatic synthesis of azacycloalkan-3-ols

Optically active ω-bromocyanohydrins are easily synthesized through an enantioselective (R)-oxynitrilase-catalyzed reaction from their corresponding ω-bromoaldehydes. These cyanohydrins are starting materials for the preparation of medium size nitrogen heterocycles. The reduction of (R)-(+)-5-bromo-2-hydroxypentanenitrile affords, in one-pot, piperidin-3-ol. Azepan-3-ol and azocan-3-ol are readily obtained from their corresponding cyanohydrins in high enantiomeric excesses.     

Synthesis of a (piperazin-1-ylmethyl)biaryl library via microwave-mediated Suzuki-Miyaura cross-couplings

Boc-protected (piperazin-1-ylmethyl)biaryls have been synthesised from (Boc-piperazin-1-ylmethyl)phenylboronic acid pinacol esters via a microwave-mediated Suzuki-Miyaura coupling with aryl bromides viz. 1-bromo-, 2-, 3- or 4-nitrobenzene or 2-bromo-5-nitropyridine. Judicial removal of the protecting group on the piperazine, or facile reduction of the nitro group on the biaryl system enabled the manipulation of two points of functionality in order to diversify the scope of the resulting biaryl library.     

Biocatalytic reduction system for the production of chiral methyl (R)/(S)-4-bromo-3-hydroxybutyrate

An effective method for producing methyl 4-bromo-3-hydroxybutyrate enantiomers was developed using an engineered protein. Escherichia coli transformant cells containing a mutant β-keto ester reductase (KER-L54Q) from Penicillium citrinum and a cofactor-regeneration enzyme such as glucose dehydrogenase (GDH) or Leifsonia sp. alcohol dehydrogenase (LSADH) were used to produce methyl (S)-4-bromo-3-hydroxybutyrate from methyl 4-bromo-3-oxobutyrate. On the other hand, the production of methyl (R)-4-bromo-3-hydroxybutyrate was achieved by asymmetric reduction of methyl 4-bromo-3-oxobutyrate with a mutant phenylacetaldehyde reductase (PAR-HAR1) from Rhodococcus sp. ST-10.     

A hydrogen pump: Transfer of four hydrogens from a cyclohexane ring to a triple bond during a menthofuran/bromoacetylene adduct rearrangement

The cycloadducts of menthofuran with acylbromoacetylenes, (3-bromo-1,6-dimethyl-5,6,7,8-tetrahydro-2H-2,4a-epoxynaphthalen-4-yl)(aryl)methanones, rearrange (CHCl₃, reflux, 1 h) to 2-(2-acylethyl)benzofurans (along with the expected 2-bromo-3-hydroxy-4,7-dimethyl-5,6,7,8-tetrahydronaphthalene-1-yl)(aryl)methanones) via 2-acylethynylmenthofurans, thus indicating the exceptionally mild and rapid transfer of four hydrogens from a cyclohexane ring to a triple bond through the furan moiety in the key intermediate 2-acylethynylmenthofuran.     

Pyridine-substituted hydroxythiophenes. I. Preparation of o-(2-, 3- and 4-pyridyl)-3-hydroxythiophenes.

2-(2-, 3- and 4-pyridyl)-3-hydroxythiophenes and 4-(2-, 3- and 4-pyridyl)- 3-hydroxythiophenes have been prepared by hydrogen peroxide oxidation of the corresponding boronic esters. In the former case the boronic esters were obtained in three steps from 2,3-dibromothiophene via the corresponding 3-bromo-2-pyridylthiophenes synthesized by Pd(0)-catalyzed coupling between 3-bromo-2-trimethylstannylthiophene and the corresponding bromopyridines. In the latter case the known isomeric pyridylthiophenes were converted into the corresponding boronic esters in three steps via tribromo- and 3-bromo-4-pyridylthiophenes successively. 4-(3- and 4-pyridyl) thiophen-2(5H)-ones were also obtained in the syntheses of 4-(3- and 4-pyridyl)-3-hydroxythiophene. They are suggested to arise from rearrangement during the halogen-metal exchange. Spectroscopic investigations by 1H NMR and IR show that these hydroxythiophene systems exist exclusively as enol forms.     

Synthesis,cytotoxic activity,and fluorescence properties of a set of novel 3-hydroxyquinolin-4(1H)-ones

The targeted solid-phase synthesis of 3-hydroxyquinolin-4(1H)-one derivatives is described. Primary and secondary amines, 3-amino-4-(methoxycarbonyl)benzoic acid and 2-bromo-1-(4-chloro-3-nitrophenyl)ethanone were used as starting materials. The structures of the final compounds were designed in accordance with previous information obtained from structure–activity relationship studies of similar cytotoxic derivatives. Representative prepared compounds were subjected to in vitro screening of cytotoxic activity against various cancer cell lines; the results obtained are discussed. Fluorescence properties of selected compounds were also studied to compare the data with those obtained in analogous derivatives.     

MIRC reactions of 2-bromo-5-(l-menthyloxy)furan-2(5H)-one with stabilized anions. Preparation of homochiral bicyclic γ-butyrolactones

Homochiral (5R)-4-bromo-5-(l-menthyloxy)furan-2(5H)-one with stabilized carbanions (from nitroalkanes, malononitrile and ethyl acetoacetate) afforded enantiopure bicyclic compounds in good yield (70–90%). 3-Oxabicyclic[3.1.0]hexan-2-one derivatives were obtained with nitromethane and malonic acid derivatives. However, dihydrofuro[3,4-d]isoxazol-6-one and dihydrofuro[3,4-b]furan-6(4H)-one derivatives were obtained from nitroethane and ethyl acetoacetate, respectively.     

The first enantioselective synthesis of (S)-5-bromo-3-(1-methyl-2-pyrrolidinyl)pyridine: a key intermediate for the preparation of SIB-1508Y

The first enantioselective synthesis of (S)-5-bromo-3-(1-methyl-2-pyrrolidinyl)pyridine is described via intramolecular hydroboration–cycloalkylation of an azido-olefin intermediate. The chiral homoallylic alcohol was efficiently synthesized by enantioselective reduction of the corresponding ketone using (+)-diisopinocamphenylchloroborane as the key reaction. The total synthesis of (S)-SIB-1508Y was achieved with an enantiomeric excess (e.e.) of 94% in ten steps and in 18% overall yield from the commercially available 5-bromo-3-pyridinecarboxylic acid.