Visible-light induced cascade radical cyclization of sulfinic acids and o-(allyloxy)arylaldehydes towards functionalized chroman-4-ones

An efficient method for the synthesis of functionalized chroman-4-ones induced by visible light via the radical cyclization reaction of sulfinic acids and o-(allyloxy)arylaldehydes at room temperature was described. The corresponding products were isolated with moderate to good yields. Radical mechanism was proposed for this transformation. Anti-microbial activity of some desired compounds were screened.     

Benzofurans. Improved syntheses of bufuralol, 7-ethyl-2-(2-tert-butylamino-1-hydroxyethyl)benzofuran,and 1″-oxobufuralol, 7-acetyl-2-(2-tert-butylamino-1-hydroxyethyl)benzofuran

An improved laboratory scale synthesis of bufuralol ( 1 ) and 1″-oxobufuralol ( 4 ) was accomplished. The intermediate benzofurans were prepared via aromatization of 2,3-dihydrobenzofurans or by a one-step acidcatalyzed cyclization from 2,2-diethoxyethyl 4-bromo-6-ethyl-2-formylphenyl ether ( 23 ). Base-catalyzed cyclization of 3-(5-bromo-3-ethyl-2-hydroxyphenyl)-1.2-epoxypropane ( 16 ) provided the key intermediate, 5-bromo-7-ethyl-2-hydroxymethyl-2,3-dihydrobenzofuran ( 17 ). Selective functionalization of the C-2 and C-7 positions of the benzofuran ring system was accomplished to afford both 1 and 4 .     

Synthesis of 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-ones via Pd-catalyzed regioselective cross-coupling reaction and cyclization

An efficient and novel route for the synthesis of 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-one 1 via palladium-catalyzed site-selective cross-coupling reaction and cyclization process was described. Reaction of 3-bromo-4-trifloxy-quinolin-2(1H)-one 3 with arylboronic acid catalyzed by PdCl₂(PPh₃)₂ afforded 3-bromo-4-aryl-quinolin-2(1H)-one 4, which then reacted with 2-ethynylaniline 5 via Pd-catalyzed Sonogashira coupling and CuI-mediated cyclization leading to the desired 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-one 1 in good yields.     

AuBr3-catalyzed cyclization of o-(alkynyl)nitrobenzenes. Efficient synthesis of isatogens and anthranils

The cyclization of o-(arylalkynyl)nitrobenzenes was catalyzed by AuBr₃ to produce the corresponding isatogens in good to high yields together with small amounts of anthranils. On the other hand, anthranils were obtained selectively when the AuBr₃-catalyzed reaction was carried out using o-(alkylalkynyl)nitrobenzenes.     

Some fatty acids having an O-heterocycle in their terminal positions. II. ω-(3-Coumarinyl)alkanoic acids and ω-(2-chromonyl)alkanoic acids

Some ω-3-coumarinyl)alkanoic acids 1a , n = 3-6 were synthesized by cyclization of corresponding ethyl o-formylphenyl alkanedioate 3 with DBU followed by hydrolysis. By a similar cyclization, some ω-(2-chromonyl)alkanoic acids 2a , n = 3-6 were also obtained from the cyclization of corresponding o-acetylphenyl ethyl alkanedioate 4 .     

Synthesis of quinazolin-4(3H)-ones and 1,2-dihydroquinazolin-4(3H)-ones with the aid of a low-valent titanium reagent

A short and facile synthesis of a series of quinazolin-4(3H)-ones and 1,2-dihydroquinazolin-4(3H)-ones was accomplished in good yields via the novel reductive cyclization of o-nitrobenzamides and triethyl orthoformate, aldehydes or ketones promoted by TiCl₄/Zn.     

Revisited synthesis of fused diazepines from 3-(3-aryl-3-oxopropenyl)chromen-4-ones and binucleophilic amino enones in a three-step domino process

The synthesis of tetracyclic 11,12,13,14b-tetrahydrodi-benzo[b, f]pyrido[1,2-d][1,4]diazepines was revisited via a catalyst-free three-step domino reaction involving a pyrone ring-opening/aza-Michael addition/intramolecular cyclization, the reactants having been o-arylenediamine–dimedone adducts and 3-(3-aryl-3-oxopropenyl)chromen-4-ones. The 3-positioned exocyclic α,β-enone fragment on the chromone moiety is involved in the cyclization into the final products at the last step of the process.     

Synthesis and reactions of 2-hydroxy-4-oxo-4-(2,3,5,6-tetrafluoro-4-methoxyphenyl)-but-2-enoic acid methyl ester

2-Hydroxy-4-oxo-4-(2,3,5,6-tetrafluoro-4-methoxyphenyl)-but-2-enoic acid methyl ester (1) was synthesized by the reaction of pentafluoroacetophenone with dimethyl oxalate in the presence of sodium methylate. Subsequently, reactions of compound 1 with aniline, o-phenylenediamine, and o-aminophenol were investigated. In addition, the thermal cyclization of ester 1 was studied and led to the formation of 5,6,8-trifluoro-7-methoxy-4-oxo-4H-chromene-2-carboxylic acid methyl ester (6) due to nucleophilic substitution of the 3-fluoro group. Hydrolysis of compound 1 and subsequent cyclization by treatment with SOCl₂ gave 5-(2,3,5,6-tetrafluoro-4-methoxyphenyl)-furan-2,3-dione (3). Thermal decarbonylation of compound 3 under mild conditions resulted in the formation of 3-(2,3,5,6-tetrafluoro-4-methoxyphenyl)-propene-1,3-dione (4) which dimerized to pyranone 5.     

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.     

Facile synthesis of sulfenyl-substituted isocoumarins,heterocycle-fused pyrones and 3-(inden-1-ylidene)isobenzofuranones by FeCl3-promoted regioselective annulation of o-(1-alkynyl)benzoates and o-(1-alkynyl)heterocyclic carboxylates with disulfides

Reported herein is the FeCl₃-promoted intermolecular sulfoesterification of o-(1-alkynyl)benzoates with disulfides, which provides a convenient and efficient method for synthesis of 4-sulfenylisocoumarins. Various functional groups such as methoxy, halides, ester, cyano and silicon groups in the substrates are tolerated, and heterocycle-fused chalcogenylpyrones are also successfully achieved directly from the corresponding heterocyclic precursors under the same reaction conditions. In addition, starting from diynylbenzoate, this reaction sequence can be combined with a bicyclization step leading to the tetracyclic (E)-3-(2-phenyl-3-phenylchalcogenylinden-1-ylidene)isobenzofuranone frameworks with high regiospecificity and exclusive trans stereoselectivity.     

Synthetic entry to 8-(o-nitrophenyl-2-azabicyclo[3.3.1]nonan-7-ones. Intermediates for the synthesis of strychnos-type systems.

The first synthetic route to 8-aryl-2-azabicyclo-[3.3.1]nonan-7-ones (e.g. 5) is reported. The synthesis involves acid cyclization of an appropriate 4-acetonyl-2-piperidinecarbonitrile (4) which, in turn, is obtained from the corresponding piperidine (3) by a modified Polonovski reaction. The o-nitrophenyl substituent of 3 is introduced by arylation of 4-piperidineacetoacetate 1 with o-fluoronitrobenzene followed by acid hydrolysis. The conversion of α-(o-nitrophenyl)ketone 5 to the bridged azocinoindole 7, an intermediate in the synthesis of deethyltubifolidine, is also reported.     

Oxidative dehydrobromination of 3-(α-bromobenzyl)quinoxalin-2(1H)-ones according to Kornblum as a simple and efficient synthetic route to quinoxalyl aryl ketones

Condensation of ethyl 3-aryl-3-bromo-2-oxopropanoates with o-phenylenediamine in acetic acid gave 3-(α-bromobenzyl)quinoxalin-2(1H)-ones which were converted in high yield into the corresponding 3-aroylquinoxalin-2(1H)-ones via oxidative dehydrobromination in dimethyl sulfoxide according to Kornblum.     

Synthesis and heterocyclization of 2-{[2-(4-bromophenyl)-2-oxoethyl]sulfanyl}pyrimidin-4(3<Emphasis Type="Italic">h</Emphasis>)-ones

Alkylation of sodium 4(5)-alkyl-6-oxo-1,6-dihydropyrimidine-2-thiolates with 2-bromo-1-(4-bromophenyl)ethan-1-one afforded 2-{[2-(4-bromophenyl)-2-oxoethyl]sulfanyl}pyrimidin-4(3H)-ones. Analogous reaction with sodium 4-trifluoromethyl-6-oxo-1,6-dihydropyrimidine-2-thiolate gave a mixture of 2-{[2-(4-bromophenyl)-2-oxoethyl]sulfanyl}-4-(trifluoromethyl)pyrimidin-4(3H)-one and its intramolecular cyclization product, 3-(4-bromophenyl)-3-hydroxy-7-trifluoromethyl-2,3-dihydro[1,3]thiazolo[3,2-a]-pyrimidin-5-one.     

Preparation and biological properties of inclusion compounds of calix[4]arene and 1,4-benzodiazepinone derivatives

The possibility of enhancing the oral bioavailability of certain 1,4-benzodiazepinones by using them as complexes with a series of calix[4]arene derivatives was examined. All the inclusion compounds prepared exhibit anticonvulsant activity by antagonism with Corazol spasmodic agent. Complexes with 25,27-bis[(hydrazinocarbonyl)methoxy]-26,28-dihydroxy-p-tert-butylcalix[4]arene exhibit higher pharmacological activity compared to the starting 7-bromo-5-(o-chloro)phenyl-and 1-hydrazinocarbonylmethyl-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ones.     

Synthesis of spiro[4.5]decane and bicyclo[4.3.0]nonane ring systems by self-cyclization of (Z)- and (E)-2-(trimethylsilylmethyl)pentadienal derivative

The two title carbon frameworks were synthesized utilizing a new type of iron-induced cyclization reaction of 2-(trimethylsilylmethyl)pentadienal. 2-Methylspiro[4.5]dec-2-en-1-one was obtained from (Z)- and (E)-4-cyclohexylidene-2-(trimethylsilylmethyl)but-2-enal. It was found that the (Z)-substrate isomerized to (E)-intermediate followed by cyclization to afford the initial product, 2-methylenespiro[4.5]dec-3-en-1-ol, which was isomerized to the above product. The cyclization of 4-(4-alkyl)cyclohexylidene-2-(trimethylsilylmethyl)but-2-enal proceeded stereoselectively. While, (E)-3-(cyclohex-1-en-1-yl)-2-(trimethylsilylmethyl)prop-2-en-1-al cyclized immediately affording 8-methylenebicyclo[4.3.0]non-9-en-7-ol. The corresponding (Z)-isomer gave several cyclization products as a complex mixture.     

The Richter reaction of ortho-(alka-1,3-diynyl)aryldiazonium salts

The cyclisation of various ortho-buta-1,3-diynylaryldiazonium salts was studied and shown to depend on the reaction conditions and nature of the substituents on the benzene ring. The reaction leads to 4-chloro-3-ethynylcinnolines, and/or 3-ethynyl-4-hydroxycinnolines, the latter undergoing subsequent cyclisation to give furo[3,2-c]cinnolines.     

(S)-(4-溴-2-甲苯)(3-甲基吗啉)甲酮的合成

以(S)-2-氨基丙醇和氯乙酰氯为起始原料,经酰化和环合反应制得(S)-5-甲基吗啉-3-酮（4）; 4经还原制得(S)-3-甲基吗啉(5); 5与4-溴-2-甲基苯甲酸酰化缩合合成了(S)-(4-溴2-甲基苯基)(3-甲基吗啉)-甲酮,总收率57%,其结构经¹H NMR 和 ¹³C NMR确证。     

Domino synthesis of 2-arylbenzo[b]furans by copper(II)-catalyzed coupling of o-iodophenols and aryl acetylenes

A wide range of 2-arylbenzo[b]furans are synthesized through domino intermolecular C_(aryl)-C_(alkynyl) bond formation followed by intramolecular C_(alkynyl)-O bond forming cyclization via copper(II)-catalyzed coupling of o-iodophenols and aryl terminal acetylenes. This method requires neither expensive palladium catalyst nor oxophilic phosphine ligands, can tolerate different functional groups. The methodology is successfully utilized in formal synthesis of β-amyloid aggregation inhibitor 5-chloro-3-[4-(3-diethylaminopropoxy)benzoyl]-2-(4-methoxyphenyl) benzofuran.     

Reactions of 3,5-dibromo-1-(thiiran-2-ylmethyl)-1,2,4-triazole with NH-azoles

Reactions of 3,5-dibromo-1-(thiiran-2-ylmethyl)-1,2,4-triazole with 3,5-dimethylpyrazole, 1,3-dimethyl-3,7-dihydropurine-2,6-dione, 3,5-dibromo-1,2,4-triazole, 2,4,5-tribromoimidazole, and 2-chlorobenzimidazole lead to the formation of 5-azolylmethyl-2-bromo-5,6-dihydrothiazolo[3,2-b]-1,2,4-triazoles. In the case of 8-bromo-1,3-dimethyl-3,7-dihydropurine-2,6-dione the intermediate thiolate anion undergoes cyclization into 7-[(3,5-dibromo-1,2,4-triazol-1-yl)methyl]-1,3-dimethyl-6,7-dihydrothiazolo[2,3-f]purine-2,4(1H,3H)-dione. The structure of reaction products depends on the relative rate of substitution of leaving groups in the reagents.     

Synthesis of 2H-1,4-thiazin-3(4H)-one 1-oxide and 2H-1,4-thiazin-3-(4H)-one 1,1-dioxide,structural analogs of uracil

The synthesis of 1,4-thiazine 1-oxide and 1,1-dioxide analogs of the antibiotic emimycin is described. Reaction of methylthioglycolate with 1-bromo-2,2-diethoxyethane gave methyl (2,2-diethoxyethylthio)acetate ( 2 ). Treatment of 2 with methanolic ammonia followed by cyclization furnished 2H-1,4-thiazin-3(4H)-one ( 5 ). Oxidation of 5 with m-chloroperoxybenzoic acid converted it to 2H-1,4-thiazin-3(4H)-one 1-oxide ( 6 ). Oxidation of 2 with potassium permanganate, followed by treatment with methanolic ammonia, and cyclization gave 2H-1,4-thiazin-3(4H)-one 1,1-dioxide.