Polyfluoroether derivatives via nucleophilic fluorination of glyoxal hydrates with deoxofluor

Various glyoxal hydrates have been reacted with Deoxofluor [(CH(3)OCH(2)CH(2))(2)NSF(3)]. In concentrated solutions of dichloromethane, Deoxofluor (1) efficiently fluorinates a variety of glyoxal hydrates, RCOCHO.H(2)O (R = 4-methoxyphenyl, 3,4-methylenedioxyphenyl, 4-methylphenyl, 4-fluorophenyl, phenyl, 2-thienyl, methyl) (6a-g) to form polyfluoroethers 7a-g and 8a-g as meso and racemic mixtures (approximately 1:1) in good yields. The meso and racemic compounds were separated by flash chromatography and characterized. When the reactant comprised two different glyoxal hydrates, mixed polyfluoroethers (9h-j) were observed as the major products. The yields of the mixed polyfluoroethers depend on the ratio of the two different glyoxal hydrates used. Reactions of some other hydrates, such as hydrindantin dihydrate (10) and 1,1,1,5,5,5-hexafluoro-2,2,4,4-pentanetetrol (11), were also studied with Deoxofluor to give a cyclic polyfluoroether (12) and beta-ketoamine (13), respectively. When the reactions of 6a-d were carried out under very dilute conditions, difluoro aldehydes (14a-d) or tetrafluoroalkanes (15a-d) were formed rather than polyfluoroethers. Reactions of concentrated solutions of nonhydrated glyoxals (16k-m) in methylene chloride with Deoxofluor produced the tetrafluoroalkanes (18k-m) in good yields with only trace amounts of difluoroaldehydes (17k-m) being found. The structures of 7a (meso), 8b (racemic), and 12 have been confirmed by single-crystal X-ray analysis.     

Diene hydroacylation from the alcohol or aldehyde oxidation level via ruthenium-catalyzed C-C bond-forming transfer hydrogenation: synthesis of beta,gamma-unsaturated ketones

Under the conditions of ruthenium-catalyzed transfer hydrogenation, isoprene couples to benzylic and aliphatic alcohols 1a-g to deliver beta,gamma-unsaturated ketones 3a-g in good to excellent isolated yields. Under identical conditions, aldehydes 2a-g couple to isoprene to provide an identical set of beta,gamma-unsaturated ketones 3a-g in good to excellent isolated yields. As demonstrated by the coupling of butadiene, myrcene, and 1,2-dimethylbutadiene to representative alcohols 1b, 1c, and 1e, diverse acyclic dienes participate in transfer hydrogenative coupling to form beta,gamma-unsaturated ketones. In all cases, complete branch regioselectivity is observed, and, with the exception of adduct 3j, isomerization to the conjugated enone is not detected. Thus, formal intermolecular diene hydroacylation is achieved from the alcohol or aldehyde oxidation level. In earlier studies employing a related ruthenium catalyst, acyclic dienes were coupled to carbonyl partners from the alcohol or aldehyde oxidation level to furnish branched homoallylic alcohols. Thus, under transfer hydrogenative coupling conditions, all oxidation levels of substrate (alcohol or aldehyde) and product (homoallyl alcohol or beta,gamma-unsaturated ketone) are accessible.     

Lithiation of 1-chloromethylbenzotriazole: generation and elaboration of benzotriazolyloxiranes

1-Benzotriazolylchloromethyllithium generated from 1-chloromethylbenzotriazole (1) and LDA reacts with enolizable and nonenolizable ketones to give benzotriazolyloxiranes 2a-g in good yields. The oxiranyllithiums 4a-d generated from 2a-d and n-BuLi at -78 degrees C were trapped by a variety of electrophiles to give oxiranyl derivatives 5a-j in good to excellent yields. Lewis-acid-promoted nucleophilic ring opening of benzotriazolyloxiranes 2a,f,g with allyltrimethylsilane gave the corresponding 1,7-octadien-4-ols 6a-c in 68-75% yield. Hydrolysis of alpha-acylbenzotriazolyloxiranes 5g,h provided 3-hydroxy-1,2-diones 7a and 7b in 73 and 86% yield, respectively.     

C2轴对称樟脑磺酰胺基醇配体催化环己烯乙炔对酮的不对称加成反应

应用C2轴对称的樟脑磺酰胺基醇配体和Cu(OTf)2催化带官能团的环己烯乙炔对酮的不对称加成反应. 芳香酮、脂肪酮和杂环酮都适用于此体系, 并且在室温下最高e.e.值约为89%, 其中脂肪酮首次被应用于此反应, 极大地扩展了底物的范围. 研究结果表明, 脂肪酮的立体位阻对反应的对映选择性起着至关重要的作用.     

Photocyclization reactions. Part 3 . Synthesis of naphtho[1,8-bc]-furans and Cyclohepta[cd]benzofurans using photocyclization of 8-alkoxy-1,2,3,4-tetrahydro-1-naphthalenones and 4-alkoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ones

Photocyclization reactions were carried out on 8-alkoxy-1,2,3,4-tetrahydro-1-naphthalenones (six-membered ring ketones) 4a-g and 4-alkoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ones (seven-membered ring ketones) 5a -e in acetonitrile. Irradiation of 4a-f gave rearranged naphthyl alcohols 8a-f as major products. In the case of 4g , 2a,3,4,5-tetrahydronaphtho[1,8-bc]furan-2a-ol 6g was obtained. In contrast, irradiation of 5a-e afforded 2,2a,3,4,5,6-hexahydrocyclohepta[cd]benzofuran-2a-ols 9a-e in good yields. The difference in reactivities between 4a-g and 5a-e is attributed to the conformation of six- and seven-membered rings. Conformational and substituent effects in cyclization step of 1,5-biradicals are discussed along with reaction pathways.     

Synthesis of carbazoles via an intramolecular cyclization of 2-(6-substituted 3(Z)-hexen-1,5-diynyl)anilines and their related molecules

Various 2-(6-substituted 3(Z)-hexen-1,5-diynyl)anilines 1a-g were treated with potassium tert-butoxide or potassium 3-ethylpentanoxide in NMP at 60 degrees C for 2 h to give the corresponding 5-substituted carbazoles 2a-g in 36-65% yields together with indoles 9a-g in 21-40% yields, respectively. Exposing the trifluoroacetamide analogues 10h-k under the same reaction conditions gave the carbazoles 2b-e in 37-57% yields and indoles 9b-e in 15-27% yields. Subsequent cyclizations of acetamide analogues 10a-g gave carbazoles 2a-g in 53-86% yields.     

Haloacetylated enol ethers. 7 . Synthesis of 3-aryl-5-trihalomethylisoxazoles and 3-aryl-5-hydroxy-5-trihalomethyl-4,5-dihydroisoxazoles

β-Aryl-β-methoxyvinyl trihalomethyl ketones 1a-g, 2a-g [aryl = p-YC₆H₄ where Y= H, Me, OMe, F, Cl, Br, NO₂] are cyclocondensed with hydroxylamine hydrochloride to afford the 3-aryl-5-hydroxy-5-trihalomethyl-4,5-dihydroisoxazoles 3a-g, 4a-f in good yield. The dehydratation of compounds 3a-g with concentrated sulfuric acid, led the corresponding 3-aryl-5-trichloromethylisoxazoles 5a-g . An alternative one-pot procedure yields 3-aryl-5-trihalomethylisoxazoles 5,6a-g directly by cyclocondesation of 1,2a-g with hydroxylamine hydrochloride in the presence of an excess of concentrated hydrochloric acid.     

Synthesis of pyrimidine derivatives by the reaction of ketene dithioacetals with amides

Reactions of methyl 2-cyano-3,3-bis(methylthio)acrylate ( 1a ) with carboxamides 2a-g in the presence of sodium hydride in a mixture of benzene and N,N-dimethylacetamide took place displacement with the methylthio group to give the corresponding methyl 3-N-acylamino-2-cyano-3-(methylthio)acrylates 3a-g which were readily converted to the corresponding pyrimidine derivatives at reflux in methanol in good yields. Reactions of 2-cyano-3,3-bis(methylthio)acrylonitrile ( 1b ) with the carboxamides 2a-f gave directly pyrimidine-5-carbonitrile derivatives 7a-f . Ketene dithioacetals 1a,b smoothly reacted with thioamide 2g or urea 2h,i to give the expected pyrimidine derivatives 9,10a,b . Polyfunctionalized pyrimidines, thus obtained, were also used for the synthesis of fused pyrimidine derivatives.     

Synthesis and Cytotoxic Activity of Coumarin Derivatives Containing Benzotriazole Moieties

Three coumarin derivatives containing benzotriazole moieties, 3-(1-benzotriazolyl)-4-methyl-coumarin (BMC), 3-(1-benzotriazolyl)-4-methyl-benzo[7,8]coumarin (BMBC), and 3-(4-methyl-1-benzotriazolyl)-4-methyl-benzo[7,8]coumarin (MBMBC), were synthesized. Among them, 3-(4-methyl-1-benzotriazolyl)-4-methyl-benzo[7,8]coumarin has been structurally characterized by X-ray crystallography. The cytotoxic effect by Sulforhodamine B (SRB) assay with these compounds against the human hepatocellular carcinoma cell lines (HepG-2) was carried out in vitro. The preliminary results showed that all compounds inhibit HepG-2 growth effectively.     

New substituent effects of the trimethylsilyl group: photochemistry of 3-trimethylsilyl-2,5-cyclohexadienones and preparation of 4-alkylidenecyclopentenones

The 4-acetoxymethyl-4-alkyl-3-trimethylsilyl-2,5-cyclohexadien-1-ones 9a-g were prepared from methyl 2-trimethylsilylbenzoate by the Birch reduction-alkylation reaction. Type A photorearrangements of 9a-g were regiospecific to give mixtures of two diastereomers of the corresponding 5-trimethylsilylbicyclo[3.1.0]hex-3-en-2-ones 11a-g. These bicyclohexenones are uniquely photostable; the diastereomers do not photointerconvert nor do they undergo the type B photorearrangement. Bicyclohexenones 11a-g undergo acid-catalyzed protiodesilylative rearrangement to give the 4-alkylidene-2-cyclopenten-1-ones 25a-g. It was of interest to find that the 4-(3'-butenyl)-2,5-cyclohexadienone 9e photorearranged to the 5-trimethylsilylbicyclo[3.1.0]hex-3-en-2-one 11e rather than undergoing the intramolecular 2 + 2 photocycloaddition. Furthermore, the 4-acetoxymethyl-3-methoxy-4-methyl-5-trimethylsilyl-2,5-cyclohexadienone 30a did not show type A photobehavior at 366 and 300 nm, while the 4-(3'-butenyl) analogue 30b gave the intramolecular 2 + 2 cycloadduct 31b. The effects of the trimethylsilyl and methoxy substituents on the photochemical reactivity of 2,5-cyclohexadien-1-ones are discussed from the perspective of n --> p* vs pi --> p* character of the triplet states of the dienones.     

3-BocNH-ABNO-catalyzed aerobic oxidation of alcohol at room temperature and atmospheric pressure

A transition-metal-free catalytic system has been developed for selective transformation of alcohol to aldehydes or ketones. The reactions were performed with 3-(tert-butoxycarbonylamino)-9-azabicyclo[3.3.1]nonane N-oxyl (3-BocNH-ABNO) as the catalyst, NaNO₂ as the co-catalyst, molecular oxygen as the terminal oxidant, and AcOH as the solvent under room temperature. This catalytic system exhibited broad functional group tolerance. A series of alcohol substrates, including primary and secondary benzylic alcohols, heteroaromatic analogues, primary and secondary aliphatic alcohols, could be converted into their corresponding aldehydes and ketones in good conversions and selectivities.     

Stereospecific Syntheses of 5-Alkyl-3-ethoxy-2-((phenylchalcogeno)methylene)tetrahydrofurans

2-Ethoxy-4-(phenylchalcogeno)but-3-ynyl ketones 1-10 were reduced with LiBH(4) in Et(2)O diastereoselectively to give 5-(phenylchalcogeno)pent-4-yn-1-ols 11-20. Treatment of the phenylchalcogen-substituted alkynyl alcohols 11-20 with t-BuOK in t-BuOH provided useful (Z)-2-((phenylchalcogeno)methylene)tetrahydrofurans 21-31 stereoselectively.     

4-Substituted-3,4-dihydro-3-methyl-2H-1,3-benzoxazin-2-ones. III (2,3). Solvolytic-reductive transformation of 4-(2-keto)-benzoxazin-2-ones into oxazin-2-ones

A series of 4-(2-keto-substituted)-3,4-dihydro-3-methyl-2H-1,3-benzoxazin-2-ones 1 (Table I) was synthesized by condensation of 3-alkyl-3,4-dihydro-4-hydroxy-2H-1,3-benzoxazin-2-ones 4 with ketones 5 having active alpha hydrogens. In the presence of alcoholic potassium borohydride, compounds 1 underwent reductive transacylation to give 1,3-oxazin-2-one derivatives 3 (Table III, a,b,c). When the other side of the ketone possessed substituents other than hydrogen, there were always also normal reduction products, i.e., secondary alcohols 2 (Table II) in addition to 3.     

Synthesis and Chemistry of 4-Aroyl-3-oxo- and 3-Chloropyridazine Derivatives

4H,5H-6-Phenyl (1a) and 6-p-phenoxyphenyl (1b) pyridazin-3(2H)-ones were reacted with aromatic aldehydes to give 4-arylmethylpyridazm-3(2H)-ones (2a-g), Oxidation of (2a-g) with various oxidising agents (selenium dioxide in ethanol or chromium trioxide in acetic acid) gave 4-aroyl-6-arylpyridazin-3(2H)-ones (3a-g). Chlorination of (3a-g) with phosphorous oxychloride afforded 4-aroyl-6-aryl-3-chloropyridazine (4a-g). 1H-3-Aryl-5-phenylpyrazolo[3,4-c]pyridazines (5a-d) were obtained by heating (4a-d) with excess hydrazine hydrate. Hydroxyamination of (3e-g) with iydroxylamine gave aryl-4(6-p-phenoxyphenyl-2,3-dihydro-3-oxo)pyridazinyl oxime (6a-c). Silylation of oximes (6b & 6c) gave (7a & 7b) as acyclic compound instead of the expected seven - membered - ring compound (8).     

Synthesis of 2,2,3,3-tetracyanocyclopropyl ketones and their reactions with oxygen-centered nucleophiles

A procedure for the synthesis of 2,2,3,3-tetracyanocyclopropyl ketones has been developed on the basis of three-component Wideqvist reaction of dihydroxymethyl ketones, 2-bromomalononitrile, and malononitrile. The presence of five electron-withdrawing groups in the resulting cyclopropyl ketones determines high acidity of proton in the cyclopropane ring. Facile deprotonation by the action of bases promotes opening of the three-membered ring with formation of either 1,1,3,3-tetracyanopropenides or (in the presence of alcohols or oximes), [2-alkoxy(aminooxy)-5-amino-4-cyanofuran-3(2H)-ylidene]malononitriles. The reaction with acetone oxime was not accompanied by cleavage of the three-membered ring, and nucleophilic attack was directed at the cyano groups in the trans position with respect to the carbonyl group to give the corresponding (1R*,5S*,6R*)-4-amino-2,2-bis(prop-2-ylideneaminooxy)-3-azabicyclo[3.1.0]hex-3-ene-1,5-dicarbonitriles.     

Reductive ring cleavage of 1-alkyl-4-benzoylamino-5-phenyl-3-pyrazolidinones with raney-nickel alloy. Synthesis of N-benzoyl-3-alkylamino-3-phenylalanine amides from rel-(4R,5R)-4-benzoylamino-5-phenyl-3-pyrazolidinone

rel-(4R,5R)-4-Benzoylamino-5-phenyl-3-pyrazolidinone ( 1 ) was alkylated at position 1 with carbonyl compounds 2a-g . The corresponding rel-(4R,5R)-4-benzoylamino-5-phenyl-3-pyrazolidinone-1-azomethine imines 3a-g , were treated with sodium borohydride to give rel-(4R,5R)-1-alkyl-4-benzoylamino-5-phenyl-3-pyrazolidinones 4a-g . Reduction of pyrazolidinones 4a-g with Raney-nickel alloy in methanolic potassium hydroxide furnished rel-(4R,5R)-N-benzoyl-3-alkylamino-3-phenylalanine amides 5a-f .     

4H—1,2,4—三唑—4—基酮和醇的合成及其生物活性

1-(4H-1,2,4-三唑-4-基)频哪酮(2)与卤代烃在相转移催化条件下反应,得到具有较高产率的4H-1,2,4-三唑-4-基酮(3);进一步用硼氢化钾还原,得到近乎定量产率的醇(4)。初步的生物活性测定表明3和4有一定的延缓植物生长的作用和杀菌活性。     

Highly efficient catalytic aerobic oxidations of benzylic alcohols in water

A highly efficient catalytic system without transition metals in water has been developed for aerobic oxidations of benzylic alcohols. The newly developed catalyst system could oxidize benzylic alcohols and heteroaromatic analogues with 1 mol % TEMPO as a catalyst and with a catalytic amount of 1,3-dibromo-5,5-dimethylhydantoin and NaNO2 as cocatalysts. Under the optimal conditions, various alcohols could be converted into their corresponding aldehydes or ketones in high yields.     

Synthesis and Synthetic Application of alpha-Formylvinylphosphonates. Facile Synthesis of Phosphono-Substituted Heterocyclic Compounds

The beta-ethoxy-alpha-phosphonovinyl anion, generated from beta-(ethoxy)vinylphosphonate 1 and LDA, reacted with aldehydes and ketones or phenyl isocyanate to give the corresponding allylic alcohols 2a-m or 1,3-diphenyl-5-phosphonouracil 4 in good or moderate yields. Treatment of the alcohols 2a-d,g,h,j with trifluoroacetic acid led to alpha-formylvinylphosphonates 5a-d,g,h,j in excellent yields. Synthetic application of the alpha-formylvinylphosphonates 5a-d,g,h to phosphono-substituted heterocyclic compounds was studied.     

Microwave assisted condensation reactions of 2-aryl hydrazonopropanals with nucleophilic reagents and dimethyl acetylenedicarboxylate

The reaction of methyl ketones 1a-g with dimethylformamide dimethylacetal (DMFDMA) afforded the enaminones 2a-g, which were coupled with diazotized aromatic amines 3a,b to give the corresponding aryl hydrazones 6a-h. Condensation of compounds 6a-h with some aromatic heterocyclic amines afforded iminoarylhydrazones 9a-m. Enaminoazo compounds 12a,b could be obtained from condensation of 6c with secondary amines. The reaction of 6e,h with benzotriazolylacetone yielded 14a,b. Also, the reaction of 6a,b,d-f,h with glycine and hippuric acid in acetic anhydride afforded pyridazinone derivatives 17a-f. Synthesis of pyridazine carboxylic acid derivatives 22a,b from the reaction of 6b,e with dimethyl acetylenedicarboxylate (DMAD) in the presence of triphenylphosphine at room temperature is also reported. Most of these reactions were conducted under irradiation in a microwave oven in the absence of solvent in an attempt to improve the product yields and to reduce the reaction times.