Facile generation method for conjugated allenyl esters based on retro-Dieckmann-type ring-opening reactions

α-Alkynyl-α-ethoxycarbonyl cyclopentanones 1a-c and cyclohexanones 2a-c were readily synthesized by the reaction of ethyl 2-oxocyclopentanonecarboxylate 6 and ethyl 2-oxocyclohexanonecarboxylate 7 with alkynyllead triacetates 5a-c obtained from lithium acetylides 4a-c and lead tetraacetate. Treatment of 1a-c and 2a-c with 1 N KOH in THF or with n-Bu₄N⁺OEt⁻ in EtOH and THF gave the corresponding conjugated allenyl esters 8a-c, 9a-c, 10a-c, and 11a-c in good to excellent yields, respectively.     

Asymmetric synthesis of 3-substituted unsaturated prolines from chiral sulfoximine substituted allyl titanium(IV) complexes

An asymmetric synthesis of the 3-substituted Δ^3,4-unsaturated prolines 7a-e and 3-substituted 4-methylene prolines 14a-c starting from the corresponding γ,δ-unsaturated α-amino acids 4a-e and 11a-c, respectively, is described. Amino acid derivatives 4a-e and 11a-d were obtained through aminoalkylation of the corresponding sulfoximine substituted allyl titanium(IV) complexes 2a-e and 10a-d, respectively, with the N-tert-butylsulfonyl imino ester 3. Activation of sulfoximines 4a-e and 11a-c through methylation of the sulfoximine group followed by a KF mediated isomerization of the vinyl aminosulfoxonium salts 5a-e and 12a-c, respectively, to the corresponding allyl aminosulfoxonium salt 6a-e and 13a-c, respectively, and a subsequent intramolecular nucleophilic substitution of the allylic aminosulfoxonium group afforded the enantio- and diastereomerically pure proline derivatives in medium to high yields.     

Syntheses, crystal structures, and electrochemical properties of multi-ferrocenyl resorcinarenes

Tetraaryl and tetraferrocenyl resorcinarenes 1a-1c have been synthesized by the HCl-catalyzed condensation of resorcinol with aromatic aldehydes or ferrocenecarbaldehyde, which were fully alkylated with ethyl α-chloroacetate to give the activated ethyl resorcinarylacetates 2a-2c. Reaction of 2a-2c with hydrated hydrazine yielded the resorcinarene acylhydrazine derivatives 3a-3c, from which the multi-ferrocenyl functional groups were selectively and efficiently introduced on the upper rim, or on the lower rim, or both on the upper and lower rims of resorcinarenes 4a-4c and calixarenes 4d-4f based upon the condensation reactions of acylhydrazones with ferrocenecarboxaldehyde.     

The first reductive cyclization by lithium aluminum hydride: stereospecific reductive cyclization of 1-(methoxycarbonylmethyl)imidazolidin-4-ones

The first LiAlH₄-driven reductive cyclization of the bifunctional 1-(methoxycarbonylmethyl)imidazolidin-4-ones, (−)-1a-c or(+)-1a-c, stereospecifically generated the corresponding 1,6-diaza-4-oxa-bicyclo[3.2.1]octanes, (−)-3a-c or(+)-3a-c, with a novel bicyclic system.     

Synthesis of γ-fluoro-α-amino acids by Claisen rearrangement

A series of N-protected glycine and alanine esters 4-7 of different fluorinated allylic alcohols 1 was prepared using the dicyclohexylcarbodiimide/dimethylaminopyridine method. All fluorinated esters of this type failed to react in an esterenolate Claisen rearrangement under the general conditions of the Kazmaier variant of this rearrangement. Change of the solvent from tetrahydrofuran to the less coordinating diethyl ether enabled the rearrangement of N-Boc-protected glycine esters 4a-c of 2-fluoroalken-3-ols 1a-c to form N-Boc-2-amino-4-fluoroalk-4-enecarboxylic acids 8a-c, while the rearrangement failed with N-Boc-alanine esters and all amino acid esters of 2-fluoroallylic alcohol (1e). This might be due to competing deprotonation of the position β to fluorine. Similarly to the esters 4a-c, the TFA-protected glycine esters 5a-c of 2-fluoroalken-3-ols 1a-c were rearranged. Deprotection of the Boc or the TFA group under salt-free conditions yielded the free amino acids 11a-c, which might be seen as mimics for N-alkylasparagines a group of lipoproteins.     

Synthesis of a new class of azathia crown macrocycles containing two 1,2,4-triazole or two 1,3,4-thiadiazole rings as subunits

A series of new 1,2/1,3-bis[o-(N-methylidenamino-5-aryl-3-thiol-4H-1,2,4-triazole-4-yl)phenoxy]alkane derivatives 3a-d and bis[o-(N-methylidenamino-2-thiol-1,3,4-thiadiazole-5-yl)phenoxy]alkanes 6a-c were prepared by condensation of 4-amino-5-(aroyl)-4H-1,2,4-triazole-3-thiols 2a-b or 2-amino-5-mercapto-1,3,4-thiadiazole with bis-aldehydes 1a-c. Further reaction of compounds 3a-d and 6a-c with dibromoalkanes afforded the new macrocycles 5a-f and 8a-d. The cyclization does not require high dilution techniques and provides the expected azathia macrocycles in good yields, ranging from 55% to 68%.     

Short-step syntheses and complexation properties of Z,Z-tribenzodidehydro- and all-Z-tribenzo[12]annulenes

Syntheses of all-Z-tribenzo[12]annulenes (1a-c) and Z,Z-tribenzodidehydro[12]annulenes (2a-c) by the reduction of the corresponding tribenzohexadehydro[12]annulenes 3a-c were carried out using a low valent titanium complex generated from Ti(O-i-Pr)₄ and i-PrMgCl. The unique structure of the first reduction products 2a-c as well as 1a-c was fully characterized. Complexation of these annulenes with silver(I) ions produces the corresponding silver complexes. Among them, the silver complexes of 2a-c exhibit interesting monomer-dimer equilibrium.     

Efficient synthesis of cephalotaxine- and deoxyharringtonine analogues by a trimethylaluminium-mediated domino reaction

The synthesis of cephalotaxine- and cephalotaxine amide analogues 14a-c and 16a-c as well as of the deoxyharringtonine analogues 5a,b was performed employing a trimethylaluminium-mediated domino reaction of 9a-c and 8 to give the spirocyclic compounds 7a-c, which was followed by a palladium catalyzed α-arylation.     

Synthesis of fluorine containing glycolurils and oxazolines from oxides of internal perfluoroolefins

The reaction of oxides of internal perfluoroolefins 1-3 with urea gave two kinds of novel fluorine containing N-heterocyclic compounds depending on the solvent nature: 1,5-bis(perfluoroalkyl)tetraazabicyclo[3.3.0]octane-3,7-diones 4a-c and 2-amino-5-fluoro-4,5-bis(perfluoroalkyl)-4,5-dihydrooxazol-4-ols 7a-d. Use of polar dimethylsulfoxide, N,N-dimethylacetamide and acetonitrile afforded glycolurils 4a-c in moderate yields. In dioxane, unexpected cyclization occurred resulting in oxazolines 7a-d in high yields. A similar reaction of oxiranes 2, 3 with urea in aqueous dioxane gave mixtures of 4,5-dihydroxy-4,5-bis(perfluoroalkyl)imidazolidine-2-ones 9b, c, glycolurils 4b, c and oxazolines 7b-d. The molecular structure of trans-isomers of oxazoline 7b and imidazolidine 9b has been established by X-ray crystallography.     

Synthesis of 2,2′-bipyridyl derivatives using aza Diels-Alder methodology

Amidrazone 1 and the tricarbonyl derivatives 2a-c gave the triazines 3a-c, respectively, which reacted with 2,5-norbornadiene 4 in boiling ethanol yielding the corresponding novel 2,2′-bipyridines 5a-c in good yield. Triazine 6 gave the 2,2′-bipyridyl derivative 7 (65%) with compound 4 in 1,2-dichlorobenzene at 140°C.     

A clay-mediated eco-friendly thiocyanation of indoles and carbazoles

Indoles 1a-f and carbazoles 3a-c on treatment with ammonium thiocyanate on montmorillonite K10 clay at 80°C furnished the corresponding 3-thiocyanato derivatives 2a-f and 4a-c in good to high yields. Skatole 5 furnished the dimeric oxindole 6, which resulted from autoxidation.     

Facile synthesis of 4-phenylquinolin-2(1H)-one derivatives from N-acyl-o-aminobenzophenones

An efficient synthesis of 4-phenylquinolin-2(1H)-one derivatives has been achieved in a one-pot reaction from N-acyl-o-aminobenzophenones 1a-c (a: acyl=acetyl; b: acyl=propanoyl; c: acyl=heptanoyl) using NaH as a base. Treatment of 1 with NaH provided the quinolones 2a-c with 62-83% yields, whereas the reaction in the presence of alkyl iodide (alkyl=methyl, ethyl, n-octyl) gave the corresponding N-alkylated quinolones 3a-g in 75-95% yields. The alkylation reaction of 4-phenylquinolin-2(1H)-one 2a with alkyl halide gave a mixture of N-alkylated and O-alkylated products. Comparison of IR and NMR data of the N-alkylated and O-alkylated compounds with those of 2a-c indicated that 2a-c exist as the lactam form.     

Rapid syntheses of (±)-pterocarpans and isoflavones via the gold-catalyzed annulation of aldehydes and alkynes

(±)-Pterocarpan and analogues (4a-c) have been synthesized efficiently via the annulation of salicylaldehydes (1a, 1b and 1c) and o-methoxymethoxylphenylacetylene (2a), followed by a one-pot reduction and acidic cyclization of the ketones (3a-c). In addition, isoflavone derivatives (5a-c) have been synthesized rapidly, in two steps, via the annulation of salicylaldehyde (1a) and arylacetylenes (2b, 2c and 2d), followed by IBX/DMSO oxidation of the isoflavanones (3d, 3e and 3f).     

Microwave-assisted manganese(III) acetate based oxidative cyclizations of alkenes with β-ketosulfones

The microwave-assisted synthesis of 5-(4-nitrophenyl)-2-phenyl-4-(phenylsulfonyl)-2,3-dihydrofuran (5a) was performed via manganese(III) acetate based oxidative cyclization of 1-(4-nitrophenyl)-2-(phenylsulfonyl)ethanone (3a) with vinylbenzene (4a). This new protocol was applied to four sulfone derivatives (3a-d), using vinylbenzene (4a) and diphenylethene (4b), affording a series of 2,3-dihydrofurans (5a-d, 6a-d) in moderate to good yields (26-55%). Similar methodology, applied on allylbenzene (4c), surprisingly, led to dehydronaphthalene derivatives (7a-d) in moderate yields. The unexpected mechanism and the role of allylbenzene (4c) are herein discussed.     

Investigation of hydrazine addition to functionalized furans: synthesis of new functionalized 4,4′-bipyrazole derivatives

The addition of hydrazine to functionalized furans 2a-d leads to a variety of 4,4′-bipyrazoles 4a-c depending on the structure of the starting materials. In one example, compound 2c was first converted to an intermediate, furo[3,4-d]pyridazine 3c which was then transformed into 4,4′-bipyrazole 4c on reacting with hydrazine.     

Synthesis and self-assembly of novel calix[4]arenocrowns: formation of calix[4]areno[2]catenanes

A series of novel calix[4]arenocrowns 1a-c were efficiently synthesized by a one-pot reaction of calix[4]monohydroquinone diacetate 5 with ditosylate 6 and its analogues in the presence of sodium hydroxide. It was found that the calix[4]arenocrowns could form stable pseudorotaxane-type complexes 2a-c with paraquat, and further self-assemble into calix[4]areno[2]catenanes 3a-c with dicationic salt 8 and p-bis(bromomethyl)benzene.     

Substituent-induced regioselective synthesis of 1,2-teraryls and pyrano[3,4-c]pyran-4,5-diones from 2H-pyran-2-ones

Substituent-controlled regioselective synthesis of highly functionalized 1,2-teraryls 3a-k has been achieved through ring transformation of 6-aryl-4-(pyrrolidin-1-yl/piperidin-1-yl)-2H-pyran-2-one-3-carbonitriles 1a-g by aryl acetones 2a-c in the presence of powdered KOH in DMF in very good yield. Under similar reaction conditions, 6-aryl-4-methylsulfanyl-2H-pyran-2-ones 5a-f afforded 1,7-diaryl-2-methyl-4H,5H-pyrano[3,4-c]pyran-4,5-diones 6a-j as major products and 3,4-diaryl-2-methyl-6-methylsulfanylbenzonitriles as minor constituents 7a-j.     

Synthesis and properties of 7,7-bis(heteroazulen-3-yl)-8,8-dicyano-1,4-quinodimethanes

The synthesis and properties of a novel type of 7,7-bis(heteroazulen-3-yl)-8,8-dicyano-1,4-quinodimethanes (9a-c) are studied. The synthetic method is based on a TFA-catalyzed electrophilic aromatic substitution on the heteroazulenes with 4-(dicyanomethyl)benzaldehyde to afford the corresponding methane derivatives, followed by oxidative hydrogen abstraction with DDQ. The polarization of 9a-c is evaluated by the inspection of their ¹³C NMR and IR spectra. Based on the investigation of the UV-Vis spectra of 9a-c and protonated cations 10a-c, conformational changes of the heteroazulene-moiety and (dicyanomethyl)phenyl group are suggested. In the CV measurements of 9a-c, two reversible reduction waves are observed, indicating the stabilizing ability of heteroazulenes toward the corresponding radical and anion species. Furthermore, 9a-c exhibit two irreversible oxidation waves, which suggest a conformational change in the radical cation during the redox process. The conformational change is rationalized on the basis of the MO calculations.     

Carbonyl complexes of manganese, rhenium and molybdenum with 2-pyridylimino acid ligands

[MBr(CO)₃{κ²(N,O)-pyca}] [M = Mn(1a), Re(1b), pyca = pyridine-2-carboxaldehyde] and [MoCl(η³-C₃H₄Me-2)(CO)₂{κ²(N,O)-pyca}] (1c) react with aminoacid β-alanine to give the corresponding iminopyridine complexes 2a-2c. The same method affords the iminopyridine derivatives from γ-aminobutyric acid (GABA) (3a-3c) and 3-aminobenzoic acid (4a-4c). For complexes 2a-2c, 3a, 3c and 4a, the solid state structures have been determined by X-ray crystallography, revealing interesting differences in their hydrogen-bonding patterns in solid state.     

Synthesis and properties of 5-[bis(1-heteroazulen-3-yl)methylidene]pyrimidine-2,4,6(1,3,5H)-triones

The synthesis and properties of a novel type of 5-[bis(1-heteroazulen-3-yl)methylidene]pyrimidine-2,4,6(1,3,5H)-triones (13a-c) and (14a-c) are studied. The synthetic procedure is based on addition of bis(1-heteroazulen-3-yl)methyl cations with barbituric acid and subsequent oxidation by o-chloranil. Structural characteristics of 13a-c and 14a-c were clarified on inspection of the ¹³C NMR spectral data and X-ray crystal analysis. Based on the investigation of the UV-vis spectra of 13a-c and 14a-c and their protonated cations, conformational change of the heteroazulene-moiety and the barbituric acid-moiety is suggested. In the CV measurements of 13a-c and 14a-c, two reversible reduction waves are observed, indicating the stabilizing ability of heteroazulenes toward the corresponding radical and anion species. Furthermore, 13a-c and 14a-c exhibit one irreversible oxidation wave and the corresponding reduction wave appearing in a far negative region, which suggested a conformational change in the radical cation during the redox process. The conformational change is rationalized on the basis of the MO calculations.