One-pot synthesis of hydrazine derivatives from aldehydes via radical addition reactions

A one-pot procedure for the synthesis of hydrazine derivatives from aldehydes via radical addition reactions was developed. Lewis acids promoted both the condensation between aldehydes and benzhydrazide, and the alkyl radical addition to the Cdbnd?N bond of hydrazones, affording moderate-to-high yields of hydrazine derivatives. The present process provides a tin-free radical, sustainable, and eco-friendly synthetic method.     

Microwave-assisted synthesis of 4,4′-diaminotriphenylmethanes

A fast, efficient and versatile route of synthesis of 4,4′-diaminotriphenylmethanes under microwave irradiation, suitable for parallel library syntheses were developed.     

Nucleophile-assisted Pt-catalyzed cyclization of enynones: an access to synthesis of highly substituted furans

A new and efficient Pt-catalyzed hydroxy- or alkoxy cyclization of 2-(1-alkynyl)-2-alkene-1-ones offers a general synthetic pathway to a wide range of highly substituted furans in good to excellent yields.     

Diastereoselective addition of dimethyl phosphite to 3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene-2-carboxaldehyde

Addition of dimethyl phosphite to racemic 3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene-2-carboxaldehyde gives almost exclusively one diastereomer of the corresponding α-hydroxyphosphonate (d.r. ?96:4). Its absolute configuration (S, R_p)-(R, S_p) was established by X-ray diffraction.     

5′-Noraristeromycin derivatives isomeric to aristeromycin and 2′-deoxyaristeromycin

A straightforward synthesis of (1S,2R,3R,4R)-4-(6-aminopurin-9-yl)-2-hydroxymethylcyclopentane-1,3-diol (2), an isomer of aristeromycin, and its 2′-deoxy derivative 3 from readily available disubstituted cyclopentenes is presented. An antiviral analysis of 2 showed it to have significant activity versus Epstein-Barr virus (IC₅₀ 0.62 μg/mL in the Elisa assay) and to be free of cytotoxicity effects against the host cells. In a much less comprehensive antiviral analysis, 3 also was active towards Epstein-Barr (IC₅₀ 7.58 μg/mL in the Elisa assay) but this was accompanied by cellular toxicity.     

Convenient synthesis of functionalized 4,4′-disubstituted-2,2′-bipyridine with extended π-system for dye-sensitized solar cell applications

Exploration of new ruthenium-based sensitizers for dye-sensitized solar cell (DSC) applications requires an easy access to multifunctionalized ligands for efficient screening of sensitizers’ properties. Based on the Horner-Emmons-Wadsworth reaction, a convenient synthetic route for the extension of the π-system on 4,4′-disubstituted-2,2′-bipyridines was used to develop a novel series of functionalized 2,2′-bipyridine ligands with either electron-withdrawing or donating end-capping group. ¹H NMR spectroscopy revealed that all the new bipyridyl ligands were obtained exclusively in their fully E isomers.     

Efficient synthesis of functionalized furans via ruthenium-catalyzed cyclization of epoxyalkyne derivatives

Ruthenium catalyst TpRuPPh(3)(CH(3)CN)(2)Cl is found to effect the cyclization of epoxyalkynes to furans in the presence of Et(3)N. The reactions worked well for various epoxyalkynes with suitable oxygen and nitrogen functionalities with low loading of catalyst. It failed with disubstituted epoxyalkynes. The mechanism was elucidated by a deuterium labeling experiment that suggested that the mechanism involved a ruthenium-vinylidenium intermediate.     

An efficient synthesis of 4,4′,5,5′-tetraiododibenzo-24-crown-8 and its highly conjugated derivatives

4,4′,5,5′-Tetraiododibenzo-24-crown-8 (9), a practical building block, was prepared under efficient and mild reaction conditions starting from the simple starting material, catechol (1). Highly conjugated 4,4′,5,5′-tetraethynyldibenzo-24-crown-8 (10a,b) were prepared via a Sonogashira coupling reaction from tetraiodocrown ether 9. These highly conjugated crown ethers form complexes in CD₂Cl₂ with dibenzylammonium hexafluorophosphate in a 1:1 ratio. Emission spectrum of pseudorotaxane 11 shows a dramatic shift from the non-complexed precursor.     

Improved synthesis of 4,4′-diamino-2,2′-bipyridine from 4,4′-dinitro-2,2′-bipyridine-N,N′-dioxide

A superior synthetic route to 4,4′-diamino-2,2′-bipyridine has been developed. This procedure compares favorably with existing methods, producing 4 times the yield previously reported. In addition, mild reaction conditions are utilized, allowing a considerably more efficient production, and subsequent purification, of the diamino complex.     

Synthesis of densely functionalized cispentacin derivatives through selective aziridination and aziridine opening reactions: orthogonally protected di- and triaminocyclopentanecarboxylates

A novel substrate-directed synthetic route to a series of highly functionalized, orthogonally protected di- or triaminocyclopentanecarboxylate derivatives with multiple chiral centres from an unsaturated bicyclic β-lactam has been accomplished by applying stereoselective ring C–C double bond aziridination with chloramine-T and phenyltrimethylammonium tribromide, followed by regioselective aziridine opening with different N,O nucleophiles and hydrides. The functionalization strategy was successfully extended for access to enantiomerically pure orthogonally protected triaminocarboxylates.     

Synthesis of annelated pyranosides: a rapid and efficient entry to highly functionalized optically pure branched-pyrazoles

Pyrazolo-pyranosides prepared from methyl-2,3:4,6-di-O-benzylidene-α-d-mannopyranoside were functionalized to design new scaffolds suitable for peptidomimetic construction. Under certain acidic conditions, they undergo only pyranose ring-opening generating highly functionalized optically pure pyrazoles bearing an aldehyde function.     

One pot four-component reaction for the efficient synthesis of spiro[indoline-3,4′-pyrano[2,3-c]pyrazole]-3′-carboxylate derivatives

A novel one pot protocol has been developed to synthesize various spiro[indoline-3,4′-pyrano[2,3-c]pyrazole]-3′-carboxylate derivatives from the four-component reaction of isatin, malononitrile, hydrazine derivatives and dialkyl acetylenedicarboxylates. In this process two C–C bonds, two C–N bonds and one C–O bond have formed in one pot. The notable features of this protocol are simple and environmentally benign reaction condition, easy isolation of products, applicable to a wide range of readily available starting materials and good yields.     

Structure and isomerization in 4,4′-biimidazoles: a comparison of crystal structures and theoretical calculations of 2,2′-dimethyl-4,4′-biimidazole and 2,2′-dimethyl-4,4′-biimidazolium bis-trifluoroactate

The crystal structures of the compounds 2,2′-dimethyl-4,4′-biimidazole dihydrate (1) and 2,2′-dimethyl-4,4′-biimidazolium bistrifluoroacetate (2) have been determined. Compound 1 is linked into a three dimensional network via hydrogen bonding between the imidazole nitrogens and the water molecules, while compound 2 forms sheets through hydrogen bonding between the acetate and imidazolium ions. Theoretical calculations for 1 show that the particular prototropic tautomer observed in the crystal structure is not the lowest energy isomer. This observation is justified in terms of hydrogen bonding to the lattice water molecules.     

Dichlorocarbene adducts of alkyl enol ethers as precursors to furans: application to a total synthesis of the furanosesquiterpene (±)-pallescensin A

A novel method for annulating furans to ketones, involving treatment of the dichlorocarbene adduct of the derived methyl enol ether with base, has been exploited in the synthesis of the title natural product 1 from the known trans-decalone 2.     

Improved synthesis of 2,2′-dimethoxy-1,1′-binaphthyl-3,3′-diacetic acid derivatives

During the past decade, the chemistry of BINAP, BINAM, and BINOL derivatives experienced an important development due to multiple applications in catalysis, metallo-supramolecular chemistry and material science. Consequently, the need to develop functionalized binaphthyl derivatives became crucial. In this context, we were interested in preparing 2,2′-dimethoxy-1,1′-binaphthyl-3,3′-diacetic acid species. The latter were efficiently prepared using a modified Arndt-Eistert reaction that afforded the expected chiral diacid in good yield. Compared to the method we described earlier, this new strategy allows the preparation of the target homologated diacid chloride in a very efficient manner, limiting wastes and tedious column chromatographies.     

Sodium borohydride or potassium carbonate-mediated intramolecular Michael addition: a general method for the synthesis of fused dihydrofuran and furan derivatives

A simple and convenient method for the synthesis of fused dihydrofuran derivatives using NaBH₄-mediated reductive cyclization and fused furan derivatives by K₂CO₃-mediated intramolecular Michael addition followed by acid-catalyzed methanol elimination has been developed.     

5′-Noraristeromycin possessing a C-1′ cyclopentyl double bond: a new carbanucleoside structural prototype

Prior to this work only two examples of carbanucleosides possessing a C-1′/C-6′ double bond had been reported and they were minor derivatized side products arising during other targeted syntheses. To develop this structural feature into a new class of potential antiviral agents, the 5′-nor derivative of aristeromycin with such an olefinic structure (6) represents the first example. In this regard, treatment of (1′S,2′S,3′S,4′R,5′S)-6-chloro-9-(2′,3′-isopropylidenedioxy-6′-oxabicyclo[3.1.0]hex-4′-yl)purine (7) with sodium methoxide yielded 6 via an E′₂-like elimination pathway. A convenient way to the C-4′ epimer of 6 (that is, 17) also arose during these studies and is described. Antiviral analysis of 6 and 17 failed to produce any significant activity.     

A convenient synthesis of 2,2′-bipyridine derivatives

Picolinates 7 were prepared from the corresponding α-chloro-β-keto-esters 6. Esters 7 were converted into 2,2′-bipyridine derivatives 10 via triazines 9 using an aza Diels-Alder reaction.     

An efficient synthesis of chiral terminal 1,2-diamines using an enantiomerically pure [1-(1′R)-methylbenzyl]aziridine-2-yl]methanol

Enantiomerically pure terminal 1,2-diamines, which can serve as precursors for the synthesis of many biologically important compounds, were synthesized efficiently from a commercially available chiral [1-(1′R)-methylbenzyl]aziridine-2-yl]methanol. Various enantiomerically pure 2-vinylaziridines were prepared by Wittig reactions from aziridine-2-carboxaldehyde and the corresponding phosphonium salts. The C(2)-N bond of the vinyl substituted aziridine ring was regioselectively cleaved by azidotrimethylsilane (TMSN₃). The azido group and the double bond were reduced successively to give the target compounds in high yields.     

Syntheses and properties of complexes with bis(2,2′-bipyridyl)ruthenium(II) moieties coordinated to 4,4′:2′,2′′:4′′,4′′′-quaterpyridinium ligands

Eleven new complexes of the form cis-[Ru^II(bpy)₂(L^A)]⁴⁺ (bpy = 2,2′-bipyridyl; L^A = a pyridinium-substituted bpy derivative) have been prepared and isolated as their PF₆⁻ salts. Characterisation involved various techniques including ¹H NMR spectroscopy and MALDI mass spectrometry. The UV-Vis spectra show intense intraligand π → π^∗ absorptions and metal-to-ligand charge-transfer (MLCT) bands with two distinct maxima in the visible region. Small shifts in the MLCT bands correlate with the electron-withdrawing strength of the ligand L^A. Cyclic voltammograms show quasi-reversible or reversible Ru^III/II oxidation waves, and two or more ligand-based reductions with varying degrees of reversibility. The variations in the redox potentials correlate with changes in the structure of L^A, and also with the MLCT energies. Differential pulse voltammetry allows the first reduction process for two of the complex salts to be resolved into two peaks. Single-crystal X-ray structures have been solved for three of the new complex salts and also for a pro-ligand salt. Two carboxylate-functionalised compounds have been tested as photosensitizers on TiO₂-coated electrodes, but show only negligible efficiencies, in accord with expectations.