C-Nucleosides. 8. Synthesis of 5-hydroxy-2-(β-D-ribofuranosyl)pyridine

The synthesis of 5-hydroxy-2-(β-D-ribofuranosyl)pyridine ( 12 ) from 2-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)furan ( 1 ) is described. Treatment of 1 with α-methoxycarbamate in the presence of p-toluenesulfonic acid in benzene at reflux temperature afforded furfurylcarbamate ( 2 ) and its α-isomer in a 5/1 ratio. The anomerization was circumvented by treatment of 1 with α-methoxycarbamate in the presence of boron trifluoride in benzene at room temperature. Compound 2 was electrochemically oxidized to give dihydrofuran 4 . However, conversion of 4 into 11 was unsuccessful. Treatment of azide 8 with bromine and methanol afforded 9 . Reduction of 9 with zinc powder gave dihydrofurfurylamine 10 , in 80% yield. Treatment of this with concentrated hydrochloric acid in methanol yielded 11 , which on deblocking with 5% sodium hydroxide aqueous solution gave 12.     

Copper(I)- and Copper(II)-catalyzed Diels-Alder Additions of α-Substituted Acrylonitrile to Furan. The Synthesis of 7-Oxa-bicyclo[2.2.1]hept-5-en-2-one

The difficult Diels-Alder additions of α-acetoxy- and α-chloroacrylonitrile to furan can be run at 20–35° and atmospheric pressure in the presence of CuCl. Cu(BF₄) · 6 H₂O, Cu(OOCCH₃)₂ · H₂O or cupric tartrate · 3H₂O. Under kinetic control, the exo-carbonitrile adducts 2 and 8 , respectively, are favoured. Saponification of the 2endo-acetoxy-7-oxabicyclo[2.2.1]hept-5-ene-2exo-carbonitrile ( 2 ) furnished the 7-oxabicyclo[2.2.1]hept-5-en-2-one ( 4 ). Basic hydrolysis of the adducts ( 8 + 9 ) of α-chloroacrylonitrile to furan and its 5exo, 6exo-isopropylidenedioxy derivatives did not give the corresponding ketones, the carboxamides 14 + 15 and 16 + 17 , respectively, were isolated.     

Synthesis of haloconduritols from an endo-cycloadduct of furan and vinylene carbonate

A method for preparing haloconduritols having a conduritol-A construction is described. A mixture of endo- and exo-cycloadduct derivatives prepared from the Diels-Alder reaction of furan and vinylene carbonate was converted into diacetate derivatives by hydrolysis (K₂CO₃/MeOH) followed by acetylation (Ac₂O/pyridine). Boron trihalide (BBr₃ or BCl₃)-assisted ring-opening of the endo-diacetate in CH₂Cl₂ at −78°C gave (1α,2α,3β,6β)-6-halogeno-4-cyclohexene-1,2,3-triol 1,2-diacetate from which the corresponding triacetate was prepared by acetylation (AcCl). trans-Esterification of the triacetate (MeOH/HCl) afforded (1α,2α,3β,6β)-6-halogeno-4-cyclohexene-1,2,3-triol (X=Br or Cl). BF₃-Assisted ring-opening of the endo-diacetate in CH₂Cl₂ gave (1α,2α,3β,6β)-6-chloro-4-cyclohexene-1,2,3-triol 1,2-diacetate by means of halogen exchange.     

Side‐chain conformations in the isomorphous polyfluorinated {4,4′‐bis[(2,2‐difluoroethoxy)methyl]‐2,2′‐bipyridine‐κ2N,N′}dichloridopalladium and ‐platinum complexes

The polyfluorinated title compounds, [M Cl₂(C₁₆H₁₆F₄N₂O₂)] or [4,4′‐(HCF₂CH₂OCH₂)₂‐2,2′‐bpy]M Cl₂ [M = Pd, ( 1 ), and M = Pt, ( 2 )], have –C(H_α)₂OC(H_β)₂CF₂H side chains with H‐atom donors at the α and β sites. The structures of ( 1 ) and ( 2 ) are isomorphous, with the nearly planar (bpy)M Cl₂ molecules stacked in columns. Within one column, π‐dimer pairs alternate between a π‐dimer pair reinforced with C—H…Cl hydrogen bonds (α,α) and a π‐dimer pair reinforced with C—H_β…F(—C) interactions (abbreviated as C—H_β…F—C,C—H_β…F—C). The compounds [4,4′‐(CF₃CH₂OCH₂)₂‐2,2′‐bpy]M Cl₂ [M = Pd, ( 3 ), and M = Pt, ( 4 )] have been reported to be isomorphous [Lu et al. (2012). J. Fluorine Chem. 137 , 54–56], yet with disorder in the fluorous regions. The molecules of ( 3 ) [or ( 4 )] also form similar stacks, but with alternating π‐dimer pairs between the (α,β; α,β) and (β,β) forms. Through (C—)H…Cl hydrogen‐bond interactions, one molecule of ( 1 ) [or ( 2 )] is expanded into an aggregate of two inversion‐related π‐dimer pairs, one pair in the (α,α) form and the other pair in the (C—H_β…F—C,C—H_β…F—C) form, with the plane normals making an interplanar angle of 58.24 (3)°. Due to the demands of maintaining a high coordination number around the metal‐bound Cl atoms in molecule ( 1 ) [or ( 2 )], the ponytails of molecule ( 1 ) [or ( 2 )] bend outward; in contrast, the ponytails of molecule ( 3 ) [or ( 4 )] bend inward.     

Selective carbometallation of α,β-unsaturated carbonyl compounds and substituted oxacyclopropanes with zirconium-diene complexes

The reactions of zirconium-dience complexes, ZrCp₂(s-cis-diene), with bifunctional electrophiles, i.e. α,β-unsaturated ketones, unsaturated esters and substituted oxacyclopropanes, were investigated. Reaction of ZrCp₂(s-cis-isoprene) with an equivalent of 3-buten-2-one or alkyl acrylates, selectively gives 1,2-addition products. CC bond formation occured at the C(1) atom of the isoprene moiety whereas 1,3-pentadiene-, 2-methyl-1,3-pentadiene- and 2,4-dimethyl-1,3-pentadiene complexes induced the regioselective 1,2-addition at the C(4) position of the diene moiety. Phenyloxacyclopropane and 2-methyl-3-phenyl-oxacyclopropane also react with ZrCp₂(isoprene) leading to CC bond formation from the C(1) atom of isoprene to the oxirane carbon bearing the phenyl group. The corresponding reactions of 2-methyl-2-butene-1,4-diylmagnesium with α,β-unsaturated carbonyl compounds were also studied and found to give quite different products.     

An efficient reagent for synthesis of α,β-unsaturated aldehydes 3-methylthio-2-propenyl p-tolyl sulfone

Alkylation of 3-methylthio-2-propenyl p-tolyl sulfone (1) with an alkyl halide and a base (NaH or KOH-TOMAC) took place at the position α to the sulfonyl group to give optionally a mono- or dialkylated product (2 or 3), which was converted to β-monosubstituted or β,β-disubstituted α,β-unsaturated aldehyde (6 or 7), respectively, by TiCl₄-assisted hydrolysis followed by the removal of p-toluenesulfinic acid.     

Facile Fabrication of Porous Bi2O3 Microspheres by Thermal Treatment of Bi2O2CO3 Microspheres and its Photocatalysis Properties

β- and α-phase porous Bi₂O₃ microspheres with an average size of around 4 μm had been synthesized by thermal treatment of Bi₂O₂CO₃ microspheres at 350 and 400–500 °C respectively in an air atmosphere. The Bi₂O₂CO₃ microspheres had been synthesized at a temperature of 180 °C by a hydrothermal process using Bi(NO₃)₃ as the bismuth source with the assist of citric acid. By combining the results of X-ray powder diffraction, transmission electron microscope, scanning electron microscopy, and UV–Visible absorption spectra, the structural, morphological and optical properties characterization of the products were performed. The photocatalytic activity of the as-prepared α- and β-phase porous Bi₂O₃ microspheres have been tested by degradation of methylene orange under visible light, indicating that porous β-Bi₂O₃ microspheres showed enhanced photocatalytic performance compared to P25 and α-Bi₂O₃ microspheres.     

Nucleophilic addition of 2-(trimethylsilyloxy)furan to a d-glucopyranose oxocarbenium ion

Cp₂Zr(ClO₄)₂ was used as a promoter for nucleophilic addition of 2-(trimethylsilyloxy) furan (TMSOF) to 2,3,4,6-tetra-O-benzyl-d-glucopyranosyl fluoride to give a 2:1:1 mixture of adducts in 80% yield. NMR data and postulated transition states are consistent with a 3:1 ratio of regioisomers at C-5 and C-3 of TMSOF and a 2:1 ratio of threo and erythro α-adducts at C-5.     

β-Peptides: Synthesis by Arndt-Eistert homologation with concomitant peptide coupling. Structure determination by NMR and CD spectroscopy and by X-ray crystallography. Helical secondary structure of a β-hexapeptide in solution and its stability towards pepsin

The β-hexapeptide (H-β-HVal-β-HAla-β-HLeu)₂-OH ( 2 ) was prepared from the component L -β-amino acids by conventional peptide synthesis, including fragment coupling. A cyclo-β-tri- and a cyclo-β-hexapeptide were also prepared. The β-amino acids were obtained from α-amino acids by Arndt-Eistert homologation. All reactions leading to the β-peptides occur smoothly and in high yields. The β-peptides were characterized by their CD and NMR spectra (COSY, ROESY, TOCSY, and NOE-restricted modelling), and by an X-ray crystal-structure analysis. β-Sheet-type structures (in the solid state) and a compact, left-handed or (M) 3₁ helix of 5-Å pitch (in solution) were discovered. Comparison with the analogous secondary structures of α-peptides shows fundamental differences, the most surprising one at this point being the greater stability of β-peptide helices. There are structural relationships of β-peptides with oligomers of β-hydroxyalkanoic acids, and dissimilarities between the two classes of compounds are a demonstration of the power of H-bonding. The β-hexapeptide 2 is stable to cleavage by pepsin at pH 2 in H₂O for at least 60 h at 37°, while the corresponding α-peptide H-(Val-Ala-Leu)₂-OH is cleaved instantaneously under these conditions. The implication of the described results are discussed.     

Reaction of [HO(CH2)3]3P with α,β-Unsaturated Ketones Containing a Phenylpropanoid Backbone

Abstract

Interaction of 3,4-(MeO)₂-benzylideneacetone with [HO(CH₂)₃]₃P (THPP) was studied in CD₃OD by NMR to compare reactivity of a phenylpropanoid α,β-unsaturated ketone with a corresponding α,β-unsaturated aldehyde. In the presence of HCl, both the ketone and a related cinnamaldehyde first establish an equilibrium with the product formed by nucleophilic attack of the THPP at the C?O bond, [ArCH?CHCX(OD)PR₃]⁺Cl^?(X?H or CH₃, Ar?Ph or 3,4-(MeO)₂C₆H₃). The ketone salt then slowly transforms into [R₃PCH(Ar)CH(D)C(O)CD₃]⁺Cl^?, the phosphonium product of nucleophilic attack of THPP at the C?C bond, whereas the final product from the aldehyde is the (α-ether)phosphonium chloride [ArCH?CHCH(OCD₃)PR₃]⁺Cl^?. In aqueous media, in the absence of HCl, 4-HO-benzylideneacetone, which is similar to a lignin-type, α,β-unsaturated aldehyde model compound, interacts with THPP to afford a stable phosphonium zwitterion, in contrast to the previously studied aldehyde model, which forms dimeric, bisphosphonium products.     

Probing the Helical Secondary Structure of Short-Chain β-Peptides

Structural prerequisites for the stability of the 3₁ helix of β-peptides can be defined from inspection of models (Figs. 1 and 2): lateral non-H-substituents in 2- and 3-position on the 3-amino-acid residues of the helix are allowed, axial ones are forbidden. To be able to test this prediction, we synthesized a series of heptapeptide derivatives Boc-(β-HVal-β-HAla-β-HLeu-Xaa-β-HVal-β-HAla-β-HLeu)-OMe 13–22 (Xaa = α- or β-amino-acid residue) and a β-depsipeptide 25 with a central (S)-3-hydroxybutanoic-acid residue (Xaa = –OCH(Me)CH₂C(O)–) (Schemes 1 3). Detailed NMR analysis (DQF-COSY, HSQC, HMBC, ROESY, and TOCSY experiments) in methanol solution of the β-hexapeptide H(-β-HVal-β-HAla-β-HLeu)₂-OH ( 1 ) and of the β-heptapeptide H-β-HVal-β-HAla-β-HLeu-(S,S)-β-HAla(αMe)-β-HVal-β-HAla- β-HLeu-OH ( 22 ), with a central (2S,3S)-3-amino-2-methylbutanoic-acid residue, confirm the helical structure of such β-peptides (previously discovered in pyridine solution) (Fig.3 and Tables 1–5). The CD spectra of helical β-peptides, the residues of which were prepared by (retentive) Arndt-Eistert homologation of the (S)- or L -α-amino acids, show a trough at 215 nm. Thus, this characteristic pattern of the CD spectra was taken as an indicator for the presence of a helix in methanol solutions of compounds 13–22 and 25 (including partially and fully deprotected forms) (Figs.4–6). The results fully confirm predicted structural effects: incorporation of a single ‘wrong’ residue ((R)-β-HAla, β-HAib, (R,S)-β-HAla(α Me), or N-Me-β-HAla) in the central position of the β-heptapeptide derivatives A (see 17, 18, 20 , or 21 , resp.) causes the CD minimum to disappear. Also, the β-heptadepsipetide 25 (missing H-bond) and the β-heptapeptide analogs with a single α-amino-acid moiety in the middle ( 13 and 14 ) are not helical, according to this analysis. An interesting case is the heptapeptide 15 with the central achiral, unsubstituted 3-aminopropanoic-acid moiety: helical conformation appears to depend upon the presence or absence of terminal protection and upon the solvent (MeOH vs. MeOH/H₂O).     

Reaction between Furan‐ or Thiophene‐2‐carbonyl Chloride,Isocyanides, and Dialkyl Acetylenedicarboxy­lates: Multicomponent Synthesis of 2,2′‐Bifurans and 2‐(Thiophen‐2‐yl)furans

An efficient multi‐component synthesis of highly functionalized 2,2′‐bifurans and 2‐(thiophen‐2‐yl)furans is described. A mixture of furan‐ or thiophene‐2‐carbonyl chloride, an isocyanide, and a dialkyl acetylenedicarboxylate undergoes a smooth addition reaction in dry CH₂Cl₂ at ambient temperature to produce 2‐amino‐5‐(4‐chlorofuran‐2‐yl)furan‐3,4‐dicarboxylates and 2‐amino‐5‐(4‐chlorothiophen‐2‐yl)furan‐3,4‐dicarboxylates. A single‐crystal X‐ray‐analysis of a derivative conclusively confirms the structure of these 2,2′‐bifurans and 2‐(thiophen‐2‐yl)furans. A novel electrophilic aromatic substitution reaction can justify the formation of the Cl‐substituted furan or thiophene rings.     

Hydrodeoxygenation of Furfural over Unsupported,SiO2-supported or Metal-promoted Mo Carbides: Tunning the Selectivity between 2-Methylfuran and C10 Furoins Diesel Precursors

The hydrodeoxygenation of furfural (FF) over Mo carbides in liquid phase at 200 °C, 30 bar of H₂ for 4 h in 2-butanol was investigated. Unsupported and SiO₂-supported Mo carbide with different crystallographic phases (β-Mo₂C/SiO₂ and α-MoC/SiO₂), and in the presence of Cu and Ni as promoters were studied. The reactivation treatment under H₂ atmosphere of the passivated Mo carbides was investigated by XAS. The results show that Mo is present in different states of oxidation in the passivated catalysts, with more severe oxidation in the bimetallic systems, in which the original carbides are not restored after reactivation. Finally, the product distribution in the HDO of furfural is modified as a function of catalyst oxidation degree. Using the less oxidized Mo carbide (β-Mo₂C), a higher yield to 2-methylfuran is obtained, while C₁₀ condensation products are formed for the more oxidized catalysts.     

Reaction of 2-acyl-3-aminobenzofurans with hydrazines

While 2-acetyl and 2-benzoyl-3-aminobenzofurans did not react with hydrazine, monomethyl- and N,N-dimethylhydrazine to give the related hydrazones, their 3-N-(p-toluenesulfonyl) derivatives afforded them smoothly in good yields. Depending upon reaction conditions, products arising from hydrazone cyclization to benzofuropyrazoles and/or from furan ring cleavage at the C2 O bond to give 5-(2-hydroxyphenyl)pyrazoles were also formed. The formation of these products depends upon hydrazones configuration and is discussed. Only (E)-isomers appear to undergo furan ring opening. In acidic media at room temprature either the hydrazones or the monomethylhydrazones gave the same related α-azines. Microanalyses, ir, uv, ¹H-nmr and ms spectra are in agreement with the proposed structures.     

Zirconium borohydride piperazine complex, an efficient, air and thermally stable reducing agent

A zirconium borohydride piperazine complex (Ppyz)Zr(BH₄)₂Cl₂, obtained by the reaction of an ethereal solution of ZrCl₄ and LiBH₄ with piperazine is a stable, selective and efficient reducing agent. (Ppyz)Zr(BH₄)₂Cl₂ reduces aldehydes, ketones, silylethers, α,β-unsaturated carbonyl compounds and esters. The reactions were performed in diethyl ether at room temperature or under reflux, and the yields of the corresponding alcohols were excellent. The selective reduction of aldehydes in the presence of ketones and complete regioselectivity in the reduction of α,β-unsaturated carbonyl groups were observed.     

Copper(I) iodide dimethyl sulfide catalyzed 1,4-addition of alkenyl groups from alkenyl-alkylzincate reagents

The presence of catalytic quantities of the copper(I) iodide dimethyl sulfide complex {(CuI)₄(SMe₂)₃} with alkenyl-alkylzincate reagents allows for the complete chemoselective 1,4-addition of various alkenyl groups to a number of α,β-unsaturated carbonyl compounds in CH₂Cl₂ at +35 °C. The 1,4-addition of the mixed vinylzincate reagent is more efficient than the corresponding vinylzirconocene reagent in CH₂Cl₂ or THF. By employing CH₂Cl₂ as a medium, the asymmetric copper-catalyzed addition of the vinyl groups to α,β-unsaturated imides is facilitated by the presence of TMSOTf to give excellent yields and up to 95:5 diastereomeric ratios (dr).     

Access to the noryohimban [6,5,6,5,6] ring system via an intramolecular furan Diels-Alder reaction

Polycyclic indolic compounds containing the [6,5,6,5,6] ring system were prepared via an intramolecular furan Diels-Alder reaction of α,β-unsaturated amides generated by the N-acylation of 1-(2-furyl)-β-tetrahydrocarbolines. This chemistry can provide access to D(14)-noryohimban derivatives by exploiting the functionality on the C,D,E ring system of the corresponding cycloadducts.     

Tordanone,un stéroïde replié avec une jonction de cycle A/B β-cis (5β) et B/C α-cis(8α)

Tordanone, a Twice Bent Steroid Structure with Ring A/B β-cis(5β)- and Ring B/C α-cis(8α)-Fused The 3β, 14α, 25-trihydroxy-5β, 8α-cholestan-6-one ( = tordanone; 4 ) has been prepared by stereospecific hydrogenation of 3β, 14α, 25-trihydroxy-5β-cholesta-7,22ξ-dien-6-one ( 5 ). This is the first stereospecific synthesis of a B/C cis-fused steroid belonging to the 5β, 8α -cholestane group with a H-atom at positions 5β (A/B cis-fused) and 8α. The resulting twice bent structure shows a particularly strong steric hindrance of the β-face where CH₃(18) at the C/D ring junction and H_β? C(7) of the B ring are very close to each other. Structural features and mechanistic aspects of the hydrogenation are discussed.     

4,5‐Bis(furoylsulfanyl)‐1,3‐dithiole‐2‐thione

The title compound, C₁₃H₆O₄S₅, possesses crystallographically imposed mirror symmetry, with the atoms of the C=S group lying on the mirror plane. It is an example of the general formula [RCO]₂(dmit), where R is a furan ring and dmit is 2‐thioxo‐1,3‐dithiole‐4,5‐dithiol­ate. The components exhibit some polarization of their mol­ecular–electronic structure. The dmit and furan moieties exhibit a high degree of conjugation, as the introduction of C=O connecting the conjugated furan (donor) and dmit (acceptor) rings forms a good conjugated system with high delocalization. A polar three‐dimensional framework is built from a combination of inter­molecular contacts, namely S⋯S inter­actions and C—H⋯O hydrogen bonding. The structural characteristics lead to good second‐order non‐linear optical properties.     

Controlled Synthesis of Functionalized Mixed Thiophene/Furan Oligomers

A novel and simple synthetic route for the preparation of a series of functionalized mixed thiophene/furan oligomers is described. This method, involving a Mn(OAc)₃‐mediated oxidative addition of β‐thienyl‐β‐keto esters (=β‐oxothiophenepropanoates) to methyl 3‐thienylprop‐2‐enoates, allows the construction of highly functionalized heteropolyaromatic oligomers possessing various chain lengths (Schemes 2, 4, and 5). Moreover, the straightforward transformation of the carbonyl functions appended to the furan rings leads to polycarboxylic acid precursors of H₂O‐soluble conducting polymers (Scheme 6).