Stereoselective synthesis of alpha- and beta-glycosylamide derivatives from glycopyranosyl azides via isoxazoline intermediates

Treatment of 2-acetoxy glycopyranosyl azides with Ph3P gave isoxazolines by ring closure of the phosphorimine. Coupling of in situ generated isoxazolines with acylating reagents gave mixtures of alpha- or beta-glycopyranosyl amides. The alpha/beta ratio depended upon the acylating reagent and metal salts employed. For example, coupling of isoxazoline 3 with Z-Asp-(SPy)-OBn in the presence of CuCl2 gave exclusively alpha-N-glucopyranosylasparagine derivative 8. This general procedure has been applied to mono-, di-, and trisaccharide systems.     

Mass spectrometric studies of anomeric glycopyranosyl azides

We studied the mass spectrometric behaviour of peracetylated and underivatized anomeric hexopyranosyl azides and 5-thioglucopyranosyl azides by means of different mass spectrometric techniques. The unstable molecular ions fragment predominantly by losing either N3 radical or N2 molecule. Loss of N2 molecule and the protonation of the derived nitrene were characteristic of the studied compounds. The presence of BF3.Et2O in the ion source is favorable for producing the protonated nitrene form. The protonated nitrene shows a new type of ring expansion rearrangement. The abundances of the [M + H - N2]+ ion makes it possible to identify the anomeric configuration of the azido group.     

Infrared spectra of acetylated and benzoylated glycopyranosyl fluorides

Summary Infrared spectra of a number of acetylated and benzoylated glycopyranosyl fluorides have been taken. It has been observed that, with a single exception, compounds in which the fluorine atom is axially bound absorb in the region 748–802 cm^–1 whereas compounds with an equatorially bound fluorine atom show no absorption in this region. The infrared spectra may be used to assign the anomeric configuration of glycopyranosyl fluorides if their conformation is known.

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Zusammenfassung Die IR-Spektren einiger acetylierter und benzoylierter Glykopyranosylfluoride wurden aufgenommen. Dabei wurde beobachtet, daß alle Verbindungen mit axial gebundenem Fluor mit einer einzigen Ausnahme in dem Gebiet 748 bis 802 cm^–1 absorbieren, während Verbindungen mit äquatorial gebundenem Fluor in diesem Gebiet keine Absorption zeigen. Die IR-Spektren können daher zur Feststellung der anomeren Konfiguration solcher Verbindungen dienen, soferne deren Konformation bekannt ist.

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Résumé On a enregistré le spectre infrarouge d'un certain nombre de fluorures de glycopyranosyles acétylés et benzoylés. On a observé, à une seule exception près, que les composés dans lesquels l'atome de fluor est lié axialement absorbent dans la région 748–820 cm^–1, tandis que ceux où le fluor est lié équatorialement ne montrent pas d'absorption dans cette région. On peut utiliser les spectres d'absorption infrarouge pour déterminer la configuration anomère des fluorures de glycopyranosyle si leur conformation est connue.

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Dedicated to Prof. Dr. Ing.M. Jureek on the occasion of his 60th birthday.

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The authors are indebted to cand. pharmI. Krogh Andersen for the infrared spectra. Microanalyses were made by Mr.Preben Hansen.     

STEREOSELECTIVE SYNTHESIS OF ACETYLATED GLYCOPYRANOSYL AZIDES

The acetylated glycopyranosyl azideswere obtained inhigh yields with stereoselectivity by phase-transfer catalyzed(PTC)synthesis,and their structures were confirmed depending upon elementalanalysis and IR,~1H,~(13)C-NMR spectral data.     

Structure of C-1 substituted glycopyranosyl azides: new insights based on CD measurements

CD spectra have been recorded for a series of peracetylated d-glycopyranosyl azides (d-gluco, d-galacto, d-xylo, d-arabino configuration) substituted at the anomeric position by various groups: amido, azido, cyano, ethoxy, methoxy. Application of the azide octant rule for the interpretation of the sign for the long-wavelength azide band allowed conformation of the azido group in each mono azido derivative investigated to be established. In each 1-cyano derivative, the azido group was in a gauche-like arrangement with respect to the C-1–O^ring bond, which is considered as a manifestation of the exo-anomeric effect of the azido group. For the 1-alkoxy derivatives, an antiparallel orientation of the azido group with respect to the C-1–O^ring bond was found in solution by CD measurement analysis, as already observed for methoxyazide 5 in the solid state. For azidoamide derivatives, intramolecularly (N–H–N^x_azide) H-bonded conformers are believed to prevail in methanol, in contrast to the situation in DMSO.     

Conversion of tertiary alcohols to tert-alkyl azides by way of quinone-mediated oxidation-reduction condensation using alkyl diphenylphosphinites

A novel method for the preparation of alkyl azides from alcohols by way of oxidation-reduction condensation is described. In this reaction, the sterically-hindered tert-alkyl phosphinites that are prepared from the corresponding alcohols are converted into tert-alkyl azides with almost complete inversion of their stereochemistry: the obtained alkyl azides are then successfully reduced to afford the corresponding amines on treatment with LiAlH₄, thus, a versatile method for the preparation of chiral amines from the corresponding chiral alcohols is established.     

A mild and efficient method for preparation of azides from alcohols using acidic ionic liquid [H-NMP]HSO4

We report here an efficient method for the synthesis and characterization of [H-NMP]HSO₄ and its application as an efficient catalyst and solvent for preparation of azides from corresponding alcohols under mild conditions. This processor showed high chemoselectivity for conversion of various alcohols to their corresponding azides.     

不饱和半夹芯式16e化合物Cp*Ir(S2C2B10H10)与邻、间位取代苯基叠氮的反应性

考虑取代基的位置和电子效应对反应体系的影响, 本文系统地研究了16e化合物Cp^*Ir(S₂C₂B₁₀H₁₀) (1)与邻、间位取代苯基叠氮的反应。研究结果表明:与邻、间位取代苯基叠氮反应均生成苯环邻位碳发生C-H 活化形成C-S 键的金属配合物。这些配合物通过核磁(¹H、¹¹B、¹³C)、红外、质谱、元素分析和单晶结构解析进行了全面地表征。在光照反应结果的基础上, 提出了形成这类产物的自由基机理。     

Ph3P/Br2/n-Bu4NNO2 as an efficient system for the preparation of N-nitrosamines and azides

The combination PPh₃/Br₂/n-Bu₄NNO₂ was developed as a new reagent system for the efficient preparation of N-nitrosamines and azides from the corresponding amines and hydrazine derivatives, respectively, at 0 °C to room temperature, in excellent yields.     

A Novel and Efficient Production of Amines from Azides Using LiCl/NaBH4

A practical & efficient reagent system LiCl/NaBH₄ is used for the production of amines from azides is described.     

Reactions of Halogen Azides

Until recently, the explosive nature of halogen azides made these compounds unsuitable for preparative uses and greatly impeded investigation of their physical properties. Reactions of ClN₃ and BrN₃ with metal halides, metal carbonyls, and organometallic compounds to from metal azide halides, nitride halides, carbonyl azide halides, and alkylmetal azides were reported only very recently. The stability relationships of the halogen azides are discussed.     

Efficient synthesis of 5-fluoroalkylated 1H-1,2,3-triazoles and application of the bromodifluoromethylated triazole to the synthesis of novel bicyclic gem-difluorinated 1H-pyrano[3,4-d][1,2,3]-triazol-4-one compounds

A series of 5-fluoroalkylated 1H-1,2,3-triazoles were synthesized in good yield by the regiospecific 1,3-dipolar cycloaddition reaction of (Z)-ethyl 3-fluoroalkyl-3-pyrrolidino-acrylates with aryl or benzyl azides. In the cases of benzyl azides, addition of Na₂CO₃ was crucial for a high yield of the triazoles. Tetrakis(dimethylamino)ethylene (TDAE) promoted reaction of bromodifluoro-methylated triazole with aldehydes affording a new class of β,β-difluoro-β-triazolyl alcohol derivatives, which were lactonized with catalytic amount of p-toluenesulfonic acid in toluene at 80-90°C to give a series of novel bicyclic gem-difluorinated 1H-pyrano[3,4-d][1,2,3]-triazol-4-one compounds in good yield.     

A simple,efficient thermally promoted protocol for Huisgen-click reaction catalyzed by CuSO4·5H2O in water

A thermally promoted and CuSO₄-catalyzed new version of the Huisgen-click reaction is presented in this Letter. Notably, this protocol was suitable not only for the reactions between organic azides and alkynes, but also for one-pot three-component reactions among alkyl halides, NaN₃, and alkynes.     

Synthesis of functionalized α-CF3-α-aminophosphonates via Cu(I)-catalyzed 1,3-dipolar cycloaddition

A convenient method for the preparation of α-CF₃-α-aminophosphonates bearing alkynyl group at the α-carbon atom has been described. New alkynylphosphonates have been further utilized in the synthesis of functionalized triazole-containing α-CF₃-α-aminophosphonates via copper-catalyzed (3+2)-cycloaddition to different organic azides.     

Selective reduction of aromatic azides in solution/solid-phase and resin cleavage by employing BF3·OEt2/EtSH. Preparation of DC-81

An efficient method for the reduction of aromatic azides in both solution and solid-phase has been developed by employing BF₃·OEt₂/EtSH. This report also describes resin cleavage employing this reagent system. Further, this protocol has been utilized for the solution as well as the solid-phase synthesis of pyrrolo[2,1-c][1,4]benzodiazepines, including the naturally occurring antibiotic DC-81 and fused [2,1-b]quinazolinones.     

Réaction de N3N/BF3-OEt2 sur les alcools allyliques stéroïdques. synthèse “stéréocontrôlée” d'azides et d'amines allyiques

N₃H/BF₃-OEt₂ reacts with allylic alcohols via an ion-pair mechanism, leading to allylic azides. Stereoselective control is obtained by choosing appropriate concentrations of N₃H.     

A novel and highly selective conversion of alcohols, thiols, and silyl ethers to azides using the triphenylphosphine/2,3-dichloro-5,6-dicyanobenzoquinone(DDQ)/n-Bu4NN3 system

Alcohols, thiols, and silyl ethers are converted into alkyl azides in good to excellent yields by treatment with PPh₃/DDQ/n-Bu₄NN₃ in CH₂Cl₂ at room temperature. The method is highly selective for 1° alcohols in the presence of 2° and 3° ones, and also thiols and silyl ethers.     

Ammine Complexes of Na‐, Ag‐, Mn‐, and Zn‐Azides

The synthesis of ammine metal azides is achieved through a simple route in liquid ammonia solution. Azides of silver, sodium, manganese, and zinc were obtained as ammine complexes from liquid ammonia and the solid compounds were characterized. The NH₃ solutions were investigated by means of NMR spectroscopy as well. The triamminesilver(I) azide as well as the unusual tetraamminesilver(I) and pentaamminesodium(I) azides are presented. The structures of the hexaamminemanganese(II) and hexaamminezinc(II) azides, which crystallize with four ammonia molecules of solvation, are elucidated. From these compounds the binary azides Mn(N₃)₂ and Zn(N₃)₂ were obtained by (careful) heating.     

General and Facile Route to Isomerically Pure Tricyclic Peptides Based on Templated Tandem CLIPS/CuAAC Cyclizations

We report a one‐pot ligation/cyclization technology for the rapid and clean conversion of linear peptides into tricyclic peptides that is based on using tetravalent scaffolds containing two benzyl bromide and two alkyne moieties. These react via CLIPS/CuAAC reactions with cysteines and azides in the peptide. Flexibility in the scaffolds is key to the formation of isomerically pure products as the flexible scaffolds T4 ₁ and T4 ₂ mostly promote the formation of single isomeric tricycles while the rigid scaffolds T4 ₃ and T4 ₄ do not yield clean products. There seems to be no limitation to the number and types of amino acids present as 18 canonical amino acids were successfully implemented. We also observed that azides at the peptide termini and cysteine residues in the center gave better results than compounds with the functional groups placed the other way round.     

Synthesis of aryl azides from aryl halides promoted by Cu2O/tetraethylammonium prolinate

An efficient approach to aryl azides, in short reaction times and good to excellent yields, has been developed via the reaction of aryl halides with sodium azide under Cu₂O/tetraethylammonium prolinate catalysis.