Synthesis of 1,2-cis-Configurated Glycosylphosphonates

A synthesis of 1,2-cis-configurated, non-isosteric phosphonate analogues of aldose-1-phosphates is described. Treatment of 1-O-acyl-glycoses 1 , 7 , 13 , and 19 with trialkyl phosphite in the presence of trimethylsilyl trifluoromethanesulfonate gave the 1,2-cis-configurated glycosylphosphonates 2 , 4 , 8 , 10 , 14 , 16 , 20 , and 22 as the major anomers and the 1,2-trans-configurated glycosylphosphonates 3 , 5 , 9 , 11 , 15 , 17 , 21 , and 23 as the minor anomers. The 1,2-cis-configurated phosphonates 4 , 10 , 16 , and 22 were deprotected to give the (β-D -glucopyranosyl)phosphonate 6 , the (β-D -mannopyranosyl)phosphonate 12 , the (β-D -ribofuranosyl)phosphonate 18 , and the (β-D -arabinofuranosyl)phosphonate 24 , respectively, in high yields. The preferred formation of 1,2-cis-configurated phosphonates is explained by postulating an equilibrium between the anomeric phosphonium-salt intermediates (such as 25 and 26 ) and a stabilization of the cis-configurated salts through formation of a pentacoordinated species (such as 28 ).     

Convenient use of ortho-formylphenyl thioglycoside for regioselective conjugation with glycosyl acceptors towards regioselective 1,2-cis-glycosylation

A facile methodology is proposed for regioselective conjugation between glycosyl donors and acceptors towards the development of regioselective 1,2-cis-glycosylation method. ortho-Formylphenyl 1-thio-β-d-galactopyranoside was regioselectively tethered to methyl α-d-glucopyranoside under acidic condition to furnish an 4,6-O-arylidene acetal-linked conjugate. This conjugate can be readily converted to an ether-linked 4-O- or 6-O-derivative by regioselective cleavage of the acetal ring. In the glycosylation reaction, the ether-linked 4-OH conjugate was found to show excellent 1,2-cis selectivity via an intramolecular 1,9-transfer.     

Synthèse de spiro-pyrazolines par cycloaddition du diazométhane sur des sucres insaturés ramifiés. Influence de l'isomérie géométrique sur l'orientation de la réaction Communication préliminaire

The orientation of the cycloaddition of diazomethane on unsaturated branchedchain sugars has been studied. For 3-C-cyanomethylidene-3-deoxy-1,2-O-isopropylidene-α-D-glycero-tetrofuranose the orientation was ‘normal’ and did not depend on the configuration at the double bond. The same situation prevailed with derivatives of 3-deoxy-1,2:5,6-di-O-isopropylidene-3-C-methylidene-α-D-xylo-hexofuranose. For the 3-C-acylmethylidene- and the 3-C-cyanomethylidene-3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-ribo-hexofuranoses, the trans-(H–C(3′)–C(2))-isomer gave the ‘normal’ cycloadduct whereas the cis-isomer gave predominantly the αabnormal spiro-pyrazoline. This observation represents the first instance where the regioselectivity of a cycloaddition reaction is affected by the geometrical isomerism of the dipolarophile. The most probable explanation of the phenomenon is the conformational perturbation about the C(4)--C(5) bond of the unsaturated sugars induced by a change in the configuration at C(3). The consequence of that ‘conformational transmission’ of a difference in configuration at C(3) is that the steric crowding on the cis- than in the trans-isomer. Several novel examples of a new series of C-glycosylidenic derivatives, the spiro-pyrazolines, are described.     

A New Synthesis of Benzylidene Acetals

Aryl-halo-diazirines react under basic conditions with 1,3-cis-, 1,2-cisand 1,2-trans-diols to give acetals. Yields are high. Diastereoselectivities depend upon the diol and upon the reaction conditions. Thus, reaction of the 1,3-cis-diol 1 (Scheme 1) with 2 gave 3 as a single diastereoisomer. The 1,2-cis-diols 4 and 7 led to the endo- and exo-acetals 5 / 6 (93:7) and 8 / 9 (ca.10:1), respectively, The 1,2-trans-diols 10 , 16 , and 19 reacted with 2 to afford 11 / 12 (90:10), 17 / 18 (1:1), and 20 / 21 (6:1), respectively. Reaction of the (4-nitrophenyl)diazirine 13 with 10 at higher temperatures yielded 14 / 15 (6:4). The uracil moiety, the acetamido group, and the enol-ether moiety are compatible with the reaction conditions. The diastereoselectivity is rationalized on the basis of a reaction sequence involving alkoxy-halogen exchange, which is regioselective or not, thermolysis of the ensuing alkoxydiazirine(s), protonation of the alkoxycarbene to form an (E)-configurated oxycarbenium ion, and attack of the neighboring oxy or hydroxy group, which is only possible for a limited range of conformers.     

Proton magnetic resonance studies of compounds with bridgehead nitrogen: XXVIII—Stereochemical studies with perhydropyrido[1,2-c] [1,6,3]dioxazocines and 2-alkylperhydropyrido[1,2-c] [1,3,6]oxdiazocines

A series of perhydropyrido[1,2-c][1,6,3]dioxazocines and 2-alkylperhydropyrido[1,2-c][1,3,6]oxdiazocines have been prepared. 6-p-Nitrophenyl-3,4-dimethylperhydropyrido[1,2-c][1,6,3]-dioxazodioxazocine is shown to adopt the cis fused ring conformation in solution with the nitrogen lone pair axial with respect to the piperidine ring. The 2-alkylperhydropyrido[1,2-c][1,3,6]oxdiazocines adopt a similar cis fused ring conformation and with increasing steric requirement of the 2-alkyl substituent the 8-membered ring increasingly favours the chair-chair conformation, rather than the chair–boat conformation favoured by the 2-methyl substituted compound.     

Synthesis and NMR characterization of cobalt(III) complexes with triethylenetetramine, 2,2-bipyridine and 1,10-phenanthroline

The compounds α-cis?[Co(trien)(bipy)]Cl₃ and α-cis?[Co(trien)(phen)]Cl₃ were synthesized and characterized by one- and two-dimensional NMR spectroscopy. Compared to α-cis?[Co(trien)(NO₂)₂]Cl, the proton spectra of these two complexes were spread to a wider spectral width. With the aid of two-dimensional experiments, it was possible to assign three multiplets to specific protons, and the remaining multiplet was found to arise from overlap of three separate resonances.     

Intramolecular C-glycosylation of 2-O-benzylated pentenyl mannopyranosides: remarkable 1,2-trans stereoselectivity

The IDCP-promoted intramolecular C-glycosylation of pentenyl α-mannopyranosides carrying, at O-2, an activated benzyl group gave, unexpectedly, the 1,2-trans-fused bicyclic product which corresponds to an α-C-aryl mannopyranose derivative. This remarkable, strained C-glycosyl compound was rapidly epimerized to the more stable 1,2-cis product on treatment with BF₃·Et₂O. The IDCP-reaction product could be elaborated into a 2-(α-C-mannopyranosyl)-3,4,5-trimethoxybenzyl alcohol derivative.     

Eine Einfache Synthese von N-Acyl-Glykosylaminen

Abstract

D-Ribose, D-arabinose and D-glucose react with nitriles in liquid hydrogen fluoride to give the corresponding 1,2-cis configurated N-acyl-pento (or hexo) furanosyl amines 1-7 and 9. D-Xylose gives the ct-pyranosyl isomer 8 beside the α-furanosyl main product 7. D-Mannose and L-rhamnose yield the N-acyl-α-hexopyranosyl amines 10 and 11.     

Polycyclic systems: Synthesis of isoindolo[2,1-b]-pyrrolo[1,2-d][2,4]benzodiazocine and isoindolo-[1,2-d]pyrrolo[1,2-a] [1,5]benzodiazocine

The synthesis of isoindolo[2,1-b]pyrrolo[1,2-d][2,4]benzodiazocine 7 and isoindolo[1,2-d]pyrrolo[1,2-a]-[1,5]benzodiazocine 13 are described starting from 2-(2-methoxycarbonyl)benzylphthalimide 1a and ethyl α-bromohomophthalate 9 respectively.     

Synthesis and analysis of compounds having the skeleton of ergot alkaloids with the nitrogen atom in the D-ring transposed

Alkylation-amination of the enamine 2 in the presence of ethyl α,α-bis(dibromomethyl)acetate, triethyl-amine, and methylamine lead to the construction of the aza-transposed ergoline 3 . Sequential reduction, hydrolysis, reesterification, and indolization of 3 , produced three diastereomers of 6 . The structure of these three diastereomers was assigned on the basis of nmr and ir spectral analysis to be (α-cis) syn, (β-cis) anti, and (α-trans) syn. The isomer (β-cis) anti was reduced with lithium aluminum hydride to the corresponding alcohol.     

Application of paramagnetic shift reagents to the conformational analysis of isomeric dienones

Paramagnetic NMR shift reagents, Eu(fod)₃ and Pr(fod)₃, have been applied to study the one-ene conformations of isomeric dienones. The results obtained using various complex formation models are analysed. The preferred model suggests participation of both carbonyl oxygen Ione pairs in binding with the shift reagents. Criteria for the estimation of errors in the determination of the structure parameters of the substrate-paramagnetic reagent complexes are suggested. The data obtained using NMR shift reagents are consistent with the existence of dienone α,β-cis-isomers as s-cis-conformers only, with the carbonyl group lying out of the plane of all the other atoms of the molecule. Both s-cis and s-trans conformers occur in dienone α,β-trans-isomers.     

Asymmetric catalysis,part 91: Enantioselective monophenylation ofcis-1,2-cyclopentanediol with triphenylbismuth diacetate and chiral copper(II) complexes as catalysts

Summary The monophenylation ofcis-1,2-cyclopentanediol with triphenylbismuth diacetate in the presence of chiral Cu(II) complexes as catalysts gavecis-2-hydroxy-1-phenoxy-cyclopentane with enantiomeric excesses up to 38%. The optically active ligands used were triamine derivatives of 2,6-bis(aminomethyl)pyridine and diamine derivatives of 2-(aminomethyl)pyridine. Selectivity in the monophenylation occurred only in the presence of the latter as auxiliary ligands.

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Asymmetrische Katalysen, 91. Mitt.: Enantioselektive Monophenylierung voncis-1,2-Cyclopentandiol mit Triphenylwismutdiacetat und chiralen Kupfer(II)-Komplexen als Katalysatoren

Zusammenfassung Die Monophenylierung voncis-1,2-Cyclopentandiol mit Triphenylwismutdiacetat in Gegenwart chiraler Cu(II)-Komplexe als Katalysatoren ergabcis-2-Hydroxy-1-phenoxy-cyclopentan mit Enantiomerenüberschüssen von bis zu 38%. Die eingesetzten optisch aktiven Liganden waren Triamin-Derivate von 2,6-bis(Aminomethyl)pyridin und Diamin-Derivate von 2-(Aminomethyl)pyridin. Selektivität bei der Monophenylierung war nur in Gegenwart letzterer als Auxiliar-Liganden zu beobachten.

     

Intramolecular formation of excimers in model compounds for polyesters obtained from 2,6-naphthalene dicarboxylic acid and cyclohexanediols

The fluorescence in dilute solution has been measured as a function of solvent viscosity for four bichromophoric models for polyesters with naphthalene in the rigid aromatic unit and diols derived from cyclohexane as the flexible spacer. The spacers are 1,2-cis-cyclohexanediol, 1,2-trans-cyclohexanediol, a 1:2 mixture of 1,3-cis- and 1,3-trans-cyclohexanediols, and a 1:2 mixture of 1,4-cis- and 1,4-trans-cyclohexanediols. The shape of the emission spectra for the molecules in this series is less sensitive to the viscosity of the medium than was the case for an analogous series in which a methylene or oxyethylene spacer replaces the cyclohexanediol spacer. The dependence of the excimer emission on the type of spacer is different also in the series in which the rigid units contain naphthalene or benzene. When the rigid units contain naphthalene, excimer formation is maximal if the spacer contains 1,2-trans-cyclohexanediol, but this spacer produces a molecule with a very small tendency for excimer formation in its polymers with terephthalate. A conformational analysis correctly concludes that the spacer most conducive to excimer formation should be 1,2-trans-cyclohexanediol, but it does not identify the correct order of the remaining three bichromophoric model compounds. The problem may reside in the method for taking into account the finite width of the torsional well associated with each rotational isomer. © 1994 John Wiley & Sons, Inc.     

Compounds with bridgehead nitrogen. 44—the conformational analysis of perhydropyrido[1,2-c] [1,3]thiazine

The 270 MHz NMR data on trans- and cis-(H-4a, H-7)-7-ethylperhydropyrido[1,2-c][1,3]thiazine show heavy conformational bias to the trans- and S-inside cis-fused conformations, respectively. Comparison of the ¹³C NMR spectra of these anancomeric systems with the ¹³C NMR spectrum of perhydropyrido[1,2-c][1,3]thiazine indicates a trans-?S-inside cis-conformational equilibrium for the latter compound in CDCl₃ at 25°C, containing ca 75% trans-fused conformer. The ¹³C NMR spectrum of perhydropyrido[1,2-c][1,3]-thiazine at ?75°C showed 64% trans-fused conformer and 36% S-inside cis-conformer.     

Influence of bromide ions on the synthesis of anomeric thiocyanates

The synthesis of anomeric thiocyanates with the α- and β-configuration is described. Reactions performed under standard conditions afforded the 1,2-trans derivatives as the main products, whereas in the presence of the quaternary ammonium salts, the 1,2-cis-thiocyanates were formed preferentially. The strong influence of the bromide ions on the distribution of the products is discussed.     

Methyl 2-benzoylamino-3-dimethylaminopropenoate in the synthesis of heterocyclic systems. An attempt to prepare benzoylamino substituted azolo- and azinopyrimidines with a bridgehead nitrogen atom

Methyl 2-benzoylamino-3-dimethylaminopropenoate ( 2 ) was introduced as a new reagent for the preparation of fused pyrimidinones 4 from heterocyclic α-amino compounds in acetic acid. In this manner, derivatives of pyrido[1,2-a]pyrimidine 4a,b,f , pyrimido[1,2-b]pyridazine 4g , pyrimido[1,2-c]pyrimidine 4j , pyrazino[1,2-a]pyrimidine 4k , thiazolo[2,3-b]pyrimidine 41 , pyrazolo[1,5-a]pyrimidine 4m , and 1,2,4-triazolo-[1,5-a]pyrimidine 4n were prepared.     

The Reaction of Dihalocarbenes with Quadricyclane

The reactions of difluoro-, dichloro- and dibromocarbene with quadricyclane ( 2 ) were examined. In all cases, conversions were low (4–15%), but three distinct reaction courses were observed: cleavage, 1,2-addition, and 1,4-addition. Difluorocarbene gave mainly 6-endo-(2,2-difluorovinyl)-cis-bicyclo[3.1.0]hex-2-ene ( 8 ; 52–89% relative yield), together with minor amounts of exo-3,3-difluorotricyclo[3.2.1.0^2,4]oct-6-ene (7; 13–17%), and 4,4-difluorotetracyclo[3.3.0.0^2,8.0^3,6]octane ( 5 ; 2–4%). Dichlorocarbene gave analogous products, but in relative yields of 35 ( 17 ), 51 ( 11 ), and 12% ( 16 ). The product 11 of 1,2-endo addition underwent further rearrangement to its allylic derivative 12 . A small amount of 1,2-endo addition also occurred (2% of 14 / 15 ). Dibromocarbene gave predominantly products derived from rearrangement of the 1,2-exo (61% of 20 / 21 ) and 1,2-endo adducts (10% of 23 / 24 ). In addition, a significant amount of 4,4-dibromotetracyclo[3.3.0.0^2,8.0^3,6]octane ( 25 ; 21%) was formed. The cleavage product, 6-endo-(2,2-dibromovinyl)-cis-bicyclo[3.1.0]hex-2-ene ( 26 ) was also observed (7%). The yields and product compositions were compared to those obtained from norbornadiene ( 1 ) and found to be entirely different (Table 1), for example no cleavage occurred with difluorocarbene.     

Glycosylidene Carbenes. Part 22. α-D-Selectivity in the Glycosidation by Carbenes Derived from 2-Acetamido-hexoses

Glycosylidene carbenes derived from the GlcNAc and AllNAc diazirines 1 and 3 were generated by the thermolysis or photolysis of the diazirines. The reaction of 1 with i-PrOH gave exclusively the isopropyl α-D -glycoside of 5 besides some dihydrooxazole 9 (Scheme 2). A similar reaction with (CF₃)₂CHOH yielded predominantly the α-D -anomer of 6 , while glycosidation of 4-nitrophenol (→ 7 ) proceeded with markedly lower diastereoselectivity. Similarly, the Allo-diazirine 3 gave the corresponding glycosides 12–14 , but with a lower preference for the α-D -anomers (Scheme 3). The reactions of the carbene derived from 1 with Ph₃COH (→ 8 ) and diisopropylideneglucose 10 (→ 11 ) gave selectively the α-D -anomers (Scheme 2). The αD -selectivity increases with increasing basicity (decreasing acidity) of the alcohols. It is rationalized by an intermolecular H-bond between the acetamido group and the glycosyl acceptor. This H-bond increases the probability for the formation of a 1,2-cis-glycosidic C–O bond. The gluco-intermediates are more prone to forming a N–H…?(H)OR bond than the allo-isomers, since the acetamido group in the N-acetylallosamine derivatives forms an intramolecular H-bond to the cis-oriented benzyloxy group at C(3), as evidenced by δ/T and δ/c experiments.     

1,2,4-Triazines. VI. Imidazo[1,2-b]-as-triazines

Imidazo[1,2-b]-as-triazines were obtained in high yields by heating substituted glyoxaldoximes with 1,2-diaminoimidazoles in the presence of hydrochloric acid. Phenylglyoxal hydrate in a similar reaction afforded a mixture of 2- and 3-diphenyl-6-arylimidazo[1,2-b]-as-triazines. α-Ketoacids and 1,2-diaminoimidazoles in the presence of hydrochloric acid afforded 2,6-disubstituted-4H-imidazo[1,2-b]-as-triazin-3-ones.     

Glycosylidene Carbenes. Part 14. Glycosidation of partially protected galactopyranose-, glucopyranose-, and mannopyranose-derived vicinal diols

The relation between H-bonding in diequatorial trans-1,2 and axial, equatorial cis-1,2-diols and the regioselectivity of glycosidation by the diazirine 1 was examined. H-Bonds were assigned on the basis of FT-IR and ¹H-NMR spectra (Fig. 1). Glycosidation by 1 of the gluco-configurated diequatorial trans-2,3-diols 4–7 yielded the mono-glucosylated products 16/17/20/21 (69–89%); 1,2-/1,3-linked products (37–46:63–54), 24/25/28/29 (60–63%; 1,2-/1,3-linked products 46–51:54–49), 32–35 (69–94%; 1,2-/1,3-linked products 45–52:55–48), and 36/37/40/41 (59–63%; 1,2-/1,3-linked products 52–59:48–41), respectively (Scheme 1, Table 3). The disaccharides derived from 4, 5 , and 7 were characterized as their acetates 18/19/22/23, 26/27/30/31 , and 38/39/42/43 , respectively. Glycosidation of the galacto-configurated diequatorial 2,3-diols 8 and 9 and the manno-configurated diequatorial 3,4-diol 10 by 1 (Scheme 2, Table 3) also proceeded in fair yields to give the disaccharides 44–47 (69–80%;1,2-/1,3-linked products ca. 1:1), 48–51 (51–61%;1,2/-1,3-linked products 54–56:56–54), and 56/57/60/61 (71–80%; 1,3-/1,4-linked products 49–54:51–46), respectively. The 1,3-linked disaccharides 56/57 derived from the diol 10 were characterized as the acetates 58/59 . The regio- and stereoselectivities of the glycosidation by 1 were much better for the α-D -manno-configurated axial, equatorial cis-2,3-diol 11 and the galacto-configurated axial, equatorial cis-3,4-diol 13 (1,2-/1,3-linked disaccharides ca. 3:7 for 11 and 1,3-/1,4-linked disaccharides ca. 4:1 for 13 ; Scheme 3, Table 4). The regio- and stereoselectivity for the β-D -manno-configurated cis-2,3-diol 12 were, however, rather poor (1,2-/1,3-linked products 48:52). The 1,2-linked disaccharides 66/67 derived from 12 were characterized as the acetates 70/71 . Koenigs-Knorr-type glycosidation of the cis-diols 11–13 by 2 or 3 proceeded with a similar regio- and a higher stereoselectivity (α-D > β-D with the donor 2 and α-D < β-D with the donor 3 ) than with 1 , with the exception of 12 which did not react with 2 . The regioselectivity of the glycosidations by 1 agrees fully with the H-bonding scheme of the diols and with the hypothesis that the intermediate carbene is preferentially protonated by the most weakly H-bonded OH group. The regioselectivity of the glycosidation by 2 and by 3 is determined by a higher reactivity of the equatorial OH groups and by H-bonding. Several H-bonded and equilibrating isomers of a given diol may intervene in the glycosidation by 1 , or by 2 and 3 , resulting in the same regioselectivity. The low nucleophilicity of 12 and the low degree of regioselectivity in its reaction with 3 show that stereoelectronic effects may also profoundly influence the nucleophilicity of OH groups.