Glycosyl nitrones

Oxidation with Mn02 of N-glycosylhydroxylamines (48), obtained in the reaction of sugars (47), with A -methyl- and N -benzylhydroxylamines, leads selectively to the corresponding C -unsubstituted and C-phenyl-iV-glycosyl nitrones (49) (Scheme 2.18) (118, 119). 

I. Addition of C-Radicals to Nitrones Recently (525), the addition of alkyl radicals to chiral nitrones as a new method of asymmetrical synthesis of a-amino acids has been described. Addition of ethyl radicals to glycosyl nitrone (286) using Et3B as a source of ethyl radicals appears to proceed with a high stereo-control rate. 

Double addition of Grignard reagents to A-glycosyl nitrones (336), in a domino fashion, affords hydroxylamines. Their usefulness has been shown with the synthesis of pyrroloazepine (418) via a ring closing metathesis key step (Scheme 2.187) (564). 

Dipolar cycloaddition reactions between three A-benzyl-C-glycosyl nitrones and methyl acrylate afforded key intermediates for the synthesis of glyco-syl pyrrolidines. It was found that furanosyl nitrones (574) and (575) reacted with methyl acrylate to give mixtures of all possible 3,5-disubstituted isoxazolidines (577) and (578). On the other hand, the reaction with pyranosyl nitrone (576) was much more selective and cycloaddition at ambient temperatures afforded only one of the possible Re-endo adducts (579a). The obtained isoxazolidines were transformed into the corresponding (V-benzyl-3-hydroxy-2-pyrrolidinones (580—582) on treatment with Zn in acetic acid (Scheme 2.264) (773). 

Cycloaddition reactions of vinyl trimethylsilane with C -glycosyl nitrones gave moderate to good yields (67%-74%). Estimation of diastereoselectivities from isolated yields showed total endo preference for the reaction of the D-galacto nitrone. High endo preference was observed for the D-ribo analog, but exo preference for the D-xylo one (814). 

A -Benzyl-C-glycosyl nitrones reacted with acrylate to give glycosyl isoxazolidines which were easily converted to glycosyl pyrrolidines by reduction of the N-0 bond with Zn in acetic acid. The best result was obtained with pyranosyl nitrone 88 which quantitatively afforded the cycloadduct 89 with complete regio- and stereoselectivity <03TA3731>. 

Some excellent results for cycloadditions involving nitrones were observed by Merino et al. [99] using a solvent-free [3+2] cydoaddition of N-berrzyl-C-glycosyl nitrones to methyl acrylate. Microwave irradiation for 0.1 h was sufficient to afford a 100% yield of the isolated isoxazolidine whereas thermal heating under reflux conditions (80 °C) required 0.5 h and produced the same yield and the same stereoisomeric ratio. 

In 2002, Cavaleiro et al. [38] developed the stereoselective synthesis of glycoconjugated isoxazoUdine-fused chlorines (potential photosensitizers in photodynamic cancer therapy) by 1,3-dipolar cycloadditions of meso-tetrakis(pentafluorophenyl)porphyrin (83) with glycosyl nitrones 41-43 and 84. In all cases of sugar moieties, the configuration of the major products 85 indicated an endo addition, as shown in Fig. 18. 

A review has been published on the work of Vasella s group on asymmetric induction in 1,3-dipolar cycloadditions of, and the addition of phosphorus nucleophiles to, N-glycosyl-nitrones, with the purpose of providing a general synthesis of a-aminophosphonic... 

N-Glycosylhydroxylamine derivatives have been the subject of several reports. a- -GlycosyIhydroxylaminophosphonates resulted from additions of dialkyl phosphite salts to -glycosyl-nitrones. The stereochemistry of the reaction, which... 

In contrast to the above examples, the 1,3-dipolar cycloaddition to -(2,6-dimethylphenyl) maleimide of the -glycosylnitrone 13 gave predominantly the syn-isoxazolidine 16b, with a diastereomeric excess of more than 90%. The crude residue after cycloadditions was chromatographed, and the corresponding major products could be obtained more then 90% purity with a small amount of the minor component. In the case of 0,0-disubstituted C-(2,4,6-trimethylphenyl)-13e and C-2,6-dichlorophenyl-iV-glycosyl-nitrones 13c, the cycloaddition reaction with -arylmaleimides did not take place only the unreacted starting compounds were isolated. 

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