Anomeric glycosyl azides

The current article ties in with previous ones that were published in 1961 and 1993. In the past decade there have been reports on a number of relevant preparative approaches and uses of anomeric glycosyl azides, which provide a plethora of synthetic options for carbohydrate chemistry. 

B. Kralj, V. Kramer, D. Zigon, J. Kobe, and A. Stimac, Differentiation of anomeric glycosyl azides using mass-spectrometric results. Rapid Comm. Mass Spectrom., 1 (1993) 147-151. 

The base-catalyzed condensation of azides with activated methylene compounds is a well-established route to IJT-triazoles. In particular, it is the best route to triazoles bearing a 5-amino or hydroxy substituent and an aryl or carbonyl-containing function in the 4-position. The addition is regiospecific. The reaction is a stepwise one, since anomerism of glycosyl azides has been observed in their reaction with activated methylene compounds, indicating the presence of an intermediate. The mechanism can be envisaged as a nucleophilic attack by the car-banion on the terminal nitrogen of the azide, followed by cyclization to a... 

Azide addition to enolizable ketones is regiospecific and may be considered as a 1,3-dipolar cycloaddition occurring at the double bond of the enolate, similar to the addition of azides to electron-rich olefins. However, a stepwise reaction appears more probable because glycosyl azides exhibit anomerism when they react with activated methylene compounds, thus indicating the presence of a triazene intermediate.264 On the other hand, the formation of the triazene intermediate may be considered as a limited case of 1,3-dipolar cycloaddition where one of the bonds is formed completely before the other one starts,2 such a limited case being observed for the Diels-Alder reaction.265... 

The use of Pd/C (87,89), neutral Raney Ni (W-2) (91,95), and Lyndlar s catalyst (90) have been reported in literature. Conditions used for the reduction of glycosyl azide have to be carefully optimized in order to suppress anomerization and the formation of undesired a-glycosides. Use of basic conditions and procedures that avoid noble metals leads to decreased a-glycosides formation (94). 

Bianchi, A., Bernard , A. Selective synthesis of anomeric -glycosyl acetamides via intramolecular Staudinger ligation of the -azides. Tetrahedron Lett. 2004, 45, 2231-2234. 

Glycosyl halides are reacted with 28 to afford the corresponding glycosyl azides in quantitative yields complete inversion at the anomeric centre is observed in this reaction [107] (Scheme 4.43). 

Such benzyl-protected pyranoses as l-0-acetyl-2,3,5-tri-0-benzyl-p-D-ribo-furanose or l-(9-acetyl-2,3,4,6-tetra-0-benzyl-a-D-mannopyranose do not give single glycosyl azides but lead to anomeric mixtures. Thus 2,3,4,6-tetra-O-benzyl-ot- (97) and -p-o-mannopyranosyl azide (98) were obtained in the ratio 1 1.2. In his book Hanessian reports on a process based on the remote activation concept . For example, 3-methoxy-2-pyridyl p-o-glucopyranoside... 

Synthesis of Glycosyl Azides from Glycosyl Derivatives with an Unprotected Anomeric Center, Employing Phospho-Organic Compounds... 

Conformational studies of glycosyl azides, in particular of pyranosyl derivatives, demonstrate that the azido group behaves like the (9-acetyl group as far as the anomeric effect is concerned. These experimental results show that the dipolar character of the azido group correlates well with the presumed steric (or dipole-dipole or N-N type) and electronic (or conjugative, back-donation or N cr type) interactions governing the anomeric effect. 

W. Broder and H. Kunz, A new method of anomeric protection and activation based on the conversion of glycosyl azides into glycosyl fluorides, Carbohydr. Res., 249 (1993) 221-241. 

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