Stannylene acetals formation

Scheme 5.1.10 Stannylene acetal formation and reaction under microwave conditions ...

Hodosi and Kovac observed that, when free sugars are treated with excess dibutyltin oxide in methanol for extended periods of time at temperatures above 60°C, equilibration of the configuration at C-2 occurs.73 This observation led to the efficient formation of 6-O-trityl-D-talose from 6-0-trityl-D-galactose, but also indicates the need for care in the formation of stannylene acetals from free sugars.73... 

Alkylation requires more vigorous conditions. These reactions were originally performed on the stannylene acetal with the alkylating reagent in DMF at elevated temperatures, 45 °C for methyl iodide or 100 °C for benzyl bromide. It was then discovered that the presence of added nucleophiles markedly accelerates the reactions so that alkylation of dibutylstannylene acetals in benzene, which were very slow at reflux with benzyl bromide alone, occur at a reasonable speed at reflux in the presence of added tetra-butylammonium halides. Many other nucleophiles are also effective, including A-methylimidazole and cesium fluoride. Cesium fluoride has been used mainly in DMF and the combination of an added nucleophile with a polar aprotic solvent allows benzylation with benzyl bromide to occur efficiently at room temperature. If the stannylene acetal is a 1,2-D-stannylene acetal derivative of a carbohydrate and the electrophile is a carbohydrate-derived triflate, oligosaccharide synthesis can be achieved. More recently, both formation of the stannylene acetal and alkylation in the presence of tetrabutylammonium iodide have been performed under microwave irradiation excellent yields have been obtained in <0.5 h and the short reaction times allow the use of more sensitive reagents (Scheme 5.1.10). ... 

Dial monofunctionalization. Formation of stannylene acetals and then treatment with electrophilic reagents achieve the purpose of selective diol derivatization. A primary hydroxyl group is preferentially protected, and in the case of a secondarysecondary diol their respective steric environments have important influence on the regiochemistry, as shown in several carbohydrates. " ... 

Glycosylation of 3,4,6-tri-O-benzylglucopyranose (42) via stannylene acetal with methyl iodide resulted in the production of the 2-0-methyl ether (70%) and a-methyl glycoside (30%) [20], presumably as a result of the formation of stannylene acetal on axial 0-1 and equatorial 0-2, The equatorial 0-2 is more reactive during stannylene complexation, which leads the 2-0-methyl ether. Thus stannylene-mediated alkylation of 6-0-tritylmannose and methyl a-mannopyranoside afforded 3-0-alkylated products because of the greater reactivity of the equatorial oxygen at the 3-position [20]. The reaction mechanism is discussed in detail in Section 8.3.4. 

Epimerization at C-2 sometimes occurs during dibutylstannylene complex formation. In particular, 1,2-cis P-per-O-acylation for formation of the stannylene acetals of free mannose, rhamnose, and lyxose is accompanied by epimerization [22]. Scheme 16 shows the epimerization process schematically. 

Locked anomeric configuration method results in complete p-selectivity in oligosaccharide synthesis [25, 26]. The electrophile must be converted to an active tri-flate and inactive bromide, iodide and mesylate cannot be used. Addition of CsF or BU4NF into the reaction effectively increases the solubility of the staimylene acetals. Accompanying formation of the formate derived from the primary Inflate at room temperature can be suppressed by reducing the reaction temperature to —5°C. Table 1 shows results from coupling the 1,2-O-stannylene acetal of rhamnose (54) with primary and secondary triflates (57 and 58) in the presence of CsF. 

Isomerization of the stannylene acetal from 1,2-0 to 2,3-0 and the resultant equatorial 3-0 activation rationalize the formation of the /t.vctA/o-disaccharide as shown in Scheme 17. The epimerization of the stannylene acetal seems much faster than alkylation. The use of the analogous 3-0-benzyl ether effectively prevented the unfavorable coupling. Thus, generation of the etheric by-product was suppressed in the reaction with the same primary triflate (57). 

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