Stannylene acetals, synthesis

Hodosi and Kovac reported the highly efficient P-mannosylation, which makes use of mannose-derived 1,2-O-stannylene acetal 15 in combination with an aglycon-derived triflate (Scheme 7.13).58 A remarkable feature of this method is its extreme simplicity. Even totally unprotected mannose can be used as precursor of 15. Undoubtedly, this method can be seen as one of the most facile methods for the stereoselective synthesis of P-mannosides. 

Srivastava and Schuerch [112] and Dessings et al. [113]. reported on the potential utility of 1,2-O-stannylene acetals in /3-wianno-glycoside synthesis. Recently, Hodosi and Kovac established a highly efficient /3-mannosylation process involving alkylation of a 1,2-O-stannylene acetal with the triflate derived from an aglycon [ 114] (O Scheme 39). A remarkable feature of this method is its extreme simplicity. Even free mannose can be used as a precursor of... 

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). ... 

T.B. Grindley, Applications of Stannyl Ethers and Stannylene Acetals to Oligosaccharide Synthesis, in Synthetic Oligosaccharides Indispensable Probes for the Life Sciences, P. Kovac (Ed.), ACS, Washington, 1994. 

Kovac and Hodosi have applied stannylene chemistry for the synthesis of P-mannosides [50]. The use of 1,2-0-cw-stannylene acetals, first developed by... 

Synthesis of Methyl, Afiyl, and Benzyl Glycosides via Stannylene Acetals... 

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. 

The synthesis of sixteen methyl D-hexopyranosid-2-, 3-, or 4-ulosides by bis(tributyltin)-oxide - bromine oxidation of unprotected methyl glycosides has been described. Axial hydroxy groups in l,2-ci,s-diols are preferentially oxidised by this system. The stmctures of some of the products were confirmed by independent syntheses involving oxidation of partially protected derivatives. In related work some carbohydrate 1,2-diol dibutylstannylene acetals have been regiospecifically oxidized by NBS (rather than bromine) to give a-hydroxyketones. A Sn n.m.r. study on the stannylene acetals has shown some of them to be dimers. ... 

Protection of Alcohols. The inherent stability of the MPM ether, coupled with a large repertoire of methods for its removal under mild conditions that do not normally effect other functional groups, makes it a particularly effective derivative for the protection of alcohols. The most common method for its introduction is by the Williamson ether synthesis. A number of bases can be used to generate the alkoxide, but Sodium Hydride in DMF (eq 1) or THF (eq 2) is the most common. Other bases such as n-Butyllithium, Potassium Methylsulfinyl-methylide (dimsylpotassium) (eq 3), and Sodium Hydroxide under phase-transfer conditions are also used. From these results, it is clear that protection can be achieved without interference from Payne rearrangement, and considerable selectivity can be obtained. In the ribose case, selectivity is probably achieved because of the increased acidity of the 2 -hydroxy group. The additive Tetra-n-butylammonium Iodide is used for in situ preparation of the highly reactive p-methoxybenzyl iodide, thus improving the protection of very hindered alcohols. Selective monoprotection of diols is readily occasioned with 0-stannylene acetals. ... 

Another synthesis, described in detail in Scheme 12, was devised specifically for the introduction of deuterium at both ends of l-deoxy-D-t/ireo-pentulose.21,22 Stannylene methodology was used twice, first for glycol splitting with phenyliodonium diacetate, under strictly neutral conditions (necessary to preserve the benzylidene acetal), and secondly to convert the sequence -CHOH-CD3 to CO-CD3 by brominolysis. The final, labeled pentulose was l-deo y-D-threo-(1-2H3, 5-2H)pentulose. 

Regioselective Oxidation. Following the original discovery by David and Thieffrey, several stannylenes have been oxidized by bromine to acyloins (eq 8). Hanessian employed this reaction for the synthesis of a densely functionalized intermediate which was converted into (-i-)-spectinomycin. A detailed study of monooxidation of unprotected carbohydrates has also appeared. Stannylenes are oxidized the same way as diols, with Sodium Periodate and Lead(IV) Acetate. ... 

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