O-Stannylene Acetal

Monoalkylation of a vic-glycol.1 Selective monoalkylation or monoacylation of the vic-glycol group of dimethyl L-tartrate is possible by conversion to the O-stannylene acetal (1) by reaction with dibutyltin oxide. The acetal is converted selectively to a mono derivative (3) by reaction with an alkyl halide or acyl chloride (excess) and CsF (about 2 equiv.). KF or Bu4NF are less effective than CsF. 

Srivastava and Schuerch [255] and Desinges et al. [256] demonstrated the potential utility of glycosyl 1,2-O-stannylene acetals, and Hodosi and Kovac [257] established this method involving alkylation of a 1,2-O-stannylene acetal with a triflate derivative as an aglycon (Scheme 5.97). This glycosyl donor was prepared by the... 

O-stannylene acetals,84 glycals and 1,2-anhydrosugars,85 and to selective de-O-benzylation of position-2 with TIBAL, DIBAL-H57 or Lewis acid catalysts,86 or to the one-pot access to 3-O-benzyl-4,6-0-benzylidene glucosides by tandem catalysis recently reported.87 The 1,2-lactones recently reported by Linker and co-workers35 are also synthons which provide... 

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. 

Scheme 7.13 (3-Mannosylation using mannose-derived 1,2-O-stannylene acetal in combination with an aglycon-derived triflate.

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... 

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. 

Hodosi, G. Kovac, P., Manipulation of free carbohydrates via stannylene acetals. Preparation of beta-per-O-acyl derivatives of D-mannose, L-rhamnose, 6-0-trityl-D-talose, andD-lyxose. Carbohydr. Res. 1997,303, 239-243. 

Selective O-Substitution and Oxidation Using Stannylene Acetals and Stannyl Ethers... 

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... 

One of the most valuable properties of stannylene acetals derived from 1,2- or 1,3-diols is that in reaction with electrophiles, monosubstituted products are obtained much faster than disubstituted products. This selectivity has been used to advantage many times to break the symmetry present in simple symmetrical diols or polyols, as shown in Table III.2,12,65,69,93 100 Some examples are shown in Figs. 15 to 19 (page 48). In later work, Mash and co-workers have shown that l,n-diols can be converted to mono-O-benzyl derivatives in reasonable yields.101... 

An interesting development is the observation that alkylation of dibutyl-stannylene acetals of this type in the presence of cesium fluoride in DMF gives different regiochemistry than that obtained under all other conditions. For instance, as shown in Fig. 23, the reaction of the dibutylstannylene acetal of methyl 4,6-O-benzylidene-a-D-glucopyranoside with benzyl bromide yields ratios of 0-2 to 0-3 products of 74 8, 41 15, and 46 19, in neat benzyl bromide,110 in toluene containing tetrabutylammonium iodide,91 and in DMF,91 respectively, but 25 52 in DMF containing cesium fluoride.91 Similar reversals are obtained in allylation reactions on the same substrate.91109... 

Selective O-Substitulion and Oxidation Using Stannylene Acetals and Stan-nyl Ethers. David, S. In Preparative Carbohydrate Chemistry, Hanessian, S., Ed. Dekker New York. 1997 p 69. 

An alternative activation of the anomeric hydroxyl makes use of 1,2-0-dibutylstannylene acetals [382]. Thus, for instance condensation of the stannylene acetal of 3,4,6-tribenzylman-nose with methyl iodide, allyl or benzyl bromide afforded the corresponding /3-mannosides in almost quantitative yields (O Scheme 66). 

These compounds are less aggregated in solution. For instance, 2,2-dibutyl-l,3,2-dioxastannolane, a polymer in the solid state, has been shown, by variable temperature Sn NMR spectroscopy, to be a mixture of dimers, trimers, and tetramers in solution, with dimers predominating at room temperature and above. This technique has also indicated that most carbohydrate-derived stannylene acetals are present predominantly as dimers in solution." " " Supporting evidence has been obtained from mass spectral studies and by comparison of solid-state NMR spectra with those of solutions." Some dibutylstannylene acetals derived from cw-diols contain an observable proportion of higher oligomers benzyl 4,6-0-benzylidene-2,3-0-dibutylstannylene-o -D-mannopyranoside is present as a mixture of a dimer and a trimer in chloroform-d at -60 °C but, in the less polar solvent toluene-dg, is mainly present as a tetramer at that temperature. ... 

Scheme 5.1.14 The populated dimers for stannylene acetals of 3-O-benzyl-l,2-O-isopropylidene-a-D-glucofuranose...

Scheme 5.1.20 In competition reactions, stannylene acetals derived from isolated c s-diols are less reactive than those from trans-d/o/s ...

S. David, Selective O-Substitution and Oxidation Using Stannylene Acetals and Stannyl Ethers, in Preparative Carbohydrate Chemistry, S. Hanessian (Ed.), Marcel Dekker, New York, 1996. 

X. Kong and T. Brace Grindlqr, An improved mediod for the tegioselecsive oxidadtm of stannylene acetals and dimeiisation of the o-hytboxyfcetone products, J. Carbokydr. Chan. 72 557 (1993). 

Stannylene-mediated glycosylation was first applied to alkyl mannosylations. Condensation of the stannylene acetal of 3,4,6-tri-O-benzyImannopyranose (44) with methyl iodide and allyl bromide in DMF afforded the desired methyl and allyl P-mannopyranosides, respectively, in almost quantitative yields [20]. Benzyl p-mannopyranoside was obtained from the same stannylene acetal by use of BU4NI in benzene [21]. The electrophilic leaving group is responsible for the reactivity and stereoselectivity. Methylation with methyl tosylate and dimethyl sulfate gave methyl mannopyranosides as anomeric mixtures at temperatures above 75 °C [20]. 

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. 

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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