Alkylation stannylene acetals

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... 

The third important aspect of these structures is related to the geometries of the dimers or terminal units of oligomers of stannylene acetals (Figs. 5, 6a, and 6b).40,59 60 The tin atoms adopt a distorted trigonal bipyramidal geometry with the alkyl groups in equatorial orientations. The tricoordinate... 

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)66 or on the tributylstannyl ether in neat benzyl bromide or allyl bromide at 80-90°C.67 It was then discovered that the presence of added nucleophiles markedly accelerates the reactions, so that alkylation of both tributylstannyl ethers and dibutylstannylene acetals in benzene, which is very slow at reflux with benzyl bromide alone, occurs at a reasonable speed at reflux in the presence of added tetrabutylammonium halides.57,63 Many other nucleophiles are also effective, including A-methylimidazole68 and... 

For benzylation, the greatest preference for reaction next to the axial substituent (about 9 1) has been obtained by reaction in benzyl bromide as solvent for both tributylstannyl ethers109 and for dibutylstannylene acetals,110 with still greater preferences using larger alkyl groups in the dialkyl-stannylene acetals, such as hexyl or neopentyl groups.110 Methylation reac-... 

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... 

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... 

Scheme 5.1.13 The influence of a cyclic alkyl group on tin on the regioselectivity of p-toluenesulfonation reactions on stannylene acetals from a terminal- 1,2-dioD ...

Selective monoprotection of diols is moderately effective. Fluoride ion-promoted monoalkylation of tartrate diesters that have been activated as the stannylene acetal is an extremely effective method for the efficient monoalkylations of diols. An equimolar mixture of dimethyl tartrate (la) and dibutyltin oxide in toluene, heated under reflux to azeotropically remove the formed water, provides a stannylene acetal. The crude acetal in DMF is treated with cesium fluoride and then benzyl bromide to provide in 85% yield the dimethyl (2J ,37 )-2-0-ben-zyltartrate (421). Reaction of la with benzyl bromide and CsF in DMF proceeds to provide 421 in only 5% yield. Benzyl iodide is generally a better alkylating agent, providing 421 in 99% yield [147]. 

A study on the selectivity of stannylene acetal-mediated alkylation of methyl 4,6-0-benzylidene-a-D-glucopyranoside has concluded that increased bulk of the alkyl groups on tin and a non-polar or no co-solvent increase the proportion of 0-2 mono-ethers formed.The tin-mediated allylation and benzylation of 1,2-0-... 

Stannylene acetals formed from a 1°, 2°-diol lead to preferential alkylation of the l°-hydroxyl ... 

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. 

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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