Dibutylstannylene acetals alkylation

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... 

Before workup of the reaction of the dibutylstannylene acetal of a diol with an electrophile such as an acyl, alkyl, or sulfonyl halide, the product present in nonpolar solvents has a halodibutylstannyl group attached to the nonreacted oxygen atom. This organotin derivative can be cleaved with water or mild acid, but chromatography on silica gel is usually sufficient to remove it. Some research groups have made use of the strong Sn-F bond by washing with fluoride ions. 

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... 

Table VI also lists the numerous reactions that have been performed on dibutylstannylene acetals of inositol derivatives containing ds-diols, mostly in myo-inositol derivatives. Most reactions were alkylation reactions and, almost without exception, single products were obtained with the substituent on the equatorial oxygen atom. In most cases, yields were greater than 80%, and in only a few cases were yields lower than 70%.

Fig. 44.—Alkylation of dibutylstannylene acetals of a pyranose cis-diols having axial oxygen atoms next to a deoxy center.271,272...

From a synthetic point of view, the most important observation is that dibutylstannylene acetals and tributylstannyl ethers can be used to effect terminal substitution of diols in excellent yields, often better than can be obtained by direct reaction at low temperatures, even for benzoylation or p-toluenesulfonylation, where direct reaction is reasonably effective. Terminal O-alkylation, which cannot be performed directly, is routine through choice of the appropriate conditions, as outlined in the sections following. These types of reactions are considered first, followed by reactions where the nonterminal oxygen atom is favored. 

Cesium fluoride. 13,68 14,79 15,75-76 16,69-70 17,68 18,88-89 19,70-72 Ethers. A direct transformation of aryl silyl ethers to aryl alkyl ethers is by their reaction with alkyl halides in the presence of CsF-DMF. Monobenzylation of glycols such as methyl glycerate via dibutylstannylene acetals. ... 

The reaction proceeds via the formation of a dibutylstannylene acetal in this example alkylation occurs at the C-3 hydroxyl. 

The 2,4-Q-dibutylstannylene acetal of 1,6-anhydro- -D-glucopyranose has been used to effect selective esterification and alkylation to give the 4-Q-benzoate (55%) and 4-Q-benzyl ether (40%) preferentially, but separation from the 0-2 substituted isomer was... 

TBDMSCl has been used to selectively protect the primary hydroxyl group of 1,2- and 1,3-diols under mild conditions, via dibutylstannylene acetal intermediates. For example, treatment of the dibutylstannylene acetal of l-phenylethane-l,2-diol with TBDMSCl in chloroform affords the primary ether in excellent yield (eq 27). This selectivity for the primary hydroxyl group is different from acylation or alkylation of dibutylstannylene acetal... 

Five-membered cyclic dibutylstannylene acetals formed on vicinal cw-axial-equatorial pairs of hydroxyl groups selectively enhance the nucleophilicity of the equatorial oxygen in 0-alkylation reactions [179, 180], On the basis of this rule Schuerch surmised that alkylation of the tin complex 103, having the anomeric oxygen locked in the equatorial position, should lead to P-mannosides [181]. This assumption was proved by treating the mannose diol 102 with Bu2SnO (—> 103) followed by in situ exposure to alkyl halides whereby P-mannopyranosides 104 were formed stereospecifically (Scheme 30) [181],... 

Silyl Ethers. - Regioselective silylation of lactose derivatives using dibutylstannylene acetals has afforded the 6 -0-silyl ethers in contrast to alkylations which give the 3 -0-ethers under the same conditions. Some Tbdms ethers have been cleaved by absorption onto alumina and then irradiation in a microwave oven. The silylation of 2 -deoxynucleosides is discussed in Chapter 20. 

C3-hydroxy benzylation, through alkylation of the intermediate 2,3-0-dibutylstannylene of mannose acetal 24, gives 25 (Scheme 5). Hydroboration of the exocyclic 5-alkene derived from this material provides 26, in which the C5 stereochemistry is inverted. Benzylation and acetate methanolysis leads to the suitable glycosyl acceptor 27. 

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