Dibutylstannylene acetals

The two -OH groups in l,2 5,6-di-0-cyclohexylidene-wii/o-inositol and its di-O-isopropylidene analog are trans. The X-ray crystal structure of the latter compound suggests that the ring is in a skew conformation with the 0-3 and 0-4 -OH groups both in ax positions, but NMR studies and ab initio calculations indicate that a mixture of the skew and chair conformations, with 0-3 and 0-4 both in eq positions, is present. Formation of a dibutylstannylene acetal presumably locks these two compounds in the latter conformation. 

Glen, A. Leigh, D. A. Martin, R. P. Smart, J. P. Trascello, A. M., The Regioselective Tert-Butyldimethylsilylation of the 6 -Hydroxyl Group of Lactose Derivatives Via Their Dibutylstannylene Acetals. Carbohydr. Res. 1993,248, 365-369. 

Oxidation of the dibutylstannylene acetal derived from 3-0-benzyl-l,2-0-isopropylidene-a-D-glucofuranose (26) with NBS was finished within 5 min. The eluant for column separation was the mixture of hexane and ethyl acetate (from 4 1 to 2 1). Evaporation of solvent from the corresponding fractions afforded 27 (280 mg, 90%). Colorless crystals were obtained from ethyl acetate-hexane mp 117-118°C [ )D -114.5° (c 1.00, chloroform) IR (Nujol) 3491 cm" (OH), 1725 cm"1 (C=0), C-NMR (CDa3,62.90 MHz) 8 208.2 (C-5). 

A further method of synthesizing glyculosides is by brominolysis of 1,2-diol dibutylstannylene acetals. Thus, the /f-L-arabinoside derivative 221 gave the ketone 222, by oxidation of the axial oxy group.439... 

In related work, carbohydrate 1,2-diol dibutylstannylene acetals have been regiospecifically oxidized by IV-bromosuccinimide to give a-hydroxy-ketones. The reaction is illustrated for the preparation of 3-deoxy-l,2-O-isopropylidene-a-D-eryt/zro-hexofuranos-5-ulose (223) in Scheme 24. The endocyclic diol is also regioselectively oxidized to one product (224) in 44% yield, although 55% of the starting compound was recovered. (Scheme 24).439a... 

Dibutylstannylene acetals of diols (such as 11) were found to be oxidized regiospecifically by NBS to a-hydroxyketones (12)45 (Scheme 6). 

Chemical-shift changes for carbon nuclei in the diols on substitution of hydroxyl hydrogen atoms by a tin atom are small (<6 ppm, normally < 4 ppm) and rather unpredictable.35,44 It might be expected that the carbon atom attached to the tricoordinate oxygen atom in a dibutylstannylene acetal would be deshielded because of the assumed positive charge on the oxygen atom. In fact, the chemical shifts of these carbon atoms are almost identical to those of the parent diols.44... 

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... 

Some reactions follow paths different from the single bond per electrophile sequence. Dibutylstannylene acetals derived from all-tra/is-diols react with phenoxythiocarbonyl chloride at room temperature in 1,4-dioxane to give noncyclic phenylthionocarbonates, but when ds-diols are present, cyclic thionocarbonates spanning the oxygen atoms of the cw-diol are obtained both for pyranosides70 and for furanosides.71... 

Dibutylstannylene acetals have yielded propenylidene acetals on reaction with tetrakis(triphenylphosphinepalladium and acrolein diacetate, in some cases with excellent regioselectivity.72 For instance,D-glucal, methyl a-D-glucopyranoside, methyl a-D-mannopyranoside, and methyl /J-d-glucopyranoside yield the 4,6-O-propenylidene acetals in 89, 85, 83, and 80% yields, respectively, as mixtures of diastereomers at the acetal center. Galactose derivatives give mixtures of 3,4- and 4,6-O-propenylidene acetals.72... 

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. 

Fig. 13.—Formation and equilibration of acyl derivatives from the dibutylstannylene acetal of l-phenyl-l,2-ethanediol and their subsequent trapping reactions.53...

It has been observed that reactions of dibutylstannylene acetals of terminal 1,3-diols, or polyols having primary hydroxyl groups free, with t-butyldimethylsilyl chloride yield primary silyl ethers, even for such compounds as methyl a-D-mannopyranoside, where the expectation (see Table VI) for most reactions is for substitution to occur on a secondary oxygen atom.85 88 These observations probably arise from a very large kinetic preference for reaction with primary oxygen atoms, that is, ki2 and k]2 > k2 and K22, in Fig. 12, rather than a rearrangement from initially formed secondary silyl ethers. 

Fig. 14.—A mechanism proposed for the effect of cesium fluoride on the reactions of dibutylstannylene acetals.69...

The examples in Figs. 17 and 18 are particularly interesting. In Fig. 17,94,96 monosubstitution of the dibutylstannylene acetal of a meso-diol or -triol by a chiral acid chloride affords two diastereomers in very unequal amounts, and thus the one reaction both gives monoprotection and creates chiral intermediates. In the example in Fig. 18, 2 equiv of the dibutylstannylene acetal of a symmetrical diol were treated with 1 equiv of 1,2-dibromoethane to give the product of monosubstitution of each diol. This reaction only works effectively with 1,2-dibromoethane if electron-withdrawing groups are present on the diol, but any type of diol yields 2 1 products with 1,3-dibromopropane.100... 

Reactions of Dibutylstannylene Acetals of Symmetrical Diols to Give Monosubstituted Products... 

Reactions of Dibutylstannylene Acetals and Tributyltin Ethers of tram- 1,2-Diols... 

Dibutylstannylene acetals or tributylstannyl ethers derived from isolated rrans-diols on pyranose or inositol rings that have one adjacent substituent axial and one equatorial react preferentially on the oxygen atom adjacent to the axial substituent, as shown by many examples in Table IV. Some... 

Fio. 20.—Benzoylation and sulfation of a dibutylstannylene acetal of a (ra/ts-diol containing a phenylboronate.107... 

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-... 

Fig. 21.—Sulfation of the dibutylstannylene acetal of 2-azidoethyl /3-D-galactopyranoside 4,6-phenylboronate.115...

Fig. 22.—Methylation of a dibutylstannylene acetal under conditions that give improved regioselectivity.110...

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... 

Fig. 23.—Reversal in the regioselectivity of benzylation of a dibutylstannylene acetal of a trans-d o in the presence of cesium fluoride.91...

When reactions are performed on tributylstannyl ethers and dibutylstan-nylene acetals of hexopyranoside derivatives that have more oxygen atoms, including the primary one, unprotected, markedly different results are obtained, as shown in Figs. 24 and 25. Dibutylstannylene acetals favor reaction on the position in the 1,2-diol unit that is adjacent to an axial substituent, whereas tributyltin ethers prefer to react at the primary centers. However, this pattern was not observed for reactions of the tributylstannyl ether of l,2-(l-methoxyethylidene)-j3-D-mannopyranose, as shown in Fig. 26.122 Methylation of this compound through the tributylstannyl ether in toluene in the presence of added tetrabutylammonium bromide also gave substitution on 0-3 predominantly.123 These results may arise from distortion of the chair conformation by the fused isopropylidene acetal. 

Fig. 27.—Benzylation of the dibutylstannylene acetal of the n iis-l,2-diol in ethyl 4,6-0-benzylidene-l-thio-/3-D-glucopyranoside.135136...

Fig. 29.—Benzylation of a dibutylstannylene acetal derived from a lra/w-l,2-diol with two adjacent equatorial substituents, one of which is very large.141150...

Fig. 30.—Acylation reactions on dibutylstannylene acetals of 4-O-substituted methyl /3-d-xylopyranosides.132...

In the limited number of examples where the trans- 1,2-diols would be diaxial if the compound adopted a chair conformation, mixtures are also usually obtained. To form dibutylstannylene acetals, conformational changes to skew, boat, or alternative chair conformations are required. Conversion to the boat is easy for l,6-anhydro-/3-D-glucopyranose149 and methyl a-D-idopyranoside, but may be more difficult for methyl 4,6-0-benzylidene-a-D-altropyranoside. 

Formation of di-O- or tri-O-substituted derivatives from tributylstannyl ethers and dibutylstannylene acetals can often be performed regioselec-... 

Tributylstannyl ethers and dibutylstannylene acetals of a-D-glucopyranosides have been converted into 2,6-di-O-substituted derivatives in high yields with a wide range of electrophiles,74 107 151 152 but it should be noted that not all conditions result in selective reactions. 2,3,6-Tri-O-benzoyl derivatives can also be made in reasonable yields,74 153 constituting presumably another example of the electron-withdrawing substituent effect. 

Fig. 32.—Di-O-p-methoxybenzoylation of the dibutylstannylene acetal of methyl (methyl l-thio-a -D-glucopyranosid)uronate.1 0...

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