Methyl 4,6-O-benzylidene-a-D-glucopyranoside

C44H68012Sn2 Di-//-(methyl 4,6-O-benzylidene-a-D-glucopyranosid-2,3-diyl)bis[dibutyltin(IV)] (BZGBSN)136... 

Ethoxycarbonyl chloride is, by virtue of resonance involving the ester function, less reactive than acetyl chloride, and the reagent has found application for selective O-acylation in the steroid field.34 With this reagent, methyl 4,6-O-benzylidene-a-D-glucopyranoside yielded35 2- and 3-esters in the ratio 24 1, and the related benzyl-thiocarbonyl chloride gave the 2-ester in 58% yield.36... 

Differentiation between the secondary hydroxyl groups in methyl 4,6-O-benzylidene-a-D-glucopyranoside was observed on reaction with methyl benzoate-sodium methoxide at 200° for 45 minutes the 2- and 3-esters and the 2,3-diester were formed176 in the molar ratios of 55 23 10. 

This class of acylating agents has thus far been but little used in carbohydrate chemistry. However, unimolar benzoylation of methyl 4,6-O-benzylidene-a-D-glucopyranoside, methyl 4,6-O-benzylidene-a-D-altropyranoside, and benzyl 4,6-O-benzylidene-jS-D-galactopy-ranoside with benzoyl cyanide gave good yields of the corre-... 

However, for an apparent 0-3 to 0-2 migration of a nitro group during the alkaline methanolysis of methyl 4,6-O-benzylidene-a-D-glucopyranoside 3-nitrate, see J. Honeyman and J. W. W. Morgan,/. Chem. Soc., (1955) 3660-3674. 

A reagent system consisting of triphenylphosphine/imidazole/iodine in toluene has proven useful for the conversion of trans- 1,2-diols (547) into the corresponding alkenes (549 Scheme 120) (79S469). The imidazole probably forms a solvated complex (548) with triphenylphosphine and iodine. Methyl 4,6-O-benzylidene-a-D-glucopyranoside was transformed into 2,3-dideoxyhex-2-enopyranoside in 75% yield. 

Under the same conditions, the reactivity of hydroxyl groups is OH-2 > OH-3 for methyl 4,6-O-benzylidene-a-D-glucopyranoside, and OH-3 > OH-2 for the P-ano-mer [48] or for the corresponding galactopyranoside [49]. The hydroxyl group in position 2 is the most reactive in sucrose benzylation [27]. It seems that the cis-OR substituent activates the adjacent equatorial hydroxyl group [33] in benzylations in the presence of barium oxide. 

J. C. Lopez, E. Lameignere, and G. Lukacs, Stereospecificity in Diels-Alder reactions of dienes and dienophiles derived from methyl 4,6-O-benzylidene-a-D-glucopyranoside, J. Chem. Soc., Chem. Commun., (1988) 706-707. 

Fig. 2-17. Examples of acetals. 1, 1,2-O-lsopropylidene-a-D-glucofuranose 2, 1,2 5,6-di-0-isopropylidene-a-D-glucofuranose 3, methyl 4,6-O-benzylidene-a-D-glucopyranoside.

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... 

Alternatively, Horton and coworkers recommend the use of 2,3-disulfonic esters of methyl 4,6-O-benzylidene-a-D-glucopyranoside for the preparation of the olefin 45. Heating such compounds with potassium ethylxanthate in boiling butanol, or with the Tipson-Cohen reagent (N,N-dimethylformamide, sodium iodide, and zinc dust) afforded the product in 40-55% yield, and methyl 2,3-anhydro-4,6-0-benzylidene-a-D-allopyranoside and the 2,3-epithio analog also gave this compound under the former conditions.81 Applied to vicinal di-... 

Methyl 4,6-0-benzylidene-a-D-glucopyranoside in methanol containing a little SnCl2 2H20 treated with ethereal diazomethane -> methyl 4,6-O-benzylidene-a-D-glucopyranoside 3-methyl ether. Y 93%. - The ) -anomer gives a mixture of 2- and 3-methyl ethers. The presence of stannous chloride considerably increases the yields. F.e. s. M. Aritomi and T. Kawasaki, Chem. Pharm. Bull. 18,611 (1970). 

Such generalisations can, however, be misleading as the various hexopyr-anoses exhibit slightly different reactivity patterns and the anomeric configuration can be critical in determining the site selectivity. In particular, when a (protected) anomeric hydroxyl is cis to the 2-OH it is often found that the 2-OH shows enhanced reactivity towards etherification and esterification as exemplified by benzylation of methyl 4,6-O-benzylidene a-D-glucopyranoside under basic conditions (Figure 2.3) [6]. 

A particular mole ratio of bis(tributyltin)oxide was reportedly required to regioselectively effect the tributyltin ether mediated 2-O-alkylation of methyl 4,6-O-benzylidene-a-D-glucopyranoside Dibutyltin oxide mediated alkylation of the same compound (BnBr, DMF) afforded predominantly the 2-0-benzyl ether in contrast to previous claims (c.f. Vol 27, Ch 5, ref. 15). 

A Koenigs-Knorr reaction of the glucopyranoside benzeneboronate (56), followed by hydrolysis has provided a convenient synthesis of methyl 2-aceta-mido-2-deoxy-3-o-(2,3,4,6-tetra-o-acetyl-/ -D-galactopyranosyl)-a-D-glucopyrano-side. Periodate-oxidized methyl 4,6-o-benzylidene-a-D-glucopyranoside reacted with toluene-p-sulphonylhydrazine to yield a substituted bis(hydrozone). 

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