Sulfonyloxy group, nucleophilic displacement

The benzylidene derivative above is used, if both hydroxyl groups on C-2 and C-3 are needed in synthesis. This r/vzns-2,3-diol can be converted to the sterically more hindered a-cpoxide by tosylation of both hydroxy groups and subsequent treatment with base (N.R. Williams, 1970 J.G. Buchanan, 1976). An oxide anion is formed and displaces the sulfonyloxy group by a rearside attack. The oxirane may then be re-opened with nucleophiles, e.g. methyl lithium, and the less hindered carbon atom will react selectively. In the following sequence starting with an a-glucoside only the 2-methyl-2-deoxyaltrose is obtained (S. Hanessian, 1977). 

Nucleophilic-displacement reactions constitute some of the earliest known methods for the preparation of deoxyhalogeno sugars. A variety of leaving groups have been used, including sulfonyloxy (usually jP-tolylsulfonyloxy or methylsulfonyloxy), halide, triphenyl-methoxy (trityloxy), acetoxy, phosphate, and nitrate. As Barnett has surveyed the reactions in Volume 22 of this Series,1 this subject will not be discussed comprehensively in the present Chapter instead, only some general comments will mainly be made that will also be relevant to later discussions. 

Nucleophilic displacement of the 4-trifloxy group of 327 required only 12 h at 80°, and provided thiocyanate 262 in 85% yield, whereas the methyl-sulfonyloxy group at C-4 in 261 required 42 h at 140°, and provided the thiocyanate 262 in 68% yield, in contrast to previous reports.118 121... 

Nucleophilic displacements of sulfonyloxy groups by reagents other than halide ions had also been observed in sugar chemistry. As early as 1922, a 3-deoxy-3-hydrazino derivative had been obtained by the action of hydrazine on l,2 5,6-di-0-isopropylidene-3-0-p-tolylsul-fonyl-a-D-glucofiiranose, and this derivative was later characterized " as 3-deoxy-3-hydrazino-l,2 5,6-di-0-isopropylidene-a-D-allofuranose. 

Nucleophilic substitutions without neighboring-group participation proceed with some difficulty for 1,6-anhydrohexopyranoses owing to their rigid skeleton, they are restricted to only a few structural variants. For an equatorially attached sulfonyloxy group, only 52 undergoes513 displacement with sodium azide to yield 53. Among... 

The three major factors that inhibit nucleophilic displacement reactions in pyranose rings appear348 to be (i) a 1,3-diaxial interaction between the nucleophile and a ring substituent, (ii) a cis axial group adjacent to the sulfonyloxy group, and (iii) the electron-withdrawing effect, or unfavorable dipolar interactions at carbon atoms adjacent to the anomeric center. 

The mechanism of the elimination from the 5,6-disulfonates most probably involves nucleophilic displacement of the primary sulfonyloxy group (see other iodo-p-tolylsulfonates, on p. 101), followed by a second attack by iodide on the iodine, and by a concerted elimination of the secondary ester grouping. An elimination also occurs when 1,2-0-... 

The direct displacement of secondary sulfonyloxy groups of sugar derivatives by sulfur nucleophiles has received Umited study. Attempted displacement of p-tolylsulfonyloxy groups in methyl 4,6-0-benzylidene-3-O-methyl-2-O-p-tolylsulfonyl-a-D-altropyranoside or 1,2 5,6-di-0-isopro-pylidene-3-O-p-tolylsulfonyl-a-D-glucofuranose, by alkanethiolate anion in an alcohol medium, removed the p-tolylsuKonyl substituent and failed to give any (identifiable) thio sugar product. However, the 2,5-di-methanesulfonate of l,4 3,6-dianhydro-D-mannitol (64) reacted with... 

Dideoxynucleosides can also be prepared by hydrogenolysis of 2, 3 -dideoxy-2 -thio [158], 2, 3 -dideoxy-3 -thio [159, 160], 8,3 -S-anhydronucleo-sides of purine [161] and 2, 3 -dideoxy-3 -halogenoderivatives of nucleosides [52,162,163]. The intermediate dideoxy-3 -thio and 3 -halogeno derivatives can be easily prepared by nucleophilic displacement of the sulfonyloxy group of 2 -deoxy-3 -0-mesyl or tosyl nucleosides with mercaptide anion or with halide ion, respectively. The procedure has been successfully used for the synthesis of 3 -deoxythymidine 109h, 2, 3 -dideoxyuridine 109i and 2, 3 -dideoxy-5-... 

The regioselecdvity in tin-mediated monotosyladons of diols has been studied use of dibutyldn oxide or hexamethylenetin oxide in the example shown in Scheme 8 gave the primaiy-62 and secondary tosylate 63 in the rados 3 7 and 20 1, respecdvely. A rqxnt on the leacdons of dimesylated methyl hexopyranosides and glucofuranoses with superoxide (KOj) to give hydroxy products, either by direct hydrolysis, nucleophilic displacement, or via transient epoxides, has been published. Amberlite IRA-410 (Cl form) resin in DMF has been recommended for the selective displacement by chlorine of the primary sulfonyloxy groups in 3,5-disulfonate derivatives of 1,2-0-cyclohexylidene-a-D-xylofuranose. ... 

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