Sulfonyloxy groups, displacement reactions

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. 

Irreversible reactions of carbohydrates include the formation of glycosides and 1-deoxy-l-thioglycosides from acylglycosyl halides and thio-acetals, " respectively, esterifications by acyl and sulfonyl halides or anhydrides in pyridine, displacements of sulfonyloxy groups by various reagents, and most examples of formation and scission of anhydro rings, It is more difficult to define the influence of stereo effects on the course of these reactions and some of the results obtained await explanation. 

The most interesting behavior of the three dianhydrides is found in the displacement reactions of their 0-sulfonyl derivatives, and at present it seems that the reported results may be covered by three general rules. (1) Displacement of sulfonyloxy groups from the 0-sulfonates may be achieved under certain conditions, and occurs with inversion of configuration at the point of displacement. (2) Ammonia and halide ions displace sulfonyloxy groups, but alkali hydroxides (and perhaps alkoxides) merely hydrolyze the sulfonate esters by 0-sulfonyl fission, with retention of configuration. (3) Displacements by halide ions are possible only for endo sulfonyloxy groups. These rules are only tentative, and may be modified when more sulfonyloxy compounds, and their behavior to a wider variety of anions, have been studied. 

The formation of a quaternary salt (7) upon heating 2,3-0-isopropylidene-5-0-(p-tolylsulfonyl)adenosine, observed by Clark, Todd, and Zussman and referred to elsewhere in this review, accounts for the low yield, since this monomolecular quaterni-zation takes place much more rapidly than bimolecular displacement of the p-tolyl-sulfonyloxy group by the methyl mercaptide ion. Recently, this difficulty has been overcome and a good yield of L-2-amino-4-(5-thioaden-5-yl)butyric acid obtained by the reaction of (9b) with the disodium salt of homocysteine in liquid ammonia. This compound had also been prepared enzymically. ... 

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. 

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