Glycosyl anionic nucleophiles

Correlation of nucleophilic rate data for phenyldimethylsulfonium ions with common nucleophiles, with pX e values shows that the slopes of the lines, jS[ e, correlate qualitatively with the Edwards hardness parameter for the nucleophile and not with the Swain-Scott n parameter.144 cw,cw-2,4,6-Trimethyl-l,3,5-triaminocyclohexane is weakly basic in aqueous solution, because of steric inhibition to solvation of the conjugate acid.145 The three NH2 groups are axial and the steric effect also results in reduced reactivity as a nucleophile in, S n2 reactions. Highly stereoselective syntheses of N-. and O-glycosides have been carried out by addition of anionic nucleophiles to glycosyl iodides.146 5 n2 reactions are involved, but some substrates are susceptible to E2 elimination when treated with highly basic anions. 

The pyrimidine moiety of purines is 7t-electron deficient, whereas the imidazole ring is a Jt-electron excessive system. The direction of the dipole moment is altered by the introduction of substituents, by protoiiation, tautomerization or base pairing. The 7t-excessive character of the imidazole moiety of various purines makes it suitable for anion formation upon treatment with sodium hydride, potassium hydroxide, potassium carbonate or other reagents which are used during electrophilic reactions, such as alkylation or glycosylation. The nucleophilic attack on carbons occurs in the order C8 > C6 > C2. A number of purine syntheses use the displacement of existing substituents. 

In contrast to C-glycosylation by nucleophilic adchtion to an electrophilic carbohydrate, the use of an anomeric anion has found limited use for such a reaction due to instability. However, C-glycosylation by means of anomeric anion species is of signihcance in some special cases [74], The anomeric anion intermediate can be stereoselectively prepared by (i) reduc-hve metalation of anomeric halides or sulfones, (ii) transmetalation of glycosyl stannanes, and (iii) direct deprotonation of the anomeric proton. This section deals with three types of the reaction using different anomeric anions. 

S -Alkyl thiocarbamates (Table 4.24) have been synthesized [I] by a procedure (Scheme 4.19) which is closely analogous to that employed for the preparation of S-alkyl thiocarbonates (see Section 4.1), S-Glycosyl dithiocarbamates [2], which are useful precursors for thiosugars, have been prepared by simple nucleophilic displacement of the tosyloxy group by the N,N-diethyldithiocarbamate anion (cf preparation of S-glycosyl dithiocarbonates, 4.1.13). 

Another possible precursor to conduct free radical reactions is the glycosyl-cobait(III) dimethylglyoximato complex 33 [22,23], These organometallic compounds can readily be prepared by the displacement of the halide atom in 17 with the highly nucleophilic cobalt(I) anion 32. The latter can be generated from the dimeric Co(II) complex 31 under reducing conditions. 

The succinimide anion obtained by the NIS heterolysis is frequently observed to compete with a less potent nucleophile in NIS glycosylations. This leads to glycosyl succinimides like 25 in the 2-deoxy-D-arabino case [10] which, owing to the marked... 

P selectivity. Crich and coworkers proposed that, under preactivation conditions, the oxocarbenium ion is trapped by a triflate anion to form the more stable a-triflate 65. After addition of the acceptor, the a-triflate intermediate can then be displaced in an SN2-like manner to afford a p-mannoside product (68). The formation of a-glycosyl triflates was confirmed by II, 13C, and 19F NMR analyses of the activated mannosyl donor recorded at low temperature [37], The experimentally determined KIE is approximately 1.12, which is consistent with an oxocarbenium-like TS [38], It was hypothesized that the a-triflate converts into the contact ion pair 66 in which the triflate anion remains at the a face or that an exploded TS is formed where the nucleophile is loosely associated with the oxocarbenium ion as the triflate departs [39,40], The a product 69 can be explained by the formation of the solvent-separated ion pair 67 where the counterion is solvated and facial selectivity is lost. 

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