Glycosyl Oxocarbenium Ion Intermediates

The characteristic feature of the divalent tin compounds is that they have both a vacant orbital and a lone pair of electrons (Figure 2.5). In this glycosylation reaction, it is assumed that SnCl2 behaves as a Lewis acid, where the vacant orbital accepts one of the three lone pairs in the fluorine atom of the glycosyl fluoride. As a result of this interaction, the C—F bond cleaves to give the oxocarbenium ion intermediate that is then attacked by an alcohol to give the glycoside. 

Figure 2.5 Activation of the C—F bond of glycosyl fluoride by the divalent tin species, giving rise to oxocarbenium ion intermediate.

The C-glycosylation of pentose glycals with silylacetylenes or allylsilanes through oxocarbenium ion intermediates proceeds with high regio- and stereo-selectivity, giving the 1,4-anti compounds as the main products. ... 

Some solvents may form complexes with the oxocarbenium ion intermediates, thereby affecting the anomeric outcome of a glycosylation. For example, diethyl ether is known to increase the a anomeric selectivity. Probably, diethyl ether participates by the formation of diethyl oxonium ion (Scheme 4.9a). The (3 configuration of this intermediate is favoured because of the operation of the reverse anomeric effect (see Chapter 1). Nucleophilic displacement with inversion of configuration will give an a glycoside. Recently, it was shown that a mixture of toluene and dioxane provides a more efficient participating solvent mixture. 

Initially, it was thought that the glycosylation proceeded through the episulfonium intermediate 35. However, the measured kinetic isotope effect (KIE) of 1.17-1.20 suggests an oxocarbenium ion intermediate rather than an episulfonium ion [27], Furthermore, computational studies also indicated that the 3E oxocarbenium ion 36 is considerably more stable than the strained episulfonium ion 35. The observed stereoselectivity was explained by an inside attack on the 3E oxocarbenium ion. 

Ratcliffe and Fraser-Reid found that acetonitrile was able to trap glycosyl oxocarbenium ions (e. g. 46), arising from NPGs, to give acetonitrilium ions, e. g. 84 (O Scheme 12a) [56]. The latter reacted with water to produce intermediate 85 that evolves to a-amide 86, in a Ritter-t) e reaction [57] (O Scheme 12a). 

Noyori and Kurimoto [240] described that hydroxyl-protected and -unprotected glycosyl ary-loxides reacted with alcohols under mild electrolytic conditions to give the corresponding glycosides. They hypothesized that the glycosylation reaction proceeded via oxocarbenium ion intermediates generated from the radical cation of the easily oxidizable aryloxy substrate (O Scheme 84). 

A thiophilic electrophile (+SMe) from DMTST reacts with a lone parr on sulfur to afford a cationic sulfonium species, which is an excellent leaving group. Because of the participation of a lone pair on the ring oxygen, the C-S bond is cleaved, forming an oxocarbenium ion intermediate, with which MeCN reacts to form an axial-oriented nitrilium intermediate under kinetic control. This then undergoes Sn2 nucleophilic substitution with a hydroxyl of the glycosyl accepter to yield a-sialoside. 

Crich and co-workers reported that the remote participation of esters at the 0-3 position of allopyranosyl donors is possible in glycosylations based on the trapping experiment, in which the anomeric oxocarbenium ion intermediate generated by the activation of thioalloside 132 was trapped by the intramolecular nucleophilic attack of the tert-butoxycarbonyl (Boc) group at the 0-3 axial position to afford stable cyclic carbonate 133 (Scheme 21) [65],... 

On the other hand, much information on the hydrolysis mechanism of chitin in vivo by a chitinase enzyme has accumulated, particularly since 1995. There are mainly two mechanistic aspects in terms of the nature of the reaction intermediate (1) an oxazolinium intermediate [64-67] and (2) an oxocarbenium ion intermediate or a covalent glycosyl carboxylate intermediate (Scheme 21) [68]. An X-ray crystallographic analysis of chitinase A was performed that suggested an oxazolinium intermediate (Fig. 11) [65]. 

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