Cyclic oxocarbenium ion

The roles of nucleophilic assistance and stereoelectronic control in determining endo-versus exo-cyclic cleavage of pyranoside acetals have been investigated for a series of a- and j8-anomers.15 Exocyclic cleavage of a-anomers, via a cyclic oxocarbenium ion, is predicted by the theory of stereoelectronic control, and was found exclusively for the cases studied. The endocyclic route, with an acyclic ion, is predicted for the /1-structures, and a measurable amount was found in all cases, but its extent was dependent on temperature, solvent, and the nature of the aglycone group. 

Neighboring methoxy group assisted asymmetric induction is demonstrated in the TMSOTf-catalyzed reaction of y-alkoxy acetal 18 with allylsilane. A possible cyclic oxocarbenium ion intermediate 19 is proposed (equation 12)55. Siladioxanes 20 react with allylsilane in the presence of a catalytic amount of the Brpnsted superacid TfOH2+ B(OTf)4 to afford the allylated products 21 diastereoselectively (equation 13)56,57. 

Using a binary sensitizing system (phenanthrene P/DCNB /7-dicyanobenzene) in acetonitrile solution, O-aryl glycosides are transacetalized with alcohols after generation of aromatic radical cations [23], According to kinetic anomeric effects, the a-side attack of nucleophiles to cyclic oxocarbenium ions follows scheme 9. 

S. R. Shenoy, D. M. Smith, and K. A. Woerpel, Nucleophilic additions of trimethylsilyl cyanide to cyclic oxocarbenium ions Evidence for the loss of stereoselectivity at the limits of diffusion control, J. Am. Chem. Soc., 128 (2006) 8671-8677. 

S. R. Shenoy and K. A. Woerpel, Investigations into the role of ion pairing in reactions of heteroatom-substituted cyclic oxocarbenium ions, Org. Lett., 1 (2005) 1157-1160. 

While the confoimational analysis of stable compounds has been studied in detail, determining the conformational preferences of reactive intermediates is much more difficult. For example, knowledge of the three-dimensional structures of cyclic oxocarbenium ions is very important for imderstanding both uncatalyzed and enzymatic reactirms of carbohydrates involving the anomeric carbon, since these reactions often involve oxocarbenium ion intermediates [1-5], Since the charged intermediates are generally much too reactive, it is impossible to directly observe oxocarbenium ions, particularly in aqueous envirorunents [6, 7]. 

It has also been suggested that a similar cyclic oxocarbenium ion is involved in the process of transglycosylation and acetolysis [91]. 

Kinetic measurements have shown that both anomerization and reduction are much slower for the a-anomer than those for the p-anomer. Furthermore, the reduction takes place at far greater rate than the anomerization, regardless of the reducing agent. These results are consistent with the process proceeding via a cyclic oxocarbenium ion. The silane, which is present in fivefold excess, should be a better nucleophile than methoxytrimethylsUane. Consequently, the rate of formation of the product is much greater than that of anomerization. 

On the other hand, the p-substrate forms a substantial amount of a-anomer, in addition to 227, in 1 h. It seems to favor the acyclic oxocarbenium pathway because the intermediate can readily recyclize intramolecularly to the a-anomer. Then the question remains as to whether the cyclic oxocarbeiuum ion is the sole intermediate for reduction of both a- and p-anomers. This may be true if a weak reducing agent, such triethoxysilane is employed, which gives mily 2.6 % and 5.3 % of 227 in 0.5 and 1.0 h, respectively. However, it should be pointed out that the rate of formation from the p-anomer is about twice as high as that from the a-anomer. If the cyclic oxocarbenium ion is the sole intermediate, the rates should be very similar for both the a- and p-anomers. 

Cyclic oxocarbenium ion with nucleophilic attack by acceptor... 

Figure 8 The chemical glycosylation reaction often proceeds via a cyclic oxocarbenium ion that can produce either the a- or p-anomeric products. Stereochemical control of the glycosylation reaction as illustrated (a) without neighboring group participation (R = benzyl, etc.) and (b) with neighboring group participation (R = acetyl, benzoyl, etc.). LG, leaving group.

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