Conformations of oxocarbenium ion

The above experimental results are in full agreement with the ccmclusions that can be drawn from studying molecular models. Namely, the conversirm of a chair conformatiOTi of a hexopyranoside to the corresponding half-chair conformation requires coimterclockwise rotatirMi about the Cl-05 bond and the coimterclockwise rotatirai about the C2-C3 bond, but not about the C5-C4 bmid. The slight increase in the Pitzer strain that results from these rotations in the course of conversion of a chair to a half-chair conformation of oxocarbenium ion transition state is not... 

The primary C [63, 64], as well as secondary a-deuterium [65] isotope effects, were consistent with this SN2-type itinerary. The conformation of oxocarbenium ion requires the coplanarity of the C5,05, Cl, and C2 atoms of pyranoside ring, and there are four possible conformations of transition state structure in which the C5, 05, Cl, and C2 will be coplanar (Fig. 3.21) the 76), the B.4 (77), the B2, 5 (78), and the (79) conformer. The route from reactant to the product via transition state TS is called the substitution pathway. 

Ayala L, Lucero CG, Romero JAC, Tabacco SA, Woerpel KA (2003) Stereochemistry of nucleophilic substitution reactitms depending upon substituent evidence for electrostatic stabilization of pseudoaxial conformers of oxocarbenium ions by heteroatom substituents. J Am Chem Soc 125 15521-15528... 

Interplay of Stabilized Bicyclic Carbocation and Two H Conformations of Oxocarbenium Ions... 

Figure 3.1 Stereochemistry of oxocarbenium ions. Top the methoxymethyl cation, showing overlap between an empty p orbital on carbon and a p-type lone pair of electrons on oxygen and also the two mechanisms for isomerisation. Rotation involves breaking the n bond, via a perpendicular transition state, whereas during inversion the ion remains planar and the oxygen atom undergoes a process similar to the inversion of ammonia. Centre the two permitted conformations of a xylofuranosyl cation. Bottom the four permitted conformations of a xylopyranosyl cation.

Finally, considerable progress has been made with regard to gas-phase conformational analysis of monosaccharides and their hydrated complexes by comparison of their IR spectra with that predicted by ab initio calculations.76 78 Many of the tools are therefore available to place a sugar in the gas phase, cleave the glycosidic bond, isolate the oxocarbenium ion, and then have the opportunity to study the kinetics for nucleophilic capture by direct kinetic techniques. Experiments such as competitive KIEs for capture of the oxocarbenium ion also seem possible. Such work may allow direct experimental determination of oxocarbenium ion lifetimes, barriers for capture, and transition state structures. Differences observed between gas-phase results and those in solution may reveal the role that solvent plays in the reaction. 

Studies of Woerpel et al. of conformational preferences of oxocarbenium ions revealed that electronic effects exert strong influences on the conformational preferences of these cadmis. For reactions involving C3 and C4 alkoxy-substituted tetrahydropyran cations, the pseudoaxial conformations of the oxocarbenium imi intermediates 23 and 24 (Fig. 4.9) were consistent with the formation of the, A-tram- and the 1,3-c/s products, respectively (Fig. 4.9) [19,20]. The pseudoaxial conformations of the oxocarbenium ions are favored because they are stabilized by electrostatic interactions between the positively charged atoms of the cations and the partially negatively charged substituents [8, 11, 19, 20, 65]. The results with... 

Knowledge of the contributions of individual substituents to the conformational preferences of oxocarbenium ions, however, is not sufficient to predict the reactivities of highly substituted systems such as those formed from carbohydrates. [Other intermediates, aside from discrete oxocarbenium ions, could also lead to the nucleophilic substitution products. For an example involving ion-pair intermediate, see Crich et al. [15].] For the type of substrates presented in this work, neither the Lewis acid nor the solvent has significant influence upon product distribution as described in Ref. [19]. For instance, although the influences of the C2, C3, and C4 substituents on the mannopyranosyl cation should reinforce each other to favor P-product, a-selectivity was observed upon allylation of the mannosyl phosphate 29 (Fig. 4.10) [Allylation of maimosyl phosphate 29 has been shown to be highly a-selective with MesSiOTf [67]. C-Mannosylation reactions are generally a-selective [68-76]. a-Selectivity was also observed with acetate-protected... 

On the other hand, it has been demonstrated that the a-D-glucopyranosyl aceto-nitrilium ions are stereospecifically generated from the corresponding oxocarbenium ions in dry acetonitrile [43-45]. These results indicate that the acetonjtrilium ions are axially oriented by an anomeric effect. Recently, it has been concluded from the conformational analyses of glucopyranosyl-ammonium and glucopyranosyl-imidazolium derivatives that the reverse anomeric effect does not exist [46,47]. 

From a strictly chemical point of view, the synthesis of glycosides still presents a formidable challenge to synthetic chemists in spite of major advances in the area [1], Unlike peptidic bonds, the formation of the glycosidic linkage is subject to various factors that include, among others, electronic, stereoelectronic, conformational, substituent, and reactivity effects generally associated with incipient oxocarbenium ions derived from carbohydrates. 

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