Anomeric effects attack

The turning of the key once the complex has formed is a separate issue. In this regard, Lemieux (47) has pointed out that rotation about the glycosidic bond must weaken the exo-anomeric effect and thereby importantly activate the anomeric carbon to nucleophilic attack. Therefore, it seems likely that the role of the key hydroxyl group of the aglycon is to accommodate the rotation prior to the attack by water to form / -D-glucopyranose, which is the first product of the reaction. 

In contrast, the mannosyl radical 8 does not undergo such a conformational change, and the observed a-attack results from the shielding effect of the axial C-2 substituent in the chair conformation and the stereoelectronic effects mentioned earlier. In radicals 7b and 8 the C-O bonds adjacent to the radical center are coplanar with the singly occupied orbital. This reminds us of the anomeric effect in which an interaction between the nonbonding electron pair of the ring oxygen and the LUMO of the C-O bond stabilizes the conformation. 

The polarized-TT frontier molecular orbital (PPFMO) method has been employed to study protonation and sulphenylation of sugar-related dihydrofurans and tetrahydropy-rans. The predictions are consonant with the experimental observations62. Contrary to expectations, the proton-catalysed addition of alcohols to glycals, such as 30, has been shown by isotope labelling (2H) not to be anii-diaxial addition. This observation has been rationalized by the initial attack by deuteron from the bottom, giving ion 31, and by the anomeric effect favouring axial substituent at C-l (32)63. 

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. 

Starting with phosphite 59 stannous triflate catalyzes the formation of an oxenium ion 60, which is stabilized by the solvent (61). The complex 61 is more favored than 63, justified by the reverse anomeric effect until now. But as it is shown there is no possibility for 61 to react in an SN2 reaction to 62. The intermediate 63 can be attacked by the alcohol functionality of the glycosyl acceptor, and with MeCN as leaving group you get 64. Ultimately the equilibrium between 61 and 63 shifts completely to 63. This kind of stereocontrol during a glycosylation is known as the nitrile effect.28... 

Small differences between anomeric effects of a and p anomers and inherent ring flexibilities have complicated the development of a general method for stereoselective introduction of 1,2-m-furanosides. By examining possible conformers of the arabinofuranosyl oxocarbenium ion, factors that favor attack from the p face (a 1,2-cis attack) were identified. Oxocarbenium ions of furanosides can adopt 3E or E3 as two possible low-energy conformations (Scheme 4.15). The Newman projection of the E3 conformer of D-arabinofuranose showed that nucleophilic attack from the a face is disfavored because an eclipsed 2-H will be encountered. On the other hand, an approach from the p face is expected to be more favorable because it experiences only staggered substituents. 

Finally, the simple nucleophilic amine Me2NH attacks the epoxide with inversion of configuration to give methyl mycaminoside. The conformational drawing shows that all substituents are equatorial except the MeO group, which prefers to be axial because of the anomeric effect. 

HCl in Et0H/H20 (1 1, reflux, 30 h). In agreement with X-ray and NOE measurements of (451) and consistent with the assumed operation of an exo anomeric effect, reactive diene conformations (Q) and (R) were proposed. It was therefore inferred that the major cycloaddition pathway involves attack of the dienophile (452) at the least-hindered top face of conformer (Q). 

The observed diastereoselectivity was rationalized on the basis of a kinetic anomeric effect increasing the reactivity of certain conformers, which control the direction of the attack [44]. Vasella also applied V-ribofuranosylnitrones in the 1,3-dipolar cycloaddition to alkenes [43]. However, the selectivities obtained from these nitrones proved to be lower than those obtained with 51. 

Wulff has postulated (26) and we have previously implied that these ether solvents act to form incipient or real trialkyloxonium ions that adopt a favored equatorial configuration (the reverse anomeric effect) and are attacked... 

Regarding the reaction mechanism, Whitesides and coworkers also postulated that the presence of a j8-nitrilium ion was the source of stereocontrol. In their proposed mechanism, the xanthate 27 initially reacts with the PST promoter to form 35 (Scheme 13). Subsequent loss of 36 leads to the oxocarbenim intermediate 31. Attack by acetonitrile is presumed to occur from the less hindered a face and leads to the presumably thermodynamically more favorable equatorial nitrilium ion 37 because of the reverse anomeric effect [13,14]. However the equatorial nitrilium ion is believed to be in equilibrium with the more reactive fi species 32. Acetonitrile is then displaced from this species by the glycosyl acceptor in an SN2-like maimer for form the a-glycosidic linkage in compound 38... 

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