Anomeric effect source

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... 

The key piece of evidence for the rationalisation of the anomeric effect in terms of classical electrostatic dipole interactions has been the apparent existence of a reverse anomeric effect. Reversal of the sense of the dipole of the C-X bond, so that X now carries a net positive rather than negative charge, should, on the electrostatic picture, result in X having a more than ordinary tendency to be equatorial. The effect was first observed in glycosyl pyridinium salts and, in what at first sight seemed to be an elegant experiment, the steric demand of the bulky pyridinium salt was apparently eliminated as the source of the effect by the observation that tri-O-acetyl-ot-D-xylopyranosylimidazole changed from 65% to > 95% equatorial on addition of excess acid. Protonation of imidazole will have only a minor effect on its steric requirements, since protonation takes place at a remote site . ... 

Figure 11. Attractive interactions (attr.) in 79c as a source of the reverse anomeric effect.

Results of molecular mechanics calculations were also used by us to explain the source of the anomeric effect in the Y—C—P=X (X, Y = O, S) system (79). As model compounds we chose 55,108, and 109 (Scheme 35). 

It would be very interesting to obtain AEl and AEd values for, for example, O—C—O, S—C—S, and Se—C—Se anomeric interactions as a function of appropriate torsion angles so as to establish the relative importance of stabilizing and destabilizing interactions as a source of the observed anomeric effects. So far, NBO analysis has been applied to the elucidation of anomeric effects involving silicon centers (145) (see ref. 144 for a PMO approach), to Se—C—Se anomeric interactions (148), and to the study of fluorinated amines (146) F AH NH2. The amine study showed that due to the two... 

The dependence of the magnitude of the coupling constant Jc—p on the position of phosphorus in 2-P-substituted 1,3-diheteroanes was discussed in Section IV.B.3.b. While the argument supports ny-negative hyperconjugation as a source of the anomeric effect in 1,3-dioxane derivatives as well as in all phosphonium salts, the relationship between the Jc—p coupling constant through the axial and equatorial C(2)—P bonds in nonionic... 

Anomeric and double anomeric effects in phosphates The unusual stereoelectronic properties of negatively charged oxygen as a source of donor orbitals play a role in the formation of tetrahedral intermediates in nucleophilic addition/substitution at carbonyl. It also has important consequences for phosphate transfer reactions - one of the key types of chemical events in biology. 

Notes and discussion. In this procedure, a source of HCl is generated in situ through reaction of acetyl chloride with free A -acetyl D-glucosamine. This also results in concomitant peracetylation the peracetate then reacts as expected, with loss of anomeric acetate and, once again as a result of the anomeric effect, the a-chloride is the major product. If difficulty is experienced with crystallization then purification can be effected by flash chromatography (petroleum ether 40/60 ethyl acetate, 1 2) but yields are typically lower in this case due to partial hydrolysis ( 60%). 

While the silver and zinc salts were effective Lewis acids for these cyclizations, Kikugawa and coworkers reported that the alkoxynitrenium ions could be generated directly from hydroxamic esters (4) using hypervalent iodine oxidants such as hydroxy(tosyloxy) iodobenzene (HUB) and phenyliodine(lll)bis(trifluoroacetate) (PIFA) . Presumably, with such reagents the reactions proceed through A-(oxoiodobenzene) intermediates (54), which can themselves be regarded as anomeric hydroxamic esters and sources of alkoxynitrenium ions (55) (Scheme 11). 

Note the preferential reaction at the anomeric hydroxyl. The method is also effective for the protection of primary and secondary alcohols. A modification of this approach which uses f-Bu0C02CH2CH=CH2as the allyl source selectivity monoalkylates a tertiary hydroxyl in the erythronolide derivative. 

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