Partial anomeric effects

It is possible and probably very likely that both types of electronic effects are occurring in the acetal function. In other words, 2 could be more stable than 2 because 2 is stabilized relative to 2 by a partial electron transfer and 2 is destabilized relative to 2 by electronic repulsions. There is presently no experimental technique to differentiate between the two effects. At the present time, many chemists, including myself, prefer to consider the anomeric effect as a stabilizing rather than a destabilizing effect. The main reason is that the concept of stabilization of a system through electronic delocalization is a well established principle in organic chemistry. The resonance theory is indeed based on this principle. I believe that this concept rather than the dipole - dipole or electron pair - electron pair repulsions allows the organic chemist to rationalize his results better. 

A should be shorter than a normal C —0 ether bond because it has a partial double-bond character due to the anomeric effect, whereas the C - 0 R bond... 

Stereochemical control in 0-alkylative /3-glycosylation relies on the kinetic anomeric effect [110] namely, that the oxyanion derived from a reducing sugar is more reactive in its 8-ori-ented form 71B than the corresponding a-anion 71A which should be more abundant. This tactic has met with partial success in cases of reactive substrate [111] (O Scheme 38). For example, reaction of 72 with a primary triflate in THF in the presence of NaH afforded the 8-glycoside in 62% yield. 

As a corollary to the foregoing discussion, the computations also provide an answer to the controversial question of the influence of assumed geometry on the calculated, conformational-energy differences. The results present evidence ofthe necessity of at least a partial optimization, including the main bond lengths and bond angles, in the theoretical calculations of molecules exhibiting the anomeric and exo-anomeric effects. - ... 

In closing this short and incomplete, theoretical excursion into the field of reaction stereoselectivity in carbohydrates, we have also to mention that some other aspects in this article have been treated only partially for instance, the anomeric effect in rings other than six-membered, or in carbohydrate radicals. It is hoped that the present article has shown that many questions on the nature and various manifestations of the anomeric and related effects have already been answered. The problems still remaining to be solved will attract growing attention. " We believe that this survey. 

Let us examine equilibrium 14a 4= 14b. If only steric effects operated, the free energy difference for this process would be AG° g(, . However, anomeric effects influence the equilibrium. Substrate 14a is stabilized by two partial anomeric effects AG g,j,)x AE(a)v while 14b is stabilized by only one AG g(g,x. The free energy change for the reaction 14a t 14b, AG° g, should then be given by Eq. [6] ... 

The reverse anomeric effect occurs if the first atom bound to Cl is either positively charged (pyridinium) or carries a partial positive charge (car-bomethoxy). Mutarotation can be conveniently followed by measurements of H-NMR spectra. The hemiacetal methine proton appears at lower field than the other methine protons of the carbohydrate (e.g., at d = 4,97 ppm for an a-pyra-nose). Furthermore, large coupling constants (J = 6-9 Hz) indicate an axial-axial orientation of the protons at Cl and C2, whereas small coupling constants (J = 1-4 Hz) point to equatorial-equatorial or axial-equatorial relationships between these protons (Fig. 4.2.12). 

A second type of monoacetal is known for D-fructopyranose, namely, the 2,3-O-alkylidene-jS-D-fructopyranose structure (54). A distorted CJ(d) conformation is indicated for the isopropylidene acetal 5 (54, R = R = Me), from proton magnetic resonance data. Undoubtedly, this conformation is not favored for /3-D-fructopyranose itself, because of unfavorable steric and anomeric effects (see This Volume, Chapter 2). It is unreasonable to expect that monoacetal 54 will be formed directly from jS-D-fructopyranose, because a much more favored pathway, leading to monoacetal 52, is available. This consideration precludes a second, possible avenue to diacetal 55, namely, alkylidenation of 0-4 and 0-5 of 54. Monoacetals of type 54 can be prepared by partial hydrolysis of diacetals of type 55. 

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%). 

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