Origin of the anomeric effect

Figure 3.9a may also represent the interaction of a nonbonded ( lone-pair ) orbital with an adjacent polar n or a bond [67]. If a polar n bond, one can explain stabilization of a carbanionic center by an electron-withdrawing substituent (C=0), or the special properties of the amide group. If a polar a bond, we have the origin of the anomeric effect. The interaction is accompanied by charge transfer from to A, an increase in the ionization potential, and a decreased Lewis basicity and acidity. These consequences of the two-electron, two-orbital interaction are discussed in greater detail in subsequent chapters. 

But it can do this only if the chlorine is axial Remember what we pointed out earlier the oxygen s equatorial lone pairs are parallel with nothing but bonds in the ring, so the oxygen s axial lone pair is the only one that can help stabilize the molecule, and it can only do this when the Cl is axial. Only the axial conformation benefits from the stabilization, and this is the origin of the anomeric effect. 

Finally, a less conventional explanation of the origin of the anomeric effect may be mentioned. In a communication, " it was stated that, contrary to the results from measurements and theoretical calculations, the equilibrium coitstant for axial-equatorial equilibrium in... 

Thus, the exo anomeric effect is not manifested in the C—S—C—P( ) system, in contrast to what has been observed for the C—O—C—N system by Booth et al. (85) (40, vide supra). This finding has serious consequences, insofar as the origin of the anomeric effect in this system is concerned. They will be discussed in Section V.B.l. 

Let us focus on molecules I4a and 14b (Scheme 8) in which an anomeric effect (in AG° or AH° terms) is possible in the vapor phase. Usually, the dipole moment of 14a is less than that of 14b (125-128). Since the more polar form is stabilized in solution (114, 128) [as a rule, with several exceptions (29, 129) vide infra] it may happen that the anomeric effect (i.e., increased preference for 14a) disappears in solution or may even change its sense (from AG g > 0 to AG g < 0). Such a possibility has been supported by quantum chemical calculations for dimethoxymethane (128). It was shown that, while in CCI4 solution dimethoxymethane (11) exists almost exclusively as the most stable sc, sc conformer, in aqueous solution almost exclusive occurrence of the ap, ap conformation may be expected. Hence, all considerations regarding the presence, magnitude, or origin of the anomeric effect must take... 

Fuchs et al. (129). They suggested that when the molecular dipoles of the axial and equatorial conformers are of similar magnitude, the more polar double bond-no bond structure, resulting from hyperconjugative interactions in the axial conformer, 54a (see Scheme 20), will be stabilized in the more polar solvent. This hypothesis would support the importance of the hyperconjugative origin of the anomeric effect. The appearance of a large proportion of the axial conformers of 2-(arylseleno)-l,3-dithianes 37 (Scheme 13), even in... 

Thus the synclinal conformer of fluoromethanol (121) appears to be preferred due to overlap repulsion as well. This conclusion is of significance, since it provides additional proof for the role of destabilizing interactions in the origin of the anomeric effect. Though the importance of destabilizing interactions involving lone electron pairs seems to be well established even in the... 

From the accumulated experimental and theoretical observations it is evident that both factors contribute to the anomeric effect. Nevertheless, alternative theories have been advanced recently to account for the origin of the anomeric effect, and some of them will be discussed in Section 4. 

In principle, the examples illustrated above seem contradictory, suggesting that the origin of the anomeric effect in heterocycles is not a consequence of an effect alone, but is the result of several factors working together (95MI5, HCAR1047). 

There has been an ongoing controversy regarding the origin of the anomeric effect. Most recently, Mo denied the importance of hyperconjugation based on block-localized... 

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