Anomeric effect lone-pair orbital interactions

The paucity of information on the mechanism of reactions, and on the structure of the transition state, and the role of the anomeric effect in its stabilization, constitutes the main reason why qualitative interpretation of reactivity as shown in the aforementioned examples is still very rare. An alternative, more-popular estimation of the relative reaction-rates of con-formers is based on the lone-pair orbital interactions, and their symmetry and energy in the ground state, and could be loosely associated with the perturbation theory of chemical reactivity. ... 

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. 

In Figure 126, the tri-0-acetyl-P-D-xylopyranosyl chloride anomeric effect of the single chlorine drives the equilibrium to favor the conformation with the three acetoxy groups in the axial positions. From a molecular orbital viewpoint, the anomeric effect results from an interaction between the lone pair electrons on the pyran oxygen and the d orbital associated with the bond to the C2 substituent. 

Hence, the anomeric effect [positive value of AE(AE3)] can appear at a suitable combination of the V and V coefficients. Because the V, term is associated with the dipole-dipole interactions of polar groups, and the V2 term with delocalization interactions of lone-pair orbitals on heteroatoms, it may be concluded that the latter equation also effectively describes a balance... 

Computation of the conformational energies of 2-methoxytetrahydropyran, a model for the methyl aldopyranosides, gave results in agreement with experimental observations. A preference for the axial conformer was apparent, but the nature of the stabilizing factor (anomeric effect) was not resolved. Force-field calculations have been extended to include alcohols, ethers, simple acetals, and 2-methoxytetrahydropyran. 2 The preference of 2-methoxytetrahydropyran for the axial conformer was attributed to interaction of the axial lone-pair orbital on the ring-oxygen atom with the axial C—O bond of the methoxy-group, which can be represented by the resonance structure (501) (see also, Vol. 6, p. 163). 

In cyclic systems such as 1, the dominant conformation is the one with the maximum anomeric effect. In the case of 1, only conformation lA provides the preferred antiperiplanar geometry for both oxygens. Antiperiplanar relationships are indicated by including lone pairs in the oxygen orbitals. Other effects, such as torsional strain and nonbonded repulsion, contribute to the conformational equilibrium, of course. Normally, a value of about 1.5 kcal/mol is assigned to the stabilization due to an optimum anomeric interaction in an acetal. 

By definition, a generalized anomeric effect is observed at carbon of an XCY system when a molecule preferentially adopts a conformation that optimizes a secondary, stabilizing electronic interaction involving overlap between the lone pair on one heteroatom with the a orbital of the bond between the central carbon atom and the second heteroatom . Figure 5a illustrates that in XNY systems, as with anomeric carbon centres, two anomeric interactions are possible and involve either an ny-CT x ° nx-o NY overlap where nx and ny represent the p-type lone pairs on X and Y and NX and NY represent the N—X and N—Y a orbitals. In either case, the result is a net stabilization of the lone pair of electrons (Figure 5b). Except where the nitrogen is symmetrically substituted, one of these interactions will be strongest. 

Anomeric effects in ONCl systems are Uo-Oj a even though oxygen is more electronegative than chlorine N and O orbitals are similar in size and chlorine is a 3p element, thus favouring overlap between the p-type lone pair on O with the low-energy N-Cl <7 orbital. In XNY systems, occupation by Uy leads to transfer of electron density to the X substituent and the substantially higher electron affinity of chlorine will also favour this anomeric interaction rather than an Uci-cTno overlap. 

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