Orbitals anomeric interactions

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 interactions are also affected by the sizes of the interacting orbitals and will be best where the Y has orbitals of similar size to N. Thns, in an ONCl system, the similarity in size of orbitals on N and O and lower energy of the N—Cl a orbital favours the no-anomeric effect over the alternative nci-[Pg.844]

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. 

The anomeric effect is well reproduced at the 4-3IG level by ab initio calculations on methoxymethanol (Jeffrey et al., 1974). The most stable form, g g, is calculated to be B.Okcalmol" below the second, the ag form. In the former, two anomeric interactions are possible, and in the second only one. Similar results were obtained for dimethoxymethane with a 6-3IG basis set (Jeffrey et al., 1978). In this study, shortening of the central O—C—O bonds and lengthening of the terminal C—O bonds were observed, in agreement with experiment. These effects reflect the different degrees of double-bond character due to different degrees of back-donation of the lone pairs into the G c-o orbitals. 

Homoanomeric effects Several interactions that involve a lone pair of atom X with the acceptor orbital in a X-CH-CHY- moiety have been snggested in the literatuie. - Such skipped versions of the anomeric effect (i.e. the homoanomeric effects) include the W-effect in azacyclohexanes and the Plongh effect in oxa- and thiacyclohexanes (Figure 6.78). Such through-space effects are conceptually different from the classic anomeric interactions and will be discussed in more detail in Chapter 9. 

Similar effects apply to aromatic ethers and related compounds. Chein and Corey discovered an interesting stereoelectronic preference for heteroaromatic ethers to orient the OR group in a way that minimizes lone pan-repulsion of the exocyclic substituent o-lone pair and the lone pair of nitrogetf but maximizes the anomeric interactions between OR lone pairs and endocyclic C-X bond. The antiperiplanar interactions of this type are likely to contribute as well, more so in the six-membered cycles where the interacting orbitals can easily adopt the ideal parallel geometry (Figure 6.121). 

The rationalization of the conformational anomeric effect solely based on electrostatic interactions fails to account for these solvent effects. Another interpretation based on bond polarizability in 1,1-dialkoxyalkyl systems calls electronic transfer from a non bonding electron pair of one oxygen atom to the empty cr c 0 orbital from the other alkoxy substituent (Fig. 10).16... 

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