Anomeric effect saturation

In a previous section we have discussed the importance of n—a conjugative interactions in dictating the axial-equatorial preference of an electronegative substituent at C—1 of a pyranose ring, i. e. the anomeric effect . Here, we shall extend the discussion of n—a conjugative interactions to other saturated heterocyclic molecules. 

It is observed that only the latter, 1 J(C, Ha), is affected by the dielectric solvent effect, while (C, Hs) is notably insensitive to such an effect. The former increases monotonically when increasing s, i.e., the inhibition of the anomeric effect yields an increase in (CjHa) however, a saturation effect is observed for e close to 10. In the same paper specific interactions between solute and solvent effects were taken into account considering one-to-one complexes for solute and DMSO and one- and two-to-one for solute and water. Dielectric solvent contributions to proximity effects on (C, H) were also considered it is observed that the dielectric solvent yields a decrease in any of the proximity effects considered in the paper. In a subsequent paper, Zaccari et al394 studied medium effects on 1 J(C, H) and 2J(C, H) couplings in acetaldehyde, [45], a topic previously studied by Ando et al.413... 

An anomeric effect is observed in 3,4-dihydro-2H- pyrans. For example, a 2-alkoxy group preferentially occupies an axial position (71DOKd96)367>. Indeed, a study of the NMR spectra of some 2-alkoxy-3,4-dihydro-2//-pyrans and their 4-methyl derivatives established that the anomeric effect was more important in the unsaturated heterocycles than in the corresponding tetrahydropyrans (72BSF1077). The axial preference of an alkoxy group is even more accentuated when the double bond is associated with a fused benzenoid ring, as in the 2-alkoxychromans. It is also of interest to note that the role of the polarity of the solvent on the conformational equilibrium is less important than for the saturated analogues. 

As indicated in Scheme VII/32, cyclononanone (VII/165) is transformed into hydroperoxide hemiacetal, VII/167, which is isolated as a mixture of stereoisomers. The addition of Fe(II)S04 to a solution of VII/167 in methanol saturated with Cu(OAc)2 gave ( )-recifeiolide (VII/171) in quantitative yield. No isomeric olefins were detected. In the first step of the proposed mechanism, an electron from Fe2+ is transferred to the peroxide to form the oxy radical VII/168. The central C,C-bond is weakened by antiperiplanar overlap with the lone pair on the ether oxygen. Cleavage of this bond leads to the secondary carbon radical VII/169, which yields, by an oxidative coupling with Cu(OAc)2, the alkyl copper intermediate VII/170. If we assume that the alkyl copper intermediate, VII/170, exists (a) as a (Z)-ester, stabilized by n (ether O) —> <7 (C=0) overlap (anomeric effect), and (b) is internally coordinated by the ester to form a pseudo-six-membered ring, then only one of the four -hydrogens is available for a syn-//-elimination. [111]. This reaction principle has been used in other macrolide syntheses, too [112] [113]. 

Some substituents of saturated heterocycles prefer to be axial the anomeric effect... 

The anomeric effect is general in that broadly the same effects are shown, whether the saturated six-membered ring contains an oxygen, a nitrogen or a sulfur as the heteroatom. In the case of sulfur the C-S single bond (0.182 nm) is longer than its C-0 counterpart, and so 1,3-diaxial interactions are less important in the thiacyclohexane case. Solutions of the trithiacyclohexane 51 do not contain any equatorial isomer. 

A negative value of AG(AE1) represents the reverse anomeric effect. It could, perhaps, also be defined in the context of Eq. 4. Here, the reference saturated hydrocarbons exhibit negative energy AE(AE3), and the reverse anomeric effect could be defined as an excess energy (in al lute value) over that for the reference molecules. 

X-ray diffraction studies have suggested that the anomeric effect operates in 2-phosphinoyl derivatives of the saturated heterocycles, where the 2-substituent has no lone electron pairs. For example, in 2-diphenylphosphinoyl-l,3-dithiane, the substituent occupies an axial position, in contrast to the 1,3-dioxane and 1,3-oxathiane derivatives, where the same substituent occupies an equatorial position <84JOC3026,88JOC3609,88TL6801>. 

From a more extensive n.m.r.-spectral study of various acylated, 2,3-un saturated aldose derivatives, it was further observed that the anomeric effect is a dominant factor in determining the conformations of these derivatives. Thus, tetra-O-acetyl-3-deoxy-a-D-cryfhro-hex-2-enopyranose (39) adopts the f/ conformation, whereas the corresponding /3-D anomer (40) exists in the alternative conformation... 

The anomeric effect is an empirical, thermodynamic stereoelectronic effect that states the preference for heteroatoms to occupy the axial position in saturated six-membered heterocyclic ring systems, notably carbohydrates (Lemieux and Koto, 1974 Szarek and Horton, 1979). Features of the anomeric effect had been remarked upon many years before its advent in... 

Anomeric Effect in Saturated Heterocyclic Ring Systems... 

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