Anomeric effect interpretation

The stereoselectivity of these reactions has been interpreted in terms of chair-like six-membered ring transition states in which the substituents a to tin adopt an axial position, possibly because of steric and anomeric effects. The cc-substituted (Z)-isomers are less reactive because the axial preference of the a-substituent would lead to severe 1,3-diaxial interactions17. 

In an attempt to isolate the anomeric effects, analogous phosphonites have been studied. Equilibration of cis- (109) and /ra 5-2-methyl-5-t-butyl-l,3,2-dioxaphosphorinanes(l 10) demonstrated the thermodynamic preference for cis over trans (72% and 28% respectively at 40 °C). This surprising result must mean that axial P-methyl is more stable than equatorial even when no anomeric effects are present, and the authors interpret their n.m.r. results in terms of two equilibrating conformers for trans- 10)... 

The first interpretation of the conformational anomeric effect, given by Edward,2 invoked more favorable electrostatic interactions in the axial anomers than in the equatorial anomers of carbohydrates (Fig. 8). 

Fig. 8 Interpretation of the conformational endo-anomeric effect according to Edwards (hard/hard interactions).

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... 

Fig. 10 Stereoelectronic interpretation of the conformational endo- and exo-anomeric effects [ (()) -> a c o hyperconjugation].

In conclusion, we would like to mention that a hyperconjugative interpretation of the anomeric effect has been offered by various workers such as Romers and Altona333, Pople et a/ 43 and Salem et al.344. ... 

The very marked anomeric effect shown by 2-alkoxytetrahydropyran-3-ones (199) has been interpreted in terms of stabilizing orbital interactions (77NJC79). The influence of the heteroatom and the carbonyl group on the stabilization of the conformer in which the alkoxy group is axial is apparent. 

In the second section of this review the failures of ALPH will be discussed these failures occur very largely in the heterolytic chemistry of acetals. Such reactions are characterised by late transition states. The theoretical basis of ALPH, and the closely related frontier-orbital rationalisation of the static anomeric effect, will be described and various difficulties in these interpretations pointed out. 

The stereoelectronic situation of anomerically bound substrates is decisively influenced by the exo anomeric effect. Lemieux et al. [14] have found that the rotation around the exocyclic C-O-bond of glycosides is strongly hindered. This observation is interpreted as a delocalization of the lone pair of the oxygen into the a of the ring-C1 -O6 bond of the carbohydrate. Analogous n-a delocalization sterically adjusts glycosylamine derivatives in a preferred conformation (Scheme 2). 

The /ra -6-fluoro-3,6-dihydro-1,2-oxathiin 2-oxide 126 prefers a conformation in which the ring oxygen lies almost in the plane of the four carbon centers and the S=0 bond resides in a pseudoequatorial orientation. The fluorine substituent adopts a stable pseudoaxial orientation. Quantum-chemical calculations suggest a stabilizing anomeric effect which was interpreted in terms of an n0 a C-F hyperconjugative interaction <2002CEJ1336, CHEC-III(8.10.3)688>. 

Hphe term anomeric effect was introduced by Lemieux in 1958 as a result of a detailed study of the anomerization of acetylated pento-and hexo-pyranoses. The effect is well known to carbohydrate chemists, and refers to the tendency of an electronegative substituent at C-l of a pyranoid ring to assume the axial rather than equatorial orientation, in contrast to predictions based solely on steric grounds. However, the phenomenon is not restricted to carbohydrate systems, but is displayed in many types of heterocyclic compounds. Thus, the investigation of the anomeric effect has been of considerable interest to a variety of chemists, namely, theoreticians, structural chemists, physical organic chemists, and synthetic chemists. Chemists from all of these areas participated in the Symposium on The Origin and Consequences of the Anomeric Effect. This symposium was the first symposium devoted exclusively to a discussion of the anomeric effect, and it provided a mechanism for interactions between the diverse types of chemists. The chapters in this volume are not merely the texts as presented at the symposium, but they also incorporate some new interpretations by the authors resulting from these interactions. 

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