Anomeric effect energy

While the lone pair on the hydroxyl oxygen of hydroxamic acid 77 would be tightly bound resulting in a weak noH-cr N Qr interaction, the anion 78 would possess a high energy pair of electrons that would enhance the anomeric effect and drive the rearrangement. 

The conformational energies of monosubstituted oxanes studied to date are collected in Table I. In position 2, polar substituents (except NR2) prefer the axial position other substituents prefer the equatorial orientation, which is generally the case for groups in positions 3 and 4. Destabilizing 1,3-diaxial interactions cause the equatorial geometry to be usually favored in the 2-position, the anomeric effect stabilizes the axial conformation. A large purine moiety in position 2 of oxane, for example, prefers the equatorial position because the 1,3-diaxial interactions overcome the anomeric effect (75TL1553). 

Eliel et al. (82JA3635) examined the conformational equilibria of a number of disubstituted oxanes (Table III) by low-temperature C NMR spectroscopy (830MR94) and estimated the AG° values of 3-Me and 2-C=CH substituents (see Table I). The concentration of the axial 2-Me and 4-Me conformers, however, was so small and difficult to detect by NMR spectroscopy that they were forced to employ the use of counterpoised di-2-C=CH and ds-2-CH = CH2 groups to generate equilibria that were sufficiently balanced to measure accurately (AG° values in Table I). Eliel et al. (82JA3635) also discussed the conformational energies in terms of 1,3-diaxial interactions and the anomeric effect. 

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. 

Anomeric effects are evident from dynamic NMR studies on at least one substrate, N-benzyloxy-Af-chlorobenzamide (2c) ". In acetone-de the benzyl aromatic signal (S 7.85) de-coalesced into two signals (ratio 2 1) close to 200 K, corresponding to a free energy barrier of ca 10-11 kcalmoH Amide isomerization appeared to be faster than N—0 rotation since benzoyl resonances were largely unaffected. 

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