Anomeric effect hyperconjugation

Anomeric effects Hyperconjugative electron transfer into a C-H orbitals can lead to increased shielding and decreased chemical shift of protons antiperiplanar to unshared electron pairs. This effect in tris-amines is illustrated in Figure 12.22. In the acyclic compound, where free rotation is possible, the methyl resonance appears at 3.02 ppm. When lone pairs are forced to be syn-periplanar, the relative inefficiency of anomeric effects allows... 

The anomeric configuration is set in the reductive lithiation step, which proceeds via a radical intermediate. Hyperconjugative stabilization favors axial disposition of the intermediate radical, which after another single electron reduction leads to a configurationally stable a-alkoxylithium intermediate. Protonation thus provides the j9-anomer. The authors were unable to determine the stereoselectivity of the alkylation step, due to difficulty with isolation. However, deuterium labeling studies pointed to the intervention of an equatorially disposed a-alkoxylithium 7 (thermodynamically favored due to the reverse anomeric effect) which undergoes alkylation with retention of configuration (Eq. 2). 

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 nature of the anomeric effect in the bicyclic /ra r-fused octahydro-l-methyl-l//-2,l-benzothiazine 2,2-dioxide 37 has been examined by single crystal X-ray structure analysis (Figure 5) <1998CJC164>. The crystal structure of 37 shows that the A -Me group assumes an axial position in the solid state. The authors suggest that this conformation is also the most stable in solution and propose that this hyperconjugation effect is >2.0 kcal mol . ... 

In the corresponding nonfluorinated 4,5-dialkylsultines, the sultine ring adopts a half-chair conformation with the S=0 bond in a pseudoaxial orientation 50 (cf. Scheme 12) <20030EJ4911>. Again, hyperconjugative interactions within the sulfinyl moiety (the anomeric effect ) were found to be responsible for the conformational preference. 

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>. 

Much of the computational literature of glucose pertains to the ratio of the two anomers. This is formulated as the anomeric effect the stability of the a anomer, with its axial group, over the expectedly more stable p anomer, where the hydroxyl group occupies the equatorial position. This has been rationalized in two ways (1) minimizing the dipole-dipole repulsion because of the C-O bonds or (2) hyperconjugative stabilization by donation of the ring oxygen lone pair... 

Even less obvious in this particular case is evidence that the less-substituted radical is actually more stabilised, presumably by negative hyperconjugation with the f3 C—F bonds, than the more-substituted radical is by the attached F atoms.997 Furthermore, in the other striking reversal of expectations, the tert-butoxy radical, which is certainly more electrophilic than methyl, adds to 1,1-difluoroethylene 7.45 at the substituted carbon with a selectivity of 80 20,998 whereas the methyl radical is normal in this case. Thus the coefficients in the LUMO are hardly likely to be the explanation, and one suggestion in this particular case is that there is a growing anomeric effect between the oxygen atom and the two fluorine substituents in the transition structure for the formation of the major intermediate 7.46.988... 

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