Hyperconjugative anomeric interactions

It must be added that 2-phosphino-l,3-dithianes 44 provide a very interesting example of noncompetitive hyperconjugative anomeric interactions in a system where both heteroatoms Y = S and X = P (Scheme 8) possess lone electron pairs. In the equatorial conformer the endo interactions cannot operate, while in the axial one the exo effect is not manifested. 

In comparison with previous plots of this section, the no-crco anomeric interaction of Fig. 3.65 can be seen to be a rather typical example of hyperconjugative donor-acceptor interactions. Consequently, there seems to be no valid reason to invoke a special effect for the conformational preferences of sugars, obscuring their essential conformity with a unified donor-acceptor picture of ethane-like rotation barriers. 

We have already seen in Section 2.2.3.3 how conformation can be affected by anomeric interactions, which can lead electronegative substituents to be axial at the 2-position in tetrahydropyranyl rings, and sometimes cause a chain of atoms to adopt a seemingly more hindered gauche conformation 2.81-2.83, 2.85 and 2.86 rather than the more usual zigzag arrangement. Similar hyperconjugative interactions in neutral molecules between two a bonds, one a a donor and the other a a acceptor, can lead them to adopt conformations in which the stereoelectronic effect overrides the purely steric effect. 

The idea of competition between the anomeric interactions is strongly supported by an ab initio study (67) on proton affinities of oxygens in the sc, sc and ap, sc conformers of dimethoxymethane (11) (Figure 3). Deslong-champs (7a) suggested that oxygens involved in o hyperconjugative... 

It must be added that the hyperconjugative nature of the O—C—O anomeric interactions has recently been supported by X-ray data for orthoesters containing C(OC)3 (214) and C(OC)4 (155) groups [see, however, below for compounds containing a QSC) group]. 

For example, the higher energy p-orbital (instead of an sp hybrid) parallel to the vicinal axial acceptor maximizes the hyperconjugative anomeric n o j, Y interaction in tetrahydropyrans (see Chapter 6). NBO analysis which determines the best hybrids describing a Lewis structure finds two lone pairs of different hybridization in tetrahydropyran a purely p-orbital and an sp hybrid. The deviation from sp hybridization predicted by the idealized model is readily explained by Bent s rule, - where atoms direct orbitals of different hybridization towards neighboring atoms based on electronegativity and size. When the dominant delocalization is intermolecular, the preferred hybridization can change. For example, NBO finds two sp hybrids for the two lone pairs of the H O molecule that serves as H-bond acceptor in the water dimer. 

Generalized anomeric effect The stereoelectronic requirement that a lone pair n at a heteroatom X and C-Y bond in a YCH X moiety are aligned in an antiperiplanar geometry for maximizing the hyperconjugative n interaction also leads to interesting conformational preferences in acyclic systems (Figure 6.62). 

On the other hand, the stereoelectronic interpretation of the anomeric effect [26] dictates the antiperiplanar orientation of an occupied, high-energy donor orbital and an empty, low-energy acceptor orbital. Such hyperconjugative stabilizing interaction is found in a-sulfinyl carbanions, where the conformation allowing for n. - cr s o two-electron-two-orbital interaction corresponds to the energy minimum (Scheme 3.6). 

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. 

Product or reactant stabilizing factors that have been studied thus far include resonance/charge delocalization, solvation, hyperconjugation, intramolecular hydrogen bonding, aromaticity, inductive, jr-donor, polarizability, steric, anomeric, and electrostatic effects, as well as ring strain and soft-soft interactions. Product or reactant destabilization factors are mainly represented by anti-aromaticity, steric effects in some types of reactions, and, occasionally, electrostatic effects. What makes the PNS particularly useful is that it is completely general, mathematically provable,4 and knows no exception. 

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>. 

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