Homoanomeric effects

In our discussion of homohyperconjugation, we will limit ourselves to one well-defined class of interactions - the homoanomeric effects, the family of phenomena where the role of stereoelectronic factors in through-space interactions is well-understood. 

Evolution of n/a interaction geometries a node remains away from the donor 

Hybridization of lone pairs can change interactions Strengthen or Weaken 

Compare with back- and frontside attacks in an S,g2 reaction  

Experimental gas phase stabilization relative to phenyl anion, kcal/mol 

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In connection with the total synthesis of grandisol, an asymmetric addition of ethylene on chiral heterocyclic aminals and ketals was examined (Scheme 23). The selectivity can be high, with a preferred approach of ethylene from the less hindered side, especially when chiral pyrrolidone 97 or furanones 100 were used in place of cyclic enones [70]. The diastereoisomeric excess of 101 or 102 remains modest with 5-menthyloxy furanone, even if the dark addition of nucleophiles or radicals on 100 occurs with a total facial selectivity. From a detailed analysis of the dependence of the product ratio with temperature and substituents, it was proposed that a pyramidalization of the 3-carbon in the relaxed -ir,- of the excited furanones and a homoanomeric effect were responsible for the observed selectivity [71]. Excited cyclopentenones also possess a biradical character in their relaxed state. However, no regio and no stereoselectivity could be detected when cyclopentenone was selectively excited in the presence of 5-men-thyloxyfuranone. An initial energy transfer, followed by a cycloaddition of the triplet excited furanone with cyclopentenone, explains these poor results. With more flexible or more electron deficient cyclenones the facial selectivity increases, but mixtures of regioisomers and syn/anti stereoisomers are obtained [72]. 

Detailed nmr studies of 1,3-dioxanes, 1,3-oxathianes, 1,3-dithianes and 1,3,2-dioxathianes indicate that the equatorial C5-H bond is wesdcer and longer than the corresponding axial bond. This feature is attributed to a homoanomeric effect between the p-oxygen atom and the equatorial bond (94JA5796, 94JCS(P2)1151). 

Alabugin, I. V., Manoharan, M., Zeidan, T. A. (2003). Homoanomeric Effects in Saturated Heterocycles. Journal of the American Chemical Society, 125, 14014-14031. 

Homoanomeric effects Several interactions that involve a lone pair of atom X with the acceptor orbital in a X-CH-CHY- moiety have been snggested in the literatuie. - Such skipped versions of the anomeric effect (i.e. the homoanomeric effects) include the W-effect in azacyclohexanes and the Plongh effect in oxa- and thiacyclohexanes (Figure 6.78). Such through-space effects are conceptually different from the classic anomeric interactions and will be discussed in more detail in Chapter 9. 

Figure 8.2 Homoconjugation (a) and homohyperconjugation (b) result from the insertion of a saturated center between donor and acceptor orbitals. When the acceptor is an empty p-orbital, homohyperconjugation is referred to as the y-effect. Insertion of a saturated bridge between a lone pair and a-acceptor (anomeric effect) gives the homoanomeric effect.

Figure 12.43 (a) Reverse Perlin effect originates from homoanomeric effects in saturated heterocycles,... 

In 1,3-dithianes, the homoanomeric effects, while present, are of lesser importance than in 1,3-dioxanes. Interestingly, the C-S bonds in dithianes are better donors and acceptors than ihe C-C bonds in cyclohexane and C-0 bonds in dioxanes, giving stronger interactions with equatorial protons at C-5 (Figure 12.44, also see Chapter 5 for a discussion of donor and acceptor ability of o-bonds). ... 

The hyperconjugative interactions and their role in the structure and reactivity of organic molecules have been outlined in a review by Alabugin et al In particular, the authors discuss an influence of the homoanomeric effects in aza-, oxa-, thio-, and selenaheterocycles on the /hc couplings measured for these compounds. 

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