Overlap secondary

In all the above cases the attack from the less-hindered side (exo-orientation) was preferred and the ratio exo/endo varied from 19 (for a) to 4 (for c). The increase in weight of endo-orientation for c cannot be explained only on secondary overlap interactions. But they are accounted for by decrease of geometrical constraints. The steric requirements of saturated cyclohexane ring are higher than the steric requirements of sp2 carbon atoms in C. 

Cyclopentene gives an endo-exo mixture, but secondary overlaps with cyclopentadiene generate a pure endo product. 

Once the most reactive substrate conformations are known, it remains to look for the best approach of the nucleophile. An anti attack is promoted by a favorable secondary overlap between the nucleophile and o (C L), which is shown by the double arrow. Syn attack is disfavored, both by a negative secondary overlap (wavy line) and by the eclipsed relationship between C L and Nu---C (Figure 6.6). To summarize, the Felkin transition states are favored because they correspond to the best trajectories for attacking the most reactive conformations. 

Figure 6.6 Secondary overlaps during syn and anti attacks.

Let us first compare 3 with 5. The type (1) destabilizing interaction between 7ico and the ethyl group HOMO increases with the overlap. It is attenuated by a secondary overlap (dotted) in conformation 3 so this form is favored ... 

The two-electron interactions HOMO(Et)-7t co and LUMO(Et)-7tco [type (2) and type (3) respectively] are stabilizing. The in-phase secondary overlaps again favor conformation 3. 

The influence of secondary overlap was first observed in reactions using cyclopen-tadiene to form bicyclic ring systems. In the bicyclic product (called norbornene), the electron-withdrawing substituent occupies the stereochemical position closest to the central atoms of the diene. This position is called the endo position because the substituent seems to be inside the pocket formed by the six-membered ring of norbornene. This stereochemical preference for the electron-withdrawing substituent to appear in the endo position is called the endo rule. 

In most Diels-Alder reactions, there is secondary overlap between the p orbitals of the electron-withdrawing group and one of the central carbon atoms of the diene. Secondary overlap stabilizes the transition state, and it favors products having the electron-withdrawing groups in endo positions. 

Symmetry considerations have also been advanced to explain predominant endo addition. " In the case of [4 + 2] addition of butadiene to itself, the approach can be exo or endo. It can be seen (Fig. 15.11) that whether the HOMO of the diene overlaps with the LUMO of the alkene or vice versa, the endo orientation is stabilized by additional secondary overlap of orbitals of like sign (dashed lines between heavy dots). Addition from the exo direction has no such stabilization. Evidence for secondary orbital overlap as the cause of predominant endo orientation, at least in some cases, is that [4 + 6]-cycloaddition is predicted by similar considerations to proceed with predominant exo orientation, and that is what is found. However, this explanation does not account for endo orientation in cases where the dienophile does not possess additional n orbitals, and a number of alternative explanations have been offered. ... 

Fig. 4-19 Secondary overlap of the frontier orbitals of Diels-Alder reactions. The dotted lines show the bonding overlap which stabilizes the lendo transition...

However, they do provide an explanation for the preferred endo mode of cycloaddition for those alkenes giving meta adducts. Most c/.v-disubstitutcd alkenes like cyclopentene1159 give substantially more endo adduct 8.134 than exo 8.135. Because of the good HOMO/ HOMO and LUMO/ LUMO match with simple alkenes, there will be two sets of secondary orbital interactions to consider. One 8.136 will be between the HOMO of the doubly X-substituted alkene, crudely modelled by i >3 of butadiene, and ip 2 of benzene, and the other 8.137 will be between the LUMO of the alkene, modelled by ip4 of butadiene, and ip5 of benzene. In both cases the secondary overlap is in favour of the endo mode of cycloaddition.1157... 

The possible situations in which external overlap can occur are analyzed in Fig. 6, which shows that there are two kinds of external overlap. In primary overlap the previous construction was at the same site as the one under consideration. Hence only the a-carbon of the synthon is now part of the reactive strand for the new half-reaction, the rest of the strand lying across the previously constructed bond into the product /-list of the previous partner synthon, as in 10. Thus primary overlap can involve only half-reactions of s =2 or 3. With secondary overlap the prior construction has occurred at the /8-carbon of the present reactive strand and allows external overlap to involve only the first (a ) carbon of the prior partner synthon and so only present half-reactions of s =3. 

Secondary Overlap. The reactive strand of an s =3 half-reaction lying on the a- and -carbons of the synthon and the y-carbon across a prior construction link at the /S-carbon to a prior partner synthon. 

Extended Hiickel Theory has been used to calculate an approximate energy surface for the [1,3] sigmatropic rearrangement connecting (171) to (172). The calculated relative ease of the various reaction paths is correlated with both the experimental data and the predictions of orbital symmetry theory. A non-coplanar transition state in the Diels-Alder reaction of cyclopentadiene with maleic anhydride, or with other five-membered cyclic dienophiles of C2 symmetry, is suggested by the relationship between the primary and secondary overlap integrals in the Salem-type analysis of the reaction path. ... 

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