Front leaving group

Two stereochemical possibilities present themselves In the pathway shown in Fig ure 8 la the nucleophile simply assumes the position occupied by the leaving group It attacks the substrate at the same face from which the leaving group departs This is called front side displacement or substitution with retention of configuration... 

Front-side approach is disfavored both because the density of the a orbital is less in the region between the carbon and the leaving group and because front-side approach would involve both a bonding and an antibonding interaction with the tr orbital since it has a nodal surface between the atoms. 

Both the Se2 (front) and Se2 (back) mechanisms are designated DeAe in the lUPAC system. With substrates in which we can distinguish the possibility, the former mechanism should result in retention of configuration and the latter in inversion. The reaction of allylsilanes with adamantyl chloride and TiCU, for example, gives primarily the antiproduct via a Se2 reaction. When the electrophile attacks from the front, there is a third possibility. A portion of the electrophile may assist in the removal of the leaving group, forming a bond with it at the same time that the new C—Y bond is formed... 

Next, we need to draw the conformation in which the H (on the front carbon) and the leaving group (Cl) are antiperiplanar ... 

As shown in Fig. 1, the big lobes of these hybrids point toward each other. Therefore, if the nucleophile approaches the substrate from the front side, its HOMO overlaps in phase with the big lobe of 0c and out-of-phase with the big lobe of 0x-Numerical calculations show that the unfavourable (nucleophile-leaving group) interaction usually overrides the favourable (nucleophile - reaction center) interaction in this front-side approach, so that back-side attack is finally preferred, leading to inversion of configuration. 

Front-side attack, corresponding to an attack on the big lobe of silicon, leads to retention. When unfavorable, out-of-phase overlap between the nucleophile and the orbitals of the leaving group predominates, nucleophilic attack occurs at the rear of the molecule, opposite X, leading to... 

In the case of the p -methoxyphenoxide anion, Taft et al. (77) have shown that the oxygen atom has a high degree of sp3 character. This nucleophile is quite similar to hard alkyl anions from an electronic point of view, i.e., it is a hard nucleophile with contracted valence orbitals around oxygen, unfavorable out-of-phase overlap with the leaving group is minimized (Scheme 9), and a front-side attack leading to retention is therefore possible. The stereochemical data are summarized in Table XI. 

Intermediate 46 is responsible for the retention of configuration observed by Shoppee. The 5,6-double bond that has displaced the leaving group from the back side now shields this side from attack by the entering group, thus leaving the front side as the only available route to substitution. 

If a nucleophile attacks the carbocation in Figure 6-10 from the front side (the side the leaving group left), the product molecule shows retention of configuration. Attack from the back side gives a product molecule showing inversion of configuration. Racemization is simply a combination of retention and inversion. When racemization... 

In the SN1 reaction of cA-l-bromo-3-deuteriocyclopentane with methanol, the carbocation can be attacked from either face. Because the leaving group (bromide) partially blocks the front side as it leaves, back-side attack (inversion of configuration) is slightly favored. 

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