Nucleophilic Substitution at a Trigonal Planar Center

We can modify our familiar addition and elimination surfaces to give us a combined simplified addition-elimination energy surface (Fig. 4.46). Although this system is further complicated by additional proton transfer reactions, we can get an overview of the problem space with this simplified surface as a map. The reactants are in the upper left comer. 

In base, there are no acids strong enough to protonate the carbonyl, but basic media usually contain much better nucleophiles, so protonation of the sink is not needed. In basic media, the nucleophile adds to the carbonyl to give the anionic tetrahedral intermediate, which kicks out the leaving group to form the product. In summary, the most common basic route is straight down the left side, paths Ad j followed by Ep. 

Reactions in neutral media or in enzymes can avoid the strongly acidic intermediates such as the protonated carbonyl by proceeding via the diagonals, AdE3 followed by E2. 

The arrow pushing for the basic addition-elimination route for carboxyl derivatives follows. A very important crosscheck for this often-reversible route is the The reaction will tend to form the weaker base. If the leaving group is a lot less basic than the nucleophile, then the reaction may be irreversible (again the rule). 

The arrow pushing steps for the common acidic route (AdE2 then El) is a bit longer. This route is usually reversible. In acidic media an additional proton transfer to improve the leaving group is common. 

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This is the almost exclusive route in basic media for replacement of a leaving group hound to a donble bond. This reaction was introduced in Section 4.5, Nucleophilic Substitution at a Trigonal Planar Center. The most common substrates for this reaction are the carboxyl derivatives. A nucleophile adds first via path Adileaving group departs via the beta elimination from an anion path Ep. 

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