Leaving groups basicity

Notice too that strongly basic leaving groups are absent from Table 8 8 In gen eral any species that has greater than about 2 for its conjugate acid cannot be a... 

In the second major method of peptide synthesis the carboxyl group is activated by converting it to an active ester, usually a p-nitrophenyl ester. Recall from Section 20.12 that esters react with ammonia and amines to give fflnides. p-Nitrophenyl esters are much more reactive than methyl and ethyl esters in these reactions because p-nitrophenoxide is a better (less basic) leaving group than methoxide and ethoxide. Simply allowing the active ester and a C-protected amino acid to stand in a suitable solvent is sufficient to bring about peptide bond formation by nucleophilic acyl substitution. 

To put it another way, a more/less basic nucleophile will displace a more/less basic leaving group from a carbonyl compound. (Choose more or less in each case.)... 

As with reactions at the carbonyl group, weakly basic leaving groups are more readily displaced than strongly basic ones. 

Of course the very basic leaving group (NH2, pKaH about 35) instantaneously reacts with water (pKaH about 15) in a fast proton transfer to give NH3 and HO. ... 

Acids also catalyze the dissociation of the tetrahedral intermediate. Protonation of its carbonyl oxygen permits the leaving group to depart as a neutral carboxylic acid molecule, which is a less basic leaving group than a carboxylate anion. 

C-0 bond cleavage than of the proton transfer and hence the less basic leaving group MeO should leave faster. On the other hand, if proton transfer is ahead of C-O bond cleavage the opposite holds and the ethoxy derivative should react faster. The results suggest that the former situation applies. 

An alcohol cannot undergo a nucleophilic substitution reaction because it has a strongly basic leaving group ( OH) that cannot be displaced by a nucleophile. 

Because it has a weakly basic leaving group, a sulfonium ion readily undergoes nucleophilic substitution reactions. As with other Sn2 reactions, the reaction works best... 

Both the hydrolysis and the alcoholysis of an ester are very slow reactions because water and alcohols are poor nucleophiles and esters have very basic leaving groups. These reactions, therefore, are always catalyzed when carried out in the laboratory. Both hydrolysis and alcoholysis of an ester can be catalyzed by acids. (See Section 17.11.) The rate of hydrolysis can also be increased by hydroxide ion, and the rate of alcoholysis can be increased by the conjugate base (RO ) of the reactant alcohol (Section 17.12). 

We have seen that esters hydrolyze slowly because water is a poor nucleophile and esters have very basic leaving groups. The rate of hydrolysis can be increased by either acid or HO . When you examine the following mechanisms, notice a feature that holds for all organic reactions ... 

For a single atom, nucleophilicity parallels basicity. Leaving-group ability is inversely related to basicity. 

The triflate (trifluoromethanesul-fonate) anion, CF3SO3, or TfO-is an excellent, non-basic leaving group. It Is often used as an oxygen-based alternative to halides, and metals will insert into the C-OSO2CF3 bond. Triflates, particularly aryl and vinyl triflates, can be made conveniently with Comins reagent. 

---