Esters and related carboxylic acid derivatives

Several layers of stereoelectronic effects contribute to stability, conformational profiles and reactivity of carboxylic acid derivatives. We will illustrate the interplay between these effects using esters as an example. 

The second level is composed of the hyperconjugative interaction of alkyl groups with the carbonyl. Even though this is formally a neutral hyperconjugation pattern, it is dominated by 0=0 donation. The latter 

Umpolung of the above interactions operates in those molecular systems where n a dominant. For example, cyclopropylamine is slower to couple with a carboxylic acid than isopropylamine. Similar reactivity pattern is observed for N-alkylation. In fact, the reactivity of cyclopropylamine in these 

Z-conformer Lactones are more reactive than simple acyclic esters 

When the s-trans geometry is enforced in an ester by cyclic constraints, i.e. in the formation of lactones, the absence of this stabilizing effect leads to increased reactivity. For example, lactones are more electrophilic and susceptible to nucleophilic attack at the carbonyl carbon than acyclic esters because the anomeric Uq f c-o donation decreases the carbonyl acceptor ability in acyclic esters but is absent for lactones. 

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