Protection for the Carboxyl Group

Carboxylic acids are protected for a number of reasons: (1) to mask the acidic proton so that it does not interfere with base-catalyzed reactions, (2) to mask the carbonyl group to prevent nucleophilic addition reactions, and (3) to improve the handling of the molecule in question. Besides having stability to a planned set of reaction conditions, the protective group must also be removed without affecting other functionality in the molecule. Some activated esters that have been used as macrolide precursors and some that have been used in peptide synthesis are also described in this chapter. Some general methods for the preparation of esters are provided at the beginning of this chapter; conditions that are unique to a protective group are described with that group. To a limited extent, carboxylic acids have been protected as amides or hydrazides, derivatives that complement esters in methods used for their cleavage. Some esters that have been used as protective groups are included in Reactivity Chart 6 (Chapter 10).