Deprotection of Esters General Overview
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Generally, ester deprotection is used to unmask acids or alcohols from esters either as a means of deprotecting, or if undertaken with chiral catalysts as a route to chiral materials.
Typically deprotection falls into two classes – hydrolysis with water catalysed by base, acid or enzymes; or uncatalysed. The second class is typically run under anhydrous conditions where the substrate/product might be water sensitive or very water soluble and difficult to isolate. Certain transformations such as ester hydrolysis using enzymes can be highly stereoselective and regio-selective, hence ideal for chiral synthesis or selective deprotection of molecules containing multiple functional groups susceptible to hydrolysis. t-Butyl esters can be deprotected with strong acids or thermally – this transformation is also covered in the O-dealkylation guide.
Green criteria for ester deprotection
Deprotection should be performed with simple inorganic bases or catalytic techniques if possible e.g. enzymes or reagents that have minimal human health or environmental impact. A consideration should be given to the fate of the alkyl group, and if possible hydrolysis techniques should be chosen that avoid the production of potential genotoxic impurities such as alkyl halides. If possible, the solvent should be water, especially if this could be directly biotreated after the reaction and product isolation.
General reviews on Ester hydrolysis
Wuts, P.; Greene, T. Greene's Protective Groups in Organic Synthesis, 4th ed.; John Wiley & Sons: New Jersey, 2006
Angewandte Chemie, 2004, 44, 183
Patai, S., Ed. The Chemistry of Curboxylic Acids and Esters; John Wiley & Sons: Chichester, U.K., 1969
Ogliaruso, M.; Wolfe, J. Synthesis of Carboxylic Acids, Esters and Their Derivatives; Patai, S., Ed.; John Wiley & Sons: Chichester, U.K., 1991