Novel tert-Butylation of Carboxylic Acids and Alcohols

A Simple and Powerful tert-Butylation of Carboxylic Acids and Alcohols: C. Ogasa, K. Kayano, K. Namba
Synlett 2023, DOI: 10.1055/a-2161-9689

The tert-butyl group is a critically important protecting group in organic chemistry, especially for carboxylic acids. This is due to its excellent stability against nucleophiles and reducing agents, as well as its convenient deprotection under acidic conditions, such as diluted TFA which can readily and selectively deprotect tert-butyl esters to the corresponding carboxylic acids. Common methods for the formation of tert-butyl esters include the condensation of carboxylic acids with tert-butanol or isobutene gas in the presence of concentrated sulfuric acid; the use of tert-butylating agents, such as di-tert-butyl dicarbonate; or transesterification reactions. However, these reactions must be conducted in organic solvents, and their application to free amino acids – which are insoluble in organic solvents – is challenging. Recently, the group of Professor Kosuke Namba from Tokushima University (Japan) described a new approach to the issue of O-tert-butylation, relying on the use of bis(trifluoromethanesulfonyl)imide in tert-butyl acetate.

Professor Namba said: “A simple, safe, and powerful tert-butylation reaction was developed, in which all reactions with free amino acids, carboxylic acids, and alcohols proceeded much faster and in high yields compared with conventional methods.”