Palladium-catalyzed carbonylation of activated alkyl halides via radical intermediates

Abstract

Palladium-catalyzed carbonylation is an efficient approach to prepare carbonyl-containing compounds with high atomic economy in synthetic organic chemistry. However, in comparison with aryl halides, carbonylation of alkyl halides is relatively challenging due to the decreased stability of the palladium intermediates. Carbonylation of activated alkyl halides is even more difficult, as nucleophilic substitution reactions with nucleophiles occur more easily with them. In this article, we summarize and discuss recent achievements in palladium-catalyzed carbonylative reactions of activated alkyl halides. The transformations proceed through radical intermediates which are generated in various manners. Under a relatively high pressure of carbon monoxide, the corresponding aliphatic carboxylic acid derivates were effectively prepared with various nucleophiles as the reaction partners. Besides alcohols, amines and organoboron reagents, four-component reactions in combination with alkenes or alkynes were also developed. Case-by-case reaction mechanisms are discussed as well and a personal outlook has also been provided.

Keywords: Carbonyl group; Palladium catalysis; Carbonylation; Activated alkyl halides; Radical intermediates.