Amide Bond Formation Strategies: Latest Advances on a Dateless Transformation

Abstract

The synthesis of amides remains one of the most important transformations and it is one of the more frequently performed reactions. In the pharmaceutical industry, building of the amide group is pivotal and among the more important transformations in the design of the synthetic plan. This review presents an overview of only very recent contributions, published in the last three years, to highlight the latest progresses in this "dateless" reaction, with a special focus on metal-free methodologies. New, more efficient and/or greener stoichiometric methods as well as catalytic strategies have been discussed, either for the "classical" coupling approach between an amine and a carboxylic acid (or its activated equivalent), and for more innovative approaches, mainly involving oxidation procedures to generate amides starting from amines.

Biocatalytic routes to anti-viral agents and their synthetic intermediates

“…achieved using (harsh) chemical methods. 463,464 This not only holds for amide bonds between amino acid fragments but also for those present in integrase inhibitors such as dolutegravir and bictegravir. Hydrolases are a well-established class of enzymes capable of catalysing kinetically controlled amide forming reactions.…”

The preparation and applications of amides using electrosynthesis

“…Consequently, numerous groups have presented alternative and creative approaches to amide bond formation including: Lewis acid catalysts, tran-sition metal catalysis and various redox approaches as greener alternatives. 12 Furthermore, with the growing wave of interest in electrosynthesis, [13][14][15] it was perhaps only a matter of time before the widely acknowledged green and sustainable credentials of electrosynthesis were recognized as a tool for amide bond synthesis.…”

Transition Metal and Inner Transition Metal Catalyzed Amide Derivatives Formation through Isocyanide Chemistry

“…In 2020, Benaglia and co-workers reviewed amide synthesis from 2017, specially focusing on metal-free strategies. 4 In his review and much other literature in this field, the use of isocyanides as a reagent has been shown to be prominent. Actually, isocyanides are a very versatile reagent; they are simultaneously a one carbon building block and amine precursor which means that it is one of the best reagents for generating the amide functional group.…”