A green chemistry perspective on catalytic amide bond formation

Abstract

The synthesis of amides is of widespread importance, and there has been considerable recent interest in the development of catalytic methods to access these molecules. In this perspective article, we provide an overview of the current state-of-the-art of amide synthesis, and assess new catalytic amide formation methods in the context of efficiency and sustainability. The advantages and disadvantages of catalytic approaches are highlighted and areas for future research are identified.

ATP Regeneration System in Chemoenzymatic Amide Bond Formation with Thermophilic CoA Ligase

“…Amide function is widespread in many natural and synthetic compounds such as active pharmaceutical ingredients (API) and polymers . The amide bond formation is therefore essential for chemical industries . As an example, N ‐acylation to amide represents about 16 % of overall transformations in medicinal reactions …”

Amide Synthesis by Nickel/Photoredox‐Catalyzed Direct Carbamoylation of (Hetero)Aryl Bromides

“…For example, 70 % of the top 50 selling small molecule drugs of 2018 contain an amide bond linkage . Despite the prevalence and importance of amides, improved methods for their synthesis are still highly sought‐after, especially if they can offer high efficiency and reduced environmental impact . This is because the most common methods for amide preparation—dehydrative condensation—typically use stoichiometric amounts of high molecular weight coupling reagents, which are often expensive, toxic, and/or potentially explosive .…”

“…Catalytic methods for amide synthesis have the potential to minimize waste, improve the environmental burden, and lower costs of the process . Some recent key advances include the use of group IV metal salts or boron compounds as catalysts and the development of Pd‐catalyzed aminocarbonylation—the three‐component coupling of an aryl halide with an amine and carbon monoxide .…”

“…[3] Despite the prevalence and importance of amides,i mproved methods for their synthesis are still highly sought-after, [4] especially if they can offer high efficiency and reduced environmental impact. [5] This is because the most common methods for amide preparation-dehydrative condensation-typically use stoichiometric amounts of high molecular weight coupling reagents, which are often expensive,t oxic,a nd/or potentially explosive. [6] While often tolerable on asmall scale,this inefficiency has significant implications when it comes to the manufacture of bio-active molecules,such as drugs or agrochemicals,which may need to be synthesized on multi-ton scale.…”

“…[8] Catalytic methods for amide synthesis have the potential to minimize waste,i mprove the environmental burden, and lower costs of the process. [5] Some recent key advances include the use of group IV metal salts [9] or boron compounds [10] as catalysts and the development of Pd-catalyzed aminocarbonylation-the three-component coupling of an aryl halide with an amine and carbon monoxide. [11] However, the need for toxic gaseous CO and copious amounts of molecular sieves as drying agents complicates the use of these catalytic methods.I na ddition, most of the protocols require severe reaction conditions and elevated temperatures,w hich limit the tolerance for substrates with sensitive functional groups.T herefore,t here is still an eed for catalytic amide synthesis approaches that operate at room temperature,offer ab road substrate scope,a nd avoid the use of excess drying agents.…”