Site-specific Umpolung amidation of carboxylic acids via triplet synergistic catalysis

Catalytic amide bond-forming methods is important because they could potentially address the existing limitations of classical methods using superstoichiometric activating reagents. Here the authors show an Umpolung amidation reaction of carboxylic acids with nitroarenes and nitroalkanes enabled by FeI2, P(V)/P(III) and photoredox catalysis that avoids the production of byproducts. Development of catalytic amide bond-forming methods is important because they could potentially address the existing limitations of classical methods using superstoichiometric activating reagents. In this paper, we disclose an Umpolung amidation reaction of carboxylic acids with nitroarenes and nitroalkanes enabled by the triplet synergistic catalysis of FeI2, P(V)/P(III) and photoredox catalysis, which avoids the production of byproducts from stoichiometric coupling reagents. A wide range of carboxylic acids, including aliphatic, aromatic and alkenyl acids participate smoothly in such reactions, generating structurally diverse amides in good yields (86 examples, up to 97% yield). This Umpolung amidation strategy opens a method to address challenging regioselectivity issues between nucleophilic functional groups, and complements the functional group compatibility of the classical amidation protocols. The synthetic robustness of the reaction is demonstrated by late-stage modification of complex molecules and gram-scale applications.

Automated summary

The development of catalytic amide bond-forming methods is important as it has the potential to overcome the limitations of traditional methods using superstoichiometric activating reagents. This study demonstrates an Umpolung amidation reaction of carboxylic acids with nitroarenes and nitroalkanes enabled by FeI2, P(V)/P(III) and photoredox catalysis, avoiding the production of byproducts. This method allows for the smooth participation of a wide range of carboxylic acids in such reactions, generating structurally diverse amides in good yields.