Abstract
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.
Highlights
Development of catalytic amide bond-forming methods is important because they could potentially address the existing limitations of classical methods using superstoichiometric activating reagents
Ma et al recently achieved an elegant one-pot stoichiometric amidation protocol of carboxylic acids with nitroarenes[30]. These typical amide bond formation strategies are powerful, the development of a catalytic amidation protocol of carboxylic acids is still being actively pursued in the context of sustainable synthetic chemistry[1,31] as the carboxylic acid activating reagents result in some harmful byproducts and would compromise the functional group tolerance
Inspired by Radosevich’s recent seminal work on the P(III)/P(V) catalytic cycle[25,42,43,44,45,46], we questioned if Umpolung amidation of carboxylic acids is possible with electrophilic amination reagents of nitroarenes
Summary
The use of other organophosphine precatalysts ranging from P-B to P-F significantly decreased the reaction efficiency (entries 2-6). Control experiments suggested that all the factors, FeI2, organophosphine precatalyst, photocatalyst and light irradiation were important for the successful Umpolung amidation (entries 11-14). With the optimal conditions in hand, we explored the substrate scope of carboxylic acids. This Umpolung amidation has a satisfactory functional group compatibility and a broad carboxylic acid substrate scope. The use of organophosphine precatalyst (P-A) as the deoxygenation catalyst appears to complement Ph3P-mediated deoxygenative coupling, significantly expanding the carboxylic acid scope[32,33,34]
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