Deoxygenative arylation of secondary amides by merging iridium catalysis with electrochemical radical cross-coupling

Abstract

Given the natural abundance and industrial accessibility, inert amides have gained considerable attention in homologous amine synthesis and the development of novel catalytic strategies for their deoxygenative functionalization is highly...

Asymmetric Deoxygenative Functionalization of Secondary Amides with Vinylpyridines Enabled by a Triple Iridium-Photoredox-Chiral Phosphoric Acid System

“…Besides, the combination of the photochemical radical process under visible light irradiation with deoxygenative reduction of amides has been successfully achieved by Dixon (Scheme a-ii) and our group . Recently, a deoxygenative arylation of amides was achieved by our group via merging the electrochemical process with iridium catalysis …”

“…7 Recently, a deoxygenative arylation of amides was achieved by our group via merging the electrochemical process with iridium catalysis. 8 Although great progress has been made in the deoxygenative transformation of the amides, 1−7 asymmetric functionalization of amides to chiral amines 9 is rarely explored (Scheme 1a-iii). In 2021, asymmetric reductive cyanation and phosphonylation of secondary amides were demonstrated by the Huang group.…”

Deoxy-Arylation of Amides via a Tandem Hydrosilylation/Radical– Radical Coupling Sequence

“…We hypothesized that a photoredox catalyst could reduce both the in situ generated iminium as well as the aryl nitrile, in two separate net reductive catalytic cycles (Figure c). This strategy leverages the mild nature of photoredox catalysis to promote amide arylation, which aims to alleviate the need for aryl-metal nucleophiles …”

“…This strategy leverages the mild nature of photoredox catalysis to promote amide arylation, which aims to alleviate the need for aryl-metal nucleophiles. 19 Reaction optimization began by hybridizing conditions found in the imine/4-cyanopyrine radical−radical coupling from Rovis 20 and the seminal Vaska's/photoredox procedure from Dixon 16 (Table 1, entry 1). Under these hybrid conditions, arylated product 3a was obtained in 52% yield.…”

“…Typically, secondary amides have difficulties undergoing the hydrosilylation step catalyzed by Vaska's complex, requiring catalyst modifications to achieve iminium formation. 16,21,25 Next, the aryl portion of the amide was investigated. We found that an electron-rich para-methoxy benzamide furnished product 3t in 36% yield.…”