Merging Photoredox and Nickel Catalysis: The Direct Synthesis of Ketones by the Decarboxylative Arylation of α‐Oxo Acids

Abstract

The direct decarboxylative arylation of α-oxo acids has been achieved via synergistic visible light-mediated photoredox and nickel catalyses. This method offers rapid entry to aryl and alkyl ketone architectures from simple α-oxo acid precursors via an acyl radical intermediate. Significant substrate scope is observed with respect to both the oxo acid and arene coupling partners. This mild decarboxylative arylation can also be utilized to efficiently access medicinal agents, as demonstrated by the rapid synthesis of fenofibrate.

Hydrodecarboxylation of Carboxylic and Malonic Acid Derivatives via Organic Photoredox Catalysis: Substrate Scope and Mechanistic Insight

“…Photoredox catalysis has been utilized to implement decarboxylative functionalizations, including additions to arenes 39–42 and alkenes, 43–50 as well as decarboxylative fluorinations 51–53 and decarboxylation of keto carboxylic acids to form ketones. 54 Wallentin and co-workers recently reported a photoredox method for the hydrodecarboxylation of stabilized carboxylic acids, such as protected amino acid derivatives, and phenyl acetic acid derivatives using a similar catalyst system to our own; however, aliphatic carboxylic acids were not found to be viable substrates using this method. 24 Thus, a method for the direct catalytic hydrodecarboxylation of unstabilized aliphatic carboxylic acids has remained elusive.…”

Recent advances in dual transition metal–visible light photoredox catalysis

“…22 In 2015, MacMillan presented a Ni-Ir dual setup for decarboxylative coupling of aryl halides (10: I, Br) with 2 equivalents of ketocarboxylic acids(11) (Figure 5). 23 Similarly to the previously mentioned synergistic dual catalytic mechanism, photo-generated acyl radical adds to the Ni(0) complex. The extensibility of the reaction was studied on the side of (hetero)aryl iodides as well as the aryl ketocarboxylic acids.…”

Photoredox Catalysis in Nickel-Catalyzed Cross-Coupling

“…Decarboxylative cross-coupling of a-amino acids under photoredox/Ni dual catalysis The synthesis of aryl ketones was also developed utilizing photoredox/Ni catalysis in the decarboxylative cross-couplings of a-keto acids [46]. Reaction conditions were developed to carry out an efficient coupling of a variety of a-keto acids bearing aromatic and aliphatic substituents as well as for aryl-, heteroaryl-, alkenyl-, and secondary alkyl halides (Scheme 30).…”