Carbene and photocatalyst-catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles to form ketones

Abstract

The carbene and photocatalyst co-catalyzed radical coupling of acyl electrophile and a radical precursor is emerging as attractive method for ketone synthesis. However, previous reports mainly limited to prefunctionalized radical precursors and two-component coupling. Herein, an N-heterocyclic carbene and photocatalyst catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles is disclosed, in which the carboxylic acids are directly used as radical precursors. The acyl imidazoles could also be generated in situ by reaction of a carboxylic acid with CDI thus furnishing a formally decarboxylative coupling of two carboxylic acids. In addition, the reaction is successfully extended to three-component coupling by using alkene as a third coupling partner via a radical relay process. The mild conditions, operational simplicity, and use of carboxylic acids as the reacting partners make our method a powerful strategy for construction of complex ketones from readily available starting materials, and late-stage modification of natural products and medicines.

Cooperative NHC and Photoredox Catalysis for the Synthesis of 1,4-Dicarbonyl Compounds via Diacylation of Alkenes

“…Recently, Studer, Scheidt, and Chi et al fabricated various aryl ketone derivatives with aroyl fluorides or phenyl acyl imidazole as substrates by cooperative photoredox and NHC catalysis. Inspired by this work, we hypothesized that the benzoate species can form acyl radicals through PPh 3 deoxidation reduction, and then form a benzyl radical with the reaction for alkenes.…”

Cooperative NHC/Photoredox Catalysis: Three Component Radical Coupling of Aroyl Fluorides, Styrenes and Alcohols

“…The removal of M t BE from the B1 ‐O t Bu solution under reduced pressure and conducting the reaction in CH 2 Cl 2 alone afforded a worse yield (34%). Lower yields were also noted upon using acetonitrile or acetone (50% and 20%) as cosolvents which proved to be competent in other NHC/photoredox catalysed processes [7–12] . Notably, with benzoyl imidazole as acyl azolium precursor, yield decreased to 33% (Table 1, entry 9).…”

“…Thus, Hantzsch esters, [7a] electron rich toluene derivatives [8] and tertiary amines [9] were successfully applied as C‐radical precursors for the direct coupling with the persistent ketyl radicals. After our implementation of a three‐component coupling using the Langlois reagent as CF 3 radical source and alkenes as additional coupling partners, [7b] the strategy was extended to carboxylic acids, [10] α‐oxocarboxylic acids, [11] and RBF 3 K‐salts [12] as C‐radical precursors (Scheme 1a). To further broaden this NHC radical catalysis approach for the synthesis of α‐substituted ketones, the implementation of additional radical precursors has to be considered.…”

“…benzoyl imidazole instead of 1 a 33 [a] Unless otherwise noted, all reactions were carried out with benzoyl fluoride (0.40 mmol), styrene (0.10 mmol), B1-OtBu (0.17 be competent in other NHC/photoredox catalysed processes. [7][8][9][10][11][12] Notably, with benzoyl imidazole as acyl azolium precursor, yield decreased to 33% (Table 1, entry 9). With optimized reaction conditions in hand, the scope with respect to the alkene component was explored first, keeping benzoyl fluoride (1 a) and the NHC'-OtBu adduct 3 a as coupling partners (Scheme 2, top).…”

Photoredox cooperative N-heterocyclic carbene/palladium-catalysed alkylacylation of alkenes

“…Recently, the NHC-catalyzed radical reactions provide possibility for chemical transformations (Fig. 1a ) 25 – 28 . In 2019, Ishii et al disclosed the NHC-catalyzed radical decarboxylative coupling of aldehydes with N -hydroxyphthalimide (NHP) esters 29 , 30 .…”