Decarboxylative Acylation of Carboxylic Acids: Reaction Investigation and Mechanistic Study

Abstract

Ketones serve as one of the most critical building blocks in organic synthesis, involving in numerous functional group transformations. Herein, we report an unprecedented photoredox/nickel metallaphotoredox-catalyzed decarboxylative acylation of common aliphatic acids with readily available aromatic and aliphatic thioesters. A wide range of structural diverse unsymmetrical arylalkyl and dialkyl ketones have been constructed in yields of up to 98% with this strategy. The protocol has excellent reaction selectivity and functional group compatibility, representing a significant step forward in ketone synthesis. The one-pot decarboxylative acylation at the gram scale from two different carboxylic acids and the late-stage application for the synthesis of complex ketones shows its synthetic robustness. Both mechanistic experiments and DFT calculations suggest that the decarboxylative acylation reaction tends to operate via an underdeveloped Ni(I)−Ni(II)−Ni(I)−Ni(III)-Ni(I) catalytic cycle.

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

“…6b ). It is well known that excited state of photocatalyst can promote the oxidative decarboxylation of carboxylic acids 84 , 85 . Meanwhile, the acyl azolium intermediate II (Int.…”

“…The resulting or pre-prepared acyl imidazole 1 can subsequently react with NHC catalyst to form an acyl azolium intermediate II . In the same solution, an iridium complex photocatalyst is excited by visible light to mediate oxidative decarboxylation of another carboxylic acid ( 2 ) to form a transient radical intermediate III 84 , 85 , 90 . The reduced iridium species from the above photo process then reduces the acyl azolium intermediate ( II ) to the corresponding persistent NHC-bound radical intermediate V with regeneration of the original iridium photocatalyst 57 – 63 .…”

A Practically Unified Electrochemical Strategy for Ni-Catalyzed Decarboxylative Cross-Coupling of Aryl Trimethylammonium Salts

“…Driven by the fundamental role of aldehydes, ketones, amides, and esters in synthetic chemistry, medicines, agrochemicals, and electronic materials, the development of novel methods for their rapid synthesis under mild reaction conditions is one of the essential targets in modern chemistry . Particularly, inspired by the power of transition-metal-catalyzed cross-coupling strategies to construct versatile C–C and C–X bonds, recent decades have also witnessed the emergence of many elegant methods for the synthesis of aromatic carbonyl compounds enabled by transition-metal-catalyzed decarboxylative coupling reactions using cheap and biologically common α-oxocarboxylic acids and other derivatives. − In 2008, Goossen and co-workers first demonstrated that aryl halides and potassium α-oxocarboxylates can be coupled via Pd/Cu-catalyzed decarboxylation to form aryl ketones (Scheme A) .…”

Visible-light-mediated amidation from carboxylic acids and tertiary amines via C–N cleavage

“…9 Although these typical strategies are powerful, the development of efficient and highly compatible amidation reactions from tertiary amines remains highly desired. In this paper, with our ongoing interest in the efficient transformations of carboxylic acids, 10 we developed a photocatalytic strategy for direct construction of tertiary amides from carboxylic acids and tertiary amines via C–N bond cleavage, delivering a wide range of tertiary amides in up to 93% yields (Scheme 1c). Under mild conditions, both aliphatic and aromatic carboxylic acids are competent coupling partners, thus avoiding the use of largely excessive activation reagents or condensation reagents.…”

“…The mechanism study indicates a new pathway for the deoxygenation of carboxylic acids to produce acyl radicals. 10…”