Decarboxylative Acylation Research Articles

Photoredox decarboxylative acylation of carboxylic acid by 4-acyl-1,2,3-triazoliums

Recent advancements in NHC-based radical coupling reactions have introduced NHC-derived ketyl radicals as innovative persistent radicals. However, current work involves NHC-based radical-radical coupling reactions that are limited to some stable alkyl radicals of the radical partners. This is mainly due to the high barriers among the transition state in the coupling process. Our study, supported by density functional theory (DFT) calculations, demonstrates that ketyl radicals derived from mesoionic carbenes (MICs) exhibit significantly lower barriers for radical-radical coupling. This facilitates rapid reactions with short-lived alkyl radicals. Herein, we disclose 4-acyl-1,2,3-triazoliums as versatile acylation reagents, which can be converted to MIC-derived ketyl radicals by photocatalyst. Photoredox decarboxylative acylation of primary, secondary, and tertiary carboxylic acids afford the corresponding ketones with broad substrate scope and excellent functional group tolerance.

Recent Developments in Photoinduced Decarboxylative Acylation of α-Keto Acids.

Ketones are ubiquitous patterns found in various biological molecules and natural products. In recent years, a number of acylation methods have been developed based on the use of α-oxocarboxylic acids as acyl-transfer reagents, with particular emphasis on the photoinduced decarboxylative acylation of α-keto acids. This review focuses on the latest advancements in acylation methodologies through the decarboxylation of α-keto acids over the past several years, highlighting their product diversity, selectivity, and applicability. Where possible, the mechanistic rationale is presented, providing a positive outlook for the promising future of this field.

Visible-Light-Driven Regioselective Decarboxylative Acylation of N-Methyl-3-phenylquinoxalin-2(1H)-one by Dual Palladium-Photoredox Catalysis Through C-H Activation.

We report herein an efficient visible-light-promoted approach for the regioselective decarboxylative C-H acylation of N-methyl-3-phenylquinoxalin-2(1H)-ones using α-oxo-2-phenylacetic acids via dual palladium-photoredox catalysis. The reactions were carried out at room temperature in the presence of 24 W blue LEDs. The established protocol tolerated a wide range of functional groups and enabled the synthesis of several acylated N-methyl-3-phenylquinoxalin-2(1H)-ones in good to excellent yields. The proposed mechanism for this transformation was supported by control experiments.

Nickel‐Catalyzed Enantioselective Decarboxylative Acylation: Rapid, Modular Access to α‐Amino Ketones**

AbstractA new approach to the enantiocontrolled synthesis of α‐amino ketone derivatives is disclosed by employing a decarboxylative acylation strategy. Thus, when an acyl chloride and an α‐amido‐containing redox‐active ester are exposed to a nickel catalyst, chiral ligand, and metal reductant, α‐amido ketones are produced in good yield and high ee. The reaction exhibits broad substrate scope, can be easily scaled up, and is applied to dramatically simplify the synthesis of several known structures.

Nickel-Catalyzed Enantioselective Decarboxylative Acylation: Rapid, Modular Access to α-Amino Ketones.

A new approach to the enantiocontrolled synthesis of α-amino ketone derivatives is disclosed by employing a decarboxylative acylation strategy. Thus, when an acyl chloride and an α-amido-containing redox-active ester are exposed to a nickel catalyst, chiral ligand, and metal reductant, α-amido ketones are produced in good yield and high ee. The reaction exhibits broad substrate scope, can be easily scaled up, and is applied to dramatically simplify the synthesis of several known structures.

Silver-Catalyzed Decarboxylative Acylation of Isocyanides Accesses to α-Ketoamides with Air as a Sole Oxidant.

α-Ketoamide moieties, as privileged units, may represent a valuable option to develop compounds with favorable biological activities, such as low toxicity, promising PK and drug-like properties. An efficient silver-catalyzed decarboxylative acylation of α-oxocarboxylic acids with isocyanides was developed to derivatize the α-ketoamide functional group via a multicomponent reaction (MCR) cascade sequence in one pot. A series of α-ketoamides was synthesized with three components of isocyanides, aromatic α-oxocarboxylic acid analogues and water in moderate yields. Based on the research, the silver-catalyzed decarboxylative acylation confirmed that an oxygen atom of the amide moiety was derived from the water and air as a sole oxidant for the whole process.

Construction of C(CO)–C(CO) Bond via NHC-Catalyzed Radical Cross-Coupling Reaction

A C(sp2)-C(sp2) bond can be constructed via a photoredox/N-heterocyclic carbene (NHC)-cocatalyzed radical cross-coupling reaction, which provides a complementary strategy to classic electron pair processes. The present protocol represents the first example of an NHC-catalyzed two-component radical cross-coupling reaction involving C(sp2)-centered radical species. The decarboxylative acylation of oxamic acid with acyl fluoride was conducted under mild conditions and allowed the preparation of a variety of useful α-keto amides, including sterically congested ones.

Regioselective Pd-catalyzed decarboxylative C-6 acylation of 7-O-carbamate coumarins and their anti-inflammatory evaluation

O-Carbamate assisted Palladium (II) catalyzed regioselective C–H acylation of coumarins at C-6 position with arylglyoxylic acids has been achieved. The decarboxylative acylation of diverse 7-O-carbamate coumarins with wide range of arylglyoxylic acids produced solely the C-6 acylated coumarins. The synthesized molecules have been evaluated for their anti-inflammatory activity against RAW 264.7 macrophage cell line. Compounds 3aa, 3ab, and 3ia showed anti-inflammatory activity. Moreover, compound 3ia was found to be the most active with IC50 value of 5.471 μM in IL-1β expression. Further studies revealed that carbamate-based C-6 acylated coumarin derivatives 3aa, 3ab, and 3ia inhibits the nuclear translocation of p65 which mitigates the activation of inflammatory cascade by decreasing the expression of NF-κB. Compound 3ia was found to be the most active compound in inhibiting the NF-κB expression.

Piezocatalyzed Decarboxylative Acylation of Quinoxalin-2(1H)-ones Using Ball Milling

The first piezochemically driven decarboxylative coupling of the C–H bond was developed. The agitation of BaTiO3 via ball milling converts mechanical energy into electrical potential, leading to the production of a benzoyl radical via a single-electron transfer pathway analogous to the photocatalytic reaction. This mechanoredox BaTiO3 catalytic strategy to synthesize C3-acylated quinoxalin-2(1H)-ones requires no solvent, a short reaction time, and simple handling skills, exhibiting promising potential in large-scale chemical manufacturing.

Electrochemically mediated decarboxylative acylation of N-nitrosoanilines with α-oxocarboxylic acids

An efficient palladium-catalyzed electrooxidation C–H acylation reaction of N -nitrosoanilines with α -oxocarboxylic acids was developed. The anodic oxidation of the Pd(II) intermediate was found to be the key to complete the reaction. In this case, the N -nitroso group was observed to be an effective directing group for C–H activation reaction. Moreover, the synthetic transformation of derivatives of natural products (L-menthol, dehydroepiandrosterone, and pregnenolone) was successfully realized. Finally, flow electrochemical synthesis of some substrates was achieved. An efficient palladium-catalyzed electrooxidation C–H acylation reaction of N -nitrosoanilines with α -oxocarboxylic acids was developed.

A Palladium-Catalyzed 4CzIPN-Mediated Decarboxylative Acylation Reaction of O-Methyl Ketoximes with α-Keto Acids under Visible Light.

This work presents a palladium-catalyzed oxime ether-directed ortho-selective benzoylation using benzoylformic acid as the acyl source with a palladium catalyst and 4CzIPN as the co-catalyst under light. Various non-symmetric benzophenone derivatives were obtained in moderate to good yields. A preliminary mechanism study revealed that the reaction proceeds through a free radical pathway.

Synthesis of α‐Ketoamides via Electrochemical Decarboxylative Acylation of Isocyanides Using α‐Ketoacids as an Acyl Source

AbstractA catalyst‐, transition metal‐, oxidant‐free strategy for the synthesis of α‐ketoamides via an electrochemical decarboxylative acylation of isocyanides at room temperature with carbon dioxide as a sole by‐product was developed in this work. This is a simple, rapid and practical strategy under mild conditions for synthesizing highly functionalized α‐ketoamides with high atom economy.

Decarboxylative Acylation of Carboxylic Acids: Reaction Investigation and Mechanistic Study

Ketones serve as one of the most critical building blocks in organic synthesis, involving numerous functional group transformations. Herein, we report an unprecedented photoredox–nickel metallaphot...

Visible‐Light‐Induced Decarboxylative Acylation of Pyridine N‐Oxides with α‐Oxocarboxylic Acids Using Fluorescein Dimethylammonium as a Photocatalyst

AbstractHerein, the development of a visible‐light‐induced catalytic system to achieve the decarboxylative acylation of pyridine N‐oxides with α‐oxocarboxylic acids, at room temperature and using the organic dye fluorescein dimethylammonium as a new type of photocatalyst, is reported. A series of 2‐arylacylpyridine N‐oxides were selectively synthesized in moderate to good yields by controlling the polarity of the reaction solvent. The developed strategy was successfully applied in the synthesis of an important intermediate of the drug, acrivastine, on a gram scale. Notably, this is the first time that fluorescein dimethylammonium has been used to catalyze the Minisci‐type C−H decarboxylative acylation reaction. The mechanism of decarboxylative acylation was studied by capturing adducts of acyl radicals and 1,1‐diphenylethylene to confirm a radical mechanism. The disclosed catalytic system provides a green synthetic strategy for decarboxylative acylation without the use of additional oxidants or metal catalysts.magnified image

Ag-catalyzed decarboxylative acylation of pyridazines using α-keto acids in aqueous media

An efficient and general protocol for Ag-Catalyzed decarboxylative acylation of pyridazines using α-keto acids as acylation reagent in aqueous media has been described. This method provides a new avenue for the synthesis of diverse array of acylated pyridazines with different substitution patterns. The reaction proceeds smoothly in water under mild conditions and exhibits a good functional group tolerance.

Ag-Catalyzed Oxidative ipso-Cyclization via Decarboxylative Acylation/Alkylation: Access to 3-Acyl/Alkyl-spiro[4.5]trienones.

A strategy to functionalized spiro[4.5]trienones, by domino silver-catalyzed decarboxylative acylation or alkylation/ ipso-cyclization of N-arylpropiolamides with α-keto acids/alkyl carboxylic acids, is presented. This transformation offers a wide range of substituted 3-acyl/alkyl-spiro[4.5]trienones in high yields with a broad substrate scope. The approach was further extended to access fused tricyclic frameworks, 6,7-dihydro-3H-pyrrolo[2,1-j]quinoline-3,9(5H)-diones.

Photoredox Catalyst Free, Visible Light‐Promoted C3−H Acylation of Quinoxalin‐2(1H)‐ones in Water

AbstractA method for the synthesis of 3‐acyl quinoxalin‐2(1H)‐ones through visible‐light promoted decarboxylative acylation of α‐oxo‐carboxylic acids with quinoxalin‐2(1H)‐ones was developed. The reaction was performed in aqueous phase and photoredox catalyst was not required to run the process.magnified image

Hydroperoxide-Mediated Decarboxylative Acylation of Amines with α-Keto Acids

Hydroperoxide-Mediated Decarboxylative Acylation of Amines with α-Keto Acids

Visible-light-induced decarboxylative acylation of quinoxalin-2(1H)-ones with α-oxo carboxylic acids under metal-, strong oxidant- and external photocatalyst-free conditions

An eco-friendly visible-light-induced decarboxylative acylation of quinoxalin-2(1H)-ones and α-oxo carboxylic acids with air as the oxidant under external-photocatalyst-free conditions was established.

Visible-light-promoted acridine red catalyzed aerobic oxidative decarboxylative acylation of α-oxo-carboxylic acids with quinoxalin-2(1H)-ones

Visible-light-mediated procedure has been developed for the synthesis of 3-acyl quinoxalin-2(1H)-ones through acridine red catalyzed decarboxylative acylation of α-oxo-carboxylic acids with quinoxalin-2(1H)-ones.