Aerobic Oxidative Amidation Research Articles

Direct Synthesis of Sugar Amides by Aerobic One-Pot Oxidative Amidation of Unprotected Carbohydrates

Direct Synthesis of Sugar Amides by Aerobic One-Pot Oxidative Amidation of Unprotected Carbohydrates

Fluorinated solvent-assisted photocatalytic aerobic oxidative amidation of alcohols via visible-light-mediated HKUST-1/Cs-POMoW catalysis

Successful synthesis and characterization of HKUST-1/Cs-POMoW binary composite, and application in the photocatalytic aerobic oxidative amidation reaction of alcohols under light illuminating in the visible region.

Synthesis of aliphatic α-ketoamides from α-substituted methyl ketones via a Cu-catalyzed aerobic oxidative amidation

α-Ketoamides are an important key functional group and have been used as versatile and valuable intermediates and synthons in a variety of functional group transformations. Synthetic methods for making aryl α-ketoamides as drug candidates have been greatly improved through metal-catalyzed aerobic oxidative amidations. However, the preparation of alkyl α-ketoamides through metal-catalyzed aerobic oxidative amidations has not been reported because generating α-ketoamides from aliphatic ketones with two α-carbons theoretically provides two distinct α-ketoamides. Our strategy is to activate the α-carbon by introducing an N-substituent at one of the two α-positions. The key to this strategy is how heterocyclic compounds such as triazoles and imidazoles affect the selectivity of the synthesis of the alkyl α-ketoamides. From this basic concept, and by optimizing the reaction and elucidating the mechanism of the synthesis of aryl α-ketoamides via a copper-catalyzed aerobic oxidative amidation, we prepared fourteen aliphatic α-ketoamides in high yields (48-84%).

Iron-catalyzed aerobic oxidative cross-coupling amidation of N,N-dimethylanilines

An efficient iron-catalyzed dehydrogenative cross-coupling amidation/imidation reaction between N,N-dimethylanilines and amides/imides is reported. The protocol uses an inexpensive and readily available Fe(NO3)3·9H2O/O2 catalytic system in the absence of additional ligands at room temperature.

Ionic liquid catalysed aerobic oxidative amidation and thioamidation of benzylic amines under neat conditions

Tetrabutylammonium hydroxide catalysed oxidative amidation and thioamidation of benzylamines with oxygen and elemental sulfur under solvent/metal/base-free conditions have been developed.

Cobalt(II)/N,N′,N′′‐Trihydroxyisocyanuric Acid Catalyzed Aerobic Oxidative Esterification and Amidation of Aldehydes

AbstractA protocol for a CoII/N,N′,N′′‐trihydroxyisocyanuric acid (THICA)‐catalyzed aerobic oxidative esterification and amidation of aldehydes has been developed. Preliminary insight into the mechanism indicates that such an oxidative C−O/N cross‐coupling reaction proceeds by masking the aldehyde in a nucleophilic addition reaction with an alkoxy/amino source, thereby keeping the highly reactive formyl group from undesired oxidation. This protocol for the oxidative esterification and amidation of aldehydes proceeds through two different pathways that are characterized by the intrinsic nucleophilicity of the alkanol and amine substrates The former occurs in the presence of p‐CH3C6H4SO3H as a cocatalyst and orthoformates as the alkoxy sources, instead of alkanols, to efficiently afford the transient acetals. In contrast, the coupling of the more nucleophilic amines with aldehydes renders a readily accessible cross‐coupling reaction that occurs without any cocatalyst but is limited by the potential inhibition of THICA upon nucleophilic substitution by an amine. Consequently, only sterically hindered amines were tolerated in this catalytic system, whereas further condensation occurred in the presence of primary amines to lead to imines.

Cu(II)-catalyzed aerobic oxidative amidation of azoarenes with amides

A method for Cu(II)-catalyzed dehydrogenative amidation of azoarene using air as the terminal oxidant was developed. Various amides, such as arylamides, alkylamides, lactams, and imides, are all effective amidation reagents and provide the desired products in moderate to excellent yields. Notably, good yields can also be obtained on a gram-scale with this amidation reaction. In this protocol of azoarene amidation, the catalyst (Cu(OAc)2) and oxidant (air) are inexpensive and readily available, and the process is highly efficient and atom economical.

Aerobic oxidative decyanation–amidation of arylacetonitriles with urea as a nitrogen source

An iron-catalyzed aerobic oxidative amidation of aryl acetonitriles to afford amides is achieved using urea as a convenient nitrogen source.

Copper-Catalyzed Aerobic Oxidative Amidation of Benzyl Alcohols

A Cu-catalyzed synthesis of amides from alcohols and secondary amines using the oxygen in air as the terminal oxidant has been developed. The methodology is operationally simple requiring no high pressure equipment or handling of pure oxygen. The commercially available, nonprecious metal catalyst, Cu(phen)Cl2, in conjunction with di-tert-butyl hydrazine dicarboxylate and an inorganic base provides a variety of benzamides in moderate to excellent yields. The pKa of amine conjugate acid and electronics of alcohol were shown to impact the selection of base for optimal reactivity. A mechanism consistent with the observed reactivity trends, KIE, and Hammett study is proposed.

Synthesis of Ag/g‐C3N4 Composite as Highly Efficient Visible‐Light Photocatalyst for Oxidative Amidation of Aromatic Aldehydes

AbstractIn this contribution, an Ag/g‐C3N4 nanocomposite was synthesized and utilized as highly efficient and green photocatalyst for organic reactions under visible light irradiation. A layered, porous g‐C3N4 was synthesized following a modified solvothermal‐roasting process by using melamine and cyanuric chloride as precursor. Silver nanoparticles (NPs) were well anchored on g‐C3N4 nanosheets, which were prepared by a facile impregnation–roasting method. The inexpensive, stable g‐C3N4 coupled with the localized surface plasmon resonance (LSPR) effect of Ag NPs exhibited high photocatalytic activities toward aerobic oxidative amidation of aromatic aldehydes under visible light irradiation. Good to excellent yields were achieved for various substrates under the light of a 25 W compact fluorescent light (CFL) bulb in air. The operationally easy procedure provides an economical, green, and mild alternative for the formation of amide bonds.magnified image

ChemInform Abstract: The Copper‐Catalyzed Aerobic Oxidative Amidation of Tertiary Amines.

A general and efficient method for the synthesis of tertiary amides has been developed via the copper-catalyzed aerobic oxidative amidation of tertiary amines. Due to the use of the O2 oxidant, various functional groups were well tolerated under the present conditions. Extensive substrates studies demonstrated its potential as a practical approach for the synthesis of tertiary amides.

Formation of Amides from Imines via Cyanide-Mediated Metal-Free Aerobic Oxidation.

A new protocol for the direct formation of amides from imines derived from aromatic aldehydes via metal-free aerobic oxidation in the presence of cyanide is described. This protocol was applicable to various aldimines, and the desired amides were obtained in moderate to good yields. Mechanistic studies suggested that this aerobic oxidative amidation might proceed via the addition of cyanide to imines followed by proton transfer from carbon to nitrogen in the original imines, leading to carbanions of α-amino nitriles, which undergo subsequent oxidation with molecular oxygen in air to provide the desired amide compounds.

ChemInform Abstract: Cu‐Catalyzed Aerobic Oxidative Amidation of Aryl Alkyl Ketones with Azoles to Afford Tertiary Amides via Selective C—C Bond Cleavage.

Chemoselective cleavage of the C(CO)–C(alkyl) bond in aryl ketones leading to azole amides is disclosed with a broad substrate scope. Aryl ketones with a variety of long-chain alkyl groups have been demonstrated to be active substrates and mechanism studies suggested that molecular oxygen serves both as an oxidant and a reactant in this strategy.

Iron-catalyzed aerobic oxidative amidation of tertiary amines with carboxylic acids

An oxidative amidation of tertiary amines with carboxylic acids has been developed in the presence of FeCl3·6H2O as catalyst and oxygen as oxidant. A variety of tertiary amides were obtained in good to excellent yields from inexpensive and readily available reagents. The possible reaction pathways were investigated.

Copper catalysed direct amidation of methyl groups with N-H bonds.

An efficient copper catalyzed direct aerobic oxidative amidation of methyl groups of azaarylmethanes with N-H bonds producing amides is successfully developed, which can produce primary, secondary and tertiary amides, including those with functional groups. This reaction represents a straightforward method for the preparation of amides from the readily available hydrocarbon starting materials.

The copper-catalyzed aerobic oxidative amidation of tertiary amines

A general and efficient method for the synthesis of tertiary amides has been developed via the copper-catalyzed aerobic oxidative amidation of tertiary amines. Due to the use of the O2 oxidant, various functional groups were well tolerated under the present conditions. Extensive substrates studies demonstrated its potential as a practical approach for the synthesis of tertiary amides.

Cu-catalyzed aerobic oxidative amidation of aryl alkyl ketones with azoles to afford tertiary amides via selective C–C bond cleavage

Chemoselective cleavage of the C(CO)–C(alkyl) bond in aryl ketones leading to azole amides is disclosed. Aryl ketones with a variety of long-chain alkyl groups have been demonstrated to be active substrates and mechanism studies suggested that molecular oxygen serves both as an oxidant and a reactant in this strategy.

Phenazinium salt-catalyzed aerobic oxidative amidation of aromatic aldehydes.

Amides are prevalent in organic synthesis. Developing an efficient synthesis that avoids expensive oxidants and heating is highly desirable. Here the oxidative amidation of aromatic aldehydes is reported using an inexpensive metal-free visible light photocatalyst, phenazine ethosulfate, at low catalytic loading (1-2 mol %). The reaction proceeds at ambient temperature and uses air as the sole oxidant. The operationally easy procedure provides an economical, green, and mild alternative for the formation of amide bonds.

Copper-catalyzed aerobic oxidative inert C-C and C-N bond cleavage: a new strategy for the synthesis of tertiary amides.

A copper-catalyzed aerobic oxidative amidation reaction of inert C-C bonds with tertiary amines has been developed for the synthesis of tertiary amides, which are significant units in many natural products, pharmaceuticals, and fine chemicals. This method combines C-C bond activation, C-N bond cleavage, and C-H bond oxygenation in a one-pot protocol, using molecular oxygen as the sole oxidant without any additional ligands.

ChemInform Abstract: Aerobic Oxidative Amidation of Aromatic and Cinnamic Aldehydes with Secondary Amines by CuI/2‐Pyridonate Catalytic System.

A simple and convenient CuI/2-pyridonate catalytic system for the oxidative amidation of aldehydes with secondary amines has been developed. With this system, a variety of useful arylamides have been synthesized in moderate to good yields in the presence of small amount of copper catalyst and the pyridonate ligand, generating only water as a coproduct. Synthesis of cinnamamides was also achieved by the reactions of cinnamaldehydes with secondary amines in moderate yields. Air was successfully employed as a green oxidant in this catalytic system, achieving a safe and atom-efficient system for the synthesis of amides.