Oxidative Amidation Research Articles

ChemInform Abstract: Cobalt‐Catalyzed Dehydrogenative Coupling of Alcohols/Aldehydes and Amines: An Important Role for Imine Hydration.

AbstractA cobalt and iodide co‐catalyzed oxidative amidation reaction between alcohols or aldehydes and amines smoothly proceeds under mild conditions affording amides with broad functional group tolerance.

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: Recent Developments in Oxidative Esterification and Amidation of Aldehydes

AbstractReview: [33 refs.

SeO2 mediated efficient synthesis of amides and α-ketoamides of secondary amines with wide substrate scope

SeO2 mediated oxidative amidation of acetophenones, phenylacetylenes, and phenylacetaldehydes to α-ketoamides and aldehydes to amides is reported. Amidation selectively proceeds with secondary amines. α-Ketoamide derivatives of natural products 16-dehydropregnenolone acetate (8), pregnenolone acetate (10), and progesterone (11) were synthesized.

Recent Advances in the Catalytic Synthesis of α-Ketoamides

α-Ketoamides and their derivatives are key constituents of natural products, biologically relevant molecules, drug and drug candidates, and functional materials. Further, they are versatile and valuable intermediates and synthons in a number of functional group transformations and total syntheses. In recent years tremendous growth has been realized in the development of synthetic methods for α-ketoamide preparation and their applications in synthetic and medicinal chemistry. Among the various catalytic methods of α-ketoamide formation, two approaches, namely double aminocarbonylation and oxidative amidation, have received much more attention and have been greatly studied because of the ready availability of the starting materials, use of carbon monoxide (CO) as a direct source of carbonyl functionalities, and use of molecular oxygen (O2) or air as a green terminal oxidant and/or reactants. Catalyzed α-ketoamide formation can be roughly classified into metal- and nonmetal-catalyzed processes. In the contex...

Sterically Demanding Oxidative Amidation of α‐Substituted Malononitriles with Amines Using O2

AbstractAn efficient amidation method between readily available 1,1‐dicyanoalkanes and either chiral or nonchiral amines was realized simply with molecular oxygen and a carbonate base. This oxidative protocol can be applied to both sterically and electronically challenging substrates in a highly chemoselective, practical, and rapid manner. The use of cyclopropyl and thioether substrates support the radical formation of α‐peroxy malononitrile species, which can cyclize to dioxiranes that can monooxygenate malononitrile α‐carbanions to afford activated acyl cyanides capable of reacting with amine nucleophiles.

Sterically Demanding Oxidative Amidation of α-Substituted Malononitriles with Amines Using O2.

An efficient amidation method between readily available 1,1‐dicyanoalkanes and either chiral or nonchiral amines was realized simply with molecular oxygen and a carbonate base. This oxidative protocol can be applied to both sterically and electronically challenging substrates in a highly chemoselective, practical, and rapid manner. The use of cyclopropyl and thioether substrates support the radical formation of α‐peroxy malononitrile species, which can cyclize to dioxiranes that can monooxygenate malononitrile α‐carbanions to afford activated acyl cyanides capable of reacting with amine nucleophiles.

Copper(I)-catalysed amidation and successive oxidation of benzylic C(sp3)–H bond: synthesis of 1H-pyrrolo[3,4-b]quinoline-1,3(2H)-diones

An efficient copper(I)-catalysed intramolecular arylmethyl C(sp3)–H direct oxidative amidation reaction has been developed for the preparation of drug-like 1H-pyrrolo[3,4-b]quinoline-1,3(2H)-diones from readily available 2-methyl-3-carbamoyl-quinolines.

ChemInform Abstract: IBX‐Promoted Domino Reaction of α‐Hydroxy Amides: A Facile One‐Pot Synthesis of Isatins.

A novel and temperature-controlled oxidation of α-hydroxy amides in the presence of IBX is described. The divergent one-pot synthesis of isatins and α-formyl amides was achieved in good to excellent yields under metal-free conditions. And these two mild methods can tolerate a variety of functional groups, and are operationally simple.

An Oxidation–Amidation Approach for the Synthesis of Glycuronamides

AbstractA route for the synthesis of glycuronamides via the intermediacy of 6‐S‐tolyl‐substituted glycosides and uronic acid thioesters, is reported. The route, which is compatible with a variety of carbohydrate residues and protecting groups, was used to synthesize the repeating unit of the E. coli K54 capsular polysaccharide.

ChemInform Abstract: Rhodium‐Catalyzed Oxidative Amidation of Allylic Alcohols and Aldehydes: Effective Conversion of Amines and Anilines into Amides.

The rhodium-catalyzed oxidative amidation of allylic alcohols and aldehydes is reported. In situ generated [(BINAP)Rh]BF4 catalyzes the one-pot isomerization/oxidative amidation of allylic alcohols or direct amidation of aldehydes using acetone or styrene as the hydrogen acceptor. The conditions are general, affording good to excellent yields with a wide array of amine and aniline nucleophiles, and chemoselective, other alcohols do not participate in the oxidation reaction. Utilization of biphasic conditions is critical, as they promote an equilibrium between the imine/enamine byproducts and the hemiaminal, which can undergo oxidation to the amide.

Oxidative Amidation of Aldehydes Using Phosphotungstate Ionic Liquids

Oxidative Amidation of Aldehydes Using Phosphotungstate Ionic Liquids

(Organic and Biological Electrochemistry Division Manuel M. Baizer Award) Following the Lead of R. B. Woodward and M. M. Baizer: Using Concepts in Physical Organic Chemistry to Shape the Course of Electrochemical Reactions

One of R. B. Woodward’s many contributions to organic chemistry was the way in which he used physical organic chemistry and an understanding of mechanism to shape the development of new synthetic methods. From the use of temporary, conformational constraints to dictate the stereochemistry of a complex target to the interception of a key intermediate to bring about a cis-hydroxylation reaction from the most hindered face of a molecule, the Woodward group beautifully demonstrated that the outcome of a reaction could be predetermined by considering and then controlling its mechanistic features. In a similar manner, Manuel M. Baizer taught us much about how to think about electrochemical reactions. His work helped take the “magic” out of electroorganic processes and demonstrated that electroorganic reactions were indeed organic reactions. They were triggered by electron-transfer processes and had additional parameters that needed to be considered, but to a great extent they could be understood and optimized as synthetic transformations by considering their chemical mechanism. This perspective served to make organic electrochemistry accessible to the larger synthetic community. The combination of lessons learned from these two pioneers laid the foundation for our own studies concerning electrochemical reactions and their use in synthesis. From the oxidation of amides used in the synthesis of peptidomimetics, to the use of oxidative cyclization reactions in synthesis, to the site-selective generation of chemical reagents for the functionalization of microelectrode array surfaces, we have continually relied on the fact that electroorganic reactions are simply organic reactions and can thus be optimized as such. The overall approach has fueled not only our own work, but also that of so many others, far too many to name here. In the talk to be presented, an overview of electrochemical synthetic methods will be presented against a backdrop of the mechanistic insights and findings that enabled and enhanced their development. An emphasis will be placed on the synthetic utility of reactions that take advantage of reactive radical cation intermediates,1 site-selective reactions on conducted on microelectrode arrays,2 and a look toward the future use of paired electrochemical reactions for the on-site generation of chemical reagents.3

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.

Theoretical mechanistic investigation of zinc(II) catalyzed oxidative amidation of benzyl alcohols with amines

Density functional theory (DFT) calculations have been performed to investigate the mechanism of Zn(II)-catalyzed oxidative amidation of benzylic alcohol with amines. A two-step oxidation mechanism is proposed where oxidation of benzyl alcohol to benzaldehyde is the first step. In the 2nd step, hemiaminal generated from the aldehyde is converted to amide through oxidation. Inner sphere, out sphere and intermediate sphere mechanisms for the oxidation of benzyl alcohol to benzaldehyde, are investigated. The inner sphere mechanism is kinetically more demanding (Ea=30.59kcalmol−1), and not believed to contribute to the progress of the reaction under the experimental conditions (at 40°C). The activation barrier associated with outer sphere mechanism is 24.4kcalmol−1, which can be easily surpassed under the reaction conditions. Therefore, the more plausible mechanism is outer sphere mechanism. The oxidation of hemiaminal to amide is also kinetically highly favorable with Ea=7.88kcalmol−1 (outer sphere mechanism). The intermediate sphere mechanism involving transfer of hydrogen to tert-butyl hydrogen peroxide (TBHP) has activation barrier of 25.98kcalmol−1, and therefore cannot be excluded safely. The preference of zinc (II) for outer sphere mechanism is quite contrary to the other later transition metals (Ru, Ir, Pd) catalysis for the similar reaction where inner sphere mechanism is the predominant one.

Mechanism of Oxidative Amidation of Nitroalkanes with Oxygen and Amine Nucleophiles by Using Electrophilic Iodine.

Recently, we developed a direct method to oxidatively convert primary nitroalkanes into amides that entailed mixing an iodonium source with an amine, base, and oxygen. Herein, we systematically investigated the mechanism and likely intermediates of such methods. We conclude that an amine-iodonium complex first forms through N-halogen bonding. This complex reacts with aci-nitronates to give both α-iodo- and α,α-diiodonitroalkanes, which can act as alternative sources of electrophilic iodine and also generate an extra equimolar amount of I(+) under O2. In particular, evidence supports α,α-diiodonitroalkane intermediates reacting with molecular oxygen to form a peroxy adduct; alternatively, these tetrahedral intermediates rearrange anaerobically to form a cleavable nitrite ester. In either case, activated esters are proposed to form that eventually reacts with nucleophilic amines in a traditional fashion.

ChemInform Abstract: Iodine‐Catalyzed Efficient Amide Formation from Aldehydes and Amines.

AbstractThe operationally simple radical oxidative amidation of aldehydes with amines shows good functional group tolerance and provides the corresponding amides in excellent yields.

ChemInform Abstract: Organocatalytic Oxidative Amidation of Aldehydes with Tetrazoles to Construct 2,5‐Diaryl 1,3,4‐Oxadiazoles.

AbstractThe gram‐scale reaction is also realized.

ChemInform Abstract: Polyethylene Glycol as a Recyclable Reaction Medium for Gold‐Catalyzed Direct Oxidative Amide Synthesis from Aldehydes and Amines.

AbstractThe catalyst as well as the solvent can be easily recovered and reused without significant loss of activity.

ChemInform Abstract: Metal Free Synthesis of α‐Keto Amides from 2‐Hydroxy Acetophenones Through Domino Alcohol Oxidation—Oxidative Amidation Reaction.

AbstractAn economic and environment friendly IBX promoted synthesis of α‐keto amides from α‐oxoalcohols and amines through domino alcohol oxidation—oxidative amidation reaction sequence under metal‐free conditions is reported.