Oxidative Amidation Reaction Research Articles

Metal free synthesis of α-keto amides from 2-hydroxy acetophenones through domino alcohol oxidation–oxidative amidation reaction

An efficient method for the synthesis of α-keto amides using 2-iodoxybenzoic acid (IBX) promoted domino alcohol oxidation and oxidative amidation reaction sequence between 2-oxoalcohols and amines under metal-free conditions is developed. In this protocol, IBX is used as an oxidizing agent to synthesize the α-keto amides, which makes this methodology highly efficient, practical, and environmentally benign.

α‐Carbonylimine to α‐Carbonylamide: An Efficient Oxidative Amidation Approach

AbstractOur interest in generating amide bonds by employing the activated C=N system has led to the development of an efficient oxidative amidation reaction between 2‐oxoaldehyde and weak nucleophilic amines (anilines, benzamides and sulfonamides). Mechanistic studies support the involvement of α‐carbonylimine (–CO–C=N–) based compounds or intermediates as a central feature of the reaction, in which an adjacent CO moiety enhances the electrophilicity of the C=N system, which favors attack of the oxidant (TBHP or SeO2), thereby resulting in the generation of the desired products in good yields. The direct oxidative coupling of 2‐oxoaldehydes and weak nucleophilic amines has been accomplished through either MgSO4–TBHP–pyridine/CuBr, or SeO2·pyridine promoted methods. In the current study, SeO2·pyridine emerged as a versatile reagent with which to promote initial α‐carbonylimine formation between 2‐oxoaldehyde and weak nucleophilic amine, and subsequent oxidation to the corresponding α‐carbonylamide. The reported methodology constitutes one of the few reports of the synthesis of α‐ketoamides from anilines, perhaps the second report for the generation of α‐ketoimides, and the first report of the generation of 2‐oxoamides with sulfonamides.

A novel and one-pot method for synthesis of unprecedented 3,3-dimethyl-2-amide indoles under metal-free conditions

A novel and efficient method for the synthesis of 3,3-dimethyl-2-amide indoles, employing a I2/DMSO-promoted oxidative amidation reaction between 1,2,3,3-tetramethyl-3H-indolium iodide and cyclic secondary amines under metal-free conditions has been developed.

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: nBu4NI‐Catalyzed Oxidative Amidation of Aldehydes with Tertiary Amines.

AbstractA novel oxidative amidation reaction of aldehydes with different tertiary amines in the presence of excess tBuOOH and Bu4NI as catalyst is developed.

Metal-Free Oxidative Amidation of 2-Oxoaldehydes: A Facile Access to α-Ketoamides

A novel and efficient method for the synthesis of α-ketoamides, employing a dimethyl sulfoxide (DMSO)-promoted oxidative amidation reaction between 2-oxoaldehydes and amines under metal-free conditions is presented. Furthermore, mechanistic studies supported an iminium ion-based intermediate as a central feature of reaction wherein C1-oxygen atom of α-ketoamides is finally derived from DMSO.

Multistep synthesis of amides from alcohols and amines in continuous flow microreactor systems using oxygen and urea hydrogen peroxide as oxidants

By integrating a heterogeneous oxidation step, gas–liquid separation, and an oxidative amidation reaction to form a continuous system, a multistep synthetic protocol has been demonstrated to produce amides under mild conditions using alcohols and amines as the starting materials. The use of inexpensive oxygen and urea hydrogen peroxide as the only oxidants affords an economical and adaptable synthetic route for amides.

Synthesis of glycosylamines and glyconamides using molecular iodine

We describe herein the synthesis of glyconamides and glycosylamines using molecular iodine on benzylated carbohydrates. During the improvement and the optimization of the direct oxidative amidation reaction, we also discovered the possibility to form glycosylamines with excellent yields and short reaction times in comparison with the previously reported procedures. Advantages of these methods are the operational simplicity, elimination of use of complicated reagents and procedures, and generality of the reactions. Our methodology is an excellent access to precursors of N-alkyliminosugars and imino-C-glycosides.

Hydrogen-Bond-Directed Highly Stereoselective Synthesis of Z-Enamides via Pd-Catalyzed Oxidative Amidation of Conjugated Olefins

An efficient procedure for the preparation of Z-enamides has been developed, involving the reaction of primary amides with conjugated olefins using a Pd/Cu cocatalyst system. It was found that certain additives, such as phosphine oxides and phosphonates, increase the efficiency of the reaction in nonpolar solvents under an oxygen atmosphere, thus producing a variety of Z-enamides in high yields with excellent stereoselectivity under Wacker-type conditions. The oxidative amidation reaction has a broad substrate scope, allowing alkyl, aryl, and vinyl amides to react with olefins conjugated with ester, amide, phosphonate, and ketone groups. The notable preference for the formation of Z-enamides is presumably due to the presence of an intramolecular hydrogen bond between the amido proton and the carbonyl oxygen. The energy difference between two plausible sigma-alkylamidopalladium intermediates, leading to Z- and E-isomeric enamide products, respectively, was calculated to be 4.18 kcal/mol. The beta-hydride elimination step is assumed to be a stereochemistry-determining step in the overall oxidative amidation process, with the energy level for the transition state leading to the Z-enamide being 5.35 kcal/mol lower than that leading to the E-isomer. The efficiency of photoisomerization between Z- and E-enamides was observed to be largely dependent on the substrates' substituents, and certain E-enamides could be obtained in synthetically useful yields by photoirradiation of Z-isomers. Synthetic application of the present method was successfully demonstrated by a direct formal synthesis of cis-CJ-15,801.