Palladium-catalyzed Amidation Research Articles

Palladium-catalyzed amidation of carbazole derivatives via hydroamination of isocyanates.

The first amidation of carbazoles at the N9 position via palladium-catalyzed hydroamination of isocyanates is demonstrated. This simple, general and efficient method could deliver a wide range of carbazole-N-carboxamides in up to 99% yield. The salient features of this transformation include simple conditions with no need for a strong base, high chemo- and regio-selectivities and good functional group tolerance. In particular, this work-up-free and chromatography-free protocol is time-saving, cost-effective and user-friendly.

Palladium catalyzed amidation of phenyl carboxylates and anilines using aqueous micellar catalysis

Amidation is one of the most important and frequently run reactions, especially in the pharmaceutical industry. Amides are usually synthesized by stoichiometric methods in organic solvents. We herein report an operationally simple and scalable method for the palladium-catalyzed amidation of phenyl carboxylates under mild micellar conditions.

Palladium-Catalyzed Amide N-C Hiyama Cross-Coupling: Synthesis of Ketones.

N-Acylglutarimides and arylsiloxanes reacted in the presence of Pd(OAc)2/PCy3, Et3N·3HF, and LiOAc to provide the corresponding arylketones in good yields. Aryl-, vinyl-, and alkyl-substituted N-acylglutarimides showed good activity in the coupling reactions of arylsiloxanes. The reaction had a broad substrate scope and showed good functional group tolerance. N-Benzoylsuccinimide and N-protected N-phenylbenzamides showed good activities in coupling reactions with phenylsiloxane. The employment of CuF2 as an activor afforded the decarbonylative products at 160 °C.

Palladium-Catalyzed Amidation and Amination of (Hetero)aryl Chlorides under Homogeneous Conditions Enabled by a Soluble DBU/NaTFA Dual-Base System

The palladium-catalyzed coupling of aryl and heteroaryl chlorides with primary amides under mild homogeneous reaction conditions is reported. Successful C–N coupling is enabled by the use of a uniq...

Palladium-Catalyzed Amide Synthesis via Aminocarbonylation of Arylboronic Acids with Nitroarenes.

A palladium-catalyzed aminocarbonylation of aryl boronic acids with nitroarenes for the synthesis of amides has been developed. A wide range of substrates were well-tolerated and gave the corresponding amides in moderate to good yields. No external oxidant or reductant was needed in this procedure. This procedure provides a redox-economical process for the synthesis of amides.

Practical and Scalable Synthetic Method for Preparation of Dolutegravir Sodium: Improvement of a Synthetic Route for Large-Scale Synthesis

A practical and scalable synthetic method to obtain dolutegravir sodium (1) was established starting from the readily accessible material maltol (2). This synthetic method includes a scalable oxidation process of maltol and palladium-catalyzed amidation for introduction of an amide moiety, leading to a practical manufacturing method in short synthetic steps. The synthetic method demonstrated herein enables multikilogram scale manufacturing of 1 of high purity.

Mechanistic investigation of palladium-catalyzed amidation of aryl halides.

A mechanistic investigation using Becke3LYP density functional theory (DFT) was carried out on the palladium-catalyzed amidition of bromobenzene and (t)Bu-isocyanide. The whole catalytic cycle consists of five steps: oxidative addition, migratory insertion, anion exchange, reductive elimination, and hydrogen migration. The rate-determining step is oxidative addition, with a small Gibbs free energy of 14.6 kcal mol(-1). In the migratory insertion step, (t)Bu-isocyanide provides an important source of carboxy and amino groups to establish the amide group. For anion exchange, path 1a is suggested as the most favorable pathway with the help of the base, and water provides a source of oxygen which is perfectly in line with experimental observations. Finally, in the hydrogen migration step, we illustrate that the six-membered ring path is energetically favored due to the assisting influence of water. In addition, our calculations indicate that using dimethyl sulfoxide as a solvent does not change the rate-determining step.

Copper- and Palladium-Catalyzed Amidation Reactions for the Synthesis of Substituted Imidazo[4,5-c]pyridines

Imidazo[4,5-c]pyridines were synthesized in three steps utilizing a palladium-catalyzed amidation/cyclization strategy. N-Aryl substrates were synthesized using copper-catalyzed amidation of 3-amino-N-Boc-4-chloropyridine. Complementary protocols for the selective chlorination of imidazo[4,5-c]pyridines at the C2 and C7 positions were also developed.

Copper- or Palladium-Catalyzed Amidation and Cyclization Route for the Synthesis of Pyrimido[4,5-b]carbazoles

Pyrimido[4,5-b]carbazole derivatives were synthesized by a copper- or palladium-catalyzed sequential amidation and cyclization process in which a C–N bond formed at the 2-position of a 3-formylcarbazole afforded a new 9-substituted N-(3-formyl-9H-carbazol-2-yl)amide.

Palladium-Catalyzed Amidation of Aryl Halides Using 2-Dialkylphosphino-2′-alkoxyl-1,1′-binaphthyl as Ligands

Palladium-catalyzed intermolecular C-N bond-forming reactions between aryl halides and amides are described using 2-dialkylphosphino-2'-alkoxyl-1,1'-binaphthyl, which is both bulky and electron-rich, as the ligand. A variety of amides, including aliphatic and aromatic primary amides, lactams, and carbamates, were viable substrates for the amidation, which exhibited good functional group compatibility. By tuning the substituents at the 2,2'-position of 1,1'-binaphthyl of the ligand, the palladium-catalyzed amidation of bulky aryl halides was realized and this coupling reaction was used to synthesize 2-amino-2'-methoxy-1,1'-binaphthyl in high yield.

A Bulky Biaryl Phosphine Ligand Allows for Palladium‐Catalyzed Amidation of Five‐Membered Heterocycles as Electrophiles

Palladium-catalyzed amidation of five-membered heterocyclic bromides that contain multiple heteroatoms was achieved for the first time using the Pd/1 catalyst system. This system allows for efficient access to N-arylated imidazoles, pyrazoles, thiazoles, pyrroles, and thiophenes in moderate to excellent yield. Experimental results and DFT calculations point to the need for electron-rich and especially sterically demanding biaryl phosphine ligand to promote these difficult cross-coupling reactions.

A Bulky Biaryl Phosphine Ligand Allows for Palladium‐Catalyzed Amidation of Five‐Membered Heterocycles as Electrophiles

The incredible bulk: The first palladium-catalyzed amidation of five-membered heterocyclic bromides with multiple heteroatoms was achieved using the Pd/1 catalyst system. N-Arylated imidazoles, pyrazoles, thiazoles, pyrroles, and thiophenes were synthesized in moderate to excellent yield. Experimental results and DFT calculations point to the need for an electron-rich and sterically demanding biaryl phosphine ligand to promote these difficult reactions.

Palladium‐Catalyzed Amidation by Chemoselective C(sp3)H Activation: Concise Route to Oxindoles Using a Carbamoyl Chloride Precursor

Quite select: a new strategy was developed for the synthesis of various oxindoles from carbamoyl chlorides. Under the optimum reaction conditions, with Ad(2)PBu as a ligand, tBuCONHOH as an additive, and a CO atmosphere, selective C(sp(3))-H activation proceeded in the presence of a C(sp(2))-H bond. Ad=adamantyl.

Synthesis of Amides via Palladium-Catalyzed Amidation of Aryl Halides

A new and efficient method for the synthesis of amides via palladium-catalyzed C-C coupling of aryl halides with isocyanides is reported, by which a series of amides were formed from readily available starting materials under mild conditions. This transformation could extend its use to the synthesis of natural products and significant pharmaceuticals.

Palladium-catalyzed amidation of 2-chloropyrimidines

A mild and efficient Pd-catalyzed coupling of amides with 2-chloropyrimidines is described. The use of bidentate phosphines, such as Xantphos (7), as supporting ligands was found to be crucial for providing high yields of 2-(N-acylamino)pyrimidine coupling products 1.

ChemInform Abstract: Carbamoylation of Aryl Halides by Molybdenum or Tungsten Carbonyl Amine Complexes.

AbstractIt provides a simple approach to aromatic and heteroaromatic amides.

Carbamoylation of Aryl Halides by Molybdenum or Tungsten Carbonyl Amine Complexes

When aryl halide is treated with molybdenum carbonyl amine complex in the presence of base, carbamoylation proceeds to give amide in good yield. The proposed mechanism involves oxidative addition of aryl halide to molybdenum(0) complex, migratory insertion to carbon monoxide giving acyl(amino)molybdenum(II) or aryl(carbamoyl)molybdenum(II) intermediate, and reductive elimination of the amide. This method is simple and provides an alternative method to the conventional palladium-catalyzed amide formation using gaseous carbon monoxide.

Synthesis of a TRPV1 Receptor Antagonist

A five-step synthesis of a TRPV1 receptor antagonist 1 is described. The key step involves a novel palladium-catalyzed amidation reaction of 4-chloro-1-methylindazole 8 with the benzyl urea 9 to form the unsymmetrically substituted urea 1.

Palladium-Catalyzed Carbamoylation of Aryl Halides by Tungsten Carbonyl Amine Complex

In the presence of aminepentacarbonyltungsten, base, and a catalytic amount of palladium(0) complex, carbamoylation of aryl halide proceeds to afford amide. The reaction may involve transmetalation between palladium(II) intermediate and carbamoyltungstenate that is generated in situ. This catalytic cross-coupling reaction provides an alternative method to the conventional palladium-catalyzed amidation by using gaseous carbon monoxide.

Palladium‐Catalyzed Amidation of Unactivated C(sp3)H Bonds: from Anilines to Indolines

Palladium‐Catalyzed Amidation of Unactivated C(sp³)H Bonds: from Anilines to Indolines