Zirconium catalyzed amide formation without water scavenging

A scalable homogeneous metal‐catalyzed protocol for direct amidation of carboxylic acids is presented. The use of 2–10 mol% of the commercially available Zr(Cp)2(OTf)2·THF results in high yields of amides at moderate temperature, using an operationally convenient reaction protocol that circumvents the use of water scavenging techniques

Catalytic amide formation from non-activated carboxylic acids and amines

The amide functionality is found in a wide variety of biological and synthetic structures such as proteins, polymers, pesticides and pharmaceuticals. Due to the fact that synthetic amides are still mainly produced by the aid of coupling reagents with poor atom-economy, the direct catalytic formation of amides from carboxylic acids and amines has become a field of emerging importance. A general, efficient and selective catalytic method for this transformation would meet well with the increasing demands for green chemistry procedures. This review covers catalytic and synthetically relevant methods for direct condensation of carboxylic acids and amines. A comprehensive overview of homogeneous and heterogeneous catalytic methods is presented, covering biocatalysts, Lewis acid catalysts based on boron and metals as well an assortment of other types of catalysts.AuthorCount:4;</p

Catalytic Reductive Dehydration of Tertiary Amides to Enamines under Hydrosilylation Conditions

Tertiary amides are efficiently reduced to their corresponding enamines under hydrosilylation conditions, using a transition-metal-free catalytic protocol based on <i>t</i>-BuOK (5 mol %) and (MeO)₃SiH or (EtO)₃SiH as the reducing agent. The enamines were formed with high selectivity in good-to-excellent yields

Mechanistic Elucidation of Zirconium-Catalyzed Direct Amidation

The mechanism of the zirconium-catalyzed condensation of carboxylic acids and amines for direct formation of amides was studied using kinetics, NMR spectroscopy, and DFT calculations. The reaction is found to be first order with respect to the catalyst and has a positive rate dependence on amine concentration. A negative rate dependence on carboxylic acid concentration is observed along with S-shaped kinetic profiles under certain conditions, which is consistent with the formation of reversible off-cycle species. Kinetic experiments using reaction progress kinetic analysis protocols demonstrate that inhibition of the catalyst by the amide product can be avoided using a high amine concentration. These insights led to the design of a reaction protocol with improved yields and a decrease in catalyst loading. NMR spectroscopy provides important details of the nature of the zirconium catalyst and serves as the starting point for a theoretical study of the catalytic cycle using DFT calculations. These studies indicate that a dinuclear zirconium species can catalyze the reaction with feasible energy barriers. The amine is proposed to perform a nucleophilic attack at a terminal η²-carboxylate ligand of the zirconium catalyst, followed by a C–O bond cleavage step, with an intermediate proton transfer from nitrogen to oxygen facilitated by an additional equivalent of amine. In addition, the DFT calculations reproduce experimentally observed effects on reaction rate, induced by electronically different substituents on the carboxylic acid

Catalytic Water Oxidation by a Molecular Ruthenium Complex: Unexpected Generation of a Single-Site Water Oxidation Catalyst

The increasing energy demand calls for the development of sustainable energy conversion processes. Here, the splitting of H₂O to O₂ and H₂, or related fuels, constitutes an excellent example of solar-to-fuel conversion schemes. The critical component in such schemes has proven to be the catalyst responsible for mediating the four-electron oxidation of H₂O to O₂. Herein, we report on the unexpected formation of a single-site Ru complex from a ligand envisioned to accommodate two metal centers. Surprising N–N bond cleavage of the designed dinuclear ligand during metal complexation resulted in a single-site Ru complex carrying a carboxylate–amide motif. This ligand lowered the redox potential of the Ru complex sufficiently to permit H₂O oxidation to be carried out by the mild one-electron oxidant [Ru­(bpy)₃]³⁺ (bpy = 2,2′-bipyridine). The work thus highlights that strongly electron-donating ligands are important elements in the design of novel, efficient H₂O oxidation catalysts

Metal-Free N-Arylation of Secondary Amides at Room Temperature

The arylation of secondary acyclic amides has been achieved with diaryliodonium salts under mild and metal-free conditions. The methodology has a wide scope, allows synthesis of tertiary amides with highly congested aryl moieties, and avoids the regioselectivity problems observed in reactions with (diacetoxyiodo)benzene