Amide | EPFL Graph Search

In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent any group, typically organyl groups or hydrogen atoms. The amide group is called a peptide bond when it is part of the main chain of a protein, and an isopeptide bond when it occurs in a side chain, such as in the amino acids asparagine and glutamine. It can be viewed as a derivative of a carboxylic acid () with the hydroxyl group () replaced by an amine group (); or, equivalently, an acyl (alkanoyl) group () joined to an amine group. Common examples of amides are formamide (), acetamide (), benzamide (), and dimethylformamide (). Some uncommon examples of amides are N-chloroacetamide () and chloroformamide (). Amides are qualified as primary, secondary, and tertiary according to whether the amine subgroup has the form , , or , where R and R' are groups other than hydrogen. The core of amides is called the amide group (specifica

Migrative Carbofluorination of Saturated Amides Enabled by Pd-Based Dyotropic Rearrangement

Simone Gallarati, Qian Wang, Hua Wu, Guoqiang Yang, Jieping Zhu

Directly editing an all-carbon quaternary carbon itself of nonstrained acyclic molecules remains underexploited despite the recent advances in the fields of both C–H and C–C bond activation. Herein, we report a palladium-catalyzed migrative carbofluorination of saturated amides enabled by the activation of both the C(sp3)–H and the Cquaternary–Cσ bonds. In this transformation, the α-quaternary carbon of Weinreb amides is converted to α-tertiary fluoride with concurrent migration of an aryl or an amido group from the α- to β-carbon. DFT calculations indicate that the dyotropic rearrangement proceeds through an unusual anti-selective [2.1.0] bicyclic transition state. The reaction, compatible with a broad range of functional groups, is stereospecific and is applicable to the synthesis of enantioenriched products.

ACS2022

Mechanistic Studies of Two Ni-Catalyzed Reactions: Reductive Amidation of Esters with Nitroarenes and Hydrosilylation of Alkenes

Marten Leendert Ploeger

Mechanistic investigations into homogeneously catalyzed reactions are essential for the fur-ther development of synthetic methodologies. Insights in the overall reaction pathway and vital steps such as the rate-determining and selectivity-determining steps allow for rational design of improved catalysts. Moreover, mechanistic investigations may reveal the existence of unexpected intermediates in the catalytic cycle. The discovery of such intermediates may inspire new methodologies that would not have been considered if their formation was un-known. Because of economic advantages over heavier congeners, there has been a recent surge in the use of nickel -based homogeneous catalysts. Although much progress has been made into methodology development, the mechanistic understanding of the new reactivities is relatively primitive. In-depth mechanistic investigations into nickel catalyzed reactions are therefore of considerable interest. Chapters 2-4 deal with the mechanism of reductive coupling of nitroarenes and esters to form amides. In chapter 2, the initial reduction pathway that occurs before the reaction with ester is investigated, revealing the crucial intermediate to be azobenzene and the source of the proton in the final amide product. In chapter 3, kinetics, Hammett plots, competition experi-ments and stoichiometric reactions with a potential intermediate are described. These studies reveal azobenzene is reductively cleaved by low-valent nickel before the ester gets involved in the reaction. Moreover, ZnCl2, a byproduct of the reduction of the nickel precursor by zinc, is revealed to play an important role in several steps of the reaction. In chapter 4, the computa-tional investigation based on the experimental data is discussed. By combining the computa-tional exploration of the potential energy surface with qualitative kinetic analysis, a catalytic cycle for the reaction between azobenzene and ester could be proposed. The finding that the reaction between azobenzene and ester goes through nickel imide inter-mediates is intriguing as nickel imides are known to react with a variety of substrates and azo-benzene would be a relatively benign precursor to them. Chapter 5 reports a preliminary explo-ration of several types of reactivities can be expected to work on the basis that the reactivity with imides is already known. Several types of these reactivities seem to be inaccessible as they are incompatible with the highly reductive nature of the nickel catalyst that is required for the azobenzene activation. However, some other reactivities show promise. Chapter 6 reports an investigation in the alkene hydrosilylation catalyzed by a nickel pincer complex developed in our group. Previous investigations had indicated a nickel alkyl complex was the resting state. However, a combination of reaction progress analysis, transmission elec-tron microscopy and competition reactions reveal that this is merely a precatalyst. Under cata-lytic conditions, it slightly decomposes under to form the true catalyst, which is tentatively identified as nickel nanoparticles.

EPFL2020

Manganese-mediated reductive amidation of esters with nitroarenes

Chi Wai Cheung, Xile Hu, Ning Shen, Peng Wang

Amides are ubiquitous molecules in nature and in synthetic chemistry. Here we report a convenient and efficient method to synthesize N-aryl amides via amidation of esters with nitroarenes. In the presence of manganese metal, this amidation proceeded smoothly without the need for additional catalysts or ligands. Various esters and nitroarenes are suitable substrates to afford a wide range of N-aryl amides, including bio-active molecules and intermediates to drug molecules.

ROYAL SOC CHEMISTRY2019

Mechanistic Studies of Two Ni-Catalyzed Reactions: Reductive Amidation of Esters with Nitroarenes and Hydrosilylation of Alkenes

Marten Leendert Ploeger

EPFL2020