Catalytic reductive N-alkylation of amines using carboxylic acids

Andrews, Keith G.; Summers, Declan; Donnelly, Liam J.; Denton, Ross M.

doi:10.1039/c5cc08881j

Cited by 56 publications

(36 citation statements)

References 36 publications

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“…Intuitively, the product might be expected to arise from silane-mediated amidation47, followed by amide reduction by an activated silane; however, an activated reductant is not consistent with the high functional group tolerance observed.…”

Section: Resultsmentioning

confidence: 92%

A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid

2017

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Amines are a fundamentally important class of biologically active compounds and the ability to manipulate their physicochemical properties through the introduction of fluorine is of paramount importance in medicinal chemistry. Current synthesis methods for the construction of fluorinated amines rely on air and moisture sensitive reagents that require special handling or harsh reductants that limit functionality. Here we report practical, catalyst-free, reductive trifluoroethylation reactions of free amines exhibiting remarkable functional group tolerance. The reactions proceed in conventional glassware without rigorous exclusion of either moisture or oxygen, and use trifluoroacetic acid as a stable and inexpensive fluorine source. The new methods provide access to a wide range of medicinally relevant functionalized tertiary β-fluoroalkylamine cores, either through direct trifluoroethylation of secondary amines or via a three-component coupling of primary amines, aldehydes and trifluoroacetic acid. A reduction of in situ-generated silyl ester species is proposed to account for the reductive selectivity observed.

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Section: Resultsmentioning

confidence: 92%

A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid

2017

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“…Developing efficient methods for the amines synthesis is of high interest in both laboratory research and chemical industry, due to the wide application of alkyl‐substituted amines in pharmaceuticals, agrochemicals and organic materials . In recent years, sustainable and eco‐friendly approaches have been established for N ‐methylation/ N ‐alkylation of amines using carbon dioxide, dimethyl carbonate (DMC), methanol and formic acid/carboxylic acids as methyl/alkyl sources. Among them, carboxylic acid has highly stable, readily available and easily‐handled property in comparison with air‐sensitive aldehydes which have been generally used in reductive amination to generate alkyl‐substituted amines.…”

Section: Methodsmentioning

confidence: 99%

Efficient Iron‐Catalyzed Reductive N‐Alkylation of Aromatic Amines with Carboxylic Acid and Phenylsilane

et al. 2018

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The development of efficient catalysts for the alkylation of amines with carboxylic acids is attracting much attention. Herein, we would like to report an earthabundant iron-catalyzed protocol for the N-alkylation of anilines using carboxylic acid as alkyl source and phenylsilane as reducing agent. With Fe 2 (CO) 9 as a catalyst, a broad range of primary and secondary anilines are successfully converted to the corresponding tertiary anilines. Furthermore, this N-alkylation mainly goes through the amide pathway; while the aldehyde pathway can not be ruled out.

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“…Another report from Sakai described the catalytic construction of N ‐substituted five‐ and six‐membered lactams from keto acids with primary amines by reductive amination . However, the alkylations of amines with the carboxylic acids mentioned above proceed mainly by using homogeneous Pt,, Ru,, Ir, Rh, and In catalysts …”

Section: Introductionmentioning

confidence: 99%

“…Beller and other groups,, proposed two possible pathways for the transition‐metal‐catalyzed N‐alkylation of amines with carboxylic acids (Scheme ). Path A includes acid–amine condensation and in situ amide reduction steps.…”

Section: Introductionmentioning

confidence: 99%

Density Functional Theory Mechanistic Study of Boron‐Catalyzed N‐Alkylation of Amines with Formic Acid: Formic Acid Activation by Silylation Reaction

Zhao

2018

Chemistry An Asian Journal

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New methodology for the alkylation of amines is an intriguing issue in both academia and industry. Recently, several groups reported the metal-free B(C F ) -catalyzed N-alkylation of amines, but the mechanistic details of these important reactions are unclear. Herein, a computational study was performed to elucidate the mechanism of the N-alkylation of amines with formic acid catalyzed by the Lewis acid B(C F ) in the presence of hydrosilane. We found that the reaction started with the activation of formic acid through a novel model. Then, the high electrophilicity of the C center of the formic acid unit and the nucleophilic character of the amine resulted in a C-N coupling reaction. Finally, two sequential silyl-group and H transfer steps occurred to generate the final product. Upon comparing the reaction barrier and the hydrogenation of indole, our mechanism is more favorable than that proposed by the group of Yu and Fu.

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Catalytic reductive N-alkylation of amines using carboxylic acids

Cited by 56 publications

References 36 publications

A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid

A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid

Efficient Iron‐Catalyzed Reductive N‐Alkylation of Aromatic Amines with Carboxylic Acid and Phenylsilane

Density Functional Theory Mechanistic Study of Boron‐Catalyzed N‐Alkylation of Amines with Formic Acid: Formic Acid Activation by Silylation Reaction

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