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H-D exchange in deuterated trifluoroacetic acid via ligand-directed NHC-palladium catalysis: a powerful method for deuteration of aromatic ketones, amides, and amino acids.

ABSTRACT: A method has been developed for one-step ortho-selective ligand-directed H-D exchange, accompanied in some cases by concurrent acid-catalyzed electrophilic deuteration. This method is effective for deuteration of aromatic substrates ranging from ketones to amides and amino acids, including compounds of biological and pharmaceutical interest such as acetaminophen and edaravone. Use of a palladium catalyst featuring an NHC ligand is critical for the observed reactivity. Experimental evidence strongly suggests that palladium facilitates C-H activation of the aromatic substrates, a mechanism seldom observed under strongly acidic conditions. 2015 Elsevier Ltd. All rights reserved.

SUBMITTER: Giles R

PROVIDER: S-EPMC4610012 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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H-D exchange in deuterated trifluoroacetic acid via ligand-directed NHC-palladium catalysis: a powerful method for deuteration of aromatic ketones, amides, and amino acids.

Giles Richard R Ahn Green G Jung Kyung Woon KW

Tetrahedron letters 20151101 45

A method has been developed for one-step <i>ortho</i>-selective ligand-directed H-D exchange, accompanied in some cases by concurrent acid-catalyzed electrophilic deuteration. This method is effective for deuteration of aromatic substrates ranging from ketones to amides and amino acids, including compounds of biological and pharmaceutical interest such as acetaminophen and edaravone. Use of a palladium catalyst featuring an NHC ligand is critical for the observed reactivity. Experimental evidenc ...[more]

PMID: 26494929

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