Ruthenium-Catalyzed Reductive Arylation of N-(2-Pyridinyl)amides with Isopropanol and Arylboronate Esters

Thomas O Ronson; Evelien Renders; Ben F Van Steijvoort; Xubin Wang; Clarence C D Wybon; Hana Prokopcová; Lieven Meerpoel; Bert U W Maes

doi:10.1002/anie.201810947

Ruthenium-Catalyzed Reductive Arylation of N-(2-Pyridinyl)amides with Isopropanol and Arylboronate Esters

Angew Chem Int Ed Engl. 2019 Jan 8;58(2):482-487. doi: 10.1002/anie.201810947. Epub 2018 Dec 11.

Authors

Thomas O Ronson¹, Evelien Renders¹, Ben F Van Steijvoort¹, Xubin Wang¹, Clarence C D Wybon¹, Hana Prokopcová², Lieven Meerpoel², Bert U W Maes¹

Affiliations

¹ Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium.
² Janssen Research & Development, Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340, Beerse, Belgium.

PMID: 30380163
DOI: 10.1002/anie.201810947

Abstract

A new three-component reductive arylation of amides with stable reactants (iPrOH and arylboronate esters), making use of a 2-pyridinyl (Py) directing group, is described. The N-Py-amide substrates are readily prepared from carboxylic acids and PyNH₂ , and the resulting N-Py-1-arylalkanamine reaction products are easily transformed into the corresponding chlorides by substitution of the HN-Py group with HCl. The 1-aryl-1-chloroalkane products allow substitution and cross-coupling reactions. Therefore, a general protocol for the transformation of carboxylic acids into a variety of functionalities is obtained. The Py-NH₂ by-product can be recycled.

Keywords: amides; amines; arylation; multicomponent reactions; ruthenium.

Abstract

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