The Suzuki–Miyaura Cross-Coupling Reaction of Halogenated Aminopyrazoles: Method Development, Scope, and Mechanism of Dehalogenation Side Reaction
† Institute of Molecular and Translation Medicine, Faculty of Medicine, Palacký University, Hněvotínská 5, 77900 Olomouc, Czech Republic
‡ Department of Organic Chemistry, Faculty of Science, Palacký University, 17. listopadu 1192/12, 77146 Olomouc, Czech Republic
J. Org. Chem., Article ASAP
DOI: 10.1021/acs.joc.6b02306
Publication Date (Web): December 8, 2016
Copyright © 2016 American Chemical Society
*E-mail: petr.cankar@upol.cz.
Abstract
The efficient Suzuki–Miyaura cross-coupling reaction of halogenated aminopyrazoles and their amides or ureas with a range of aryl, heteroaryl, and styryl boronic acids or esters has been developed.
The method allowed incorporation of problematic substrates: aminopyrazoles bearing protected or unprotected pyrazole NH,
as well as the free amino or N-amide group.
Direct comparison of the chloro, bromo, and iodopyrazoles in the Suzuki–Miyaura reaction revealed that Br and Cl derivatives were superior to iodopyrazoles, as a result of reduced propensity to dehalogenation.
Moreover, the mechanism and factors affecting the undesired dehalogenation side reaction were revealed.
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.6b02306.
- Copies of 1H and 13C NMR spectra, representative HPLC chromatograms for the optimization and dehalogenation experiments (PDF)
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