The Suzuki-Miyaura Cross-Coupling Reaction of Halogenated Aminopyrazoles: Method Development, Scope, and Mechanism of Dehalogenation Side Reaction

J Org Chem. 2017 Jan 6;82(1):157-169. doi: 10.1021/acs.joc.6b02306. Epub 2016 Dec 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't