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Updated: Jul 3, 2026

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
Published on: June 23, 2019
Alpha-pyridylation of chiral amines via urea coupling, lithiation and rearrangement
Jonathan Clayden1, Ulrich Hennecke
1School of Chemistry, Univesity of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom. clayden@man.ac.uk
Abstract:
2-, 3- and 4-Bromopyridine, along with other brominated electron-deficient arenes, undergo palladium-catalyzed coupling with ureas of structure RNMeCONHMe. Where R is a chiral, alpha-substituted benzyl group, treatment with LDA leads to a benzylic organolithium which undergoes rearrangement with stereospecific and regiospecific transfer of the pyridyl group, generating a quaternary stereogenic center with high enantioselectivity. Alcoholysis of the urea under neutral conditions reveals the pyridyl amine.
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