We acknowledge Novartis International AG for funding. The Bruker NMR spectrometers used in this work were supported by grants from the National Science Foundation (CHE-9808061 and DBI-9729592) and the National Institutes of Health (1S10RR13886-01). We thank Dr. Nathan T. Jui for helpful discussions and Dr. Christine Nguyen for experimental assistance. MIT has patents on some of the ligands and precatalysts used in this work as well as metal-catalyzed cross-coupling reactions with hydrazine from which S.L.B. receives royalty payments.
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Communication
Mild and Rapid Pd-Catalyzed Cross-Coupling with Hydrazine in Continuous Flow: Application to the Synthesis of Functionalized Heterocycles†
Article first published online: 13 FEB 2013
DOI: 10.1002/anie.201208544
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
DeAngelis, A., Wang, D.-H. and Buchwald, S. L. (2013), Mild and Rapid Pd-Catalyzed Cross-Coupling with Hydrazine in Continuous Flow: Application to the Synthesis of Functionalized Heterocycles . Angew. Chem. Int. Ed., 52: 3434–3437. doi: 10.1002/anie.201208544
- †
Publication History
- Issue published online: 13 MAR 2013
- Article first published online: 13 FEB 2013
- Manuscript Received: 23 OCT 2012
Funded by
- Novartis International AG
- National Science Foundation. Grant Numbers: CHE-9808061, DBI-9729592
- National Institutes of Health. Grant Number: 1S10RR13886-01
Keywords:
- continuous flow;
- cross-coupling;
- hydrazine;
- palladium;
- transition-metal catalysis
Minimizing risk: The synthesis of arylhydrazines through C![[BOND]](http://onlinelibrarystatic.wiley.com/undisplayable_characters/00f8ff.gif)
N cross-coupling of aryl chlorides with hydrazine is described. Through the use of continuous flow, the hazards associated with the use of hydrazine in the presence of transition metals are decreased. In addition, multistep flow sequences have also been developed for the generation of functionalized heterocycles utilizing the arylhydrazine intermediates.