Sustainable ppm level palladium-catalyzed aminations in nanoreactors under mild, aqueous conditions

Yitao Zhang; Balaram S Takale; Fabrice Gallou; John Reilly; Bruce H Lipshutz

doi:10.1039/c9sc03710a

Sustainable ppm level palladium-catalyzed aminations in nanoreactors under mild, aqueous conditions

Chem Sci. 2019 Sep 20;10(45):10556-10561. doi: 10.1039/c9sc03710a. eCollection 2019 Dec 7.

Authors

Yitao Zhang¹, Balaram S Takale¹, Fabrice Gallou², John Reilly³, Bruce H Lipshutz¹

Affiliations

¹ Department of Chemistry and Biochemistry , University of California Santa Barbara , Santa Barbara , CA 93106 , USA . Email: lipshutz@chem.ucsb.edu.
² Novartis Pharma AG , Basel , Switzerland.
³ Novartis Institutes for BioMedical Research (NIBR) , Cambridge , MA , USA.

Abstract

A 1 : 1 Pd : ligand complex, [t-BuXPhos(Pd-π-cinnamyl)]OTf, has been identified as a highly robust pre-catalyst for amination reactions leading to diarylamines, where loadings of metal are typically at 1000 ppm Pd, run in water at temperatures between rt and 45 °C. The protocol is exceptionally simple, is readily scaled, and compares very favorably vs. traditional amination conditions. It has also been shown to successfully lead to key intermediates associated with several physiologically active compounds.