Lawrence Berkeley National Laboratory
Palladium-Catalyzed α-Arylation of Carboxylic Acids and Secondary Amides via a Traceless Protecting Strategy.
- Author(s): He, Zhi-Tao
- Hartwig, John F
- et al.
Published Web Locationhttps://doi.org/10.1021/jacs.9b03291
A novel traceless protecting strategy is presented for the long-standing challenge of conducting the palladium-catalyzed α-arylation of carboxylic aids and secondary amides with aryl halides. Both of the presented coupling processes occur with a variety of carboxylic acids and amides and with a variety of aryl bromides containing a broad range of functional groups, including base-sensitive functionality like acyl, alkoxycarbonyl, nitro, cyano, and even hydroxyl groups. Five commercial drugs were prepared through this method in one step in 81-96% yield. Gram-scale synthesis of medication Naproxen and Flurbiprofen with low palladium loading further highlights the practical value of this method.