|
|||||
|
|
Palladium-Catalyzed Benzylic C(sp3)−H Carbonylative Arylation with Aryl Bromides |
|
| Authors: | Dr Bowen Hu Dr Haoqiang Zhao Yu Wu Prof Patrick J Walsh |
| Institution: | 1. Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, Department of Chemistry, University of Pennsylvania, 231 S. 34 Street, Philadelphia, PA, 19104 USA
These authors contributed equally to this work.;2. Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, Department of Chemistry, University of Pennsylvania, 231 S. 34 Street, Philadelphia, PA, 19104 USA School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029 China These authors contributed equally to this work.;3. Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, Department of Chemistry, University of Pennsylvania, 231 S. 34 Street, Philadelphia, PA, 19104 USA |
| Abstract: | A novel, selective and high-yielding palladium-catalyzed carbonylative arylation of a variety of weakly acidic (pKa 25–35 in DMSO) benzylic and heterobenzylic C(sp3)−H bonds with aryl bromides has been achieved. This system is applicable to a range of pro-nucleophiles for access to sterically and electronically diverse α-aryl or α,α-diaryl ketones, which are ubiquitous substructures in biologically active compounds. The Josiphos SL-J001-1-based palladium catalyst was identified as the most efficient and selective, enabling carbonylative arylation with aryl bromides under 1 atm CO to provide the ketone products without the formation of direct coupling byproducts. Additionally, (Josiphos)Pd(CO)2 was identified as the catalyst resting state. A kinetic study suggests that the oxidative addition of aryl bromides is the turnover-limiting step. Key catalytic intermediates were also isolated. |
| Keywords: | Carbonylation Deprotonation C−H Functionalization Josiphos Palladium |