ORGN 560 |
| Present in many pharmaceuticals and other biologically active molecules, carbon-nitrogen bonds form important building blocks in organic synthesis. The Pd-catalyzed amination of aryl/heteroaryl halides has become an efficient and useful process for the preparation of various functionalized anilines. Recent efforts in this area have focused on the development of more stable and active catalytic systems that operate at lower catalyst loadings, shorter reaction times and allow the coupling of challenging substrate combinations. Unprecedented in literature, aminoheterocycles are successfully arylated using a catalyst system based on Pd and the bulky, electron-rich monophosphine ligands 1 or 2. Previously, only catalyst systems based on bidentate phosphines (Pd/XantPhos or BINAP) were successful in coupling this class of substrates. We also demonstrate that through the use of Pd/1-2, we can achieve excellent chemoselectivity in the coupling of amines (anilines, primary and secondary amines) and aryl/heteroaryl halides containing amides and indole functional groups. We also demonstrate that lower reaction times can be achieved though the use of microwave irradiation and amine bases (MTBD), indicating our catalyst retains its activity at higher temperatures and is very stable under these forcing conditions. We have also developed a water-soluble ligand based on 1, which allows the coupling of water-soluble aryl halides and aryl amines in water for the first time.
|
|
Heterocycles, Aromatics, Metal-Mediated Reactions and Syntheses, Materials, Devices, and Switches
8:00 PM-10:00 PM, Wednesday, 29 March 2006 Georgia World Congress Center -- Ex. Hall B4, Poster
Division of Organic Chemistry |
