Studies were undertaken to develop a general and practical room temperature protocol for the Buchwald-Hartwig reaction, whereby any aryl halide might be coupled with any N-H moiety using Pd-NHC (AT-Heterocyclic Carbene) catalysis. Efforts using imidazolium salts, where the Pd-NHC complex is formed in situ, resulted in high- yielding reactions of aryl bromides and secondary cyclic amines within 7 h at room temperature, with yields typically in the range of 78-89%. However, only modest yields were obtained with primary amines, secondary acyclic amines and aryl chlorides. Subsequent research with an isolated (NHC)Pd(R-allyl)Cl complex enabled the efficient high-yielding coupling of a wider range of substrates (including aryl chlorides) in as little as 1 min. The commercially-available base lithium hexamethyldisilazide (LHMDS) was found to be key to the success of both protocols. Additionally, intramolecular Heck reactions of benzyl halides with pendant olefin chains have also been performed to afford several seven-membered rings with the use of a commercial laboratory microwave reactor. It was possible to effect the cyclisation of 2-(A-homoallyltosylamino)benzyl chloride and (2-chloromethylbenzyl)malonic acid diethyl ester in yields of 98% and 95% respectively yield within 20 min at 90°C. 2-Homoallyloxybenzyl chloride also underwent reaction in 33% yield at 140°C.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:498642 |
| Date | January 2008 |
| Creators | Cawley, Mark James |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1445273/ |
Page generated in 0.0017 seconds