Fast and easy copper-free Sonogashira couplings: The much overlooked solvent and base dependence

ORGN 638

Thomas G. Ljungdahl, thoma@chembio.chalmers.se and Jerker Mårtensson, jerker@chembio.chalmers.se. Department of Chemistry and Bioscience, Chalmers University of Technology, Kemivägen 10, 412 96 Göteborg, Sweden
In this presentation a new approach to the optimization of the Heck alkynylation, also known as the copper-free Sonogashira reaction, is presented. Instead of focusing on the ligand the choice of solvent and base is scrutinized. The catalyst precursor is throughout the investigation the air-stable Pd2(dba)3•CHCl3 and the ligands are either triphenylarsine or triphenylphosphine, both cheap, easy-to-handle, air stable ligands. The most successful modification has proven to be the addition of methanol as a co-solvent together with the use of a moderately to highly nucleophilic tertiary base, i.e. triethylamine or a less sterically hindered tertiary base. The success of the methanol additive is hypothesized to be caused by the presence of a rate determining deprotonation step featuring a charge separated transition state. A model study is included to substantiate the effectiveness and generality of the new reaction conditions in copper-free Sonogashira.
 

Metal-Mediated Reactions and Syntheses
8:00 AM-12:00 PM, Wednesday, 16 March 2005 Convention Center -- Room 10, Oral

Division of Organic Chemistry

The 229th ACS National Meeting, in San Diego, CA, March 13-17, 2005