Development of an efficient acid-free palladium(II) catalyzed hydroarylation of acetylene

Title : Development of an efficient acid-free palladium(II) catalyzed hydroarylation of acetylene

Abstract:

Hydroarylation of alkynes is a useful organic reaction to generate aryl alkenes as building blocks for more complex molecules. The direct addition of arenes to alkynes may serve as an efficient methodology to shorten the lengthy multi-step synthesis of natural products or drug molecules. While intramolecular hydroarylation is relatively easy to realize, the intermolecular version is far more challenging regarding chemo-, regio-, or stereoselectivity. In the last two decades a large number of catalytic systems containing transition and main group metals have been developing, which still display certain limitations including high catalyst load, a large amount of acid co-catalyst, higher temperature, relatively long reaction time, and a narrow scope of substrates. We have studied the hydroarylation reaction using dicationic Pt^II and Pd^II pincer complexes. Initially, stoichiometric reactions were performed to elucidate the Friedel-Crafts type mechanism. Screening a series of Pt^II and Pd^II complexes, a dicationic Pd^II complex containing SbF₆^– counter-anion was found to be the most active catalyst. Further optimization of various reaction parameters afforded a TON of 200 and completion of the hydroarylation test reaction at room temperature within 24 h in the absence of any acid co-catalyst. The rule of water as a co-catalyst will be discussed. Overall, a methodology for direct C-H addition of an arene to acetylene as  unfunctionalized alkyne substrate was developed working efficiently under mild reaction conditions and acid-free conditions

Audience Take Away :

• The catalytic system may help to shorten the multi-step synthesis of drug molecules by several steps.
• The discussed catalytic hydroarylation reaction is a showcase how a catalytic system has been developed iteratively by optimization of various reaction parameters and attention to unforeseen impact of certain reaction conditions such as the amount of water in the system.

Biography:

Dr. Christine Hahn received her Master's (1993) and Ph.D. (1997) degrees from the Martin-Luther University Halle-Wittenberg (Germany). She spent one year as Research Assistant at the University of Würzburg with Professor H. Werner, she won a fellowship from the German Academy of Sciences Leopoldina for research at the University of Naples. She returned to Germany and joined the group of Professor J. A. Gladysz at the University of Erlangen-Nuremberg. She is currently an Associate Professor and Chair of the Department of Chemistry at the Texas A&M University-Kingsville. Her research interests are in the fields of organometallic and homogeneous catalysis.