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 PtII and PdII pincer complexes. Initially, stoichiometric reactions were performed to elucidate the Friedel-Crafts type mechanism. Screening a series of PtII and PdII complexes, a dicationic PdII 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.