Highly Selective Continuous-Flow Synthesis of Potentially Bioactive Deuterated Chalcone Derivatives

Abstract

The selective synthesis of various dideuterochalcones as potentially bioactive deuterium-labeled products is presented, by means of the highly controlled partial deuteration of antidiabetic chalcone derivatives. The benefits of continuous-flow processing in combination with on-demand electrolytic D₂ gas generation has been exploited to avoid over-reaction to undesired side products and to achieve selective deuterium addition to the carbon-carbon double bond of the starting enones without the need for unconventional catalysts or expensive special reagents. The roles of pressure, temperature, and residence time proved crucial for the fine-tuning of the sensitive balance between the product selectivity and the reaction rate. The presented flow-chemistry-based deuteration technique lacks most of the drawbacks of the classical batch methods, and is convenient, time- and cost-efficient, and safe.

Keywords: chalcones; chemoselectivity; continuous-flow processing; deuteration; heterogeneous catalysis.