Non-redox Lewis Acids Supported Pd-Catalyzed C-C /C-H Activation and Accession to Produce Pharmaceutical Intermediates.

Palladium is a simple and versatile redox-active metal that plays a crucial role in the oxidation reactions for organic synthesis and production of pharmaceutical intermediates. Notably, there has been significant progress with Lewis acids (LAs), which are non-redox metal ions promoting Pd(II)-catalyzed oxidation via C-H and C-C bond activation. A new catalytic species is formed through the strong interaction between a Lewis acid and palladium as dimer catalyst. This active complex in this system, which is a Lewis acid promoter, facilitates a Wacker-type oxidation reaction via the activation of C-H and/or C-C bonds. This system of dimer catalysis is based on the key active species for oxidation reactions in pharmaceutical production. The Pd(II)/LA-catalytic oxidation of olefins and N-heteroaromatic alkylation we developed offers a robust method for generating intermediate compounds for drug discovery. This study demonstrates that non-redox Lewis acid-promoted Pd catalysis is highly effective in synthesizing chemically diverse compounds featuring hydrogen-bonding acceptors and donors (HBA/HBD). These functional groups are crucial for interactions with biological targets, making the resulting molecules strong candidates for development as active pharmaceutical ingredients. Their potential applications span pharmaceutical sciences, medicinal delivery systems, and cosmetic formulations.