CH Bond Arylation of Diamondoids Catalyzed by Palladium(II) Acetate

We have developed an effective approach to 1,2-disubstituted diamondoids by palladium(II) acetate catalyzed functionalization of CH bond. Selective mono-arylation of the adamantane framework was achieved using picolylamide as a directing group in yields up to 87%. Kinetic studies in combination with deuterium labeling experiments, competitive experiments and mass spectrometry contribute to the mechanistic understanding of the arylation process of alkanes with number of CH bonds neighboring the directing group. Triflic anhydride promoted cyclization of the directing group generates imidazo[1,5-a]pyridine derivatives. Acid-mediated removal of the directing group provides access to 2-aryl diamondoid carboxylic acids, which are common precursors for the synthesis of various bioactive compounds (drug candidates).