CH Bond Arylation of Diamondoids Catalyzed by Palladium(II) Acetate

Abstract

Abstract:We have developed an effective approach to 1,2-disubstituted diamondoids by palladium(II) acetate catalyzed functionalization of C À H 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 C À H 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).

Directed C−H Bond Oxidation of Bridged Cycloalkanes Catalyzed by Palladium(II) Acetate

“…As in our previous study dealing with the C−H bond arylation of the same molecule 1 f , the properties of the directing group were tested (Figure ). The structural arrangement of two five membered rings in the palladacycle intermediate does not play a role and in the same manner it is possible to acetoxylate methylene amine derivatives on the adamantane framework to get the compound 4 in 37 % yield.…”

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…The PM DG was also employed in the Pd-catalysed arylation of diamondoids with aryl iodides (36–87%), a synthetic challenge due to the large number of possible C–H bonds to be functionalised ( Scheme 92C ). 555 …”

Directed C–H Functionalization of the Adamantane Framework

“…Catalytic monoarylation of adamantane derivatives 87 (diamondoids) was achieved using N-picolylamide as a directing group in up to 87% yield (Scheme 36). 54 Directed C-H functionalization was designed to proceed through a five-membered palladacycle C3, which reacts further to give the corresponding aryl derivative (Scheme 37); the existence of complex C4 was not proven. Deuterium-labeling experiments indicated that the palladacycle formation is reversible (acidolysis of the palladacycle is the slowest step in this case) and kinetic studies showed that the arylation step is slower than the C-H activation step.…”