Palladium(II)-Catalyzed C(sp3)–H Activation of N,O-Ketals towards a Method for the β-Functionalization of Ketones

Abstract

A method for the formal β-functionalization of aliphatic ketones via a palladium-catalyzed sp3 C–H activation pathway is reported. An N,O-ketal directs an aliphatic C–H carbonylation to form γ-lactams which upon hydrolysis generate γ-keto carboxylic acids. This C–C bond-forming reaction is tolerant of a range of functional groups, enabling the synthesis of a range of synthetically important building blocks. Furthermore, the concepts underlying this transformation have also enabled the development of a related C–H alkenylation process to highly functionalised heterocycles.

Construction of aziridine, azetidine, indole and quinoline-like heterocycles via Pd-mediated C–H activation/annulation strategies

“…These useful bicyclic rings could also be converted onto β-functionalized ketones after hydrolysis. 56 As described in Scheme 32, ketal 130a was successfully converted to the tricyclic pyrrolidinone 131a in good yield and further hydrolysed to give the keto carboxylic acid 132a in excellent 93% yield.…”