Palladium-Catalysed Functionalisation of Csp3–H Bonds Directed by Aliphatic Amines

Abstract

Synthetic transformations on medicinally-relevant aliphatic amines are valuable in the diversification of molecules designed as pharmaceutical agents. This thesis describes two Csp3–H functionalisation reactions, using native amines (secondary and tertiary) to direct C–H activation.

Chapter 2 describes a palladium-catalysed Csp3–H acetoxylation directed by native secondary amines. A range of cyclic amines could be acetoxylated with excellent functional group tolerance to form the desired functionalised products. Kinetic experiments and DFT calculations elucidated the mechanism of the transformation, which features C–O bond formation via an external acetate attack onto the electrophilic C–Pd bond.

Chapter 3 describes a palladium-catalysed Csp3–H alkenylation directed by tertiary aliphatic amines. A diverse set of amines were functionalised using alkenyl boronic ester coupling partners to give the desired olefinated products. The work includes enantioselective functionalisation using a chiral ligand and a preliminary study of stoichiometric aminoalkyl palladium(II) complexes.