Development of new concepts for the C-H functionalization of cyclic amines

The functionalization of non-activated C–H bond of cyclic amines is of great importance due to the ubiquity of complex molecular structures containing functionalized cyclic amine moieties. Most previously developed methods for this purpose involve the use of deprotonating bases, external oxidants and/or metal catalysts. An alternative pathway for the C–H functionalization of cyclic amines via the intermediacy of azomethine ylides will be discussed in this dissertation. Transformations developed combine a reductive N-alkylation with an oxidative C–H functionalization, thus enabling the functionalization of cyclic amines in a redox-neutral fashion. Specific research projects outlined include α-cyanation, α-arylation, the redox-Mannich reaction, α,β-difunctionalization and the redox-annulation involving β-ketoaldehydes. Functionalized amine products are obtained from readily available starting materials in the presence of simple carboxylic acid, and in some cases, no additive is required. The majority of established methods for the C–H functionalization of cyclic amines require pre-functionalization on the amine nitrogen, thus extra steps for the removal of directing/protecting group are often needed in order to obtain N-H amines. To avoid this limitation, an α-functionalization of cyclic N-H amines via intermolecular hydride transfer is developed and will also be discussed in this dissertation. Aryllithium reagents are used as nucleophiles for most reactions of this type demonstrated in this dissertation, and a few examples involving trans-styryllithium and alkyllithium reagents are also shown.Ph.D.Includes bibliographical referencesby Weijie Che