Directed Organocatalytic Intermolecular Cope-type Hydroamination of Alkenes

Abstract

Intermolecular reactions are inherently more difficult than intramolecular reactions, and several transformations can only occur as cyclizations, often to form 5-membered rings. The use of directing or tethering groups allowing preassociation with a reagent or catalyst is a common strategy to overcome such low reactivity, which can lead to increases in the rate, regioselectivity and stereoselectivity of intermolecular reactions. Typically, such preassociation involves hydrogen bonds, coordination to a metal ion/catalyst or stepwise installation of a temporary tether. As part of ongoing investigations on metal-free hydroaminations, it was speculated that a simple organic molecule could allow the formation of a temporary tether and enable directed intermolecular Cope-type hydroaminations to proceed at room temperature. Recently, it was found that alkylhydroxylamines add to allylic amines regioselectively in the presence of an aldehyde catalyst. This thesis presents the background material, design elements, optimization and scope of this reactivity.