| The alpha-functionalization of amines is a synthetic challenge of much interest to organic chemists. Common methods involve deprotonation with strong bases or oxidation with stoichiometric oxidants or transition metal catalysts. An alternative redox-neutral azomethine ylide-mediated approach to amine functionalization that harnesses the intrinsic reactivity of simple aldehyde and amine precursors without the need for harsh oxidants or bases will be detailed in this dissertation. The development of non-pericyclic amine annulations yielding aminal, N,O-acetal and N,S-thioacetal products will be discussed along with joint computational and experimental mechanistic studies on these reactions. The aminals are closely related to several naturally-occurring alkaloids and multiple methods were developed to synthesize these bioactive natural products and analogs. Additionally, two more azomethine ylide-based reactions will be discussed. The first is a variant on the classical Strecker reaction using alpha-amino acids which decarboxylatively gives rise to cyclic alpha-amino nitriles. Finally, a redox-neutral 1,5-electrocyclization reaction between secondary amines and alpha,beta-unsaturated carbonyl compounds yielding amine heterocycles will be demonstrated. |
