Enantioselective Synthesis Using Azides: Mechanism And Methods

Abstract

With the increasing demand of complex sp3-hybridized molecules and the importance of sustainability and environmental impact, it is imperative for chemists to develop creative and efficient synthetic methods to synthesize these molecules. As a molecular subclass, chiral-α,α-disubstituted amines are particularly challenging to access via traditional methods. Our approach has focused on developing dynamic kinetic resolutions (DKR) to access chiral amines from azides. DKR is a fundamentally interesting strategy because racemic starting materials can be converted into enantioenriched products in high yield and stereoselectivity. This work describes the initial discovery of a dynamic kinetic resolution of allylic azides (Chapter 2), followed by subsequent fundamental mechanistic investigations (Chapter 3). Insights from these fundamental studies led in exploration of catalysts to promote racemization of activated azides (Chapter 4). This racemization was used to recycle the excess scalemic starting material in a kinetic resolution of cyclic secondary azides (Chapter 5). Finally, efforts to utilize the catalyst-promoted racemization in a dynamic kinetic resolution are discussed (Chapter 6).