Allylic Azides: Versatile Building Blocks to Heterocycles

Abstract

Organic azides are versatile building blocks because they can be derivatized to a variety of functionalities. Allylic azides, as a subclass of organic azides, are viewed as a problematic precursor in organic synthesis because of the spontaneous rearrangement. The Topczewski lab has focused on the reactivity of allylic azides. This graduate work describes the unique reactivity of allylic azides to access enantioenriched heterocycles or densely functionalized heterocycles. Enantioselective copper-catalyzed alkyne-azide cycloaddition (E-CuAAC) by dynamic kinetic resolution (DKR) opens gates to α-N-chiral triazoles with high yields and enantioselectivity (Chapter 2). The spontaneous rearrangement of allylic azides was utilized as a racemization method. The newly developed chiral ligand in the E-CuAAC reaction can be further applied to non-allylic azides (Chapter 3). Enantioenriched benzylic triazoles can be accessed by kinetic resolution (KR). Enantioselective nickel-catalyzed alkyne-azide cycloaddition (E-NiAAC) was explored (Chapter 4). The E-NiAAC reaction gives the complementary 1,4,5-trisubstituted triazoles, which are not accessible via CuAAC reaction. Finally, densely functionalized tetrahydro-pyrrolo-pyrazoles can be prepared via a cascade reaction of cinnamyl azides (Chapter 5).