Desymmetrization of an Allylic Azide via Tandem Rearrangement/Friedel-Crafts Alkylation

Abstract

Allylic azides present a variety of potential opportunities in organic synthesis, particularly as a starting point for the preparation of α,α-disubstituted chiral amines, a key functional group that appears in amino acids and many pharmaceutically relevant compounds. However, their utility has been limited by an incomplete understanding of the Winstein rearrangement, the process by which an allylic azide equilibrates between a pair of regioisomers. A recent publication by members of the Topczewski group1 demonstrated that allylic azides can be cyclized by Friedel-Crafts alkylation with high diasterioselectivity despite this rearrangement. This project seeks to extend the tandem rearrangement/Friedel-Crafts alkylation and achieve enantioselectivity by performing a dynamic kinetic resolution (DKR) through the use of a chiral Brønsted acid catalyst.