Brønsted acid promoted olefin functionalization (anti-aminohydroxylation) and progress toward (+)-zwittermicin A

Abstract

The vicinal aminoalcohol moiety is a common structural motif in various groups of natural products, pharmaceuticals, ligands for metals, and chiral auxiliaries. A variety of synthetic molecules containing 1,2-aminoalcohols are used as drugs or pharmacological agents. This dissertation describes the application of Brønsted acid promoted azide-olefin [3+2] cycloaddition and triazoline fragmentation using thermal and water catalyzed protocols for the development of diastereoselective olefin functionalization as a route to α-hydroxy-β-amino acid derivatives. Additionally, we have identified the intervening steps in the Brønsted acid-catalyzed conversion of triazoline to oxazolidine dione. Significant rate acceleration is provided by triflic acid to the azide-olefin addition step, leading to an intermediate triazoline under anhydrous conditions that has been characterized by in situ IR spectroscopy. Additionally, we have further characterized the effect of water on the triazolinium stability in which it works in concert with triflic acid at low temperature to promote triazoline fragmentation in a nonhydrolytic step. The final part of the dissertation outlines the application of this Brønsted acid-catalyzed anti aminohydroxylation to the natural product (+)-zwittermicin A. We have studied the diastereoselection of intramolecular and intermolecular azide-olefin cycloaddition. Additionally, we have initiated bidirectional synthesis approach to the construction of the zwittermicin backbone.