The Diastereoselective Synthesis of 1,3-Diamines and Amino Alcohols via 2-Azaallyl Anion Ring-Opening of Aziridines and Epoxides

Abstract

Nitrogen-substituted stereogenic centers are ubiquitous throughout naturally occurring, synthetically useful, and biologically active molecules. Among these, the 1,3-diamine and 1,3-amino alcohol scaffolds are important and commonly occurring motifs. Despite the frequent occurrence of these moieties in complex molecules, few methods exist that allow for their direct, stereoselective, and redox-efficient synthesis. Herein, we report the stereoselective synthesis of over sixty-five 1,3-diamines and amino alcohols via 2-azaallyl anion nucleophilic ring-opening of aziridines (Chapter 1) and epoxides (Chapter 2). Transformations occur stereospecifically (>98%), diastereoselectively (up to >20:1 d.r.), site-selectively (up to >98%), and efficiently (up to >98% yield) to generate 1,3-diamines and amino alcohols bearing 2–3 stereogenic centers in a redox-efficient manner. The products generated readily undergo a variety of synthetic manipulations, including imine hydrolysis and heterocycle synthesis.