A Regio- and Stereoselective Approach to Quaternary Centers from Chiral Trisubstituted Aziridines

A thorough investigation of a regio- and stereospecific aziridine ring opening reaction presents new synthetic technology for the construction of a variety of quaternary β-substituted-α-amino functional groups. Mild, metal-free reaction conditions allow for application in highly functionalized systems. This reaction has been applied to the challenging stereoselective formation of tertiary alkyl-aryl ethers. The strategy for the formation of these hindered ethers has been investigated using a variety of functionalized aziridines and phenols to determine the scope of the reaction. Other nucleophiles, such as thiolate, azide, and chloride, have also been examined to encompass the synthesis of a broader range of functionalities. This aziridine ring opening reaction manifold has demonstrated utility in assembling: β-substituted-α-amino carboxamides, β-substituted-α-amino esters, β-substituted-α-amino silyl ethers, β-thio-α-amino carboxamides, β-azido-α-amino carboxamides, and β-halo-α-amino carboxamides. Studies to probe the effect of the aziridine substitution patterns show that alkyl aziridines display similar reactivity to alkynyl aziridines, giving insight into mechanistic possibilities.