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.