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.

本研究对区域及立体专一性吖丙啶（aziridine）开环反应开展了系统探究，为构建各类β-取代-α-氨基季碳官能团提供了全新合成技术。该反应采用温和无金属的反应条件，可适用于高官能团化的反应体系。此反应还被用于极具挑战性的叔烷基芳基醚立体选择性构建。本研究通过使用多种官能团化吖丙啶与酚类底物，对该类位阻型醚的合成策略进行了探究，以明确该反应的适用范围。此外，本研究还考察了硫醇盐、叠氮根及氯离子等其他亲核试剂，以覆盖更广泛的官能团合成需求。该吖丙啶开环反应策略已被证实可用于构建以下产物：β-取代-α-氨基羧酰胺、β-取代-α-氨基酯、β-取代-α-氨基硅醚、β-硫代-α-氨基羧酰胺、β-叠氮基-α-氨基羧酰胺以及β-卤代-α-氨基羧酰胺。针对吖丙啶取代模式影响的研究表明，烷基取代吖丙啶与炔基取代吖丙啶具有相近的反应活性，这为反应机理的探索提供了重要思路。