Regio- and stereoselective synthesis of quaternary centers from chiral trisubstituted aziridines and its application toward the total synthesis of ceanothine D

Most nucleophilic aziridine ring opening reactions suffer from poor regio- and stereoselectivity. A thorough investigation of a regio- and stereospecific aziridine ring opening reaction presents new synthetic technology for the construction of a variety of quaternary beta-substituted-alpha-amino functional groups. Mild, metal-free reaction conditions allow for application in highly functionalized systems; and the reaction has been applied to the difficult stereoselective formation of tertiary alkyl-aryl ethers, beta-substituted-alpha-amino carboxamides, beta-substituted-alpha-amino esters, beta-substituted-alpha-amino silyl ethers, beta-thio-alpha-amino carboxamides, beta-azido-alpha-amino carboxamides, and beta-halo-alpha-amino carboxamides. Studies to probe the effect of both the nucleophile and the aziridine substitution patterns show that alkyl aziridines display similar reactivity to alkynyl aziridines, giving insight into mechanistic possibilities. The reaction has been applied toward the synthesis of the cyclopeptide alkaloid ceanothine D to allow construction of its unique alkyl-aryl ether functionality.