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 beta-substituted-alpha-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: 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 the aziridine substitution patterns show that alkyl aziridines display similar reactivity to alkynyl aziridines, giving insight into mechanistic possibilities.
Forbeck
Erin M
EM
Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104, USA.
Evans
Cory D
CD
Gilleran
John A
JA
Li
Pixu
P
Joullié
Madeleine M
MM
D000473:Alkanes / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry; D000577:Amides / Q000138:chemical synthesis*; D000588:Amines / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D001388:Aziridines / Q000737:chemistry*; D004987:Ethers / Q000138:chemical synthesis*; D006846:Hydrocarbons, Halogenated / Q000737:chemistry; D008956:Models, Chemical; D012821:Silanes / Q000737:chemistry; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry
D000473:Alkanes; D000480:Alkynes; D000577:Amides; D000588:Amines; D001386:Azides; D001388:Aziridines; D004987:Ethers; D006846:Hydrocarbons, Halogenated; D012821:Silanes; D013438:Sulfhydryl Compounds