title: Highly enantioselective organocatalytic oxidative kinetic resolution of secondary alcohols using chiral alkoxyamines as precatalysts: catalyst structure, active species, and substrate scope.
abstract: The development and characterization of enantioselective organocatalytic oxidative kinetic resolution (OKR) of racemic secondary alcohols using chiral alkoxyamines as precatalysts are described. A number of chiral alkoxyamines have been synthesized, and their structure-enantioselectivity correlation study in OKR has led us to identify a promising precatalyst, namely, 7-benzyl-3-n-butyl-4-oxa-5-azahomoadamantane, which affords various chiral aliphatic secondary alcohols (ee up to >99%, k(rel) up to 296). In a mechanistic study, chlorine-containing oxoammonium species were identified as the active species generated in situ from the alkoxyamine precatalyst, and it was revealed that the chlorine atom is crucial for high reactivity and enantioselectivity. The present OKR is the first successful example applicable to various unactivated aliphatic secondary alcohols, including heterocyclic alcohols with high enantioselectivity, the synthetic application of which is demonstrated by the synthesis of a bioactive compound.
authors.affiliation: Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences and ‡Research and Analytical Center for Giant Molecules, Graduate School of Science, Tohoku University , 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Murakami
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sasano
authors.forename: Masaki
authors.initials: M
authors.lastname: Tomizawa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Shibuya
authors.forename: Eunsang
authors.initials: E
authors.lastname: Kwon
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Iwabuchi
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000737:chemistry; D000438:Alcohols / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D003497:Cyclic N-Oxides / Q000737:chemistry; D007700:Kinetics; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: C522607:2-azaadamantane N-oxyl; D000438:Alcohols; D000588:Amines; D003497:Cyclic N-Oxides; C059688:alkoxyl radical; D000218:Adamantane