title: Dynamic kinetic resolution via dual-function catalysis of modified cinchona alkaloids: asymmetric synthesis of alpha-hydroxy carboxylic acids.
abstract: A highly enantioselective catalytic transformation of racemic alpha-hydroxy acids to optically active alpha-hydroxy acids is reported. A new procedure was developed for the condensation of racemic alpha-hydroxy acids with trichloromethyl chloroformate (diphosgene) at room temperature in the presence of activated charcoal to form 5-substituted-1,3-dioxolane-2,4-diones in 90-100% yield. An efficient dynamic kinetic resolution of 5-aryl dioxolanediones was realized via a modified cinchona alkaloid-catalyzed alcoholytic opening of the dioxolanedione ring, generating a variety of optically active alpha-hydroxy esters in 91-96% ee and 61-85% chemical yield. In this dynamic kinetic resolution, the modified cinchona alkaloid was found to serve dual catalytic roles, mediating both the rapid racemization of the 5-aryl dioxolanediones and the enantioselective alcoholytic ring opening of the 5-aryl dioxolanediones. Consequently, both enantiomers of the 5-aryl dioxolanediones were converted to highly enantiomerically enriched aromatic alpha-hydroxy esters in yields (61-85%), far exceeding the maximum of 50% for a normal kinetic resolution. This development not only represents an expansion of the scope of asymmetric acyl-transfer catalysis of synthetic catalysts but also provides a new approach for the development of efficient chemical dynamic kinetic resolutions promoted by a single catalyst. 5-Alkyl dioxolanediones were resolved by a conventional but highly enantioselective kinetic resolution to provide alpha-hydroxy acids and esters in high optical purity and good yields.
authors.affiliation: Department of Chemistry, Brandeis University, Waltham, MA 02454-9110, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Deng
mesh_terms: D002264:Carboxylic Acids / Q000138:chemical synthesis*; D002384:Catalysis; D002930:Cinchona Alkaloids / Q000737:chemistry*; D004148:Dioxolanes / Q000138:chemical synthesis*; D007700:Kinetics
chemical_list: D002264:Carboxylic Acids; D002930:Cinchona Alkaloids; D004148:Dioxolanes