The palladium-catalyzed aerobic kinetic resolution of secondary alcohols: reaction development, scope, and applications.
The first palladium-catalyzed enantioselective oxidation of secondary alcohols has been developed, utilizing the readily available diamine (-)-sparteine as a chiral ligand and molecular oxygen as the stoichiometric oxidant. Mechanistic insights regarding the role of the base and hydrogen-bond donors have resulted in several improvements to the original system. Namely, addition of cesium carbonate and tert-butyl alcohol greatly enhances reaction rates, promoting rapid resolutions. The use of chloroform as solvent allows the use of ambient air as the terminal oxidant at 23 degrees C, resulting in enhanced catalyst selectivity. These improved reaction conditions have permitted the successful kinetic resolution of benzylic, allylic, and cyclopropyl secondary alcohols to high enantiomeric excess with good-to-excellent selectivity factors. This catalyst system has also been applied to the desymmetrization of meso-diols, providing high yields of enantioenriched hydroxyketones.
Ebner
David C
DC
The Arnold and Mabel Beckman Laboratories of Chemical Synthesis, Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd., MC 164-30, Pasadena, CA 91125, USA.
Bagdanoff
Jeffrey T
JT
Ferreira
Eric M
EM
McFadden
Ryan M
RM
Caspi
Daniel D
DD
Trend
Raissa M
RM
Stoltz
Brian M
BM
D002384:Catalysis; D006860:Hydrogen Bonding; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism; D020002:tert-Butyl Alcohol / Q000737:chemistry*
D008024:Ligands; D009942:Organometallic Compounds; D010165:Palladium; D020002:tert-Butyl Alcohol