Mechanistic investigations into the asymmetric transfer hydrogenation of ketones catalyzed by pseudo-dipeptide ruthenium complexes.
The combination of N-Boc-protected alpha-amino acid hydroxyamides (pseudo-dipeptides) and [{Ru(p-cymene)Cl(2)}(2)] resulted in the formation of superior catalysts for the asymmetric transfer hydrogenation (ATH) of non-activated aryl alkyl ketones in propan-2-ol. The overall kinetics of the ATH of acetophenone to form 1-phenylethanol in the presence of ruthenium pseudo-dipeptide catalysts were studied, and the individual rate constants for the processes were determined. Addition of lithium chloride to the reaction mixtures had a strong influence on the rates and selectivities of the processes. Kinetic isotope effects (KIEs) for the reduction were determined and the results clearly show that the hydride transfer is rate-determining, whereas no KIEs were detected for the proton transfer. From these observations a novel bimetallic outer-sphere-type mechanism for these ATH process is proposed, in which the bifunctional catalysts mediate the transfer of a hydride and an alkali metal ion between the hydrogen donor and the substrate. Furthermore, the use of a mixture of propan-2-ol and THF (1:1) proved to enhance the rates of the ATH reactions. A series of aryl alkyl ketones were reduced under these conditions in the presence of 0.5 mol % of catalyst, and the corresponding secondary alcohols were formed in high yields and with excellent enantioselectivities (>99% ee) in short reaction times.
Wettergren
Jenny
J
Dept. of Organic Chemistry, Stockholm University, The Arrhenius Laboratory, 10691 Stockholm, Sweden.
Buitrago
Elina
E
Ryberg
Per
P
Adolfsson
Hans
H
D000098:Acetophenones / Q000737:chemistry; D000438:Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D002384:Catalysis; D004151:Dipeptides / Q000737:chemistry*; D006865:Hydrogenation; D007659:Ketones / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D009942:Organometallic Compounds / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*
D000098:Acetophenones; D000438:Alcohols; D000596:Amino Acids; D004151:Dipeptides; D007659:Ketones; D009942:Organometallic Compounds; D012428:Ruthenium; D012238:Rhodium