Combined Ruthenium(II) and Lipase Catalysis for Efficient Dynamic Kinetic Resolution of Secondary Alcohols. Insight into the Racemization Mechanism

Pentaphenylcyclopentadienyl ruthenium complexes (3) are excellent catalysts for the racemization
of secondary alcohols at ambient temperature. The combination of this process with enzymatic resolution
of the alcohols results in a highly efficient synthesis of enantiomerically pure acetates at room temperature
with short reaction times for most substrates. This new reaction was applied to a wide range of functionalized
alcohols including heteroaromatic alcohols, and for many of the latter, enantiopure acetates were efficiently
prepared for the first time via dynamic kinetic resolution (DKR). Different substituted cyclopentadienyl
ruthenium complexes were prepared and studied as catalysts for racemization of alcohols. Pentaaryl-substituted cyclopentadienyl complexes were found to be highly efficient catalysts for the racemization.
Substitution of one of the aryl groups by an alkyl group considerably slows down the racemization process.
A study of the racemization of (S)-1-phenylethanol catalyzed by ruthenium hydride η5-Ph5CpRu(CO)2H (8)
indicates that the racemization takes place within the coordination sphere of the ruthenium catalyst. This
conclusion was supported by the lack of ketone exchange in the racemization of (S)-1-phenylethanol
performed in the presence of p-tolyl methyl ketone (1 equiv), which gave <1% of 1-(p-tolyl)ethanol. The
structures of ruthenium chloride and iodide complexes 3a and 3c and of ruthenium hydride complex 8
were confirmed by X-ray analysis.