Racemization of secondary alcohols catalyzed by cyclopentadienylruthenium complexes: Evidence for an alkoxide pathway by fast beta-hydride elimination - Readdition

The racemization of sec-alcohols catalyzed by pentaphenylcyclopentadienyl-ruthenium complex 3a has been investigated. The mechanism involves ruthenium-alkoxide intermediates: reaction of tert-butoxide ruthenium complex 4 with a series of sec-alcohols with different electronic properties gave ruthenium complexes bearing a secondary alkoxide as a ligand. The characterization of these alkoxide complexes by NMR spectroscopy together with a study of the reaction using in situ IR spectroscopy is consistent with a mechanism in which the alkoxide substitution step and the beta-hydride elimination step occur without CO dissociation. The alkoxide substitution reaction is proposed to begin with hydrogen bonding of the incoming alcohol to the active ruthenium-alkoxide intermediate. Subsequent alkoxide exchange can occur via two pathways: i) an associative pathway involving a eta(3)-CpRu intermediate; or ii) a dissociative pathway within the solvent cage. Racemization at room temperature of a 1:1 mixture of (S)-l-phenylethanol and (S)-l-phenyl-[D-4]-ethanol gave only rac-1-phenylethanol, and rac-1-phenyl[D-4]-ethanol, providing strong support for a mechanism in which the substrate stays coordinated to the metal center throughout the racemization, and does not leave the coordination sphere. Furthermore, racemization of a sec-alcohol bearing a ketone moiety within the same molecule does not result in any reduction of the original ketone, which rules out a mechanism where the intermediate ketone is trapped within the solvent cage. These results are consistent with a mechanism where eta(3)- Ph5C5-ruthenium intermediates are involved. Competitive racemization on nondeuterated and alpha-deuterated alpha-phenylethanols was used to determine the kinetic isotope effect k(H)/k(D), for the ruthenium-catalyzed racemization. The kinetic isotope effect k(H)/k(D) for p-X-C6H4CH(OH)CH3 was 1.08, 1.27 and 1.45 for X=OMe, H, and CF3, respectively.