(#beta#-Amino alcohol)(arene)ruthenium(II)-Catalyzed Asymmetric Transfer Hydrogenation of Functionalized Ketones-Scope, Isolation of the Catalytic Intremediates, and Deactivation Processes

摘要

The asymmetric transfer hydrogenation of functionalized ketones with (#beta#-amino alcohol)(arene)Ru~II catalysts using 2-propanol as the hydrogen source has been studied. The structure of the catalyst has been systematically screened using a wide vriety of [(#eta#~6-arene)RuCl_2]_2 complexes and #beta#-amino alcohols R~1CH(OH)CHR~2NHR~3, some of which were specifically designed for optimized performance, e.g.(1S,2R)-N-(4-biphenylmethyl)norephedrine (9o). The efficiencies of the catalytic combinations have been evaluated in the reduction of #beta#-oxo esters and ketones bearing heteroatoms at the #alpha#-position. The catalyst precursor [{#eta#~6-p-cymene}{#eta#~2-N,O-(9o)}RuCl] (35), the 16-electron true catalyst [(#eta#~6-p-cymene}{#eta#~2-N,O-(9o~(1-))}Ru] (36), and the hydride [{#eta#~6-p-cymene}{#eta#~2-N,O-(9o)}RuH} (37) involved in the reduction process have been isolated, characterized by NMR and ESI-MS, as well as by X-ray crystllography in the case of 35, and their reactivities have been investigated. The results reveal two general trends regarding this catalytic process: (1) the apparent reaction rate and the enantioselectivity are largely controlled by the nature of the nature of the amine functionality of the chiral ligand and the arene ring of the the Ru~II precursor; (2) side reactions occur between the ketone substrate and the latter and consequently the apparent rate; the formation of inactive (#beta#-diketonato)Ru~II complexes is demonstrated in the case of #beta#-oxo esters.