(beta-Amino alcohol)(arene)ruthenium(II)-catalyzed asymmetric transfer hydrogenation of functionalized ketones - Scope, isolation of the catalytic intermediates, and deactivation processes

The asymmetric transfer hydrogenation of functionalized ketones with (beta -amino alcohol)(arene)Ru-II catalysts using 2-propanol as the hydrogen sour ce has been studied. The structure of the catalyst has been systematically screened using a wide variety of [(eta (6)-arene)RuCl2](2) complexes and be ta -amino alcohols (RCH)-C-1(OH)(CHRNHR3)-N-2, some of which were specifica lly designed for optimized performance, e.g. (1S,2R)-N-(4-biphenylmethyl)no rephedrine (9o). The efficiencies of the catalytic combinations have been e valuated in the reduction of beta -oxo esters and ketones bearing heteroato ms 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}{e ta (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, cha racterized by NMR and ESI-MS, as well as by X-ray crystallography in the ca se of 35, and their reactivities have been investigated. The results reveal two general trends regarding this catalytic process: (1) the apparent reac tion rate and the enantioselectivity are largely controlled by the nature o f the amine functionality of the chiral ligand and the arene ring of the Ru -II precursor; (2) side reactions occur between the ketone substrate and th e active catalytic species that affect the concentration of 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.