Hai-Feng Zhou

Hydrogenation of Quinolines Using a Recyclable Phosphine‐Free Chiral Cationic Ruthenium Catalyst: Enhancement of Catalyst Stability and Selectivity in an Ionic Liquid

Room-temperature ionic liquids (RTILs) have recently received a great deal of attention as alternative reaction media. Numerous catalytic reactions have proven feasible in a variety of ionic liquids, with many reactions displaying enhanced reactivities and selectivities, and some of which were not possible in common organic solvents. Furthermore, RTILs have served as a promising means to immobilize a catalyst, therefore facilitating product isolation and offering an opportunity to reuse the catalyst. However, the use of RTILs in asymmetric catalytic reactions is still limited. The recycling and reuse of chiral catalysts in ionic liquids have often been problematic because of the instability and/or leaching of the catalysts. From a practical standpoint, development of highly effective and recyclable catalysts in ionic liquids for use in asymmetric hydrogenation remains a challenge: in particular for heteroaromatic substrates which are difficult to hydrogenate. Although a variety of chiral Rh, Ru, and Ir complexes have been efficient and enantioselective reagents for the hydrogenation of prochiral olefins, ketones, and imines, most of these catalysts failed to give satisfactory results in the asymmetric hydrogenation of heteroaromatic compounds. A few successful examples for the asymmetric hydrogenation of quinolines have recently been reported. However, all catalysts for such reactions have at least one phosphine ligand around the metal center and are often air sensitive. From the viewpoints of both scientific interest and practical application, it is highly desirable to develop recyclable and phosphine-free chiral catalysts for the highly enantioselective hydrogenation of quinolines. Few examples of phosphine-free homogeneous catalysts capable of activating molecular hydrogen have been reported. Recently, Noyori and co-workers reported that chiral h-arene/Ntosylethylenediamine–Ru complexes (which are known as excellent catalysts for asymmetric transfer hydrogenation, for example Ru/Ts-dpen) can be used for the asymmetric hydrogenation of prochiral ketones under slightly acidic conditions. Inspired by this important breakthrough and following our continued pursuit of developing effective and environmentally benign catalyst systems for asymmetric hydrogenations, herein we report a practical and efficient catalyst system of Ru/Ts-dpen in [BMIM]PF6 (BMIM = 1-nbutyl-3-methylimidazolium) for the enantioselective hydrogenation of quinolines (Scheme 1).

Asymmetric hydrogenation of quinolines with high substrate/catalyst ratio

The chiral diphosphinite ligand derived from (R)-1,1-spirobiindane-7,7-diol has been found to be highly effective in the Ir-catalyzed asymmetric hydrogenation of quinolines with high substrate/catalyst ratio (up to 5000) and high enantioselectivity (up to 94% ee).

Highly enantioselective hydrogenation of quinolines under solvent-free or highly concentrated conditions

The phosphine-free chiral cationic Ru(OTf)(TsDPEN)(η6-cymene) complex was found to be an efficient catalyst for the enantioselective hydrogenation of quinolines under more environmentally friendly solvent-free or highly concentrated conditions. Excellent yields and enantioselectivities (up to 97% ee) were obtained at only 0.02–0.10 mol% catalyst loading.