Asymmetric hydrogenation of ketones: Tactics to achieve high reactivity, enantioselectivity, and wide scope

Abstract

Ru complexes with chiral diphosphines and amine-based ligands achieve high catalytic activity and enantioselectivity for the hydrogenation of ketones under neutral to slightly basic conditions. The chiral environment is controllable by changing the combination of these two ligands. A concerted six-membered transition state is proposed to be the origin of the high reactivity. The η6-arene/TsDPEN–Ru and MsDPEN–Cp*Ir catalysts effect the asymmetric reaction under slightly acidic conditions. A variety of chiral secondary alcohols are obtained in high enantiomeric excess.

Amine‐Tunable Ruthenium Catalysts for Asymmetric Reduction of Ketones

“…A remarkable inversion of the stereoselectivity was observed when using 3c in combination with 12 (entry 16) instead of diamines 4-7 (entries [11][12][13][14]. Although some scattered examples of inversion of stereoselectivity can be found in the literature, no general evaluation has been undertaken.…”

“…Although some scattered examples of inversion of stereoselectivity can be found in the literature, no general evaluation has been undertaken. [11] The reduction of other heterocycles to provide isoquinolines 16-17, benzothiophene 18, benzofuranone 19, and pyrazole 20 also resulted in high selectivities (Table 4). Complete inversion of enantioselectivity was also observed in these cases using pre-made complexes 26 and 27.…”

Asymmetric Hydrogenation and Transfer Hydrogenation of Ketones

“…This catalyst system chemoselectively afforded the corresponding chiral alcohols in almost quantitative yields and up to 99% optical yields. Since then, a number of AHs catalyzed by Ru(II) complexes, like C1 bearing chiral diphosphine, and diamine ligands for structurally diverse substrates, like alkyl-aryl ketones, heteroaromatic ketones, unsymmetrical benzophenones, aliphatic and , -unsaturated ketones, has been reported (Noyori & Ohkuma, 2001;Ohkuma, 2010). Furthermore, proper matching of a chiral ruthenium diphosphine with the correct enantiomer of diamine leads to exceptionally enantioselective catalysts, which are also highly chemoselective for C=O group vs. C=C and C≡C bonds, and tolerate many functionalities, like NO2, CF3, halogen, acetal, CO2R, NH2, NHCOR, etc.…”

Asymmetric Hydrogenation

“…After examining numerous chiral diamines, Noyori, Ohkuma, and their co-workers found that the most effective catalyst systems were BINAP-DPEN (DPEN = 1,2-diphenylethylenediamine) (33) and BINAP-DAIPEN (DAIPEN = 1,1-di-4-anisyl-2-isopropyl-1,2-ethylenediamine) (34) (Fig. 2) [16,17,47]. In particular, the latter catalytic system (34), which has sterically more demanding 3,5-xylyl moieties on the phosphorus atoms exhibited exceedingly high catalytic activities and enantioselectivities in the hydrogenation of a wide range of ketone substrates.…”