Application of tethered ruthenium catalysts to asymmetric hydrogenation of ketones, and the selective Hydrogenation of aldehydes

An improved method for the synthesis of tethered ruthenium(II) complexes of monosulfonylated diamines is described, together with their application to the hydrogenation of ketones and aldehydes. The complexes were applied directly, in their chloride form, to asymmetric ketone hydrogenation, to give products in excess of 99% ee in the best cases, using 30 bar of hydrogen at 60 °C, and to the selective reduction of aldehydes over other functional groups

Synthesis and catalytic applications of an extended range of tethered ruthenium(II)/η6-Arene/diamine complexes

A series of novel enantiopure Ru(II) complexes containing a chiral diamine and η6-arene connected by a tethering group have been prepared and were evaluated in the asymmetric reductions of a range of ketones. Changes to the level of steric hindrance and the addition of an electron-withdrawing functionality on the sulfonyl group have a significant effect on the reactivity and enantioselectivity of the catalysts

Transfer Hydrogenation and Hydrogenation of Commercial-Grade Aldehydes to Primary Alcohols Catalyzed by 2-(Aminomethyl)pyridine and Pincer Benzo[h]quinoline Ruthenium Complexes

5siThe chemoselective reduction of commercial-grade aldehydes (97–99 %) to primary alcohols is achieved with cis-[RuCl2(ampy)(PP)] [ampy=2-(aminomethyl)pyridine; PP=1,4-bis(diphenylphosphino)butane, 1,1′-ferrocenediyl-bis(diphenylphosphine)] and pincer [RuCl(CNNR)(PP)] [PP=1,3-bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,1′-ferrocenediyl-bis(diphenylphosphine); HCNNR=4-substituted-2-aminomethyl-benzo[h]quinoline; R=Me, Ph] complexes by transfer hydrogenation and hydrogenation reactions. Aromatic, conjugated, and aliphatic aldehydes are converted quantitatively to the corresponding alcohols using 2-propanol with potassium carbonate at substrate/catalyst ratios up to 100 000 by transfer hydrogenation, whereas aldehyde hydrogenation (5–20 atm of H2) is achieved efficiently in MeOH in the presence of KOtBu at substrate/catalyst ratios up to 40 000.reservedmixedBaldino, Salvatore; Facchetti, Sarah; Zanotti-Gerosa, Antonio; Nedden, Hans Günter; Baratta, WalterBaldino, Salvatore; Facchetti, Sarah; Zanotti Gerosa, Antonio; Nedden, Hans Günter; Baratta, Walte

The Development of an Asymmetric Hydrogenation Process for the Preparation of Solifenacin

The successful development of a catalytic imine asymmetric hydrogenation process for the reduction of the hydrochloride salt of 1-phenyl-3,4-dihydroisoquinoline to 1-(<i>S</i>)-phenyl-1,2,3,4-tetrahydroisoquinoline is described. This represents a novel approach to the key intermediate in preparing the urinary antispasmodic drug solifenacin, (1<i>S</i>)-(3<i>R</i>)-1-azabicyclo­[2.2.2]­oct-3-yl-3,4-dihydro-1-phenyl-2­(1<i>H</i>)-isoquinoline carboxylate. Suitable reaction conditions were identified through an extensive screen of catalysts and combination of solvents and additives. The best reaction conditions: [Ir­(COD)­Cl]₂-(<i>S</i>)-P-Phos, molar substrate to catalyst ratio (S/C) of >1000/1, THF, 1–2 equiv of H₃PO₄, 60 °C, 20 bar H₂, were reproduced on a 200 g scale (95% isolated yield, 98% ee and >99% HPLC product purity)