The Hydrogenation/Transfer Hydrogenation Network:  Asymmetric Hydrogenation of Ketones with Chiral η⁶-Arene/N-Tosylethylenediamine−Ruthenium(II) Catalysts

Abstract

Chiral eta6-arene/N-tosylethylenediamine-Ru(II) complexes, known as excellent catalysts for asymmetric transfer hydrogenation of aromatic ketones in basic 2-propanol, can be used for asymmetric hydrogenation using H2 gas. Active catalysts are generated from RuCl[(S,S)-TsNCH(C6H5)CH(C6H5)NH2](eta6-p-cymene) in methanol, but not 2-propanol, or by combination of Ru[(S,S)-TsNCH(C6H5)CH(C6H5)NH](eta6-p-cymene) and CF3SO3H or other non-nucleophilic acids. This method allows, for the first time, asymmetric hydrogenation of simple ketones under acidic conditions. Hydrogenation of base-sensitive 4-chromanone and its derivatives with the S,S catalyst proceeds in methanol with a substrate-to-catalyst molar ratio of 1000-3000 (10 atm) to 7000 (100 atm), giving (S)-4-chromanols with 97% ee quantitatively. The reaction can be achieved even on a 2.4 kg scale. The mechanistic rationale for the catalytic efficiency is presented.

Synthesis and Catalytic Applications of an Extended Range of Tethered Ruthenium(II)/η6-Arene/Diamine Complexes

“…2,3 This versatile class of catalyst operates successfully with a range of reducing agents including isopropanol, formic acid, sodium formate (in the case of asymmetric transfer hydrogenation -ATH) 2 and, when modified with non-coordinating counterions, hydrogen gas (in the case of asymmetric pressure hydrogenation -APH). 4 Supported versions of the catalysts have also been developed. 5 The introduction of a 'tethering' group between the arene and the diamine, i.e.…”

Application of Tethered Ruthenium Catalysts to Asymmetric Hydrogenation of Ketones, and the Selective Hydrogenation of Aldehydes

“…[1][2][3][4][5][6] The majority of catalysts for asymmetric hydrogenation contain either phosphorus/nitrogen-donor ligands or a combination of each type. [2] Asymmetric hydrogenation catalysts which lack phosphine-based ligands are relatively rare.…”

“…[2] Asymmetric hydrogenation catalysts which lack phosphine-based ligands are relatively rare. [3][4][5][6] Catalysts of this type [3] can be prepared in situ by combining Ru(II), Rh(III) and Ir(III) complexes with chiral diamine ligands, [4] however a number of very efficient, well-defined complexes derived from chiral amines have recently been reported. [5,6] An important breakthrough in this area was provided by complex 1, [6] the OTf derivative of the well-established asymmetric transfer hydrogenation catalyst 2, [7] itself an organometallic complex of the ligand N-tosyl-1,2-diphenyl-ethane-1,2-diamine (TsDPEN).…”

“…[3][4][5][6] Catalysts of this type [3] can be prepared in situ by combining Ru(II), Rh(III) and Ir(III) complexes with chiral diamine ligands, [4] however a number of very efficient, well-defined complexes derived from chiral amines have recently been reported. [5,6] An important breakthrough in this area was provided by complex 1, [6] the OTf derivative of the well-established asymmetric transfer hydrogenation catalyst 2, [7] itself an organometallic complex of the ligand N-tosyl-1,2-diphenyl-ethane-1,2-diamine (TsDPEN). Although complex 2 is reported to be a poor catalyst for ketone hydrogenation, replacement of its chloride with triflate, and conducting the hydrogenation in methanol rather than isopropanol, results in the formation of a much more active hydrogenation system (Scheme 1) which was first tested on a series of chromanone substrates.…”

Catalytic organometallic anticancer complexes

“…Here we consider the anticancer activity of ruthenium(II) arene complexes. Such complexes are well known as catalysts in industry, for example, for hydrogenation reactions (4). Although organometallic complexes can catalyze hydrogenation of intracellular biomolecules (5), metal-centered catalysts might be readily poisoned and be ineffective in biological media.…”