Hydrogenation of Aldehydes, Esters, Imines, and Ketones Catalyzed by a Ruthenium Complex of a Chiral Tridentate Ligand

Abstract

A noVel ruthenium complex prepared from a chiral tridentate amine functionalized phosphine has been characterized by X-ray crystallography and been found to be actiVe in the hydrogenation of an unprecedented range of CdO and CdN double bonds, including the enantioselectiVe hydrogenation and transfer hydrogenation of normally unreactiVe bulky ketones with up to 90% ee.Reduction of CdO and CdN double bonds using molecular hydrogen is, due to its low cost and complete atom efficiency, a very important process in industrial organic syntheses. 1-3 There has consequently been a massive research effort aimed at developing homogeneous catalysts that can carry out this goal with high efficiency, chemoselectivity, and, in the case of prochiral ketones, enantioselectivity. Asymmetric hydrogenation of -keto esters and related substrates has been an industrial process for some time. 3 Homogeneous hydrogenation of unfunctionalized ketones could not be carried out with sufficient efficiency or chemoselectivity until Noyori's pioneering research on ruthenium complexes containing both diphosphine and diamine ligands. 4 These catalysts are highly chemoselective for CdO bonds, 5 show industrially relevant turnover numbers, and if the catalyst shown in Figure 1 is used, extremely high enantioselectivity for a range of acetophenone derivatives. Since Noyori's publications, several other catalysts have appeared that are based on the same design blueprint and have also given excellent results for reduction of acetophenone derivatives. [6][7][8][9][10] The key to the massively enhanced reactivity relative to that of simple Ru-phosphine catalysts is proposed to be the unique mechanism in which the substrate hydrogen bonds to the NH functionality in the diamine ligand. 11,12 However, [Ru(BINAP)(DAIPEN)Cl 2 ] and related catalysts do have some important limitations and are far less effective for the hydrogenation of tetralones, dialkyl ketones, bulky ketones, and some heterocyclic ketones and imines. We therefore initiated a project aimed at successfully hydrogenating these difficult substrates, with the general impression that a departure from the [Ru(diphosphine)(diamine)Cl 2 ] blueprint would be required. In this communication, we report preliminary results showing the promise of ruthenium complexes of chiral tridentate ligands as hydrogenation catalysts. Phosphine-amine ligands have provided some interesting niche applications in catalysis, 13-15 and given the absence of data on hydrogenation catalysis using tridentate ligands, 16,17 ruthenium complexes of tridentate P ∧ N ∧ NH 2 type ligands seemed worthy of investigation. This type of ligand could form octahedral ruthenium complexes with a more open coordination environment, thus increasing substrate scope or reactivity in hydrogenation. Another feature of interest was applying a single ligand to play the roles carried out by both diphosphine and diamine ligands in Noyori catalysts. [18][19][20] Ligand 1 is readily available in both racemic and enantiomerically pure forms from chea...

New phosphine-diamine and phosphine-amino-alcohol tridentate ligands for ruthenium catalysed enantioselective hydrogenation of ketones and a concise lactone synthesis enabled by asymmetric reduction of cyano-ketones

“…These catalysts give excellent results in the hydrogenation of a range of acetophenone derivatives, as have a number of structurally related catalysts [4,5]. However, [RuCl 2 (BINAP)(DAIPEN)] and related catalysts do have some important limitations, that have spurred significant interest in new catalyst development [6-21]. Given that so many drugs, agrochemicals, materials, and natural products can be disconnected back to enantiopure secondary alcohols, it is of significant importance to extend asymmetric hydrogenation chemistry such that it is effective for every major class of substrate.…”

Catalytic Hydrogenation of Low-Reactivity Carbonyl Groups Using Bifunc­tional Chiral Tridentate Ligands

“…Reduction of other carboxylic acid derivatives, some of which are even less activated to reduction, are also of interest. 27 I believe this general class of catalyst (chiral ligands with PNX-donor sets) could well have other applications in enantioselective catalysis outside the hydrogenation arena; enantioselective C-C bond forming reactions are also conceivable with these systems. Overall, in the last ten years, a wide range of catalytic chemistry has been made possible by using the more general class of bifunctional tridentate ligands.…”

“…While these can be removed by chromatography or recrystallisation, a good procedure was to use microwave heating to heat the ligand and [RuCl 2 (dmso) 4 ] in THF at 120°C for 20 minutes to give the desired air-stable complex in pure form such that it can be dried and used immediately. 27 The structure of 2 was determined by X-ray crystallography. We have also found that the phosphine-diamine ligand or its borane complex can simply be added with [RuCl 2 (dmso) 4 ] to hydrogenation reactions to generate the catalysts in situ; a method we have used in some cases where novel ligands were only prepared on a very small scale.…”

Ruthenium(II)-Arene Complexes of the Water-Soluble Ligand CAP as Catalysts for Homogeneous Transfer Hydrogenations in Aqueous Phase

“…Some of them display high reactivity and selectivity in many catalytic transformations and, in particular, in the hydrogenation of different unsaturated compounds, such as α,β-unsaturated ketones and imines, using molecular H 2 and transfer hydrogenation (TH) protocols as reducing agents [6][7][8][9]. The employment of these last methodologies offers attractive advantages including the use of inexpensive and easy to handle hydrogen donors instead of explosive hydrogen gas, mild reaction conditions, and the possibility of using environmentally friendly solvents such as water [10][11][12].…”