New Ruthenium Catalysts for Asymmetric Transfer Hydrogenation of Prochiral Ketones

Abstract

Tridentate N,N,N-pyridinebisimidazolines have been studied as new ligands for the enantioselective transfer hydrogenation of prochiral ketones. High yields and excellent enantioselectivity up to > 99 % ee have been achieved with an in situ generated catalytic system containing dichlorotris(triphenylphosphine)ruthenium and 2,6-bis-([4R,5R]-4,5-diphenyl-4,5-dihydro-1H-imidazol-2-yl)-pyridine (3a) in the presence of sodium isopropoxide.Keywords: asymmetric transfer hydrogenation; ketones; phosphines; ruthenium; tridentate nitrogen ligands Enantiomerically pure alcohols have a wide range of applications, for example, building blocks and synthons for pharmaceuticals, agrochemicals, polymers, syntheses of natural compounds, auxiliaries, ligands and key intermediates in organic syntheses.[1] Within the different molecular transformations to chiral alcohols, transition metal-catalyzed reactions offer efficient and versatile strategies, such as addition of organometallic compounds to aldehydes, hydrosilylation, and hydrogenation of prochiral ketones.[2] From an economic and environmental point of view the asymmetric hydrogenation, in particular the transfer hydrogenation, represents a powerful tool for their synthesis because of its high atom economy and safety advantages.[3] Here, Noyoris ruthenium-based catalysts comprising chiral tosylated diamines constitute state-of-the-art transfer hydrogenation systems.[3d,4] Based on this seminal work an increasing number of ruthenium catalysts with chiral bidentate N,N-ligands were developed in the last decade.[3] Significantly fewer systems are known in which transfer of chiral information is promoted by tridentate ligands. [5,6] Up to now only a limited number of auspicious tridentate nitrogen-containing N,N,N ligands were established in the field of transfer hydrogenation. For example (R)-phenyl-ambox (1) [5] and different pyridinebisoxazoline (pybox) ligands (2) [6] have been applied for the reduction of acetophenone (Scheme 1).Recently, we reported the synthesis of a new class of chiral tridentate amines.[7] The preparation and tunability of these pyridinebisimidazolines (3) (socalled pybim ligands, Scheme 1) are easier and more flexible compared to the popular pyboxes, making the former a suitable ligand tool box for various asymmetric transformations. To date there is no report on the performance of these ligands in hydrogenation reactions. The resemblance between pybim (3) and pybox (2) stimulated our research to study the potential of this class of ligands in the transfer hydrogenation of aromatic and aliphatic ketones.In exploratory experiments, isopropyl alcohol-based transfer hydrogenation of acetophenone was examined using a simple in situ catalyst system composed of [RuCl 2

Copper‐Catalyzed Enantioselective Hydrosilylation of Ketones by Using Monodentate Binaphthophosphepine Ligands

“…[8c, 10b] In recent years, we and others [16] demonstrated the usefulness of monodentate ligands derived from the binaphthophosphepine backbone in asymmetric hydrogenations, [17] transfer hydrogenations, [18] and hydroformylations. [19] Although the potential of chiral monodentate ligands for hydrosilylation reactions has been pointed out in several reviews, [20] to the best of our knowledge there is no reported example of such a copper-catalyzed reaction.…”

Ru(II) pyridyl-based NNN complex catalysts for (asymmetric) transfer hydrogenation of ketones at room temperature

“…As the bulkiness of the substituents decreased from bromo to chloro, the resultant enantioselectivity decreased from 95% to 93% (entries 4 and 5, Table 3). We have previously shown that a benzimidazolyl N-H in a ligand can accelerate the TH and ATH of ketones [28][29][30], and an imidazolinyl N-H functionality has also been reported as improving the enantioselectivity in ATH [38]. In our case, the combination of the two N-H functionalities may provide the complex catalysts with high catalytic activity and good selectivity for ATH of ketones under mild conditions.…”

“…Chiral imidazolines have been used in a number of applications in asymmetric synthesis [33], among which bidentate phosphine imidazolines have been used in the enantioselective hydrogenation of olefins [34] and allylic substitutions [35], tridentate benzene-bis(imidazolinyl) palladium complexes in asymmetric aza-Morita-Baylis-Hillman reactions [36] and Friedel-Crafts alkylations [37], and pyridinebisimidazoline NNN ligands in ATH [38], asymmetric epoxidation [39] and Henry reactions [40]. Herein, we report the synthesis of Ru(II) complexes bearing a tridentate NNN ligand containing benzimidazolyl and imidazolinyl moieties.…”

Highly Active Ruthenium(II) Complex Catalysts Bearing an Unsymmetrical NNN Ligand in the (Asymmetric) Transfer Hydrogenation of Ketones

“…All the major alcohol products had an R configuration, the highest final TOF value was 14850 h À1 (Table 3, entry 7). Notably, Ru II complexes bearing a PhPybox [18] or a chiral bis(2-imidazolyl)pyridine ligand [19] exhibited much lower catalytic efficiency than 13 b in the asymmetric transfer hydrogenation of aromatic ketones.…”