Jan Pecháček

Practical Aspects and Mechanism of Asymmetric Hydrogenation with Chiral Half-Sandwich Complexes

This review is oriented toward the asymmetric transfer hydrogenation (ATH) of imines regarding mostly fundamental, yet important topics from the practical point of view. Development of analytical methods for the monitoring of ATH (i.e., kinetics and stereoselectivity) belongs to those topics, as well as studies on the influence of reaction conditions and structural variations on the reaction performance. The second part is devoted to the reaction mechanism with the emphasis on imine ATH and catalyst behaviour under acidic conditions. The review also addresses the asymmetric hydrogenation (AH) of ketones and imines using molecular hydrogen and the application of ATH in pharmaceutical projects. The contributions of our group to each area are included.

New insight into the role of a base in the mechanism of imine transfer hydrogenation on a Ru(II) half-sandwich complex

Asymmetric transfer hydrogenation (ATH) of cyclic imines using [RuCl(η(6)-p-cymene)TsDPEN] (TsDPEN = N-tosyl-1,2-diphenylethylenediamine) was tested with various aliphatic (secondary, tertiary) and aromatic amines employed in the HCOOH-base hydrogen donor mixture. Significant differences in reaction rates and stereoselectivity were observed, which pointed to the fact that the role of the base in the overall mechanism could be more significant than generally accepted. The hydrogenation mixture was studied by nuclear magnetic resonance (NMR), Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and vibrational circular dichroism (VCD) with infrared spectroscopy. The results suggested that the protonated base formed an associate with the active ruthenium-hydride species, most probably via a hydrogen bond with the sulfonyl group of the complex. It is assumed that the steric and electronic differences among the bases were responsible for the results of the initial ATH experiments.

Experimental and Theoretical Perspectives of the Noyori-Ikariya Asymmetric Transfer Hydrogenation of Imines

The asymmetric transfer hydrogenation (ATH) of imines catalyzed by the Noyori-Ikariya [RuCl(η6-arene)(N-arylsulfonyl-DPEN)] (DPEN = 1,2-diphenylethylene-1,2-diamine) half-sandwich complexes is a research topic that is still being intensively developed. This article focuses on selected aspects of this catalytic system. First, a great deal of attention is devoted to the N-arylsulfonyl moiety of the catalysts in terms of its interaction with protonated imines (substrates) and amines (components of the hydrogen-donor mixture). The second part is oriented toward the role of the η6-coordinated arene. The final part concerns the imine substrate structural modifications and their importance in connection with ATH. Throughout the text, the summary of known findings is complemented with newly-presented ones, which have been approached both experimentally and computationally.

Molecular Structure Effects in the Asymmetric Transfer Hydrogenation of Functionalized Dihydroisoquinolines on ( S , S )-[RuCl( η 6 - p -cymene)TsDPEN]

The asymmetric transfer hydrogenation of five dihydroisoquinolines (DHIQs) was studied by NMR spectroscopy. The DHIQs differed by substitution with methoxy groups, which had a significant effect upon the reaction performance in terms of reaction rate and enantioselectivity. The differences are most probably related to the basicity of DHIQs.Graphical Abstract

Synthesis and characterization of two new chiral Kemp’s acid derivatives: structures fixed by a peculiar system of N–H···O, C–H···O and C–H···N hydrogen bonds

Abstract New chiral imide-oxazoline derivatives of Kemp’s acid were synthesized with the aim to produce new ligands suitable for catalytic asymmetric reactions. Compound 1 is C18H28N2O3, systematic name (1R, 5S, 7R)-7-[(S)-4-tert-butyl-4,5-dihydrooxazole-2-yl]-1,5,7-trimethyl-3-azabicyclo-[3.3.1]-nonane-2,4-dione. Compound 2 is C21H26N2O3, systematic name (1R,5S,7R)-7-[(S)-4-benzyl-4,5-dihydrooxazole-2-yl]-1,5,7-trimethyl-3-azabicyclo-[3.3.1]-nonane-2,4-dione. Both compounds contain two molecules with very similar conformations in the asymmetric unit. The two structures were characterized by single crystal X-ray diffraction. DFT calculations of two possible distinct conformations were performed to elucidate the differences between the preferred conformation in vacuo and the one observed in the single crystal. Also, charges on the key atoms of the compounds were compared with a common ligand used for asymmetric transfer hydrogenation.

Computational evaluation of the η6-arene during the ATH of imines on Noyori’s RuII catalyst

Asymmetric hydrogenation ranks to the most intensively researched way of preparation of enantiomerically pure compounds which are demanded e.g. in pharmaceutical industry, cosmetics or agriculture. In the field of asymmetric transfer hydrogenations (ATH) of C=N and C=O double bonds Noyori’s ruthenium (II) complexes represent significant breakthrough. This catalytic system consists of three integral parts - chiral monotosylated diamine ligand – i.e. N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine (TsDPEN), η6-coordinated aromatic molecule (e.g. benzene or p-cymene) and halogen counteranion (usually chloride). General formula of the catalyst can be written as [RuCl(η6-arene)(N-arylsulfonylDPEN)]. Aforementioned fragments/ligands offer countless number of possibilities for structural modifications – e.g. elongation of carbonaceous spacer between phenyl rings within 1,2-diphenylethylendiamino fragment, alkylation of amino group, usage of diversely substituted η6-aromatic molecule, employment of different aryls within arylsulfonyl fragment etc. Systematic evaluation of these modifications has multilateral benefits because it not only helps to clarify mechanistic phenomena but also contributes to the deeper understanding of relationship between structure and catalytic activity. With sufficiently big and rich data base it should be possible to tailor catalyst’s properties specifically for given substrate (or class of substrates) and reaction conditions (solubility, stability, etc.). Our research is focused primarily on comprehension of role of the η6-aromatic molecule during asymmetric transfer hydrogenation of imines. This ligand plays very important mechanistic role because its structure (respectively interaction with the substrate) allows asymmetric course of the reaction. Arene ligand can in certain cases form stabilizing CH/π interaction between aromatic part of substrate and therefore lower energy of transition state. This led us to the hypothesis that alteration of its structure could strongly affect enantioselectivity and reaction rate. This hypothesis has been brought up and discussed but only in case of ATH of C=O bonds, which dramatically differs from hydrogenation of C=N bonds. Usually only simply alkyl-substituted arene molecules are used as aromatic ligands. In our study we have prepared and compared four catalysts with different aromatic ligands (benzene, p-cymene, mesitylene, 1,2,3,4,5,6-hexamethylbenzene) according to their performance (reaction rate, enantioselectivity) during hydrogenation of variously substituted 3,4-dihydroisoquinolines and tried to interpret obtained results via means of computational chemistry.