**2.3. Influence of the base on the asymmetric transfer hydrogenation of imines**

where the most probable structures have been studied. Furthermore, the resulting high

It was assumed that a protonated substrate is attached to the molecule of the catalyst by the hydrogen bond between the hydrogen of the protonated substrate and the oxygen of the sulfonyl amide group of the catalyst and by that transition state is stabilized. Nonbinding interactions between π electrons of aromatic ring of the substrate and hydrogen atoms of *p*cymene (i.e., CH/π interactions [7]), which also stabilize the favorable transition state, play a crucial role in the determination of enantiomeric excess (*ee*). Depending on energetic differences between "favorable" and "not favorable" transition states, geometry of the transition

Besides, corresponding calculations allowed to suggest the pathway toward ATH of 1 methyl-3,4-dihydroisoquinoline using formic acid/triethylamine azeotrope as the source of hydro-

The proposed cycle starts with the transformation of the [Ru(Cl)(η6 *p* cymene)(*S,S)* TsDPEN] complex (**a**) onto ruthenium-hydride (**b**), where this action is accompanied by the release of HCl, further neutralized by the present base (triethylamine), leading to the 16 ecomplex (**c**). In the next step, the complex (**c**) receives a proton from formic acid to form the complex (**d**), followed by the complex (**d**) turning in the presence of formate ion into ruthenium-hydride (**b**) and releasing CO2. Finally, ruthenium-hydride participates in the asymmetric transfer hydrogenation process of the protonated substrate (**1'**). With the transfer of hydrogen from the complex (**b**) to the substrate (**1'**) the catalytic complex turns back to the intermediate (**d**). By

**2.2. Asymmetric transfer hydrogenation of acyclic imines (***N***-benzyl-1-phenylethan-1-imin)**

Asymmetric transfer hydrogenation of acyclic imines proceeds rather differently than in the case of cyclic imines such as substituted 3,4-dihydroisoquinolines. ATH of *N* benzyl-1 phenylethan-1-imin using Noyori's based catalyst with (*S, S*) ligand configuration lead to the

enantioselectivity of the ATH of cyclic imines was explained.

40 New Advances in Hydrogenation Processes - Fundamentals and Applications

state determines *ee* of the product at the end of the reaction.

**Figure 3.** Suggested scheme of the catalytic cycle in ATH of 1-methyl-3,4 dihydroisoquinoline.

gen (**Figure 3**).

this, the whole cycle is closed.

To clarify the role of the base in asymmetric transfer hydrogenation of cyclic imines using Noyori's Ru(Cl)(η6 ‐*p*‐cymene)(*S,S)-*TsDPEN], catalyst is a rather complex problem [9]. The series of aliphatic (secondary, tertiary) or aromatic amines were employed into the formic acid/ base system used for ATH. This work is divided into two parts, kinetic studies using *in situ* monitoring by nuclear magnetic resonance (NMR) spectroscopy and spectroscopic studies, including NMR spectroscopy, Fourier transform ion cyclotron resonance mass spectroscopy (FT‐ICR MS), and vibrational circular dichroism (VCD) together with infrared (IR) spectro‐ scopy. At first, during kinetic study of ATH of (*R*) 1,4 dimethyl‐3,4‐dihydroisoquinoline, substantially different reaction rates with various bases were observed. The highest reaction rates were measured after using tertiary bases, such as triethylamine (TEA), whose rate was over four times higher than *N, N* diisopropyl(ethyl)amine (DIPEA). Nevertheless, the secon‐ dary bases such as morpholine, piperidine, or pyrrolidine performed with even a lower reaction rate. Surprisingly, the reaction rate was rather high for aromatic amine, pyrrole and certainly low for pyridine. Both the reaction rate and asymmetric tendencies were significantly affected. In the case of diastereomeric excess (*de*), the lowest value was observed for DIPEA, followed by TEA. The secondary amines performed with a higher *de* over 60% and the highest value was obtained for pyrrolidine as one of the smallest molecules in the mixture. Also, *de* values for aromatic amines were in the range of 65–75%. These results suggested that differ‐ ences in diastereoselectivity were triggered by the steric demands of the bases applied. A very similar procedure was performed using 1‐methyl‐3,4‐dihydroisoquinoline as the substrate. As in the previous case, significant differences between additions of tertiary, secondary and aromatic bases were observed in terms of the reaction rate. Interestingly enough, a slightly higher reaction rate was observed using DIPEA, than TEA. However, the enantioselectivity was not significantly changed with the usage of various bases.

The spectroscopic methods were applied to understand the influence of the base in depth. For the NMR examinations, the mixture of [Ru(Cl)(η6 -*p*-cymene)(*S,S)-*TsDPEN] catalyst together with pure formic acid or the mixture of formic acid and TEA with different molar ratio were used. Employing pure formic acid was accompanied by the formation of the ruthenium-hydride species, which solely decomposed under acidic conditions. Furthermore, TEA addition has positive effect regarding the formation of catalytic hydride (**Figure 3**, complex **b**), positive effect was observed to the ratio of TEA/formic acid 5:1, and above this value no significant improvement in the case of hydride concentration was observed. Also, using <sup>1</sup> H-NMR spectrum, three intermediates were found in the mixture: (1) ruthenium-hydride species, (2) ruthenium formate complex [Ru(HCOO- )(η6 *p* cymene)(*S,S)-* TsDPEN and (3) a species, which is assumed to be the second diastereomer of the ruthenium-hydride. After NMR experiments, ESI+ FT-ICR MS to observe active rutheniumhydride species using TEA/formic acid in molar ratio 5:2 was applied. The MS spectrum contained three clusters, the first one, with *m/z* 595.1500 which belonged to the 16 e- complex (**Figure 3**, complex **c**), the second one, was determined as the cluster of active ruthenium-hydride associated with TEA. The last one, was assigned to the associate of a precatalyst (**Figure 3**, complex **a**) with TEA. From the results obtained, authors suggested that the binding of the base could be realized by three different ways: (1) the base is coordinated to the central Ru atom, (2) the base forms N⋅⋅⋅H-N bond with chiral ligand of the catalyst, or (3) the protonated base forms a N+ -H⋅⋅⋅O hydrogen bond with a sulfonyl group of the chiral ligand (**Figure 4**). To exactly determine which is the right way, the application of the VDC analytical method combined with IR spectroscopy concluded that the protonated base is connected with the catalytic complex *via* N+ -H⋅⋅⋅O hydrogen bond with a sulfonyl group of TsDPEN ligand. The consequence of these findings can be that the base selection has a huge impact on the reaction rate and enantioselectivity of the ATH of cyclic imines.

**Figure 4.** A scheme of binding of both substrate (red) and base (blue) to the active site of ruthenium-hydride species.
