**2. Advances in ruthenium catalyzed transfer hydrogenation**

Realistic relevance of the asymmetric synthesis by TH/ATH in fine chemicals, pharmaceuticals, materials and industrial use required designing and exploration of efficient catalysts. Ru with versatile oxidation states, coordination geometries offered by a variety of ligand moieties make it a good candidate for catalytic

TH/ATH. The crucial requirement for the efficient catalysts is to have a labile coordination site/anionic ligands and efficient chelation or backbone of the ligands to give high turnover numbers (TONs). In this regard, to get good selectivity and activity of the catalysts, the multi-talented ligand architectures are essential. Literature reveals that various ligands such as pincer NHC, cyclophanes, half-sandwich, organo-phosphine, pyridylideneamide, polydentate etc. [7] have been developed by different research groups to improve the selectivity of the catalysts. The following section will discuss the recent advancements in the modification of ligands architecture and their influence on catalytic efficacy.

#### **2.1 Homogeneous transfer hydrogenation**

### *2.1.1 Transfer hydrogenation of carbonyl compounds*

The transfer hydrogenation (TH) and asymmetric transfer hydrogenation (ATH) of carbonyl substrates are the most explored and favorable due to polar nature of C=O bond. Although Noyori has set the milestone for TH using TsDEPN ligands however, researchers still used this system with various modifications to improve stability and selectivity of the catalysts. Anderson and co-workers have reported extremely active proline based 2-aza-norbornyl amino alcohol ligands (**Figure 4**) for the ATH process. The [Ru(p-cymene)(**13**)] in presence of *<sup>i</sup>* PrOH catalyzed TH of acetophenone with S/C = 1000 to give *ca*. 97% conversion, *ca.* 96% *ee* (TOF50 = 8500 h<sup>1</sup> ) within 25 min. The reason for this enhanced activity in comparison with the [Ru(p-cymene)(**12**)] (*ca.* 90% conversion, *ca.* 94% *ee*, TOF50 = 1050 h<sup>1</sup> ) was due to the incorporation of polarized C-O bond/dioxolane ring in the ligand frame. This catalyst was able to reduce various aromatic ketones having electron donating and withdrawing substituents (at various positions *e.g. ortho, meta, para)* with admirable enantioselectivity. Theoretical calculations have indicated the lowering of transition state energy (1.3 kcal mol<sup>1</sup> ) in the case of [Ru(p-cymene)(**13**)] catalyst, and the increased catalytic rate was rationalized through involving the dipole interactions between dioxolane moiety and the substrate (**13a**) [8].

In search of new ligand frame-work for effective and selective TH reaction of aromatic ketones, Ramaiah and co-workers [9] have established a promising new class of air/moisture-stable ruthenophane/ruthenium(II)-π complexes (**19**–**20**) and compared their TH activity (**Figure 5**), for the first time with the literature reported catalysts. The structure stiffness of the ligands allows forming the complexes (**19**–**20**) through π-interactions between the anthracene moiety and ruthenium cation instead of insertion or NHC coordinated complexes. These catalysts were highly selective to aromatic ketones over to aliphatic and aldehyde groups and showed efficient conversion (*ca.* 100%) of acetophenone to 1-phenylethanol in

#### **Figure 4.**

*Blueprint of aza-norbornyl amino alcohol ligands (12, 13) and low energy TS (13a) determined theoretically involving remote dipole interactions (Ref. [8]).*

*Recent Advances in Ru Catalyzed Transfer Hydrogenation and Its Future Perspectives DOI: http://dx.doi.org/10.5772/intechopen.96464*

**Figure 5.**

*(A) Few selected reduced products (14–18) along with structures of (B) ruthenophane catalysts 19, 20.*

presence of a base, *<sup>i</sup>* PrOH and 2 mol% catalyst loading (80 °C). A series of substrates were scrutinized which showed efficient conversion to the reduced products (selected alcohols shown in **Figure 5**). In comparison to **20**, the catalyst **19** showed a better catalytic efficiency ascribed to different binding interactions through coordinative and cation-π interactions. The presence of labile ancillary ligands also participates in enhancement of efficient TH capabilities. Additionally, these robust catalysts showed exceptionally good conversion of the ketones to the reduced products (**14**–**18**) in comparison with the commercially available [Ru(p-cymene) Cl2]2 and the "Hoveyda-Grubbs" catalysts, under identical catalytic conditions.

*N*-heterocyclic carbenes (NHC) are another significantly important class of ligands for homogeneous ruthenium catalyzed TH reactions. Recently, different versions of NHC based ligands have been designed with an aim to synthesize thermally stable and efficient catalysts. These ligands in turn can influence steric and electronic properties of metal center through strong σ-donor capability [10]. The mononuclear and binuclear ruthenium complexes (**Figure 6**, **21–25**) (cationic/ neutral) having NHC ligands with "three-legged piano-stool" type geometry was reported by Ramaiah and co-workers [11]. These anthracene/arene based catalysts interestingly showed efficient and selective TH of a variety of aromatic ketones. Notably, very small amount of cationic catalysts (**21**–**23**) (0.5 mol%) exhibited efficient reduction of ketones (*ca.* 100%) in comparison to neutral catalysts (2 mol %) in presence of *<sup>i</sup>* PrOH and base (0.1 mM) within 2 h at 80 °C. Whereas [Ru(pcymene)Cl2]2 and the second generation "Hoveyda-Grubbs" catalysts showed moderate yields of reduced products (ca. 47% and ca. 60%, respectively) under identical situations.

The cooperative binding of NHC and pyridine substituents to the ruthenium center in cationic catalysts facilitates high catalytic activity in comparison to the neutral complexes. Reduction of the substrate was supported by well-established mechanism (**Figure 7**), wherein the active catalyst **A** formed by the addition of *iso*-propoxide, upon *β*-hydride transfer intermediate and Ru-H species **B** formed. Interaction of substrate **B** to give **C**, which upon subsequent hydride transfer to the substrate form the intermediate **D**. Furthermore, the reduced product resulted by the reaction of **D** with *<sup>i</sup>* PrOH in presence of the base with regeneration of the active species **A**. *In-silico* studies have further confirmed that the intermediates hypothesized were energetically constructive and reaction follows a thermodynamically steady pathway [11].

An innovative class of pincer pyridylideneamides (PYAs) with strong *σ*-donating ability was disclosed by Albrecht and co-workers [12]. PYAs core was tethered with different chelating groups (cyclo-metalated aryl ring/pyridine/ pyridylidene/one-more PYA/triazolylidene), which can bind to metal center either *via* π-acidic (neutral donor) or π-basic (zwitterionic pyridinium amide) donor

**Figure 6.** *Structures of NHC based cationic and anionic ruthenium catalysts 21–25 (Ref. [11]).*

**Figure 7.** *Proposed mechanism of transfer hydrogenation of ketones using cationic ruthenium catalyst (21).*

*Recent Advances in Ru Catalyzed Transfer Hydrogenation and Its Future Perspectives DOI: http://dx.doi.org/10.5772/intechopen.96464*

capability. A series of ruthenium complexes (**26**–**30**) (**Figure 8**) customized with PYA ligands were synthesized and confirmed through various techniques *e.g.* NMR, X-ray crystal structure, HR-MS and other studies. These robust Ru-PYA catalysts (1 mol%) displayed high catalytic activity (*ca.* 100% conversion) in TH of benzophenone (as model substrate) and established a relationship between chelate potency and ruthenium centered catalytic activity. The catalytic activity of the complexes (**26**–**30**) were tuned by electronic configuration of the ligands and the enhanced catalytic activity in the case of **26** correlated by NMR (with large shift difference Δδ = 1.03 ppm, then the other complexes) and electrochemical studies. It was concluded that the substrate reduction was followed first-order reaction rate *via* mononuclear reaction pathway [12].

Transfer hydrogenation of the mixed acetate/acetylacetonate ruthenium phosphine catalyst (**31**), [Ru(OAc)(acac)PP] (PP=PPh3/bis(diphenylphosphino) butane) with superior stability and activity was reported. As in the earlier cases, the addition of basic additive significantly enhanced the catalytic efficiency. The effect of NH function of these mixed ruthenium(II) phosphine complexes was demonstrated by incorporating (aminomethyl)pyridine (ampy) to [Ru(OAc)(acac)PP]. The Ampy moiety binds to the metal center upon opening/de-coordination of the acetate. The mixed catalysts (*ca.* 0.1 mol%) in absence of basic additives (ampy/en/ bza) showed very low conversion (*ca.* 38–75%, TOF = 100–930 h<sup>1</sup> ) at 90 °C in 8 h. Addition of 10 equivalents of ampy surpasses the catalytic conversion up to *ca.* 99% (TOF = 125,000 h<sup>1</sup> ) at a very low 0.03 mol% [Ru(OAc)(acac)(ampy)(dppb)] catalyst (**31**) loading in 5 min. The pathway proposed (**Figure 9**) displayed the important role of NH function for rapid reduction of the substrate *via* outer sphere mechanism, in which the first step was the formation of a five-coordinated species **A** after dissociation of the acetate ion. The second step was the coordination of *i* PrOH with the six-member TS (**B**). The third step was the formation of Ru-H species (**C**), which formed the substrate coordinated TS (**D**) and finally upon transfer of hydrogen led to the regeneration of species **A** [13].

#### *2.1.2 Transfer hydrogenation of olefins and imines*

Imines and olefins are also demanding and challenging substrates for TH/ATH. Noyori's catalyst [RuCl(TsDPEN)(η<sup>6</sup> -p-cymene)] in azeotropic mixture showed

#### **Figure 10.**

*Selected examples of few activated alkenes (32–37) investigated.*

ATH of activated alkenes (α,α-dicyano alkenes) (**32**–**37, Figure 10**) in good yields with moderate enantioselectivity [14]. Various alkenes were tested and to enhance the enantioselectivity, TsDPEN and η-arene ligands with different substitutions were explored. For example*,* 1-naphthylsulfonyl-DPEN gave high yields and enantioselectivity (*ca.* 96% and *ca.* 81% *ee*) at 85 °C. Different optimization studies revealed that temperature as well as steric hindrances on the arene moiety was important parameters for the observed catalytic activity. **Figure 10** shows few examples of activated alkenes (**32–37**), which gave moderate to good yields and high enantioselectivity. Of these examples, the reduction of the five membered analogue, 1-indanylidenemalononitrile (**33**) gave the product (*ca.* 37%, 58.2% *ee*) along with high yields of the byproduct and negligible enantioselectivity. This was confirmed that the 1,4 addition product was formed due to high acidity of *γ*-allylic C–H in **33**. Furthermore, the chiral *β*,*β*- disubstituted acids were effortlessly achieved by hydrolyzing the chiral malononitriles with concentrated HCl [14].

Another recent ATH application of Noyori's catalyst (RR-**1**/SS-**1**) was reported by Meyer and Cossy. ATH of the strained difluorocyclopropenes and their analogues are appealing substrates because of emerging application of *gem*-difluorocyclopropanes in different drugs (Zosuquidar, phase III clinical trials, for acute myeloid leukemia). The *gem*-difluorocyclopropenyl methyl ester as the model substrate was tested for ATH in *<sup>i</sup>* PrOH/CH2Cl2 (10/1) (RT, 1 h) using the catalyst (S,S)- **1** (10 mol%), which afforded *ca.* 85% yield of **38** with a measurable *cis* diastereomer (*cis*/*trans* > 96:4) (*ca.* 94% *ee*), whereas (RR)-**1** yielded, *ca.* 83% *ent*-**38** in *ca.* 98% *ee*. Reduction, condensation and subsequent reaction of **38** with *p*-bromobenzoyl

#### *Recent Advances in Ru Catalyzed Transfer Hydrogenation and Its Future Perspectives DOI: http://dx.doi.org/10.5772/intechopen.96464*

chloride yielded *p*-bromobenzoate (*ca.* 61%). Ester substituents were selected because of their cleavability specifically, under acidic and basic conditions to give *cis*-(*ca.* 67%) and *trans-(ca. 81%)*-*gem*-difluorocyclopropane-carboxylic acids, respectively. The scope of ATH on few selected substrates in presence of (S,S)-**1** is represented in **Figure 11**, (**38**–**44**). Detailed mechanistic studies have shown that the first step showed the formation of (S,S)-**II**, (**45**) with the loss of acetone and followed by hydride transfer to yield Michael acceptor (**A**) (**Figure 12**). To decrease the steric hindrance between *gem*-difluorinated C3 and *p*-cymene moieties, two different TS-I, **46** and TS-II, **46** were proposed. To restore, (S,S)-**1** gave enols (**47** and *ent-***47**), while the former upon tautomerization gave *cis*-difluorocyclopropane (**48**) as the major enantiomer. However, *ent-***47** under the kinetically controlled conditions and with proton transfer from the less hindered face at C1 yielded *ent-***48**. The synthetic applications of these difluorocyclopropane was investigated further for the formation of a variety of nitrogen heterocycles as future building blocks in medicinal chemistry [15].

**Figure 11.**

*Few selected enantioenriched* gem*-difluorocyclopropanes (38–44) achieved.*

**Figure 12.**

*Proposed mechanism for asymmetric transfer hydrogenation of* gem*-difluorocyclopropanes (48, ent-48).*

In-depth study of the pyrazole/phosphine-supported ruthenium complex in TH of olefins and alkynes under semi-hydrogenation conditions resulted in unusual *E*selectivity. The catalyst **49**/**49**<sup>0</sup> was synthesized in moderate yields by refluxing RuCl2(PPh3)2 and pyrazole ligand in acetonitrile while its structure was analyzed through NOE experiments (**Figure 13**) and X-ray analysis, which confirmed the dimeric nature in chlorobenzene/hexane. Interestingly, upon addition of two equivalents of acetonitrile in chlorobenzene, the dimer was found to undergo dissociation to yield the active catalyst. Efficient reduction of 3,3- dimethylbutene-1 was achieved in good yields (*ca*. 90%) in presence of 1 mol% of **49**/**49**<sup>0</sup> and 2 mol% of KO*<sup>t</sup>* Bu in *<sup>i</sup>* PrOH at 80 °C. Different types of alkene substrates (mono/disubstituted/terminal/*α*,*β*-unsaturated esters/anthracene) were investigated and which could be reduced easily without any isomerization (in case of terminal hexane). The mechanism of this reduction was suggested through the involvement of conventional dihydride intermediate (**50**), which was formed by the reaction of **49**/**49**<sup>0</sup> in presence *<sup>i</sup>* PrOH and base (**Figure 13**). The labile solvent further replaced the substrate to give the adduct **51**, while the alkyl adduct **52** was formed by a reversible step through alkene insertion into Ru-H bond. The alcohol coordination to the vacant site of **53** followed by reductive elimination of cyclohexane and upon subsequent proton transfer shift generated **54**. The alkoxide (**54**), upon *β*-H shift afforded π-coordinated ketone dihydride species, (**55**), which after alkene substitution regenerated **51** to activate the catalytic cycle again [16].

Guijarro and co-workers have reported the first example of chemoselective ATH of the conjugated sulfinylimines substrates, (**56a-k**). Desulfinylation of these reduced products (**57a-k**) gave the corresponding deprotected allylic amines, which could be

**Figure 13.** *(A). Structure of the catalyst (49) and its structure (49'a-49'd). (B). Proposed mechanism for TH of cyclohexene.*

*Recent Advances in Ru Catalyzed Transfer Hydrogenation and Its Future Perspectives DOI: http://dx.doi.org/10.5772/intechopen.96464*

**Figure 14.**

*Ruthenium-catalyzed asymmetric transfer hydrogenation of α,β-unsaturated imines (57a-57 k).*

**Figure 15.**

*(A) Catalysts [Ru(Cl)2(R-pybox)(C2H4)] (58–59) with a monodentate phosphane and phosphite ligands. (B) Proposed intermediates 60–62 for transfer hydrogenation of imines. (C) Proposed mechanism of transfer hydrogenation of imine with dihydro Ru complex (63).*

important for pharmaceutical applications. **Figure 14**, shows ATH of various *α,β*unsaturated imines functionalized with different substituents (for *eg.* electron releasing/electron withdrawing/naphthyl/pyridyl *etc*). The substituents on C=C and C=N affect the chemoselectivity of the reduced products. In general, the substrate with R1: aromatic/heteroaromatic, R2: alkyl/aryl, R3: alkyl, functionality yielded excellent *ee* of the allylic amines. It is also interesting to note that ATH of the imines with (E)-Ph-CH=CH- fragment preferred to reduce both C=C and C=N bonds. This simple and straight forward method of reduction of the allylic imines opens up a new avenue for the synthesis of building blocks useful in designing of new drugs [17].

The *trans*-isomers of [Ru(Cl)2(R-pybox)(L)] (**58**–**59**, **Figure 15A**) with a monodentate phosphane and phosphite ligands were developed to catalyze HY/ ATH of *N*-aryl imines (in *<sup>i</sup>* PrOH) derived from acetophenones to yield the amine products in significantly high enantioselectivity (c*a*. 99%). It is interesting to note that the reduction reactions were performed under hydrogen pressure behaved as TH reactions, which was confirmed by various labelling experiments as well as by the proposed intermediates (**60**–**62**, **Figure 15B**). From these analysis, it was speculated that a common hydride [Ru(H)(Ph-pybox)(P(OMe)3)]+ species was produced *in situ* under either HY or TH [18].

Azua and co-workers have recently reported the first example of microwave assisted ruthenium catalyzed TH of imines in presence of glycerol as the hydrogen donor. Reduction of *in-situ* synthesized imine using NHC ruthenium complex (1 mol %) with sulfonate N-wingtips yielded enhanced conversion of amine in glycerol (*ca.* 77%) and base under microwave conditions (200 W). This improved yield in comparison to the conventional method (*ca.* 17%) was due to the formation of a highly polar zwitterionic nature of the complex to absorb microwave irradiation efficiently. Additionally, the base free catalytic conversion showed quantitative yield of imine (*ca.* 63%) due to sulfonated wingtip as an internal base [19]. RuH2(PPh3)4 was a well-known active TH catalyst for the reduction of imine in the absence of a base. This catalyst was efficiently catalyzed by several imine derivatives as well as cyclic imines. The proposed mechanism (**Figure 15C**) proceeds through classical hydride transfer steps from Ru-H (**63**) to imine, which was confirmed through isotope labelling experiments, wherein incorporation of deuteride to methylidene carbon was observed [20].

#### *2.1.3 Ruthenium catalyzed synthesis of heterocycles*

The functionalized heterocyclic compounds have attracted attention due to their predominant applications in pharmaceutical industries for designing of new drugs. Recently, the Food and Drug Administration (FDA) had declined to grant new chemical entity (NCE) exclusivity to enantiomers that were part of the previously approved racemic mixtures. Therefore, the purity of enantiomers is very important and can be overcome by using appropriately designed catalysts. Although the reports on synthesis of heterocycles using ruthenium catalysts are well-known but their synthesis *via* ruthenium catalyzed ATH is not much explored. Pabalo and coworkers have reported an admirable example of ruthenium catalyzed ATH for production of enantiomerically enhanced heterocycles *eg*. aziridines, pyrrolidines, piperidines and azepanes. They have employed their established approach of enantiomerically pure *N*-(*tert*-butylsulfinyl)haloimines as the substrate, and imine bond was reduced *via* ATH in presence of *<sup>i</sup>* PrOH, [RuCl2(p-cymene)]2 catalyst and achiral 2-amino-2-methylpropan-1-ol ligand (50 °C) (**Figure 16**). The reduced haloamines in presence of a base (*<sup>t</sup>* BuOK) yielded the *N*-protected saturated heterocycles through intramolecular nucleophilic substitution in excellent yields with diastereomeric ratio up to >99:1. The *N*-protected aziridines and pyrrolidines were synthesized by one-pot ATH-cyclization sequence (Ru:L:*<sup>t</sup>* BuOK = 1:2:5 mol %) in high yields (*ca.* 85–90%) and diastereomeric ratios (selected examples **66**–**69** are shown in **Figure 17**). In the case of piperidines and azepanes, the process was

**Figure 16.** *Synthesis of selected* N*-protected heterocycles.*

*Recent Advances in Ru Catalyzed Transfer Hydrogenation and Its Future Perspectives DOI: http://dx.doi.org/10.5772/intechopen.96464*

**Figure 17.**

*Asymmetric transfer hydrogenation examples of selected N-protected aziridine (66), pyrrolidine (67), piperidines (68) and azepane (69) and X-ray crystal structures of 67, 69 (from ref. [21]) as well as structure of free pyrrolidines (70, 71).*

modified with treatment of potassium bis(trimethylsilyl)amide (KHMDS), which gave moderate yields and diastereoselectivity (**68**–**69**). On the other hand, the pyrrolidine derivatives (**70–71**) were obtained by desulfinylation of N-sulfinylpyrrolidines by the reaction with HCl/MeOH. As representative examples, the single crystal of **67** and **69** were analyzed, which confirmed the stereogenic center obtained by Ru catalyzed ATH [21].

Asymmetric tetrahydroisoquinolines (THIQs) are yet another indispensable class of heterocycles with pharmacological applications due to their structural resemblance with neurotransmitters. In this context, Noyori-Ikariya catalysts (arene/Ru/TsDPEN) were found applications in ATH of electron-rich/ortho substituted 3,4-dihydroisoquinolines (DHIQs) only to give THIQs in high enantioselectivity (*ee'*s). In contrast, these catalysts were found to be ineffective with the meta/para substituted electron-poor DHIQs, which are important for the synthesis of solifenacin and TRPM8 antagonists (pharama targets). Wills and co-workers have modified the arene/Ru/TsDPEN catalysts with tethered thiophene/furan/ester groups to basic nitrogen of TsDPEN ligand. It was found that the ATH of these demanding substrates (DHIQs) showed good catalytic efficiency with the modified catalyst (1 mol %) in presence of formic acid-triethylamine (5:2) azeotrope. The furan-based catalyst (**77**) exhibited best results of ATH of DHIQs with remarkable enantioselectivity (*ee)* of *ca.* 90% and 93% for the conversion to THIQs (**72**–**76**) (**Figure 18**).

**Figure 18.**

*Asymmetric transfer hydrogenation of few selected dihydroisoquinolines (DHIQs).*

#### **Figure 19.**

*Stabilization of TS state for asymmetric transfer hydrogenation of dihydroisoquinolines (DHIQs).*

The proposed mechanism (**Figure 19**) of this asymmetric reduction supported the extra stabilization of TS state **78** through the interaction of furan moiety of the catalyst with the aryl moiety of substrate [22]. Recently, the pyrazole/phosphine based ruthenium catalyst (1 mol %) also showed high TH activity of a variety of *N*heterocyclic substrates. For example, TH of isoquinoline surprisingly gave the product with reduced all-carbon rings, which are accountable to the electronic properties of the catalyst [16].

#### *2.1.4 Selected transfer hydrogenation/asymmetric transfer hydrogenation of nitriles, esters and acetates*

The nitrile-based substrates have received less attention for TH/ATH reactions, in spite of their industrial significance. In earlier studies, TH of benzonitrile catalyzed by RuH2(PPh3)4 gave very low yields of the reduced product and showed the requirement of focused research in this area [20]. Beller and co-workers have reported NHC based [Cp(IPr)Ru(pyr)2][PF6], catalyst (0.5 mol% catalyst, 1.5 mol% KO*<sup>t</sup>* Bu, *<sup>i</sup>* PrOH), which effectively catalyzed TH of various aromatic nitriles to give the corresponding aromatic imines (*ca.* 24–99%). The function of base was to convert [Cp(IPr)Ru(pyr)2][PF6] to Cp(IPr)RuH3 which was confirmed through kinetic data as well as mechanistic steps, migratory insertion and release of the product after a metathesis with IPA [23]. Additionally, the extensive screening experiments of various ruthenium pre-catalysts in presence and absence of different ligands was performed. The best catalyst system ({Ru(p-cymene)Cl2}2 (1 mol %)/DPPB (2 mol%) in presence of NaOH (10 mol %) and 2-butanol at 120 °C, showed the reduction of various aliphatic/aromatic/hetero aromatic nitriles to primary amines [24]. Remarkably, high TH catalytic activity of bifunctional RuII( phenpy-OH) catalyst was reported for a variety of nitrile substrates *via* outersphere mechanism in the presence of excess of PPh3. The presence of –OH in the ligand support as a supplementary for the metal hydride formation *via* direct interaction of –OH with the metal coordinated halide ion [25].

Kim and co-workers have disclosed RuH2(CO)(PPh3)3 (10 mol%) catalyst stabilized with pyridine ligand (20 mol%), which showed selective method of imine formation from nitriles substrate under base free conditions through hemiaminal intermediate mechanism [26]. Nikonov and co-workers have revealed half-sandwich [Cp(IPr)Ru(py)2]PF6 complexes for TH of nitriles with comparatively high catalyst loading [24]. To further improve pyrazole/ phosphine-supported cationic ruthenium complex (**49**/**49**<sup>0</sup> ) was reported that showed high activity in the catalytic TH of nitriles. This active catalyst (**49**/**49**<sup>0</sup> , 1 mol%) in presence of nitriles, KO*<sup>t</sup>* Bu (5 mol %), *<sup>i</sup>* PrOH (80 °C, 24 h) gave moderate to excellent imine products. Further, upon treatment of imine with HCl yielded the analogous primary ammonium salts [16].

Another and less explored substrate for TH is the esters and acetates. In this context, Nikonov and co-workers have reported the first example of [Cp(PiPr3)Ru *Recent Advances in Ru Catalyzed Transfer Hydrogenation and Its Future Perspectives DOI: http://dx.doi.org/10.5772/intechopen.96464*

(CH3CN)2]PF6 catalyzed reductive conversion of the electrophilic phenyl benzoates and trifluoroacetates, which gave alcohols in low yields [27]. The catalyst [Cp(IPr) Ru(pyr)2][PF6], effectively catalyzed TH of conjugated systems such as α,β-unsaturated esters to give β-isopropoxy substituted esters (Michael addition of IPA) along with TH reduced products (ca*.* 45–99%) [23].
