Supporting Information for An air and moisture tolerant iminotrihydroquinoline-ruthenium ( II ) catalyst for the transfer hydrogenation of ketones

a College of Chemistry and Material Science, Hebei Normal University, Shijiazhuang 050024, China b Key Laboratory of Engineering Plastics and Beijing National Laboratory for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China c CAS Research/Education Center for Excellence in Molecular Sciences, University of Chinese Academy of Sciences, Beijing 100049, China d Department of Chemistry, University of Leicester, University Road, Leicester LE1 7RH, UK. *E-mail: qbinliu@sina.com (Q. L.); whsun@iccas.ac.cn (W.-H.S); gas8@leicester.ac.uk (G.A.S.). Tel: +86-10-62557955


Introduction
The hydrogenation of unsaturated carbonyl and imine substrates has attracted considerable attention with regard to developing more sustainable, efficient and environmentally friendly processes. 1,2esides the significant breakthrough made by Noyori, 3 some recent developments in metal-mediated transfer hydrogenation 4-7 have been achieved through ligand modification of Ru-1b,4i-n,6 and Oscatalysts, 1b,4b,c,5e and in particular those based on phosphine and amino-containing alkylpyridines by the groups of Baratta, 4 Yu 6 and Mezzetti 7 (see A -D in Chart 1).Driven by demand for such processes that can operate effectively in the presence of moisture and oxygen, 8 good stability, air/water tolerance and straightforward preparation represent desirable features of a potential catalyst.†Corresponding Authors: whsun@iccas.ac.cn; liuqingb@sina.com;gas8@leicester.ac.uk (G.A.S.) Electronic Supplementary Information (ESI) available: Figures, tables, and giving NMR spectra of the new complexes and a selected substrate; CCDC 1586459 for E, CCDC 1586458 for F. For ESI and crystallographic data in CIF or other electronic format see DOI: However, to the best of our knowledge, there are only limited reports of efficient transfer hydrogenation catalysts that are capable of tolerating such conditions.1a In this article, we are concerned with the preparation of two structurally related ruthenium(II) complexes namely E and F (Chart 1), with the aim to explore their independent use in the transfer hydrogenation of ketones to secondary alcohols.In particular, we are interested in investigating how the distinct imine and primary amine donors impact on catalytic efficiency as well as on their tolerance to air and moisture conditions.Full details of the synthetic procedures for complexes and ligands are presented as is This journal is © The Royal Society of Chemistry 20xx Please do not adjust margins Please do not adjust margins an in-depth investigation of their catalytic performance in transfer hydrogenation of a diverse range of alkyl-, aryl-and cycloalkylcontaining ketones.In the first instance we focused on synthesizing (8-NH2-C9H10N)RuCl2(PPh3)2 (E) by reacting 8-amino-5,6,7,8tetrahydroquinoline 9 with RuCl2(PPh3)3. 10Pleasingly, with dichloromethane as the solvent and under ambient conditions, E was isolated in 85% yield after one hour (Scheme 1).With a view to potentially forming the trans geometrical isomer of E, we also performed the reaction in toluene at reflux over 16 hours.Unexpectedly, on work-up the oxidized/dehydrogenated iminecontaining product, (8-NH-C9H9N)RuCl2(PPh3)2 (F), was isolated in 65% yield (Scheme 1).Moreover, heating E in toluene at reflux for 4 hours also resulted in this ligand oxidation/dehydrogenation to give F in 90% yield (Scheme 1).Indeed, monitoring of this reaction by 31 P NMR spectroscopy in CDCl3 showed that full conversion to F could be achieved after just one hour at 100 o C (in a closed reactor) (see SI).Both ruthenium complexes have been characterized by 1 H, 13 C, and 31 P NMR spectroscopy, elemental analysis and have been the subject of single crystal X-ray diffraction studies.
Crystals of E and F suitable for the X-ray determinations were grown by the slow diffusion of n-pentane into their corresponding dichloromethane solutions.Views of each structure are shown in Figures 1 and 2; selected bond distances and angles are given in the figure captions.Both structures consist of a ruthenium center surrounded by two nitrogen atoms belonging to a neutral N,N-chelating ligand, two chlorides and two triphenylphosphines to complete a distorted octahedral arrangement.The key difference between the structures relates to the nature of the N,N ligand (viz.8-amino-5,6,7,8tetrahydroquinoline in E and 8-imino-5,6,7-trihydroquinoline in F) and the disposition of each pair of phosphines or chlorides.Specifically in E the phosphines are cis [P1-Ru1-P2 98.09(6) o ] and the chlorides trans [Cl1-Ru1-Cl2 167.74(6) o ], while in F the phosphines are trans [P1-Ru1-P2 176.56(3) o ] and the chlorides cis [Cl2-Ru1-Cll 96.77(3) o ].With regard to the N,N ligand, the N1-C5-C6-N2 torsion angles (-30.14 o E, 3.85 o F) highlight the deviation from co-planarity in E as a result of the sp 3 -hybridized CH-NH2 carbon (N2-C6-C5 108.2(5) o ); in F this distortion is minimized with the incorporation of an imine C=NH unit into the chelate ring.Comparison of the C6-N2 distances in E (1.473(8) Å) and F (1.319(5) Å) further supports the presence of an imine unit in F. This variation in donor atoms of the N,N-ligand also affects the Ru-N distances Please do not adjust margins Please do not adjust margins with those in E (2.152(5), 2.161(5) Å) longer than in F (2.057(3), 2.059(3) Å), underlining the more effective binding of the 8-imino-5,6,7-trihydroquinoline in F. There are also some differences in the Ru-P distances with those in E [2.3258(16)The 31 P{ 1 H} NMR spectrum (recorded in CDCl3) of E shows two mutually coupled doublets at δ 42.98 and δ 39.09 with a two-bond coupling constant of ca. 31 Hz, consistent with a cis arrangement of the two phosphine ligands.4o, 10 In its 1 H NMR spectrum, signals for the aliphatic CH2 and CH protons belonging to 8-amino-5,6,7,8tetrahydroquinoline ligand are seen as multiplets in the range δ 1.5 -3.5.In the 13 C{ 1 H} NMR spectrum, the CHN carbon is seen at δ 58.97 for E which is only shifted slightly downfield with respect to that seen in the free ligand (δ 47.09).For F the 31 P{ 1 H} NMR spectrum shows two relatively close doublets at δ 69.31 and 66.49 with a 2 J(PP) mutual coupling of ca.113 Hz indicating that the two P atoms are in slightly different environments; this inequivalency is likely due to non-planarity of the saturated ring in the 8-imino-5,6,7-trihydroquinoline chelating ligand.As with E, the 1 H NMR spectrum of F shows signals for the CH2 protons of the N,N ligand as multiplets between δ 1.57 and 2.61, while the C=NH proton is assigned as a 1H-singlet at δ 8.47.In the 13 C{ 1 H} NMR spectrum, the C=NH carbon is seen clearly at δ 160.60.Related ligand dehydrogenation involving the transformation of a R2CH-NH2 unit to a R2C=NH group has been previously reported for complexes containing pyridylalkylamines and is likely that conversion of E to F follows in a similar manner. 14

Catalytic evaluation in transfer hydrogenation
To explore the potential of the 8-amine-containing E and imine F to serve as catalysts for the transfer hydrogenation of ketones, E was used in the first instance to allow an optimization of the conditions (Table 1).The transfer hydrogenation of acetophenone to 1phenylethanol was chosen as the transformation to be screened and a preliminary study initiated to determine the optimal catalyst loading, type of base as well as the most suitable loading of base.
The reactions were typically performed with freshly distilled and degassed 2-propanol at 82 o C over 30 minutes under an atmosphere of nitrogen.Initially, a selection of different bases, t-BuOK, t-BuONa, NaOMe, KOH and NaOH, was investigated with the loading of base set at 10 mol% and the loading of E fixed at 0.1 mol% (Table 1).Of the five bases, t-BuOK was found to achieve the best conversion of 94% (entry 2, Table 1); a similarly high conversion was notably achieved when F was used in place of E with t-BuOK again as the base (entry 9, Table 1).Meanwhile the blank tests performed in the absence of base (entry 1, Table 1) or without ruthenium catalyst showed no conversion to 1phenylethanol (entry 8, Table 1).In addition, it was found that the combination of RuCl2(PPh3)2 and 8-amino-5,6,7,8tetrahydroquinoline as catalyst exhibited only a modest conversion (44%, entry 10, Table 1).To ascertain the optimal quantity of t-BuOK required, the conversion of acetophenone was monitored with the amount of E fixed at 0.1 mol% and the loading of t-BuOK varied between 2 and 20 mol% (Table 2).A peak of 94% conversion was observed after 30 minutes using 10 mol% of t-BuOK.With the amount of t-BuOK now fixed at 10 mol%, the amount of E was changed between 0.1 and 0.025 mol% resulting in conversions of 94% (0.1 mol%), 93% (0.05 mol%), 58% (0.03 mol%) and 16% (0.025 mol%) (Table 3).This lowering in conversions may be ascribed to the quicker decomposition of the lower concentration active species under strongly basic conditions. 8verall the optimal amounts of catalyst and base for the transfer hydrogenation were established as 0.1 mol% E and 10 mol% t-BuOK.
In order to investigate the tolerance of the ruthenium catalyst to air and moisture, the dry and degassed 2-propanol used initially was replaced with bench 2-propanol (analytical reagent) and the transfer hydrogenation of acetophenone carried out in the air.It was observed that the efficiency of E was greatly affected and the conversion dramatically decreased to 51% after 30 minutes with little improvement after 60 minutes (entry 1, Table 4).By contrast, This journal is © The Royal Society of Chemistry 20xx Please do not adjust margins Please do not adjust margins  replacing E with F with the conditions of the transfer hydrogenation otherwise the same (bench 2-propanol and an air atmosphere), acetophenone was converted to 1-phenylethanol in 92% yield (entry 2, Table 4).It is apparent that F is less sensitive to oxygen and apparently more tolerant to the conditions than E. Indeed, when oxygen gas was separately passed through a solution of E and t-BuOK in 2-propanol for 1 hour at 82 o C, triphenylphosphine oxide (ca.95%) was isolated (see SI) and what was presumed to be insoluble ruthenium oxide; similar deactivation of iridium catalysts has been reported. 8In addition, monitoring of the 31 P{ 1 H} NMR spectrum of E during this catalyst deactivation at intervals of 1 min, 5 min, 10 min and 30 min (see SI), also showed the gradual formation of triphenylphosphine oxide.Alternatively, if the transfer hydrogenation using E was conducted under nitrogen with dry degassed 2-propanol, a 94% conversion of acetophenone was noted (entry 3, Table 4).To examine the influence of water, the reaction mediated by E was performed under nitrogen with controlled amounts of water introduced (5 μL: entry 4, Table 4) and (10 μL: entry 5, Table 4).Only slightly lower conversions (entries 4 and 5, Table 4) were observed suggesting that E displays some tolerance to moisture.
To examine the general applicability of F as an air and moisture tolerant catalyst, a broad range of ketone substrates were screened including aryl, alkyl and cycloalkyl examples differing in their electronic and steric properties (entries 1-20, Table 5).Typically, the catalytic runs were performed in the air using the optimal conditions established of 8 mmol ketone, 0.1 mol% F, 10 mol% t-BuOK at 82 o C over 30 minutes with bench 2-propanol.To complement this study, E was employed in a parallel investigation using the same ratio of substrate: catalyst: base, but under inert conditions and using dry and degassed solvent.Notably, the hydrogenation of all twenty ketones was achieved using F with conversions between 60 and 100% (entries 1-20, Table 5).Ketones incorporating aryl groups containing both electron withdrawing (entries 1-4, Table 5) and donating groups (entry 7, Table 5) were equally well hydrogenated.Similarly, ketones containing n-alkyl groups with and without halide substituents could be readily transformed (entries 8, 11, 12, 13, Table 5).In the same way, the cyclic ketones, cyclohexanone, cyclopentanone, adamantan-2-one, cyclododecanone along with cyclic systems appended with ester and acetal groups could be transformed to their corresponding alcohols with good conversions (entries, 14-17, 19, 20, Table 5).Indeed, the lowest conversion of 60% was obtained with the bis(arene)-fused cyclopentanone, 9-fluorenone.Inspection of the results obtained using E show good conversions albeit obtained under more rigorous conditions.Furthermore, high isolated yields of 90 and 88% of tert-butyl-4-hydroxypiperidine-1-carboxylate were obtained using both E and F, respectively (entry 17, Table 5).Clearly, both electronic and steric effects associated with the particular ketone influence the reactivity of E and F. For example, the electron-rich aromatic ketones (entries 8 -10, Table 5) catalyzed by E gave somewhat higher yields of the corresponding alcohols when compared to that seen with F. Overall, this study highlights not only the versatility of imine-containing F as a transfer hydrogenation catalyst but also its ability to operate effectively in air and moisturecontaining environments, conditions that lend themselves to industrial applications.

Conclusions
In summary, synthetic routes to 8-amino-5,6,7,8-tetrahydroquinoline-containing E and imino-5,6,7-trihydroquinoline-containing F have been developed with the latter accessible by a dehydrogenative pathway involving E. Each complex has been independently assessed as a catalyst in the transfer hydrogenation of ketones to give secondary alcohols.Imine-containing F has proved an oxygen-stable catalyst for transfer hydrogenation allowing the transformations to be effectively carried out in the open air with bench solvent.By contrast, amine-containing E undergoes catalyst deactivation when exposed to air but is nevertheless an efficient catalyst in the absence of air and under dry conditions.Furthermore, the scope of E and F to mediate the transfer hydrogenation of more than twenty examples of ketones including aryl and alkyl ones as well as cycloalkyl ketones have been studied resulting in the formation of their corresponding alcohol products in good to high yields.

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General information
All manipulations involving ruthenium complexes were carried out under a nitrogen atmosphere using standard Schlenk techniques.2-Propanol (analytical reagent) was either used directly from the bottle or was dried over sodium wire, distilled and stored under nitrogen before being degassed prior to use. 1 H NMR (500 MHz), 13 [15][16][17] Complex RuCl2(PPh3)3 was synthesized according to the literature procedure. 10

Synthesis of 8-amino-5,6,7,8-tetrahydroquinoline
2][13] In the first step, 1-phenylethanamine (10.4 mL, 82.2 mmol) was added to a stirred solution containing 6,7-dihydro-5Hquinolin-8-one (12.0 g, 82.2 mmol) and NaBH(OAc)3 (25.6 g, 120.8This journal is © The Royal Society of Chemistry 20xx Please do not adjust margins Please do not adjust margins mmol) in 1,2-dichloroethane (100 mL) under a nitrogen atmosphere.The reaction mixture was stirred at room temperature for 16 h (monitored by TLC) before being quenched with a saturated aqueous solution of NaHCO3 until basic.The mixture was diluted with water and extracted with ethyl acetate (3 x 50 mL).The organic layer was dried with anhydrous Na2SO4 and concentrated under reduced pressure to afford amine intermediate 1-phenylethyl (5,6,7,8-tetrahydroquinolin-8-yl)amine as a yellow liquid (20.0 g, 95%).In the second step, the amine was taken up in acetic acid (4 mL) and dry MeOH (200 mL) and the solution flushed with nitrogen and transferred to a stainless steel 250 mL autoclave, equipped with a magnetic stirring bar.10% Palladium on carbon (5.5 g) was then added to the mixture.The autoclave was purged by three cycles of pressurization/venting with hydrogen gas (10 bar), then pressurized with hydrogen (35 bar), sealed and disconnected from the hydrogen source.The vessel was stirred and heated to 50 o C (bath temperature) for 18 h.After cooling to room temperature and venting the hydrogen pressure, the reaction mixture was filtered and concentrated under reduced pressure to afford a green oil.Concentrated HCl (35% wt%) (8 -10 mL) was then added dropwise followed by cold MeOH to give 8-amino-5,6,7,8-tetrahydroquinoline hydrochloride as a white solid.The free base could be formed by treating the HCl salt with an ammonium hydroxide solution and dichloromethane to give 8-amino-5,6,7,8-tetrahydroquinoline as a yellow oil (5.5 g, 45%

Synthesis of E 4o
RuCl2(PPh3)3 10 (400 mg, 0.42 mmol) and 8-amino-5,6,7,8tetrahydroquinoline (64.5 mg, 0.44 mmol) were treated with dichloromethane (5 mL) and the suspension stirred at room temperature for 1 h.The mixture was then concentrated and npentane (4 mL) added to afford a yellow precipitate.The precipitate was filtered, washed with n-heptane (3 × 1 mL) and dried to give E as a yellow solid (0.302 g, 85% General procedure for the transfer hydrogenation of ketones under nitrogen or air (a) Under nitrogen.The selected ketonic substrate (8.0 mmol) was dissolved in dry and degassed 2-propanol (15 mL) under a nitrogen atmosphere and the solution stirred and heated to 82 o C. On reaching this temperature, a solution of base (0.16 -1.6 mmol) in 2propanol (4 mL) was introduced followed by a solution of either E, F (2.0 -8.0 μmol) or RuCl2(PPh3)3/8-amino-5,6,7,8-tetrahydroquinoline in 2-propanol (1 mL), taking the total volume of solvent to 20 mL.At the specified reaction time (10 -60 min), 0.1 mL of the reaction mixture was sampled and immediately diluted with 0.5 mL of 2-propanol precooled to 0 o C, dodecane introduced, before being analyzed by GC.The composition of the reaction mixture was confirmed by running GC of a mixture of pure ketone, alcohol and dodecane.
(b) Under air.The selected ketonic substrate (8.0 mmol) was dissolved in bench 2-propanol (15 mL) in a vessel open to the air and the solution stirred and heated to 82 o C. On reaching this temperature, a solution of t-BuOK (0.8 mmol) in 2-propanol (4 mL) was introduced followed by a solution of either E or F (6.75 mg, 8.0 μmol) in 2-propanol (1 mL), taking the total volume of solvent to 20 mL.At the specified reaction time (10 -60 min), 0.1 mL of the reaction mixture was sampled and immediately diluted with 0.5 mL of 2-propanol precooled to 0 o C, dodecane introduced, before being analyzed by GC.The composition of the reaction mixture was confirmed by running GC of a mixture of pure ketone, alcohol and dodecane.

Synthesis of tert-butyl 4-hydroxypiperidine-1-carboxylate (entry
Please do not adjust margins Please do not adjust margins (b) Using E as catalyst.Using the same procedure and molar ratios as described in (a) above, but under an atmosphere of nitrogen and with dry and degassed 2-propanol as solvent and E as catalyst, tertbutyl-4-hydroxypiperidine-1-carboxylate 19 was isolated as a light yellow oil (1.41 g, 88%).The 1 H and 13 C NMR data obtained of the product were as given above.

X-ray crystallographic studies
The single crystal X-ray diffraction studies for E and F were carried out on a Rigaku Saturn 724+ CCD with graphite-monochromatic Mo-Kα radiation (λ = 0.71073 Å) at 173(2) K. Cell parameters were obtained by global refinement of the positions of all collected reflections (See SI, Table S1).Intensities were corrected for Lorentz and polarization effects and empirical absorption.The structures were solved by direct methods and refined by full-matrix least squares on F 2 .All hydrogen atoms were placed in calculated positions.The structural solution and refinement were performed using the SHELXL-97 package. 20lease do not adjust margins Please do not adjust margins

H H
Both amine-and imine-containing E and F have been prepared by reactions of 8-amino-5,6,7,8-tetrahydroquinoline with RuCl2(PPh3)3, the latter via a thermally induced route involving ligand oxidation/dehydrogenation. Both E and F are highly effective in the transfer hydrogenation of a wide range of ketones with F notably operating in bench quality 2-propanol and in vessels open to the air.

a
College of Chemistry and Material Science, Hebei Normal University, Shijiazhuang 050024, China b Key Laboratory of Engineering Plastics and Beijing National Laboratory for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China c CAS Research/Education Center for Excellence in Molecular Sciences, University of Chinese Academy of Sciences, Beijing 100049, China d Department of Chemistry, University of Leicester, University Road, Leicester LE1 7RH, UK # Yingmiao Ma, Jiaoyan Li and Zheng Wang made equal contributions in this work.

FChart 1 .
Ruthenium and osmium complexes that have been used effectively in transfer hydrogenation (A -D) along with the systems to be developed in this work (E and F)

Table 1 .
The effect of base and catalyst on the transfer hydrogenation of acetophenone a bDetermined by GC: based on acetophenone consumption with dodecane as the internal standard.

Table 2 .
Transfer hydrogenation of acetophenone using E at different loadings of t-BuOK a a Experimental conditions: 8 mmol acetophenone, 8 μmol E, 20 mL i-PrOH, monitored at 82 o C after 30 minutes.b Determined by GC analysis: based on acetophenone consumption with dodecane as the internal standard.

Table 3 .
Transfer hydrogenation of acetophenone at different catalyst loadings of E with t-BuOK as base a The conversion to the product was measured by GC: based on acetophenone consumption with dodecane as the internal standard. b

Table 4 .
Effects of air and water on the transfer hydrogenation of acetophenone using E or F a Conditions: 8 mmol acetophenone, 8 µmol catalyst (0.1 mol%), 0.8 mmol t-BuOK, 20 mL i-PrOH, 82 o C and open to the air or N2; conversion was monitored by GC after 10, 30 and 60 minutes.b Conditions as in 'a' but with distilled and degassed i-PrOH.

Table 5 .
Exploring the substrate scope of F as an air and moisture tolerant catalyst; the corresponding data for E under inert conditions are also tabulated a a Reaction conditions: 8 mmol ketone, 8 µmol E or F, 0.8 mmol t-BuOK, 20 mL i-PrOH, monitored at 82 o C over 30 minutes.b Using bench i-PrOH in the air; the conversion was determined by GC: based on ketone consumption with dodecane as the internal standard.c Using distilled and degassed i-PrOH under nitrogen; the conversions was determined by GC: based on ketone consumption with dodecane as the internal standard.
b,c, * ( # Yingmiao Ma, Jiaoyan Li and Zheng Wang made an equal contribution in this work.)a College of Chemistry and Material Science, Hebei Normal University, Shijiazhuang 050024, China b Key Laboratory of Engineering Plastics and Beijing National Laboratory for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China c CAS Research/Education Center for Excellence in Molecular Sciences, University of Chinese Academy of Sciences, Beijing 100049, China d Department of Chemistry, University of Leicester, University Road, Leicester LE1 7RH, UK.