Selective reduction of aldehydes and ketones

Abstract

The present invention relates to a selective reduction of specific aldehydes and ketones to their corresponding alcohols.

Claims

1. A process of production of a compound of formula (IIa): ##STR00046## wherein R is H or a C.sub.1-C.sub.4 alkyl group, or R forms together with carbon atom (2) a 4 to 8 membered aliphatic ring system, which can be substituted; R.sub.1 is H; an aromatic ring system which is unsubstituted or an aromatic ring system which is substituted; a heteroaromatic ring system which is unsubstituted or a heteroaromatic ring system which is substituted; an aliphatic ring system which is unsubstituted or an aliphatic ring system which is substituted; a heteroaliphatic ring system which is unsubstituted or a heteroaliphatic ring system which is substituted; —CH.sub.3; —CH.sub.2CH.sub.3; a C.sub.3-C.sub.10 alkyl group, which can be linear or branched and which can be partially unsaturated; or a C.sub.11-C.sub.20 alkyl group, which can be linear or branched and which can be partially unsaturated; or R.sub.1 forms together with the C—C double bond of formula (IIa) a substituted or unsubstituted 5 to 8 membered aliphatic ring system, a substituted or unsubstituted 5 to 8 membered aromatic ring system, or a substituted or unsubstituted 5 to 8 membered heteroaliphatic ring system, and R.sub.2 is H; —CH.sub.3; —CH.sub.2CH.sub.3; or a C.sub.3-C.sub.10 alkyl group, which can be linear or branched and which can be partially unsaturated, wherein the process comprises conducting a selective reduction of a compound of formula (I): ##STR00047## wherein R, R.sub.1 and R.sub.2 have the same meaning as defined in the compound of formula (IIa), in the presence of at least one transition metal catalyst of formula (III):
[M(L)(X).sub.a(L′).sub.b],  (III) wherein M is a transition metal, X is an anion, L′ is a monodentate ligand, and L is a tridentate ligand of formula (IV): ##STR00048## wherein R.sub.3 is a linear C.sub.1-C.sub.4 alkyl group, which can be substituted; a branched C.sub.3-C.sub.4 alkyl group, which can be substituted; or a phenyl group, which can be substituted, R.sub.4 is H; a linear C.sub.1-C.sub.4 alkyl group, which can be substituted; a branched C.sub.3-C.sub.4 alkyl group, which can be substituted; or OC.sub.1-C.sub.2alkyl, R5 is H; a linear C.sub.1-C.sub.4 alkyl group, which can be substituted; a branched C.sub.3-C.sub.4 alkyl group, which can be substituted; or OC.sub.1-C.sub.2alkyl, or R.sub.4 and R.sub.5 form a C.sub.4-C.sub.8 ring system, which can be aliphatic or aromatic, R.sub.6 is H; a linear C.sub.1-C.sub.4 alkyl group, which can be substituted; a branched C.sub.3-C.sub.4 alkyl group, which can be substituted; or OC.sub.1-C.sub.2alkyl, R.sub.7 is H; a linear C.sub.1-C.sub.4 alkyl group, which can be substituted; a branched C.sub.3-C.sub.4 alkyl group, which can be substituted; or OC.sub.1-C.sub.2alkyl, R.sub.8 is H or a a linear C.sub.1-C.sub.4 alkyl group, which can be substituted; a branched C.sub.3-C.sub.4 alkyl group, which can be substituted, R.sub.9 is —CH.sub.3 or —CH.sub.2CH.sub.3, m is 0, 1 or 2, and n is 0, 1 or 2, with the proviso that the sum of m+n is 1 or 2, o is 2 or 3, a is 0, 1, 2, or 3, b is 0, 1, 2, or 3, and with the proviso that the sum of a+b is 2, 3 or 4.

2. The process according to claim 1, wherein the process is carried out in the presence of at least one base.

3. The process according to claim 1, wherein the process is carried out in the presence of at least one base of formula (VIII):
M.sup.1(OC.sub.1-C.sub.5alkyl)   (VIII), wherein M.sup.1 is an alkali metal.

4. The process according to claim 1, wherein the process is carried out in the presence of at least one base of formula (VIII′):
M.sup.1(OC.sub.3-C.sub.5alkyl)   (VIII′), wherein M.sup.1 is Li, Na or K.

5. The process according to claim 1, wherein the process is carried out in the presence of at least one base selected from the group consisting of KOtBu, NaOtBu and LiOtBu.

6. The process according to claim 1, wherein the selective reduction is carried out in the presence of the catalyst of formula (III):
[M(L)(X).sub.a(L′).sub.b],  (III) wherein M is a transition metal chosen from the group consisting of Os, Co, Ru and Fe, and X is a halogen anion, a carboxylate, borohydride, hydride, BF.sub.4.sup.− or PF.sub.6.sup.−, and L′ is a monodentate phosphine ligand, and L is a tridentate ligand of formula (IV): ##STR00049## wherein R.sub.3 is —CH.sub.3 or —CH.sub.2CH.sub.3, R.sub.4 is H; —CH.sub.3.sup.−; —CH.sub.2CH.sub.3.sup.−; —OCH.sub.3 or —OCH.sub.2CH.sub.3, R.sub.5 is H; —CH.sub.3.sup.−; —CH.sub.2CH.sub.3.sup.−; —OCH.sub.3 or —OCH.sub.2CH.sub.3, or R.sub.4, and R.sub.5 form a C.sub.4-C.sub.8 ring system, which can be aliphatic or aromatic, R.sub.6 is H; —CH.sub.3.sup.−; —CH.sub.2CH.sub.3.sup.−; —OCH.sub.3 or —OCH.sub.2CH.sub.3, R.sub.7 is H; —CH.sub.3.sup.−; —CH.sub.2CH.sub.3.sup.−; —OCH.sub.3 or —OCH.sub.2CH.sub.3, R.sub.8 is H; —CH.sub.3 or —CH.sub.2CH.sub.3, R.sub.9 is —CH.sub.3 or —CH.sub.2CH.sub.3, m is 0, 1 or 2, and n is 0, 1 or 2, with the proviso that the sum of m+n is 1 or 2, o is 2 or 3, a is 0, 1, 2, or 3, and b is 0, 1, 2, or 3, with the proviso that the sum of a+b is 2 or 3.

7. The process according to claim 1, wherein the catalyst is a catalyst of formula (III′)
M(L)(X).sub.2(L′),   (III′) wherein M is Ru or Fe, X is Cl.sup.31, L′ is PPh.sub.3, and L is a tridentate ligand selected from the group consisting of the ligands of formulae (IVa)-(IVI): ##STR00050##

8. The process according to claim 1, wherein the catalyst of formula (III) is used in an amount of 0.001 -0.5 mol-%, based on the number of moles of the compounds of formula (I).

9. The process according to claim 1, wherein the reduction is a transfer hydrogenation.

10. The process according to claim 1, wherein the process is carried out with H.sub.2 gas.

11. The process according to claim 10, wherein the process is carried out at a pressure of 10 to 50 bar.

12. The process according to claim 1, wherein the process is carried out at an elevated temperature.

13. The process according to claim 12, wherein the elevated temperature is 30-150° C.

14. The process according to claim 6, wherein X in the catalyst of formula (III) is an acetate, a benzoate or BH.sub.4−.

15. A catalyst of formula (III):
[M(L)(X).sub.a(L′).sub.b],  (III) wherein M is a transition metal chosen from the group consisting of Ru and Fe, and X is a halogen anion, and L′ is triphenylphosphine, and L is a tridentate ligand of formula (IV) ##STR00051## wherein R.sub.3 is —CH.sub.3 or —CH.sub.2CH.sub.3, R.sub.4 is H; —CH.sub.3.sup.−; —CH.sub.2CH.sub.3.sup.−; —OCH.sub.3 or —OCH.sub.2CH.sub.3, R.sub.5 is H or —CH.sub.3, or R.sub.4, and R.sub.5 form a C.sub.4-C.sub.8 ring system, which can be aliphatic or aromatic, R.sub.6 is H or —CH.sub.3, R.sub.7 is H or —CH.sub.3, R.sub.8 is H or —CH.sub.3, R.sub.9 is —CH.sub.3, m is 0 or 1, and n is 0 or 1, with the proviso that the sum of m+n is 1, o is 2, a is 1 or 2, b is 1 or 2, with the proviso that the sum of a+b is 3.

16. The catalyst according to claim 15, wherein X in formula (III) is Cl.sup.−.

17. A catalyst of formula (III′):
M(L)(X).sub.2(L′),   (III′) wherein M is Ru or Fe, X is Cl.sup.−, L′ is PPh.sub.3, and L is a tridentate ligand selected from the group consisting of the ligands of formulae (IVa)-(IVI): ##STR00052##

Description

EXAMPLES

(1) General:

(2) Transition metal precursors, reagent and solvents were obtained from commercial sources and used as received unless noted otherwise. GC analysis was carried out on an Agilent 7890B GC system with a HP-5 normal-phase silica column, using Helium as a carrier gas and dodecane as an internal standard. NMR spectra were recorded on a Bruker AV400, Bruker AV300 or Bruker Fourier300 NMR spectrometer. .sup.1H and .sup.13C-NMR spectra were referenced w.r.t. the solvent signal. Chemical shifts are in ppm, coupling constants in Hz. HR-MS measurements were recorded on an Agilent 6210 Time-of-Flight LC/MS, peaks as listed correspond to the highest abundant peak and are of the expected isotope pattern.

(3) Ligand Synthesis

Example 1: 2-(ethylthio)-N-((6-methylpyridin-2-yl)methyl)ethan-1-amine [ligand of Formula (IVg)]

(4) ##STR00030##

(5) 6-methylpyridine-2-carboxaldehyde (3.0 g, 25 mmol) and 2-(Ethylthio)ethylamine (2.63 g, 2.8 mL, 25 mmol) were dissolved in CH.sub.2Cl.sub.2 (75 mL), then Na.sub.2SO.sub.4 (7.1 g, 50 mmol) was added. The suspension was stirred at room temperature overnight, filtered and the filter cake was washed with CH.sub.2Cl.sub.2. The combined volatiles were removed in vacuo, yielding 5.45 g of imine as brown oil, which was used directly in the following step without further purification. Therefore, the imine was dissolved in MeOH (50 mL) and NaBH.sub.4 (1.9 g, 51 mmol) was added portionwise at 0° C. The mixture was stirred at room temperature for another hour, after which the solvent was removed in vacuo. Then CH.sub.2Cl.sub.2 (20 mL) and water (20 mL) were added. The aqueous layer was extracted with CH.sub.2Cl.sub.2 (three times 20 mL). The combined organic layers were washed with brine (20 mL) and dried over Na.sub.2SO.sub.4. Evaporating the solvent and drying in vacuo yielded 4.95 g (94%) of the ligand of formula (IVg) as an orange oil, which was directly used for complex synthesis.

(6) .sup.1H-NMR (300 MHz, CDCl.sub.3): δ 7.45 (t, 1H, J=7.6, CH.sub.arom), 7.07 (d, 1H, J=7.8, CH.sub.arom), 6.96 (d, 1H, J=7.5, CH.sub.arom), 3.84 (s, 2H), 2.80 (dt, 2H), 2.66 (dt, 2H), 2.48 (m, 5H), 1.23 (t, 3H, J=7.4) ppm. .sup.13C-NMR (75 MHz, CDCl.sub.3): δ 158.9, 157.8, 136.5, 121.3, 118.9, 54.9, 48.2, 31.8, 25.6, 24.4 ppm.

(7) HRMS (ESI+): calculated for C.sub.11H.sub.18N.sub.2S: 210.1191; found 211.1265 (M+H), 233.1082 (M+Na).

Example 2: 2-(methylthio)-N-((pyridin-2-yl)methyl)ethan-1-amine [ligand of Formula (IVa)]

(8) ##STR00031##

(9) The ligand of formula (IVa) was prepared in analogy to Example 1.

(10) .sup.1H NMR (300 MHz, CD.sub.2Cl.sub.2) δ 8.43 (ddd, 1H, J=4.9 Hz, J=1.8 Hz, J=0.9 Hz, CH.sub.arom), 7.57 (td, 1H, J=7.7 Hz, J=1.8 Hz, CH.sub.arom), 7.24 (d, 1H, J=7.8 Hz, CH.sub.arom), 7.07 (dd, 1H, J=7.5 Hz, J=5.0.7 Hz, CH.sub.arom), 3.81 (s, 2H), 2.75 (td, 2H, J=6.5 Hz, J=0.8 Hz, CH.sub.2), 2.58 (td, 2H, J=6.5 Hz, J=0.6 Hz, CH.sub.2), 1.99 (s, 3H, CH.sub.3) ppm.

(11) .sup.13C NMR (75 MHz, CD.sub.2Cl.sub.2): δ 160.2, 149.1, 136.2, 121.9, 121.7, 54.8, 47.6, 34.4, 15.0 ppm.

(12) HRMS (ESI+): calculated for C.sub.9H.sub.14N.sub.2S: 182.0878 (M+H): 183.0950; found 183.0950 (M+H).

Example 3: 2-(ethylthio)-N-((pyridin-2-yl)methyl)ethan-1-amine [ligand of Formula (IVb)]

(13) ##STR00032##

(14) The ligand of formula (IVb) was prepared according to Example 1.

(15) .sup.1H NMR (300 MHz, CD.sub.2Cl.sub.2): δ 8.51 (ddd, 1H, J=4.8 Hz, J=1.5 Hz, J=0.9 Hz, CH.sub.arom), 7.64 (td, 1H, J=7.5 Hz, J=1.8 Hz, CH.sub.arom), 7.32 (d, 1H, J=7.8 Hz, CH.sub.arom), 7.19-7.12 (m, 1H, CH.sub.arom), 3.88 (s, 2H, CH.sub.2), 2.85-2.79 (m, 2H, CH.sub.2), 2.72-2.66 (m, 2H, CH.sub.2), 2.52 (q, 2H, J=7.5 Hz, CH.sub.2), 2.09 (d, 1H, J=9.6 Hz, NH), 1.23 (t, 3H, J=7.4 Hz, CH.sub.3) ppm.

(16) .sup.13C NMR (75 MHz, CD.sub.2Cl.sub.2): δ 161.6, 149.7, 136.8, 122.5, 122.3, 55.4, 48.9, 32.5, 26.2, 15.3 ppm.

(17) HRMS (ESI+): calculated for C.sub.10H.sub.16N.sub.2S: 196.1034; (M+H): 197.1107; (M+Na): 219.0926; found 197.1108 (M+H), 219.0929 (M+Na).

Example 4: 2-(ethylthio)-N-((6-methoxy-pyridin-2-yl)methyl)ethan-1-amine [ligand of Formula (IVk)]

(18) ##STR00033##

(19) The ligand of formula (IVk) was prepared according to Example 1 in a 84% yield. .sup.1H-NMR (300 MHz, CDCl.sub.3): δ 7.54 (dd, 1H, J=8.1, J=7.4, CH.sub.arom), 6.87 (d, 1H, J=7.2), 6.63 (d, 1H, J=8.1), 4.55 (s, NH), 3.92 (s, 3H), 3.90 (m, NH), 3.80 (s, 2H), 2.83 (t, 2H, J=6.5), 2.66 (t, 2H, J=6.5), 2.52 (t, 2H, J=7.5), 1.23 (t, 3H, J=7.2) ppm. .sup.13C-NMR (75 MHz, CDCl.sub.3): δ 163.8, 157.3, 138.8, 114.5, 108.7, 54.3, 53.2, 48.1, 32.0, 25.8, 14.8 ppm.

(20) HRMS (ESI+): calculated for C.sub.11H.sub.18N.sub.2OS: 227.1213 (M+H); found 227.1217 (M+H), 227.1217 (M+Na).

Example 5: 2-(ethylthio)-N-((quinolin-2-yl)methyl)ethan-1-amine [ligand of Formula (IVI)]

(21) ##STR00034##

(22) The ligand of formula (IVI) was prepared according to Example 1 and purification by Kugelrohr distillation.

(23) .sup.1H NMR (300 MHz, CD.sub.2Cl.sub.2): δ 8.13 (d, 1H, J=8.4 Hz, CH.sub.arom), 8.00 (d, 1H, J=8.7 Hz, CH.sub.arom), 7.82 (dd, 1H, J=8.3 Hz, J=1.5 Hz, CH.sub.arom), 7.69 (ddd, 3H, J=8.5 Hz, J=6.9 Hz, J=1.5 Hz, CH.sub.arom), 7.55-7.45 (m, 2H, CH.sub.arom), 4.08 (s, 2H, CH.sub.2), 2.89 (td, 2H, J=6.8 Hz, J=1.2 Hz, CH.sub.2), 2.73 (td, 2H, J=6.4 Hz, J=0.9 Hz, CH.sub.2), 2.55 (q, 2H, J=7.4 Hz, CH.sub.2), 2.14 (d, 1H, J=11.4 Hz, NH), 1.24 (t, 3H, J=7.4 Hz, CH.sub.3) ppm.

(24) .sup.13C NMR (75 MHz, CD.sub.2Cl.sub.2): δ 161.5, 136.7, 129.8, 129.5, 128.1, 127.9, 126.5, 121.0, 56.0, 49.1, 32.6, 26.2, 15.29 ppm.

(25) HRMS (ESI+): calculated for C.sub.14H.sub.18N.sub.2S: 246.1191; (M+H): 247.1264; found 247.1267 (M+H).

Example 6: 2-(ethylthio)-N-(1-(pyridin-2-yl)ethyl)ethan-1-amine [ligand of Formula (IVe)]

(26) ##STR00035##

(27) The ligand of formula (IVe) was prepared according to Example 1 with imine formation performed in the presence of 5 mol % of p-toluenesulfonic acid in toluene under reflux conditions and purification by Kugelrohr distillation.

(28) .sup.1H NMR (300 MHz, CD.sub.2Cl.sub.2): δ 8.51 (ddd, 1H, J=4.8 Hz, J=1.9 Hz, J=1.0 Hz, CH.sub.arom), 7.64 (td, 1H, J=7.6 Hz, J=1.8 Hz, CH.sub.arom), 7.32 (dt, 1H, J=7.8 Hz, J=1.1 Hz, CH.sub.arom), 7.14 (ddt, 1H, J=7.5 Hz, J=4.8 Hz, J=1.2 Hz, CH.sub.arom), 3.84 (q, 1H, J=6.9 Hz, CH), 2.71-2.55 (m, 4H, CH.sub.2), 2.47 (q, 2H, J=7.4 Hz, CH.sub.2), 2.05 (d, 1H, J=39.3 Hz, NH), 1.34 (d, 3H, J=6.9 Hz, CH.sub.3), 1.20 (d, 3H, J=7.5 Hz, CH.sub.3) ppm. .sup.13C NMR (75 MHz, CD.sub.2Cl.sub.2): δ 165.4, 149.7, 136.9, 122.3, 121.4, 59.7, 47.1, 32.7, 26.1, 23.2, 15.2 ppm.

(29) HRMS (ESI+): calculated for C.sub.11H.sub.18N.sub.2S: 210.1191; (M+H), 211.1264; (M+Na): 233.1083; found 211.1265 (M+H), 233.1083 (M+Na).

Example 7: 2-(ethylthio)-N-methyl-N-(pyridin-2-ylmethyl)ethan-1-amine [ligand of Formula (IVd)]

(30) ##STR00036##

(31) 2-(Ethylthio)-N-(pyridin-2-ylmethyl)ethan-1-amine (ligand of formula (IVb), 850 mg, 3.75 mmol), formal in (4 mL of 37% wt formaldehyde in water) and formic acid (4 mL) were stirred at 70° C. overnight. All volatiles were removed in vacuo and CH.sub.2Cl.sub.2 (10 mL) and saturated NaHCO.sub.3 solution (10 mL) were added. The aqueous layer was extracted with CH.sub.2Cl.sub.2 (three times 10 mL). The combined organic layers were washed with brine (20 mL) and dried over Na.sub.2SO.sub.4. Removal of the solvent yielded 754 mg (3.59 mmol, 96%) of 2-(ethylthio)-N-methyl-N-(pyridin-2-ylmethyl)ethan-1-amine as an orange liquid (p=1.081 g cm.sup.−3). The ligand of formula (IVb) was further purified by Kugelrohr distillation.

(32) .sup.1H-NMR (300 MHz, CDCl.sub.3): δ 8.46 (d, 1H, J=5.1, CH.sub.arom), 7.58 (dt, 1H, J=7.8, J=1.8, CH.sub.arom), 7.38 (d, 1H, J=7.8, CH.sub.arom), 7.08 (ddd, 1H, J=7.5, J=4.8, J=1.2, CH.sub.arom), 3.62 (S, 2H), 2.62 (S, 4H), 2.45 (q, 2H, J=7.4), 2.31 (s, 3H, N—CH.sub.3), 1.17 (t, 3H, J=7.4) ppm.

(33) .sup.13C NMR (101 MHz, CDCl.sub.3): δ 159.2, 149.0, 136.4, 123.1, 122.0, 63.6, 57.3, 56.9, 42.4, 31.9, 29.3, 26.1, 14.8 ppm.

(34) HRMS (ESI+): calculated for C.sub.11H.sub.18N.sub.2S: 210.1191; found 211. 1265 (M+H), 233.1084 (M+Na).

Catalyst Synthesis

Example 8: Ru(6-MeNNS.SUP.Et.)(PPh.SUB.3.)Cl.SUB.2

(35) ##STR00037##

(36) RuCl.sub.2(PPh.sub.3).sub.3 (1 g, 1.04 mmol) and the ligand of formula (IVg) (obtained from Example 1) (231.4 mg, 1.1 mmol) were placed in a 25 mL Schlenk tube under argon atmosphere, and dissolved in dry diglyme (2 mL). The reaction mixture was heated to 165° C. for 2 h, allowed to cool down to room temperature and stored at −18° C. to precipitate further overnight. Cold Et.sub.2O (2 mL) was added while cooling with a dry ice/iso-propanol bath. The precipitate was filtrated by cannula, and washed with Et.sub.2O (5 times 2 mL). The orange powder was dried in vacuo, affording 530 mg (79%) of Ru(6-MeNNS.sup.Et)(PPh.sub.3)Cl.sub.2 as an orange powder. An equilibrium of two conformations of Ru(6-MeNNS.sup.Et)(PPh.sub.3)Cl.sub.2 are existent in solution, delivering a doubled set of signals in NMR. For .sup.1H-NMR only data of the major conformation is given due to overlapping signals.

(37) .sup.1H-NMR (300 MHz, CD.sub.2Cl.sub.2): δ 7.67-7.16 (m, 17H, CH.sub.arom), 7.01 (d, 1H, J=7.8, CH.sub.arom), 5.65 (m, 2H), 4.47 (m, 1H), 3.5 (m, 1H), 3.34 (m, 1H), 3.22 (d, 1H, J=11.1), 2.98 (m, 1H), 2.59 (m, 1H), 1.53 (m, 2H), 0.87 (t, 3H, J=7.5) ppm.

(38) .sup.31P-NMR (122 MHz, CD.sub.2Cl.sub.2): δ 48.8, 45.8 ppm.

(39) HRMS (ESI+): calculated for C.sub.29H.sub.32Cl.sub.2N.sub.2PRuS (M+H): 644.0518; found 644.0518 (M+H), 667.0412 (M+Na).

Example 9: Ru(NNS.SUP.Me.)(PPh.SUB.3.)Cl.SUB.2

(40) ##STR00038##

(41) Ru(NNS.sup.Me)(PPh.sub.3)Cl.sub.2 was prepared according to Example 8. An equilibrium of two conformations was obtained.

(42) .sup.1H-NMR (300 MHz, CD.sub.2Cl.sub.2): δ 8.47 (d, 1H, J=5.7), 7.72 (m, 1H), 7.56 (m, 6H), 7.32 (m, 10H), 6.86 (t, 1H, J=6.3), 5.45 (s, broad, 1H, NH), 5.20 (t, 1H, J=12.6), 4.38 (m, 1H), 3.41 (m, 2H), 3.26 (d, 1H, J=11.1), 2.55 (m, 1H), 1.50 (s, 3H).

(43) .sup.31P-NMR (122 MHz, CD.sub.2Cl.sub.2): δ 51.8, 50.7

(44) HRMS (ESI+): calculated for C.sub.27H.sub.29C.sub.12N.sub.2PRuS: 616.0210 (M+); found 616.0197 (M+).

Example 10: Ru(NNS.SUP.Et.)(PPh.SUB.3.)Cl.SUB.2

(45) ##STR00039##

(46) Ru(NNS.sup.Et)(PPh.sub.3)Cl.sub.2 was prepared according to Example 8. An equilibrium of two conformations was obtained in 84% yield.

(47) .sup.1H-NMR (300 MHz, CD.sub.2Cl.sub.2): δ 8.45 (d, 1H, J=5.7), 7.72 (m, 1H), 7.57 (m, 6H), 7.34 (m, 10H), 6.86 (t, 1H, J=6.3), 5.49 (s, broad, 1H, NH), 5.22 (t, 1H, J=13.5), 4.40 (m, 1H), 3.47 (m, 2H), 3.36 (m, 1H), 2.80 (m, 1H), 2.52 (m, 1H), 1.27 (m, 2H), 1.19 (m, 1H), 0.95 (t, 3H, J=7.5)

(48) .sup.31P-NMR (122 MHz, CD.sub.2Cl.sub.2): δ 51.8, 50.7

(49) HRMS (ESI+): calculated for C.sub.28H.sub.31C.sub.12N.sub.2PRuS: 630.0366 (M+); found 630.0388 (M+), 653.0270 (M+Na).

Example 11: Ru(6-MeONNS.SUP.Et.) (PPh.SUB.3.)Cl.SUB.2

(50) ##STR00040##

(51) Ru(6-MeONNS.sup.Et)(PPh.sub.3)Cl.sub.2 was prepared according to Example 8. An equilibrium of two conformations was obtained in 88% yield.

(52) .sup.1H-NMR (400 MHz, CD.sub.2Cl.sub.2): δ 7.94 (m, 2H), 7.65 (m, 2H), 7.42-7.14 (m, 12H), 7.07 (d, 1H, J=7.6), 6.56 (d, 1H, J=8.4), 5.56-5.36 (m, 2H), 4.46 (m, 1H), 3.50-3.19 (m, 2H), 3.21 (dd, 1H, J=11.0, J=2.2), 2.87 (m, 1H), 2.83 (s, 3H, twinned), 2.50 (m, 1H), 1.33 (m, 1H), 0.87 (t, 3H, twinned, overlapping)

(53) .sup.31P-NMR (122 MHz, CD.sub.2Cl.sub.2): δ 47.2, 45.9

(54) HRMS (ESI+): calculated for C.sub.29H.sub.32C.sub.12N.sub.2OPRuS (M+H): 660.0468; found: 660.0469 (M+H), 683.0363 (M+Na).

Example 12: Ru(QuinNS.SUP.Et.) (PPh.SUB.3.)Cl.SUB.2

(55) ##STR00041##

(56) Ru(QuinNS.sup.Et)(PPh.sub.3)Cl.sub.2 was prepared according to Example 8. An equilibrium of two conformations was obtained.

(57) .sup.1H-NMR (300 MHz, CD.sub.2Cl.sub.2): δ 8.12 (d, 2H, J=8.4), 7.74-6.66 (m, 19H), 5.90 (s, broad, NH), 5.74 (t, 1H, J=13.3), 4.72 (m, 1H), 3.58-3.40 (m, 3H), 3.05 (m, 1H), 2.72 (m, 1H), 1.66 (m, 1H), 0.95 (t, 3H, J=7.5)

(58) .sup.31P NMR (122 MHz, CD.sub.2Cl.sub.2): δ 48.90, 45.86

(59) HRMS (ESI+): calcd. for C.sub.32H.sub.33Cl.sub.2N.sub.2PRuS: 680.0519 (M+); found 680.0500 (M+).

Example 13: Ru(N-Me-NS.SUP.Et.) (PPh.SUB.3.)Cl.SUB.2

(60) ##STR00042##

(61) Ru(N-Me-NS.sup.Et)(PPh.sub.3)Cl.sub.2 was prepared according to Example 8. An equilibrium of two conformations was obtained.

(62) .sup.1H-NMR (300 MHz, CD.sub.2Cl.sub.2): δ 8.53 (d, 1H, J=5.7), 7.72 (m, 1H), 7.57 (m, 6H), 7.33 (m, 10H), 6.85 (t, 1H, J=6.6), 5.35 (m, 1H), 4.93 (s, broad, NH), 3.68-3.31 (m, 3H), 2.81 (m, 1H), 2.53 (m, 1H), 1.80 (d, 3H, J=6.9), 1.25 (m, 1H), 0.97 (t, 3H, J=7.2)

(63) .sup.31P NMR (122 MHz, CD.sub.2Cl.sub.2): δ 51.5, 50.3

(64) HRMS (ESI+): calculated for C.sub.29H.sub.33Cl.sub.2N.sub.2PRuS: 644.0518 (M+); found 644.0513 (M+).

Example 14: Ru(NN.SUP.Me.S.SUP.Et.)(PPh.SUB.3.)Cl.SUB.2

(65) ##STR00043##

(66) Ru(NN.sup.MeS.sup.Et)(PPh.sub.3)Cl.sub.2 was prepared according to Example 8. An equilibrium of two conformations was obtained in 54%.

(67) .sup.1H-NMR (300 MHz, CD.sub.2Cl.sub.2): δ 8.11 (d, 1H, J=5.7), 7.92 (m, 6H), 7.47 (dt, 1H, J=7.5, J=1.5), 7.30 (m, 10H), 6.56 (t, 1H, J=7.5), 5.67 (d, 1H, J=14.4), 3.87 (d, 1H, J=14.4), 3.15 (s, 3H), 2.86 (m, 1H), 2.70 (m, 1H), 2.30 (m, 2H), 0.74 (m, 1H), 0.67 (t, 3H, J=6.9), 0.42 (m, 1H)

(68) .sup.31P-NMR (122 MHz, CD.sub.2Cl.sub.2): δ 51.4, 50.4

(69) HRMS (ESI+): calculated for C.sub.29H.sub.33Cl.sub.2N.sub.2PRuS: 644.0518 (M+); found 644.0505 (M+).

(70) Hydrogenation Reactions

Example 15: Selective Hydrogenation of Cinnamaldehyde

(71) ##STR00044##

(72) 4 mL glass reaction vials and stirring bars were dried overnight at 110° C. The reaction vessels were charged with LiOtBu (1 mg, 0.0125 mmol, 1.25 mol %), closed with PTFE/rubber septa, placed in a multiple reactor inlet suitable for a pressure vessel, and brought under argon atmosphere by three vacuum-argon cycles. With a syringe Ru(NNS.sup.Et)(PPh.sub.3)Cl.sub.2 (catalyst of Example 10) was added as stock solution in iPrOH (1 mL, 0.0005 mol/L, 0.05 mol %), followed by a solution of cinnamaldehyde in iPrOH (1 mL, 1 mol/L, 1 mmol). The reaction mixtures were transferred to an argon-filled pressure vessel, which was immediately flushed with three nitrogen and three hydrogen cycles, then pressurized to 30 bar hydrogen, heated to 80° C. and stirred for 16 h. After that, the pressure vessel was allowed to cool down to room temperature and depressurized. The reaction mixtures were filtered over silica and rinsed with ethanol (2 mL) after which dodecane was added as an internal standard prior to GC analysis. The products are determined based on GC analysis retention time. The given values for conversion (C), yield (Y), and selectivity (S) [%] are mol % with regard to the initial cinnamaldehyde amount, and corrected by dodecane.

(73) The results are summarized in Table 1

(74) The same conditions were chosen for the hydrogenation wherein the catalyst of example 9 (Ru(NNS.sup.Me)(PPh.sub.3)Cl.sub.2 was used. These results are summarized in Table 2

(75) TABLE-US-00001 TABLE 1 Cinnamyl- 3-phenyl-1- Base Conversion alcohol propanol Exp 1-2 mol % C [%] Y [%] S [%] Y [%] S [%] 15a — 19 0 0 0 0 15b LiOtBu 96 72 75 4 4 15c KOtBu 99 84 85 5 5 15d CaCO.sub.3 16 2 13 0 0 15e Na(COOPh) 15 0 0 0 0

(76) TABLE-US-00002 TABLE 2 Cinnamyl- 3-phenyl-1- Base Conversion alcohol propanol Exp 1-2 mol % C [%] Y [%] S [%] Y [%] S [%] 15f — 19 0 0 0 0 15g LiOtBu >99 78 78 3 3 15h KOtBu >99 69 69 3 3 15i K.sub.2CO.sub.3 52 23 43 0 0

Example 16

(77) 4 mL glass reaction vials and stirring bars were dried overnight at 110° C. The reaction vessels were charged with LiOtBu (1 mg, 0.0125 mmol, 1.25 mol %), closed with PTFE/rubber septa, placed in a multiple reactor inlet suitable for a pressure vessel, and brought under argon atmosphere by three vacuum-argon cycles. With a syringe the reaction vessels were charged with the catalyst as stock solution in iPrOH (1 mL, 0.0005 mol/L, 0.05 mol %), followed by a solution of cinnamaldehyde in iPrOH (1 mL, 1 mol/L). The reaction mixtures were transferred to an argon-filled pressure vessel, which was immediately flushed with three nitrogen and three hydrogen cycles, then pressurized to 30 bar hydrogen, heated to 80° C. and stirred for 16 h. After that, the pressure vessel was allowed to cool down to room temperature and depressurized. The reaction mixtures were filtered over silica and rinsed with ethanol (2 mL) after which dodecane was added as an internal standard prior to GC analysis. The products are determined based on GC analysis retention time. The given values for conversion (C), yield (Y), and selectivity (S) [%] are mol % with regard to the initial cinnamaldehyde amount, and corrected by dodecane.

(78) Catalyst screening experiments with KOtBu were performed accordingly.

(79) TABLE-US-00003 TABLE 3 Cat. Base Con- Cinnamyl- 3-phenyl-1- 0.05 1-2 version alcohol propanol Exp. mol % mol % C [%] Y [%] S [%] C [%] Y [%] 16a Cat of LiOtBu 100 77 77 3 3 Exp. 9 16b Cat of KOfBu 100 75 75 4 4 Exp. 9 16c Cat of LiOtBu 100 69 69 8 8 Exp. 10 16d Cat of KOtBu 100 67 67 10 10 Exp. 10 16e Cat of KOtBu 100 64 64 3 3 Exp. 8 16f Cat of LiOtBu 100 65 65 0 0 Exp. 13 16g Cat of KOtBu 100 74 74 5 5 Exp. 13 16hi Cat of LiOtBu 100 81 81 3 3 Exp. 14 16i Cat of KOtBu 100 46 46 2 2 Exp. 14

Example 17: Hydrogenation of Different Aldehydes/Ketones

(80) The compounds of formulae (A), (B) and (C) were hydrogenated.

(81) ##STR00045##

(82) 4 mL glass reaction vials and stirring bars were dried overnight at 110° C., closed with PTFE/rubber septa, placed in a multiple reactor inlet suitable for a pressure vessel, and brought under argon atmosphere by three vacuum-argon cycles. With a syringe the reaction vessels were charged with the catalyst as stock solution in iPrOH (1 mL, 0.0005 mol/L, 0.05 mol %), followed by a solution of the compound A, B or C in iPrOH (1 mL, 1 mol/L, 1 mmol). After that a solution of freshly sublimed the base in THF (12.5 μL, 1 mol/L, 0.0125 mmol, 1.25 mol %) was added with a Hamilton syringe. The reaction mixtures were transferred to an argon-filled pressure vessel, which was immediately flushed with three nitrogen and three hydrogen cycles, then pressurized to 30 bar hydrogen, heated to 80° C. and stirred for 16 h. After that the pressure vessel was cooled down to room temperature and depressurized. The reaction mixtures were filtered over silica and rinsed with ethanol (2 mL). The products are determined based on GC analysis retention time. The given values [%] are related to GC area %. The results are summarized in the following tables 4a, 4b and 4c.

(83) TABLE-US-00004 TABLE 4a hydrogenation of the compound of formula (A) Product Cat. Base Conversion Compund A′ Exp. 0.05 mol % 1-2 mol % C [%] Y [%] S [%] 17a Cat of Exp. 10 KOtBu 97 97 100

(84) TABLE-US-00005 TABLE 4b hydrogenation of the compound of formula (B) Product Cat. Base Conversion Compund B′ Exp. 0.05 mol % 1-2 mol % C [%] Y [%] S [%] 17b Cat of Exp. 9 LiOtBu 100 100 100 17c Cat of Exp. 9 KOtBu 100 100 100 17d Cat of Exp. 10 LiOtBu 100 100 100 17e Cat of Exp. 10 KOtBu 100 100 100

(85) TABLE-US-00006 TABLE 4c hydrogenation of the compound of formula (C) Product Cat. Base Conversion Compund C′ Exp. 0.05 mol % 1-2 mol % C [%] Y [%] S [%] 17f Cat of Exp. 9 LiOtBu 99 96 96 17g Cat of Exp. 9 KOtBu 100 96 96 17h Cat of Exp. 10 LiOtBu 99 94 95 17i Cat of Exp. 10 KOtBu 99 93 94

Example 18: Hydrogenation of Benzaldehyde

(86) A 100 mL hastelloy autoclave with mechanical stirrer was charged with the catalyst of example 10 (3 mg, 0.005 mmol, 0.05 mol %), benzaldehyde (1.06 g, 10 mmol, 1.01 mL), 20 mL of isopropanol, and freshly sublimed KOtBu (14 mg, 0.125 mmol, 1.25 mol %) under an argon atmosphere. The autoclave vessel was flushed with nitrogen three times, pressurized to 30 bar H.sub.2 and heated to 80° C. After stirring for 1 hour the vessel was allowed to cool down to room temperature and depressurized.

(87) The reaction mixture was filtered over SiO.sub.2, and concentrated in vacuo. Kugelrohr distillation under vacuum afforded 1.08 g (99% yield) of benzyl alcohol as colourless liquid.

Example 19: Hydrogenation of Furfural

(88) Furfural was hydrogenated according to Example 18 and afforded 0.95 g furfuryl alcohol (99%) as pale yellow liquid.

Example 20: Hydrogenation of 5-(Hydroxymethyl)furfural

(89) 5-(hydroxymethyl)furfural was hydrogenated according to Example 18, with a catalyst amount of 0.5 mol % and a base amount of 5 mol %. The hydrogenation afforded 1.20 g (93%) of 2,5-di(hydroxylmethyl)furan as a white crystalline solid.

Example 21: Hydrogenation of 3-(2-Furyl)acrolein

(90) 3-(2-Furyl)acrolein was hydrogenated according to Example 18 and afforded 1.23 g 3-(2-furyl)-2-propen-1-ol (99% yield) as colourless oil (mixture of isomers).

Example 22: Hydrogenation of 1-Cyclohexene-1-carboxaldehyde

(91) 1-Cyclohexene-1-carboxaldehyde was hydrogenated according to Example 18 and afforded 1.1 g 1-cyclohexene-1-methanol (99% yield) as colourless oil.

Example 23: Hydrogenation of Cinnamaldehyde

(92) Cinnamaldehyde (F) was hydrogenated according to Example 18 using 25 mmol of substrate, and 50 mL of isopropanol. The resulting yellow oil was purified by column chromatography (SiO2; n-pentane:ethyl acetate 4:1), yielding 3.16 g (94%) of cinnamyl alcohol as white crystals.

Example 24: Hydrogenation of Perillaldehyde

(93) Perillaldehyde was hydrogenated according to Example 18. The product was isolated by column chromatography (SiO2; heptane:ethyl acetate 5:1), yielding 1.48 g (96%) of perillyl alcohol as a colourless liquid.

(94) 1H NMR (300 MHz, CDCl.sub.3): δ 5.63 (broad, 1H), 4.65 (m, 2H), 3.93 (s, 2H), 2.10-1.70 (m, 5H), 1.67 (s, 3H), 1.50 (s, broad, 1H), 1.43 (m, 1H). 13C NMR (75 MHz, CDCl3): δ 149.8, 137.2, 122.4, 108.6, 67.2, 41.1, 30.4, 27.5, 26.1, 20.8. HRMS (ESI+): calculated for C10H16O: 153.12739 (M+H); found 153.12757 (M+H)+, 175.10946 (M+Na)+.

Example 25: Hydrogenation of 4,5,6,7-tetrahydro-4-benzofuranone

(95) 4,5,6,7-tetrahydro-4-benzofuranone was hydrogenated according to Example 18, affording 1.37 g (99%) of 4,5,6,7-tetrahydro-4-benzofuranol as a colourless liquid. .sup.1H-NMR (300 MHz, CDCl.sub.3): δ 7.31 (m, 1H), 6.44 (d, J.sub.H-H=2.0, 1H), 4.77 (t, J.sub.H-H=4.4, 1H), 2.60 (m, 2H), 2.09-1.81 (m, 5H). .sup.13C NMR (75 MHz, CDCl.sub.3): δ 152.6, 141.1, 120.0, 109.1, 64.1, 32.7, 23.0, 19.0. HRMS (ESI+): calculated for C.sub.8H.sub.10O.sub.2: 139.07536 (M+H); found 139.07548 (M+H), 161.05749 (M+Na).

Example 26: Hydrogenation of 4-(2-Furanyl)-3-buten-2-one

(96) 4-(2-Furanyl)-3-buten-2-one was hydrogenated according to Example 18, affording 1.28 g (93%) of 4-(2-furanyl)-3-buten-2-ol.

(97) 1H NMR (300 MHz, CD.sub.2Cl.sub.2): δ 7.38 (d, J.sub.H-H=1.8, 1H), 6.41 (m, 2H), 6.26 (m, 2H), 4.49 (qd, J.sub.H-H=6.3, 1H), 2.06 (s, broad, 1H), 1.38 (d, J.sub.H-H=6.6, 3H). 13C NMR (75 MHz, CD.sub.2Cl.sub.2): δ 152.4, 141.9, 132.3, 117.7, 111.3, 108.0, 68.4, 23.4. HRMS (ESI+): calculated for C8H10O2: 161.0573 (M+Na); found 161.05774 (M+Na).

Example 27: Hydrogenation of 1-(1-Cyclohexen-1-yl)-ethanone

(98) 1-(1-Cyclohexen-1-yl)-ethanone was hydrogenated according to Example 18, affording 1.25 g (99%) of α-methyl-1-cyclohexene-1-methanol as a colourless liquid.

(99) .sup.1H NMR (300 MHz, CDCl.sub.3): δ 5.57 (s, broad, 1H), 4.06 (q, J.sub.H-H=6.3, 1H), 2.15 (s, 1H), 1.93 (m, 4H), 1.53 (m, 4H), 1.16 (d, J.sub.H-H=6.3, 3H). .sup.13C NMR (75 MHz, CDCl.sub.3): δ 141.3, 121.3, 72.0, 24.9, 23.6, 22.6, 22.6, 21.5. HRMS (ESI+): calculated for C.sub.8H.sub.14O: 149.09369 (M+Na); found 149.09364 (M+Na).