Use of a transition metal catalyst comprising a tetradentate ligand for hydrogenation of esters and/or formation of esters, a process for hydrogenation of esters, a process for formation of esters and a transition metal complex comprising said tetradentate ligand

Abstract

The present invention relates to the use of a transition metal catalyst TMC1, which comprises a transition metal M selected from metals of groups 7, 8, 9 and 10 of the periodic table of elements according to IUPAC and a tetradentate ligand of formula I wherein R.sup.1 are identical or different and are each an organic radical having from 1 to 40 carbon atoms, and R.sup.2 are identical or different and are each an organic radical having from 1 to 40 carbon atoms, as catalyst in processes for formation of compounds comprising at least one carboxylic acid ester functional group —O—C(═O)— starting from at least one primary alcohol and/or hydrogenation of compounds comprising at least one carboxylic acid ester functional group —O—C(═O)—. The present invention further relates to a process for hydrogenation of a compound comprising at least one carboxylic acid ester functional group —O—C(═O)—, to a process for the formation of a compound comprising at least one carboxylic acid ester functional group —O—C(═O)— by dehydrogenase coupling of at least one primary alcohol with a second alcoholic OH-group, to a transition metal complex comprising the tetradentate ligand of formula I and to a process for preparing said transition metal complex. ##STR00001##

Claims

1. A transition metal catalyst TMC1 comprising: ruthenium, a tetradentate ligand of formula I, ##STR00046## wherein R.sup.1 are each independently selected from the group consisting of a C.sub.1 to C.sub.40 alkyl radical, a C.sub.3 to C.sub.40 cycloalkyl radical, a C.sub.2 to C.sub.40 heterocycloalkyl radical, a C.sub.6 to C.sub.40 aryl radical, and a C.sub.2 to C.sub.40 heteroaromatic radical, and wherein R.sup.2 are each independently selected from the group consisting of a C.sub.1 to C.sub.40 alkyl radical, a C.sub.3 to C.sub.40 cycloalkyl radical, a C.sub.2 to C.sub.40 heterocycloalkyl radical, a C.sub.6 to C.sub.40 aryl radical, and a C.sub.2 to C.sub.40 heteroaromatic radical, and a carbon monoxide ligand and comprising one or more additional ligands selected from the group consisting of hydrides, alkoxides, aryloxides, carboxylates and acyls.

2. The transition metal catalyst of claim 1, wherein R.sup.1 and R.sup.2 are identical.

3. The transition metal catalyst of claim 1, further comprising one or more additional ligands, comprising a neutral ligand selected from the group consisting of triaryl phosphines, amines, N-heterocyclic carbenes and isonitriles.

4. The transition metal catalyst of claim 1, wherein R.sup.1 are each identical and wherein R.sup.2 are each identical.

5. The transition metal catalyst of claim 1, wherein R.sup.1 and R.sup.2 are each independently an alkyl radical selected from the group consisting of methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 1-hexyl, 1-octyl-iso-butyl, adamantyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, cyclohexyl, cyclopentyl, tert.-butyl, p-tert.-butyl-phenyl, o-tolyl, m-tolyl, p-tolyl, p-methoxy-phenyl, p-trifluoromethyl-phenyl, 4-biphenyl, naphthyl and phenyl.

6. A transition metal complex of formula II: ##STR00047##  wherein M is ruthenium, wherein R.sup.1 are each independently selected from the group consisting of a C.sub.1 to C.sub.40 alkyl radical, a C.sub.3 to C.sub.40 cycloalkyl radical, a C.sub.2 to C.sub.40 heterocycloalkyl radical, a C.sub.6 to C.sub.40 aryl radical, and a C.sub.2 to C.sub.40 heteroaromatic radical, and wherein R.sup.2 are each independently selected from the group consisting of a C.sub.1 to C.sub.40 alkyl radical, a C.sub.3 to C.sub.40 cycloalkyl radical, a C.sub.2 to C.sub.40 heterocycloalkyl radical, a C.sub.6 to C.sub.40 aryl radical, and a C.sub.2 to C.sub.40 heteroaromatic radical, and wherein R.sup.3 is selected from the group consisting of a C.sub.1 to C.sub.40 alkyl radical, a C.sub.3 to C.sub.40 cycloalkyl radical, a C.sub.2 to C.sub.40 heterocycloalkyl radical, a C.sub.6 to C.sub.40 aryl radical, a C.sub.7 to C.sub.40 arylalkyl radical, and a C.sub.2 to C.sub.40 heteroaromatic radical, or wherein R.sup.3 is C(═O)R.sup.4, wherein R.sup.4 is selected from the group consisting of a hydrogen, a C.sub.1 to C.sub.40 alkyl radical, a C.sub.3 to C.sub.40 cycloalkyl radical, a C.sub.2 to C.sub.40 heterocycloalkyl radical, a C.sub.6 to C.sub.40 aryl radical, a C.sub.7 to C.sub.40 arylalkyl radical, and a C.sub.2 to C.sub.40 heteroaromatic radical, wherein R.sup.3 in each case is bound via a carbon atom to the oxygen atom.

7. The transition metal complex of claim 6, wherein R.sup.1 are each identical and wherein R.sup.2 are each identical.

8. The transition metal complex of claim 6, wherein R.sup.1 and R.sup.2 are identical.

9. The transition metal complex of claim 6, wherein R.sup.1 and R.sup.2 are each independently an alkyl radical selected from the group consisting of methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 1-hexyl, 1-octyl-iso-butyl, adamantyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, cyclohexyl, cyclopentyl, tert.-butyl, p-tert.-butyl-phenyl, o-tolyl, m-tolyl, p-tolyl, p-methoxy-phenyl, p-trifluoromethyl-phenyl, 4-biphenyl, naphthyl and phenyl.

10. The transition metal complex of claim 6, wherein R.sup.3 is a C.sub.1 to C.sub.6 alkyl radical comprising methyl, ethyl, isopropyl, cyclohexyl, cyclopentyl or tert.-butyl, or a substituted or unsubstituted C.sub.6 to C.sub.18 aryl radical comprising p-tert.-butyl-phenyl, o-tolyl, m-tolyl, p-toly, naphthyl or phenyl, or a substituted or unsubstituted C.sub.7 to C.sub.18 arylalkyl radical comprising benzyl.

11. The transition metal complex of claim 6, wherein R.sup.3 is a C.sub.1 to C.sub.15 alkanoyl radical comprising formyl, acetyl or propionyl, or a substituted or unsubstituted benzoyl.

12. A transition metal catalyst comprising: a transition metal complex of formula II: ##STR00048##  wherein M is ruthenium, wherein R.sup.1 are each independently selected from the group consisting of a C.sub.1 to C.sub.40 alkyl radical, a C.sub.3 to C.sub.40 cycloalkyl radical, a C.sub.2 to C.sub.40 heterocycloalkyl radical, a C.sub.6 to C.sub.40 aryl radical, and a C.sub.2 to C.sub.40 heteroaromatic radical, and wherein R.sup.2 are each independently selected from the group consisting of a C.sub.1 to C.sub.40 alkyl radical, a C.sub.3 to C.sub.40 cycloalkyl radical, a C.sub.2 to C.sub.40 heterocycloalkyl radical, a C.sub.6 to C.sub.40 aryl radical, and a C.sub.2 to C.sub.40 heteroaromatic radical, and wherein R.sup.3 is selected from the group consisting of a C.sub.1 to C.sub.40 alkyl radical, a C.sub.3 to C.sub.40 cycloalkyl radical, a C.sub.2 to C.sub.40 heterocy-cloalkyl radical, a C.sub.6 to C.sub.40 aryl radical, a C.sub.7 to C.sub.40 arylalkyl radical, and a C.sub.2 to C.sub.40 heteroaromatic radical, or wherein R.sup.3 is C(═O)R.sup.4, wherein R.sup.4 is selected from the group consisting of a hydrogen, a C.sub.1 to C.sub.40 alkyl radical, a C.sub.3 to C.sub.40 cycloalkyl radical, a C.sub.2 to C.sub.40 heterocycloalkyl radical, a C.sub.6 to C.sub.40 aryl radical, a C.sub.7 to C.sub.40 arylalkyl radical, and a C.sub.2 to C.sub.40 heteroaromatic radical, wherein R.sup.3 in each case is bound via a carbon atom to the oxygen atom; and one or more ligand comprising an anion selected from the group consisting of hydrides, alkoxides, aryloxides, carboxylates and acyls, or a neutral ligand selected from the group consisting of carbon monoxide, triaryl phosphines, amines, N-heterocyclic carbenes and isonitriles.

13. A composition comprising: the transition metal catalyst of claim 1; and a liquid reaction mixture, wherein the transition metal catalyst is in an amount of about 0.1 ppm to about 2000 ppm (parts per weight) based on the total weight of the liquid reaction mixture.

14. A composition comprising: the transition metal complex of claim 6; and a liquid reaction mixture, wherein the transition metal complex is present in an amount of about 0.1 ppm to about 2000 ppm (parts per weight) based on the total weight of the liquid reaction mixture.

15. A method of using the transition metal catalyst of claim 1 for base-free hydrogenation of dimethyl terephthalate, comprising: contacting the dimethyl terephthalate with the transition metal catalyst in the presence of hydrogen without adding a base, wherein the transition metal catalyst provides about a 90% yield of 1,4-phenylenedimethanol.

Description

(1) The invention is illustrated by the examples which follow, but these do not restrict the invention.

(2) Figures in percent are each based on % by weight, unless explicitly stated otherwise.

(3) General

(4) All chemicals and solvents were purchased from Sigma-Aldrich or ABCR and used without further purification.

(5) .sup.1H-, .sup.13C- and .sup.31P NMR spectra were recorded on Bruker Avance 200 or 400 MHz spectrometer and were referenced to the residual proton (.sup.1H) or carbon (.sup.13C) resonance peaks of the solvent. Chemical shifts (δ) are reported in ppm. .sup.31P NMR spectra were referred to an external standard (sample of D.sub.3PO.sub.4)

I. Preparation of Transition Metal Catalyst TMC1

I.1 Preparation of Tetradentate Ligands of Formula

I.1.a Preparation of tris(2-(diphenylphosphino)ethyl)amine (L)

(6) ##STR00019##

(7) A 100 ml round bottom glass flask equipped with a condenser, was charged under argon with an anhydrous degassed solution of KOtBu (1.81 g) in THF (25 ml). Diphenylphosphine (1.1 mL, 6.3 mmol) was added under argon and the red/orange mixture was stirred for 5 minutes. 0.5 g tris(2-chloroethyl)ammoniumhydrochloride was added under argon and the mixture was heated to reflux for 20 h under argon. The mixture was then cooled to RT, and poured into degassed, deionized water (70 mL) in a round bottom glass flask. The flask was cooled in an ice bath for 1 h to induce precipitation. The precipitate was then filtered and rapidly washed with ethanol (2×10 mL). The white precipitate was dried under high vacuum to yield 1.1 g white powder (73% yield). The purity of the product was analyzed by .sup.1H and .sup.31P NMR spectroscopy and found to be >95% pure by 1H-NMR, and >99% pure by .sup.31P{.sup.1H}-NMR

I.1.b Preparation of tris((2-(diphenylphosphino)ethyl)amino)ruthenium Monocarbonyl-Ru(L)CO (I)

(8) ##STR00020##

(9) In a dry argon filled glove box, a 100 mL glass Schlenk flask was charged with triruthenium dodecacarbonyl (Ru.sub.3CO.sub.12, 162 mg) and tris(2-(diphenylphosphino)ethyl)amine (L, 500 mg) and toluene (15 ml). The flask was equipped with a condenser and the system was mounted under argon at a Schlenk line. The solution was heated in an oil bath to reflux (oil temperature 135° C.) with stirring under argon for 16 hrs. Upon cooling to room temperature, the product precipitated as an orange powder. The workup procedure was performed in an argon filled glove-box: The solvent was removed, and the orange powder was washed with degassed, dry benzene (20 ml). The orange residue was then introduced into a 100 ml Teflon capped pressure vessel, with degassed, dry benzene (25 ml). Degassed anhydrous methanol (2.5 ml) was added, and the solution was heated in the closed vessel, under argon, to 80° C. for 3 h, until a clear yellow solution was obtained. The solution was then cooled to room temperature and filtered through a 0.2 μm filter. The filtrate was evaporated fully under high vacuum to afford a bright orange powder (445 mg, 74% yield). The product was analyzed by elemental analysis (at the Mikroanalytisches Laboratorium der Chemischen Institute der Universität Heidelberg), and FTIR (Varian 2000, Scimitar Series, FTS2000).

I.1.c Preparation of methoxy [tris((2-(diphenylphosphino)ethyl)amino)hydridoruthenium monocarbonyl][RuH(L)CO].SUP.+.OMe.SUP.−

(10) ##STR00021##

(11) In a dry argon filled glove box, a 100 mL glass Schlenk flask was charged with Ru(L)CO (50 mg) and benzene (12 mL). Methanol (1.0 mL) was added and the flask was sealed with a Teflon cap. The solution was heated in an oil bath to 80° C. (oil temperature) with stirring under argon for 3 hours, by-which the orange slurry turned to a clear yellow solution. The product complex is only stable in solution, with excess methanol and was not isolated completely. The product was analyzed by NMR (Bruker 200, 400). Single crystals were grown by slow diffusion of diethyl ether/pentane to a benzene/methanol solution of the product. X-ray crystallography provided the confirmation of structure of the [RuH(L)CO].sup.+ cation.

(12) .sup.1H NMR (400 MHz, C.sub.6D.sub.6) δ 7.89 (dt, J=12.7, 4.1 Hz, 4H), 7.22 (dd, J=11.4, 4.2 Hz, 4H), 7.18-7.11 (m, 2H), 7.01-6.86 (m, 8H), 6.79 (t, J=7.4 Hz, 2H), 6.74-6.63 (m, 6H), 6.60 (td, J=7.6, 2.0 Hz, 4H), 3.16-2.96 (m, 4H), 2.73-2.60 (m, 4H), 2.50-2.32 (m, 4H), −6.60 (dt, J=83.0, 21.7 Hz, 1H).

(13) .sup.13C NMR (101 MHz, C.sub.6D.sub.6) δ 205.7 (td, J=12.0, 8.8 Hz), 160.0 (s), 138.3 (td, J=27.3, 4.6 Hz), 133.4 (t, J=6.4 Hz), 130.6-130.4 (m), 130.0 (t, J=5.6 Hz), 129.8 (d, J=11.3 Hz), 129.3 (s), 129.0 (d, J=1.9 Hz), 128.6 (t, J=4.7 Hz), 128.5 (d, J=4.6 Hz), 128.4-128.2 (m), 63.4 (t, J=4.4 Hz), 59.5 (d, J=7.8 Hz), 52.4 (s), 31.5 (d, J=23.6 Hz), 30.6 (t, J=13.4 Hz).

(14) .sup.31P NMR (81 MHz, C.sub.6D.sub.6) δ 55.7 (d, J=15 Hz), 44.6 (t, J=15 Hz).

I.1.d Preparation of Phenoxy [tris((2-(diphenylphosphino)ethyl)amino) hydridoruthenium monocarbonyl][RuH(L)CO].SUP.+.OPh.SUP.−

(15) ##STR00022##

(16) In a dry argon filled glove box, a capped NMR tube was charged with Ru(L)CO (22 mg) and benzene-d.sub.6 (0.7 mL). Phenol (8 mg, 3 equiv) was added and the tube was shaken for 30 min. at 80° C. The solution turned to a clear yellow solution. The product was analyzed by NMR (Bruker 200, 400), and FTIR (Varian 2000, Scimitar Series, FTS2000).

(17) .sup.1H NMR (400 MHz, C.sub.6D.sub.6) δ 12.92 (b, 2H, free PhOH), 7.89 (dd, J=12.5, 6.5 Hz, 4H, PPh.sub.2), 7.58 (dt, J=3.4, 1.7 Hz, 6H, PhO.sup.− and PhOH), 7.34-7.26 (m, 6H, PhO.sup.− and PhOH), 7.13 (dd, J=14.4, 7.1 Hz, 4H, PPh.sub.2), 7.06-7.00 (m, 3H, PPh.sub.2), 6.98 (ddd, J=9.8, 3.9, 1.5 Hz, 7H, PPh.sub.2), 6.80-6.73 (m, 3H, PhO.sup.− and PhOH), 6.70-6.52 (m, 12H, PPh.sub.2), 3.52 (dt, J=23.8, 6.7 Hz, 2H, NCH.sub.2), 3.28 (dd, J=33.2, 17.2 Hz, 2H, NCH.sub.2), 2.82 (dd, J=13.1, 6.5 Hz, 2H, NCH.sub.2), 2.75-2.61 (m, 2H, CH.sub.2P), 2.40-2.17 (m, 4H, 2(CH.sub.2P)), −6.60 (dt, J=82.5, 21.4 Hz, 1H, Ru-H).

(18) .sup.13C NMR (101 MHz, C.sub.6D.sub.6) δ 206.7 (dt, J=20.7, 11.9 Hz), 139.3 (td, J=26.9, 4.7 Hz), 134.7 (dt, J=36.9, 2.1 Hz), 134.3 (td, J=20.8, 1.5 Hz), 134.0 (t, J=6.4 Hz), 130.6 (t, J=5.6 Hz), 130.6-130.5 (m, overlapping), 130.4 (m, overlapping), 129.3 (s), 129.0 (d, J=4.6 Hz), 128.8 (d, J=9.5 Hz), 128.6 (t, J=5.3 Hz), 63.9 (t, J=3.7 Hz), 60.3 (d, J=7.2 Hz), 32.3 (d, J=24.0 Hz), 31.2 (t, J=13.3 Hz).

(19) .sup.31P NMR (81 MHz, C.sub.6D.sub.6) δ 66.6 (d, J=15.0 Hz), 55.0 (t, J=15.0 Hz).

(20) v.sub.CO=1934 cm.sup.−1

I.1.e Preparation of [tris((2-(diphenylphosphino)ethyl)amino) hydridoruthenium monocarbonyl]benzoate[RuH(L)CO].SUP.+.PhCOO.SUP.−

(21) ##STR00023##

(22) In a dry argon filled glove box, a capped NMR tube was charged with Ru(L)CO (15 mg) and benzene-d.sub.6 (0.7 mL). Benzoic acid (2.3 mg, 1 equiv) was added and the tube was shaken for 30 min. at 80° C. The solution turned to a clear pale yellow solution. The product was analyzed by NMR (Bruker 200). Single crystals were grown by slow diffusion of diethyl ether to a benzene solution of the product. X-ray crystallography provided the confirmation of structure of the [RuH(L)CO].sup.+PhCOO.sup.− complex.

(23) .sup.1H NMR (200 MHz, C.sub.6D.sub.6) δ 9.18-8.86 (dd, J=8.2, 1.4 Hz, 2H, PhCOO), 7.96 (d, J=5.8 Hz, 4H, PPh.sub.2), 7.53 (b, 1H, overlapping, PhCOO and PPh.sub.2), 7.53-7.43 (m, 2H, overlapping, PhCOO), 7.33 (d, J=8.4 Hz, 8H, PPh.sub.2), 7.14-6.91 (m, 8H, PPh.sub.2), 6.67 (s, 10H, PPh.sub.2), 4.78 (d, J=22.8 Hz, 2H, NCH.sub.2—), 3.95 (m, N(CH.sub.2-).sub.2), 2.74-2.15 (m, 4H, (—CH.sub.2P).sub.2), −6.31 (dt, J=82.4, 20.4 Hz, 1H, Rh-H).

(24) .sup.31P NMR (81 MHz, C.sub.6D.sub.6) δ 68.4 (d, J=15.2 Hz), 57.6 (t, J=15.3 Hz).

II. Use of Transition Metal Catalysts TMC1 as Catalyst Hydrogenation of Esters and Formation of Esters by Dehydrogenative Coupling of Primary Alcohols

II.1 Base-Free Hydrogenation of Esters (Dimethyl Terephthalate) with MeOH as Activator

(25) ##STR00024##

(26) In a dry argon filled glove box, a 20 mL Teflon coated stainless steel autoclave was charged with the catalyst Ru(L)CO (I) (0.003 mmol), dimethyl terephthalate (1.2 mmol), methanol (0.01 mL) and toluene (6 mL). The argon atmosphere in the autoclave was replaced with H.sub.2 by twice pressurization to 30 bar, and pressure release at room temperature. The autoclave was then pressurized with H.sub.2 gas (60 bar). The solution was heated at 130° C. (heating mantel temperature) with stirring for 18 hrs. After cooling to 0° C., the system was vented carefully and purged for 1 minute with argon. The conversion of starting material was analyzed by GC-MS, using an Agilent Technologies 6890N gas chromatography system coupled with an Agilent Technologies 5975B mass spectrometer and equipped with an Agilent Technologies HP-5MS capillary column (30 m×0.250 mm/0.25 μm). Full conversion, with no residual dimethyl terephthalate was observed. The solution was then filtered, and the product 1,4-phenylenedimethanol, was collected and dried under vacuum. 147 mg product (90% yield) were obtained as a white crystalline powder. The product identification and purity (>99%) were analyzed by .sup.1H-NMR (tetrachloroethane as internal standard, 200 MHz Bruker Avance, in CD.sub.3O).

II.2 Base-Free Hydrogenation of Esters (Dimethyl Terephthalate) without an Alcohol as Activator (Comparative Example)

(27) ##STR00025##

(28) In a dry argon filled glove box, a stainless steel autoclave was charged with the catalyst Ru(L)CO (I) (0.02 mmol), dimethyl terephthalate (1 mmol), and toluene (14 mL). The argon atmosphere in the autoclave was replaced with H.sub.2 by twice pressurization to 30 bar, and pressure release at room temperature. The autoclave was then pressurized with H.sub.2 gas (60 bar). The solution was heated at 130° C. (heating mantel temperature) with stirring for 18 hrs. After cooling to 0° C., the system was vented carefully and purged for 1 minute with argon. The conversion of starting material was analyzed by GC-MS, using an Agilent Technologies 6890N gas chromatography system coupled with an Agilent Technologies 5975B mass spectrometer and equipped with an Agilent Technologies HP-5MS capillary column (30 m×0.250 mm/0.25 μm). No conversion was detected, dimethyl terephthalate as the only component was observed.

II.3 Base-Free Hydrogenation of Esters (Ethylacetate) with EtOH as Activator

(29) ##STR00026##

(30) In a dry argon filled glove box, a 20 mL Teflon lined stainless steel autoclave was charged with the catalyst Ru(L)CO (I) (0.008 mmol), and ethyl acetate (5.0 mL, 85.7 mmol, anhydrous, 99.8% purchased from Sigma Aldrich). The ethylacetate used contained 0.01% EtOH (determined by GC; amount given in GC area %) which is a sufficient amount to act as catalyst activator. The argon atmosphere in the autoclave was replaced with H.sub.2 by twice pressurization to 30 bar, and pressure release at room temperature. The autoclave was then pressurized with H.sub.2 gas (60 bar). The solution was heated at 130° C. (heating mantel temperature) with stirring for 40 hrs. After cooling to 0° C., the system was vented carefully and purged for 1 minute with argon. The product solution was analyzed by .sup.1H-NMR (tetrachloroethane as internal standard, 200 MHz Bruker Avance, in C.sub.6D.sub.6). Yield measured to be 91%, corresponding to a turn over number (TON) of 5700.

II.4 Base-Free Dehydrogenative Coupling of Alcohols (1-Pentanol) to Esters (Pentyl Pentanoate)

(31) ##STR00027##

(32) In a dry argon filled glove box, a 100 mL round-bottomed glass Schlenk flask was charged with the catalyst Ru(L)CO (I) (0.006 mmol), 1-pentanol (0.48 mL, 4.41 mmol), and benzene (10 mL). The flask was equipped with a condenser and the system was mounted under argon at a Schlenk line. The solution was heated in an oil bath to reflux (oil temperature 100° C.) with stirring under argon for 18 hrs. After cooling to room temperature the conversion of starting material was analyzed by GC on an Agilent Technologies 6890N gas chromatography system equipped with a FID detector and an Agilent Technologies DB-1 capillary column (30 m×0.250 mm/1.0 μm). Full conversion was observed. The solution was then eluted through a silica column in pentanes/ethyl acetate (9:1) and the combined fractions to yield 296 mg as a colorless liquid. The product identification and purity were analyzed by .sup.1H-NMR (tetrachloroethane as internal standard, 200 MHz Bruker Avance, in C.sub.6D.sub.6). Isolated yield measured to be 78%.

II.5 Base-Free Dehydrogenative Coupling of Alcohols (1-hexanol) to Esters (Hexyl Hexanoate)

(33) ##STR00028##

(34) In a dry argon filled glove box, a 100 mL round-bottomed glass Schlenk flask was charged with the catalyst Ru(L)CO (I) (0.01 mmol), 1-hexanol (13.5 mmol), and toluene (10 mL). The flask was equipped with a condenser and the system was mounted under argon at a Schlenk line. The solution was heated in an oil bath to reflux (oil temperature 135° C.) with stirring under argon for 18 hrs. After cooling to room temperature the conversion of starting material was analyzed by GC-MS, using an Agilent Technologies 6890N gas chromatography system coupled with an Agilent Technologies 5975B mass spectrometer and equipped with an Agilent Technologies HP-5MS capillary column (30 m×0.250 mm/0.25 μm). 97% conversion (by area) was measured. The solution was then evaporated under vacuum, and the product hexyl hexanoate, was collected and dried under vacuum. 1.26 g product (93% yield) were obtained as a colorless liquid. The product identification and purity were analyzed by .sup.1H-NMR (tetrachloroethane as internal standard, 200 MHz Bruker Avance, in C.sub.6D.sub.6). Isolated yield measured to be 90%.

II.6 Rehydrogenation of Hexyl Hexanoate, Formed by Additive-Free Dehydrogenation of Hexanol

(35) ##STR00029##

(36) In a dry argon filled glove box, the product from the above (Example 5) described dehydrogenative coupling of hexanol to hexyl hexanoate: 1.2 g hexyl hexanoate, at 97% purity, containing catalyst carried over from dehydrogenation, with 0.5 mol % hexanol (determined by GC-FID; amount given in GC-area %), along with toluene (5 mL) were charged in a 20 mL Teflon lined stainless steel autoclave. The argon atmosphere in the autoclave was replaced with H.sub.2 by twice pressurization to 30 bar, and pressure release at room temperature. The autoclave was then pressurized with H.sub.2 gas (60 bar). The solution was heated at 130° C. (heating mantel temperature) with stirring for 18 hrs. After cooling to 0° C., the system was vented carefully and purged for 1 minute with argon. The conversion of starting material was analyzed by GC on an Agilent Technologies 6890N gas chromatography system equipped with a FID detector and an Agilent Technologies DB-1 capillary column (30 m×0.250 mm/1.0 μm). The solution was then fully evaporated, yielding 1.1 g product as a slightly pale yellow liquid. Purity was measured by .sup.1H-NMR (tetrachloroethane as internal standard, 200 MHz Bruker Avance, in C.sub.6D.sub.6). Yield measured to be 88%.

II.7 Hydrogenation of Symmetric Esters, or Methyl Esters Catalyzed by Ru(L)CO Activated by Methanol. General Procedure

(37) ##STR00030##

(38) In an argon filled glove-box, a ca. 80 mL Premex stainless steel autocalve fitted with a PTFE inner chamber and a PTFE coated magnetic stirring bar was charged with Ru(L)CO (I) (6×10.sup.−3 mmol, 4.7 mg), the specified ester (0.6 mmol), degassed, anhydrous 1,4-dioxane (6.0 mL) and degassed anhydrous methanol (0.05 mL). Hexamethylbenzene (0.15 mmol, as internal standard) was added and the mixture was stirred vigorously at room temperature until full dissolution. A sample (0.1 mL) was then taken for t.sub.0-analysis (GC and NMR). After closing the reaction vessel was removed from the glove-box. The argon atmosphere in the autoclave was replaced with H.sub.2 by twice pressurization to 30 bar, and pressure release at room temperature. The autoclave was then pressurized with H.sub.2 gas (60 bar). The solution was heated at 130° C. (heating mantel temperature) with stirring for 17 hrs. After cooling to 0° C., the system was vented carefully and purged for 1 minute with argon. A sample of the crude mixture (0.1 mL) was transferred to a vial and was analyzed as-is by GC on an Agilent Technologies 6890N gas chromatography system equipped with a FID detector and an Agilent Technologies DB-1 capillary column (30 m×0.250 mm/1.0 μm). Another sample (0.1 mL) was diluted with CDCl.sub.3 (0.6 mL) in an NMR tube and analyzed by .sup.1H-NMR. Conversion was determined by comparison to the samples at to (with hexamethylbenzene as internal standard). NMR yield was determined by the ratio of product to starting material in the crude sample after reaction.

(39) TABLE-US-00001 TABLE 1 Entry ester alcohol Conv. (Yield).sup.b II.7.1 >99 II.7.2 >99 II.7.3 >99 II.7.4 >99 II.7.5 0  80 II.7.6 >99 (>99).sup.d .sup.aReaction conditions: ester (0.1 M), Ru(L)CO (I) (1 mol %), and 1,4-dioxane (6 mL) were pressurized with 60 bar H.sub.2 and heated at 130° C. (heating block temperature) for 17 h. .sup.bPercent conversion, in solution, by % area in GC-FID, and confirmed by .sup.1H-NMR in CDCl.sub.3 with hexamethylbenzene as internal standard. .sup.cPerformed in toluene. .sup.dPercent yield determined after isolation of 2f by partial evaporation and filtration, by .sup.1H-NMR in CD.sub.3OD with 1,1,2,2-tetrachloroethane as internal standard

II.8 Base-Free Hydrogenation of Esters (Dimethyl Terephthalate) with Phenol as Activator

(40) ##STR00041##

(41) In a dry argon filled glove box, a stainless steel autoclave was charged with the catalyst Ru(L)CO (I) (0.02 mmol), and phenol (0.04 mmol) and toluene (12 mL). The mixture was stirred for 30 min at RT. Then dimethyl terephthalate (3 mmol) was added. The argon atmosphere in the autoclave was replaced with H.sub.2 by twice pressurization to 30 bar, and pressure release at room temperature. The autoclave was then pressurized with H.sub.2 gas (60 bar). The solution was heated at 130° C. (heating mantel temperature) with stirring for 18 hrs. After cooling to 0° C., the system was vented carefully and purged for 1 minute with argon. The conversion of starting material was analyzed by GC-MS, using an Agilent Technologies 6890N gas chromatography system coupled with an Agilent Technologies 5975B mass spectrometer and equipped with an Agilent Technologies HP-5MS capillary column (30 m×0.250 mm/0.25 μm). The solution was then evaporated under vacuum to remove all volatiles, and a sample was measured by .sup.1H-NMR in methanol-d.sub.4 with 1,1,2,2-tetrachloroethane as internal standard. 88% yield of NP1 was obtained with a ratio of: 10/1/0.4 of the components NP1:BDM:DMT respectively.

II.9 Hydrogenation of Esters (Dimethyl Terephthalate) Catalyzed by [Ru(L)CO(H)].SUP.+.PhCOO.SUP.− with Methanol as Activator

(42) ##STR00042##

(43) In a dry argon filled glove box, a ca. 80 mL Premex stainless steel autocalve fitted with a PTFE inner chamber and a PTFE coated magnetic stirring bar was charged with the complex [Ru(L)CO(H)].sup.+PhCOO.sup.− (0.015 mmol), dimethyl terephthalate (1.0 mmol) and toluene (6 mL). Methanol was added (0.1 mL) and the autoclave was sealed. The argon atmosphere in the autoclave was replaced with H.sub.2 by twice pressurization to 30 bar, and pressure release at room temperature. The autoclave was then pressurized with H.sub.2 gas (60 bar). The solution was heated at 130° C. (heating mantel temperature) with stirring for 19 hrs. After cooling to 0° C., the system was vented carefully and purged for 1 minute with argon. The conversion of starting material was analyzed by GC-MS, using an Agilent Technologies 6890N gas chromatography system coupled with an Agilent Technologies 5975B mass spectrometer and equipped with an Agilent Technologies HP-5MS capillary column (30 m×0.250 mm/0.25 μm). By % area, ca. 85% NP1 was obtained, with LT 5% BDM, and then rest unreacted DMT.

II.10 Base-Free Hydrogenation of Esters (Dimethyl terephthalate) with Ru(PPh.SUB.3.)(CO).SUB.2 .(PPh.SUB.3.=tris-(diphenylphosphinoethyl)phosphine)—Comparative Example

(44) ##STR00043##

(45) In a dry argon filled glove box, a stainless steel autoclave was charged with the complex Ru(PPh.sub.3)(CO).sub.2 (0.008 mmol), dimethyl terephthalate (0.5 mmol), and toluene (6 mL). Methanol was added (0.1 mL) and the autoclave was sealed. The argon atmosphere in the autoclave was replaced with H.sub.2 by twice pressurization to 30 bar, and pressure release at room temperature. The autoclave was then pressurized with H.sub.2 gas (60 bar). The solution was heated at 130° C. (heating mantel temperature) with stirring for 19 hrs. After cooling to 0° C., the system was vented carefully and purged for 1 minute with argon. The conversion of starting material was analyzed by GC-MS, using an Agilent Technologies 6890N gas chromatography system coupled with an Agilent Technologies 5975B mass spectrometer and equipped with an Agilent Technologies HP-5MS capillary column (30 m×0.250 mm/0.25 μm). No conversion was detected, dimethyl terephthalate as the only component was observed.

II.11 Base-Free Hydrogenation of Esters (Dimethyl terephthalate) with Ru.SUB.3.(CO).SUB.12.+ Triphos (Triphos=1,1,1-Tris(diphenylphosphinomethyl)ethane)—Comparative Example

(46) ##STR00044##

(47) In a dry argon filled glove box, a stainless steel autoclave was charged with the complex Ru.sub.3(CO).sub.12 (0.01 mmol), Triphos (0.04 mmol), dimethyl terephthalate (1.08 mmol), and toluene (6 mL). Methanol was added (0.1 mL) and the autoclave was sealed. The argon atmosphere in the autoclave was replaced with H.sub.2 by twice pressurization to 30 bar, and pressure release at room temperature. The autoclave was then pressurized with H.sub.2 gas (60 bar). The solution was heated at 130° C. (heating mantel temperature) with stirring for 17 hrs. After cooling to 0° C. the system was vented carefully and purged for 1 minute with argon. The conversion of starting material was analyzed by GC-MS, using an Agilent Technologies 6890N gas chromatography system coupled with an Agilent Technologies 5975B mass spectrometer and equipped with an Agilent Technologies HP-5MS capillary column (30 m×0.250 m/0.25 μm). No conversion was detected, only starting material was observed.

II.12 Hydrogenation of Unsaturated Esters (methyl trans-3-hexenoate) Catalyzed by Ru(L)CO with Methanol as Activator

(48) ##STR00045##

(49) In a dry argon filled glove box, a ca. 80 mL Premex stainless steel autocalve fitted with a PTFE inner chamber and a PTFE coated magnetic stirring bar was charged with the complex Ru(L)CO (0.006 mmol), methyl trans-3-hexenoate (0.6 mmol) and toluene (6 mL). Methanol was added (0.05 mL) and the autoclave was sealed. The argon atmosphere in the autoclave was replaced with H.sub.2 by twice pressurization to 30 bar, and pressure release at room temperature. The autoclave was then pressurized with H.sub.2 gas (60 bar). The solution was heated at 130° C. (heating mantel temperature) with stirring for 18 hrs. After cooling to 0° C., the system was vented carefully and purged for 1 minute with argon. The conversion of starting material was analyzed by GC on an Agilent Technologies 6890N gas chromatography system equipped with a FID detector and an Agilent Technologies DB-1 capillary column (30 m×0.250 mm/1.0 μm). Another sample (0.1 mL) was diluted with CDCl.sub.3 (0.6 mL) in an NMR tube and analyzed by .sup.1H-NMR. Full conversion of the starting material was measured, to a mixture of ca. 65% hex-3-en-1-ol, and ca. 35% 1-hexnaol (as well as methanol).

II.13 Hydrogenation of Sclareolide (3a,6,6,9a-tetramethyl-1,4,5,5a,7,8,9,9b-octahydronaphtho[8,7-d]furan-2-one)

(50) Ru.sub.3(CO).sub.12 (8.5 mg, 0,013 mmol), tris(2-(diphenylphosphinol)ethyl)amine (L) (26 mg, 0.04 mmol), NaOMe (27 mg, 0.5 mmol) and (3aR)-(+)-Sclareolide (Sigma-Aldrich, 2.5 g, 10 mmol) are transferred into a stainless steel autoclave (V2A steel, Premex) under inert atmosphere. THF (40 mL, dry) was added finally into the autoclave. The autoclave was then pressurized with H.sub.2 gas (60 bar) and stirred at 700 rpm. The solution was heated to 150° C. (solution temperature) for 16 hrs and the pressure was kept at 80 bar. The conversion of starting material was analyzed by GC, using an Optima FFAP column (30 m×0.25 mm/0.5 μm; 15 min at 140° C. then heat with 20° C./min to 250° C.; const. flow: 2.0 ml/min; Helium as carrier gas). Conversion (GC-area %) was 75% and the selectivity for Ambroxdiol was 90%. t.sub.R(Sclareolide)=29.4 min; t.sub.R(Ambroxdiol)=32.5 min.

II.14 Hydrogenation of Sclareolide (3a,6,6,9a-tetramethyl-1,4,5,5a,7,8,9,9b-octahydronaphtho[8,7-d]furan-2-one) (Base-Free Conditions)

(51) Ru.sub.3(CO).sub.12 (8.5 mg, 0,013 mmol), tris(2-(diphenylphosphinol)ethyl)amine (26 mg, 0.04 mmol) and (3aR)-(+)-Sclareolide (Sigma-Aldrich, 2.5 g, 10 mmol) are transferred into a stainless steel autoclave (V2A steel, Premex) under inert atmosphere. THF (40 mL, dry) was added finally into the autoclave. The autoclave was then pressurized with H.sub.2 gas (60 bar) and stirred at 700 rpm. The solution was heated to 150° C. (solution temperature) for 16 hrs and the pressure was kept at 80 bar. The conversion of starting material was analyzed by GC, using an Optima FFAP column (30 m×0.25 mm/0.5 μm; 15 min at 140° C. then heat with 20° C./min to 250° C.; const. flow: 2.0 ml/min; Helium as carrier gas). Conversion (GC-area %) was 90% and the selectivity for Ambroxdiol was 89%. t.sub.R(Sclareolide)=29.4 min; t.sub.R(Ambroxdiol)=32.5 min.