Selective hydrogenation of aldehydes with Ru/bidentate ligands complexes

Abstract

The present invention relates to processes for the reduction by hydrogenation, using molecular H.sub.2, of a C.sub.5-C.sub.20 substrate containing one or two aldehydes functional groups into the corresponding alcohols or diol, characterized in that said process is carried out in the presence of at least one catalyst or pre-catalyst in the form of a ruthenium complex having a coordination sphere of the N.sub.1P.sub.3O.sub.2, wherein the coordinating atom N and one coordinating atom P are provided by a first bidentate ligand, and the two other coordinating atoms P.sub.2 are provided by a second bidentate ligand and the coordinating atoms O.sub.2 are provided by two non-linear carboxylate ligands; and optionally of an acidic additive.

Claims

1. A process for the reduction by hydrogenation, using molecular H.sub.2, of a C.sub.5-C.sub.20 substrate of formula ##STR00016## wherein R.sup.a represents a C.sub.4-C.sub.19 linear, branched or cyclic alkyl, alkenyl or alkadienyl group optionally comprising an aromatic ring and optionally comprising one, two or three functional groups selected among ketone, ether, carbon-carbon double or triple bond and carboxylic groups; into the corresponding alcohol or diol, characterized in that said process is carried out in the presence of at least one complex of formula
[Ru(PP)(PN)(RCOO).sub.2](1) wherein PP represents a C.sub.6-C.sub.50 bidentate ligand of formula ##STR00017## wherein R.sup.11 and R.sup.12, when taken separately, represent, simultaneously or independently, a C.sub.3-6 branched or cyclic alkyl group or a C.sub.6-10 aromatic group optionally substituted; and Q represents a group of formula ##STR00018## wherein m is 1, 2, 3 or 4 and R.sup.5 and R.sup.6 represent, simultaneously or independently, a hydrogen atom, a C.sub.1-6 linear or branched alkyl group or a C.sub.6-10 aromatic group optionally substituted; two distinct R.sup.6 and/or R.sup.5 groups, taken together, may form a C.sub.3 to C.sub.8 saturated or unsaturated ring optionally substituted, including the atoms to which said R.sup.6 and/or R.sup.5 groups are bonded, and optionally containing one or two additional nitrogen or oxygen atoms; or a C.sub.10-C.sub.16 metallocenediyl, a 2,2-diphenyl, a 1,1-binaphthalene-2,2-diyl, a benzenediyl, a naphthalenediyl, 2,3-bicyclo[2:2:1]hept-5-enediyl, 4,6-phenoxazinediyl, 4,5-(9,9-dimethyl)-xanthenediyl, or bis(phen-2-yl)ether group optionally substituted; PN represents a C.sub.2-C.sub.20 bidentate ligand of formula ##STR00019## wherein a represent 0 or 1, R.sup.11 and R.sup.12 being defined as for PP; R.sup.1 represent, simultaneously or independently, a hydrogen atom or a C.sub.1-6 linear, branched or cyclic alkyl group or a benzyl group optionally substituted; R.sup.2 represents a hydrogen atom, a C.sub.1-6 linear, branched alkyl group or a C.sub.6-10 aromatic group optionally substituted; R.sup.1 and R.sup.2, taken together, may form a saturated heterocycle containing 5 to 8 atoms and including the atoms to which said R.sup.1 and R.sup.2 are bonded, and optionally containing one additional nitrogen or oxygen atom; and Q represents a group of formula ##STR00020## wherein m is 1, 2 or 3, and R.sup.5 and R.sup.6 represent, simultaneously or independently, a hydrogen atom, a C.sub.1-6 linear, branched or cyclic alkyl or, a C.sub.6-10 aromatic group optionally substituted; two distinct R.sup.6 and/or R.sup.5 groups, taken together, may form a C.sub.3-8 saturated ring optionally substituted, including the atoms to which said R.sup.6 and/or R.sup.5, groups are bonded, and optionally containing one or two additional nitrogen or oxygen atoms; or a C.sub.10-C.sub.16 metallocenediyl group, a benzenediyl group, or a naphthalenediyl group, said group being optionally substituted; the optional substituents of R.sup.5, R.sup.6, R.sup.11 and R.sup.12 are one to five halogen atoms (in particular when said substituents are on aromatic moieties), or one, two or three i) C.sub.1-6 linear or branched alkyl alkoxy, groups or halo- or perhalo-hydrocarbon, amine groups, ii) COOR.sup.h wherein R.sup.h is a C.sub.1-6 linear, branched or cyclic alkyl group, iii) NO.sub.2 group, or iv) a benzyl group or a fused or non-fused phenyl group, said group being optionally substituted by one, two or three halogen atoms, C.sub.1-8 alkyl, alkoxy, amino, nitro, ester, sulfonate or halo- or perhalo-hydrocarbon groups; and each R represents, simultaneously or independently, a C.sub.2-C.sub.12 hydrocarbon group branched or cyclic in the and/or position, and said hydrocarbon group is optionally comprising one to five heteroatom selected amongst halogen, oxygen and nitrogen atoms; and optionally an acidic additive.

2. A process according to claim 1, characterised in that each R represents, simultaneously or independently: a C.sub.2-12 alkyl group branched or cyclic in the and/or position optionally substituted by one phenyl group optionally substituted by one to five halogen atoms and/or by C.sub.1-4 alkyl or alkoxyl groups; and optionally comprising one OH, amino or ether functional group; or a phenyl group optionally substituted by one to three, or live, halogen atoms and/or by C.sub.1-4 alkyl or alkoxyl groups and/or by nitro groups.

3. A process according to claim 1, characterised in that the bidentate PN ligand is a compound of formula ##STR00021## wherein a represents 0 or 1, R.sup.11 and R.sup.12 being defined in claim 1; and Q represents a group of forms ##STR00022## wherein in is 1 or 2, and R.sup.6 represents, simultaneously or independently, a hydrogen atom, a C.sub.1-4 linear or branched alkyl group; or a benzenediyl group optionally substituted.

4. A process according to claim 1, characterised in that each R.sup.11 and R.sup.12 represent each, simultaneously or independently, a C.sub.4-6 branched or cyclic alkyl group or a phenyl group optionally substituted.

5. A process according to claim 1, characterised in that said PP ligand is a compound of formula (C) wherein R.sup.11 and R.sup.12 represent, simultaneously or independently, a C.sub.4-6 branched or cyclic alkyl group or a phenyl group optionally substituted; and Q represents a C.sub.1-C.sub.4 alkanediyl radical optionally substituted, a C.sub.10-C.sub.12 ferrocenediyl, a 2,2-diphenyl, a 1,2-benzenediyl or a naphthalenediyl group.

6. A process according to claim 1, characterised in that said acidic additive may be selected amongst the weak protic acids having a pK.sub.a comprised between 2 and 11.

7. A process according to claim 1, characterised in that acidic; additive is selected amongst: a carboxylic acid of formula RCOOH, wherein R is as defined above in formula (1); and phenol (C.sub.6H.sub.5OH) and a phenol substituted by one or two, or up to five, halogen atoms and/or C.sub.1-4 alkyl or alkoxyl groups and/or nitro groups and/or carboalkoxy groups.

8. A ruthenium complex of formula
[RU(PP)(PN)(RCOO).sub.2](1) as defined in claim 1.

9. The ruthenium complex of claim 8 wherein the hydrocarbon group of R comprises one to five heteroatoms selected amongst halogen, oxygen and nitrogen atoms.

10. The process of claim 1 wherein the hydrocarbon group of R comprises one to five heteroatoms selected amongst halogen, oxygen and nitrogen atoms.

Description

EXAMPLES

(1) The invention will now be described in further detail by way of the following examples, wherein the temperatures are indicated in degrees centigrade and the abbreviations have the usual meaning in the art.

(2) All the procedures described hereafter have been carried out under an inert atmosphere unless stated otherwise. Hydrogenations were carried out in stainless steel autoclave. H.sub.2 gas (99.99990%) was used as received. All substrates and solvents were distilled from appropriate drying agents under Ar. NMR spectra were recorded on a Bruker AM-400 (.sup.1H at 400.1 MHz, .sup.13C at 100.6 MHz, and .sup.31P at 161.9 MHz) spectrometer and normally measured at 300 K, in CD.sub.2Cl.sub.2 unless indicated otherwise. Chemical shifts are listed in ppm.

Example 1

(3) The invention's complexes were generally synthesized according to a two steps procedure going through the corresponding [Ru(PP)(RCOO).sub.2]ruthenium(diphosphine) (biscarboxylate) derivatives, those being isolated or not.

(4) Two Step Procedure:

(5) A) The [Ru(diene)(RCOO).sub.2] (in general [Ru(COD)(RCOO).sub.2], see the application PCT/IB2011/052108) precursor was loaded into a schlenck tube. It was then purged with three vacuum-nitrogen cycles. Degazed xylene (technical quality can be used) was then added to generally afford a suspention. Diphosphine (1 eq./Ru) was then added to the stirred suspention that was then heated to reflux (140-144 C.) under nitrogen for several hours (duration depending on nature of diphosphine ligand). After cooling down and xylene removal, degassed MeOH was generally added for product precipitation (nature of solvent used can obviously depends on the nature of both diphosphine and carboxylate ligands). It was then filtered under nitrogen, washed several times with degassed MeOH (again, nature of solvent used can obviously depends on the nature of both diphosphine and carboxylate ligands) and then dried under vacuum to afford the desired corresponding [Ru(diphosphine)(RCOO).sub.2] complex in generally more than 90 mol. % yields.

(6) B) The obtained [Ru(diphosphine)(RCOO).sub.2] precursor was loaded into a schlenck tube. It was then purged with three vacuum-nitrogen cycles. Degazed THF was then added followed by aminophosphine ligand (1 eq./Ru). Reaction mixture was then heated to reflux (66 C.) under nitrogen for several hours (duration depending on nature of the aminophosphine ligand. After cooling down and THF removal under vacuum, degassed 30/50 petroleum ether was generally added for product precipitation (nature of solvent used can obviously depends on the nature of aminopohsphine, diphosphine and carboxylate ligands). It was then filtered under nitrogen and washed several times with degassed 30/50 petroleum ether (again, nature of solvent used can obviously depends on the nature of aminophosphine, diphosphine and carboxylate ligands). After drying under vacuum, desired [Ru(PP)(PN)(RCOO).sub.2] complex was obtained in more than 60 mol. % yield as cis or trans isomer (carboxylate in cis or trans position) or cis/trans isomers mixture, both stereochemistry and yields mainly depending on the nature of the ligands used.

[(2-(diphenylphosphino)ethanamine)[1,4-bis(diphenylphosphino)butane]Ru(pivalate)2]

(7) .sup.31P NMR: 26.19 (dd, J=300.0 and 30.9, 1P trans isomer), 35.75 (t, 30.9, 1P trans isomer), 46.92 (dd, J=300 and 30.9, 1P trans isomer).

(8) .sup.13C NMR (trans isomer): 21.15 (d, J=4.4, CH.sub.2), 24.63 (broad s, CH.sub.2), 24.72 (d, J=18.4, CH.sub.2), 27.07 (d, J=24.0, CH.sub.2), 28.84 (s, CH.sub.3), 33.28 (dd, J=22.8 and 3.5, CH.sub.2), 40.11 (s, C), 40.66 (t, J=6.2, CH.sub.2), 127.26 (d, J=8.8, CH), 127.41 (d, J=8.2, CH), 128.13 (d, J=8.4, CH), 129.01 (broad s, CH), 129.18 (s, CH), 133.74 (broad s, CH), 134.96 (broad s, CH), 138.0 (broad s, C), 140.90 (broad s, C), 188.30 (broad s, C).

[(2-(diphenylphosphino)ethanamine)[1,3-bis(diphenylphosphino)propane]Ru(pivalate)2]

(9) .sup.31P NMR: 25.30 (dd, J=29.0 and 43.5, 1P trans isomer), 27.98 (dd, J=300.0 and 43.5, 1P trans isomer), 42.33 (dd, =300.0 and 29.0, 1P trans isomer).

(10) .sup.13C NMR (trans isomer): 19.37 (d, J=2.9, CH.sub.2), 26.89 (dd, J=26.4 and 3.6, CH.sub.2), 27.96 (d, J=23.7, CH.sub.2), 28.93 (s, CH.sub.3), 32.57 (dd, J=21.2 and 4.0, CH.sub.2), 40.11 (s, C), 40.67 (t, J=7.0, CH.sub.2), 127.40 (d, J=9.0, CH), 127.91 (d, J=7.8, CH), 128.33 (d, J=8.6, CH), 129.02 (broad s, CH), 129.13 (d, J=1.6, CH), 129.27 (broad s, CH), 133.40 (d, J=9.8, CH), 134.44 (d, J=8.8, CH), 136.27 (d, J=3.2, C), 136.63 (d, J=3.4, C), 188.4 (broad s, C).

[(2-(diphenylphosphino)ethanamine)[1,2-bis(diphenylphosphino)ethane]Ru(pivalate)2]

(11) .sup.31P NMR: 44.46 (dd, J=318.0 and 27.8, 1P trans isomer), 58.75 (dd, J=318.0 and 20.6, 1P trans isomer), 59.39 (dd, =27.8 and 20.6, 1P trans isomer).

(12) .sup.13C NMR (trans isomer): 28.15 (dd, J=28.3 and 13.1, CH.sub.2), 28.74 (s, CH.sub.3), 30.26 (ddd, J=27.2, 15.9 and 4.0, CH.sub.2), 33.26 (dd, J=21.2 and 3.3, CH.sub.2), 39.77 (s, C), 41.71 (dd, J=7.5 and 4.5, CH.sub.2), 127.80 (d, J=8.8, CH), 128.13 (d, J=8.7, CH), 128.31 (d, J=8.6, CH), 129.03 (d, J=1.5, CH), 129.15 (d, J=1.8, CH), 129.42 (d, J=1.8, CH), 133.08 (d, J=9.5, CH), 133.56 (d, J=9.9, CH), 133.91 (d, J=10.0, CH), 135.84 (dd, J=33.6 and 4.2, C), 136.49 (d, J=33.8 and 3.0, C), 141.40 (d, J=36.8, C), 187.44 (s, C).

[(2-(diphenylphosphino)ethanamine)[1,1-bis(diphenylphosphino)methane]Ru(pivalate)2]

(13) .sup.31P NMR: 3.91 (dd, J=334.8 and 43.4, 1P trans isomer), 9.18 (dd, J=43.4 and 30.0, 1P trans isomer), 53.54 (dd, J=334.8 and 30.0, 1P trans isomer).

(14) .sup.13C NMR: 28.12 (CH.sub.3), 31.69 (dd, J=21.4 and 3.0, CH.sub.2), 39.7 (s, C), 41.99 (t, J=6.6, CH.sub.2), 46.69 (t, J=17.5, CH.sub.2), 128.13 (d, J=9.5, CH), 128.27 (d, J=9.0, CH), 129.35 (t, J=2.5, CH), 129.64 (d, J=2.5, CH), 133.15 (d, J=12.0, CH), 133.50 (d, J=10.6, CH), 133.86 (d, J=11.6, CH), 135.43 (dd, J=21.7 and 2.5, C), 135.95 (dt, J=25.8 and 5.0, C), 137.37 (dd, J=33.5 and 5.8, C), 187.94 (s, C).

[(2-(diphenylphosphino)ethanamine)[9,9-dimethyl-4,5-bis(diphenylphosphino) xanthene]Ru(pivalate)2]

(15) .sup.31P NMR: 23.84 (dd, J=28.0 and 24.0, 1P isomer 1), 37.59 (dd, J=37.0 and 28.0, 1P isomer 1), 47.31 (broad t, J=25.0, 1P isomer 2), 49.82 (dd, J=37.0 and 23.0, 1P isomer 1), 51.26 (dd, J=32.8 and 24.5, 1P isomer 2), 58.12 (d, J=30.0, 2P isomer 3), 66.68 (dd, J=32.8 and 26.0, 1P isomer 2), 74.77 (t, 30.0, 1P isomer 3).

[(2-(diphenylphosphino)ethanamine)[2,2-bis(diphenylphosphino)-1,1-binaphthalene]Ru(pivalate)2]

(16) .sup.31P NMR: 27.61 (d, J=31.8, 1P isomer 1), 29.56 (d, J=31.6, 1P isomer 2), 31.62 (d, J=27.9, 1P isomer 2), 33.57 (d, J=27.9, 1P isomer 1), 38.00 (dd, J=31.6 and 27.9, 1P isomer 2), 40.50 (dd, J=31.8 and 27.9, 1P isomer 1).

[(2-(diphenylphosphino)ethanamine)[(oxybis(2,1-phenylene))bis(diphenylphosphine)]Ru(pivalate)2]

(17) .sup.31P NMR: 34.97 (dd, J=29.2 and 24.2, 1P isomer 1), 40.54 (dd, J=36.3 and 29.2, 1P isomer 1), 45.01 (braod s, 1P isomer 2), 47.65 (dd, J=36.3 and 24.2, 1P isomer 1), 50.64 (d, J=32.0, 1P isomer 2), 73.28 (d, J=32.0, 1P isomer 2).

[(2-(diphenylphosphino)ethanamine)[1,1-Bis(diphenylphosphino)ferrocene]Ru(pivalate)2]

(18) .sup.31P NMR: 45.62 (dd, J=34.6 and 28.6, 1P isomer 1), 48.25 (dd, J=28.6 and 24.5, 1P isomer 1), 50.56 (d, J=31.7, 1P isomer 2), 55.39 (dd, J=34.6 and 24.5, 1P isomer 1), 64.23 (broad s, 1P isomer 2), 73.30 (d, J=32.4, 1P isomer 2).

[(2-(di-tert-butylphosphino)ethanamine)[1,4-bis(diphenylphosphino)butane]Ru(pivalate)2]

(19) .sup.31P NMR: 17.14 (broad s, 1P isomer 1), 22.21 (broad s, 1P isomer 2), 49.96 (d, J=41.2, 1P isomer 2), 59.41 (very broad s, 2P isomer 1), 66.34 (d, J=41.2, 1P isomer 2).

[(2-(diphenylphosphino)phenyl)methanamine)[9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]Ru(pivalate)2]

(20) .sup.31P NMR: 27.00 (dd; J=11.8 and 7.2, 1P isomer 1), 40.54 (t, J=16.0, 1P isomer 2), 44.89 (dd, J=37.6 and 7.2, 1P isomer 1), 53.72 (d, J=31.0, 2P isomer 3), 55.54 (dd, J=38.8 and 16.0, 1P isomer 2), 66.28 (dd, J=37.6 and 11.8, 1P isomer 1), 74.84 (t, J=31.0, 1P isomer 3), 75.99 (dd, J=38.8 and 16.0, 1P isomer 2).

[(3-(diphenylphosphino)propan-1-amine)[9,9-dimethyl-4,5-bis(diphenylphosphino) xanthene]Ru(pivalate)2]

(21) .sup.31P NMR: 55.22 (d, J=30.4, 2P isomer 1), 56.41 (d, J=29.8, 2P isomer 2), 57.20 (t, J=30.4, 1P isomer 1), 61.98 (t, J=29.8, 1P isomer 2).

[(2-(diphenylphosphino)ethanamine)[1,2-bis(diphenylphosphino)ethane]Ru(benzoate)2]

(22) .sup.31P NMR: 43.75 (dd, J=309.8 and 25.6, 1P trans isomer), 59.50 (dd, J=25.6 and 20.9, 1P trans isomer), 61.36 (dd, J=310.7 and 20.9, 1P trans isomer).

(23) .sup.13C NMR (trans isomer): 28.36 (dd, J=28.8 and 12.6, CH.sub.2), 29.36 (ddd, J=28.0, 15.7 and 4.1, CH.sub.2), 33.85 (dd, J=21.6 and 3.2, CH.sub.2), 42.08 (dd, J=8.2 and 4.7, CH.sub.2), 127.35 (s, CH), 128.00 (d, J=8.9, CH), 128.23 (d, J=8.5, CH), 128.29 (d, J=8.5, CH), 129.02 (s, CH), 129.29 (d, J=1.8, CH), 129.34 (d, J=1.7, CH), 129.57 (d, J=1.5, CH), 129.65 (s, CH), 133.07 (d, J=9.5, CH), 133.52 (d, J=9.9, CH), 133.72 (d, J=10.1, CH), 135.17 (dd, J=34.3 and 3.6, C), 135.95 (dd, J=33.8 and 2.8, C), 137.72 (s, C), 140.60 (d, J=37.1, C), 176.67 (s, C).

[(2-(diphenylphosphino)ethanamine)[1,2-bis(diphenylphosphino)ethane]Ru(1-adamantanecarboxylate)2]

(24) .sup.31P NMR: 44.08 (dd, J=318.1 and 27.9, 1P trans isomer), 58.69 (dd, J=318.1 and 20.6, 1P trans isomer), 59.22 (dd, J=27.9 and 20.6, 1P trans isomer).

(25) .sup.13C NMR (trans isomer): 28.17 (dd, J=28.5 and 12.6, CH.sub.2), 29.19 (s, CH), 30.41 (ddd, J=27.2, 15.5 and 4.2, CH.sub.2), 33.06 (dd, J=20.8 and 3.5, CH.sub.2), 42.08 (dd, J=4.8 and 4.1, CH.sub.2), 37.36 (s, CH.sub.2), 40.38 (s, CH.sub.2), 41.47 (t, J=6.7, CH.sub.2), 41.93 (s, C), 127.74 (d, J=8.9, CH), 128.24 (t, J=8.6, CH), 129.08 (d, J=1.4, CH), 129.18 (d, J=3.0, CH), 129.43 (d, J=1.6, CH), 133.23 (d, J=9.5, CH), 133.67 (d, J=10.0, CH), 134.08 (d, J=9.8, CH), 135.96 (dd, J=33.4 and 3.6, C), 136.23 (dd, J=33.6 and 3.2, C), 141.49 (d, J=37.0, C), 187.03 (s, C).

[(2-(diphenylphosphino)ethanamine)[9,9-dimethyl-4,5-bis(diphenylphosphino) xanthene]Ru(1-adamantanecarboxylate)2]

(26) .sup.31P NMR: 23.97 (dd, 27.6 and 24.0, 1P isomer 1), 37.57 (dd, J=38.1 and 27.6, 1P isomer 1), 47.12 (broad t, J=25.5, 1P isomer 2), 49.55 (dd, J=38.1 and 24.0, 1P isomer 1), 51.24 (dd, J=32.4 and 24.5, 1P isomer 2), 58.11 (d, J=30.2, 2P isomer 3), 66.68 (dd, J=32.4 and 26.5, 1P isomer 2), 74.76 (t, 30.2, 1P isomer 3).

[(2-(diphenylphosphino)ethanamine)[1,2-bis(diphenylphosphino)ethane]Ru(isobutyrate)2]

(27) .sup.31P NMR: 43.41 (dd, J=313.5 and 24.1, 1P trans isomer), 60.18 (dd, J=24.1 and 21.6, 1P trans isomer), 61.42 (dd, J=313.5 and 21.6, 1P trans isomer).

(28) .sup.13C NMR (trans isomer): 20.00 (s, CH.sub.3), 20.41 (s, CH.sub.3), 28.31 (dd, J=28.5 and 12.6, CH.sub.2), 30.74 (ddd, J=26.39, 15.8 and 4.0, CH.sub.2), 33.33 (dd, J=20.8 and 3.1, CH.sub.2), 37.82 (s, CH), 41.72 (dd, J=8.2 and 4.4, CH.sub.2), 127.71 (d, J=8.7, CH), 128.00 (d, J=8.6, CH), 128.33 (d, J=8.5, CH), 129.10 (d, J=1.5, CH), 129.17 (d, J=1.4, CH), 129.54 (d, J=1.4, CH), 133.03 (d, J=9.6, CH), 133.43 (d, J=10.2, CH), 133.74 (d, J=9.6, CH), 135.58 (dd, J=31.0 and 2.8, C), 135.61 (d, J=33.7, C), 136.10 (dd, J=33.8 and 3.0, C), 141.35 (d, J=37.9, C), 186.25 (s, C).

[(2-(diphenylphosphino)ethanamine)[1,2-bis(diphenylphosphino)ethane]Ru(3,3-dimethylbutyrate)2]

(29) .sup.31P NMR: 43.06 (dd, J=317.2 and 26.1, 1P trans isomer), 60.38 (dd, J=26.1 and 20.8, 1P trans isomer), 62.28 (dd, J=317.2 and 20.8, 1P trans isomer).

(30) .sup.13C NMR (trans isomer): 28.49 (dd, J=29.3 and 12.2, CH.sub.2), 29.97 (s, CH.sub.3), 30.21 (s, C), 30.76 (ddd, J=27.6, 15.8 and 3.6, CH.sub.2), 32.96 (dd, J=21.0 and 3.3, CH.sub.2), 41.49 (dd, J=9.2 and 4.8, CH.sub.2), 52.73 (s, CH.sub.2), 127.54 (d, J=8.9, CH), 127.99 (d, J=8.6, CH), 128.34 (d, J=8.5, CH), 129.15 (broad s, CH), 129.45 (d, J=1.6, CH), 133.13 (d, J=9.8, CH), 133.57 (d, J=10.1, CH), 133.81 (d, J=9.7, CH), 135.38 (dd, J=33.0 and 3.0, C), 135.76 (dd, J=33.2 and 3.7, C), 141.34 (d, J=37.6, C), 181.61 (s, C).

[(2-(diphenylphosphino)ethanamine)[1,2-bis(diphenylphosphino)ethane]Ru(2,2-dimethylbutyrate)2]

(31) .sup.31P NMR: 44.11 (dd, J=317.6 and 26.1, 1P trans isomer), 57.59 (dd, J=317.6 and 20.6, 1P trans isomer), 59.23 (dd, J=26.1 and 20.6, 1P trans isomer).

(32) .sup.13C NMR (trans isomer): 8.97 (s, CH.sub.3), 24.73 (s, CH.sub.3), 25.18 (s, CH.sub.3), 28.27 (dd, J=28.4 and 13.1, CH.sub.2), 30.40 (ddd, J=27.1, 14.9 and 4.0, CH.sub.2), 32.97 (dd, J=21.2 and 3.4, CH.sub.2), 33.35 (s, CH.sub.2), 41.57 (dd, J=7.8 and 4.7, CH.sub.2), 43.00 (s, C), 127.78 (d, J=8.8, CH), 128.10 (d, J=8.5, CH), 128.29 (d, J=8.6, CH), 129.02 (d, J=1.4, CH), 129.15 (d, J=1.8, CH), 129.34 (d, J=1.5, CH), 133.14 (d, J=9.5, CH), 133.59 (d, J=10.2, CH), 134.00 (d, J=9.8, CH), 136.09 (dd, J=33.7 and 3.5, C), 136.24 (dd, J=33.6 and 3.2, C), 141.65 (d, J=37.1, C), 187.29. (s, C).

[(2-(diphenylphosphino)ethanamine)[1,2-bis(diphenylphosphino)ethane]Ru(cyclohexanecarboxylate)2]

(33) .sup.31P NMR: 43.37 (dd, J=315.4 and 25.2, 1P trans isomer), 60.12 (dd, J=25.2 and 21.5, 1P trans isomer), 61.78 (dd, J=315.4 and 21.5, 1P trans isomer).

(34) .sup.13C NMR (trans isomer): 26.54 (s, CH.sub.2), 26.66 (s, CH.sub.2), 26.87 (s, CH.sub.2), 28.37 (dd, J=29.1 and 12.4, CH.sub.2), 30.19 (s, CH.sub.2), 30.70 (s, CH.sub.2), 30.81 (ddd, J=32.0, 15.9 and 4.2, CH.sub.2), 33.32 (dd, J=20.8 and 3.2, CH.sub.2), 41.66 (dd, J=7.7 and 4.6, CH.sub.2), 48.18 (s, CH), 127.63 (d, J=8.8, CH), 128.00 (d, J=8.7, CH), 128.27 (d, J=8.7, CH), 129.08 (d, J=1.4, CH), 129.17 (d, J=1.3, CH), 129.53 (d, J=1.4, CH), 133.08 (d, J=9.5, CH), 133.48 (d, J=10.2, CH), 133.84 (d, J=9.8, CH), 135.65 (dd, J=34.0 and 3.2, C), 135.98 (dd, J=33.8 and 3.0, C), 141.29 (d, J=37.5, C), 185.48. (s, C).

[(2-(diphenylphosphino)ethanamine)[1,2-bis(diphenylphosphino)ethane]Ru(cyclopropanecarboxylate)2]

(35) .sup.31P NMR: 43.16 (dd, J=313.6 and 25.2, 1P trans isomer), 60.67 (dd, J=25.2 and 22.0, 1P trans isomer), 62.64 (dd, J=313.6 and 22.0, 1P trans isomer).

(36) .sup.13C NMR (trans isomer): 5.99 (s, CH.sub.2), 16.38 (s, CH), 28.22 (dd, J=29.3 and 12.3, CH.sub.2), 30.57 (ddd, J=32.3, 16.1 and 4.3, CH.sub.2), 33.64 (dd, J=21.0 and 3.3, CH.sub.2), 41.86 (dd, J=8.8 and 5.0, CH.sub.2), 127.61 (d, J=8.9, CH), 127.91 (d, J=8.8, CH), 128.29 (d, J=8.6, CH), 129.15 (d, J=1.2, CH), 129.48 (d, J=1.8, CH), 133.07 (d, J=9.6, CH), 133.59 (d, J=8.4, CH), 133.68 (d, J=8.4, CH), 135.25 (dd, J=33.2 and 3.8, C), 136.16 (dd, J=33.6 and 3.1, C), 141.11 (d, J=37.6, C), 183.09. (s, C).

Example 2

Catalytic Hydrogenation of Aldehydes Using the Invention's Process: Comparative Example with Various Prior Art Catalysts

Influence of Nature of Ruthenium Precursor on Catalytic Activity in 3,7-Dimethyloct-6-Enal (Citronellal) Selective Hydrogenation

(37) General Procedure:

(38) 3,7-dimethyloct-6-enal (15.4 g, 0.1 mol), isopropanol (15.4 g, 100 wt. %), ruthenium complex (0.01 mmol., 0.01 mol. %) and, whenever required tBuOK as additive (112 mg, 1 mmol., 1 mol. %, 100 eq./Ru) were loaded altogether in a 60 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 30 bars hydrogen. It was then heated to 90 C. and hydrogen pressure was maintained to 30 bars for several hours. Upon reaction completion or after 24 h, autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. Crude product was then flash distilled in order to determine the quantity of residues formed during the reaction and yield was calculated based on GC purity of distilled product.

(39) TABLE-US-00001 Time.sup.1) Conv..sup.2) Yield.sup.3) Remarks Complex according the invention (dppae)(dppe)Ru(OCOC.sub.6H.sub.5).sub.2 6 100 99 no tBuOK added (dppae)(dppe)Ru(OCO.sup.tBu).sub.2 3 100 99 no tBuOK added Comparative complexes* (En)(dppe)RuCl.sub.2 24 0 0 no tBuOK added (En)(dppe)RuCl.sub.2 24 100 10 100 eq. tBuOK/Ru 90 wt. % residues (En)(dppe)Ru(H)Cl 24 0 0 no tBuOK added (En)(dppe)Ru(H)Cl 24 100 15 100 eq. tBuOK/Ru 85 wt. % residues (En)(dppe)Ru(H)(HBH.sub.3) 24 17 17 no tBuOK added [(En)(dppe)(OAc)][BF.sub.4] 24 30 30 no tBuOK added [(En)(dppe)[BF.sub.4].sub.2 24 22 22 no tBuOK added (En)(dppe)Ru(OAc).sub.2 24 25 25 no tBuOK added (En)(dppe)Ru(OCOC.sub.2H.sub.5).sub.2 24 26 26 no tBuOK added (En)(dppe)Ru(OCOCF.sub.3).sub.2 24 20 16 no tBuOK added *catalyst of the prior art and not being of formula (1) .sup.1)In hours .sup.2)Conversion of the starting aldehyde in % (GC) .sup.3)Isolated yield of the primary alcohol obtained (mol. %) En: ethylenediamine (NN) dppe: 1,2-bis(diphenylphosphino)ethane (PP) dppae: 2-(diphenylphosphino)ethanamine (PN)

Influence of Nature of Ruthenium Precursor on Catalytic Activity in 2-methyl-4-((R)-2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-enal Selective Hydrogenation

(40) General Procedure:

(41) 2-methyl-4-((R)-2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-enal (as a 40/60 (2S,4R)/(2R,4R) diastereoisomers mixture) (10.3 g, 0.05 mol.), isopropanol (10.3 g, 100 wt. %), ruthenium complex (0.01 mmol., 0.02 mol. %) and, whenever required, tBuOK as additive (56 mg, 0.5 mmol., 1 mol. %, 50 eq./Ru) were loaded altogether in a 60 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stiffing with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 50 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was maintained to 50 bars for several hours. Upon reaction completion (checked by GC) or after 24 h, autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. Crude product was then flash distilled in order to determine the quantity of residues formed during the reaction and yield was calculated based on GC purity of distilled product.

(42) TABLE-US-00002 Time.sup.1) Conv..sup.2) Yield.sup.3) Remarks Complex according the invention (dppae)(dppe)Ru(OCOC.sub.6H.sub.5).sub.2 9 100 99 no tBuOK added (dppae)(dppe)Ru(OCO.sup.tBu).sub.2 7 100 99 no tBuOK added Comparative complexes* (En)(dppe)RuCl.sub.2 24 0 0 no tBuOK added (En)(dppe)RuCl.sub.2 24 100 12 100 eq. tBuOK/Ru 95 wt. % residues (En)(dppe)Ru(H)Cl 24 0 0 no tBuOK added (En)(dppe)Ru(H)Cl 24 100 20 100 eq. tBuOK/Ru 80 wt. % residues (En)(dppe)Ru(H)(HBH.sub.3) 24 15 15 no tBuOK added (En)(dppe)Ru(H)(HBH.sub.3) 24 100 18 100 eq. tBuOK/Ru 82 wt. % residues [(En)(dppe)Ru(OAc)][BF.sub.4] 24 14 14 no tBuOK added [(En)(dppe)Ru][BF.sub.4].sub.2 24 22 22 no tBuOK added (En)(dppe)Ru(OAc).sub.2 24 25 25 no tBuOK added (En)(dppe)Ru(OCOC.sub.2H.sub.5).sub.2 24 23 23 no tBuOK added (En)(dppe)Ru(OCOCF.sub.3).sub.2 24 20 15 no tBuOK added *catalyst of the prior art and not being of formula (1) .sup.1)In hours .sup.2)Conversion of the starting aldehyde in % (GC) .sup.3)Isolated yield of the primary alcohol obtained (mol. %) En: ethylenediamine (NN) dppe: 1,2-bis(diphenylphosphino)ethane (PP) dppae: 2-(diphenylphosphino)ethanamine (PN)

Example 3

Catalytic Hydrogenation of Aldehydes Using the Invention's Process: Influence of the R Group on the Reactivity of the Catalysts

Influence of Nature of Carboxylate Ligand on Catalytic Activity in 2-methyl-4-((R)-2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-enal Selective Hydrogenation

(43) General Procedure:

(44) 2-methyl-4-((R)-2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-enal (as a 40/60 (2S,4R)/(2R,4R) diastereoisomers mixture) (20.6 g, 0.1 mol) and [2-(diphenyl phosphino)ethanamine][1,2bis(diphenylphosphino)ethane]ruthenium(biscarboxylate) complex (0.01 mmol., 0.01 mol. %) were loaded altogether in a 60 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 50 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was maintained to 50 bars for several hours. Upon reaction completion or after 48 h, autoclave was then cooled down to 25 C. and product purity was checked by GC analysis. It was then depressurized and purged with nitrogen (3 times 5 bars). Crude neat product was then flash distilled in order to determine the quantity of residues formed during the reaction and isolated yield was calculated based on GC purity of distilled product.

(45) TABLE-US-00003 Time.sup.1) Conv..sup.2) Yield.sup.3) Remarks Complex according the invention (R group) .sup.iPrCH.sub.2 48 75 75 conv. 4 h: 50% GC cyclopropyl 24 100 99 conv. 4 h: 65% GC cyclohexyl 17 100 99 conv. 4 h: 79% GC .sup.iPr 14 100 99 conv. 4 h: 85% GC Ph 14 100 99 conv. 4 h: 85% GC 1-adamantyl 10 100 99 conv. 4 h: 90% GC .sup.tBu 6 100 99 conv. 4 h: 94% GC .sup.tBuCH.sub.2 6 100 99 conv. 4 h: 94% GC (Et)(Me).sub.2C 4 100 99 Comparative complexes* (R group) *CF.sub.3 48 15 10 *Me 48 15 15 *Et 48 18 18 *catalyst not being of formula (1) .sup.1)In hours .sup.2)Conversion of the starting aldehyde in % (GC) .sup.3)Isolated yield of the primary alcohol obtained (mol. %) En: ethylenediamine (NN) dppe: 1,2-bis(diphenylphosphino)ethane (PP) dppae: 2-(diphenylphosphino)ethanamine (PN)

Example 4

Catalytic Hydrogenation of Aldehydes Using the Invention Process: Influence of the PP or PN Ligands on the Reactivity of the Catalysts

Influence of Nature of Diphosphine Ligand

(46) General Procedure:

(47) 3,6,7-Trimethyl-octa-2,6-dienal (as a 40/60 Z/E isomers mixture) (12.62 g, 0.075 mol), octane (12.62 g, 100 wt. %) and (2-(diphenylphosphino)ethanamine) (diphosphine)ruthenium(bispivalate) complex (0.00375 mmol., 0.005 mol. %) were loaded altogether in a 60 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stiffing with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 50 bars for several hours. Upon reaction completion or after 48 h, autoclave was then cooled down to 25 C. and product purity was checked by GC analysis. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. Crude product was then flash distilled in order to determine the quantity of residues formed during the reaction and isolated yield was calculated according to GC purity of distilled product.

(48) TABLE-US-00004 Diphosphine ligand PP Time.sup.1) Conv..sup.2) Yield.sup.3) Remarks bis(diphenylphosphino)methane 17 100 99 conv. 4 h: (dppm) 77% GC 1,2- 8.5 100 99 conv. 4 h bis(diphenylphosphino)ethane (dppe) >90% GC 1,3- 8.5 100 99 conv. 4 h bis(diphenylphosphino)propane (dppp) >90% GC 1,4- 8 100 99 conv. 4 h bis(diphenylphosphino)butane (dppb) >90% GC (oxybis(2,1-phenylene)) 7 100 99 conv. 4 h bis(diphenylphosphine) >90% GC (dpephos) 2,2-bis(diphenylphosphino)-1,1- 6 100 99 conv. 4 h binaphthalene >90% GC (rac-Binap) 1,1- 6 100 99 conv. 4 h bis(diphenylphosphino)ferrocene >90% GC (dppFc) 9,9-dimethyl-4,5- 4 100 99 bis(diphenylphosphino)xanthene (Xantphos) .sup.1)In hours .sup.2)Conversion of the starting aldehyde in % (GC) .sup.3)Isolated yield of the primary alcohol obtained (mol. %)

Influence of Nature of Aminophosphine Ligand

(49) General Procedure:

(50) 3,6,7-Trimethyl-octa-2,6-dienal (as a 40/60 Z/E isomers mixture) (12.62 g, 0.075 mol), octane (12.62 g, 100 wt. %) and (aminophosphine)(9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene)ruthenium(bispivalate) complex (0.00375 mmol, 0.005 mol. %) were loaded altogether in a 60 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 50 bars for several hours. Upon reaction completion or after 48 h, autoclave was then cooled down to 25 C. and product purity was checked by GC analysis. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. Crude product was then flash distilled in order to determine the quantity of residues formed during the reaction and isolated yield was calculated according to GC purity of distilled product.

(51) TABLE-US-00005 Aminophosphine ligand PN Time.sup.1) Conv..sup.2) Yield.sup.3) Remarks 2-(di-isopropylphosphino)ethanamine 8 100 99 conv. 4 h >90% GC 2-(di-tert-butylphosphino)ethanamine 6 100 99 conv. 4 h >90% GC 2-(diphenylphosphino)phenyl)methanamine 5 100 99 conv. 4 h >90% GC 3-(diphenylphosphino)propan- 4.5 100 99 conv. 4 h 1-amine >90% GC 2-(diphenylphosphino)ethanamine 4 100 99 (dppae) .sup.1)In hours .sup.2)Conversion of the starting aldehyde in % (GC) .sup.3)Isolated yield of the primary alcohol obtained (mol. %)

Example 5

Catalytic Hydrogenation of Aldehydes Using the Invention Process: Influence of the Additive and In Situ Generation of the Complex (1)

Influence of Acidic Additive and In Situ Generation of Complex (1)

(52) General Procedure:

(53) 2-methyl-4-((R)-2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-enal (as a 40/60 (2S,4R)/(2R,4R) diastereoisomers mixture) (20.66 g, 0.1 mol), ruthenium complex (0.01 mmol., 0.01 mol. %) and, whenever required, pivalic acid as additive (102 mg, 1 mmol, 1 mol. %) were loaded altogether in a 60 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 50 bars for several hours. Upon reaction completion or after 48 h, autoclave was then cooled down to 25 C. and product purity was checked by GC analysis. It was then depressurized and purged with nitrogen (3 times 5 bars). Crude neat product was then flash distilled in order to determine the quantity of residues formed during the reaction and isolated yield was calculated based on GC purity of distilled product.

(54) TABLE-US-00006 Pivalic Ruthenium catalyst acid Time.sup.1) Conv..sup.2) Yield.sup.3) (dppae)(dppe)Ru(OCO.sup.tBu).sub.2 no 6 100 99 (dppae)(dppe)Ru(OCO.sup.tBu).sub.2 yes 2 100 99 .sup.1)In hours .sup.2)Conversion of the starting aldehyde in % (GC) .sup.3)Isolated yield of the primary alcohol obtained (mol. %) dppae: 2-(diphenylphosphino)ethanamine (PN) dppe: 1,2-bis(diphenylphosphino)ethane (PP)

Influence of Acidic Additives on Catalytic Activity

(55) General Procedure:

(56) 3,7-dimethyloct-6-enal (30.85 g, 0.2 mol), [2-(diphenylphosphino) ethanamine][1,2-bis(diphenylphosphino)ethane]ruthenium(bispivalate) complex (4.6 mg, 0.005 mmol., 0.0025 mol. %) and acidic additive (2 mmol., 1 mol. %) were loaded altogether in a 60 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stiffing with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 90 C. and hydrogen pressure was then increased and maintained to 50 bars for several hours. Upon reaction completion or after 72 h, autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars). Crude neat product was then flash distilled in order to determine the quantity of residues formed during the reaction and yield was calculated based on GC purity of distilled product.

(57) TABLE-US-00007 Acidic additive Time.sup.1) Conv..sup.2) Yield.sup.3) Remarks none 48 80 79 blocked after 24 h Hexylboronic acid 48 100 98 Diphenylphosphinic acid 44 100 98 2,4-dichlorobenzoic acid 40 100 98 2,4,6-trimethylbenzoic acid 24 100 99 pentafluorophenol 24 100 99 4-methoxyphenol 24 100 99 4-nitrobenzoic acid 20 100 99 4-carbomethoxyphenol 16 100 99 (1R)-1,2,2- 15 100 99 trimethylcyclopentane- 1,3-dicarboxylic acid (camphoric acid) Terephtalic acid 14 100 99 4-methoxybenzoic acid 12 100 99 3,4,5-trimethoxybenzoic acid 12 100 99 1-naphtoic acid 12 100 99 4-(tert-butyl)benzoic acid 12 100 99 4-biphenylcarboxylic acid 12 100 99 Benzoic acid 12 100 99 4-nitrophenol 12 100 99 2-naphtoic acid 10 100 99 1-adamantane carboxylic acid 10 100 99 Pivalic acid 9 100 99 3,3-dimethylbutanoic acid 9 100 99 2,2-dimethylbutanoic acid 8 100 99 .sup.1)In hours .sup.2)Conversion of the starting aldehyde in % (GC) .sup.3)Isolated yield of the primary alcohol obtained (mol. %) dppae: 2-(diphenylphosphino)ethanamine; dppe: 1,2-bis(diphenylphosphino)ethane.

(58) Despite that the amount of the catalyst in this example is half of the above examples, the additive allows to reach similar conversions and reaction time.

Example 6

Catalytic Hydrogenation of Various Aldehydes Using the Invention Process

3,6,7-Trimethyl-octa-2,6-dien-1-ol synthesis

(59) 3,6,7-Trimethyl-octa-2,6-dienal (as a 40/60 Z/E isomers mixture) (166 g, 1 mol.), heptanes (332 g, 200 wt. %, technical grade), pivalic acid (0.510 g, 5 mmol., 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (56 mg, 0.05 mmol., 0.005 mol. %) were loaded altogether in a 1 L autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stiffing with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 80 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with 96% selectivity as a 40/60 Z/E isomers mixture. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After initial flash distillation followed by further fractional distillation, pure 3,6,7-trimethyloct-2,6-dien-1-ol was obtained in 91% yield.

3,6,7-trimethyloct-6-en-1-ol synthesis

(60) 3,6,7-Trimethyloct-6-enal (168 g, 1 mol.), 2,2-dimethylbutanoic acid (0.581 g, 5 mmol., 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][1,2-bis(diphenylphosphino)ethane]ruthenium(bispivalate) complex (23 mg, 0.025 mmol, 0.0025 mol. %) were loaded altogether in a 300 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with complete selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars). After flash distillation, pure 3,6,7-trimethyloct-6-en-1-ol was obtained in 99% yield.

3,7-dimethylocta-2,6-dien-1-ol synthesis

(61) 3,7-Trimethyl-octa-2,6-dienal (as a 40/60 Z/E isomers mixture) (152 g, 1 mol.), heptane (304 g, 200 wt. %, technical grade), benzoic acid (0.610 g, 5 mmol, 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bisbenzoate) complex (58 mg, 0.05 mmol., 0.005 mol. %) were loaded altogether in a 1 L autoclave equipped with a mechanical stiffing device. Sealed autoclave was then purged under stiffing with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 80 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with 95% selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After initial flash distillation followed by further fractional distillation, pure 3,7-dimethyloct-2,6-dien-1-ol was obtained in 90% yield.

3,7-dimethyloct-6-en-1-ol synthesis

(62) 3,7-Dimethyloct-6-enal (154 g, 1 mol.), 3,3-dimethylbutanoic acid (0.581 g, 5 mmol, 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][1,2-bis(diphenylphosphino)ethane]ruthenium(biscyclopropanecarboxylate) complex (22 mg, 0.025 mmol., 0.0025 mol. %) were loaded altogether in a 300 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stiffing with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with complete selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars). After flash distillation, pure 3,7-trimethyloct-6-en-1-ol was obtained in 99% yield.

3-methylhex-2-en-1-ol synthesis

(63) 3-Methylhex-2-enal (as a 40/60 Z/E isomers mixture) (112 g, 1 mol.), heptane (224 g, 200 wt. %, technical grade), benzoic acid (0.610 g, 5 mmol., 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (56 mg, 0.05 mmol., 0.005 mol. %) were loaded altogether in a 1 L autoclave equipped with a mechanical stiffing device. Sealed autoclave was then purged under stiffing with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 80 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with 96% selectivity as a 40/60 Z/E isomers mixture. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After initial flash distillation followed by further fractional distillation, pure 3-methylhex-2-en-1-ol was obtained in 91% yield.

3-methylhex-2-en-1-yl acetate synthesis

(64) Aldehyde base-free chemoselective hydrogenation reaction can also efficiently be run in the presence of 1 molar equivalent of acetic anhydride in order to directly afford the acetate (via reduction of the aldehyde into the alcohol which reacts with the anhydride to provide the ester).

(65) 3-Methylhex-2-enal (as a 40/60 Z/E isomers mixture) (112 g, 1 mol.), acetic anhydride (107 g, 1.05 mol) and [2-(diphenylphosphino)ethanamine][1,2-bis(diphenylphosphino) ethane]ruthenium(bispivalate) complex (93 mg, 0.1 mmol., 0.01 mol. %) were loaded altogether in a 1 L autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stiffing with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with 98% selectivity as a 40/60 WE isomers mixture. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and concentrated under vacuum. After initial flash distillation followed by further fractional distillation, pure 3-methylhex-2-en-1-yl acetate was obtained in 94% yield.

(E)-2-methylpent-2-en-1-ol synthesis

(66) (E)-2-Methylpent-2-enal (98 g, 1 mol.), heptane (196 g, 200 wt. %, technical grade), benzoic acid (0.610 g, 5 mmol., 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (56 mg, 0.05 mmol., 0.005 mol. %) were loaded altogether in a 11 autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 80 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with 98% selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After initial flash distillation followed by further fractional distillation, pure (E)-2-methylpent-2-en-1-ol was obtained in 93% yield.

(E)-4-methyl-5-(p-tolyl)pent-4-enal synthesis

(67) (E)-4-Methyl-5-(p-tolyl)pent-4-enal (47 g, 0.25 mol.), pivalic acid (0.13 g, 1.25 mmol., 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][1,2-bis(diphenylphosphino)ethane]ruthenium(bis-isobutyrate) complex (5.7 mg, 0.00625 mmol., 0.0025 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with complete selectivity. After complete reaction conversion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars). After flash distillation, pure (E)-4-methyl-5-(p-tolyl)pent-4-en-1-ol was obtained in 99% yield.

2,3-dimethylbut-2-en-1-ol synthesis

(68) 2,3-Dimethylbut-2-enal (490 g, 5 mol.), 2,2-dimethylbutanoic acid (2.9 g, 0.025 mol., 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (185 mg, 0.166 mmol., 0.0033 mol. %) were loaded altogether in a 1 L autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with complete selectivity. After complete reaction conversion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars). After flash distillation, pure 2,3-dimethylbut-2-en-1-ol was obtained in 99% yield.

(Z)-oct-5-en-1-ol synthesis

(69) (Z)-Oct-5-enal (63 g, 0.5 mol.), heptane (126 g, 200 wt. %, technical grade), pivalic acid (0.13 g, 1.25 mmol, 0.25 mol. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (83 mg, 0.075 mmol., 0.015 mol. %) were loaded altogether in a 1 L autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 70 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with 97% selectivity. After complete reaction conversion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After initial flash distillation and further fractional distillation, highly pure (Z)-oct-5-en-1-ol was obtained in 92% yield.

Undec-10-en-1-ol synthesis

(70) Undec-10-enal (84 g, 0.5 mol.), heptane (168 g, 100 wt. %, technical grade), pivalic acid (0.13 g, 1.25 mmol, 0.25 mol. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (83 mg, 0.075 mmol., 0.015 mol. %) were loaded altogether in a 1 L autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 70 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with 94% selectivity. After complete reaction conversion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After initial flash distillation and further fractional distillation, highly pure undec-10-en-1-ol was obtained in 90% yield.

(2,6,6-trimethylcyclohex-2-en-1-yl)methanol synthesis

(71) (2,6,6-trimethylcyclohex-2-ene)carbaldehyde (76 g, 0.5 mol.), benzoic acid (0.31 g, 2.5 mmol, 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][1,4-bis(diphenylphosphino)butane]ruthenium(bispivalate) complex (12.0 mg, 0.0125 mmol., 0.0025 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with complete selectivity. After complete reaction conversion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars). After flash distillation, pure (2,6,6-trimethylcyclohex-2-en-1-yl)methanol was obtained in 99% yield.

(2,6,6-trimethylcyclohex-1-en-1-yl)methanol synthesis

(72) (2,6,6-trimethylcyclohex-1-ene)carbaldehyde (76 g, 0.5 mol.), benzoic acid (0.31 g, 2.5 mmol, 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][1,4-bis(diphenylphosphino)propane]ruthenium(bispivalate) complex (24.0 mg, 0.025 mmol., 0.005 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with complete selectivity. After complete reaction conversion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars). After flash distillation, pure (2,6,6-trimethylcyclohex-1-en-1-yl)methanol was obtained in 99% yield.

Trans-(2,5,6,6-tetramethylcyclohex-2-en-1-yl)methanol synthesis

(73) Racemic trans-(2,5,6,6-tetramethylcyclohex-2-ene)carbaldehyde (83 g, 0.5 mol.), benzoic acid (0.31 g, 2.5 mmol, 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][1,2-bis(diphenylphosphino)ethane]ruthenium(bispivalate) complex (11.7 mg, 0.0125 mmol., 0.0025 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with complete selectivity. After complete reaction conversion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars). After flash distillation, pure racemic trans-(2,5,6,6-tetramethylcyclohex-2-en-1-yl)methanol was obtained in 99% yield.

(2,5,6,6-tetramethylcyclohex-1-en-1-yl)methanol synthesis

(74) (2,5,6,6-tetramethylcyclohex-1-ene)carbaldehyde (41.5 g, 0.25 mol.), pivalic acid (0.13 g, 1.25 mmol, 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][1,4-bis(diphenyl phosphino)ethane]ruthenium(bis-cyclohexanecarboxylate) complex (12.3 mg, 0.0125 mmol., 0.005 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with complete selectivity. After complete reaction conversion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars). After flash distillation, pure (2,5,6,6-tetramethylcyclohex-1-en-1-yl)methanol was obtained in 99% yield.

(R)-2-ethyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)but-2-en-1-ol synthesis

(75) (R)-2-ethyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)but-2-enal (as a 95/5 E/Z isomers mixture) (206 g, 1 mol.), benzoic acid (0.61 g, 5 mmol., 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (55.1 mg, 0.05 mmol., 0.005 mol. %) were loaded altogether in a 1 L autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stiffing with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 10 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 15 bars during all the reaction to afford desired product with 99.5% selectivity as a 95/5 E/Z isomers mixture and no loss of optical purity. Upon complete reaction conversion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars). After flash distillation, highly pure (R)-2-ethyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)but-2-en-1-ol was obtained in 98.5% yield.

(R)-2-methyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)but-2-en-1-ol synthesis

(76) (R)-2-methyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)but-2-enal (as a 98/2 E/Z isomers mixture) (48.1 g, 0.25 mol.), 1-naphtoic acid (0.215 g, 1.25 mmol., 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (13.9 mg, 0.0125 mmol., 0.005 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stiffing device. Sealed autoclave was then purged under stiffing with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 5 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 10 bars during all the reaction to afford desired product with 98.5% selectivity as a 98/2 E/Z isomers mixture and no loss of optical purity. Upon complete reaction conversion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars). After flash distillation, highly pure (R)-2-methyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)but-2-en-1-ol was obtained in 97.5% yield.

2-methyl-4-((S)-2,2,3-trimethylcyclopent-3-en-1-yl)butan-1-ol synthesis

(77) 2-methyl-4-((S)-2,2,3-trimethylcyclopent-3-en-1-yl)butanal (as a 50/50 diastereoisomers mixture) (48.5 g, 0.25 mol.), benzoic acid (0.152 g, 1.25 mmol., 0.5 mol. %) and [2-(diphenylphosphino)ethanamine][1,2-bis(diphenylphosphino)ethane]ruthenium (bispivalate) complex (5.8 mg, 0.00625 mmol., 0.0025 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 5 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 10 bars during all the reaction to afford desired product with complete selectivity as a 50/50 diastereoisomers mixture and no loss of optical purity. Upon complete reaction conversion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars). After flash distillation, highly pure 2-methyl-4-((S)-2,2,3-trimethylcyclopent-3-en-1-yl)butan-1-ol was obtained in more than 99% yield.

hexa-2,4-dien-1-yl pivalate synthesis

(78) In the case of hexa-2,4-dienal, if aldehyde base-free chemoselective hydrogenation reaction generally afforded desired product in much better yields compared to classical systems due to really high starting material sensitivity to basic conditions, catalytic activity was then noticeably increased running the reaction in the presence of 1 molar equivalent of various carboxylic acid anhydrides in order to afford hexa-2,4-dien-1-ol esters via reduction of the aldehyde into the alcohol which reacts with anhydride used to provide the corresponding ester.

(79) Hexa-2,4-dienal (as a 85/15 (E,E)/(Z,E) isomers mixture) (24 g, 0.25 mol.), pivalic anhydride (48.8 g, 0.26 mol.) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (27.8 mg, 0.025 mmol., 0.01 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with 98% selectivity as a 85/15 (E,E)/(Z,E) isomers mixture. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars). After flash distillation, highly pure hexa-2,4-dien-1-yl pivalate was obtained in 96% yield.

3-((R)-4-methylcyclohex-3-en-1-yl)butan-1-ol synthesis

(80) 3-((R)-4-methylcyclohex-3-en-1-yl)butanal (as a 50/50 diastereoisomers mixture) (41.6 g, 0.25 mol.), benzoic acid (0.152 g, 1.25 mmol., 0.5 mol. %) and [3-(diphenylphosphino)propan-1-amine][1,2-bis(diphenylphosphino)ethane]ruthenium(bispivalate) complex (5.9 mg, 0.00625 mmol., 0.0025 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 5 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was then increased and maintained to 10 bars during all the reaction to afford desired product with complete selectivity as a 50/50 diastereoisomers mixture and no loss of optical purity. Upon complete reaction conversion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars). After flash distillation, highly pure 3-((R)-4-methylcyclohex-3-en-1-yl)butan-1-ol was obtained in more than 99.0% yield.

Example 7

Catalytic Hydrogenation of Various Aldehydes Using the Invention's Process: Chemoselectivity

1-((1S,3R)-3-(2-hydroxyethyl)-2,2-dimethylcyclopropyl)propan-2-one synthesis

(81) 2-((1R,3S)-2,2-Dimethyl-3-(2-oxopropyl)cyclopropyl)acetaldehyde (16.8 g, 0.1 mol.), toluene (50.4 g, 300 wt. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (16.7 mg, 0.015 mmol, 0.015 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 90 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with 97% selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After flash chromatography, highly pure 1-((1S,3R)-3-(2-hydroxyethyl)-2,2-dimethylcyclopropyl)propan-2-one was obtained in 94% yield.

1-((1S,3S)-3-(2-hydroxyethyl)-2,2-dimethylcyclobutyl)ethanone synthesis

(82) 2-((1S,3S)-3-Acetyl-2,2-dimethylcyclobutyl)acetaldehyde (16.8 g, 0.1 mol.), toluene (50.4 g, 300 wt. %) and [(2-(diphenylphosphino)ethanamine)[1,1-bis(diphenylphosphino)ferrocene]ruthenium(bispivalate) complex (16.3 mg, 0.015 mmol, 0.015 mol. %) were loaded altogether in a 125 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 90 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with complete selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After flash distillation, highly pure 1-((1S,3S)-3-(2-hydroxyethyl)-2,2-dimethylcyclobutyl) ethanone was obtained in more than 99% yield.

4-((1R,2S)-2-(hydroxymethyl)-3,3-dimethyl-7-methylenecycloheptyl)butan-2-one synthesis

(83) (1S,7R)-2,2-Dimethyl-6-methylene-7-(3-oxobutyl)cycloheptanecarbaldehyde (11.8 g, 0.05 mol.), heptane (70.8 g, 600 wt. %, technical grade) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (11.1 mg, 0.01 mmol, 0.02 mol. %) were loaded altogether in a 200 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 10 bars hydrogen. It was then heated to 80 C. and hydrogen pressure was then increased and maintained to 30 bars during all the reaction to afford desired product with 96% selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After flash chromatography, 4-((1R,2S)-2-(hydroxymethyl)-3,3-dimethyl-7-methylenecycloheptyl) highly pure butan-2-one was obtained in 92% yield.

4-((1R,4S)-4-(5-hydroxypent-1-en-2-yl)-2,2-dimethylcyclobutyl)butan-2-one synthesis

(84) 4-((1S,2R)-3,3-Dimethyl-2-(3-oxobutyl)cyclobutyl)pent-4-enal (11.8 g, 0.05 mol.), methyl(tert-butyl)ether (70.8 g, 600 wt. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (11.1 mg, 0.01 mmol, 0.02 mol. %) were loaded altogether in a 200 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 10 bars hydrogen. It was then heated to 80 C. and hydrogen pressure was then increased and maintained to 30 bars during all the reaction to afford desired product with 98% selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After flash chromatography, highly pure 4-((1R,4S)-4-(5-hydroxypent-1-en-2-yl)-2,2-dimethylcyclobutyl)butan-2-one was obtained in 95% yield.

Racemic endo 1-(3-(2-hydroxyethyl)bicyclo[2.2.1]heptan-2-yl)propan-2-one synthesis

(85) Racemic endo 2-(3-(2-oxopropyl)bicyclo[2.2.1]heptan-2-yl)acetaldehyde (19.4 g, 0.1 mol.), toluene (58.2 g, 300 wt. %) and [(2-(diphenylphosphino)ethanamine)[(oxybis(2,1-phenylene))bis(diphenylphosphine)]ruthenium(bispivalate) complex (10.7 mg, 0.01 mmol, 0.01 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 90 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with complete selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After flash distillation, highly pure racemic endo 1-(3-(2-hydroxyethyl) bicyclo[2.2.1]heptan-2-yl)propan-2-one was obtained in 99% yield.

7-hydroxyheptan-2-one synthesis

(86) 6-Oxoheptanal (12.8 g, 0.1 mol.), toluene (76.8 g, 600 wt. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (22.2 mg, 0.02 mmol, 0.02 mol. %) were loaded altogether in a 200 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 80 C. and hydrogen pressure was maintained to 50 bars during all the reaction to afford desired product with 94% selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After flash chromatography, highly pure 7-hydroxyheptan-2-one was obtained in 90% yield.

1-(5,5-dimethylcyclohex-1-en-1-yl)-6-hydroxyhexan-1-one synthesis

(87) 6-(5,5-dimethylcyclohex-1-en-1-yl)-6-oxohexanal (11.1 g, 0.05 mol.), toluene (33.3 g, 300 wt. %) and [(2-(diphenylphosphino)ethanamine([2,2-bis(diphenylphosphino)-1,1-binaphthalene]ruthenium(bispivalate) complex (5.8 mg, 0.005 mmol, 0.01 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stiffing with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 90 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with more than 99% selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After flash chromatography, highly pure 1-(5,5-dimethylcyclohex-1-en-1-yl)-6-hydroxyhexan-1-one was obtained in 98% yield.

1-(5,5-dimethylcyclohex-1-en-1-yl)-5-hydroxy-4-methylpentan-1-one synthesis

(88) 5-(5,5-dimethylcyclohex-1-en-1-yl)-2-methyl-5-oxopentanal (11.1 g, 0.05 mol.), toluene (33.3 g, 300 wt. %) and [2-(di-tert-butylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (5.4 mg, 0.005 mmol, 0.01 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 90 C. and hydrogen pressure was then increased and maintained to 50 bars during all the reaction to afford desired product with 98% selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After flash chromatography, highly pure 1-(5,5-dimethylcyclohex-1-en-1-yl)-5-hydroxy-4-methylpentan-1-one was obtained in 94% yield.

9-hydroxy-2,6-dimethylnonan-4-one synthesis

(89) 4,8-dimethyl-6-oxononanal (18.4 g, 0.1 mol.), toluene (36.8 g, 200 wt. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (11.1 mg, 0.01 mmol, 0.01 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 90 C. and hydrogen pressure was increased and maintained to 50 bars during all the reaction to afford desired product with complete selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After flash distillation, highly pure 9-hydroxy-2,6-dimethylnonan-4-one was obtained in 99% yield.

7-hydroxy-3-isopropyl-4-methylheptan-2-one synthesis

(90) 5-acetyl-4,6-dimethylheptanal (18.4 g, 0.1 mol., as one diastereoisomer), toluene (55.2 g, 300 wt. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenyl phosphino)xanthene]ruthenium(bispivalate) complex (22.2 mg, 0.02 mmol, 0.02 mol. %) were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 80 C. and hydrogen pressure was then increased ad maintained to 50 bars during all the reaction to afford desired product with more than 99% selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was then cooled down to 25 C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After flash distillation, highly pure 1-(5,5-dimethylcyclohex-1-en-1-yl)-5-hydroxy-4-methylpentan-1-one was obtained in 99% yield.

(91) Catalytic Hydrogenation of Various Aldehydes Using the Invention's Process: Chemoselectivity in Aldehyde Versus Ketone Competitive Experiments

2-methyl-4-((R)-2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-enal versus (R,E)-3,3-dimethyl-5-(2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-en-2-one

(92) 2-Methyl-4-((R)-2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-enal (as a 40/60 (2S,4R)/(2R,4R) diastereoisomers mixture) (10.3 g, 0.05 mol), (R,E)-3,3-dimethyl-5-(2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-en-2-one (11.0 g, 0.05 mol.), octane (21.3 g, 100 wt. %) and [2-(diphenylphosphino)ethanamine][1,2-bis(diphenylphosphino)ethane]ruthenium(bispivalate) complex (4.7 mg, 0.005 mmol., 0.01 mol. %/aldehyde) were loaded altogether were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 100 C. and hydrogen pressure was increased and maintained to 50 bars during all the reaction that was followed by GC analysis.

(93) TABLE-US-00008 t (h) 0 1 2 4 6 7 8 12 Aldehydic 100 49.0 25.0 9.0 2.0 0.5 0 0 substrate (relative GC %) Ketonic 100 100 100 100 100 100 100 100 substrate (relative GC %) primary vs. 100 100 100 100 100 100 100 secondary alcohols formation selectivity (%)* *no hydrogenation of alkenes observed. Note: primary vs. secondary alcohol selectivity (%) = 100 (% primary alcohol % secondary alcohol)/(% primary alcohol + % secondary alcohol).

2-methyl-4-((R)-2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-enal versus trans 1-(2,2,6-trimethylcyclohexyl)hexan-3-one

(94) 2-Methyl-4-((R)-2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-enal (as a 40/60 (2S,4R)/(2R,4R) diastereoisomers mixture) (10.3 g, 0.05 mol), racemic trans 1-(2,2,6-trimethylcyclohexyl)hexan-3-one (11.2 g, 0.05 mol.), heptane (43.0 g, 200 wt. %) and [2-(diphenylphosphino)ethanamine][9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]ruthenium(bispivalate) complex (8.3 mg, 0.0075 mmol, 0.015 mol. %/aldehyde) were loaded altogether were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 90 C. and hydrogen pressure was increased and maintained to 50 bars during all the reaction that was followed by GC analysis.

(95) TABLE-US-00009 t (h) 0 0.5 1 2 3 4 6 7 9 Aldehydic substrate 100 66 48 31 16.6 11 4 2 0 (relative GC %) Ketonic substrate 100 100 99.9 99.8 99.7 99.6 99.4 99.3 99.1 (relative GC %) primary vs. secondary 99.7 99.6 99.4 99.3 99.1 98.8 98.6 98.2 alcohol formation selectivity (%)* *no hydrogenation of alkenes observed. Note: primary vs. secondary alcohol selectivity (%) = 100 (% primary alcohol % secondary alcohol)/(% primary alcohol + % secondary alcohol).

2-methyl-4-((R)-2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-enal versus acetophenone

(96) 2-Methyl-4-((R)-2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-enal (as a 40/60 (2S,4R)/(2R,4R) diastereoisomers mixture) (10.3 g, 0.05 mol), acetophenone (6.0 g, 0.05 mol.), octane (48.9 g, 300 wt. %), and [(2-(diphenylphosphino)ethanamine][1,1-bis(diphenyl phosphino)ferrocene]ruthenium(bispivalate) complex (8.1 mg, 0.0075 mmol., 0.015 mol. %/aldehyde) were loaded altogether were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 90 C. and hydrogen pressure was increased and maintained to 50 bars during all the reaction that was followed by GC analysis.

(97) TABLE-US-00010 t (h) 0 0.5 1 2 3 5 7 Aldehydic substrate 100 68 48 22 11 2.5 0 (relative GC %) Ketonic substrate 100 99.9 99.7 99.5 99 98.6 97.9 (relative GC %) primary vs. secondary 99.1 98.9 98.7 97.8 97.2 95.9 alcohol formation selectivity (%)* *no hydrogenation of alkenes observed. Note: primary vs. secondary alcohol selectivity (%) = 100 (% primary alcohol % secondary alcohol)/(% primary alcohol + % secondary alcohol).

2-methyl-4-((R)-2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-enal versus 3-methylcyclopentadec-5-ynone

(98) 2-Methyl-4-((R)-2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-enal (as a 40/60 (2S,4R)/(2R,4R) diastereoisomers mixture) (10.3 g, 0.05 mol), 3-methylcyclopentadec-5-ynone (11.7 g, 0.05 mol.), octane (66 g, 300 wt. %), and [(2-(diphenylphosphino)ethanamine][1,2-bis(diphenylphosphino)ethane]ruthenium(bispivalate) complex (9.3 mg, 0.01 mmol., 0.02 mol. %/aldehyde) were loaded altogether were loaded altogether in a 120 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 20 bars hydrogen. It was then heated to 80 C. and hydrogen pressure was increased and maintained to 50 bars during all the reaction that was followed by GC analysis.

(99) TABLE-US-00011 t (h) 0 0.5 1 2 4 6 8 10 Aldehydic substrate 100 65 49 31 11 4 1 0 (relative GC %) Ketonic substrate 100 99.8 99.6 99.2 98.3 97.5 96.5 92.0 (relative GC %) overall selectivity 98.8 98.5 97.7 96.3 94.9 93.2 85.2 (%)* secondary alcohol 0 0 0.1 0.2 0.4 0.6 0.8 0.9 (relative GC %) primary vs. secondary 100 99 99.4 99.1 98.8 98.4 98.2 alcohol formation selectivity (%) *hydrogenation of alkyne observed as the major competitive reaction. Note: primary vs. secondary alcohol selectivity (%) = 100 (% primary alcohol % secondary alcohol)/(% primary alcohol + % secondary alcohol).