CN102134264A - Preparation method of oxazoline phosphine ligand (Ir complex oxazoline phosphine ligand) substituted by chiral benzyl position - Google Patents

Preparation method of oxazoline phosphine ligand (Ir complex oxazoline phosphine ligand) substituted by chiral benzyl position Download PDF

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CN102134264A
CN102134264A CN2010105753038A CN201010575303A CN102134264A CN 102134264 A CN102134264 A CN 102134264A CN 2010105753038 A CN2010105753038 A CN 2010105753038A CN 201010575303 A CN201010575303 A CN 201010575303A CN 102134264 A CN102134264 A CN 102134264A
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侯雪龙
吕伟静
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Shanghai Institute of Organic Chemistry of CAS
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

The invention comprises composite of Ir complex of oxazoline phosphine ligand substituted by chiral benzyl position and having a chirality center. The Ir complex has the following structural formula: the complex is applicable to the asymmetrical hydrogenation which conducts asymmetrical catalytic hydrogenation to the olefine ketone compound to composite various unsaturated substrates of a carbonyl compound containing Alpha chiral carbon.

Description

Chirality benzyl position replaces the preparation method of De oxazoline phosphine ligand i r Luo He Wu oxazoline phosphine part
The present invention is application number 200810039495.3, the applying date to be that on June 25th, 2008, denomination of invention are the patent of invention of dividing an application of " the oxazoline phosphine fits over the asymmetric catalytic hydrogenation ketene compounds to synthesize the application in the body ketone compounds that contains alpha-chiral carbon ".
Technical field
The present invention includes a class and have the Ir complex compound of the oxazoline phosphine part that the benzyl position of chiral centre replaces and synthetic, with and with the iridium complex of known chiral oxazoline phosphine part with similar structures at the asymmetric catalytic hydrogenation ketene compounds with the application in the synthetic carbonyl complex that contains alpha-chiral carbon.The central chirality of such Ir complex compound Han You oxazoline has following structural formula:
Figure BSA00000375039900011
Background technology
Ketone compounds with a-chiral carbon is the very useful compound of a class (Angew.Chem.Int.Ed.2007,46,3942 in organic synthesis; Org.Lett.2001,3,711; Synlett 2005,12, and 1853).A lot of seminars are devoted to this work, thereby but because the easy racemization of carbonyl α position causes the result of the high enantioselectivity of reaction product is not a lot.Asymmetric catalytic hydrogenation is the reaction of the very efficient and atom economy of a class, and up to the present existing a lot of seminars are devoted to the work of this respect.Alkene, ketone, the unsaturated compounds of the much latent chirality of imines or the like all can obtain chipal compounds (The Handbook of Homogeneous Hydrogenation, Wiley-VCH:Weinheim, 2007) by asymmetric catalytic hydrogenation.The ketone compounds of alpha-chiral carbon can obtain by the asymmetric reduction of ketene compounds, and the present bibliographical information of this class work is not a lot (J.Org.Chem.1995,60,357; J.Mol.Cat.A:Chemical 2002,179, and 101; J.Eur.J.Org.Chem.2002,2151; Adv.Synth.Catal.2005,347,61; J.Am.Chem.Soc.2006,128,7329).At present the reduction of the ketene compounds of bibliographical information mainly is based on carbonyl reduction, chirality is enols used be primary product (Tetrahedron:Asymmetry 1992,3,1001; J.Am.Chem.Soc.1998,120,13529; Angew.Chem.Int.Ed.1998,37,1703; Org.Lett.2000,2,4173; J.Am.Soc.Chem.2002,124,6508; J.Am.Chem.Soc.2003,125,4404).
Summary of the invention
The purpose of this invention is to provide the Ir complex compound that a kind of new and effective benzyl position replaces N, P part;
Purpose of the present invention also provides a kind of above-mentioned new and effective benzyl position to replace the synthetic method of the Ir complex compound of N, P part;
Purpose of the present invention also provide Ir complex compound that a kind of above-mentioned new and effective benzyl position replaces N, P part at the asymmetric catalytic hydrogenation ketene compounds with the application in the synthetic carbonyl complex that contains alpha-chiral carbon.
The Ir complex compound that a kind of novel benzyl provided by the invention position replaces N, P part has following structural formula:
Figure BSA00000375039900021
R wherein 1=C 1～6Alkyl, phenyl or benzyl.Wherein, the C that especially recommends 1`6Alkyl be: CH 3, CH (CH 3) 2, C (CH 3) 3, CH 2CH (CH 3) 2
Ar 1=replacement, the single replacement or dibasic phenyl,, described substituting group is C 1～4Alkoxyl group, C 1～4Perfluoroalkyl, C 1～4Alkyl or halogen atom.What especially recommend is: p-methoxyphenyl, p-trifluoromethyl phenyl, 3,5-two trifluoromethyls or o-methyl-phenyl-etc.;
Figure BSA00000375039900022
B (C 6F 5) 4 -, PF 6 -, BF 4 -, CF 3SO 3 -Or Cl -
The synthetic method of the Ir complex compound of benzyl provided by the invention position replacement N, P part is as follows:
Under the protection of inert gas condition, in the organic solvent and 0 ℃～and under refluxing, part, [IrCODCl] 2, NaX mixture stirring reaction 0.5-24h.;
Wherein, recommendation response thing mol ratio is: described part, [IrCODCl] 2With the mol ratio of NaX=be 1: 0.5: 1.5～2.
Chirality benzyl of the present invention position replaces the preparation method of De oxazoline phosphine ligand i r complex compound, and adopt following method separation and purification after the described reaction: reaction solution is washed successively, saturated NaCl solution is washed, perhaps organic solvent extraction; Dry then, filter, be spin-dried for column chromatography, thin-layer chromatography or recrystallization.
Described column chromatography is recommended with V sherwood oil/V methylene dichloride=2/1 wash-out.
The benzyl position of chirality of the present invention replaces the preparation method of De oxazoline phosphine ligand i r complex compound, it is characterized in that the elutriant that described column chromatography or thin-layer chromatography adopt is that polar solvent and non-polar solvent volume ratio are 1: 1～20 mixed solvent.
Chirality benzyl of the present invention position replaces the preparation method of De oxazoline phosphine ligand i r complex compound, and the described organic solvent of its feature is benzene, toluene, hexanaphthene, sherwood oil, tetracol phenixin, tetrahydrofuran (THF), ethyl acetate, acetonitrile, ether, methylene dichloride, acetone, trichloromethane, normal hexane or dioxane.
Another object of the present invention be use that above-mentioned a kind of new and effective benzyl position replaces the Ir complex compound of N, P part and the De oxazoline phosphine ligand i r complex compound simple in structure reported in the asymmetric hydrogenation of ketenes so that a kind of synthetic efficiently method that contains the carbonyl complex of alpha-chiral carbon to be provided.
The iridium complex that the present invention has expanded known chiral oxazoline phosphine part at the asymmetric catalytic hydrogenation ketene compounds with the application in the synthetic carbonyl complex that contains alpha-chiral carbon;
The iridium complex structural formula of known chiral oxazoline phosphine part is as follows:
R wherein 1=C 1～6Alkyl, phenyl or benzyl.Wherein, the C that especially recommends 1`6Alkyl be: CH 3, CH (CH 3) 2, C (CH 3) 3Or CH 2CH (CH 3) 2
Ar 1=replacement, the single replacement or dibasic phenyl,, described substituting group is C 1～4Alkoxyl group, C 1～4Perfluoroalkyl, C 1～4Alkyl or halogen atom.What especially recommend is: p-methoxyphenyl, p-trifluoromethyl phenyl, 3,5-two trifluoromethyls or o-methyl-phenyl-etc.;
Figure BSA00000375039900032
B (C 6F 5) 4 -, PF 6 -, BF 4 -, CF 3SO 3 -Or Cl -
Figure BSA00000375039900033
Ir complex compound of the present invention is applied in the hydrogenation of ketenes, and its reactions steps is as follows:
The recommendation response condition: complex compound, in ketenes and the organic solvent under the 1-50atm hydrogen pressure room temperature reaction 1-24h.
Wherein, recommendation response thing mol ratio is: the mol ratio of described complex compound and ketenes is 0.005-0.05: 1;
Column chromatography is recommended with V sherwood oil/V ethyl acetate=10/1-2/1 wash-out.
The structural formula of described complex compound is:
Figure BSA00000375039900041
The structure of described ketenes is:
Figure BSA00000375039900042
Wherein, R 1And Ar 1As previously mentioned;
n＝0，1；
Figure BSA00000375039900043
R 2Be C 1～6Alkyl, aryl; Wherein, the C that especially recommends 1`6Alkyl be: CH 3, CH 2CH 3, CH 2CH 2CH 3
R 3Be aryl, C 1-6Alkyl;
R 4Be C 1-6Alkyl.
In the ketenes hydrogenant method of the present invention, described organic solvent is benzene, toluene, hexanaphthene, sherwood oil, tetracol phenixin, tetrahydrofuran (THF), ethyl acetate, acetonitrile, ether, methylene dichloride, acetone, trichloromethane, normal hexane or dioxane.
Embodiment
To help to understand the present invention by following embodiment, but not limit content of the present invention.
Synthesizing of the iridium complex of embodiment 1: chiral oxazoline phosphine part
Figure BSA00000375039900051
Under the room temperature argon shield condition, [IrCODCl] 20.125mmol, part 0.25mmol, NaBAR F3H 2O 0.375mmol is dissolved in the 3mL methylene dichloride, and TLC tracks to the part disappearance behind the 3h.Column chromatography gets the orange solid.
Cat-1 (R 1=CH (CH 3) 2, Ar 1=Ph): productive rate 88%. 1H NMR (300MHz, CD 3Cl): δ 7.74 (s, 8H), 7.54-7.24 (m, 17H), 7.11-7.05 (m, 1H), 5.02 (brs, 1H), 4.90 (brs, 1H), 4.57 (brs, 1H), 4.29 (brs, 1H), 4.13 (brs, 2H), 3.47 (brs, 1H), 3.34 (brs, 1H), 3.22 (brs, 1H), 2.43 (brs, 1H), 2.11 (brs, 5H), 1.82 (brs, 1H), 1.57 (brs, 2H), 0.732-0.710 (d, J=6.6Hz, 3H), 0.34 (brs, 3H); 31P NMR (300MHz, CD 3Cl): δ 5.2 (brs); Ms (MALDI) (M-BAR F -) 580.1, (M-BAR F --COD) 688.2; 13C NMR (75MHz, CD 3Cl) δ (ppm) 14.67,18.95,26.63 (brs), 29.09 (brs), 29.71,32.30 (brs), 32.39 (brs), 34.49 (brs), 35.47 (brs), 64.16,68.00 (brs), 69.80,70.54,86.98 (brs), 92.29 (brs), 117.48,119.12,122.73,126.34,128.26 (m), 128.67 (m), 129.17 (m), 129.31,129.57 (m), 129.96,131.47 (brs), 131.80,132.01,132.38,133.73,133.86,134.80,137.07,137.22,160.72,161.37,162.04,162.69,172.29 (brs); Ultimate analysis C65H50BF24IrNOP: theoretical value: C, 50.33; H, 3.25; N, 0.90; Measured value: C, 50.64; H, 3.51; N, 0.77.
Cat-2 (R 1=CH 3, Ar 1=Ph): productive rate 91%. 1H NMR (300MHz, CD 3Cl): δ 7.75 (s, 8H), 7.54-7.46 (m, 10H), 7.39-7.27 (m, 7H), 7.05-6.99 (m, 1H), 4.79 (brs, 2H), 4.33 (brs, 1H), 3.81 (brs, 1H), 3.62-3.56 (m, 1H), 3.50 (brs, 1H), 3.31 (brs, 1H), 2.36-2.15 (m, 5H), 1.98 (brs, 1H), 1.73 (brs, 2H), 0.88 (brs, 2H), 0.41 (brs, 3H); 31P NMR (300MHz, CD 3Cl): δ 7.33; Ms (MALDI) (M-BAR F -) 659.6; 13C NMR (75MHz, CD 3Cl) δ (ppm) 18.75,28.71 (brs), 29.72,30.87,31.33 (brs), 33.07 (brs), 37.38,37.47,60.37,64.41,65.28,76.40,89.23 (brs), 92.14 (brs), 117.51,119.13,122.74,126.36,127.62,127.87 (brs), 128.25 (brs), 128.77,128.91,129.15,129.26,129.40,129.54,129.97,131.39,131.86,132.01,132.12,132.23,132.35,132.81,133.54,133.67,134.82,137.05,137.22,138.95,160.73,161.39,162.05,162.71,173.18; Ultimate analysis C63H46BF24IrNO3P: theoretical value: C, 49.68; H, 3.04; N, 0.92; Measured value: C, 49.69; H, 3.24; N, 0.89.
Cat-3 (R 1=CH 2CH (CH 3) 2, Ar 1=Ph): productive rate 88%. 1H NMR (300MHz, CD 3Cl): δ 7.76 (s, 8H), 7.55-7.32 (m, 16H), 7.24 (brs, 1H), 7.13-7.08 (m, 1H), 5.05 (brs, 1H), 4.84 (brs, 1H), 4.60 (brs, 1H), 4.15 (brs, 2H), 3.43-3.21 (brs, 3H), 2.43 (brs, 1H), 2.15 (brs, 5H), 1.80 (brs, 1H), 1.61 (brs, 2H), 1.05 (brs, 2H), 0.88 (brs, 2H), 0.82-0.79 (m, 3H), 0.20 (brs, 3H); 31P NMR (300MHz, CD 3Cl): δ 5.17; Ms (MALDI) (M-BAR F -) 702.0; 13C NMR (75MHz, CD 3Cl) δ (ppm) 11.37,11.75,26.26,26.89 (brs), 29.20 (brs), 29.72,32.46 (brs), 34.33 (brs), 35.11 (brs), 39.25 (brs), 64.12 (brs), 68.13 (brs), 68.50 (brs), 69.97 (brs), 86.70 (brs), 92.15 (brs), 177.50,119.14,122.75,126.37,127.52 (brs), 128.32,128.74,129.20,129.35,129.54,129.98,131.52,131.57,131.85,132.04,132.31,132.39,133.89,134.02,134.43,134.83,137.05,137.19,160.74,161.40,162.07,162.72,172.21; Ultimate analysis C66H52BF24IrNO3P: theoretical value: C, 50.65; H, 3.35; N, 0.89; Measured value: C, 51.04; H, 3.31; N, 0.94.
Cat-4 (R 1=C (CH 3) 3, Ar 1=Ph): productive rate 56%. 1H NMR (300MHz, CD 3Cl): δ 7.94-7.88 (m, 2H), 7.75 (s, 8H), 7.54-7.48 (m, 10H), 7.36-7.30 (m, 4H), 7.25-7.20 (m, 1H), 7.19-7.12 (m, 1H), 5.36 (brs, 1H), 4.73-4.68 (d, J=13.2Hz, 1H), and 4.41-4.36 (m, 1H), 4.32-4.25 (m, 1H), and 4.22-4.15 (m, 1H), 4.06-4.01 (m, 1H), and 3.31-3.27 (d, J=13.8Hz, 1H), 3.16-3.08 (m, 2H), 2.68-2.54 (m, 1H), 2.26-1.95 (m, 4H), 1.84-1.76 (m, 1H), 1.59-1.42 (m, 2H), 0.77 (s, 9H); 31P NMR (300MHz, CD 3Cl): δ 7.20; Ms (MALDI) (M-BAR F -) 702.4, (M-BAR F -COD) 594.2; 13C NMR (75MHz, CD 3Cl) δ (ppm) 25.43,25.62,25.66,28.36,28.39,34.21,34.33,34.43,35.25,35.32,61.25,70.73,71.78,75.04,82.65,82.88,92.12,92.23,72.71,117.38,117.44,117.48,117.54,117.59,119.13,122.75,126.36,126.59,126.64,127.27,127.38,128.25,128.28,128.32,128.36,128.67,128.70,128.74,128.78,129.09,129.12,129.16,129.20,129.27,129.31,129.41,129.45,129.50,129.54,129.59,129.98,130.10,130.69,131.34,131.44,131.72,131.75,131.83,131.86,132.14,132.17,132.73,132.76,133.03,133.17,134.81,135.58,135.73,137.18,137.32,160.75,161.41,162.07,162.73,171.74; Ultimate analysis C66H52BF24IrNOP: theoretical value: C, 50.65; H, 3.35; N, 0.89; Measured value: C, 50.65; H, 3.45; N, 0.79.
Cat-5 (R 1=CH (CH 3) 2, Ar 1=4-MeOC6H4): productive rate 75%. 1H NMR (300MHz, CD 3Cl): δ 7.72 (s, 8H), 7.53 (s, 4H), 7.46-7.20 (m, 7H), 7.11-7.04 (m, 3H), 6.96-6.94 (m, 2H), 5.03 (brs, 1H), 4.76 (brs, 1H), 4.52 (brs, 1H), 4.26-4.13 (m, 2H), 3.85 (s, 3H), 3.79 (s, 3H), 3.36 (brs, 1H), 3.22-3.19 (m, 1H), 2.44 (brs, 1H), 2.26-1.97 (m, 5H), 1.62 (brs, 3H), 0.87-0.85 (m, 2H), 0.73-0.71 (d, J=6.9,3H), and 0.36-0.35 (brs, 3H); 31PNMR (300MHz, CD 3Cl): δ 3.43; Ms (MALDI) (M-BAR F -) 747.8, (M-BAR F -COD) 639.8; 13C NMR (75MHz, CD 3Cl) δ (ppm) 14.62,18.58,26.65 (brs), 29.00 (brs), 29.70,32.35 (brs), 34.61 (brs), 55.34,55.38,63.67,68.43 (brs), 69.69,70.25,86.03 (brs), 91.56 (brs), 114.82,114.97,117.45,119.11,122.73,126.34,128.27,128.66,128.69,129.07,129.11,129.52,129.96,131.27,132.02,134.79,135.41 (brs), 135.59,135.75,136.82,136.97,160.71,161.36,162.03,162.25,162.36,162.68,172.15; Ultimate analysis C68H56BF24IrNO3P: theoretical value: C, 49.95; H, 3.38; N, 0.87; Measured value: C, 49.79; H, 3.80; N, 0.97.
Cat-6 (R 1=CH (CH 3) 2, Ar 1=2-MeC6H4): productive rate 80%. 1H NMR (300MHz, CD 3Cl): δ 9.71-9.63 (m, 1H), 7.75 (s, 8H), 7.54-7.47 (m, 8H), 7.38-7.08 (m, 7H), 5.32 (brs, 1H), 4.41-4.13 (m, 5H), 3.21-3.17 (m, 1H), 3.11-3.03 (m, 1H), 2.64-2.53 (m, 5H), 2.30-2.12 (m, 3H), 2.04-1.91 (m, 3H), 1.51-1.35 (m, 3H), and 0.88-0.86 (m, 2H), 0.78-0.76 (d, J=7.2Hz, 5H), and 0.03-0.05 (d, J=6.9Hz, 1H) 31P NMR (300MHz, CD 3Cl): δ 8.55; Ms (MALDI) (M-BAR F -) 716.1; 13C NMR (75MHz, CD 3Cl) δ (ppm) 12.43,18.46,22.84,22.88,23.49,23.63,25.96,25.99,28.29.28.32,29.68,29.72,32.81,33.13,35.26,35.32,61.66,68.51,69.29,72.71,83.38,83.58,91.18,91.07,117.49 (m), 119.14,122.16,122.75,122.84,124.77,125.47,126.11,126.31,126.36,126.45,126.49,126.60,127.05,128.19,128.29,128.33,128.36,128.67,128.71,128.75,128.79,129.08,129.12,129.16,129.20,129.57 (m), 129.98,131.22,131.32,131.88,131.92,132.09,132.19,132.41,132.43,133.33,133.36,133.44,134.27,134.31,134.35,134.44,134.84,137.31,137.46,141.56,141.71,141.92,144.67,160.74,161.40,162.06,162.73,171.98; Ultimate analysis C67H54BF24IrNOP: theoretical value: C, 50.96; H, 3.45; N, 0.89; Measured value: C, 51.54; H, 3.61; N, 0.0.85
Embodiment 2: complex compound Cat under the 50bar condition to the catalytic hydrogenation of ketenes
Figure BSA00000375039900081
With complex compound Cat 0.002mmol, ketenes 0.2mmol adds in the reaction tubes, adds the 2ml methylene dichloride; After reaction tubes put into the logical hydrogen 50bar stirring at room 24h of autoclave, reaction system was crossed the silica gel short column.Gained oily matter is used for further analysis. 1H NMR determines reaction conversion ratio, and HPLC gets product ee%.
Embodiment 3: complex compound Cat under condition of normal pressure to the catalytic hydrogenation of ketenes
With complex compound Cat 0.002mmol, ketenes 0.2mmol adds in the reaction tubes, adds the 2ml methylene dichloride; Behind the logical hydrogen stirring at room 24h, reaction system is crossed the silica gel short column.Gained oily matter is used for further analysis. 1H NMR determines reaction conversion ratio, and HPLC gets product ee%.
2a: 1H NMR (300MHz, CD 3Cl): δ 7.08-7.05 (m, 2H), 6.85-6.81 (m, 2H), 3.79 (s, 3H), 2.96-2.90 (m, 1H), 2.85-2.5073 (m, 1H), 2.55-2.48 (m, 1H), 2.08 (s, 3H), 1.09-1.07 (d, J=6.6Hz, 3H); MS (EI) m/z (relative intensity): 192 (M+), 121 (100), 43 (68.04), 77 (15.08), 41 (13.32), 91 (11.05), 192 (10.25), 65 (6.81), 55 (3.17), 108 (2.58). transformation efficiency by 1H NMR determines that the ee value is measured by chirality HPLC.(OJ-H column flow rate 1.0mL/min, n-Hex/iPrOH 95: 5, λ=210nm), t 1=13.92min (minor), t 2=16.27min (major), [a] 20 D+ 24.8 (c 1.31, CH 2Cl 2, 91%ee).
2b: 1H NMR (300MHz, CD 3Cl): δ 7.31-7.14 (m, 5H), 3.04-2.97 (m, 1H), 2.89-2.77 (m, 1H), 2.60-2.53 (m, 1H), 2.09 (s, 3H), 1.10-1.08 (d, J=6.9Hz, 3H); MS (ED m/z (relative intensity): 162 (M+), 91 (100), 147 (16.29), 162 (23.63), 119 (11.61), 77 (5.52), 65 (8.6), 43 (47.73), 105 (2.93). transformation efficiency by 1H NMR determines that the ee value is measured by chirality HPLC.(OJ-H column flow rate 1.0mL/min, n-Hex/iPrOH 97: 3, λ=210nm), t 1=10.117min (minor), t 2=11.150min (major), [a] 20 D+ 33.5 (c 0.87, CH 2Cl 2, 98%ee).
2c: 1H NMR (300MHz, CD 3Cl): δ 7.07-7.04 (m, 2H), 6.83-6.80 (m, 2H), 3.79 (s, 3H), 2.94-2.77 (m, 2H), 2.55-2.17 (m, 3H), 2.08 (s, 3H), 1.08-1.06 (d, J=6.6Hz, 3H), 0.99-0.94 (t, J=7.2Hz, 3H); MS (EI) m/z (relative intensity): 206 (M+), 121 (100), 206 (12.71), 122 (9.25), 77 (8.50), 57 (8.34), 91 (8.07), 177 (3.13), 41 (3.41), 149 (2.76), 51 (2.22). transformation efficiency by 1H NMR determines that the ee value is measured by chirality HPLC.(OJ-H column flow rate 1.0mL/min, n-Hex/iPrOH 95: 5, λ=210nm), t 1=11.832min (minor), t 2=13.823min (major), [a] 20 D+ 61.1 (c 2.005, CH 2Cl 2, 97.5%ee).
2d: 1H NMR (300MHz, CD 3Cl): δ 7.06-7.03 (m, 2H), 6.82-6.79 (m, 2H), 3.78 (s, 3H), 2.84-2.77 (m, 1H), 2.73-2.65 (m, 1H), 2.63-2.57 (m, 1H), 2.34-2.23 (m, 1H), 2.17-2.04 (m, 1H), 1.72-1.59 (m, 1H), 1.50-1.41 (m, 3H), and 0.89-0.78 (m, 6H); MS (EI) m/z (relative intensity): 234 (M+), 121 (100), 234 (11.56), 205 (8.34), 191 (5.16), 91 (6.19), 71 (9.56), 43 (31.03); 13C NMR (75MHz, CD 3Cl) δ (ppm) 214.50,157.87,131.80,129.73,113.66,55.61,55.11,45.59,36.81,24.66,16.52,13.62,11.72; EI high resolution: C15H22O 2[M+] theoretical value: 234.1620, measured value: 234.1624; Transformation efficiency by 1H NMR determines that the ee value is measured by chirality HPLC.(OJ-H column flow rate 1.0mL/min, n-Hex/iPrOH 95: 5, λ=210nm), t 1=7.146min (minor), t 2=8.372min (major), [a] 20 D+ 45.1 (c 1.745, CH 2Cl 2, 96%ee).
2e: 1H NMR (300MHz, CD 3Cl): δ 8.09-8.06 (m, 1H), 7.49-7.44 (m, 1H), 7.34-7.26 (m, 3H), 7.26-7.22 (m, 4H), 3.53-3.47 (m, 1H), 2.96-2.91 (m, 2H), 2.80-2.60 (m, 2H), 2.16-2.05 (m, 1H), 1.86-1.72 (m, 1H); MS (EI) m/z (relative intensity): 236 (M+), 91 (100), 236 (30.96), 145 (17.06), 65 (14.06), 77 (12.06), 117 (7.04), 103 (3.49), 41 (3.37), 51 (5.95), 158 (2.34). transformation efficiency by 1H NMR determines that the ee value is measured by chirality HPLC.(OJ-H column flow rate 1.0mL/min, n-Hex/iPrOH 95: 5, λ=210nm), t 1=14.270min (minor), t 2=17.616min (major), [a] 20 D-9.5 (c 1.945, CH 2Cl 2, 98%ee).
2f: 1H NMR (300MHz, CD 3Cl): δ 7.30-7.14 (m, 5H), 3.27-3.21 (m, 1H), 2.60-2.50 (m, 1H), 2.47-2.28 (m, 3H), 2.10-2.00 (m, 2H), 1.86-1.80 (m, 1H), 1.72-1.56 (m, 2H), 1.42-1.26 (m, 1H); MS (EI) m/z (relative intensity): 188 (M+), 91 (100), 43 (30.10), 117 (27.73), 77 (21.63), 105 (17.94), 131 (12.33), 145 (8.75), 65 (24.58), 169 (2.84), 159 (4.21). transformation efficiency by 1H NMR determines that the ee value is measured by chirality HPLC.(OJ-H column flow rate 1.0mL/min, n-Hex/iPrOH 97: 3, λ=210nm), t 1=11.650min (minor), t 2=13.177min (major), [a] 20 D-39.9 (c 1.615, CH 2Cl 2, 98%ee).
2g: 1H NMR (300MHz, CD 3Cl): δ 7.94-7.91 (m, 2H), 7.57-7.52 (m, 1H), 7.47-7.42 (m, 2H), 7.29-7.15 (m, 5H), 3.81-3.69 (m, 1H), 3.20-3.14 (dd, J 1=6.3Hz, J 2=13.8Hz, 1H), 2.73-2.65 (dd, J=7.8Hz, J=13.5Hz, 1H), 1.21-1.19 (d, J=6.6Hz, 3H) MS (EI) m/z (relative intensity): 224 (M+), 105 (100), 77 (52.41), 91 (33.08), 224 (31.02), 51 (30.61), 41 (10.75), 209 (6.17), 117 (3.15). transformation efficiency by 1H NMR determines that the ee value is measured by chirality HPLC.(OJ-H column flow rate 1.0mL/min, n-Hex/iPrOH 95: 5, λ=210nm), t 1=11.431min (major), t 2=12.301min, [a] 20 D+ 63.1 (c 1.98, CH 2Cl 2, 96%ee).
2h: 1H NMR (300MHz, CD 3Cl): δ 7.30-7.11 (m, 10H), 3.13-3.07 (dd, J 1=5.4Hz, J 2=13.5Hz, 2H), 2.82-2.73 (m, 2H), 2.64-2.57 (m, 2H), 1.93-1.84 (m, 2H), 1.78-1.70 (m, 2H), 1.65-1.54 (m, 2H); MS (EI) m/z (relative intensity): 278 (M+), 91 (100), 187 (29.03), 117 (23.95), 130 (21.43), 169 (16.91), 65 (15.97), 159 (8.47), 146 (11.87), 104 (12.14), 78 (7.49), 55 (6.14). transformation efficiency by 1H NMR determines that the ee value is measured by chirality HPLC.(AS-H column flow rate 0.7mL/min, n-Hex/iPrOH 90: 10, λ=210nm), t Meso=6.885min, t 1=7.385min (major), t 2=10.918min (minor), [a] 20 D-38.7 (c 1.11, CH 2Cl 2,＞99%ee).
2i: 1H NMR (300MHz, CD 3Cl): δ 7.29-7.14 (m, 10H), 3.21-3.15 (m, 2H), 2.64-2.57 (m, 2H), 2.35-2.24 (m, 2H), 2.05-1.92 (m, 2H), 1.47-1.32 (m, 2H); MS (EI) m/z (relative intensity): 264 (M+), 91 (100), 173 (95.61), 264 (51.79), 117 (50.94), 65 (18.92), 129 (10.68), 104 (10.45), 77 (8.10), 41 (5.28). transformation efficiency by 1H NMR determines that the ee value is measured by chirality HPLC.(AS-H column flow rate 0.7mL/min, n-Hex/iPrOH 90: 10, λ=210nm), t 1=8.408min (minor), t 2=10.252min (major), t Meso=9.658, [a] 20 D+ 205.4 (c 0.95, CH 2Cl 2,＞99%ee).
2j: 1H NMR (300MHz, CD 3Cl): δ 8.07-8.04 (m, 1H), 7.49-7.44 (m, 1H), 7.32-7.21 (m, 3H), 6.30 (s, 1H), 6.09-6.08 (m, 1H), 3.44-3.40 (m, 1H), 3.01-2.75 (m, 4H), 2.23-2.17 (m, 1H), 1.89-1.76 (m, 1H); MS (EI) m/z (relative intensity): 226 (M+), 81 (100), 145 (12.76), 130 (6.39), 115 (11.30), 90 (18.49), 53 (12.22), 226 (34.67); 13C NMR (75MHz, CD 3Cl) δ (ppm) 198.80,153.83,144.05,141.17,133.28,132.29,128.70,127.45,126.57,110.19,106.62,47.11,28.76,28.23,28.07; EI high resolution: C15H14O 2[M+] theoretical value: 226.0994, measured value: the 226.0995. transformation efficiency by 1H NMR determines that the ee value is measured by chirality HPLC.(OD column flow rate 0.6mL/min, n-Hex/iPrOH 98: 2, λ=210nm), t 1=13.718min (major), t 2=14.821min (minor), [a] 20 D-22.6 (c 0.89, CH 2Cl 2, 98%ee).
2k: 1H NMR (300MHz, CD 3Cl): δ 8.04-8.01 (m, 1H), 7.48-7.43 (m, 1H), 7.32-7.22 (m, 2H), 3.01-2.97 (m, 2H), 2.60-2.50 (m, 1H), 2.29-2.19 (m, 1H), 1.91-1.70 (m, 3H), 1.36-1.24 (m, 1H), 0.98-0.96 (d, J=6.3Hz, 3H), 0.93-0.91 (d, J=6.3Hz, 3H); MS (EI) m/z (relative intensity): 202 (M+), 146 (100), 131 (26.92), 90 (13.68), 118 (11.02), 159 (4.9), 41 (5.06), 55 (3.48), 77 (3.26). transformation efficiency by 1H NMR determines that the ee value is measured by chirality HPLC.(AD-H column flow rate 0.6mL/min, n-Hex/iPrOH 99: 1, λ=210nm), t 1=10.66min (minor), t 2=11.53min (major), [a] 20 D+ 2.2 (c 0.835, CH 2Cl 2, 40%ee).

Claims (5)

1. the preparation method of the oxazoline phosphine ligand i r complex compound of a chirality is characterized in that obtaining by following step:
Under the protection of inert gas condition, in the organic solvent and 0 ℃～and under refluxing, part, [IrCODCl] 2With NaX mixture stirring reaction 0.5-24h.;
Wherein, reactant molar ratio is: described part, [IrCODCl] 2With the mol ratio of NaX be 1: 0.5: 1.5～2;
Described ligand structure formula is
R 1=C 1～6Alkyl, phenyl or benzyl;
Ar 1=replacement, the single replacement or dibasic phenyl,, described substituting group is C 1～4Alkoxyl group, C 1～4Perfluoroalkyl, C 1～4Alkyl or halogen atom;
Figure FSA00000375039800012
B (C 6F 5) 4 -, PF 6 -, BF 4 -, CF 3SO 3 -Or Cl -
R 1Or Ar 1According to claim 1.
2. the chirality benzyl position described in claim 1 replaces the preparation method of De oxazoline phosphine ligand i r complex compound, it is characterized in that described substituting group is p-methoxyphenyl, p-trifluoromethyl phenyl, 3,5-two trifluoromethyls or o-methyl-phenyl-.
3. the chirality benzyl position described in claim 1 replaces the preparation method of De oxazoline phosphine ligand i r complex compound, and it is characterized in that the following method separation and purification of described reaction back employing: reaction solution is washed successively, saturated NaCl solution is washed, perhaps organic solvent extraction; Dry then, filter, be spin-dried for column chromatography, thin-layer chromatography or recrystallization.
4. the benzyl position of chirality as claimed in claim 1 replaces the preparation method of De oxazoline phosphine ligand i r complex compound, it is characterized in that the elutriant that described column chromatography or thin-layer chromatography adopt is that polar solvent and non-polar solvent volume ratio are 1: 1～20 mixed solvent.
5. the chirality benzyl position described in claim 1 replaces the preparation method of De oxazoline phosphine ligand i r complex compound, and the described organic solvent of its feature is benzene, toluene, hexanaphthene, sherwood oil, tetracol phenixin, tetrahydrofuran (THF), ethyl acetate, acetonitrile, ether, methylene dichloride, acetone, trichloromethane, normal hexane or dioxane.
CN2010105753038A 2008-06-25 2008-06-25 Preparation method of oxazoline phosphine ligand (Ir complex oxazoline phosphine ligand) substituted by chiral benzyl position Pending CN102134264A (en)

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