CN101845056A - C1 symmetrical chiral diene ligand, synthesis method and application thereof to asymmetric reactions - Google Patents
C1 symmetrical chiral diene ligand, synthesis method and application thereof to asymmetric reactions Download PDFInfo
- Publication number
- CN101845056A CN101845056A CN 201010118341 CN201010118341A CN101845056A CN 101845056 A CN101845056 A CN 101845056A CN 201010118341 CN201010118341 CN 201010118341 CN 201010118341 A CN201010118341 A CN 201010118341A CN 101845056 A CN101845056 A CN 101845056A
- Authority
- CN
- China
- Prior art keywords
- chirality
- diene ligand
- reaction
- alkali
- asymmetric
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a chiral diene ligand, a synthesis method and the application thereof to asymmetric reactions. The chiral diene ligand has the main structural features that the chiral diene ligand is in a pairwise mutual enantiomer structure with a chiral cyclopentadiene dipolymer as shown in the accompanying drawing, the chiral diene ligand can be used as cocatalysts in rhodium catalysis asymmetric reactions, such as rhodium catalysis of asymmetric 1, 4-addition reactions of arylboronic acid and alpha, beta-unsaturated carbonyl compounds and catalysis of asymmetric addition reactions of arylboronic acid and aromatic imide.
Description
Technical field
The present invention relates to a kind of chirality diene ligand and synthetic method thereof of novel texture, these chirality diene ligands can be applied in the asymmetric reaction.
Background technology
The alkene metallic compound is used in transition metal-catalyzed reaction in a large number, but the binding ratio that all the time it is believed that alkene and metal a little less than, therefore be as the occupy-place molecule with it, be used for carrying out the ligand exchange synthetic catalyst, and it does not used as part necessary in the transition-metal catalysis with other heteroatom ligands.But studies show that successively, alkene metal complex itself is catalysis transition metal reaction well just, especially cyclooctadiene (COD) metal complex can successfully apply in a lot of catalyzed reactions, people recognize that gradually the part that alkene can be used as in the reaction equally uses ((a) Brown thus, J.M.and Lloyd-jones, G.C.J.Chem.Soc.Chem.Commun.1992,710. (b) Ueda, M.; Miyaura, N.J.Organomet.Chem, 2000,595,31. (c) Itooka, R.; Iguchi, Y.; Miyaura, N.J., et al.J.Org.Chem, 2003,68,6000.).Professor Hayashi of Japan in 2003 is incorporated into the chirality factor in the diene ligand, successfully with (Hayashi, T. in its utilization and the addition reaction of the catalytic aryl boric acid of rhodium to ketenes; Ueyama, K.; Tokunaga, N.; Yoshida, K.J.Am.Chem.Soc.2003,125,11508.).In this simultaneously, the Carreira professor of Switzerland has also carried out the research work of chirality diene ligand in independently working, reported its chirality diene ligand application in the catalytic kinetic resolution reaction of Ir by the development of natural terpenes compounds Karvon in 2004, good result (Fischer, C. have been obtained; Defieber, C.; Suzuki, T.; Carreira, E.M.J.Am.Chem.Soc.2004,126,1628).The work of above-mentioned initiative has transition metal-catalyzedly been opened up new research field for asymmetric, and has been become a new research focus very soon.A series of new chirality diene ligands are synthesized in succession, and used in many asymmetric reactions, especially in the catalytic asymmetric reaction of some rhodiums, embodied than conventional higher reactive behavior and selectivity (Defieber, the C. of chiral phosphine ligand; Gr ü tzmacher, H.; Carreira, E.M.Angew.Chem., Int.Ed.2008,47,4482.).
As a brand-new research field, though development still has several factors to restrict its development rapidly.Wherein the synthetic difficulty of restriction of part diversity and part is two importances wherein.So the various chirality diene ligand of development structure, to adapt to the different asymmetric catalysis and the substrate of different structure, developing advantages of simplicity and high efficiency chirality diene ligand synthetic method simultaneously is two important research contents in present this area research.
Summary of the invention
The purpose of this invention is to provide a kind of chirality diene ligand;
Purpose of the present invention also provides a kind of synthetic method of above-mentioned diene ligand;
Another object of the present invention provides the application of a kind of above-mentioned diene ligand in asymmetric reaction, especially at the catalytic α of rhodium (Rh), and beta-unsaturated carbonyl compound asymmetric 1,4-addition reaction and to the asymmetric reduction reaction of aromatic imine.
Chirality diene ligand of the present invention, it has following structural formula (in twos enantiomer) each other:
Wherein, the main constitutional features of above-mentioned chirality diolefin is the cycle pentadiene dimer skeleton with chirality; Substituent R in the general structure
1=C
1-6Alkyl, tertiary butyl dimethyl is silica-based, and is trimethyl silicon based, and tert-butyl diphenyl is silica-based, benzyl, benzoyl; Substituent R
2=R
3Or R
4The phenyl that replaces, 1-naphthyl, 2-naphthyl, heteroaryl, benzyl, perfluorinated sulfonic acid base or diarylphosphino; R
3Or R
4=H, C
1-6Alkyl, C
1-6Alkane, trifluoromethyl or halogen; Described halogen is F, Cl or Br; Described heteroaryl is a furyl, thienyl or pyridyl; Described aryl is phenyl, p-methoxyphenyl or p-methylphenyl.
The typical compound structural formula of chirality diene ligand of the present invention following (and corresponding enantiomorph):
The preparation method of chirality diene ligand of the present invention can be obtained by following method:
For (2S, 3R)-1 or (its synthetic method is represented by following type reaction formula for 2R, 3S)-1 diene ligand.
Wherein the chiral hydroxyl group compound (2S, 3R)-1a or (2R, 3S)-1a is according to synthetic ((a) Borsato, the G. of obtaining of bibliographical information method, Lucchi, O.D., Fabris, F., Lucchini, V., Tetrahedron Lett.2003,44,3517. (b) Rosenblum, M.J.Am.Chem.Soc., 1957,79,3179. (c) Tanaka, K., Ogasawara, K., Synthesis, 1995,1237.).
In organic solvent, under-78 ℃～room temperature condition, molecular formula is the halides of RBr or RCl, in the presence of alkali, with the chiral hydroxyl group compound (2S, 3R)-1a or (2R, 3S)-1a reacts and obtained I class diene ligand of the present invention in 1-24 hour; Described alkali is organic bases or mineral alkali, and organic bases is triethylamine (TEA), nitrogen methylmorpholine (NMP), diisopropyl ethyl amine or pyridine; Mineral alkali is sodium hydride, sodium hydroxide or potassium hydroxide; Described organic solvent is chloroform, methylene dichloride, methyl alcohol, ethanol, ether, tetrahydrofuran (THF), dioxane (dioxane); Described R represents C
1-6Alkyl, tertiary butyl dimethyl is silica-based, trimethyl silicon based, tert-butyl diphenyl is silica-based, benzyl or benzoyl; The mol ratio of described oxy-compound, halides, alkali is 1: 1～3: 1～3;
For (2S, 3R)-2 or (its synthetic method is represented by following type reaction formula for 2R, 3S)-2 diene ligand.
Method one: represent by following type reaction formula:
Wherein chiral carbonyl compounds (2S, 3R)-3 or (2R, 3S)-the 3rd, according to synthetic ((a) Borsato, the G. of obtaining of bibliographical information method, Lucchi, O.D., Fabris, F., Lucchini, V., Tetrahedron Lett.2003,44,3517. (b) Rosenblum, M.J.Am.Chem.Soc., 1957,79,3179. (c) Tanaka, K., Ogasawara, K., Synthesis, 1995,1237.).
Concrete response situation can be described below step by step:
The first step: under the room temperature, organic solvent and 2,6-lutidine exist down, chiral carbonyl compounds (2S, 3R)-3 or (2R 3S)-3 obtains corresponding triflated compound (2S with trifluoromethanesulfonic acid anhydride reactant 3-12 hour, 3R)-4 or (2R, 3S)-4; Described chiral carbonyl compounds, trifluoromethanesulfanhydride anhydride and 2, the mol ratio of 6-lutidine are 1: 1～3: 1～3;
Second step: in solvent and under 50～100 ℃ the heating condition, triflated and thing (2S, 3R)-4 or (2R, 3S)-4 under the effect of low-valent transition metals catalyzer and alkali, take place with organoboron reagent or with organic grignard reagent generation linked reaction, obtained chirality diene ligand of the present invention in 1-6 hour; Described solvent is water, organic solvent or the mixed solvent of the two; Described organoboron reagent is that molecular formula is RB (OH)
2Boric acid or molecular formula be RBF
3The potassium fluoborate of K; Organic Grignard reagent is that molecular formula is the azoviolet of RMgBr or RMgCl; Described R=phenyl, R
1Perhaps R
2The phenyl, 1-naphthyl, 2-naphthyl, heteroaryl or the benzyl that replace; Described heteroaryl is furyl, thienyl or pyridyl.Described low-valent transition metals is tetrakis triphenylphosphine palladium (Pd (PPh
3)
4), two dibenzylideneacetonepalladium palladium (Pd (dba)
2), dichloro (1,1 '-ferrocene phosphoric acid) palladium (PdCl
2(dppf)), dichloro two (triphenyl phosphorus) palladium (PdCl
2(PPh
3)
2), palladium (Pd (OAc)
2) or praseodynium iron (Fe (acac)
3); Described alkali is organic bases or mineral alkali, and organic bases is triethylamine (TEA), nitrogen methylmorpholine (NMP), diisopropyl ethyl amine or pyridine; Mineral alkali is sodium hydride, sodium hydroxide or potassium hydroxide; Described organic solvent is chloroform, methylene dichloride, methyl alcohol, ethanol, ether, tetrahydrofuran (THF), dioxane (dioxane); The mol ratio of described triflated compound, organoboron reagent or Grignard reagent, transition-metal catalyst, alkali is 1: 1～3: 0.05～0.2: 3～10;
Chirality diene ligand of the present invention can use with some asymmetric catalysis in, especially the catalytic aryl boric acid of rhodium (Rh) is for α, beta-unsaturated carbonyl compound asymmetric 1,4-addition reaction and to the asymmetric reduction reaction of aromatic imine.Concrete response situation is described below:
(1) for α, the addition reaction of beta-unsaturated carbonyl compound:
In organic solvent, aryl boric acid, vinyl chlorination rhodium ([RhCl (C
2H
4)
2]
2) and the mixing of chirality diene ligand, under ℃ condition of room temperature～60, stirred 15～20 minutes, add α, beta-unsaturated carbonyl compound, the aqueous solution of adding alkali, reaction is 2-24 hour under ℃ condition of room temperature～60, obtains adduct.Described organic solvent is acetone (acetone), tetrahydrofuran (THF) (THF), dioxane (dioxane), toluene (toluene) or methyl alcohol (methol); The concentration of aqueous solution of described alkali is 0.5M～2.0M, and alkali is triethylamine (Et
3N), potassium hydroxide (KOH), sodium hydroxide (NaOH), potassiumphosphate (K
3PO
4), yellow soda ash (Na
2CO
3) or salt of wormwood (K
2CO
3); Described α, beta-unsaturated carbonyl compound, aryl boric acid, chirality diene ligand, vinyl chlorination rhodium ([RhCl (C
2H
4)
2]
2) and the mol ratio of alkali be 1: 1.5～3: 0.01～0.05: 0.01～0.05: 0.5～2.
Following form specifically enumerate its at the catalytic phenyl-boron dihydroxide of rhodium for α, the experimental result in the addition reaction of beta-unsaturated carbonyl compound cyclonene.
| Numbering | Part | Productive rate (%) | ??ee(％) |
| ??1 | ??1a | ??98 | ??95 |
| ??2 | ??1b | ??92 | ??87 |
| ??3 | ??1c | ??92 | ??88 |
| ??4 | ??1d | ??96 | ??86 |
| ??5 | ??1e | ??96 | ??-9 |
| ??6 | ??2a | ??70 | ??78 |
| ??7 | ??2b | ??77 | ??37 |
(2) for the addition reaction of aromatic imine:
In organic solvent, aryl boric acid, vinyl chlorination rhodium ([RhCl (C
2H
4)
2]
2) and the mixing of chirality diene ligand, under ℃ condition of room temperature～60, stirred 15～20 minutes, add imines, add triethylamine (Et
3N), reaction is 2-24 hour under ℃ condition of room temperature～60, obtains adduct.Described organic solvent is acetone (acetone), tetrahydrofuran (THF) (THF), dioxane (dioxane) or toluene (toluene); Described aryl imine, aryl boric acid, vinyl chlorination rhodium ([RhCl (C
2H
4)
2]
2), the mol ratio of chirality diene ligand and triethylamine is 1: 1.5～3: 0.01～0.05: 0.01～0.05: 0.5～2.
Following form specifically enumerate its at the catalytic aryl boric acid of rhodium for the experimental result in the addition reaction of group with imine moiety.
| Numbering | ??Ar 1 | ??Ar 2 | Part | Product 9 | Productive rate (%) | ??ee(％) |
| ??1 | ??4-MeOC 6H 4 | ??C 6H 5 | ??2a | ??9a | ??92 | ??93 |
| ??2 | ??4-MeOC 6H 4 | ??C 6H 5 | ??2b | ??9a | ??86 | ??32 |
| ??3 | ??4-MeOC 6H 4 | ??C 6H 5 | ??2c | ??9a | ??93 | ??88 |
| ??4 | ??4-MeOC 6H 4 | ??C 6H 5 | ??2d | ??9a | ??65 | ??-10 |
| ??5 | ??4-MeOC 6H 4 | ??C 6H 5 | ??2e | ??9a | ??94 | ??91 |
| ??6 | ??C 6H 5 | ??4-MeOC 6H 4 | ??2a | ??9a | ??92 | ??92 |
| ??7 | ??C 6H 5 | ??4-MeC 6H 4 | ??2a | ??9b | ??93 | ??92 |
| ??8 | ??4-MeC 6H 4 | ??C 6H 5 | ??2a | ??9b | ??90 | ??91 |
| ??9 | ??4-MeOC 6H 4 | ??C 6H 5 | ??2a | ??9a | ??92 | ??93 |
| ??10 | ??4-BrC 6H 4 | ??C 6H 5 | ??2a | ??9c | ??94 | ??93 |
Specific implementation method
Following example helps to understand the present invention, but can not limit content of the present invention.
Embodiment 1
Compound 1b's is synthetic:
In the 50ml dry reaction bottle, add 90mg 60%NaH (1.5mmol), dissolve with 10ml THF, 0 ℃ slowly adds 148mg (1mmol) (2S down, 3R)-and the 10ml THF solution of 1a, stirring reaction slowly dripped 93ul methyl iodide (1.5mmol) down at 0 ℃ after 30 minutes, was warming up to room temperature gradually, stir 12h, saturated NH
4The Cl cancellation, ethyl acetate extraction, organic phase is with saturated NaCl solution washing, the anhydrous sodium sulphate solid drying concentrates, and the gained crude product obtains 155mg colourless transparent liquid (2S by column chromatography (petrol ether/ethyl acetate=80/1 wash-out) separation and purification, 3R)-and 1b, productive rate 96%.
1H?NMR(400MHz，CDCl
3)：δ＝1.37(d，1H，J＝8Hz)，1.49(d，1H，J＝8Hz)，2.85(s，1H)，2.91-2.92(m，2H)，3.24(br?s，1H)，3.37(s，3H)，4.18-4.20(m，1H)，5.58-5.61(m，2H)，5.67-5.68(m，1H)，6.05-6.06(m，1H).MS：m/z＝162(M
+)
Embodiment 2
Compound 1c's is synthetic:
In the 50ml dry reaction bottle, add 200mg 60%NaH (2.5mmol), dissolve with 10ml DMF, 0 ℃ slowly adds 296mg (2mmol) (2S down, 3R)-and the 10ml DMF solution of 1a, stirring reaction slowly dripped 600ul cylite (2.5mmol) down at 0 ℃ after 30 minutes, was warming up to room temperature gradually, stir 12h, saturated NH
4The Cl cancellation, ethyl acetate extraction, organic phase is with saturated NaCl solution washing, the anhydrous sodium sulphate solid drying concentrates, and the gained crude product obtains 405mg colourless transparent liquid (2S by column chromatography (petrol ether/ethyl acetate=50/1 wash-out) separation and purification, 3R)-and 1c, productive rate 85%.
1H?NMR(400MHz，CDCl
3)：δ＝1.39(d，1H，J＝8Hz)，1.50(d，1H，J＝8Hz)，2.86(s，1H)，2.91-2.95(m，1H)，3.24-3.25(m，1H)，4.37-4.42(m，1H)，4.51(d，1H，J＝12Hz)，4.55(s，1H)，4.63(d，1H，J＝11.6Hz)，5.57-5.64(m，2H)，5.68-5.70(m，1H)，6.12-6.14(m，1H)，7.31-7.36(m，5H).
13C?NMR(100MHz，CDCl
3)：δ＝44.80，45.19，46.26，51.25，53.65，72.12，72.18，82.52，127.35，127.53，127.64，127.78，128.31，128.41，131.92，132.68，134.91，135.24.MS：m/z＝238(M
+).
Embodiment 3
Compound 1d's is synthetic:
In the 50ml dry reaction bottle, add 148mg (2S, 3R)-and 1a (1.0mmol), with the dissolving of 25ml methylene dichloride, and add 161ulPyridine (2.0mmol), 0 ℃ slowly adds down, add 138ul BzCl (1.2mmol) while heating up, be heated to backflow, stirring reaction returns to room temperature gradually after 30 minutes, stir 5h, saturated NH
4The Cl cancellation, ethyl acetate extraction, organic phase is with saturated NaCl solution washing, the anhydrous sodium sulphate solid drying concentrates, and the gained crude product obtains 236mg colourless transparent liquid (2S by column chromatography (petrol ether/ethyl acetate=50/1 wash-out) separation and purification, 3R)-and 1d, productive rate 94%.
1H?NMR(400MHz，CDCl3)：δ＝1.44(d，1H，J＝8.4Hz)，1.51(d，1H，J＝8Hz)，2.82(s，1H)，2.92(br?s，1H)，3.18-3.23(m，1H)，3.34-3.36(m，1H)，5.68-5.71(m，2H)，5.74-5.76(m，1H)，5.79(dd，1H，J＝5.2，2.8Hz)，6.04(dd，1H，J＝5.2，2.8Hz)，7.44-7.48(m，2H)，7.55-7.59(m，1H)，8.06-8.08(m，2H).
13C?NMR(100MHz，CDCl3)：δ＝44.92，45.11，46.30，51.48，53.30，78.77，128.43，129.64，130.58，130.88，132.87，133.18，134.04，137.41，166.46.MS：m/z＝252(M+).
Embodiment 4
Compound 1e's is synthetic:
In the 50ml dry reaction bottle, add 148mg (2S, 3R)-1a (1.0mmol), 2mg DMAP (0.1mmol) with 15ml DMF dissolving, and adds 350ul triethylamine (2.5mmol), 0 ℃ of 10mlDMF solution that slowly adds 300mgTBSCl (2.0mmol) down, stirring reaction is warming up to room temperature gradually after 30 minutes, stir 5h, saturated NH
4The Cl cancellation, ethyl acetate extraction, organic phase is with saturated NaCl solution washing, the anhydrous sodium sulphate solid drying concentrates, and the gained crude product obtains 220mg colourless transparent liquid (2S by column chromatography (petrol ether/ethyl acetate=100/1 wash-out) separation and purification, 3R)-and 1e, productive rate 84%.
1H?NMR(400MHz，CDCl
3)：δ＝0.07(s，3H)，0.09(s，3H)，0.92(s，9H)，1.36(d，1H，J＝8Hz)，1.46(d，1H，J＝8Hz)，2.82-2.87(m，3H)，3.18-3.20(m，1H)，4.67-4.69(m，1H)，5.44-5.50(m，2H)，5.67(dd，1H，J＝5.6，2.8Hz)，6.08(dd，1H，J＝5.6，2.4Hz).
13C?NMR(100MHz，CDCl
3)：δ＝-4.88，-4.72，18.33，26.05，45.13，46.72，46.84，51.04，53.38，75.54，131.78，133.88，135.14，135.18.MS：m/z＝262(M
+).
Embodiment 5
Compound 2a's is synthetic:
Among the dry Schlenk tube, argon shield adds 566mg PhB (OH) respectively
2, 80mgPd (PPh
3)
4, 650mg (2S, 3R)-4 (2.32mmol), 21ml toluene, 7ml ethanol, freezing ventilation three times, the Na of adding 10ml 2M
2CO
3Solution, 110 ℃ of following back flow reaction 5h after reaction is finished, add saturated NH
4The Cl cancellation, ethyl acetate extraction, organic phase is with saturated NaCl solution washing, the anhydrous sodium sulphate solid drying concentrates, the gained crude product by column chromatography (sherwood oil wash-out) separation and purification obtain the 390mg colourless transparent liquid (2S, 3R)-2a, productive rate 80%.
1H?NMR(400MHz，CDCl
3)：δ＝1.41(d，1H，J＝8.4Hz)，1.56(d，1H，J＝8Hz)，1.80-1.87(m，1H)，2.35-2.43(m，1H)，2.88-2.94(m，2H)，3.07(s，1H)，3.62-3.66(m，1H)，5.79-5.81(m，1H)，5.91(s，1H)，6.02-6.04(m，1H)，7.19-7.33(m，3H)，7.46-7.48(m，2H).
13C?NMR(100MHz，CDCl
3)：δ＝35.02，42.00，45.25，46.33，50.39，54.53，125.76，126.76，127.70，128.30，133.07，135.69，136.66，143.06.MS：m/z＝208(M
+).
Embodiment 6
Compound 2b's is synthetic:
Among the dry Schlenk tube, argon shield adds 8.8mg Fe (acac) respectively
3, 140mg (2S, 3R)-4 (0.5mmol) add 6ml THF, and 250ul NMP slowly drips 1ml BnMgCl (2M) under 0 ℃ in system, stirring reaction, and after reaction was finished, low temperature added saturated NH down
4The Cl cancellation, ethyl acetate extraction, organic phase is with saturated NaCl solution washing, the anhydrous sodium sulphate solid drying concentrates, the gained crude product by column chromatography (sherwood oil wash-out) separation and purification obtain the 90mg colourless transparent liquid (2S, 3R)-2b, productive rate 81%.
1H?NMR(400MHz，CDCl
3)：δ＝1.24(d，1H，J＝8Hz)，1.48(d，1H，J＝7.6Hz)，1.59-1.64(m，1H)，2.13-2.19(m，1H)，2.70-2.74(m，1H)，2.80(s，1H)，2.86(s，1H)，2.99-3.01(m，1H)，3.17(d，1H，J＝15.6Hz)，3.35(d，1H，J＝15.2Hz)，5.03(s，1H)，5.88-5.90(m，1H)，5.98-6.01(m，1H)，7.17-7.21(m，3H)，7.25-7.30(m，2H).
13C?NMR(100MHz，CDCl
3)：δ＝34.22，37.35，41.99，44.37，46.27，50.42，55.80，125.90，126.79，128.22，129.09，133.32，135.41，140.12，144.47.MS：m/z＝222(M
+).
Embodiment 7
Compound 2c's is synthetic:
So that (2S 3R)-4 is a raw material, operates referring to embodiment 5 productive rate 74%.
1H?NMR(400MHz，CDCl
3)：δ＝1.45(d，1H，J＝8Hz)，1.60(d，1H，J＝8Hz)，1.86-1.92(m，1H)，2.41-2.49(m，1H)，2.95-2.99(m，2H)，3.04(s，1H)，3.66-3.68(m，1H)，5.76(dd，1H，J＝5.6，2.8Hz)，6.06(dd，1H，J＝5.6，2.8Hz)，6.12(br?s，1H)，7.70(s，1H)，7.86(s，2H).
13C?NMR(100MHz，CDCl
3)：δ＝35.21，42.12，44.96，46.27，50.47，54.36，122.18，124.90，125.45，125.49，132.03，133.57，135.18，136.63，140.84.MS：m/z＝344(M
+).
Embodiment 8
Compound 2d's is synthetic:
So that (2S 3R)-4 is a raw material, operates referring to embodiment 5 productive rate 58%.
1H?NMR(400MHz，CDCl
3)：δ＝1.35(d，1H，J＝8Hz)，1.51(d，1H，J＝8Hz)，1.94-2.01(m，1H)，2.46-2.53(m，1H)，2.69(s，1H)，2.96-3.00(m，2H)，3.81-3.85(m，1H)，5.65(br?s，1H)，6.00(dd，1H，J＝5.6，2.8Hz)，6.16(dd，1H，J＝5.6，2.8Hz)，7.43-7.48(m，4H)，7.72(d，1H，J＝8Hz)，7.82-7.84(m，1H)，8.13-8.16(m，1H).
13C?NMR(100MHz，CDCl
3)：δ＝35.46，41.56，45.17，46.49，50.55，58.57，124.76，125.32，125.52，125.55，126.18，126.95，128.33，131.57，132.38，132.99，134.00，136.31，136.77，142.75.MS：m/z＝258(M
+).
Embodiment 9
Compound 2e's is synthetic:
So that (2S 3R)-4 is a raw material, operates referring to embodiment 5 productive rate 60%.
1H?NMR(400MHz，CDCl
3)：δ＝1.46(d，1H，J＝8Hz)，1.59(d，1H，J＝8Hz)，1.85-1.92(m，1H)，2.41-2.48(m，1H)，2.92-2.97(m，2H)，3.19(s，1H)，3.76-3.78(m，1H)，5.78-5.80(m，1H)，6.04-6.06(m，2H)，7.40-7.48(m，2H)，7.62-7.64(m，1H)，7.73-7.86(m，4H).
13C?NMR(100MHz，CDCl
3)：δ＝35.17，42.04，45.37，46.35，50.44，54.51，124.15，124.51，125.53，126.08，127.61，127.71，128.10，128.51，132.57，133.11，133.67，134.01，135.72，143.02.MS：m/z＝258(M
+).
Embodiment 10
The two rare parts of chirality (2S, 3R)-1a at the catalytic boric acid of rhodium to the application in the annulenones asymmetric reduction reaction
In dry Schlenk tube, argon shield adds 73mg phenylo boric acid (0.6mmol), 1.8mg[RhCl (C down
2H
4)
2]
2(0.0045mmol), and the two rare parts of 1.33g chirality (2S, 3R)-1a, the 1.5ml dioxane stirs 15min under the room temperature, adds 29ul (0.3mmol) cyclonene again, 0.15ml (1.5M) K
3PO
4The aqueous solution.Stir reaction down under the room temperature, after reaction is finished, ethyl acetate extraction three times, organic phase is with saturated NaCl solution washing, anhydrous sodium sulphate solid drying.Concentrate, column chromatography (PE/EA=15/1, wash-out) gets colourless oil liquid 51mg, productive rate 98%, 95%ee value.
1H?NMR(300MHz，CDCl
3)：δ＝1.70-1.90(m，2H)，2.05-2.20(m，2H)，2.35-2.62(m，4H)，2.95-3.08(m，1H)，7.19-7.25(m，3H)，7.34(t，J＝7.8Hz，2H).
Embodiment 11
The two rare parts of chirality (2S, 3R)-1c at the catalytic boric acid of rhodium to the application in the annulenones asymmetric reduction reaction
In dry Schlenk tube, argon shield adds 73mg phenylo boric acid (0.6mmol), 1.8mg[RhCl (C down
2H
4)
2]
2(0.0045mmol), and the two rare parts of 2.1g chirality (2S, 3R)-1c, the 1.5ml dioxane stirs 15min under the room temperature, adds 29ul (0.3mmol) cyclonene again, 0.15ml (1.5M) K
3PO
4The aqueous solution.Stir reaction down under the room temperature, after reaction is finished, ethyl acetate extraction three times, organic phase is with saturated NaCl solution washing, anhydrous sodium sulphate solid drying.Concentrate, column chromatography (PE/EA=15/1, wash-out) gets colourless oil liquid 51mg, productive rate 92%, 88%ee value.
1H?NMR(300MHz，CDCl
3)：δ＝1.70-1.90(m，2H)，2.05-2.20(m，2H)，2.35-2.62(m，4H)，2.95-3.08(m，1H)，7.19-7.25(m，3H)，7.34(t，J＝7.8Hz，2H).
Embodiment 12
The two rare parts of chirality (2S, 3R)-2a at the catalytic boric acid of rhodium to the application in the asymmetric reduction reaction of imines
In dry Schlenk tube, argon shield adds 73mg phenylo boric acid (0.6mmol), 2.9mg[RhCl (C down
2H
4)
2]
2(0.0075mmol), and the two rare parts of 3.1g chirality (2S, 3R)-2a, 2.0ml toluene, 55 ℃ are stirred 30min down, add 87mg (0.3mmol) again to the methoxyl group aryl imine, 85uL (0.6mmol) Et
3N, 55 ℃ of following reaction 5h, adding shrend goes out, ethyl acetate extraction three times, organic phase is with saturated NaCl solution washing, anhydrous sodium sulphate solid drying.Concentrate column chromatography (PE/EA=5/1,2%Et
3The N wash-out), get white solid 101mg, productive rate 92%, 93%ee value.
1H?NMR(300MHz，CDCl
3)：δ＝2.38(s，3H)，3.75(s，3H)，5.06(d，1H，J＝6.9Hz)，5.52(d，1H，J＝7.2Hz)，6.73(d，2H，J＝8.4Hz)，6.99(d，2H，J＝8.7Hz)，7.09-7.21(m，7H)，7.56(d，2H，J＝7.8Hz).
13C?NMR(75MHz，CDCl
3)：δ＝21.43，55.23，60.82，113.88，127.19，127.26，127.41，128.45，128.59，129.30，132.79，137.48，140.76，143.05，158.97.
Embodiment 13
The two rare parts of chirality (2S, 3R)-2e at the catalytic boric acid of rhodium to the application in the asymmetric reduction reaction of imines
In dry Schlenk tube, argon shield adds 73mg phenylo boric acid (0.6mmol), 2.9mg[RhCl (C down
2H
4)
2]
2(0.0075mmol), and the two rare parts of 3.1g chirality (2S, 3R)-2e, 2.0ml toluene, 55 ℃ are stirred 30min down, add 87mg (0.3mmol) again to the methoxyl group aryl imine, 85uL (0.6mmol) Et
3N, 55 ℃ of following reaction 5h, adding shrend goes out, ethyl acetate extraction three times, organic phase is with saturated NaCl solution washing, anhydrous sodium sulphate solid drying.Concentrate column chromatography (PE/EA=5/1,2%Et
3The N wash-out), get white solid 103mg, productive rate 94%, 91%ee value.
1H?NMR(300MHz，CDCl
3)：δ＝2.38(s，3H)，3.75(s，3H)，5.06(d，1H，J＝6.9Hz)，5.52(d，1H，J＝7.2Hz)，6.73(d，2H，J＝8.4Hz)，6.99(d，2H，J＝8.7Hz)，7.09-7.21(m，7H)，7.56(d，2H，J＝7.8Hz)。
Claims (7)
1. chirality diene ligand, it has following four of enantiomer kinds of structural formulas each other in twos:
Wherein, R
1=C
1-6Alkyl, tertiary butyl dimethyl is silica-based, trimethyl silicon based, tert-butyl diphenyl is silica-based, benzyl or benzoyl; R
2=R
3Or R
4The phenyl, 1-naphthyl, 2-naphthyl, heteroaryl, benzyl, perfluorinated sulfonic acid base or the diarylphosphino that replace; R
3Or R
4=H, C
1-6Alkyl, C
1-6Alkane or trifluoromethyl or halogen; Described halogen is F, Cl or Br; Described heteroaryl is furyl, thienyl or pyridyl; Described aryl is phenyl, p-methoxyphenyl, p-methylphenyl.
2. a kind of chirality diene ligand as claimed in claim 1 is characterized in that having following structural formula and corresponding enantiomorph:
3. as the preparation method of claim 1 and 2 described chirality diene ligands, its feature such as following method are synthetic:
For (2S, 3R)-1 or (2R, 3S)-1 the one-tenth method of diene ligand is as follows:
In organic solvent, under-78 ℃～room temperature condition, molecular formula is the halides of RBr or RCl, in the presence of alkali, with the chiral hydroxyl group compound (2S, 3R)-1a or (2R, 3S)-1a reacts and obtained I class diene ligand of the present invention in 1-24 hour; Described R represents C
1-6Alkyl, tertiary butyl dimethyl is silica-based, and is trimethyl silicon based, and tert-butyl diphenyl is silica-based, benzyl, benzoyl; The mol ratio of described chiral hydroxyl group compound, halides, alkali is 1: 1～3: 1～3;
For (2S, 3R)-2 or (2R, 3S)-2 the synthetic method of structure part is as follows:
(1) under a. room temperature, organic solvent and 2,6-lutidine exist down, chiral carbonyl compounds (2S, 3R)-3 or (2R 3S)-3 obtains corresponding triflated compound (2S with trifluoromethanesulfonic acid anhydride reactant 3-12 hour, 3R)-4 or (2R, 3S)-4; Described chiral carbonyl compounds, trifluoromethanesulfanhydride anhydride and 2, the mol ratio of 6-lutidine are 1: 1～3: 1～3;
B. in solvent and under 50～100 ℃ the heating condition, triflated compound (2S, 3R)-4 or (2R, 3S)-4 under the effect of low-valent transition metals catalyzer and alkali, obtained described chirality diene ligand in 1-6 hour with the organoboron reagent generation or with organic grignard reagent generation linked reaction; Described solvent is water, organic solvent or the mixed solvent of the two; Described organoboron reagent is that molecular formula is RB (OH)
2Boric acid or molecular formula be RBF
3The potassium fluoborate of K; Organic Grignard reagent is that molecular formula is the azoviolet of RMgBr or RMgCl; Described R=phenyl, R
1Perhaps R
2The phenyl, 1-naphthyl, 2-naphthyl, heteroaryl or the benzyl that replace; Described heteroaryl is a furyl, thienyl or pyridyl; Described low-valent transition metals is tetrakis triphenylphosphine palladium, two dibenzylideneacetonepalladium palladium, dichloro (1,1 '-ferrocene phosphoric acid) palladium, dichloro two (triphenyl phosphorus) palladium, palladium or praseodynium iron; The mol ratio of described triflated compound, organoboron reagent or Grignard reagent, transition-metal catalyst, alkali is 1: 1～3: 0.05～0.2: 3～10;
Described chipal compounds (2S, 3R)-1a or (2R, 3S)-1a, (2S, 3R)-3 or (2R, 3S)-3, (2S, 3R)-4 or (2R, 3S)-4, (2S, 3R)-5 or (2R, structure 3S)-5 is as follows:
4. method as claimed in claim 3 is characterized in that described alkali is organic bases or mineral alkali, and organic bases is triethylamine, nitrogen methylmorpholine, diisopropyl ethyl amine or pyridine; Mineral alkali is sodium hydride, sodium hydroxide or potassium hydroxide.
5. method as claimed in claim 3 is characterized in that described organic solvent is chloroform, methylene dichloride, methyl alcohol, ethanol, ether, tetrahydrofuran (THF) or dioxane.
6. a chirality diolefin as claimed in claim 1 is used for the promotor of rhodium catalysis asymmetric reaction.
7. the purposes of a kind of chirality diene ligand as claimed in claim 6, it is characterized in that described rhodium catalysis asymmetric reaction is rhodium catalysis aryl boric acid and α, beta-unsaturated carbonyl compound asymmetric 1,4-addition reaction or catalysis aryl boric acid and to the asymmetric reduction reaction of aromatic imine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101183410A CN101845056B (en) | 2010-03-05 | 2010-03-05 | C1 symmetrical chiral diene ligand, synthesis method and application thereof to asymmetric reactions |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101183410A CN101845056B (en) | 2010-03-05 | 2010-03-05 | C1 symmetrical chiral diene ligand, synthesis method and application thereof to asymmetric reactions |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101845056A true CN101845056A (en) | 2010-09-29 |
| CN101845056B CN101845056B (en) | 2012-08-29 |
Family
ID=42769888
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010101183410A Expired - Fee Related CN101845056B (en) | 2010-03-05 | 2010-03-05 | C1 symmetrical chiral diene ligand, synthesis method and application thereof to asymmetric reactions |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101845056B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102675017A (en) * | 2012-06-08 | 2012-09-19 | 河北博伦特药业有限公司 | Method for preparing chiral diaryl- substitute methylamine |
| CN109456236A (en) * | 2018-12-14 | 2019-03-12 | 河南科技学院 | The synthetic method of chiral N-Ts diaryl methylamines |
| CN109908954A (en) * | 2017-12-12 | 2019-06-21 | 西南大学 | A kind of chiral aldehydes catalyst and preparation method and the method for being catalyzed asymmetric nucleophilic addition |
| EP3365320A4 (en) * | 2015-10-21 | 2019-07-10 | B.G. Negev Technologies & Applications Ltd., at Ben-Gurion University | Dicyclopentadiene derivatives and polymers thereof |
| CN111217809A (en) * | 2018-11-27 | 2020-06-02 | 江苏奥赛康药业有限公司 | Chiral nitrogen-containing diene ligand and preparation method and application thereof |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB202215535D0 (en) | 2022-10-20 | 2022-12-07 | Univ Nottingham | Diastereomeric dienes |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1368945A (en) * | 1999-08-14 | 2002-09-11 | 艾夫西亚有限公司 | Transfer hydrogenation process |
-
2010
- 2010-03-05 CN CN2010101183410A patent/CN101845056B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1368945A (en) * | 1999-08-14 | 2002-09-11 | 艾夫西亚有限公司 | Transfer hydrogenation process |
Non-Patent Citations (2)
| Title |
|---|
| 19851231 Toshio Ito,et al Optical resolution of 3a,4,7,7a-tetrahydro-4,7-methano-1H-indene derivatives 3631-3632 1-2 , 2 * |
| 19981231 Peyman Salehi,et al Selective and Efficient Alcoholyses of Ailylic, Secondary- and Tertiary Benzylic Alcohols in the Presence of Iron (III) 943-948 1-7 , 2 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102675017A (en) * | 2012-06-08 | 2012-09-19 | 河北博伦特药业有限公司 | Method for preparing chiral diaryl- substitute methylamine |
| EP3365320A4 (en) * | 2015-10-21 | 2019-07-10 | B.G. Negev Technologies & Applications Ltd., at Ben-Gurion University | Dicyclopentadiene derivatives and polymers thereof |
| US11059939B2 (en) | 2015-10-21 | 2021-07-13 | B.G. Negev Technologies And Applications Ltd., At Ben-Gurion University | Dicyclopentadiene derivatives and polymers thereof |
| CN109908954A (en) * | 2017-12-12 | 2019-06-21 | 西南大学 | A kind of chiral aldehydes catalyst and preparation method and the method for being catalyzed asymmetric nucleophilic addition |
| CN109908954B (en) * | 2017-12-12 | 2021-11-16 | 西南大学 | Chiral aldehyde catalyst, preparation method thereof and method for catalyzing asymmetric nucleophilic addition reaction |
| CN111217809A (en) * | 2018-11-27 | 2020-06-02 | 江苏奥赛康药业有限公司 | Chiral nitrogen-containing diene ligand and preparation method and application thereof |
| CN111217809B (en) * | 2018-11-27 | 2021-06-08 | 江苏奥赛康药业有限公司 | Chiral nitrogen-containing diene ligand and preparation method and application thereof |
| CN109456236A (en) * | 2018-12-14 | 2019-03-12 | 河南科技学院 | The synthetic method of chiral N-Ts diaryl methylamines |
| CN109456236B (en) * | 2018-12-14 | 2021-02-26 | 河南科技学院 | Synthesis method of chiral N-Ts diaryl methylamine compound |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101845056B (en) | 2012-08-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wen et al. | Stereoselective synthesis of trisubstituted alkenes via cobalt-catalyzed double dehydrogenative borylations of 1-alkenes | |
| CN101845056B (en) | C1 symmetrical chiral diene ligand, synthesis method and application thereof to asymmetric reactions | |
| García-Rubia et al. | Cu-catalyzed silylation of alkynes: a traceless 2-pyridylsulfonyl controller allows access to either regioisomer on demand | |
| Murai et al. | Rhodium‐catalyzed synthesis of chiral spiro‐9‐silabifluorenes by dehydrogenative silylation: mechanistic insights into the construction of tetraorganosilicon stereocenters | |
| Crudden et al. | Expanding the scope of transformations of organoboron species: carbon–carbon bond formation with retention of configuration | |
| CN100482644C (en) | Chiral diene ligand, synthesis method and its application in asymmetric reaction | |
| CN111217848B (en) | Spiro-dihydrobenzothiole diphenol compound, synthesis method and application thereof | |
| CN102503966B (en) | Schiff-base ligand-based rare-earth metal complex, preparation method and applications | |
| Gu et al. | Synthesis and structural studies on the chiral phosphine-NHC rhodium and palladium complexes for their performances in the metal-catalyzed reactions | |
| Nikol et al. | Tricyclic Sulfoxide–Alkene Hybrid Ligands for Chiral Rh (I) Complexes: The “Matched” Diastereomer Catalyzes Asymmetric C–C Bond Formations | |
| CN103483363B (en) | Multifarious chiral aminoboronic acid and its preparation method and application | |
| JPWO2012137460A1 (en) | Novel ruthenium complex and method for producing optically active alcohol compound using the same as catalyst | |
| CN109956970A (en) | Biphenyl type tridentate ligand ruthenium complex and its preparation method and application | |
| Higham et al. | P-chirogenic phosphines. MOP/diPAMP hybrids, their oxide crystal structures, reduction studies and alternative syntheses | |
| CN103408573A (en) | Boric acid derivatives, and preparation method and application thereof | |
| CN110330591A (en) | Porous organic polymer and its preparation method and application of the one kind containing Phosphine ligands | |
| CN109232650A (en) | Chiral 1- phospha Norbornadiene derivatives and its synthetic method | |
| CN104744514B (en) | A kind of chiral phosphorus alkene part, synthetic method and its application in asymmetric reaction | |
| CN111217809B (en) | Chiral nitrogen-containing diene ligand and preparation method and application thereof | |
| Cadierno et al. | Stereoselective synthesis of chiral terminal (E)-1, 3-enynes derived from the aldehydes (1R)-(−)-myrtenal and (S)-(−)-perillaldehyde using the alkynyl–phosphonio complex [Ru {C CCH2 (PPh3)}(η5-C9H7)(PPh3) 2][PF6] as synthon | |
| Takei et al. | Novel catalytic hydrogenolysis of silyl enol ethers by the use of acidic ruthenium dihydrogen complexes | |
| CN111039767B (en) | Method for preparing deuterated aldehyde by using triazole carbene as catalyst | |
| CN104513274B (en) | A kind of chiral pincerlike compounds of P and its palladium complex | |
| CN102553646A (en) | Chiral diamine diphosphine metal compound catalysts as well as preparation method and application thereof | |
| CN103396426B (en) | Chirality boronic acid derivatives and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120829 Termination date: 20190305 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |