CN102464672B - Mannitol derived chiral bidentate phosphorous ester ligand and preparation method thereof as well as application thereof - Google Patents

Mannitol derived chiral bidentate phosphorous ester ligand and preparation method thereof as well as application thereof Download PDF

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CN102464672B
CN102464672B CN201010551598.5A CN201010551598A CN102464672B CN 102464672 B CN102464672 B CN 102464672B CN 201010551598 A CN201010551598 A CN 201010551598A CN 102464672 B CN102464672 B CN 102464672B
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reaction
ligand
catalyst
enantioselectivity
ring
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CN102464672A (en
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王来来
赵庆鲁
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Lanzhou Institute of Chemical Physics LICP of CAS
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Lanzhou Institute of Chemical Physics LICP of CAS
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Abstract

The invention discloses a mannitol derived bidentate phosphorous ester and a preparation method thereof as well as application thereof. The structure of the ligand is as shown in the formula I; the ligand is of a white solid and can stably exist in the atmosphere of nitrogen; used raw materials have low price and are easily obtained; and the synthesis method is simple. In the atmosphere of nitrogen, the ligand and Cu salt react in an organic solvent to prepare a ligand/Cu catalytic agent in situ; the catalytic agent catalyzes asymmetrical 1, 4- conjugated addition, thereby the beta-ethyl annular copper product with optical activity is obtained; and the yield and the enantioselectivity are respectively up to 99% and 93%. R1 and R2 in the formula (I) are as shown in the specification.

Description

Chiral bidentate phosphite ligand that sweet mellow wine is derivative and preparation method thereof and purposes
Technical field
The present invention relates to derivative chiral bidentate phosphite ligand of a kind of sweet mellow wine and preparation method thereof and purposes.Be applied to prepare part/Cu complex compound catalyst, catalysis diethyl zinc is to the asymmetric Isosorbide-5-Nitrae-conjugate addition reaction of ring-type ketenes, and synthesis has optically active beta-ethyl cyclic ketone.
Background technology
Organometallic reagent is to α, asymmetric 1 of beta-unsaturated carbonyl compound, 4-conjugate addition reaction is the important method producing new chiral centre, research and development is in recent years rapid, this reaction has been applied to synthesis and has had optically active medicine and intermediate, as muskone (R-Muscone), Antimycobacterial reagent (Erogorgiaene), anticancer class medicine (Clavularin B) etc.
With regard to asymmetric Isosorbide-5-Nitrae-conjugate addition reaction, the metal-organic complex catalyst system and catalyzing with high activity and high selectivity is very key, and chiral ligand is the important component part of this type of catalyst.At present, multiple chiral ligand is successfully applied in this reaction, and wherein, chiral phosphoramidite ester part, chirality phosphite ester ligand, chirality P, N part etc. demonstrate greater activity and enantioselectivity [Benessere, V.; Litto, R.D.; DeRoma, A.; Ruffo, F.Coord.Chem.Rev.2010,254,390-401.].Such as, US Patent No. 20070259774A, US20090124836A, US7728177B2 individually disclose dissimilar phosphorous chiral ligand and catalyst complex thereof, and their application in conjugate addition reaction.Domestic patent of invention CN 101565436 A and CN 101090904 A individually discloses chiral phosphoramidite ligand containing different skeleton and preparation method, and at organometallic reagent to α, the application in beta-unsaturated carbonyl compound conjugate addition reaction.
In asymmetric Isosorbide-5-Nitrae-conjugate addition reaction, the existing outstanding selectivity of chiral ligand display to reaction substrate; And under the reaction condition of different temperatures, the enantioselectivity of reaction is different, and result illustrates that reaction system exists different catalytic active species, and some part copper complex active specy is easy to cause product racemization, reduces the enantioselectivity of reaction; Therefore, novel chiral phosphorus part developmental research and explore its application in asymmetry catalysis synthetic method and be still very important.
Summary of the invention
The object of the present invention is to provide the chiral bidentate phosphite ligand that a kind of sweet mellow wine is derivative.
Another object of the present invention is to provide the synthetic method of above-mentioned part.
A further object of the present invention is to provide the purposes of above-mentioned part, i.e. part and Cu salt reaction in-situ Kaolinite Preparation of Catalyst, and catalysis diethyl zinc is to the asymmetric Isosorbide-5-Nitrae-conjugate addition reaction of ring-type ketenes, and synthesis has optically active β-ethyl cyclic ketone product.
The chiral bidentate phosphite ligand that sweet mellow wine is derivative, its structure formula I represents:
Wherein R 1for:
Wherein R 2for:
Wherein R 1for a or b; R 2for a ' or b ' or c ' or d '.
The invention provides the synthetic method of above-mentioned part, it is characterized in that:
Under nitrogen atmosphere, with sweet mellow wine skeleton X, wherein R 1for a or b, the sub-phosphoryl chloride phosphorus oxychloride Y of chirality is reactant, wherein R 2for a ' or b ' or c ' or d ', at DMAP (DMAP) and triethylamine (NEt 3) under existence, take carrene as solvent, after reaction certain hour, remove solvent under reduced pressure, add toluene, after fully stirring, filtering solid, after filtrate is concentrated, through dodging chromatographic isolation, can synthesis of chiral bidentate phosphite ester ligand I.
The chemical equation of reaction is such as formula shown in II:
Above-mentioned reactions steps is described as follows:
Reaction dissolvent is carrene; The mol ratio of reactants of X and Y is 1: 2 ~ 4; The mol ratio of DMAP and compounds X is 1: 4 ~ 5; The mol ratio of compounds X and triethylamine is 1: 2 ~ 4; Reaction temperature is-15 DEG C ~ 30 DEG C, and the reaction time is 1 ~ 3h.
Another object of the present invention is to provide the purposes of above-mentioned part:
The preparation process of part/Cu catalyst can represent with reaction equation below:
Part+Cu salt → part/Cu catalyst
To above-mentioned catalyst preparation process, be described as follows:
Nitrogen atmosphere, in organic solvent, part and Cu salt stir and get final product synthetic ligands/Cu catalyst.Organic solvent is selected from oxolane, ether, toluene or carrene; Cu salt is selected from Cu (OTf) 2or (CuOTf) 2c 6h 6, wherein OTf is TFMS root; The mol ratio of Cu salt and part is: 1: 0.5 ~ 3; Reaction temperature is 25 DEG C; Reaction time is 1h.
Illustrate the asymmetric Isosorbide-5-Nitrae-conjugate addition reaction process of diethyl zinc to ring-type ketenes as follows:
Nitrogen atmosphere, ring-type ketenes and diethyl zinc is added successively in the solution of described part/Cu catalyst, at a certain temperature, after reaction a period of time, add distilled water and dilute hydrochloric acid solution cancellation reaction in the reactive mixture, be extracted with ethyl acetate, merge organic phase, use saturated NaHCO successively 3solution, saturated common salt water washing, anhydrous Na 2sO 4drying, filters, concentrated, and synthesis has optically active β-ethyl cyclic ketone product, gas-chromatography (GC) assay products.
Described ring-type ketenes is selected from 2-cyclopentenone, 2-cyclonene or 2-cycloheptene ketone; The mol ratio of part/Cu catalyst, ring-type ketenes and diethyl zinc is 1: 50: 120; Reaction temperature is-40 ~ 20 DEG C; Reaction time is 4 ~ 12h.
Detailed description of the invention
Contribute to understanding the present invention further by following embodiment, but do not limit the content of invention.
Embodiment 1 ~ 6: the preparation of the chiral bidentate phosphite ligand that sweet mellow wine derives.
Embodiment 7 ~ 27: the preparation of part/Cu catalyst and the application in the asymmetric Isosorbide-5-Nitrae-addition reaction of diethyl zinc to annulenones thereof.
Embodiment 1: prepare chiral bidentate phosphite ligand, structural formula is as follows:
Under nitrogen atmosphere, in the 100mL Xiu Langke bottle that magneton is housed, add b (206mg, 0.6mmol), the sub-phosphoryl chloride phosphorus oxychloride Y of chirality (R 2for c ', shown in II) (646mg, 1.8mmol) with DMAP (14.6mg, 0.12mmol), add 10mL carrene and make solvent, stir and solid is dissolved completely, solution is chilled to-15 DEG C, slow dropping triethylamine 0.34mL also reacts 0.5h at keeping-15 DEG C, reacts 1h under being then placed on room temperature.Removal of solvent under reduced pressure, adds 20mL toluene and fully stirs, filtering solid, and after filtrate is concentrated, obtain part 266mg through dodging chromatographic isolation, yield is 45%.
White solid, fusing point: 128-130 DEG C; [α] d 20=-165 (c=0.2, CH 2cl 2); 31p NMR (162MHz, d 6-DMSO): δ 146.83ppm. 1hNMR (400MHz, d 6-DMSO): δ 7.240 (d, J=7.6Hz, 2H), 7.051 (d, J=8.0Hz, 2H), 6.939 (d, J=8.0Hz, 2H), 6.853 (d, J=8.0Hz, 2H), 4.534 (t, J=6.4Hz, 2H), 4.159 (d, J=5.2Hz, 2H), 4.012 (t, J=7.2Hz, 2H), 3.770 (t, J=6.8Hz, 2H), 2.759 (m, 8H), 2.591 (m, 4H), 2.118 (m, 4H), 1.337-1.713 (m, 36H) ppm. 13c NMR (100MHz, d 6-DMSO): δ 145.40,137.98,137.01,134.65,133.76,129.45,129.18,128.77,127.03,118.63,118.39,109.06,75.69,73.58,64.97,35.57,33.75,28.40,27.25,25.17,24.63,23.59,23.41,21.94,21.84ppm.HRMS (ESI) theoretical value: C 58h 68naO 10p 2(M+Na) +1009.4180, experiment value: 1009.4176.
Embodiment 2: prepare chiral bidentate phosphite ligand, its structural formula is as follows:
With the method in embodiment 1, b (206mg, 0.6mmol), the sub-phosphoryl chloride phosphorus oxychloride Y of derivative chirality (R 2for d ', shown in II) (646mg, 1.8mmol), DMAP (14.6mg, 0.12mmol), triethylamine 0.34mL.Obtain part 252mg, yield 43%.
White solid, fusing point: 111-112 DEG C; [α] d 20=+184 (c=0.2, CH 2cl 2); 31p NMR (162MHz, d 6-DMSO): δ 144.91ppm. 1hNMR (400MHz, d 6-DMSO): δ 7.15 (d, J=8.4Hz, 2H), 7.08 (d, J=8.0Hz, 2H), 7.01 (d, J=8.4Hz, 2H), 6.86 (d, J=8.4Hz, 2H), 4.44 (t, J=8.8Hz, 2H), 4.21 (dd, J=12.8,5.6Hz, 2H), 3.87 (dd, J=8.8,6.4Hz, 2H), 3.76 (dd, J=8.4,4.8Hz, 2H), 2.78 (m, 8H), 2.60 (m, 4H), (2.13 m, 4H), 1.73 (m, 12H), 1.56-1.28 (m, 24H) ppm. 13c NMR (100MHz, d 6-DMSO): δ 145.28,137.90,134.67,133.67,131.48,129.47,129.00,128.63,128.59,127.06,118.75,118.58,109.34,75.06,73.13,67.30,65.48,35.94,34.17,29.70,28.35,27.18,27.11,24.45,23.55,23.15,22.30,21.89,21.83,21.78ppm.HRMS (ESI) theoretical value: C 58h 68naO 10p 2(M+Na) +1009.4180, experiment value: 1009.4167.
Embodiment 3: prepare chiral bidentate phosphite ligand, its structural formula is as follows:
With the method in embodiment 1, the sub-phosphoryl chloride phosphorus oxychloride Y of a (79mg, 0.3mmol), chirality (R 2for a ', shown in II) (421mg, 1.2mmol), DMAP (7.3mg, 0.06mmol), triethylamine 0.17mL.Obtain part 200mg, yield 75%.
White solid, fusing point: 119-121 DEG C, [α] d 20=-309 (c=0.2, CH 2cl 2), 31p NMR (162MHz, d 6-DMSO): δ 153.30ppm. 1hNMR (300MHz, d 6-DMSO): δ 8.15 (d, J=8.7Hz, 2H), 8.10 (d, J=8.1Hz, 2H), 8.07 (d, J=8.1Hz, 2H), 7.96 (d, J=9.0Hz, 2H), 7.56 (d, J=9.0Hz, 2H), 7.52 (t, J=7.8Hz, 4H), 7.43 (d, J=9.0Hz, 2H), 7.36 (t, J=8.1Hz, 4H), 7.23 (m, 4H), 4.83 (m, 2H), 4.42 (dd, J=10.5, 5.7Hz, 2H), 4.00 (t, J=7.8Hz, 2H), 3..7 (m, 2H), 1.49 (s, 6H), 1.35 (s, 6H) ppm. 13c NMR (75MHz, d 6-DMSO): δ 147.45,147.39,146.53,131.97,131.56,131.15,130.76,130.57,130.03,128.58,126.68,126.50,126.00,125.89,125.32,125.09,123.57,123.50,121.76,121.56,121.37,108.28,76.06,75.72,74.28,64.44,25.71,24.28ppm.HRMS (ESI) theoretical value: C 52h 44naO 10p 2(M+Na) +913.2302, experiment value: 913.2300.
Embodiment 4: prepare chiral bidentate phosphite ligand, its structural formula is as follows:
With the method in embodiment 1, the sub-phosphoryl chloride phosphorus oxychloride Y of a (158mg, 0.6mmol), chirality (R 2for b ', shown in II) (505mg, 1.44mmol), DMAP (14.6mg, 0.12mmol), triethylamine 0.34mL.Obtain part 221mg, yield 40%.
White solid, fusing point: 115-117 DEG C, [α] d 20=+496 (c=0.2, CH 2cl 2), 31p NMR (162MHz, d 6-DMSO): δ 150.41ppm. 1hNMR (400MHz, d 6-DMSO): δ 8.11 (t, J=8.8Hz, 4H), 8.03 (d, J=8.0Hz, 2H), 7.90 (d, J=8.8Hz, 2H), 7.55 (m, 6H), 7.45 (d, J=8.8Hz, 2H), 7.40 (d, J=8.0Hz, 2H), 7.36 (d, J=7.6Hz, 2H), 7.27 (d, J=8.0Hz, 2H), 7.20 (d, J=7.2Hz, 2H), 4.63 (t, J=8.8Hz, 2H), 4.42 (dd, J=12.8, 5.6Hz, 2H), 4.06 (dd, J=8.8, 6.4Hz, 2H), 3.99 (dd, J=8.8, 4.8Hz, 2H), 1.40 (s, 6H), 1.26 (s, 6H) ppm. 13c NMR (100MHz, d 6-DMSO): δ 147.39,147.34,146.42,131.98,131.70,131.22,130.86,130.65,130.02,128.67,128.60,126.74,126.60,126.01,125.39,125.18,123.54,123.49,121.75,121.66,121.59,109.12,75.17,75.07,73.42,65.85,26.50,24.89ppm.HRMS (ESI) theoretical value: C 52h 44naO 10p 2(M+Na) +913.2302, experiment value: 913.2280.
Embodiment 5: prepare chiral bidentate phosphite ligand, its structural formula is as follows:
With the method in embodiment 1, the sub-phosphoryl chloride phosphorus oxychloride Y of a (158mg, 0.6mmol), chirality (R 2for c ', shown in II) (860mg, 2.4mmol), DMAP (14.6mg, 0.12mmol), triethylamine 0.34mL.Obtain part 273mg, yield 50%.
White solid, fusing point: 132-133 DEG C, [α] d 20=-205 (c=0.2, CH 2cl 2), 31p NMR (162MHz, d 6-DMSO): δ 146.52ppm. 1hNMR (400MHz, d 6-DMSO): δ 7.13 (d, J=8.4Hz, 2H), 7.05 (d, J=8.4Hz, 2H), 6.96 (d, J=8.0Hz, 2H), 6.88 (d, J=8.0Hz, 2H), 4.55 (dd, J=8.8, 5.6Hz, 2H), 4.19 (dd, J=11.6, 5.6Hz, 2H), 3.95 (t, J=8.0Hz, 2H), 3.73 (dd, J=8.8, 5.6Hz, 2H), 2.77 (m, 8H), 2.58-2.63 (m, 4H), 2.08-2.16 (m, 4H), 1.72 (m, 12H), 1.47 (m, 4H), 1.42 (s, 6H), 1.31 (s, 6H) ppm. 13c NMR (100MHz, d 6-DMSO): δ 145.48,145.40,137.95,136.99,134.63,133.74,129.43,129.13,128.76,128.71,127.03,118.73,118.44,108.41,75.55,75.30,74.02,64.96,28.40,27.25,27.17,25.98,24.47,21.96,21.84ppm.HRMS (ESI) theoretical value: C 52h 60naO 10p 2(M+Na) +929.3554, experiment value: 929.3559.
Embodiment 6: prepare chiral bidentate phosphite ligand, its structural formula is as follows:
With the method in embodiment 1, the sub-phosphoryl chloride phosphorus oxychloride Y of a (157mg, 0.6mmol), chirality (R 2for d ', shown in II) (517mg, 1.44mmol), DMAP (14.6mg, 0.12mmol), triethylamine 0.34mL.Obtain part 229mg, yield 42%.
White solid, fusing point: 118-120 DEG C, [α] d 20=+213 (c=0.2, CH 2cl 2), 31p NMR (162MHz, d 6-DMSO): δ 144.38ppm. 1hNMR (400MHz, d 6-DMSO): δ 7.15 (d, J=8.8Hz, 2H), 7.07 (d, J=8.0Hz, 2H), 7.02 (d, J=8.0Hz, 2H), 6.87 (d, J=8.4Hz, 2H), 4.44 (t, J=8.4Hz, 2H), 4.22 (dd, J=12.8, 5.6Hz, 2H), 3.89 (dd, J=8.4, 6.0Hz, 2H), 3.77 (dd, J=8.8, 5.2Hz, 2H), 2.78 (m, 8H), 2.61 (m, 4H), 2.08-2.17 (m, 4H), 1.73 (m, 12H), 1.47 (m, 4H), 1.37 (s, 6H), 1.28 (s, 6H) ppm. 13c NMR (100MHz, d 6-DMSO): δ 145.36,145.31,137.95,137.07,134.74,133.69,129.50,129.02,128.71,128.67,127.11,118.86,118.65,108.93,74.87,74.76,73.49,65.76,28.40,27.25,27.18,26.48,25.00,21.96,21.90,21.84ppm.HRMS (ESI) theoretical value: C 52h 60naO 10p 2(M+Na) +929.3554, experiment value: 929.3552.
Embodiment 7:
In a nitrogen atmosphere, Cu (OTf) 2part (0.01mmol, 9.1mg) described in (0.005mmol, 1.8mg) and embodiment 5 is dissolved in 4mL toluene, and stirring at room temperature 1h obtains the solution of ligand i c/Cu catalyst.Be cooled to 0 DEG C, add 2-cyclonene (0.5mmol, 0.048mL) successively, diethyl zinc (hexane solution of 1mol/L, 1.2mL), react 4 hours at 0 DEG C.Add 2mL distilled water and 2mL dilute hydrochloric acid solution (2.0mol/L) cancellation reaction, be extracted with ethyl acetate (5mL × 3), merge organic phase, use saturated NaHCO successively 3solution, saturated common salt water washing, anhydrous Na 2sO 4drying, filters, concentrated, and analyze through gas-chromatography (GC), yield is 90%, and enantioselectivity is 83%, and product absolute configuration is R.
Embodiment 8:
With embodiment 7, it is 77% that part part (0.01mmol, the 9.9mg) GC be selected from described in embodiment 1 analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 75%, and product absolute configuration is R.
Embodiment 9:
With embodiment 7, part is selected from the part (0.01mmol, 9.9mg) described in embodiment 2, and it is 73% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 47%, and product absolute configuration is S.
Embodiment 10:
With embodiment 7, part is selected from the part (0.01mmol, 8.7mg) described in embodiment 3, and it is 85% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 74%, and product absolute configuration is R.
Embodiment 11:
With embodiment 7, part is selected from the part (0.01mmol, 8.7mg) described in embodiment 4, and it is 60% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 54%, and product absolute configuration is S.
Embodiment 12:
With embodiment 7, part is selected from the part (0.01mmol, 9.1mg) described in embodiment 6, and it is 83% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 48%, and product absolute configuration is S.
Embodiment 13:
With embodiment 7, mantoquita is selected from (CuOTf) 2c 6h 6(0.0025mmol, 1.25mg), it is 77% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 77%, and product absolute configuration is R.
Embodiment 14:
With embodiment 7, the part consumption described in embodiment 5 is (0.0025mmol, 2.3mg), and it is 85% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 65%, and product absolute configuration is R.
Embodiment 15:
With embodiment 7, part consumption as described in Example 5 is (0.005mmol, 4.5mg), and it is 92% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 68%, and product absolute configuration is R.
Embodiment 16:
With embodiment 7, part consumption as described in Example 5 is (0.015mmol, 13.6mg), and it is 87% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 79%, and product absolute configuration is R.
Embodiment 17:
With embodiment 7, part consumption as described in Example 5 is (0.0055mmol, 5.0mg), and it is 98% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 80%, and product absolute configuration is R.
Embodiment 18:
With embodiment 7, solvent is selected from carrene 4mL, and it is 40% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 2%, and product absolute configuration is R.
Embodiment 19:
With embodiment 7, solvent is selected from ether 4mL, and it is 77% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 15.6%, and product absolute configuration is R.
Embodiment 20:
With embodiment 7, solvent is selected from oxolane 4mL, and it is 18% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 68%, and product absolute configuration is R.
Embodiment 21:
With embodiment 7, reaction temperature and time are: react 4 hours at 20 DEG C.It is 99% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 64%, and product absolute configuration is R.
Embodiment 22:
With embodiment 7, reaction temperature and time are: react 12 hours at-10 DEG C.It is 99% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 89%, and product absolute configuration is R.
Embodiment 23:
With embodiment 7, reaction temperature and time are: react 12 hours at-20 DEG C.It is 99% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 93%, and product absolute configuration is R
Embodiment 24:
With embodiment 7, reaction temperature and time are: react 12 hours at-30 DEG C.It is 98% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 92%, and product absolute configuration is R.
Embodiment 25:
With embodiment 7, reaction temperature and time are: react 12 hours at-40 DEG C.It is 99% that GC analyzes display product 3-ethyl cyclohexanone yield, and enantioselectivity is 88%, and product absolute configuration is R.
Embodiment 26:
With embodiment 7, annulenones substrate is selected from 2-cyclopentenone (0.25mmol, 0.022mL), and reaction temperature and time are: react 12 hours at-20 DEG C.It is 59% that GC analyzes display product 3-ethylcyclopentanone yield, and enantioselectivity is 92%, and product absolute configuration is R.
Embodiment 27:
With embodiment 7, annulenones substrate is selected from 2-cycloheptene ketone (0.25mmol, 0.035mL), and reaction temperature and time are: react 12 hours at-20 DEG C.It is 97% that GC analyzes display product 3-ethyl cycloheptanone yield, and enantioselectivity is 90%, and product absolute configuration is R.

Claims (2)

1. the chiral bidentate phosphite ligand that sweet mellow wine is derivative, it is characterized in that this part formula I represents, is any one in following structural formula:
2. the application of chiral bidentate phosphite ligand that derives of a kind of sweet mellow wine according to claim 1, it is characterized in that formula I is as catalyst, under nitrogen atmosphere, catalyst is used for diethyl zinc to the asymmetric Isosorbide-5-Nitrae-conjugate addition reaction of ring-type ketenes; In the solution of part/Cu catalyst, add ring-type ketenes and diethyl zinc successively, after reaction a period of time, add distilled water and dilute hydrochloric acid solution cancellation reaction in the reactive mixture, be extracted with ethyl acetate, merge organic phase, use saturated NaHCO successively 3solution, saturated common salt water washing, dry, filter, concentrated, synthesis has optically active β-ethyl cyclic ketone product, gas-chromatography (GC) assay products; Described ring-type ketenes is selected from 2-cyclopentenone, 2-cyclonene or 2-cycloheptene ketone; The mol ratio of part/Cu catalyst, ring-type ketenes and diethyl zinc is 1: 50: 120; Reaction temperature is-40 ~ 20 DEG C; Reaction time is 4 ~ 12h.
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