CN102464672A - 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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CN102464672A
CN102464672A CN2010105515985A CN201010551598A CN102464672A CN 102464672 A CN102464672 A CN 102464672A CN 2010105515985 A CN2010105515985 A CN 2010105515985A CN 201010551598 A CN201010551598 A CN 201010551598A CN 102464672 A CN102464672 A CN 102464672A
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CN102464672B (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 enanatioselectivity are respectively up to 99% and 93%. R1 and R2 in the formula (I) are as shown in the specification.

Description

N.F,USP MANNITOL deutero-chirality bidentate phosphite ester ligand and preparation method thereof and purposes
Technical field
The present invention relates to a kind of N.F,USP MANNITOL deutero-chirality bidentate phosphite ester ligand and preparation method thereof and purposes.Be applied to prepare part/Cu complex compound catalyst, the catalysis zinc ethyl is asymmetric 1 to the ring-type ketenes, the 4-conjugate addition reaction, and synthetic have optically active beta-ethyl cyclic ketone.
Background technology
Organometallic reagent is to α; Asymmetric 1 of beta-unsaturated carbonyl compound; The 4-conjugate addition reaction is the important method that produces new chiral centre; Researchdevelopment in recent years is rapid, and this reaction has been applied to synthetic have optically active medicine and midbody, like muskone (R-Muscone), mycobacteria reagent (Erogorgiaene), anticancer type of medicine (Clavularin B) etc.
Just asymmetric 1, the 4-conjugate addition reaction, the organometallic complex catalystsystem with high reactivity and highly selective is very key, and chiral ligand is the important component part of this type of catalyzer.At present, multiple chiral ligand is successfully applied in this reaction, wherein, chiral phosphoramidite ester part, chirality phosphite ester ligand, chirality P, N part etc. demonstrates greater activity and enantioselectivity [Benessere, V.; Litto, R.D.; DeRoma, A.; Ruffo, F.Coord.Chem.Rev.2010,254,390-401.].Such as, U.S. Pat 20070259774A, US20090124836A, US7728177B2 disclose dissimilar phosphorous chiral ligand and catalyst complex thereof respectively, and their application in conjugate addition reaction.Domestic patent of invention CN 101565436 A disclose chiral phosphoramidite ligand and the preparation method who contains different skeletons respectively with CN 101090904 A, and at organometallic reagent to α, the application in the beta-unsaturated carbonyl compound conjugate addition reaction.
Asymmetric 1, in the 4-conjugate addition reaction, existing outstanding chiral ligand shows the specificity to reaction substrate; And under the reaction conditions of differing temps, the enantioselectivity of reaction is different, and there is different catalytic active species in the presentation of results reaction system, and some part copper complex active specy is easy to cause the product racemization, has reduced the enantioselectivity of reaction; Therefore, the development research of novel chiral phosphorus part and explore its application in the asymmetry catalysis compound method and still be very important.
Summary of the invention
The object of the present invention is to provide a kind of N.F,USP MANNITOL deutero-chirality bidentate phosphite ester ligand.
Another object of the present invention provides the compound method of above-mentioned part.
Further purpose of the present invention provides the purposes of above-mentioned part, and promptly part and Cu salt reaction in prepare catalyzer, and the catalysis zinc ethyl is asymmetric 1 to the ring-type ketenes, the 4-conjugate addition reaction, and synthetic have optically active β-ethyl cyclic ketone product.
A kind of N.F,USP MANNITOL deutero-chirality bidentate phosphite ester ligand, its structure is represented with formula I:
Formula (I)
R wherein 1For:
Figure BSA00000352871200022
R wherein 2For:
Figure BSA00000352871200023
R wherein 1Be a or b; R2 is a ' or b ' or c ' or d '.
The present invention provides the compound method of above-mentioned part, it is characterized in that:
Under the nitrogen atmosphere, with N.F,USP MANNITOL skeleton X, wherein R 1Be a or b, the inferior phosphoryl chloride Y of chirality is reactant, wherein R 2For a ' or b ' or c ' or d ', at 4-Dimethylamino pyridine (DMAP) and triethylamine (NEt 3) exist down, be solvent with the methylene dichloride, behind the reaction certain hour, remove solvent under reduced pressure, add toluene, after fully stirring, the filtering solid, after filtrating concentrates, through dodging chromatographic separation, can synthesis of chiral bidentate phosphite ester ligand I.
The chemical equation of reaction is suc as formula shown in the II:
Figure BSA00000352871200024
Formula (II)
Above-mentioned reactions step is specified as follows:
Reaction solvent is a methylene dichloride; The mol ratio of reactants of X and Y is 1: 2～4; The mol ratio of 4-Dimethylamino pyridine and compounds X is 1: 4～5; The mol ratio of compounds X and triethylamine is 1: 2～4; Temperature of reaction is-15 ℃～30 ℃, and the reaction times is 1～3h.
Another object of the present invention provides the purposes of above-mentioned part:
Part/Cu Preparation of catalysts process can be represented with following reaction formula:
Part+Cu salt → part/Cu catalyzer
To above-mentioned catalyst preparation process, specify as follows:
Nitrogen atmosphere, in organic solvent, part and Cu salt stir and get final product synthetic ligands/Cu catalyzer.Organic solvent is selected from THF, ether, toluene or methylene dichloride; Cu salt is selected from Cu (OTf) 2Or (CuOTf) 2C 6H 6, wherein OTf is the trifluoromethanesulfonic acid root; The mol ratio of Cu salt and part is: 1: 0.5～3; Temperature of reaction is 25 ℃; Reaction times is 1h.
Specify zinc ethyl asymmetric 1 to the ring-type ketenes, 4-conjugate addition reaction process is following:
Nitrogen atmosphere; In the solution of described part/Cu catalyzer, add ring-type ketenes and zinc ethyl successively, at a certain temperature, after reaction for some time; In reaction mixture, add zero(ppm) water and dilute hydrochloric acid solution cancellation reaction; Use ethyl acetate extraction, merge organic phase, use saturated NaHCO successively 3Solution, saturated common salt water washing, anhydrous Na 2SO 4Drying is filtered, and concentrates, and synthesizes to have optically active β-ethyl cyclic ketone product, gc (GC) assay products.
Described ring-type ketenes is selected from 2-cyclopentenone, 2-cyclonene or 2-suberene ketone; The mol ratio of part/Cu catalyzer, ring-type ketenes and zinc ethyl is 1: 50: 120; Temperature of reaction is-40～20 ℃; Reaction times is 4～12h.
Embodiment
Help further to understand the present invention through following embodiment, but do not limit the content of invention.
Embodiment 1～6: the preparation of N.F,USP MANNITOL deutero-chirality bidentate phosphite ester ligand.
Embodiment 7～27: part/Cu Preparation of catalysts and in zinc ethyl asymmetric 1 to annulenones, the application in the 4-addition reaction.
Embodiment 1: preparation chirality bidentate phosphite ester ligand, and structural formula is as follows:
Figure BSA00000352871200041
Under the nitrogen atmosphere, in the 100mL Xiu Langke bottle that magneton is housed, add b (206mg, 0.6mmol), the inferior phosphoryl chloride Y of chirality (R 2Be c ', shown in II) (646mg is 1.8mmol) with 4-Dimethylamino pyridine (14.6mg; 0.12mmol); Add the 10mL methylene dichloride and make solvent, stirring is dissolved solid fully, solution is chilled to-15 ℃; Slowly drip triethylamine 0.34mL and keep-15 ℃ of reaction 0.5h down, be placed on then under the room temperature and react 1h.Removal of solvent under reduced pressure adds 20mL toluene and fully stirs, the filtering solid, will filtrate concentrate after, obtain part 266mg through the sudden strain of a muscle chromatographic separation, yield is 45%.
White solid, fusing point: 128-130 ℃; [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, and 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, experimental value: 1009.4176.
Embodiment 2: preparation chirality bidentate phosphite ester ligand, and its structural formula is as follows:
Figure BSA00000352871200042
With the method among the embodiment 1, and b (206mg, 0.6mmol), the inferior phosphoryl chloride Y of deutero-chirality (R 2Be d ', shown in II) (646mg, 1.8mmol), the 4-Dimethylamino pyridine (14.6mg, 0.12mmol), triethylamine 0.34mL.Obtain part 252mg, yield 43%.
White solid, fusing point: 111-112 ℃; [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, and 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, experimental value: 1009.4167.
Embodiment 3: preparation chirality bidentate phosphite ester ligand, and its structural formula is as follows:
Figure BSA00000352871200051
With the method among the embodiment 1, and a (79mg, 0.3mmol), the inferior phosphoryl chloride Y of chirality (R 2Be a ', shown in II) (421mg, 1.2mmol), the 4-Dimethylamino pyridine (7.3mg, 0.06mmol), triethylamine 0.17mL.Obtain part 200mg, yield 75%.
White solid, fusing point: 119-121 ℃; [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), 3.77 (m, 2H), 1.49 (s, 6H), 1.35 (s, 6H) ppm. 13C NMR (75MHz, d 6-DMSO): δ 147.45,147.39, and 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, experimental value: 913.2300.
Embodiment 4: preparation chirality bidentate phosphite ester ligand, and its structural formula is as follows:
Figure BSA00000352871200061
With the method among the embodiment 1, and a (158mg, 0.6mmol), the inferior phosphoryl chloride Y of chirality (R 2Be b ', shown in II) (505mg, 1.44mmol), the 4-Dimethylamino pyridine (14.6mg, 0.12mmol), triethylamine 0.34mL.Obtain part 221mg, yield 40%.
White solid, fusing point: 115-117 ℃; [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, and 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, experimental value: 913.2280.
Embodiment 5: preparation chirality bidentate phosphite ester ligand, and its structural formula is as follows:
Figure BSA00000352871200071
With the method among the embodiment 1, and a (158mg, 0.6mmol), the inferior phosphoryl chloride Y of chirality (R 2Be c ', shown in II) (860mg, 2.4mmol), the 4-Dimethylamino pyridine (14.6mg, 0.12mmol), triethylamine 0.34mL.Obtain part 273mg, yield 50%.
White solid, fusing point: 132-133 ℃; [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, and 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, experimental value: 929.3559.
Embodiment 6: preparation chirality bidentate phosphite ester ligand, and its structural formula is as follows:
Figure BSA00000352871200072
With the method among the embodiment 1, and a (157mg, 0.6mmol), the inferior phosphoryl chloride Y of chirality (R 2Be d ', shown in II) (517mg, 1.44mmol), the 4-Dimethylamino pyridine (14.6mg, 0.12mmol), triethylamine 0.34mL.Obtain part 229mg, yield 42%.
White solid, fusing point: 118-120 ℃; [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, and 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, experimental value: 929.3552.
Embodiment 7:
Under nitrogen atmosphere, Cu (OTf) 2(0.005mmol, 1.8mg) (0.01mmol 9.1mg) is dissolved in the 4mL toluene, and stirring at room 1h obtains the solution of ligand i c/Cu catalyzer with embodiment 5 described parts.Be cooled to 0 ℃, (0.5mmol, 0.048mL), (hexane solution of 1mol/L, 1.2mL), 0 ℃ was reacted 4 hours down zinc ethyl to add the 2-cyclonene successively.Add 2mL zero(ppm) water and 2mL dilute hydrochloric acid solution (2.0mol/L) cancellation reaction,, merge organic phase, use saturated NaHCO successively with ethyl acetate extraction (5mL * 3) 3Solution, saturated common salt water washing, anhydrous Na 2SO 4Drying is filtered, and concentrates, and analyzes through gc (GC), and yield is 90%, and enantioselectivity is 83%, and the product absolute configuration is R.
Embodiment 8:
With embodiment 7, part be selected from embodiment 1 described part (0.01mmol, 9.9mg) GC analyze to show that product 3-ethyl cyclohexanone yield is 77%, enantioselectivity is 75%, the product absolute configuration is R.
Embodiment 9:
With embodiment 7, part be selected from embodiment 2 described parts (0.01mmol, 9.9mg), GC analyze to show that product 3-ethyl cyclohexanone yield is 73%, enantioselectivity is 47%, the product absolute configuration is S.
Embodiment 10:
With embodiment 7, part be selected from embodiment 3 described parts (0.01mmol, 8.7mg), GC analyze to show that product 3-ethyl cyclohexanone yield is 85%, enantioselectivity is 74%, the product absolute configuration is R.
Embodiment 11:
With embodiment 7, part be selected from embodiment 4 described parts (0.01mmol, 8.7mg), GC analyze to show that product 3-ethyl cyclohexanone yield is 60%, enantioselectivity is 54%, the product absolute configuration is S.
Embodiment 12:
With embodiment 7, part be selected from embodiment 6 described parts (0.01mmol, 9.1mg), GC analyze to show that product 3-ethyl cyclohexanone yield is 83%, enantioselectivity is 48%, the product absolute configuration is S.
Embodiment 13:
With embodiment 7, mantoquita is selected from (CuOTf) 2C 6H 6(0.0025mmol, 1.25mg), GC analyzes and shows that product 3-ethyl cyclohexanone yield is 77%, and enantioselectivity is 77%, and the product absolute configuration is R.
Embodiment 14:
With embodiment 7, embodiment 5 described part consumptions be (0.0025mmol, 2.3mg), GC analyze to show that product 3-ethyl cyclohexanone yield is 85%, enantioselectivity is 65%, the product absolute configuration is R.
Embodiment 15:
With embodiment 7, as embodiment 5 described part consumptions be (0.005mmol, 4.5mg), GC analyze to show that product 3-ethyl cyclohexanone yield is 92%, enantioselectivity is 68%, the product absolute configuration is R.
Embodiment 16:
With embodiment 7, as embodiment 5 described part consumptions be (0.015mmol, 13.6mg), GC analyze to show that product 3-ethyl cyclohexanone yield is 87%, enantioselectivity is 79%, the product absolute configuration is R.
Embodiment 17:
With embodiment 7, as embodiment 5 described part consumptions be (0.0055mmol, 5.0mg), GC analyze to show that product 3-ethyl cyclohexanone yield is 98%, enantioselectivity is 80%, the product absolute configuration is R.
Embodiment 18:
With embodiment 7, solvent is selected from methylene dichloride 4mL, and GC analyzes and shows that product 3-ethyl cyclohexanone yield is 40%, and enantioselectivity is 2%, and the product absolute configuration is R.
Embodiment 19:
With embodiment 7, solvent is selected from ether 4mL, and GC analyzes and shows that product 3-ethyl cyclohexanone yield is 77%, and enantioselectivity is 15.6%, and the product absolute configuration is R.
Embodiment 20:
With embodiment 7, solvent is selected from THF 4mL, and GC analyzes and shows that product 3-ethyl cyclohexanone yield is 18%, and enantioselectivity is 68%, and the product absolute configuration is R.
Embodiment 21:
With embodiment 7, temperature of reaction and time are: 20 ℃ were reacted 4 hours down.GC analyzes and shows that product 3-ethyl cyclohexanone yield is 99%, and enantioselectivity is 64%, and the product absolute configuration is R.
Embodiment 22:
With embodiment 7, temperature of reaction and time are :-10 ℃ were reacted 12 hours down.GC analyzes and shows that product 3-ethyl cyclohexanone yield is 99%, and enantioselectivity is 89%, and the product absolute configuration is R.
Embodiment 23:
With embodiment 7, temperature of reaction and time are :-20 ℃ were reacted 12 hours down.GC analyzes and shows that product 3-ethyl cyclohexanone yield is 99%, and enantioselectivity is 93%, and the product absolute configuration is R
Embodiment 24:
With embodiment 7, temperature of reaction and time are :-30 ℃ were reacted 12 hours down.GC analyzes and shows that product 3-ethyl cyclohexanone yield is 98%, and enantioselectivity is 92%, and the product absolute configuration is R.
Embodiment 25:
With embodiment 7, temperature of reaction and time are :-40 ℃ were reacted 12 hours down.GC analyzes and shows that product 3-ethyl cyclohexanone yield is 99%, and enantioselectivity is 88%, and the product absolute configuration is R.
Embodiment 26:
With embodiment 7, the annulenones substrate is selected from the 2-cyclopentenone, and (0.25mmol, 0.022mL), temperature of reaction and time are :-20 ℃ were reacted 12 hours down.GC analyzes and shows that product 3-ethyl ketopentamethylene yield is 59%, and enantioselectivity is 92%, and the product absolute configuration is R.
Embodiment 27:
With embodiment 7, the annulenones substrate is selected from 2-suberene ketone, and (0.25mmol, 0.035mL), temperature of reaction and time are :-20 ℃ were reacted 12 hours down.GC analyzes and shows that product 3-ethyl suberone yield is 97%, and enantioselectivity is 90%, and the product absolute configuration is R.

Claims (7)

1. N.F,USP MANNITOL deutero-chirality bidentate phosphite ester ligand, its structure is represented with formula I:
Figure FSA00000352871100011
Formula (I)
R wherein 1For:
Figure FSA00000352871100012
R wherein 2For:
Figure FSA00000352871100013
R wherein 1Be a or b; R 2Be a ' or b ' or c ' or d '.
2. the preparation method of part according to claim 1 is characterized in that:
Under the nitrogen atmosphere, with N.F,USP MANNITOL skeleton X, wherein R 1Be a or b, the inferior phosphoryl chloride Y of chirality is reactant, wherein R 2For a ' or b ' or c ' or d ', in the presence of 4-Dimethylamino pyridine and triethylamine, be solvent with the methylene dichloride; Behind the reaction certain hour, remove solvent under reduced pressure, add toluene; After fully stirring, the filtering solid is after filtrating concentrates; Through dodging chromatographic separation, can synthesis of chiral bidentate phosphite ester ligand I.
3. method as claimed in claim 2, the mol ratio that it is characterized in that reactants of X and Y is 1: 2～4.
4. method as claimed in claim 2, the mol ratio that it is characterized in that 4-Dimethylamino pyridine and compounds X is 1: 4～5.
5. method as claimed in claim 2, the mol ratio that it is characterized in that reactants of X and triethylamine is 1: 2～4.
6. method as claimed in claim 2 is characterized in that temperature of reaction is-15 ℃～30 ℃, and the reaction times is 1～3h.
7. application according to claim 1 is characterized in that formula I as catalyzer, and under the nitrogen atmosphere, catalyzer is used for zinc ethyl asymmetric 1 to the ring-type ketenes, 4-conjugate addition reaction; In the solution of part/Cu catalyzer, add ring-type ketenes and zinc ethyl successively, after reaction for some time, in reaction mixture, add zero(ppm) water and dilute hydrochloric acid solution cancellation reaction, use ethyl acetate extraction, merge organic phase, use saturated NaHCO successively 3Solution, saturated common salt water washing, drying is filtered, and concentrates, and synthesizes to have optically active β-ethyl cyclic ketone product, gc (GC) assay products; Described ring-type ketenes is selected from 2-cyclopentenone, 2-cyclonene or 2-suberene ketone; The mol ratio of part/Cu catalyzer, ring-type ketenes and zinc ethyl is 1: 50: 120; Temperature of reaction is-40～20 ℃; Reaction times is 4～12h.
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