CN101003549B - Phosphine compound of possessing plane chirality cyclophane alkyl, synthetic method, and appliction - Google Patents

Phosphine compound of possessing plane chirality cyclophane alkyl, synthetic method, and appliction Download PDF

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CN101003549B
CN101003549B CN2007100366249A CN200710036624A CN101003549B CN 101003549 B CN101003549 B CN 101003549B CN 2007100366249 A CN2007100366249 A CN 2007100366249A CN 200710036624 A CN200710036624 A CN 200710036624A CN 101003549 B CN101003549 B CN 101003549B
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paracyclophane
compound
phosphine compound
phosphine
chlorine
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CN101003549A (en
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侯雪龙
张唐志
戴立信
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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

This invention discloses a method for synthesizing planar chiral cycloaralkyl phosphine compound and its application. The chirality of the compound is derived from the planar chirality of cycloaralkyl framework. The method comprises: deriving from [2.2] dicycloaralkyl to obtain the compound, performing chiral resolution with chiral annulate Pd, separating the diastereoisomers by column chromatography to obtain planar chiral cycloaralkyl phosphine compound, and recovering annulate Pd. The compound, when used as catalyst in allyl amination and alkylation, has high reactivity and high antipode selectivity. Besides, the compound can be used as a ligand in asymmetric catalytic hydrogenation and aldehyde allylation. The compound has such advantages as high stability and simple synthesis.

Description

A kind of phosphine compound, synthetic method and purposes with planar chiral paracyclophane
Technical field
The present invention relates to a class chipal compounds, synthetic method and purposes, promptly a kind of phosphine compound, synthetic method and purposes with paracyclophane of planar chiral.
Background technology
Planar chiral [2.2] paracyclophane compound is the very important planar chiral compound of a class, and a lot of distinguished characteristics are arranged, and Hou Xuelong etc. had reported once that a kind of planar chiral [2.2] was to cyclophane alkane oxazole phosphine part, synthetic method (ZL02136741.8).Wherein some compound has been obtained result preferably as part or chirality assistant agent in asymmetric synthesis, but the derivatize of paracyclophane compounds is relatively more difficult, and the preparation of planar chiral paracyclophane compound is difficult for especially.Chiral monophosphorus is widely used in asymmetric synthesis, but it also has characteristics such as preparation difficulty, complex structure and easy oxidation.Seek for this reason relatively simple for structure, be easy to synthetic and have preferably that the catalyzer of catalytic activity is one of the focus of scholar's research that organises.
Summary of the invention
The problem to be solved in the present invention provides a kind of phosphine compound with planar chiral [2.2] paracyclophane;
Purpose of the present invention is also for a kind of phosphine compound synthetic method with planar chiral [2.2] paracyclophane;
Another purpose of the present invention provides a kind of purposes with phosphine compound of planar chiral [2.2] paracyclophane.
Compound of the present invention has following structural formula:
Figure S07136624920070207D000011
X=is Sauerstoffatom or singly-bound in the formula;
R or R 1=replacement, single replacement and dibasic phenyl, C 1～16Alkyl, aryloxy, C 1～4Alkoxyl group; R, R 1Be identical or different group; Aryl is for replacing or unsubstituted phenyl in the described aryloxy, and described substituting group is C 1～4Alkoxyl group, C 1～4Perfluoroalkyl, C 1～4Alkyl, halogen atom or phenyl; Described alkyl can be the C that comprises cyclohexyl 1～16Alkyl or phenyl;
R 2=H, COO (C nH 2n+1), hydroxyl C 1～4Alkyl, hydroxyl, C 1～16Alkyl, OC (O) N (C nH 2n+1) or C (O) N (C nH 2n+1) 2, n=1～4 wherein;
R 3=H, C (O) N (C nH 2n+1) 2, COO (C nH 2n+1), hydroxyl C 1～4Alkyl or hydroxyl; Wherein, as X=singly-bound or oxygen, R and R 1During=phenyl, R 2And R 3Can not be H simultaneously.
Phosphine compound with planar chiral [2.2] paracyclophane of the present invention is meant [2.2] the paracyclophane list phosphine compound that has planar chiral or has planar chiral [2.2] paracyclophane oxa-list phosphine compound, especially is recommended as the compound of following structure:
Figure S07136624920070207D000021
R, R in the formula 1, R 2Or R 3As mentioned above.R or R 1During=substituted-phenyl, especially recommending substituting group is 4-methoxyl group, 4-trifluoromethyl, 4-methyl, 2-methyl, (3,5)-dimethyl, (3,5)-two (trifluoromethyl), (3,5)-phenylbenzene, 4-fluorine.
The present invention also provides the synthetic method of above-claimed cpd.Synthetic method of the present invention is by 4-bromine [2.2] paracyclophane derive the paracyclophane list phosphine compound that obtains racemization and the paracyclophane oxa-list phosphine compound of racemization, split with ring palladium compound A again, the a pair of diastereomer that obtains can obtain the phosphine compound with planar chiral paracyclophane of two kinds of conformations respectively with the reagent that dissociates, the ring palladium compound B of generation and 10% hydrochloric acid effect are recyclable ring palladium compound A.
Figure S07136624920070207D000022
Figure S07136624920070207D000031
Described ring palladium compound A structural formula is
R, R in the formula 1, R 2, R 3As previously mentioned, organic bases is generally triethylamine or pyridine, and the reagent that dissociates is generally amino acid sodium or diamine compound.
The reaction conditions of recommending is: 1) in organic solvent, under the 0 ℃～room temperature, 4-bromine [2.2] paracyclophane derivative and butyllithium effect, add the phosphine chlorine compound again, the mol ratio of 4-bromine [2.2] paracyclophane, butyllithium and dialkyl phosphine chlorine or two-oxyl phosphorus chlorine is 1: 1～2: 1～2, and recommending mol ratio is 1: 2: 2.React and to obtain racemization paracyclophane list phosphine compound in 2～10 hours.Preferably separate by silica gel column chromatography.2) in organic solvent and under the 0 ℃～room temperature, react the paracyclophane oxa-list phosphine compound that obtained racemization in 6～18 hours in organic solvent and under the 0 ℃～room temperature by 4-hydroxyl [2.2] paracyclophane, organic bases, dialkyl phosphine chlorine or two-oxyl phosphorus chlorine, the mol ratio of 4-hydroxyl [2.2] paracyclophane, organic bases, dialkyl phosphine chlorine or two-oxyl phosphorus chlorine is 1: 4～8:1～2, and recommending mol ratio is 1: 6: 2.The suggestion product directly separates through silica gel column chromatography; Described dialkyl phosphine chlorine or two-oxyl phosphine chlorine are: RR 1PCl.3) in organic solvent and under the 0 ℃～room temperature, the phosphine compound and the ring palladium compound A reaction of racemization paracyclophane obtained the paracyclophane list phosphine compound of diastereomer in 0.5-3 hour.Racemization paracyclophane list phosphine compound and the mol ratio 1: 0.2～1 of encircling palladium compound A, recommending mol ratio is 1: 0.5; Recommendation obtains two diastereomers by the silica gel column chromatography separation.4) diastereomer can obtain (R) or/and the phosphine compound of two optical purity paracyclophanes (S) with different dissociating reagent react 0.5-3 hour under organic solvent and room temperature, diastereomer and the mol ratio 1: 1～2 of dissociating reagent, recommending mol ratio is 1: 1.The ring palladium compound B that disintegrates down can reclaim ring palladium compound A with 10% salt acid treatment.
Described organic solvent is recommended benzene, toluene, methylene dichloride, tetrahydrofuran (THF), tetracol phenixin, ether, methyl alcohol etc.Described column chromatography recommends to adopt silica gel column chromatography, and sherwood oil is adopted in the leacheate suggestion: ethyl acetate=1～20: 1, recommend sherwood oil: ethyl acetate=3～15: 1.
The present invention also provides the purposes of this compounds, as catalyzer, especially is applied in the asymmetric catalysis such as allyl group amination and alkylated reaction; As part, can be applied in the asymmetric reactions such as allylation reaction of asymmetric catalytic hydrogenation reaction and aldehyde.Wherein be applied in the allyl group amination reaction, with MBH ester class substrate, can well productive rate and higher enantioselectivity obtain product.In the allylation reaction of asymmetric catalytic hydrogenation reaction and aldehyde, also obtained good result equally, can high reactivity and the narrow spectrum preferably product that obtains correspondence.This compounds may have application promise in clinical practice in catalytic other reactions of organic phosphine.
Embodiment
Following examples help to understand the present invention, but are not limited to content of the present invention.
Embodiment 1: planar chiral paracyclophane list phosphine compound is synthetic
Under 0 ℃, add (3.444g, 12mmol) 4-bromine [2.2] paracyclophane in the reaction flask, use the 150mL ether dissolution, add butyllithium, stirred 1 hour, add dialkyl phosphine chlorine, two-oxyl phosphorus chlorine (is example with diphenylphosphine chlorine) (3.5ml again, 18mmol), rise to room temperature reaction 8 hours, add the cancellation of 10mL methyl alcohol, removal of solvent under reduced pressure, silica gel column chromatography (sherwood oil ethyl acetate=15: 1) obtains corresponding racemization paracyclophane list phosphine compound Hla 3.669g, productive rate: 78%.Racemization Hla (0.392g, 1mmol) with ring palladium A (0.339g, 0.5mmol) in 10mL methyl alcohol, reacted 0.5 hour, (sherwood oil: ethyl acetate=3: 1) separation obtains two diastereomers to silica gel column chromatography, and they and reagent (0.5mmol the recommends Sodium proline) reaction of dissociating can be obtained chirality Hla and ring palladium B.Ring palladium B and 10% hydrochloric acid effect can be reclaimed ring palladium A by 98% yield.
(R)-(X is a singly-bound to Hla, R, R 1=Ph, R 2=H, R 3=H)
1H NMR (300MHz, CDCl 3) 67.40-7.39 (m, 5H), 7.25-7.20 (m, 6H), 6.54-6.43 (m, 4H), 6.20 (dd, J=8.1,2.2Hz, 1H), 5.72 (dd, J=7.3,1.5Hz, 1H), 3.56-3.47 (m, 2H), 3.11-2.70 (m, 6H); 13C NMR (CDCl 3, 75MHz) 634.2,34.8,35.1,35.2,128.3,128.6,129.2,130.6,132.2,132.8,133.1,133.3,133.5,134.3,135.1,135.4,135.8,13/.2,139.4,139.6,139.8; 31PNMR (161.92MHz, CDC1 3)-2.46ppm; EIMS m/z (relative intensity %): 392 (M +, 73), 304 (47), 288 (100), 178 (34); HRMS: high resolution calculated value C 28H 26P + 1: 393.1766. measured value: 393.1765.
(R)-(X is a singly-bound to Hlb, R, R 1=(4-MeO) C 6H 4, R 2=H, R 3=H)
1H NMR (300MHz, CDCl3 )67.33-7.11 (m, 5H), 6.93 (d, J=8.2Hz, 2H), 6.77 (d, J=7.7Hz, 2H), 6.51-6.42 (m, 4H), 6.20 (d, J=7.9Hz, 1H), 5.72 (dd, J=7.6,1.7Hz, 1H), 3.84 (s, 3H), 3.74 (s, 3H), 3.51-3.47 (m, 2H), 3.05-2.92 (m, 4H), 2.75 (m, 2H); 13C NMR (CDCl 3, 75MHz) 634.7,34.9,35.1,35.2,55.1,55.2,113.8,113.9,114.2,114.3,127.5,128.9,130.3,132.1,132.7,133.1,134.2,134.5,134.7,135.7,136.3,136.6,138.4,139.4,139.5,139.8,143.3,143.6,159.8,160.4; 31P NMR (161.92MHz, CDCl 3)-10.5ppm; EIMS m/z (relative intensity %): 452 (M +, 64), 346 (100), 315 (23), 239 (34), 104 (35); HRMS high resolution: calculated value C 30H 29O 2P:452.1905. measured value: 452.1916.
(R)-(X is a singly-bound to H1c, R, R 1=4-CF 3C 6H 4, R 2=H, R 3=H)
1HNMR (300MHz, CDCl 3) 67.67 (d, J=8.0Hz, 2H), 7.50 (m, 4H), 7.28 (m, 2H), 7.12 (d, J=8.1Hz, 1H), 6.60-6.52 (m, 4H), 6.19 (d, J=7.9Hz, 1H), 5.67 (m, 1H), 3.50-3.43 (m, 2H), 3.12-2.96 (m, 6H); 13CNMR (CDCl 3, 75MHz) 634.2,34.3,34.7,34.9,35.0,35.1,125.1,125.5,130.5,130.6,132.0,132.9,133.0,133.2,133.3,134.3,134.6,134.7,135.5,135.7,139.5,140.2,144.0; 31P NMR (161.92MHz, CDCl 3)-7.56ppm; 19F NMR (56.4MHz)-63.1ppm; EIMS m/z (relative intensity %): 530 (M+2,40), 426 (100), 277 (21), 104 (83), 78 (33); HRMS high resolution: calculated value C 30H 23F 6P:528.1442. measured value: 528.1450
(R)-(X is a singly-bound to H1d, R, R 1=4-MeC 6H 4, R 2=H, R 3=H)
1H NMR (300MHz, CDCl 3) 67.21 (m, 1H), 7.03 (m, 3H), 6.87 (m, 3H), 6.53-6.43 (m, 4H), 6.15 (m, 2H), 5.77 (m, 1H), 3.52 (m, 2H), 3.05-2.76 (m, 6H), 2.28 (s, 3H), 2.21 (s, 3H); 31P NMR (161.92MHz, CDCl 3)-6.60ppm; EIMSm/z (relative intensity %): 420 (M +, 57), 44 (100); Ultimate analysis: calculated value C 30H 29P:C, 85.68; H, 6.95. measured value: C, 85.33; H.6.97.
(R)-(X is a singly-bound to Hle, R, R 1=2-MeC 6H 4, R 2=H, R 3=H)
1H NMR (300MHz, CDCl 3) 67.23 (m, 1H), 7.03 (m, 3H), 6.85 (m, 3H), 6.53-6.43 (m, 4H), 6.15 (m, 2H), 5.74 (m, 1H), 3.53 (m, 2H), 3.05-2.76 (m, 6H), 2.25 (s, 3H), 2.26 (s, 3H); 31P NMR (161.92MHz, CDCl 3)-6.66ppm; EIMSm/z (relative intensity %): 420 (M +, 58), 44 (100); Ultimate analysis: calculated value C 30H 29P:C, 85.68; H, 6.95. measured value: C, 85.43; H.6.91.
(R)-(X is a singly-bound to H1f, R, R 1=3,5-Me 2C 6H 3, R 2=H, R 3=H)
1H NMR (300MHz, CDCl 3) 67.23 (m, 1H), 7.03 (m, 3H), 6.85 (m, 3H), 6.53-6.43 (m, 4H), 6.18 (d, J=3.2Hz, 1H), 5.71 (dd, J=7.7,1.7Hz, 1H), 3.50 (m, 2H), 3.05-2.76 (m, 6H), 2.31 (s, 6H), 2.19 (s, 6H); 13C NMR (CDCl 3, 75MHz) 621.2,21.4,34.1,34.8,35.1,35.2,130.1,130.4,130.7,131.0,132.1,132.6,132.7,133.0,133.1,133.3,134.2,135.7,137.4,137.5,137.8,137.9,139.3,139.8; 31P NMR (161.92MHz, CDCl 3)-6.70ppm; EIMSm/z (relative intensity %): 448 (M +, 67), 342 (42), 327 (32), 240 (34), 104 (34), 84 (28), 44 (100); HRMS: high resolution: calculated value C 32H 33P:448.2320. measured value: 448.2328.
(R)-(X is a singly-bound to H1g, R, R 1=3,5-(CF 3) 2C 6H 3, R 2=H, R 3=H)
1H NMR (300MHz, CDCl 3) 67.60 (d, J=8.0Hz, 2H), 7.43 (m, 4H), 7.22 (m, 2H), 7.09 (d, J=8.1Hz, 1H), 6.67-6.52 (m, 3H), 6.11 (d, J=7.9Hz, 1H), 5.56 (m, 1H), 3.54-3.43 (m, 2H), 3.17-2.99 (m, 6H); 31P NMR (161.92MHz, CDCl 3)-7.86ppm; 19FNMR (56.4MHz)-63.4ppm EIMS m/z (relative intensity %): 664 (M+, 35), 277 (100); Ultimate analysis: calculated value C 32H 21F 12P:C, 57.54; H, 3.19. measured value: C, 57.82; H, 3.15.
(R)-(X is a singly-bound to H1h, R, R 1=3,5-Ph 2C 6H 3, R 2=H, R 3=H)
1H NMR (300MHz, CDCl 3) 67.88 (s, 1H), 7.77-7.74 (m, 3H), 7.64-7.29 (m, 23H), 6.62-6.53 (m, 4H), 6.26 (m, 1H), 5.98 (m, 1H), 3.70-3.55 (m, 2H), 3.15-2.91 (m, 6H); 31P NMR (161.92MHz, CDCl 3)-4.98ppm; EIMS m/z (relative intensity %): 696 (M +, 48), 186 (100); Ultimate analysis: calculated value C 30H 29P:C, 89.62; H, 5.93. measured value: C, 89.43; H, 5.91.
(R)-(X is a singly-bound to Hli, R, R 1=4-FC 6H 4, R 2=H, R 3=H)
1H NMR (300MHz, CDCl 3) 67.67 (d, J=8.0Hz, 2H), 7.50 (m, 4H), 7.28 (m, 2H), 7.12 (d, J=8.1Hz, 1H), 6.60-6.52 (m, 4H), 6.19 (d, J=7.9Hz, 1H), 5.67 (m, 1H), 3.50-3.43 (m, 2H), 3.12-2.96 (m, 6H); 31PNMR (161.92MHz, CDCl 3)-7.85ppm; 19FNMR (56.4MHz)-67.1ppm; EIMS m/z (relative intensity %): 428 (M +, 48), 104 (100); Ultimate analysis: calculated value C 28H 23F 2P:C, 78.49; H, 5.41. measured value: C, 78.43; H, 5.53.
(R)-(X is a singly-bound to H2, R, R 1=c-C 6H 11, R 2=H, R 3=H)
1H NMR (300MHz, CDCl 3) 66.60-6.31 (m, 7H), 3.97 (m, 1H), 3.26-2.84 (m, 7H), 2.04-0.79 (m, 22H); 13C NMR (CDCl 3, 75MHz) 626.1,26.5,26.7,26.9,27.1,27.6,27.8,28.8,30.3,34.3,34.7,34.9,35.1,35.3,35.4,131.9,132.2,132.5,133.1,133.3,133.6,134.5,138.1,139.1,139.8,144.9,145.3; 31P NMR (161.92MHz, CDCl 3)-4.76ppm; EIMS m/z (relative intensity %): 403 (M-1,17), 322 (26), 300 (32), 240 (23), 105 (46), 91 (61), 41 (100); HRMS: high resolution calculated value C 28H 37P:404.2633; Measured value: 404.2632.
(R)-(X is a singly-bound to H3, R, R 1=i-C 3H 7, R 2=H, R 3=H)
1H NMR (300MHz, CDCl 3) 66.63-6.54 (m, 3H), 6.47-6.36 (m, 4H), 4.04-3.94 (m, 1H), 3.32-2.84 (m, 7H), 2.16 (m, 1H), 1.80 (m, 1H), 1.46 (m, 3H), 1.32 (m, 3H), 0.93 (m, 3H), 0.48 (m, 3H); 31P NMR (161.92MHz, CDCl 3)-0.95ppm; EIMS m/z (relative intensity %): 324 (M +, 30), 220 (100); HRMS: high resolution calculated value C 22H 29P:324.2007; Measured value: 324.2018.
(R)-(X is a singly-bound to H4, R, R 1=t-C 4H 9, R 2=H, R 3=H)
1H NMR (300MHz, CDCl 3) 66.98-6.76 (m, 3H), 6.60-6.18 (m, 4H), 3.60-3.48 (m, 1H), 3.09-2.41 (m, 7H), 1.59 (s, 9H), 1.54 (s, 9H); 31P NMR (161.92MHz, CDCl 3) 26.2ppm; EIMS m/z (relative intensity %): 351 (M-1,14), 41 (100); HRMS: high resolution calculated value C 24H 33P:352.2320; Measured value: 352.2351.
(R)-(X is a singly-bound to H5, R, R 1=Ph, R 2=OH, R 3=H)
1H NMR (300MHz, CDCl 3) 67.63-7.58 (m, 2H), 7.42-7.26 (m, 8H), 6.72 (s, 2H), 6.62 (m, 1H), 6.50-6.43 (m, 2H), 6.23 (m, 1H), 5.36 (m, 1H), 3.47-3.39 (m, 1H), 3.25-2.94 (m, 5H), 2.83-2.52 (m, 2H); 31P NMR (161.92MHz, CDCl 3)-16.4ppm; EIMS m/z (relative intensity %): 408 (M +, 63), 320 (53), 304 (100), 194 (34); Ultimate analysis calculated value C 28H 25OP:C, 82.33; H, 6.17. measured value: C, 82.42; H, 6.13.
(R)-(X is a singly-bound to H6, R, R 1=Ph, R 2=OC (O) NEt 2, R 3=H)
1H NMR (300MHz, CDCl 3) 67.62-7.56 (m, 2H), 7.45-7.39 (m, 2H), 7.24 (m, 3H), 7.16 (m, 4H), 6.73 (m, 1H), 6.57-6.53 (m, 3H), 6.38 (m, 1H), 3.53-3.45 (m, 1H), 2.99-2.43 (m, 11H), 1.23 (t, J=7.2Hz, 3H), 0.83 (t, J=7.2Hz, 3H); 31P NMR (161.92MHz, CDCl 3)-4.90ppm; EIMS m/z (relative intensity %): 508 (M ++ 1,53), 304 (100); Ultimate analysis calculated value C 33H 34NO 2P:C, 78.08; H, 6.75. measured value: C, 78.04; H, 6.63.
(R)-(X is a singly-bound to H7, R, R 1=Ph, R 2=OMe, R 3=H)
1H NMR (300MHz, CDCl 3) 67.61-7.54 (m, 2H), 7.45-7.26 (m, 8H), 6.72 (s, 2H), 6.61 (m, 1H), 6.50-6.43 (m, 2H), 6.23 (m, 1H), 3.86 (s, 3H), 3.47-3.39 (m, 1H), 3.25-2.94 (m, 5H), 2.83-2.52 (m, 5H), 2.46 (s, 3H); 31P NMR (161.92MHz, CDC1 3)-13.7ppm; EIMS m/z (relative intensity %): 422 (M +, 42), 194 (100); Ultimate analysis calculated value C 29H 27OP:C, 82.44; H, 6.44. measured value: C, 82.42; H, 6.18.
(R)-(X is a singly-bound to H8, R, R 1=Ph, R 2=CH 2OH, R 3=H)
1H NMR (300MHz, CDCl 3) 67.61-7.57 (m, 2H), 7.40-7.26 (m, 8H), 6.72 (s, 2H), 6.61 (m, 1H), 6.50-6.43 (m, 2H), 6.23 (m, 1H), 5.86 (s, 2H), 3.47-3.39 (m, 1H), 3.25-2.94 (m, 5H), 2.83-2.52 (m, 2H); 31P NMR (161.92MHz, CDCl 3)-15.7ppm; EIMS m/z (relative intensity %): 422 (M +, 52), 254 (100); Ultimate analysis calculated value C 29H 27OP:C, 82.44; H, 6.44. measured value: C, 82.32; H, 6.25.
(R)-(X is a singly-bound to H9, R, R 1=Ph, R 2=Me, R 3=H)
1H NMR (300MHz, CDCl 3) 67.52-7.29 (m, 4H), 7.25-6.99 (m, 6H), 6.68-6.51 (m, 4H), 6.23-6.14 (m, 2H), 3.38-3.37 (m, 1H), 3.61-3.49 (m, 1H), 3.18-2.82 (m, 5H), 2.73-2.64 (m, 1H), 2.34 (s, 3H); 31P NMR (161.92MHz, CDCl 3)-15.4PPm; EIMS m/z (relative intensity %): 406 (M +, 64), 184 (100); Ultimate analysis calculated value C 29H 27P:C, 85.69; H, 6.69. measured value: C, 85.37; H, 6.44.
(R)-(X is a singly-bound to H10, R, R 1=Ph, R 2=H, R 3=COOMe)
1H NMR (300MHz, CDCl 3) 67.35 (m, 3H), 7.25-7.20 (m, 2H), 6.72-6.66 (m, 2H), 6.62-6.50 (m, 4H), 4.45-4.34 (m, 1H), 3.89 (s, 3H), 3.65-3.50 (m, 1H), 3.18-2.86 (m, 7H); 31P NMR (161.92MHz, CDCl 3)-7.85ppm; EIMS m/z (relative intensity %): 450 (M +, 82), 334 (100); Ultimate analysis calculated value C 30H 27O 2P:C, 79.98; H, 6.04. measured value: C, 79.82; H, 6.13.
(R)-(X is a singly-bound to H11, R, R 1=Ph, R 2=H, R 3=C (O) NMe 2)
1H NMR (300MHz, CDCl 3) 67.65 (m, 3H), 7.45-7.32 (m, 2H), 6.72-6.66 (m, 2H), 6.68-6.55 (m, 4H), 4.45-4.34 (m, 1H), 3.65-3.50 (m, 1H), 3.18-2.86 (m, 7H), 2.58 (s, 3H), 2.42 (s, 3H); 31P NMR (161.92MHz, CDCl 3)-7.85ppm; EIMS m/z (relative intensity %): 464 (M ++ 1,73), 253 (100); Ultimate analysis calculated value C 31H 30NOP:C, 80.32; H, 6.52. measured value: C, 79.86; H, 6.23.
(R)-(X is a singly-bound to H12, R, R 1=Ph, R 2=H, R 3=CH 2OH)
1H NMR (300MHz, CDCl 3) 67.61-7.57 (m, 2H), 7.40-7.26 (m, 8H), 6.72 (s, 2H), 6.61 (m, 1H), 6.50-6.43 (m, 2H), 6.23 (m, 1H), 5.86 (s, 2H), 3.47-3.39 (m, 1H), 3.25-2.94 (m, 5H), 2.83-2.52 (m, 2H); 31P NMR (161.92MHz, CDCl 3)-14.9PPm; EIMS m/z (relative intensity %): 422 (M +, 52), 254 (100); Ultimate analysis calculated value C 29H 27OP:C, 82.44; H, 6.44. measured value: C, 82.32; H, 6.25.
(R)-(X is a singly-bound to H13, R=Me, R 1=Ph, R 2=H, R 3=H)
1H NMR (300MHz, CDCl 3) 66.63-6.54 (m, 3H), 6.47-6.36 (m, 4H), 4.04-3.94 (m, 1H), 3.32-2.84 (m, 7H), 2.16 (s, 3H), 1.98 (s, 3H); 31P NMR (161.92MHz, CDCl 3)-27.9ppm; EIMS m/z (relative intensity %): 330 (M +, 35), 218 (100); Ultimate analysis calculated value C 23H 23P:C, 83.61; H, 7.02. measured value: C, 83.32; H, 6.85.
Embodiment 2: planar chiral paracyclophane oxa-list phosphine compound is synthetic
Reference literature (Cram, D.J.; Day, A.C.J.Org Chem.1966,31,1227), and adding 4-bromine [2.2] paracyclophane in the three-necked bottle of 250ml (3.444g, 12.0mmol), ether (150ml) is chilled to 0 ℃, adds butyllithium (15ml, 24mmol), stirring at room 20 minutes has faint yellow solid to separate out, be chilled to 0 ℃ once more, the new steaming of adding trimethyl borate (2.7ml, 24mmol), stirring at room is after 1 hour, add 0.5M aqueous sodium hydroxide solution (6m1,3mmol), and 30% hydrogen peroxide solution (4.5ml, 45mmol), be warming up to 40 ℃ of reactions 3 hours, be chilled to room temperature, add 30ml water, the 100ml methylene dichloride, separatory, removal of solvent under reduced pressure, column chromatography purification (methylene dichloride) obtains known compound 4-hydroxyl [2.2] paracyclophane.
Adding 4-hydroxyl [2.2] paracyclophane in the dry reaction pipe (202mg, 0.90mmol), toluene (5ml), (0.5ml 6mmol), is chilled to 0 ℃ to pyridine, slowly drip dialkyl phosphine chlorine, two-oxyl phosphorus chlorine (is example with diphenylphosphine chlorine) (0.35ml, toluene solution 1.8mmol) (1ml).Naturally be warming up to room temperature, reaction is spent the night.Removal of solvent under reduced pressure, silicagel column purifying (sherwood oil: ethyl acetate=10:1), obtain raceme H14219mg, productive rate 60%.Racemization H14 (0.204g, 0.5mmol) and ring palladium A (0.170g, 0.25mmol) in 10mL methyl alcohol, reacted 0.5 hour, column chromatography for separation obtains two diastereomers, and they and reagent (0.5mmol the recommends Sodium proline) reaction of dissociating can be obtained chirality H14.
(R)-H14(X＝O，R、R 1＝Ph，R 2＝H，R 3＝H)
1H NMR (300MHz, C 6D 6) 67.87-7.82 (m, 2H), 7.63-7.57 (m, 2H), 7.21-7.00 (m, 8H), 6.52-6.18 (m, 5H), 3.61-3.53 (m, 1H), 3.01-3.44 (m, 7H); 31P NMR (161.92MHz, C 6D 6) δ 107.3ppm; EIMS m/z (relative intensity) is (%): 408 (M +, 5.0), 201 (15), 45 (100). ultimate analysis calculated value C 28H 25OP:C, 82.18; H, 6.15. measured value: C, 82.33; H, 6.17.
(R)-H15(X＝O，R、R 1＝OPh，R 2＝H，R 3＝H)
1H NMR (300MHz, C 6D 6) 67.94-7.88 (m, 4H), 7.73-7.64 (m, 2H), 7.431-7.29 (m, 6H), 6.87-6.73 (m, 5H), 3.61-3.53 (m, 1H), 3.01-3.44 (m, 7H); 31P NMR (161.92MHz, C 6D 6) 6136.2ppm; EIMS m/z (relative intensity) is (%): 440 (M +, 37), 336 (100). ultimate analysis calculated value C 28H 25O 3P:C, 76.35; H, 5.72. measured value: C, 76.23; H, 5.39.
(R)-H16(X＝O，R、R 1＝OEt，R 2＝H，R 3＝H)
1H NMR (300MHz, C 6D 6) 67.83-7.75 (m, 2H), 7.53-7.42 (m, 2H), 7.21-7.03 (m, 8H), 6.62-6.24 (m, 5H), 3.84-3.64 (m, 4H), 3.61-3.53 (m, 1H), 3.01-3.44 (m, 7H), 2.08-1.99 (m, 6H); 31P NMR (161.92MHz, C 6D 6) 6146.2ppm; EIMS m/z (relative intensity) is (%): 344 (M +, 54), 218 (100). ultimate analysis calculated value C 20H 25O 3P:C, 69.75; H, 7.32. measured value: C, 69.42; H, 7.53.
(R)-H17(X＝O，R、R 1＝OPh，R 2＝CH 2OH，R 3＝H)
1H NMR (300MHz, C 6D 6) 67.98-7.86 (m, 2H), 7.73-7.67 (m, 2H), 7.35-7.18 (m, 8H), 6.72-6.18 (m, 5H), 4.56 (s, 2H), 3.61-3.53 (m, 2H), 3.01-3.44 (m, 7H); 31PNMR (161.92MHz, C 6D 6) 6142.7ppm; EIMS m/z (relative intensity) is (%): 470 (M +, 53), 386 (100). ultimate analysis calculated value C 29H 27O 4P:C, 74.03; H, 5.78. measured value: C, 74.28; H, 5.39.
(R)-H18(X＝O，R、R 1＝OPh，R 2＝H，R 3＝COOMe)
1H NMR (300MHz, C 6D 6) 67.89-7.86 (m, 3H), 7.68-7.54 (m, 2H), 7.29-7.10 (m, 7H), 6.73-6.68 (m, 2H), 6.52-6.18 (m, 3H), 4.13 (s, 3H), 3.61-3.53 (m, 1H), 3.41-2.94 (m, 7H); 31P NMR (161.92MHz, C 6D 6) 6145.2ppm; EIMS m/z (relative intensity) is (%): 498 (M +, 47), 296 (100). ultimate analysis calculated value C 30H 27O 5P:C, 72.28; H, 5.46. measured value: C, 72.33; H, 5.39.
(R)-H19(X＝O，R、R 1＝Ph，R 2＝H，R 3＝C(O)NMe 2)
1H NMR (300MHz, CDCl 3) 67.65 (m, 3H), 7.45-7.32 (m, 2H), 6.72-6.66 (m, 2H), 6.68-6.55 (m, 4H), 4.45-4.34 (m, 1H), 3.65-3.50 (m, 1H), 3.18-2.86 (m, 7H), 2.58 (s, 3H), 2.42 (s, 3H); 31P NMR (161.92MHz, CDCl 3) 115.4ppm; EIMS m/z (relative intensity %): 480 (M ++ 1,64), 243 (100); Ultimate analysis calculated value C 31H 32NO 2P:C, 77.64; H, 6.31; N, 2.92. measured value: C, 77.32; H, 6.23; N, 2.97..
Embodiment 3: the application in the asymmetric allyl group amination reaction
General operation is an example with 2-(acetoxyl group p-nitrophenyl methyl) methyl acrylate.Under the argon shield, with raw material (0.5mmol), phthalic imidine (1.0mmol), chiral catalyst (0.01mmol) is dissolved in the 2ml tetrahydrofuran (THF), and the some plate is followed the tracks of reaction and is finished, and directly the silica gel column chromatography separation obtains product.If use (R)-H2 as catalyzer, yield is 95%, ee (%): 70%.
1H NMR (300MHz, CDCl 3) 68.21 (d, J=8.9Hz, 2H), 7.87-7.75 (m, 4H), 7.61 (d, J=9.0Hz, 2H), 6.63 (s, 1H), 6.52 (s, 1H), 5.66 (s, 1H), 3.72 (s, 3H); EIMS m/z (relative intensity) is (%): 367 (M +,＜1), 147 (51), 76 (100).
Embodiment 4: the application in the asymmetric catalytic hydrogenation reaction
General operation is an example with 2-acetamidoacrylic acid methyl esters. is full of in the glove box of nitrogen, one [Rh (COD) 2] BF 4(0.2mg, 0.005mmol) and chiral ligand (0.011mmol) be dissolved in the 1ml methylene dichloride, after the stirring at room 20 minutes, adding dehydroamino acid methyl esters (1mmol) is dissolved in the 1ml dichloromethane solution, above-mentioned reactor is transferred in the stainless steel autoclave, close still and take it out of glove box, behind hydrogen exchange 5 times, charge into hydrogen to setting reaction pressure, close still, be allowed to condition under the room temperature reaction 10 hours, carefully discharge hydrogen, reaction solution through silica gel column chromatography (sherwood oil: ethyl acetate=5: 1) the hydrogenation product. its optical purity and transformation efficiency are determined by gas phase or liquid-phase chromatographic analysis.If use (R)-Hla as part, transformation efficiency is 100%, ee (%): 77%.The racemization product obtains as Preparation of Catalyst by Pd/C.
1H NMR (300MHz, CDCl 3) δ 6.17 (s, 1H), 4.61 (m, 1H), 3.77 (s, 3H), 2.03 (s, 3H), 1.42 (d, J=6.7Hz, 3H); EIMS m/z (relative intensity) is (%): 145 (M +, 4.6), 86 (51), 44 (100).
Embodiment 5: the application in the allylation reaction of asymmetric aldehyde
General operation is an example with the phenyl aldehyde. under the protection of normal temperature noble gas, and [Pd (C 3H 5) Cl] 2(2.7mg, 7.5 μ mol), chiral ligand (30 μ mol) complexing in THF (1.0mL), under 0 ℃, phenyl aldehyde (31 μ L, 0.3mmol), the tetrahydrobenzene acetic ester (50.4mg, 0.36mmol) and Et 2(0.7mL, 1.0M in hexane 0.7mmol) is added into Zn successively, rises to 4 ℃ of reactions 12 hours, uses NH then 4The Cl cancellation, extracted with diethyl ether reduces pressure out and desolvates, silica gel column chromatography (sherwood oil: ethyl acetate=10: 1) obtain product.If use (R)-H1b as part, yield is 90%, ee (%): 56%.
1H NMR (300MHz, CDCl 3) 67.25-7.16 (m, 5H), 5.74-5.69 (m, 1H), 5.30-5.26 (m, 1H), 4.46 (dd, J=6.7,1.7Hz, 1H), 2.39 (m, 1H), 1.99 (m, 1H), 1.89 (m, 2H), 1.67-1.60 (m, 2H), 1.46-1.40 (m, 2H); EIMSm/z (relative intensity %): 216 (M +＜1), 134 (45), 91 (100).

Claims (7)

1. phosphine compound with planar chiral [2.2] paracyclophane is characterized in that this compound has following structural formula:
Figure FSB00000266684700011
X is Sauerstoffatom or singly-bound in the formula;
R or R 1=single replacement and dibasic phenyl, C 1～16Alkyl, aryloxy, C 1～4Alkoxyl group; R, R 1Be identical or different group; Aryl is for replacing or unsubstituted phenyl in the described aryloxy, and described substituting group is C 1～4Alkoxyl group, C 1～4Perfluoroalkyl, C 1～4Alkyl, halogen atom or phenyl;
R 2=H, COO (C nH 2n+1), hydroxyl C 1～4Alkyl, hydroxyl, C 1～16Alkyl or C (O) N (C nH 2n+1) 2, n=1～4 wherein;
R 3=H, C (O) N (C nH 2n+1) 2, COO (C nH 2n+1), hydroxyl C 1～4Alkyl or hydroxyl;
Perhaps X is a singly-bound, R, R 1=Ph, R 2=OC (O) NEt 2, R 3=H;
Wherein, as X=singly-bound or oxygen, R and R 1During=phenyl; R 2And R 3Can not be H simultaneously, and R 2During for H, R 3Can not be C (O) N (C nH 2n+1) 2
2. a kind of phosphine compound with planar chiral [2.2] paracyclophane as claimed in claim 1 is characterized in that this compound has following structural formula:
R or R in the formula 1=single replacement and dibasic phenyl, C 1～16Alkyl, aryloxy, C 1～4Alkoxyl group; R, R 1Be identical or different group; Aryl is for replacing or unsubstituted phenyl in the described aryloxy, and described substituting group is 4-methoxyl group, 4-trifluoromethyl, 4-methyl, 2-methyl, 3,5-dimethyl, 3,5-two (trifluoromethyl), 3,5-phenylbenzene, 4-fluorine;
R 2And R 3According to claim 1;
Wherein, as X=singly-bound or oxygen, R and R 1During=phenyl, R 2And R 3Can not be H simultaneously.
3. a kind of phosphine compound with planar chiral [2.2] paracyclophane as claimed in claim 1 or 2 is characterized in that described C 1～16Alkyl be cyclohexyl, C 1～16Alkyl or phenyl.
4. a kind of phosphine compound synthetic method with planar chiral [2.2] paracyclophane as claimed in claim 1 is characterized in that by following step synthetic:
(1) the paracyclophane list phosphine compound of racemization is synthetic
In organic solvent and under the 0 ℃～room temperature, obtained the paracyclophane list phosphine compound of racemization in 2～10 hours by 4-bromine [2.2] paracyclophane, butyllithium and dialkyl phosphine chlorine or the reaction of two-oxyl phosphorus chlorine; Wherein, the mol ratio of described 4-bromine [2.2] paracyclophane, butyllithium and dialkyl phosphine chlorine or two-oxyl phosphorus chlorine is 1: 1～2: 1～2;
(2) the paracyclophane oxa-list phosphine compound of racemization is synthetic
React the paracyclophane oxa-list phosphine compound that obtained racemization in 6～18 hours in organic solvent and under the 0 ℃～room temperature by 4-hydroxyl [2.2] paracyclophane, organic bases, dialkyl phosphine chlorine or two-oxyl phosphorus chlorine; Wherein, described organic bases is triethylamine or pyridine, and the mol ratio of described 4-hydroxyl [2.2] paracyclophane, organic bases, dialkyl phosphine chlorine or two-oxyl phosphorus chlorine is 1: 4～8: 1～2;
(3) the paracyclophane list phosphine compound of diastereomer is synthetic
In organic solvent and under the 0 ℃～room temperature, with phosphine compound and two diastereomers of ring palladium compound A reaction acquisition in 0.5-3 hour of racemization paracyclophane, the mol ratio of the phosphine compound of described racemization paracyclophane and ring palladium compound A is 1: 0.2～1;
(4) phosphine compound of optical purity paracyclophane is synthetic
Under organic solvent and room temperature, the phosphine compound of the paracyclophane of diastereomer and the ring palladium compound B that obtained disintegrating down in reagent react 0.5-3 hour and (R) or the optical purity paracyclophane list phosphine compound (S) of following structural formula of dissociating: described reagent amino acid sodium or the diamine compound of dissociating; The phosphine compound of the paracyclophane of described diastereomer is 1: 1～2 with the mol ratio of the reagent that dissociates;
In the above-mentioned steps, the structural formula of described 4-bromine [2.2] paracyclophane is:
The structural formula of described 4-hydroxyl [2.2] paracyclophane is:
Figure FSB00000266684700031
The structural formula of the phosphine compound of the paracyclophane of described racemization is:
Figure FSB00000266684700032
Described ring palladium compound A structural formula is:
Figure FSB00000266684700033
The structural formula of the phosphine compound of described (R) or optical purity paracyclophane (S) is:
Figure FSB00000266684700034
Described ring palladium compound B structural formula is:
Figure FSB00000266684700035
Described dialkyl phosphine chlorine or two-oxyl phosphine chlorine are: RR 1PCl
R, R in the formula 1, R 2, R 3, X according to claim 1.
4. a kind of synthetic method with phosphine compound of planar chiral [2.2] paracyclophane as claimed in claim 3 is characterized in that described organic solvent is benzene, toluene, methylene dichloride, tetrahydrofuran (THF), tetracol phenixin, ether or methyl alcohol.
5. a kind of synthetic method with phosphine compound of planar chiral [2.2] paracyclophane as claimed in claim 3, the product that it is characterized in that described step (1), (2), (3) or (4) is through column chromatographic isolation and purification.
6. a kind of synthetic method with phosphine compound of planar chiral [2.2] paracyclophane as claimed in claim 3 is characterized in that described ring palladium compound B obtains encircling palladium compound A with 10% salt acid treatment recovery.
7. a kind of purposes with phosphine compound of planar chiral [2.2] paracyclophane as claimed in claim 1 is characterized in that being used for the catalyzer of allyl group amination asymmetric catalysis or alkylated reaction asymmetric catalysis; The part of asymmetric reaction that is used for the allylation reaction of asymmetric catalytic hydrogenation reaction or aldehyde.
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