CN103193830A - Preparation method of chiral ferrocene phosphine ligand - Google Patents

Preparation method of chiral ferrocene phosphine ligand Download PDF

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CN103193830A
CN103193830A CN2013101018243A CN201310101824A CN103193830A CN 103193830 A CN103193830 A CN 103193830A CN 2013101018243 A CN2013101018243 A CN 2013101018243A CN 201310101824 A CN201310101824 A CN 201310101824A CN 103193830 A CN103193830 A CN 103193830A
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lithium
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陈卫平
张生勇
聂惠芳
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Fourth Military Medical University FMMU
Xian Modern Chemistry Research Institute
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Abstract

The invention discloses a preparation method of a chiral ferrocene phosphine ligand. The method comprises the following steps of: performing lithiation on Ugi's amine under a room temperature condition by using BuLi to obtain Ugi's amine subjected to ortho activation; putting Ugi's amine at the temperature of -60 DEG C; slowly injecting PCl3 and heating to be the room temperature; reacting overnight to generate turbid liquid of dichlorinated product; adding excessive lithium compound RLi or grignard reagent RMgX to react to obtain the chiral phosphine ligand, or adding RLi or RMgX with the equal molar rate, slowly heating to the room temperature and reacting; and adding the excessive RLi or RMgX to react to obtain the chiral phosphine ligand. According to the preparation method, various of substituent groups are conveniently introduced into phosphorus atoms so as to conveniently change electrons and three-dimensional properties of the phosphine ligand.

Description

The preparation method of chiral ferrocene phosphine part
Technical field
The present invention relates to the synthetic method of chiral ferrocene phosphine part, belong to technical field of organic synthesis.
Background technology
Chiral ferrocene phosphine part be the very important part of a class in the asymmetric catalysis field (Array á s R G, Angew. Chem. Int. Ed. 2006,45,7675-7676.).1-(2-diphenyl phosphine) ferrocenyl- N, N-dimethyl amine (PPFA) compounds self is exactly the outstanding part of a class, (Hayashi T, Tetrahedron Letters. 1974,15,4405-4408.), the PPFA compounds also is synthetic many chiral ferrocene phosphine parts simultaneously, as: Josiphos (Togni A, J. Am. Chem. Soc. 1994,116,4062-4066.) and BoPhoz (Boaz, N. W. Org. Lett.2002, 4, 2421) key intermediate.Known PPFA compounds synthetic method is Ugi ' s amine cis-selectivity lithiumation, react with the basic phosphonium chloride of two virtues (alkane) then (Hayashi T, Bull. Chem. Soc. Jpn. 1980,53,1138-1151.).The shortcoming of known PPFA compounds synthetic method is that the basic phosphonium chloride of many two virtues (alkane) is difficult for obtaining.
Because the P-chiral ligand is synthetic than other chiral ligand difficulties, so the part type of development is less, because P-chiral ligand chiral centre tends to obtain stereoselectivity preferably from transition metal is nearer, therefore, the method for easy synthetic P-chiral material is the direction that the chemist makes great efforts always.A kind of method of known synthetic ferrocene class P-chiral phosphine ligand is: with Ugi ' s amine cis-selectivity lithiumation, then with virtue (alkane) basic dichloride phosphine reaction, again with a kind of organometallic reagent reaction (Chen W, J. Am. Chem. Soc.2006 , 128,3922 .).This method has stereoselectivity height, yield height, simple operation and other advantages, many outstanding parts such as Trifer (Chen W have been synthesized in this way, Angew. Chem. Int. Ed. 2007,46,4141), ChenPhos (WO2007116081.) and C1-Trifer (WO2008101868.).But the shortcoming of this method is the basic dichloride phosphine of many virtues (alkane) to be difficult for obtaining, and the substituting group on the phosphorus atom can only carry out limited change.
As everyone knows, the electronics of chiral phosphine ligand and tridimensional character play a decisive role to catalytic activity and enantioselectivity, different substrates and different catalyzed reactions have different requirements to the electronics of chiral phosphine ligand with tridimensional character, therefore, the phosphine part of the convenient synthetic various different electronics of development and tridimensional character has very important significance.
Summary of the invention
The object of the invention is to provide a kind of preparation method of chiral ferrocene phosphine part of simple synthetic method.
Implementation procedure of the present invention is as follows:
The preparation method of compound shown in the general structure (I) is characterized in that may further comprise the steps:
Figure 266964DEST_PATH_IMAGE001
R 1And R 2Be independently selected from the alkyl of C1-C25,
Or aryl, as:
Figure 184105DEST_PATH_IMAGE002
Or heteroaryl, as:
Figure 963842DEST_PATH_IMAGE003
Or cycloalkyl, as:
Figure 359051DEST_PATH_IMAGE004
Or ferrocenyl, as:
Figure 298057DEST_PATH_IMAGE005
(1) organo-metallic lithium reagent activation RConfiguration or SBehind the configuration Ugi ' s amine with PCl 3Reaction obtains dichloro-thing (II);
Figure 120520DEST_PATH_IMAGE006
(2) RLi or the RMgX of 2～3 times of amount of substances of adding dichloro-thing (II) react compound, wherein R=R shown in the general structure (I) that obtains not having the P-chirality 1=R 2, X is halogen;
Perhaps, the R that adds 1～1.05 times of molar weight of dichloro-thing (II) earlier 1Li or R 1The MgX reaction obtains monochloro for thing (III), and then adds excessive R 2Li or R 2MgX reacts compound, wherein R shown in the general structure (I) that obtains the P-chirality 1≠ R 2,
Figure 387553DEST_PATH_IMAGE007
。
In the above-mentioned steps (1), the organo-metallic lithium reagent is lithium methide, n-Butyl Lithium, s-butyl lithium, tert-butyl lithium, hexyl lithium or phenyl lithium; Adding organo-metallic lithium reagent activation Ugi ' s amine reaction solvent is methyl tertiary butyl ether, ether, toluene or tetrahydrofuran (THF), and temperature is-15 ℃～35 ℃; Add PCl 3Temperature be-120 ℃～-60 ℃, the reaction times is 6～18h.
In the above-mentioned steps (2), the temperature that adds RLi or RMgX is-60 ℃～35 ℃.Add R 1Li or R 1The temperature of MgX is-120 ℃～-60 ℃, rises to room temperature afterreaction 1～6h.Add R 2Li or R 2The temperature of MgX is-60 ℃～35 ℃, R 2Li or R 2The amount of substance of MgX be monochloro for 1～2 times of thing (III), rise to room temperature afterreaction 4-16h.
Advantage of the present invention and positively effect: can on phosphorus atom, introduce various substituting groups easily, change electronics and the tridimensional character of phosphine part easily, thereby can expand the phosphine part to greatest extent not to the range of application in the catalyzed reaction.
Embodiment
With BuLi with Ugi ' s amine at ambient temperature lithiumation obtain the Ugi ' s amine of ortho position activation, place again below-60 ℃, slowly inject PCl 3After rise to the suspension liquid that room temperature reaction generates the dichloro-thing, used phosphonate reagent is PCl 3, used lithium reagent is the organo-metallic lithium reagent in the reaction, as: lithium methide, n-Butyl Lithium, s-butyl lithium, tert-butyl lithium, hexyl lithium or phenyl lithium etc.The reaction solvent for use is methyl tertiary butyl ether, ether, toluene or tetrahydrofuran (THF) etc.; Temperature of reaction is-15 ℃～35 ℃ during lithiumation, adds PCl 3Temperature be-120 ℃～-60 ℃, the reaction times is 6～18h, synthetic route is as follows:
According to (
Figure 379965DEST_PATH_IMAGE009
) with (
Figure 373329DEST_PATH_IMAGE010
) route generate respectively non-P-chirality and P-chirality ( R)- S-PPFA compounds:
( ) excessive lithiumation thing RLi or the Grignard reagent RMgX of adding under cold condition, be warming up to back flow reaction then and obtain not having the PPFA compounds of P-chirality, reaction times is 4-16h, the amount of substance of RLi or RMgX is that 2～3 times of R of dichloro-thing are aliphatic group, heterocycle or aryl radical, and synthetic route is as follows:
Figure 995164DEST_PATH_IMAGE011
(
Figure 518549DEST_PATH_IMAGE010
) adding equimolar RLi or RMgX below-60 ℃, slowly rising to room temperature reaction 2h then, the reaction solvent for use is methyl tertiary butyl ether, ether, toluene or tetrahydrofuran (THF) etc.; The amount of substance that adds RLi or RMgX is 1～1.05 times of dichloro-thing, and slowly rising to room temperature reaction, to obtain monochloro be 1～6h for the thing suspension liquid time; Add excessive RLi or RMgX more at low temperatures, be warming up to the PPFA compounds that back flow reaction 4-16h obtains the P-chirality then, the amount of substance of R ' Li or R ' MgX be monochloro for 1～2 times of thing, being warming up to reflux time is 4-16h; R and R ' are inequality, and synthetic route is as follows:
Figure 73027DEST_PATH_IMAGE012
Embodiment 1: preparation ( R)- S-1-(2-diphenyl phosphine) ferrocenyl- N, N-dimethyl amine 1
Add in the 250 mL there-necked flasks ( R)-Ugi ' s amine 2.57 g (10 mmol), through vacuumize/inject the dry methyl tertiary butyl ether of crossing of 40 mL with syringe after the nitrogen circulation, place ice-water bath to be stirred to dissolving, slowly inject s-BuLi 11 mL (1 M, 11 mmol), reaction 2h generates brick-red floss precipitation in ice-water bath, there-necked flask is placed-78 ℃ low-temp reaction device, slowly injects the PCl that is dissolved in 10 mL methyl tertiary butyl ethers 30.96 mL (11 mmol) rises to room temperature reaction and spends the night and obtain the suspension liquid of dichloro-thing.
Add bromobenzene 2.4 mL (23 mmol) in the 100 mL single port bottles, through vacuumize/after nitrogen circulation, inject the dry methyl tertiary butyl ether of crossing of 40 mL with syringe, place-40 ℃ low-temp reaction device to be stirred to dissolving, slowly inject n-BuLi 15 mL (1.6 M, 24 mmol) slowly rise to room temperature reaction 2h and generate phenyl lithiumation thing.
The suspension liquid of dichloro-thing is placed-20 ℃ of low-temp reaction devices, phenyl lithiumation thing is added in the suspension liquid of dichloro-thing with double needle, be warming up to back flow reaction 8h, remove by filter insolubles, water, saturated common salt water washing successively, the solvent evaporated column chromatography gets orange solid product 2.4 g, productive rate 54.4%.
mp?141-143℃;?
Figure 439286DEST_PATH_IMAGE013
?-350.9?(c?=?0.25,?CHCl 3);? 1H?NMR?(500?Hz,?CDCl 3)：δ?7.62-7.56?(m,?2H),?7.37-7.32?(m,?3H),?7.22-7.14?(m,?5H),?4.37?(s,?1H),?4.25-4.24?(m,?1H),?4.16-4.14?(dd,?J?=?2.5,?2.5?Hz,?1H),?3.94?(s,?5H),?3.86?(s,?1H),?1.77?(s,?6H),?1.27-1.26?(d,?J?=?7?Hz,?3H)。
Embodiment 2: preparation ( R)- S-1-[2-two (3,5-3,5-dimethylphenyl) phosphino-] ferrocenyl- N, N-dimethyl amine 2
The preparation method obtains orange oily matter 2.2 g, productive rate 44.2% with embodiment 1.
Figure 714410DEST_PATH_IMAGE013
?-278.5?(c?=?0.25,?CHCl 3);? 1H?NMR?(500?Hz,?CDCl 3)?δ?7.25-7.23?(m,?2H),?6.98?(s,?1H),?6.80-6.78?(m,?3H),?4.35?(s,?1H),?4.23-4.22?(m,?1H),?4.10-4.08?(dd,?J?=?2.5,?2.5?Hz,?1H),?3.92?(s,?5H),?3.87?(s,?1H),?2.32?(s,?6H),?2.18?(s,?6H),?1.81?(s,?6H),?1.28-1.27?(d,?J?=?7?Hz,?3H)。
Embodiment 3: preparation ( R)- S-1-[2-two (3,5-di-t-butyl base phenyl) phosphino-] ferrocenyl- N, N-dimethyl amine 3
The preparation method obtains yellow spumescence solid 3.1 g, productive rate 46.6% with embodiment 1.
Figure 482515DEST_PATH_IMAGE013
?-246.8?(c?=?0.25,?CH 2Cl 2);? 1H?NMR?(500?Hz,?CDCl 3)?δ?7.65-7.55?(dd,?J?=?2,?1.5?Hz,?2H),?7.44?(s,?1H),?7.25-7.21?(m,?3H),?4.37?(s,?1H),?4.26?(s,?1H),?4.21-4.17?(dd,?J?=?3,?2.5?Hz,?1H),?3.97?(s,?5H),?3.90?(s,?1H),?1.73?(s,?6H),?1.36?(s,?18H),?1.34-1.30?(d,?J?=?6.5?Hz,?3H),?1.26?(s,?18H);? 31P?NMR?(202?Hz,?CDCl 3)?δ?-22.78?(s).
Embodiment 4: preparation ( R)- S-1-[2-two (4-bromophenyl) phosphino-] ferrocenyl- N, N-dimethyl amine 4
The preparation method obtains yellow spumescence solid 1.38 g, productive rate 23.1% with embodiment 1.
?-302.8?(c?=?0.25,?CH 2Cl 2);? 1H?NMR?(500?Hz,?CDCl 3)?δ?7.52-7.46?(d,?J?=?7.5?Hz,?2H),?7.44-7.36?(m,?2H),?7.34-7.28?(d,?J?=?7.5?Hz,?2H),?7.04-6.98?(m,?2H),?4.39?(s,?1H),?4.20?(s,?1H),?4.15-4.10?(d,?J?=?4.5?Hz,?1H),?3.96?(s,?5H),?3.77?(s,?1H),?1.76?(s,?6H),?1.16-1.12?(d,?J?=?3?Hz,?3H);? 31P?NMR?(202?Hz,?CDCl 3)?δ?-24.36?(s)。
Embodiment 5: preparation ( R)- S-1-[2-(two (2-thienyl) phosphino-] ferrocenyl- N, N-dimethyl amine 5
The preparation method is with embodiment 1, orange solid product 2.38 g, productive rate 52.5%.
mp?118.6-119.8℃;?
Figure 546603DEST_PATH_IMAGE013
?-424?(c?=?0.25,?CH 2Cl 2);? 1H?NMR?(500?Hz,?CDCl 3)?δ?7.60-7.56?(d,?J?=?5?Hz,?1H),?7.52-7.46?(m,?1H),?7.36-7.32?(d,?J?=?5?Hz,?1H),?7.15-7.05?(m,?2H),?7.00-6.90?(m,?1H),?4.37?(s,?1H),?4.32?(s,?1H),?4.27?(s,?1H),?4.20-4.10?(m,?1H),?3.95?(s,?5H),?1.80?(s,?6H),?1.30-1.20?(d,?J?=?7?Hz,?3H);? 31P?NMR?(202?Hz,?CDCl 3)?δ?-52.08?(s)。
Embodiment 6: preparation ( R)- S-1-[2-two (4-phenyl) phosphino-] ferrocenyl- N, N-dimethyl amine 6
The preparation method obtains safran solid 2.5 g, productive rate 42.0% with embodiment 1.
mp?95.6-97℃;? ?-387.6?(c?=?0.25,?CH 2Cl 2);? 1H?NMR?(500?Hz,?CDCl 3)?δ?7.80-7.74?(m,?2H),?7.72-7.66?(m,?4H),?7.66-7.62?(d,?J?=?7.5?Hz,?2H),?7.54-7.32?(m,?10H),?4.46?(s,?1H),?4.34?(s,?1H),?4.30-4.20?(dd,?J?=?2,?1.5?Hz,?1H),?4.04?(s,?5H),?4.00?(s,?1H),?1.88?(s,?6H),?1.36-1.32?(d,?J?=?6?Hz,?3H);? 31P?NMR?(202?Hz,?CDCl 3)?δ?-24.35?(s)。
Embodiment 7:( R)- S-1-[2-two n-decane base phosphino-s)] ferrocenyl- N, N-dimethyl amine 7
The preparation of dichloro-thing is with embodiment 1.
Have to frame and add 0.96 g (40 mmol) magnesium ribbon in the 100 mL there-necked flasks of prolong, injecting dry ether slowly stirs, slowly inject the initiation reaction of 0.8 mL (3.8 mmol) bromo n-decane to refluxing, drip 7.5 mL (36.2 mmol) the bromo n-decane that is dissolved in 20 mL anhydrous diethyl ethers then, add back back flow reaction 4h, set aside for use.
The suspension liquid of dichloro-thing is placed-20 ℃ of low-temp reaction devices, Grignard reagent is added in the suspension liquid of dichloro-thing with double needle, be warming up to back flow reaction 8h, remove by filter insolubles, water, saturated common salt water washing successively, the solvent evaporated column chromatography gets orange oily matter 2.6 g, productive rate 45.7%.
Figure 248028DEST_PATH_IMAGE013
?-92.1?(c?=?0.7,?CH 2Cl 2);? 1H?NMR?(500?Hz,?CDCl 3)?δ?4.26?(s,?1H),?4.19?(s,?1H),?4.11?(s,?1H),?4.10-4.02?(m,?6H),?2.06?(s,?6H),?1.70-1.43?(m,?6H),?1.42-1.16?(m,?33H),?0.92-0.83?(m,?6H);? 31P?NMR?(202?Hz,?CDCl 3)?δ?-39.17?(s)。
Embodiment 8: preparation ( R)- S-1-[2-[( R)-(2-o-methoxyphenyl) (phenyl)] phosphino-] ferrocenyl- N, N-dimethyl amine 8
The preparation of dichloro-thing is with embodiment 1.
Add O-methoxy bromobenzene 1.25 mL (10 mmol) in the 100 mL single port bottles, through vacuumize/after nitrogen circulation, inject the dry methyl tertiary butyl ether of crossing of 20 mL with syringe, place-40 ℃ low-temp reaction device to be stirred to dissolving, slowly inject n-BuLi 6.6 mL (1.6 M, 10.56 mmol) rise to room temperature reaction 2h and generate phenyl lithiumation thing; The suspension liquid of dichloro-thing is placed-70 ℃ of low-temp reaction devices, with double needle phenyl lithiumation thing is added in the suspension liquid of dichloro-thing, rise to room temperature reaction 2h and obtain monochloro for thing.
Add bromobenzene 1.26 mL (12 mmol) in the 100 mL single port bottles, through vacuumize/after nitrogen circulation, inject the dry methyl tertiary butyl ether of crossing of 20 mL with syringe, place-40 ℃ low-temp reaction device to be stirred to dissolving, slowly inject n-BuLi 8 mL (1.6 M, 12.8 mmol) rise to room temperature reaction 2h and generate the lithiumation thing; Monochloro is placed-20 ℃ of low-temp reaction devices for the suspension liquid of thing, with double needle the lithiumation thing is added in the suspension liquid of monochloro for thing, be warming up to back flow reaction 8h, remove by filter insolubles, water, saturated common salt water washing successively, the solvent evaporated column chromatography gets orange solid product 2.1 g, 44.6%.
mp?127.?-128.4℃;? ?-237.2?(c?=?0.25,?CH 2Cl 2);? 1H?NMR?(500?Hz,?CDCl 3)?δ?7.36-7.30?(m,?1H),?7.22-7.10?(m,?6H),?6.98-6.92?(m,?1H),?6.90-6.84?(m,?1H),?4.37?(s,?1H),?4.25?(s,?1H),?4.32-4.05?(dd,?J?=?2.5,?3?Hz,?1H),?3.97?(s,?5H),?3.96-3.93?(m,?1H),?3.93?(s,?3H),?1.79?(s,?6H),?1.34-1.24?(d,?J?=?1.5?Hz,?3H);? 31P?NMR?(202?Hz,?CDCl 3)?δ?-40.51?(s)。
Embodiment 9: preparation ( R)- S-1-[2-[( S)-(2-o-methoxyphenyl) (phenyl)] phosphino-] ferrocenyl- N, N-dimethyl amine 9
The preparation of dichloro-thing is with embodiment 1.
Add bromobenzene 1.05 mL (10 mmol) in the 100 mL single port bottles, through vacuumize/after nitrogen circulation, inject the dry methyl tertiary butyl ether of crossing of 20 mL with syringe, place-40 ℃ low-temp reaction device to be stirred to dissolving, slowly inject n-BuLi 6.6 mL (1.6 M, 10.56 mmol) rise to room temperature reaction 2h and generate phenyl lithiumation thing; The suspension liquid of dichloro-thing is placed-70 ℃ of low-temp reaction devices, with double needle phenyl lithiumation thing is added in the suspension liquid of dichloro-thing, rise to room temperature reaction 2h and obtain monochloro for thing.
Add O-methoxy bromobenzene 1.5 mL (12 mmol) in the 100 mL single port bottles, through vacuumize/after nitrogen circulation, inject the dry methyl tertiary butyl ether of crossing of 20 mL with syringe, place-40 ℃ low-temp reaction device to be stirred to dissolving, slowly inject n-BuLi 8 mL (1.6 M, 12.8 mmol) rise to room temperature reaction 2h and generate the lithiumation thing; Monochloro is placed-20 ℃ of low-temp reaction devices for the suspension liquid of thing, with double needle the lithiumation thing is added in the suspension liquid of monochloro for thing, be warming up to back flow reaction 8h, remove by filter insolubles, water, saturated common salt water washing successively, the solvent evaporated column chromatography gets orange solid product 1.9 g, 40.3%.
mp?127.?-128.4℃;?
Figure 970314DEST_PATH_IMAGE013
?-106?(c?=?0.25,?CH 2Cl 2);? 1H?NMR?(500?Hz,?CDCl 3)?δ?7.34-7.28?(m,?1H),?7.18-7.08?(m,?2H),?6.98-6.80?(m,?4H),?6.78-6.72?(m,?1H),?6.70-6.65?(m,?1H),?4.39?(s,?1H),?4.26?(s,?1H),?4.20-4.08?(dd,?J?=?3.5,?3.5?Hz,?1H),?3.97?(s,?5H),?3.90?(s,?1H),?3.58?(s,?3H),?1.84?(s,?6H),?1.35-1.25?(d,?J?=?6.5?Hz,?3H);? 31P?NMR?(202?Hz,?CDCl 3)?δ?-53.36?(s)。
Embodiment 10: preparation ( R)- S-1-[2-[( S)-(3, the 5-3,5-dimethylphenyl) (phenyl)] phosphino-] ferrocenyl- N, N-dimethyl amine 10
The preparation method is with embodiment 9, yellow solid product 2.3 g, productive rate 49.0%.
mp?177.3-178.6℃;? ?-317.6?(c?=?0.25,?CH 2Cl 2);? 1H?NMR?(500?Hz,?CDCl 3)?δ?7.72-7.60?(m,?2H),?7.44-7.36?(m,?3H),?6.90-6.80?(m,?3H),?4.43?(s,?1H),?4.28?(s,?1H),?4.22-4.12?(d,?J?=?4?Hz,?1H),?3.96?(s,?5H),?3.91?(s,?1H),?2.23?(s,?6H),?1.87?(s,?6H),?1.44-1.28?(d,?J?=?1.5?Hz,?3H)。

Claims (7)

1. the preparation method of compound shown in the general structure (I) is characterized in that may further comprise the steps:
Figure 2013101018243100001DEST_PATH_IMAGE002
R 1And R 2Be independently selected from the alkyl of C1-C25, or aryl, heteroaryl, cycloalkyl, ferrocenyl,
(1) organo-metallic lithium reagent activation RConfiguration or SBehind the configuration Ugi ' s amine with PCl 3Reaction obtains dichloro-thing (II);
Figure 2013101018243100001DEST_PATH_IMAGE004
(2) RLi or the RMgX of 2～3 times of amount of substances of adding dichloro-thing (II) react compound, wherein R=R shown in the general structure (I) that obtains not having the P-chirality 1=R 2, X is halogen;
Perhaps, the R that adds 1～1.05 times of molar weight of dichloro-thing (II) earlier 1Li or R 1The MgX reaction obtains monochloro for thing (III), and then adds excessive R 2Li or R 2MgX reacts compound, wherein R shown in the general structure (I) that obtains the P-chirality 1≠ R 2,
Figure 2013101018243100001DEST_PATH_IMAGE006
。
2. according to the preparation method of the described compound of claim 1, it is characterized in that: in the step (1), the organo-metallic lithium reagent is lithium methide, n-Butyl Lithium, s-butyl lithium, tert-butyl lithium, hexyl lithium or phenyl lithium.
3. according to the preparation method of the described compound of claim 1, it is characterized in that: in the step (1), adding organo-metallic lithium reagent activation Ugi ' s amine reaction solvent is methyl tertiary butyl ether, ether, toluene or tetrahydrofuran (THF), and temperature is-15 ℃～35 ℃.
4. according to the preparation method of the described compound of claim 1, it is characterized in that: in the step (1), add PCl 3Temperature be-120 ℃～-60 ℃, the reaction times is 6～18h.
5. according to the preparation method of the described compound of claim 1, it is characterized in that, it is characterized in that: in the step (2), the temperature that adds RLi or RMgX is-60 ℃～35 ℃.
6. according to the preparation method of the described compound of claim 1, it is characterized in that, it is characterized in that: in the step (2), add R 1Li or R 1The temperature of MgX is-120 ℃～-60 ℃, rises to room temperature afterreaction 1～6h.
7. according to the preparation method of the described compound of claim 1, it is characterized in that: in the step (2), add R 2Li or R 2The temperature of MgX is-60 ℃～35 ℃, R 2Li or R 2The amount of substance of MgX be monochloro for 1～2 times of thing (III), rise to room temperature afterreaction 4-16h.
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Cited By (7)

* Cited by examiner, † Cited by third party
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CN103831133A (en) * 2014-02-25 2014-06-04 中国人民解放军第四军医大学 Bi-functional phosphine thiourea organic catalyst based on ferrocene skeleton as well as preparation method and application thereof
CN104592313A (en) * 2014-12-30 2015-05-06 陕西师范大学 Double functional hydrogen bond organic catalyst based on ferrocene as well as preparation method and application of double functional hydrogen bond organic catalyst
CN107098932A (en) * 2017-06-29 2017-08-29 管德新 A kind of synthetic method of benzyl class part available for hydroformylation reaction
CN114085251A (en) * 2021-11-02 2022-02-25 中国人民解放军空军军医大学 Chiral ferrocene-spiro skeleton diphosphine ligand and preparation method thereof
CN114085250A (en) * 2021-11-02 2022-02-25 中国人民解放军空军军医大学 Preparation and application of P-chiral phosphine-oxazoline ligand metal complex catalyst containing Ugi's amine building blocks
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CN103804432A (en) * 2014-02-25 2014-05-21 中国人民解放军第四军医大学 Double-functionalized amine-thiourea organic catalyst based on ferrocene and preparation method and application thereof
CN103831133A (en) * 2014-02-25 2014-06-04 中国人民解放军第四军医大学 Bi-functional phosphine thiourea organic catalyst based on ferrocene skeleton as well as preparation method and application thereof
CN103804432B (en) * 2014-02-25 2017-01-25 中国人民解放军第四军医大学 Double-functionalized amine-thiourea organic catalyst based on ferrocene and preparation method and application thereof
CN104592313A (en) * 2014-12-30 2015-05-06 陕西师范大学 Double functional hydrogen bond organic catalyst based on ferrocene as well as preparation method and application of double functional hydrogen bond organic catalyst
CN104592313B (en) * 2014-12-30 2017-08-25 陕西师范大学 Difunctional hydrogen bond organic catalyst based on ferrocene and its preparation method and application
CN107098932A (en) * 2017-06-29 2017-08-29 管德新 A kind of synthetic method of benzyl class part available for hydroformylation reaction
CN114085251A (en) * 2021-11-02 2022-02-25 中国人民解放军空军军医大学 Chiral ferrocene-spiro skeleton diphosphine ligand and preparation method thereof
CN114085250A (en) * 2021-11-02 2022-02-25 中国人民解放军空军军医大学 Preparation and application of P-chiral phosphine-oxazoline ligand metal complex catalyst containing Ugi's amine building blocks
CN114085250B (en) * 2021-11-02 2024-01-19 中国人民解放军空军军医大学 Preparation and application of P-chiral phosphine-oxazoline ligand metal complex catalyst containing Ugi's amine building block
CN114085251B (en) * 2021-11-02 2024-01-19 中国人民解放军空军军医大学 Chiral ferrocene-spiro framework biphosphine ligand and preparation method thereof
CN116178455A (en) * 2023-04-26 2023-05-30 江苏欣诺科催化剂股份有限公司 Preparation method of ferrocene chiral phosphine ligand
CN116178455B (en) * 2023-04-26 2023-08-18 江苏欣诺科催化剂股份有限公司 Preparation method of ferrocene chiral phosphine ligand

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