CN101121730A - Phosphaalkene ligand and its preparing method and use - Google Patents
Phosphaalkene ligand and its preparing method and use Download PDFInfo
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Abstract
The invention relates to a phosphine ene ligand and the synthesis method and applications. The structural formula of the phosphine ene ligand is: in the formula, R1 is the phenyl or cyclohexyl; R2 is the benzoyl, 4 - trifluoromethyl phenyl, and allyl amine-N-formyl. The phosphine ene ligand provided in the invention is a pi-acid ligand, which can receive the central metal d electronics when coordinated with the transitionall metal to reduce the central metal from the high valence state to the low valence state. The stability of the phosphine ene ligand and the catalyst system are good; in particular, the synthesis of the ligand is simple; the total collection rate is high; the phosphine ene ligand can be synthesized in the large amount; the structure and the charge quality are easy to adjust and modify. The application scope of the phosphine ene ligand and the catalyst provided in the invention is wide; in the catalytic reaction, the catalytic activity high; the selectivity is good; the reaction conditions are mild. The phosphine ene ligand can be used in the palladium-catalyzed cross-coupling reaction of the organic metal reagents and the aryl halides.
Description
Technical field
The present invention relates to a class novel have π-tart Phosphaalkene ligand and synthetic method thereof and the application of its palladium complex in the cross-coupling reaction of catalysis organometallic reagent and aryl halides.
Background technology
Transition metal-catalyzed cross-coupling reaction is one of important method that forms C-C, and in nearly 30 years, this type of reaction has obtained extensive studies and obtained huge progress, has also obtained a large amount of application in organic synthesis.In general, this reaction is finished a catalytic cycle and is comprised three committed steps: the oxidation addition, change metallization and reduction elimination.The research major part in past concentrates on this stage of oxidation addition, studies show that: the phosphorus part that utilizes electron rich is (as tri-butyl phosphine, tricyclohexyl phosphine) can the promotes oxidn addition, (, R-Cl) reasonable effect is arranged also for some substrates that are not easy to the oxidation addition as R-Br.It is finally to cause carbon-to-carbon Cheng Jian in three steps that reduction is eliminated, and obtains a step of cross-coupling product, and many difficult problems that cross-coupling reaction faced are (as sp
3Carbon-sp
3Carbon Cheng Jian) all coming from reduction eliminates too slow.Yet, up to now to how promoting to reduce the research report eliminated also seldom.Therefore, how to control or quicken to reduce and eliminate to realize that whole catalytic cycle has important theory and practical significance.
Though the catalytic cross-coupling reaction of transition metal such as palladium has been obtained huge achievement, this field still has many problems not solved well.Sp for example
3Carbon-sp
3The Cheng Jian of carbon contains the sp of β-hydrogen
3The Cheng Jian of carbon, FuGregory C. in recent years, people such as Knochel P. have done a large amount of research to this, and they are with Ni or the catalytic Negishi of Pd, Suzuki, Stille and Hiyama reaction have realized sp
3The cross-coupling reaction of carbon, in addition, Kambe N.Oshima K. and NakamuraE. use Pd respectively, and the catalytic Kumada reaction of Co or Fe has realized above-mentioned purpose, but the selectivity of reaction is generally not high, and reaction conditions is gentle, consuming time longer inadequately.Mainly contain the reason of following two aspects: the one, sp
3It is too slow that speed is eliminated in the reduction of carbon.The 2nd, be easy to take place side reaction β-hydrogen and eliminate.
Bibliographical information is just arranged a long time ago, utilize the part of electron deficiency, or have strong π-tart part and can promote reduction to eliminate, yet, the example that is applied to catalytic coupling up to now may be because this type of part has but suppressed the oxidation addition when promoting reduction to eliminate seldom.Thereby difficulty has been improved catalytic effect.We find do not adding under the situation of part Pd (dba) in addition in the catalytic oxidative coupling reaction of research Pd
2At catalysis sp
3-Zn and sp
3Can obtain good result in the oxidative coupling of-Zn.This means that dba may be a kind of π-sour part that can promote the reduction elimination.On this basis, in order further to improve the oxidation addition and to improve our imagination of coordination ability and on dba, introduce phosphorus atom, designed a class π-sour Phosphaalkene ligand.And its palladium complex is applied in the catalysis cross-coupling reaction.
Summary of the invention
The purpose of this invention is to provide Phosphaalkene ligand and synthetic method and application that a class has π-acid matter, simultaneously also to develop a class efficient for the cross-coupling reaction of organometallic reagent and aryl halides, the palladium of highly selective/Phosphaalkene ligand catalyst system.
In order to reach above purpose, the present invention is that basic raw material has synthesized a series of novel Phosphaalkene ligands with π-acid matter with adjacent bromobenzaldehyde, methyl phenyl ketone, 4-trifluoromethylated benzaldehyde, adjacent bromobenzyl bromine, diphenyl phosphine chloride, dialkyl group phosphonium chloride etc.
Its general structure is as follows:
R in the formula
1Be phenyl or cyclohexyl; R
2Be benzoyl, 4-trifluoromethyl or allyl amine-N-formyl radical.
Preferred The compounds of this invention is R wherein
1Be phenyl; R
2Compound 1 for benzoyl, 4-trifluoromethyl, allyl amine-N-formyl radical.
Preferred The compounds of this invention also is R wherein
1Be cyclohexyl; R
2Be benzoyl.
The present invention also provides the synthetic method of this type of Phosphaalkene ligand:
Work as R
1Be phenyl; R
2During for benzoyl, allyl amine-N-formyl radical; under nitrogen protection; add the 1-1.2 doubly Witting reagent of normal alpha-chloro acetophenone or the Witting reagent of N-allyl group-alpha-brominated ethanamide in the toluene solution of 2-diphenyl phosphine phenyl aldehyde; reflux concentrates after raw material disappears, and recrystallizing methanol gets Phosphaalkene ligand then.
Work as R
1Be cyclohexyl; R
2During for benzoyl; protect the carbonyl of 2-bromine phenyl styryl ketone earlier with the doubly normal triethyl orthoformate of 3.0-5.0; after this carry out the exchange of bromine lithium with the doubly normal butyllithium of 1.2-2.0; and then reacted 10 hours under the doubly normal dicyclohexyl phosphonium chloride of the adding 1.2-2.0 room temperature, add the dilute hydrochloric acid deprotection at last and obtain Phosphaalkene ligand.
Work as R
1Be phenyl; R
2During for the 4-trifluoromethyl, add the aqueous sodium hydroxide solution of 50wt% in the chloroformic solution of the Witting reagent that is dissolved with 4-trifluoromethylated benzaldehyde and the 1-1.2 times of normal adjacent bromobenzyl bromine of 4-trifluoromethylated benzaldehyde, stirring at room to raw material disappears; Through separatory, washing back reconcentration organic phase gets 4 '-trifluoromethyl-2-bromo-1.2-toluylene; Then 4 '-trifluoromethyl-2-bromo-1.2-toluylene is dissolved in the tetrahydrofuran (THF), adding 1.2-2.0 times of 4 '-trifluoromethyl-normal butyllithium of 2-bromo-1.2-toluylene under nitrogen protection reacted 2 hours down at-78 ℃, add doubly 4 '-trifluoromethyl-normal diphenyl phosphine chloride of 2-bromo-1.2-toluylene of 1.2-2.0 after lithiumation is finished again, reaction is 10 hours under the room temperature; Add the dilute hydrochloric acid stopped reaction after finishing; Through separatory, washing back reconcentration organic phase gets Phosphaalkene ligand.
Phosphaalkene ligand provided by the present invention is a kind of π-acid ligand, can accept central metal d electronics when itself and transition-metal coordination, thereby can promote central metal to be reduced into lower valency by high valence state.This type of Phosphaalkene ligand and catalyst system good stability, particularly part are synthetic easy, the total recovery height, and can synthesize in a large number, structure and charge property also are easy to adjust and modify.Phosphaalkene ligand provided by the present invention can be applied in catalytic various organometallic reagents of palladium and the aryl halides cross-coupling reaction as π-acid ligand, reaction only needs at room temperature (20 ℃ to 30 ℃), with tetrahydrofuran (THF) or toluene is solvent, for all kinds of alkyl zinc reagents with β-H, but the also acquisition cross-coupling product of highly selective.Separation yield is up to 99%.The ratio of substrate and catalyzer can be above to 100000/1, and substrate feeds intake and can reach the scale of 50 grams.
The present invention has the following advantages:
1. part has π-acidity (accepting the ability of central metal d electronics), can promote reduction to eliminate.
2. the structure of part and charge property are easy to adjust and modify.
3. Phosphaalkene ligand and catalysis catalyst system good stability, particularly part are synthetic easy, the total recovery height, and can synthesize in a large number.
4. catalyst system is applied widely, catalytic activity height during catalyzed reaction, and selectivity is good, reaction conditions gentleness, and scalable reaction.With practical value on synthesizing.
Embodiment:
The following examples can make those skilled in the art more fully understand the present invention, but do not limit the present invention in any way.
Embodiment one, be raw material synthetic ligands 1a with adjacent bromobenzaldehyde.
Synthesizing of compound 6:
With the adjacent bromobenzaldehyde 5 of 75.3g, 50.7g ethylene glycol and 1.1g p-TsOH and adding successively fills in the single port bottle of 400mL toluene, reflux, and the TLC monitoring reaction, raw material all is chilled to room temperature with reaction system after the conversions, adds saturated NaHCO then
3The aqueous solution, separatory, water extracted with diethyl ether, organic phase washing back anhydrous Na
2SO
4Dry.Concentrate the back underpressure distillation and get compound 6, yield is greater than 95%.
1H NMR(300MHz，CDCl
3)：δ7.47(m，2H)，7.22(m，1H)，7.12(m，1H)，5.99(s，1H)，3.90-4.15(m，2H)；
13C NMR(75MHz，CDCl
3)：δ140.7，136.8，129.2，128.7，127.2，103.5，65.7。
Synthesizing of compound 7:
At N
2Protection adds the 9.6g magnesium chips, 5mLTHF and 1.0g compound 6 down in the there-necked flask that dropping funnel and reflux are housed; after question response causes; again to the solution 200mL of the THF that wherein adds compound 6 (2.0M), add post-heating and be back to magnesium and disappear, be cooled to 0 ℃ after again to wherein adding Ph
2The THF solution 100mL (4.0M) of PCl is warming up to 50 ℃ with reaction system after adding and reacted 12 hours.The TLC monitoring reaction, treat that raw material disappears after, to wherein adding the saturated aqueous ammonium chloride termination reaction.Separatory, water CH
2Cl
2Extraction merges organic phase and washing, anhydrous Na
2SO
4Dry back concentrates, and recrystallizing methanol gets white solid compound 7, yield 51%.
1H NMR(300MHz，CDCl
3)：δ6.94-7.75(m，14H)，6.13(s，1H)，4.07(m，2H)；
13C NMR(75MHz，CDCl
3)：δ142.4，137.1，135.1，133.7，133.3，128.8，128.7，127.4，100.5，64.7；
31P NMR(300MHz，CDCl
3)：δ-16.1。
Synthesizing of compound 4:
At N
2Protection joins 53.0g starting compound 7 and 1.2gp-TsOH in the 2L Schlenk bottle that fills 600mL acetone and water (through the degassing) down.Reflux is the concentration response system after 9 hours, adds ether then, separatory, water CH
2Cl
2Extraction merges organic phase, anhydrous Na
2SO
4Drying, concentrate product 4.Yield is greater than 95%.
1H NMR(300MHz，CDCl
3)：δ10.50(d，J＝6.0Hz，1H)，7.99-7.96(m，1H)，7.53-7.43(m，2H)，7.36-7.25(m，10H)，6.99-6.95(m，1H)；
13C NMR(75MHz，CDCl
3)：δ192.1，191.8，141.5，141.2，138.7，138.5，136.4，136.2，134.4，134.3，133.9，131.0，129.3，129.1，129.0，128.9；
31P NMR(300MHz，CDCl
3)：δ-4.09。
Phosphaalkene ligand 1a's is synthetic
At N
2Protection joins the Witting reagent of compound 4 and 1.2 times of normal alpha-chloro acetophenones in the Schlenk bottle that fills toluene down successively.After reflux to compound 4 disappears, be cooled to room temperature, concentrate, recrystallizing methanol gets faint yellow solid 1a.Yield 82%.
1H NMR(300MHz，CDCl
3)：δ8.35(dd，J
PH＝16.2Hz，J
HH＝4.5Hz 1H)，7.76-7.71(m，3H)，7.53-7.50(m，1H)，7.42-7.25(m，14H)，7.17(d，J
PH＝15.9Hz，1H)，6.95-6.91(m，1H)；
13C NMR(75MHz，CDCl
3)：δ192.2，143.9，143.6，140.1，139.8，138.8，138.5，138.2，136.1，136.0，134.5，134.2，133.9，132.7，130.2，129.4，129.2，128.9，128.7，127.2，125.8；
31P NMR(300MHz，CDCl
3)：δ-12.87.HRMS(APCI)calcd for C27H21OP(M
+)：393.1408；found：393.1329。
Embodiment two.Synthetic ligands 1b
Synthesizing of compound 9
In the there-necked flask of thorough drying, add new methylene dichloride and the 26mL bromoacetyl bromide that steams of 240mL, after system is cooled off with ice-water bath and to the dichloromethane solution that wherein slowly drips (adding in 10 minutes) 28mL allylamine.Reacted again after dripping off 5 hours, and added 100mL water then, use dichloromethane extraction, separatory, organic layer is washed with 5% (weight ratio) dilute hydrochloric acid, washing, anhydrous sodium sulfate drying gets weak yellow liquid after concentrating.Under 0 ℃, carry out recrystallization with normal hexane and ether, get white solid chemical compound 9.Yield is 80%.
1H NMR
(300MHz，CDCl
3)：δ6.62(s，1H)，5.85(m，1H)，5.23(m，1H)，5.19(m，1H)，3.96-3.90(m，4H)；
13C NMR(75MHz，CDCl
3)：δ165.9，133.3，116.8，42.5，29.1。
Synthesizing of compound 10
With 14.4g compound 9,22.3g triphenylphosphine and 100mL toluene join in the 250mL single port bottle, and stirring reaction under the room temperature, TLC are monitored to starting compound 9 reactions finishing back stopped reaction, and suction filtration obtains thick product.The thick product of gained is dissolved in methanol (volume ratio the is 1/1) mixing solutions, with aqueous sodium hydroxide solution (0.1M) the pH value of this solution is transferred to 7-8, separate out a large amount of solids, suction filtration gets 14.0g white solid compound 10.Yield is 47%.
1H NMR(300MHz，CDCl
3)：δ7.30-7.45(m，15H)，5.87(m，1H)，5.70(br，1H)，5.22-5.19(m，2H)，3.95-3.91(m，2H)，2.2(d，J
PH＝15.0Hz，2H)。
Phosphaalkene ligand 1b's is synthetic
At N
2Protection adds 4.3g 4 down in exsiccant 100mL there-necked flask, 7.2g 10,20mL toluene and 4.0g salt of wormwood.Reflux is stopped reaction after 36 hours.Add 10mL water, separatory, the water dichloromethane extraction merges organic phase, anhydrous sodium sulfate drying.Concentrate the back silica gel column chromatography separate 1b.
1H NMR(300MHz，CDCl
3)：δ8.15(dd，J
PH＝15.3Hz，J
HH＝3.9Hz 1H)，7.59-7.55(m，1H)，7.34-7.25(m，12H)，6.95-6.91(m，1H)，6.24(d，J
PH＝15.3Hz，1H)，5.89-5.80(m，1H)，5.52(br，1H)，5.19-5.12(m，2H)，3.95-3.91(m，2H)。
Embodiment three.Synthetic ligands 1c
Synthesizing of compound 11
In 250mL single port bottle, add 10.0g NaOH, 100mL water and 60mL ethanol, be cooled to 0 ℃ after to wherein adding the 24.0g methyl phenyl ketone, and then to wherein adding the adjacent bromobenzaldehyde 5 of 39.0g.With this system at room temperature stirring reaction disappear up to raw material, reaction system is poured in the 100mL frozen water diluted then, separate out solid, suction filtration, ethyl alcohol recrystallization get yellow solid (compound 11) 48.0g, yield 84%.
1HNMR(300MHz，CDCl
3)：δ8.13(d，J＝16.2Hz，1H)，8.03-8.00(m，2H)，7.75-7.72(m，1H)，7.65-7.67(m，2H)，7.53-7.48(m，2H)，7.43(d，J＝15.3Hz，1H)，7.38-7.34(m，1H)，7.27-7.22(m，1H)；
13C NMR(75MHz，CDCl
3)：δ186.1，140.9，135.5，132.7，131.2，130.7，129.0，126.3，125.6，123.6，122.7。
Synthesizing of compound 12
In the 200mL ethanolic soln that is dissolved with 28.8g compound 11 and 1.0gp-TsOH, add the 50mL triethyl orthoformate, reflux (80 ℃) then, the TLC monitoring reaction, treat to be cooled to room temperature after raw material disappears, again to wherein adding 300mL (2.0M) wet chemical, the anhydrous diethyl ether extraction, the organic phase washing, anhydrous sodium sulfate drying gets compound 12 after concentrating, and yield is greater than 95%.
1H NMR(300MHz，C
6C
6)：δ7.86-7.84(m，2H)，7.71(d，J＝15.3Hz，1H)，7.41-7.39(m，1H)，7.34-7.29，(m，2H)，7.22-7.17(m，1H)，7.13-7.19(m，1H)，6.88-6.83(m，1H)，6.73-6.78(m，1H)，6.13(d，J＝15.9Hz，1H)，3.62-3.46(m，4H)，1.24(t，J＝7.2Hz，6H)；
13CNMR(75MHz，C
6C
6)：δ142.0，136.9，135.1，133.0，129.7，128.9，124.3，101.1，57.4，15.3。
Phosphaalkene ligand 1c's is synthetic
At N
2Protection down adds 1.7g compound 12 and 6mL tetrahydrofuran (THF) in exsiccant 25mL Schlenk bottle, add 6mLt-BuLi (1.3M) again after being cooled to-78 ℃.Add 1.5mL dicyclohexyl phosphonium chloride after stirring 2 hours under-78 ℃, restir was warming up to room temperature with system after 10 minutes.Reacted 10 hours, and added 5mL 5% dilute hydrochloric acid stopped reaction, separatory, the anhydrous diethyl ether extraction, organic phase silica gel column chromatography after concentrated separate 1c, yield 50%.
1H NMR (300MHz, CDCl
3): δ 8.82 (dd, J
PH=16.2Hz, J
HH=6.0Hz 1H), and 8.03-8.01 (m, 2H), 7.80-7.76 (m, 1H), 7.60-7.47 (m, 4H), 7.41-7.38 (m, 2H), 7.33 (d, J
PH=16.2Hz, 1H), 1.99-0.94 (m, 22H);
13C NMR (75MHz, CDCl
3): δ 186.2,140.7, and 140.3,137.9,123.8,128.8,128.0,124.5,124.3,124.1,124.0,122.2,119.0,28.9,28.7,25.8,25.6,24.4,24.3,22.7,22.6,22.4,21.8; HRMS (APCI) calcd forC
27H
33OP (M
+): 404.2260; Found:404.2269.
Embodiment four.Synthetic ligands 1d
Synthesizing of compound 14
In 500mL single port bottle, add 120mL DMF successively, adjacent bromobenzyl bromine 13 of 57.0g and 65.0g triphenylphosphine, at room temperature stirring reaction is 2 hours, reaction solution is poured in the 300mL ether separated out solid then, suction filtration, ether wash compound 14, yield 97%.
1H NMR(300MHz，CDCl
3)7.99-7.90(m，3H)，7.80-7.54(m，13H)，7.34-7.28(m，2H)，7.22-7.16(m，1H)，5.21(d，J
PH＝14.5Hz，2H)。
Synthesizing of compound 15
In 500mL single port bottle, add 300mL methylene dichloride 25.6g compound 14 and 8.7g to trifluoromethylated benzaldehyde.Stir molten clear back to wherein adding 25mL (50%) the NaOH aqueous solution.Reaction at room temperature, TLC monitors, and treats raw material disappearance back separatory, and organic phase concentrates the compound 15 (the mixed body of Z formula and E formula needn't separate, and can be directly used in next step and synthesize) of back silica gel column chromatography, yield 99%.
1H NMR(300MHz，CDCl
3)：δ7.76(m，2H)，7.62-7.60(m，3H)，7.41-7.39(m，2H)，7.22-7.18(m，1H)，6.83(m，1H)，6.72(m，1H)；
13C NMR(75MHz，CDCl
3)：δ140.8，135.8，132.6，130.2，128.9，127.6，127.4，127.0，125.0，124.1，122.4。
Phosphaalkene ligand 1d's is synthetic
At N
2Protection down adds 2.3g compound 15 and 10mL tetrahydrofuran (THF) in exsiccant 50mL Schlenk bottle, add 4mL n-BuLi (2.5M) again after being cooled to-78 ℃.Add the 2.7mL diphenyl phosphine chloride after stirring 2 hours under-78 ℃, restir was warming up to room temperature with system after 10 minutes.Reacted 10 hours, and added 5mL 5% dilute hydrochloric acid stopped reaction, separatory, the anhydrous diethyl ether extraction, organic phase silica gel column chromatography after concentrated separate 1d, (the Z formula can be separated by the method for silica gel column chromatography with the E formula) yield 50%.
1H NMR(300MHz，CDCl
3)：δ7.83-7.70(m，10H)，7.63-7.60(m，3H)，7.38-7.33(m，5H)，7.22(d，J
PH＝15.6Hz，1H 1H)，6.78(d，J
PH＝15.6Hz，1H)；
13C NMR(75MHz，CDCl
3)：δ140.8，140.1，137.1，133.7，132.5，130.2，128.9，128.8，128.7，128.4，127.4，126.4，125.4，125.0，124.1。
Embodiment five.Application in the cross-coupling reaction of catalytic organometallic reagent of palladium and aryl halides.
1, the comparison of catalyzer of the present invention or Phosphaalkene ligand and other catalyzer or part
Under nitrogen atmosphere, in exsiccant 10mL Schlenk pipe, add PdCl
2(MeCN)
2(0.05mmol), Phosphaalkene ligand 1a (0.05mmol) and 1.5mLTHF, stir after 10 minutes again to wherein adding substrate (16) (1.0mmol), after the stirred for several minute, add 3.5mL zinc ethyl (hexane solution of 2.5M) with syringe.Add 2mL (3N) dilute hydrochloric acid termination reaction under the room temperature behind the stirring reaction 2h, extracted with diethyl ether, anhydrous sodium sulphate is carried out drying, concentrates the back silica gel column chromatography.Get the cross-coupling product.
| The experiment sequence number | Catalyst system (5mol%) | The selectivity (17/18) of reaction | 17 separation yield (%) |
| 1 | PdCl 2(PPh 3) 2 | 39/61 | 38 |
| 2 | PdCl 2(PPh 3) 2/PPh 3(1∶1) | 12/88 | 11 |
| 3 | Pd(PPh3) 4 | 56/44 | 54 |
| 4 | PdCl 2(CH 3CN) 2/1a(1∶1) | 94/6 | 91 |
| 5 | PdCl 2(dppf) | 61/39 | 59 |
| 6 | PdCl 2(PPh 3) 2/ tBu 3PHBF 4(1∶1) | 70/30 | 68 |
| 7 | PdCl 2(PPh 3) 2/ tBu 3PHBF 4(1∶2) | 40/60 | 39 |
| 8 | PdCl 2(PPh 3) 2/ 1a (1: 1) (dew is put in air and reacted) | 94/6 | 91 |
| 9 | Pd(dba) 2 | 45/40 | 44 |
| 10 | PdCl 2(PPh 3) 2/DPPBZ(1∶1) | 0/0 | 0 |
2, the cross-coupling reaction between alkyl zinc reagent and the aryl halides
Under nitrogen protection, anhydrous ZnCl is housed to one
2(3.0mmol) and in the 10mL Schlenk pipe of 1.5mL tetrahydrofuran (THF) with syringe add RMgX (2.5mmol, 3mL), stirring reaction 1h prepares organic zinc reagent under the room temperature, then under nitrogen atmosphere with substrate (1.0mmol), PdCl
2(MeCN)
2(0.05mmol), Phosphaalkene ligand 1a (0.05mmol) joins in the zincon.Add 2mL (3N) dilute hydrochloric acid termination reaction under the room temperature behind the stirring reaction 2h, extracted with diethyl ether, anhydrous sodium sulphate is carried out drying, concentrates the back silica gel column chromatography.Get the cross-coupling product.
With 1a is part, and when being substrate with the o-iodobenzoic acid ethyl ester, part alkyl zinc reagent applicatory and yield are as follows:
nBuZnCl
nC
8H
17ZnCl
nC
12H
25ZnCl
93％ 84％ 86％ 96％ 86％ 76％ 86％
With 1a, 1c, 1d are part, are alkyl zinc reagent with cyclohexyl chlorination zinc, and part aryl halides applicatory and yield are as follows:
With 1c is part, and part alkyl zinc reagent applicatory and aryl halides and yield are as follows:
With 1a is part, and when being substrate with o-iodobenzoic acid ethyl ester and cyclohexyl chlorination zinc, the ratio of substrate (o-iodobenzoic acid ethyl ester) and catalyzer can be above to 100000/1, and substrate feeds intake and can reach the scale of 50 grams.
3, alkyl indium reagent and aryl iodide are for the cross-coupling reaction between the thing
Under nitrogen protection, anhydrous InCl is housed to one
3Add the 1mL tetrahydrofuran (THF) in the 10mL Schlenk pipe (1.2mmol), reflux is molten clear, adds RMgX (3.5mmol) with syringe after being cooled to 0 ℃, and stirring reaction 1.5h under the room temperature prepares organo indium reagent.Then under nitrogen atmosphere with aryl halides (1.0mmol), Pd (dba)
2(0.05mmol) join in the indium reagent with part 4 (0.05mmol).Add 2mL (3N) dilute hydrochloric acid termination reaction under the room temperature behind the stirring reaction 12h, extracted with diethyl ether, anhydrous sodium sulphate is carried out drying, concentrates the back silica gel column chromatography.Get the cross-coupling product.
With 1a is part, and when being substrate with the o-iodobenzoic acid ethyl ester, part alkyl indium reagent applicatory and yield are as follows: (
nC
4H
9)
3Ln (
iC
8H
17)
3Ln
nC
12H
25ZnCl
72％ 99％ 81％ 89％ 75％ 90％
With 1a is part, is alkyl indium reagent with the thricyclohexyl indium, and part aryl iodide applicatory is as follows for thing and yield:
3, the cross-coupling reaction between organotin reagent and the aryl halides
Under nitrogen atmosphere, in exsiccant 10mL Schlenk pipe, add PdCl
2(MeCN)
2(0.05mmol), Phosphaalkene ligand 1a (0.05mmol) and 1.5mL THF, stir after 10 minutes again to wherein adding substrate A rI (1.0mmol) and phenylacetylene base tributyl tin (1.5mmol), reaction was at room temperature carried out 50 minutes, add the saturated KF aqueous solution of 5mL stopped reaction, extracted with diethyl ether, organic phase is carried out drying with anhydrous sodium sulphate, concentrates the back silica gel column chromatography.Get the cross-coupling product.
With 1a is part, and part aryl iodide applicatory is as follows for thing and yield:
Claims (8)
1. Phosphaalkene ligand, its general structure is:
R in the formula
1Be phenyl or cyclohexyl; R
2Be benzoyl, 4-trifluoromethyl or allyl amine-N-formyl radical.
2. according to the described Phosphaalkene ligand of claim 1, it is characterized in that: R
1Be phenyl; R
2Be benzoyl or allyl amine-N-formyl radical.
3. according to the described Phosphaalkene ligand of claim 1, it is characterized in that: R
1Be cyclohexyl; R
2Be benzoyl.
4. according to the described Phosphaalkene ligand of claim 1, it is characterized in that: R
1Be phenyl; R
2Be the 4-trifluoromethyl.
5. the preparation method of the described Phosphaalkene ligand of claim 2; it is characterized in that: under nitrogen protection; add the 1-1.2 doubly Witting reagent of normal alpha-chloro acetophenone or the Witting reagent of N-allyl group-alpha-brominated ethanamide in the toluene solution of 2-diphenyl phosphine phenyl aldehyde; reflux concentrates after raw material disappears, and recrystallizing methanol gets Phosphaalkene ligand then.
6. the preparation method of the described Phosphaalkene ligand of claim 3; it is characterized in that: the carbonyl of protecting 2-bromine phenyl styryl ketone earlier with the doubly normal triethyl orthoformate of 3.0-5.0; after this carry out the exchange of bromine lithium with the doubly normal butyllithium of 1.2-2.0; and then reacted 10 hours under the doubly normal dicyclohexyl phosphonium chloride of the adding 1.2-2.0 room temperature, add the dilute hydrochloric acid deprotection at last and obtain Phosphaalkene ligand.
7. the preparation method of the described Phosphaalkene ligand of claim 4, it is characterized in that: add the aqueous sodium hydroxide solution of 50wt% in the chloroformic solution of the Witting reagent that is dissolved with 4-trifluoromethylated benzaldehyde and the 1-1.2 times of normal adjacent bromobenzyl bromine of 4-trifluoromethylated benzaldehyde, stirring at room to raw material disappears; Through separatory, washing back reconcentration organic phase gets 4 '-trifluoromethyl-2-bromo-1.2-toluylene; Then 4 '-trifluoromethyl-2-bromo-1.2-toluylene is dissolved in the tetrahydrofuran (THF), adding 1.2-2.0 times of 4 '-trifluoromethyl-normal butyllithium of 2-bromo-1.2-toluylene under nitrogen protection reacted 2 hours down at-78 ℃, add doubly 4 '-trifluoromethyl-normal diphenyl phosphine chloride of 2-bromo-1.2-toluylene of 1.2-2.0 after lithiumation is finished again, reaction is 10 hours under the room temperature; Add the dilute hydrochloric acid stopped reaction after finishing; Through separatory, washing back reconcentration organic phase gets Phosphaalkene ligand.
8. claim 1, the application of 2 or 3 described Phosphaalkene ligands in the cross-coupling reaction of palladium catalysis organometallic reagent and aryl halides.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102603797A (en) * | 2012-01-16 | 2012-07-25 | 南开大学 | Phosphine imide ligand (E)-(2-(diphenyl phosphino) benzylidene) hydrazine as well as synthetic method and application of phosphine imide ligand (E)-(2-(diphenyl phosphino) benzylidene) hydrazine |
| CN103483383A (en) * | 2013-09-11 | 2014-01-01 | 南开大学 | Synthetic method and application of (1E, 2E)-1,2-bi(5-methoxyl-2-diphenylphosphine benzylidene) hydrazine |
| CN104478927A (en) * | 2014-11-24 | 2015-04-01 | 苏州乔纳森新材料科技有限公司 | Organic phosphinic compound and synthesis method thereof |
| CN107098932A (en) * | 2017-06-29 | 2017-08-29 | 管德新 | A kind of synthetic method of benzyl class part available for hydroformylation reaction |
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2007
- 2007-09-26 CN CNB2007100533631A patent/CN100560595C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102603797A (en) * | 2012-01-16 | 2012-07-25 | 南开大学 | Phosphine imide ligand (E)-(2-(diphenyl phosphino) benzylidene) hydrazine as well as synthetic method and application of phosphine imide ligand (E)-(2-(diphenyl phosphino) benzylidene) hydrazine |
| CN103483383A (en) * | 2013-09-11 | 2014-01-01 | 南开大学 | Synthetic method and application of (1E, 2E)-1,2-bi(5-methoxyl-2-diphenylphosphine benzylidene) hydrazine |
| CN104478927A (en) * | 2014-11-24 | 2015-04-01 | 苏州乔纳森新材料科技有限公司 | Organic phosphinic compound and synthesis method thereof |
| CN107098932A (en) * | 2017-06-29 | 2017-08-29 | 管德新 | A kind of synthetic method of benzyl class part available for hydroformylation reaction |
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