CN107445989A - A kind of Phosphine ligands of indoles skeleton and its preparation method and application - Google Patents
A kind of Phosphine ligands of indoles skeleton and its preparation method and application Download PDFInfo
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- CN107445989A CN107445989A CN201610387558.9A CN201610387558A CN107445989A CN 107445989 A CN107445989 A CN 107445989A CN 201610387558 A CN201610387558 A CN 201610387558A CN 107445989 A CN107445989 A CN 107445989A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2442—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems
- B01J31/2447—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring
- B01J31/2452—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring with more than one complexing phosphine-P atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
- B01J2231/4294—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues using S nucleophiles, e.g. thiols
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/824—Palladium
Abstract
The invention provides Phosphine ligands of one kind 3 (two substitution phosphino-s) 2 (2 (two substitution phosphino-s) substituted-phenyl) 1 alkyl-indol skeleton and its preparation method and application.The Phosphine ligands of described 3 (two substitution phosphino-s) 2 (2 (two substitution phosphino-s) substituted-phenyl) 1 alkyl-indol skeleton, its structure is as shown in following formula I：Wherein, the R is hydrogen-based, alkyl, substitutes alkyl, substituted amido, alkoxy, alkylene, aryl or fluorine, the R1For alkyl, substitution alkyl, alkyl ether, oxyalkyl, alkoxy or aryl, the R2For alkyl, substitution alkyl, alkoxy or fluorine, the R3For alkyl, substitution alkyl or aryl.
Description
Technical field
The invention belongs to organic compound and synthesis technical field, it is related to Phosphine ligands and its preparation side of a kind of indoles skeleton
Method and application, more particularly to a kind of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol bones
Phosphine ligands of frame and its preparation method and application.
Background technology
Transition metal-catalyzed cross-coupling reaction is one of important method to form carbon-to-carbon and carbon-heteroatom bond.In shape
Into in the field of carbon-carbon bond, Suzuki (Suzuki), Hui Shan (Hiyama), root bank (Negishi), bear field (Kumada), Shi Dile
(Stille) and α-mono- arylation reaction (α-arylation of carbonyl compounds) of carbonyls etc. friendship
Coupling reaction is pitched to prepare the common method of biaryl and/or related compound.And in the field for forming carbon-heteroatom bond
In, boryl, amination, formation carbon-oxygen and carbon-sulfide linkage coupling reaction are to manufacture the important plan of organic boron, amine, oxygen and sulphur compound
Slightly.These products can form many natural products being widely present and drug synthesis intermediate.In transition metal-catalyzed friendship
Pitch in coupling reaction, part plays considerable role.Specifically, part can effectively adjust the performance of catalyst,
Coupling reaction is drilled and translates more perfect.
At present, more commonly used part is generally organic phosphine compound, and the research of Phosphine ligands over the years shows, Phosphine ligands
The trickle change of the position of substituent, size, steric hindrance, electrical etc. can produce important shadow to the result of coupling reaction on skeleton
Ring.Central, famous Phosphine ligands, such as：The tri-butyl phosphine of Fu seminar, the Phosphine ligands of Beller seminar, Buchwald
The biaryl Phosphine ligands of seminar, the Phosphine ligands of Hartwig seminar, the indoles Phosphine ligands of Kwong seminar (be shown in respectively by structure
Shown in following formula) provide outstanding catalytic performance in the intersection association response of palladium chtalyst.
Kwong seminar of Hartwig seminar of Buchwald seminar of Beller seminar of Fu seminar
Different cross-coupling reactions needs different catalyst system and catalyzings, and suitable catalyst system and catalyzing, especially effective phosphine are matched somebody with somebody
Body is the important key for breaking through coupling reaction limitation.Although many Phosphine ligands have been widely used in transition metal-catalyzed friendship
Pitch in coupling reaction, but design high catalytic activity, Stability Analysis of Structures and convieniently synthesized Phosphine ligands still in cross-coupling reaction
It is significant.
The content of the invention
It is an object of the invention to provide a kind of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1-
The Phosphine ligands of alkyl-indol skeleton, it is intended to solve association of the existing phosphorus part as transition-metal catalyst in cross-coupling reaction
The problem of catalytic activity is poor when imitating agent.
Another object of the present invention is to provide a kind of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted benzenes
Base) -1- alkyl-indol skeletons Phosphine ligands preparation method.
The present invention's is to provide 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- in a purpose
The application of the Phosphine ligands of alkyl-indol skeleton.
The present invention is achieved in that a kind of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkane
The Phosphine ligands of base-indoles skeleton, its structure is as shown in following formula I：
Wherein, the R is hydrogen-based, alkyl, substitutes alkyl, alkoxy, substituted amido, alkylene, aryl or fluorine, the R1
For alkyl, alkyl ether, oxyalkyl, alkoxy, substitution alkyl or aryl, the R2For alkyl, substitute alkyl, alkoxy or fluorine,
The R3For alkyl, substitution alkyl or aryl.
And two kinds of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol skeletons
The preparation method of Phosphine ligands, wherein,
A kind of Phosphine ligands of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol skeletons
Preparation method, comprise the following steps：
After 2 '-bromoacetophenone and N- alkyl phenylhydrazine are carried out into mixed processing, phosphoric acid is added as catalyst, is stirred place
After reason, polyphosphoric acid is added, heating response is carried out, 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates is prepared, wherein,
The heating-up temperature of the heating response is 80-120 DEG C, and the reaction time is 1-2 hours；
The 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and N- bromo-succinimides are dissolved in dimethyl
In formamide, processing is stirred at room temperature, obtains 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates；
The 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates are dissolved in tetrahydrofuran, -75 to -
N-BuLi is added under the conditions of 80 DEG C, uniform stirring 0.5-1 hours, two substitution phosphonium chlorides is then added, reacts 12- at room temperature
24 hours, obtain 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl -1H- indoles Phosphine ligands.
A kind of Phosphine ligands of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol skeletons
Preparation method, comprise the following steps：
After 2 '-bromoacetophenone and phenylhydrazine are carried out into mixed processing, phosphoric acid is added as catalyst, after being stirred,
Polyphosphoric acid is added, carries out heating response, is prepared and prepares 2- (2 '-bromophenyl) -1H- Indole Intermediates, wherein, heating response
Heating-up temperature be 80-120 DEG C, the reaction time is 1-2 hours；
It is 1 in molar ratio by the 2- (2 '-bromophenyl) -1H- Indole Intermediates and sodium hydride, dialkyl sulfate:
(1.1-2.0):(1.05-1.5) is mixed, and forms tetrahydrofuran mixed liquor, 1-2 hours are stirred at room temperature, obtain 2- (2 '-bromobenzenes
Base) -1- alkyl -1H- Indole Intermediates；
The 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and N- bromo-succinimides are dissolved in dimethyl
In formamide, processing is stirred at room temperature, obtains 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates；
The 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates are dissolved in tetrahydrofuran, -75 to -
N-BuLi is added under the conditions of 80 DEG C, uniform stirring 0.5-1 hours, two substitution phosphonium chlorides is then added, reacts 12- at room temperature
24 hours, obtain 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl -1H- indoles Phosphine ligands.
And a kind of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol skeletons
Synergist application in cross-coupling reaction of the Phosphine ligands as transition-metal catalyst.
3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol skeletons provided by the invention
Phosphine ligands, constitutionally stable complex compound can be formed with transition metal such as palladium metal, it is anti-so as to improve transition metal such as palladium chtalyst
Seasonable catalytic activity, and it is applied widely, and selectivity is good, and reaction condition is gentle.3- (the two substitution phosphino-s) -2- (2-
(two substitution phosphino-) substituted-phenyl) -1- alkyl-indol skeletons the catalytic body that is formed with transition metal such as palladium metal of Phosphine ligands
System, can prepare the compound of all kinds of synthetic products such as sulfur-bearing, have in the synthesis of natural products and pharmaceutical intermediate very big
Application potential.Particularly, 3- provided by the invention (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl -
The catalyst system and catalyzing that the Phosphine ligands of indoles skeleton are formed with palladium metal, in the formation carbon-sulfide linkage reaction that can be suitably used for aryl bromide,
Transition-metal catalyst such as palladium catalyst urge the amount of applying flexibly can as little as 0.5mol%, yield is up to 90%, to cross-coupling reaction
In have far-reaching significance.In addition, 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- of the present invention
The Phosphine ligands of alkyl-indol skeleton, stability is respectively provided with to air and moisture, is easy to preserve；And can be by changing on indoles
Substituted radical come adjust the space structure of part and electrically, so as to change the coordination property of part.
3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol skeletons provided by the invention
Phosphine ligands preparation method, not only raw material is simple and easy to get, and method is simple, only need to pass through Fischer indole synthesis, alkane
Change, bromination and phosphineization reaction can largely be made, total recovery height.
The 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indols provided by the invention
The Phosphine ligands of skeleton, the synergist of transition-metal catalyst is widely used as, in cross-coupling reaction, with transition metal such as
Palladium metal forms constitutionally stable complex compound, so as to improve catalytic activity during transition metal such as palladium-catalyzed reaction, particularly energy
Suitable for formation carbon-sulfide linkage reaction of aryl bromide, transition-metal catalyst such as palladium catalyst urges the amount of applying flexibly can be as little as
0.5mol%, yield are up to 90%.
Embodiment
In order that technical problems, technical solutions and advantageous effects to be solved by the present invention are more clearly understood, below in conjunction with
Embodiment, the present invention will be described in further detail.It should be appreciated that specific embodiment described herein is only explaining
The present invention, it is not intended to limit the present invention.
The embodiments of the invention provide a kind of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkane
The Phosphine ligands of base-indoles skeleton, its structure is as shown in following formula I：
Wherein, the R is hydrogen-based, alkyl, substitutes alkyl, alkoxy, substituted amido, alkylene, aryl or fluorine, the R1
For alkyl, substitution alkyl, alkyl ether, alkoxy, oxyalkyl or aryl, the R2For alkyl, alkoxy, substitute alkyl or fluorine,
The R3For alkyl, substitution alkyl or aryl.
Specific preferable in structure above I, the R is hydrogen-based, C1-10 alkyl, C1-C10 alkoxy, C3-
One kind in C10 cycloalkyloxy, dimethylamino, 1,3- butadienes, phenyl, Benzyl epoxides, fluorine, trifluoromethyl；The R1For C1-
One in C10 alkyl, C3-C10 cycloalkyl, cycloalkyl ethers, epoxy alkyl, alkyl alkoxy, alkyl-cycloalkyl ether, phenyl
Kind；The R2For one kind in C1-C10 alkyl, methoxyl group, fluorine, trifluoromethyl；Described is phenyl, ethyl, isopropyl, uncle
One kind in butyl, cyclopenta, cyclohexyl, o-tolyl, p-methylphenyl, p-methoxyphenyl.
Further, in the R, the alkyl of the C1-10 include methyl, ethyl, n-propyl, isopropyl, normal-butyl,
Isobutyl group, sec-butyl, the tert-butyl group and C5-10 alkyl, the alkoxy of the C1-C10 include methoxyl group, ethyoxyl, positive third oxygen
The alkoxy of base, isopropoxy and C4-C10, the cycloalkyloxy of the C3-C10 include ring propoxyl group, cyclobutoxy group and C5-C10
Cycloalkyloxy；
The R1In, the alkyl of the C1-C10 includes methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, secondary
The alkyl of butyl, the tert-butyl group and C5-C10, the cycloalkyl of the C3-10 include cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl and
C7-C10 cycloalkyl, the cycloalkyl ethers include tetrahydrofuran, and the epoxy alkyl includes glycidyl, the alkyl alcoxyl
Base includes methyl methoxy base, and the alkyl-cycloalkyl ether includes methyltetrahydrofuran；
The R2In, the alkyl of the C1-C10 includes the alkyl of methyl, ethyl and C3-C10.
3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol bones of above-mentioned preferred situation
It the Phosphine ligands of frame, can be combined to obtain the more preferable catalyst system and catalyzing of catalytic effect with transition metal such as palladium metal, prepare all kinds of synthesis productions
The compound of thing such as sulfur-bearing.
3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-Yin provided in an embodiment of the present invention
The Phosphine ligands of diindyl skeleton, constitutionally stable complex compound can be formed with transition metal such as palladium metal, so as to improve transition metal such as palladium
Catalytic activity during catalytic reaction, and it is applied widely, and selectivity is good, and reaction condition is gentle.The 3- (two substitution phosphino-s)-
The Phosphine ligands of 2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol skeletons are urged with what transition metal such as palladium metal was formed
Change system, the compound of all kinds of synthetic products such as sulfur-bearing can be prepared, had very in the synthesis of natural products and pharmaceutical intermediate
Big application potential.Particularly, 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted benzenes provided in an embodiment of the present invention
Base) -1- alkyl-indol skeletons the catalyst system and catalyzing that is formed of Phosphine ligands and palladium metal, can be suitably used for the formation carbon of aryl bromide -
In sulfide linkage reaction, transition-metal catalyst such as palladium catalyst urge the amount of applying flexibly can as little as 0.5mol%, yield is up to 90%, to handing over
Have far-reaching significance in fork coupling reaction.In addition, 3- described in the embodiment of the present invention (two substitution phosphino-s) -2- (2- (two substitution phosphines
Base) substituted-phenyl) -1- alkyl-indol skeletons Phosphine ligands, stability is respectively provided with to air and moisture, is easy to preserve；And it can lead to
Cross change indoles on substituted radical come adjust the space structure of part and electrically, so as to change the coordination property of part.
3- described in the embodiment of the present invention (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indols
The Phosphine ligands of skeleton can be prepared by following several methods.
As one embodiment, there is provided a kind of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1-
The preparation method of the Phosphine ligands of alkyl-indol skeleton, comprises the following steps：
S01. after 2 '-bromoacetophenone and N- alkyl phenylhydrazine being carried out into mixed processing, phosphoric acid is added as catalyst, is stirred
After mixing processing, polyphosphoric acid is added, heating response is carried out, 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates is prepared,
Wherein, the heating-up temperature of the heating response is 80-120 DEG C, and the reaction time is 1-2 hours；
S02. the 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and N- bromo-succinimides are dissolved in two
In NMF, processing is stirred at room temperature, obtains 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates；
S03. the 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates are dissolved in tetrahydrofuran, -75
N-BuLi is added under the conditions of to -80 DEG C, uniform stirring 0.5-1 hours, two substitution phosphonium chlorides is then added, reacts at room temperature
12-24 hours, obtain 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl -1H- indoles Phosphine ligands.
Specifically, in above-mentioned steps S01, the reaction of the 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates is prepared
Formula is as follows：
In order to obtain more preferable reaction effect, it is preferred that the mol ratio of 2 '-bromoacetophenone and N- the alkyl phenylhydrazine is 1:
(1.1-1.2), for stir process for processing is stirred at room temperature, mixing time is preferably 0.5-1 hours, is more elected as 0.5 hour.
It is further preferred that after reaction terminates, mixture is poured into frozen water, and adds ether extraction, separation.To have
Machine mutually merges, concentrate after, draw 2- (2 '-bromophenyl) -1- alkyl -1H- indoles of high-purity after purification through column chromatography.
It is worth noting that, prepare can also be by by the 2 '-bromoacetophenone and N- alkyl phenylhydrazines for the embodiment of the present invention
Using mol ratio as 1:After (1.1-1.2) carries out mixed processing, it is preferably at 80 DEG C under the conditions of 70-80 DEG C to add acetic acid, ethanol
0.5-1.5 hours are reacted, all solvents are taken in then decompression away, add polyphosphoric acid, 80-120 DEG C of reaction 1-2 hour, prepare 2-
(2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates, its reaction equation are as follows：
In above-mentioned steps S02, as the presently preferred embodiments, the 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Yin are prepared
In the step of diindyl intermediate, 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and the N- bromo-succinimides
Mol ratio be 1:(1.05-1.2), mixing time are 1-2 hours.As specific embodiment, by the 2- (2 '-bromophenyl)-
1- alkyl -1H- Indole Intermediates and N- bromo-succinimides are 1 in molar ratio:(1.05-1.2) is dissolved in dimethylformamide
In, processing 1-2 hours are stirred at room temperature, obtain 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates, its reaction equation is such as
Shown in lower：
It is further preferred that after reaction terminates, product is poured into frozen water, and adds dichloromethane extraction, separation；So
A large amount of water are added to clean by organic afterwards, after organic phase is merged, concentrate, show that high-purity 3- is bromo- after purification through column chromatography
2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates.
In above-mentioned steps S03, as the presently preferred embodiments, the 3- (two substitution phosphino-s) -1- alkyl -2- substituted benzenes are prepared
In the step of base-indoles Phosphine ligands, the bromo- 2- of 3- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and the normal-butyl
The mol ratio of lithium is 1:(1.1-1.2)；The bromo- 2- of 3- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and described two take
Mol ratio for phosphonium chloride is 1:(1.1-1.2).As specific embodiment, by the 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -
1H- Indole Intermediates are dissolved in tetrahydrofuran, under the conditions of -75 to -80 DEG C, more preferably -78 DEG C, and by the bromo- 2- of the 3-
The mol ratio of (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and the n-BuLi is 1:(1.1-1.2), the 3- are bromo-
The mol ratio of 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and the two substitutions phosphonium chloride is 1:(1.1-1.2), adds
Enter n-BuLi, uniform stirring 0.5-1 hours, then add two substitution phosphonium chlorides, react 12-24 hours at room temperature, obtain
3- (two substitution phosphino-s) -1- alkyl -2- substituted-phenyls-indoles Phosphine ligands, its reaction equation are as follows：
It is further preferred that after reaction terminates, all solvents are taken in decompression away, after being washed three times with cold methanol, obtain white powder
3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol Phosphine ligands of shape.
The embodiment of the present invention additionally provides a kind of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1-
The preparation method of the Phosphine ligands of alkyl-indol skeleton, comprises the following steps：
D01. after 2 '-bromoacetophenone and phenylhydrazine being carried out into mixed processing, phosphoric acid is added as catalyst, is stirred
Afterwards, polyphosphoric acid is added, carries out heating response, is prepared and prepares 2- (2 '-bromophenyl) -1H- Indole Intermediates, wherein, heating
The heating-up temperature of reaction is 80-120 DEG C, and the reaction time is 1-2 hours；
D02. it is in molar ratio by the 2- (2 '-bromophenyl) -1H- Indole Intermediates and sodium hydride, dialkyl sulfate
1：(1.1-2.0)：(1.05-1.5) is mixed, and forms tetrahydrofuran mixed liquor, 1-2 hours are stirred at room temperature, obtain 2- (2 '-bromobenzenes
Base) -1- alkyl -1H- Indole Intermediates.
D03. the 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and N- bromo-succinimides are dissolved in two
In NMF, processing is stirred at room temperature, obtains 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates；
D04. the 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates are dissolved in tetrahydrofuran, -75
N-BuLi is added under the conditions of to -80 DEG C, uniform stirring 0.5-1 hours, two substitution phosphonium chlorides is then added, reacts at room temperature
12-24 hours, obtain 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl -1H- indoles Phosphine ligands.
Specifically, in above-mentioned steps D01, the reaction equation for preparing 2- (2- bromophenyls) -1H- Indole Intermediates is as follows：
In order to obtain more preferable reaction effect, it is preferred that the mol ratio of the 2 '-bromoacetophenone and phenylhydrazine is 1：(1.1-
1.2), for stir process for processing is stirred at room temperature, mixing time is preferably 0.5-1 hours, is more elected as 0.5 hour.
It is further preferred that after reaction terminates, mixture is poured into frozen water, and adds ether extraction, separation.To have
Machine mutually merges, concentrate after, draw 2- (2 '-bromophenyl) -1H- indoles of high-purity after purification through column chromatography.
It is worth noting that, the embodiment of the present invention prepare can also by by the 2 '-bromoacetophenone and phenylhydrazine with mole
Than for 1：After (1.1-1.2) carries out mixed processing, acetic acid is added, ethanol reacts 0.5- under the conditions of 70-80 DEG C preferably 80 DEG C
1.5 hours, all solvents were taken in then decompression away, added polyphosphoric acid, 80-120 DEG C of reaction 1-2 hour, prepared 2- (2 '-bromobenzenes
Base) -1H- Indole Intermediates, its reaction equation is distinguished as follows：
In above-mentioned steps D02, the reaction equation for preparing 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates is as follows：
Preferably, the hydrogenation is first received into uniform stirring in tetrahydrofuran, then adds and mixed 2- (2 '-bromobenzenes
Base) -1H- Indole Intermediates and tetrahydrofuran solution, 0.25-0.5 hours are stirred at room temperature；It is subsequently added into sulfuric acid dialkyl group
Ester, 1-2 hours are reacted at room temperature.
It is further preferred that after the completion of reaction, ethanol is added to stop reacting；Then all solvents are taken in decompression away, add
Enter ethyl acetate and water extraction and separation；After organic phase is merged and concentrated, 2- (2 '-bromobenzenes are drawn after purification through column chromatography
Base) -1- alkyl -1H- Indole Intermediates.
In above-mentioned steps D03, as the presently preferred embodiments, the 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Yin are prepared
In the step of diindyl intermediate, 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and the N- bromo-succinimides
Mol ratio be 1:(1.05-1.2), mixing time are 1-2 hours.As specific embodiment, by the 2- (2 '-bromophenyl)-
1- alkyl -1H- Indole Intermediates and N- bromo-succinimides are 1 in molar ratio：(1.05-1.2) is dissolved in dimethylformamide
In, processing 1-2 hours are stirred at room temperature, obtain 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates, its reaction equation is such as
Shown in lower：
It is further preferred that after reaction terminates, product is poured into frozen water, and adds dichloromethane extraction, separation；So
A large amount of water are added to clean by organic afterwards, after organic phase is merged, concentrate, show that high-purity 3- is bromo- after purification through column chromatography
2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates.
In above-mentioned steps D04, as the presently preferred embodiments, the 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) are prepared
Substituted-phenyl) -1- alkyl-indol Phosphine ligands the step of in, among the bromo- 2- of 3- (2 '-bromophenyl) -1- alkyl -1H- indoles
The mol ratio of body and the n-BuLi is 1:(1.1-1.2)；In the bromo- 2- of 3- (2 '-bromophenyl) -1- alkyl -1H- indoles
The mol ratio of mesosome and the two substitutions phosphonium chloride is 1:(1.1-1.2).As specific embodiment, by the bromo- 2- of the 3- (2 '-
Bromophenyl) -1- alkyl -1H- Indole Intermediates are dissolved in tetrahydrofuran, under the conditions of -75 to -80 DEG C, more preferably -78 DEG C,
It is 1 by the mol ratio of the 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and the n-BuLi:(1.1-
1.2), the mol ratio of the bromo- 2- of the 3- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and the two substitutions phosphonium chloride is
1:(1.1-1.2), n-BuLi is added, uniform stirring 0.5-1 hours, two substitution phosphonium chlorides is then added, reacts at room temperature
12-24 hours, 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol Phosphine ligands are obtained, its
Reaction equation is as follows：
It is further preferred that after reaction terminates, all solvents are taken in decompression away, after being washed three times with cold methanol, obtain white powder
3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol Phosphine ligands of shape.
3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-Yin provided in an embodiment of the present invention
The preparation method of the Phosphine ligands of diindyl skeleton, not only raw material is simple and easy to get, and method is simple, only need to pass through Fischer indole synthesis
Method, alkanisation, bromination and phosphineization reaction can largely be made, and total recovery is high.
And the embodiment of the present invention additionally provides above-mentioned 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted benzenes
Base) -1- alkyl-indol skeletons synergist application in cross-coupling reaction of the Phosphine ligands as transition-metal catalyst.
Further, as the presently preferred embodiments, described 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted benzenes
Base) -1- alkyl-indol skeletons Phosphine ligands as palladium catalyst synergist aryl bromide the reaction of formation carbon-sulfide linkage
In application, and the phosphine of the 3- (two substitution phosphino-) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol skeletons
Part make it that mole dosage of the catalyst in formation carbon-sulfide linkage reaction system of aryl bromide is 0.5-1.0%.
The 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkane provided in an embodiment of the present invention
The Phosphine ligands of base-indoles skeleton, the synergist of transition-metal catalyst is widely used as, in cross-coupling reaction, with mistake
Cross metal such as palladium metal and form constitutionally stable complex compound, so as to improve catalytic activity during transition metal such as palladium-catalyzed reaction,
In the formation carbon-sulfide linkage reaction that particularly can be suitably used for aryl bromide, urging for transition-metal catalyst such as palladium catalyst is applied flexibly
Amount can as little as 0.5mol%, yield is up to 90%.
In the embodiment of the present invention, the room temperature refers to 10-30 DEG C of indoor temperature, and the N- alkyl phenylhydrazine includes but unlimited
In N- procarbazines, the dialkyl sulfate includes but is not limited to dimethyl suflfate.
Illustrated with reference to being embodied.
Embodiment 1：The conjunction of 3- (dicyclohexyl phosphino-) -2- (2- (dicyclohexyl phosphino-) phenyl) -1- Methyl-1H-indoles
Into
In 100 milliliters of round-bottomed flasks, 1.31 milliliters of 2 '-bromoacetophenones (10mmol) and 1.30 milliliters of N- methylbenzenes are added
Hydrazine (11mmol), 5 milliliters of phosphoric acid are then slowly added into, and be uniformly stirred at room temperature 0.5 hour.Then 30 grams are slowly added to gather
Phosphoric acid.As the progress of reaction, system heat release are obvious.Then mixture is slowly heated to 120 DEG C, and is maintained at 120 DEG C instead
Answer 1 hour.Mixture is poured into terminating reaction in frozen water, 150 milliliters of ether, then each addition in three times are then added into system
150 milliliters of ether extractions, merge organic phase, anhydrous sodium sulfate drying.After all solution are taken in decompression away, concentrated reaction mixture
Purified through column chromatography, then obtain light yellow powder.Then 5 milliliters of n-hexanes are respectively added to carry out clean and filtering in three times,
Obtain 2.13 grams of light yellow powder pure products 2- (2- bromophenyls) -1- Methyl-1H-indoles intermediate, yield 75%.1H NMR
(400MHz,CDCl3)δ3.61(s,3H),6.56(s,1H),7.20-7.45(m,6H),7.70-7.75(m,2H)。
In 100 milliliters of round-bottomed flasks, 2.85 grams of 2- (2- bromophenyls) -1- Methyl-1H-indoles (10mmol) are added, so
20 milliliters of anhydrous dimethyl formamides and uniform stirring are added afterwards.It is subsequently added into the 1.95 grams of N- bromo-succinimides mixed
(11mmol) and 10 milliliters of anhydrous dimethyl formamides solution, react two hours at room temperature.After completing to react, reaction
Mixture is poured into frozen water, then adds 100 milliliters of dichloromethane and 50 milliliters of water.Then by organic phase each addition in five times again
100 milliliters of water are cleaned, and are merged organic phase.After all solution are taken in decompression away, concentrated reaction mixture is purified through column chromatography, so
After obtain 2.8 grams of white powder pure products 3- bromo- 2- (2- bromophenyls) -1- Methyl-1H-indoles intermediate, yield 77%.1H
NMR(400MHz,CDCl3)δ3.61(s,3H),7.28-7.31(m,1H),7.35-7.52(m,5H),7.67-7.69(m,1H),
7.78-7.81(m,1H)。
In 50 milliliters of two-mouth bottles, the 1.81 grams of bromo- 2- of 3- (2- bromophenyls) -1- Methyl-1H-indoles (5.0mmol) are weighed into.
After 3 circulations exchange back and forth in vacuum nitrogen, 15 milliliters of tetrahydrofurans newly distilled are added in the case of logical nitrogen, are uniformly stirred
Mix.After mixture is cooled to -78 DEG C, n-BuLi (11mmol) is then slowly added into, is reacted 0.5 hour.Then again slowly
Add the 2.64 milliliters of dicyclohexyl phosphonium chlorides (12mmol) mixed and 5 milliliters of tetrahydrofuran solutions newly distilled.Anti-
Progress 18-24 hours at room temperature should be placed on.After all solution are pumped under reduced pressure, washed three times, obtained white with cold methanol
Color powdered pure products 3- (dicyclohexyl phosphino-) -2- (2- (dicyclohexyl phosphino-) phenyl) 5.12 grams of -1- Methyl-1H-indoles,
Yield 71%.1H NMR(400MHz,CDCl3)δ1.16-1.28(m,22H),1.63-1.94(m,23H),2.10-2.19(m,
2H), 2.50-2.52 (m, 1H), 3.44 (s, 3H), 7.17 (d, J=7.2Hz, 1H), 7.25-7.28 (m, 2H), 7.37 (d, J=
8.0Hz,1H)；7.41-7.50 (m, 2H), 7.67 (d, J=7.6Hz, 1H), 7.83 (d, J=7.2Hz, 1H).
In addition, referring to method shown in following reaction equations, preparing 3- shown in table 1 below (two substitution phosphino-s), ((two take 2- -2-
For phosphino-) substituted-phenyl) -1- alkyl-indol skeleton phosphorus parts.
Table 1
Embodiment 2：3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol Phosphine ligands exist
The application formed in carbon-sulfide linkage reaction of palladium chtalyst aryl bromide.
3- of the embodiment of the present invention (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol phosphines
Several catalyst of part, for structure as shown in following formula cat1-3, catalysis forms carbon-sulfide linkage reaction：
By three (dibenzalacetone) two palladium (0.0023 gram, 0.0025mmol), Phosphine ligands (palladium：Phosphine ligands ratio is
0.5mol%：1mol%), sodium tert-butoxide (3.0mmol) and the magnetic stirring bar equipped with polytetrafluorethylecoatings coatings are put into 20mL
In Schlenk pipes, system is replaced into nitrogen protection.4- bromoanisoles (1.0mmol) then are added in the case of logical nitrogen, so
3mL is added afterwards and newly distills dioxanes, is continuously stirred at room temperature 1 minute.Then benzenethiol or 3- methylbenzene phenyl-sulfhydrates or 2- are added
Naphthyl mercaptan (1.05mmol), continuously stir at room temperature 1 minute.Then Schlenk pipes are placed in anti-in the oil bath of 110 DEG C of preheating
Answer 2-18 hours, reaction equation is as follows.After completion of the reaction, reaction tube is cooled to room temperature, stops reaction, added to system
Ethyl acetate (6.0mL) and water (2.0mL), then carry out gas chromatographic analysis by organic layer, and detect and determine coupled product
Yield.
Wherein, above-mentioned catalysis is formed in carbon-sulfide linkage reaction, and catalyst Phosphine ligands and yield situation are as shown in table 2 below.
Table 2
From table 2 it can be seen that above-mentioned each 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl -
Indoles Phosphine ligands can show good catalytic performance in above-mentioned formation carbon-sulfide linkage reaction.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
All any modification, equivalent and improvement made within refreshing and principle etc., should be included in the scope of the protection.
Claims (9)
1. a kind of Phosphine ligands of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol skeletons,
Its structure is as shown in following formula I：
Wherein, the R is hydrogen-based, alkyl, substitutes alkyl, alkoxy, substituted amido, alkylene, aryl or fluorine, the R1For alkane
Base, substitution alkyl, alkyl ether, oxyalkyl, alkoxy or aryl, the R2For alkyl, substitution alkyl, alkoxy or fluorine, the R3
For alkyl, substitution alkyl or aryl.
2. 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indols as claimed in claim 1
The Phosphine ligands of skeleton, it is characterised in that the R is hydrogen-based, C1-10 alkyl, C1-C10 alkoxy, C3-C10 cycloalkanes oxygen
One kind in base, dimethylamino, 1,3- butadienes, phenyl, Benzyl epoxides, fluorine, trifluoromethyl；The R1For C1-C10 alkyl,
One kind in C3-C10 cycloalkyl, cycloalkyl ethers, epoxy alkyl, alkyl alkoxy, alkyl-cycloalkyl ether, phenyl；The R2
For one kind in C1-C10 alkyl, methoxyl group, fluorine, trifluoromethyl；The R3For phenyl, ethyl, isopropyl, the tert-butyl group, ring
One kind in amyl group, cyclohexyl, o-tolyl, p-methylphenyl, p-methoxyphenyl.
3. 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol bones stated such as claim 2
The Phosphine ligands of frame, it is characterised in that in the R, the alkyl of the C1-10 includes methyl, ethyl, n-propyl, isopropyl, positive fourth
Base, isobutyl group, sec-butyl, the tert-butyl group and C5-10 alkyl, the alkoxy of the C1-C10 include methoxyl group, ethyoxyl, positive third
The alkoxy of epoxide, isopropoxy and C4-C10, the cycloalkyloxy of the C3-C10 include ring propoxyl group, cyclobutoxy group and C5-
C10 cycloalkyloxy；
The R1In, the alkyl of the C1-C10 include methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, sec-butyl,
The alkyl of the tert-butyl group and C5-C10, the cycloalkyl of the C3-10 include cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl and C7-C10
Cycloalkyl, the cycloalkyl ethers includes tetrahydrofuran, and the epoxy alkyl includes glycidyl, and the alkyl alkoxy includes
Methyl methoxy base, the alkyl-cycloalkyl ether include methyltetrahydrofuran；
The R2In, the alkyl of the C1-C10 includes the alkyl of methyl, ethyl and C3-C10.
4. a kind of Phosphine ligands of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol skeletons
Preparation method, comprise the following steps：
After 2 '-bromoacetophenone and N- alkyl phenylhydrazine are carried out into mixed processing, phosphoric acid is added as catalyst, is stirred
Afterwards, polyphosphoric acid is added, heating response is carried out, 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates is prepared, or it is described
After 2 '-bromoacetophenone and N- alkyl phenylhydrazine carry out mixed processing, acetic acid is added, ethanol reacts 0.5-1.5 under the conditions of 70-80 DEG C
Hour, all solvents are taken in then decompression away, add polyphosphoric acid, carry out heating response, prepare 2- (2 '-bromophenyl) -1- alkyl -
1H- Indole Intermediates, wherein, the heating-up temperature of the heating response is 80-120 DEG C, and the reaction time is 1-2 hours；
The 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and N- bromo-succinimides are dissolved in dimethyl formyl
In amine, processing is stirred at room temperature, obtains 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates；
The 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates are dissolved in tetrahydrofuran, at -75 to -80 DEG C
Under the conditions of add n-BuLi, uniform stirring 0.5-1 hours, then add two substitution phosphonium chlorides, it is small to react 12-24 at room temperature
When, obtain 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl -1H- indoles Phosphine ligands.
5. 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indols as claimed in claim 4
The preparation method of the Phosphine ligands of skeleton, it is characterised in that prepare in the bromo- 2- of the 3- (2- bromophenyls) -1- alkyl -1H- indoles
In the step of mesosome, 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and the N- bromo-succinimides rub
You are than being 1:(1.05-1.2), mixing time are 1-2 hours；
And/or
Prepare the 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl -1H- indoles Phosphine ligands
In step, the mol ratio of the bromo- 2- of 3- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and the n-BuLi is 1:
(1.1-1.2)；Mole of the bromo- 2- of 3- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and the two substitutions phosphonium chloride
Than for 1:(1.1-1.2).
6. a kind of Phosphine ligands of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol skeletons
Preparation method, comprise the following steps：
After 2 '-bromoacetophenone and phenylhydrazine are carried out into mixed processing, phosphoric acid is added as catalyst, after being stirred, is added
Polyphosphoric acid, heating response is carried out, prepare 2- (2 '-bromophenyl) -1H- Indole Intermediates, or the 2 '-bromoacetophenone and phenylhydrazine enter
After row mixed processing, addition acetic acid, ethanol react 0.5-1.5 hours under the conditions of 70-80 DEG C, and then decompression is taken away all molten
Agent, polyphosphoric acid is added, carry out heating response, prepare 2- (2 '-bromophenyl) -1H- Indole Intermediates, wherein, heating response
Heating-up temperature is 80-120 DEG C, and the reaction time is 1-2 hours；
It is 1 in molar ratio by the 2- (2 '-bromophenyl) -1H- Indole Intermediates and sodium hydride, dialkyl sulfate:(1.1-
2.0):(1.05-1.5) is mixed, and forms tetrahydrofuran mixed liquor, 1-2 hours are stirred at room temperature, obtain 2- (2 '-bromophenyl) -1- alkane
Base -1H- Indole Intermediates；
The 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and N- bromo-succinimides are dissolved in dimethyl formyl
In amine, processing is stirred at room temperature, obtains 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates；
The 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates are dissolved in tetrahydrofuran, at -75 to -80 DEG C
Under the conditions of add n-BuLi, uniform stirring 0.5-1 hours, then add two substitution phosphonium chlorides, it is small to react 12-24 at room temperature
When, obtain 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl -1H- indoles Phosphine ligands.
7. 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indols as claimed in claim 6
The preparation method of the Phosphine ligands of skeleton, it is characterised in that prepare in the 3- bromo- 2- (2 '-bromophenyl) -1- alkyl -1H- indoles
In the step of mesosome, 2- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and the N- bromo-succinimides rub
You are than being 1:(1.05-1.2), mixing time are 1-2 hours；
And/or
Prepare the 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl -1H- indoles Phosphine ligands
In step, the mol ratio of the bromo- 2- of 3- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and the n-BuLi is 1:
(1.1-1.2)；Mole of the bromo- 2- of 3- (2 '-bromophenyl) -1- alkyl -1H- Indole Intermediates and the two substitutions phosphonium chloride
Than for 1:(1.1-1.2).
8. 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkane as described in claim 1-3 is any
Synergist application in cross-coupling reaction of the Phosphine ligands of base-indoles skeleton as transition-metal catalyst.
9. 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) substituted-phenyl) -1- alkyl-indol bones as claimed in claim 8
The application of the Phosphine ligands of frame, it is characterised in that 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) the substituted-phenyl) -1-
The Phosphine ligands of alkyl-indol skeleton are applied as the synergist of palladium catalyst in formation carbon-sulfide linkage reaction of aryl bromide,
And the Phosphine ligands of 3- (two substitution phosphino-s) -2- (2- (two substitution phosphino-s) the substituted-phenyl) -1- alkyl-indol skeletons to urge
Mole dosage of the agent in formation carbon-sulfide linkage reaction system of aryl bromide is 0.5-1.0%.
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| CN114907404B (en) * | 2021-02-09 | 2024-05-14 | 香港理工大学深圳研究院 | 5- (2- (Disubstituted phosphino) phenyl) -1-alkyl-1H-pyrazolyl phosphine ligand and preparation method and application thereof |
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| CN104945434A (en) * | 2015-06-19 | 2015-09-30 | 香港理工大学深圳研究院 | (2-disubstituted phosphino-phenyl)-1-alkyl-indol-phosphine ligand and synthetic method and application thereof |
| CN105152827A (en) * | 2015-08-12 | 2015-12-16 | 香港理工大学深圳研究院 | Cross coupling reaction of arenesulphonate substrate and organic titanium |
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| CN104945434A (en) * | 2015-06-19 | 2015-09-30 | 香港理工大学深圳研究院 | (2-disubstituted phosphino-phenyl)-1-alkyl-indol-phosphine ligand and synthetic method and application thereof |
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| CN114907404A (en) * | 2021-02-09 | 2022-08-16 | 香港理工大学深圳研究院 | 5- (2- (disubstituted phosphino) phenyl) -1-alkyl-1H-pyrazolylphosphine ligand and preparation method and application thereof |
| CN114907404B (en) * | 2021-02-09 | 2024-05-14 | 香港理工大学深圳研究院 | 5- (2- (Disubstituted phosphino) phenyl) -1-alkyl-1H-pyrazolyl phosphine ligand and preparation method and application thereof |
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