CN109096338B - Benzaphosphepillocenyl phosphine oxide ligand, complex containing same, preparation method and application - Google Patents

Benzaphosphepillocenyl phosphine oxide ligand, complex containing same, preparation method and application Download PDF

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CN109096338B
CN109096338B CN201811053009.3A CN201811053009A CN109096338B CN 109096338 B CN109096338 B CN 109096338B CN 201811053009 A CN201811053009 A CN 201811053009A CN 109096338 B CN109096338 B CN 109096338B
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汤文军
司腾达
李博文
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Shanghai Institute of Organic Chemistry of CAS
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    • B01J31/2461—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 ring members in the condensed ring system or in a further ring
    • B01J31/2471—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 ring members in the condensed ring system or in a further ring with more than one complexing phosphine-P atom
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Abstract

The invention discloses a benzoazaphosphole phosphine oxide ligand, a complex containing the same, a preparation method and application thereof. The invention provides a benzoazaphosphole phosphine oxide ligand shown as a formula I and a complex containing the same. The complex of the benzoazaphosphole phosphine oxide ligand and the transition metal halide can realize the direct coupling of carbon-carbon bonds between alkyl groups with large steric hindrance and aryl groups; the reaction condition is mild; has high catalytic efficiency; the coupling reaction process of the carbon-carbon bond between the alkyl with large steric hindrance and the aryl can be greatly simplified; the method has very high practicability, can obviously reduce the reaction cost and shorten the reaction period; the complexes of the invention are free of other undesirable by-products during the catalytic process.

Description

Benzaphosphepillocenyl phosphine oxide ligand, complex containing same, preparation method and application
Technical Field
The present invention relates to the field of metal catalysts. More particularly, the invention relates to a novel benzoazaphosphole phosphine oxide ligand, a metal complex containing the ligand and a Kumada coupling reaction of the ligand and the metal complex in high-efficiency catalysis of a large steric hindrance aryl halide and a branched chain alkyl Grignard reagent, namely the benzoazaphosphole phosphine oxide ligand, the complex containing the benzoazaphosphole phosphine oxide ligand, a preparation method and application of the complex.
Background
However, the existing method still has great limitation on the carbon-carbon bond coupling with large steric hindrance, and the applicable high-efficiency catalyst and ligand are still rare, especially for the formation of the carbon-carbon bond between the aryl with large steric hindrance and the alkyl, the lack of high-efficiency method is mainly caused by the existence of β -hydrogen in the alkyl, and the existing reaction method can cause the generation of a large amount of reduction and isomerization byproducts.
In view of the foregoing, there is a strong need in the art to develop a ligand compound and a catalyst thereof that can achieve direct coupling of carbon-carbon bonds between bulky hindered alkyl and aryl groups.
Disclosure of Invention
The invention aims to overcome the defects of low coupling yield of carbon-carbon bonds with large steric hindrance and more byproducts in the prior art, and provides a benzoazaphosphole phosphine oxide ligand, a complex containing the benzoazaphosphole phosphine oxide ligand, a preparation method and application of the benzoazaphosphole phosphine oxide ligand. The benzoazaphosphole phosphine oxide ligand and the transition metal halide complex are used as a catalytic system, so that the reaction of direct coupling of carbon-carbon bonds between alkyl groups with large steric hindrance and aryl groups is realized, the reaction yield is high, and byproducts are few.
The invention solves the technical problems through the following technical scheme.
The invention provides a benzoazaphosphole phosphine oxide ligand shown as a formula I,
Figure BDA0001795060830000021
wherein the content of the first and second substances,
R1is H, halogen, -OR5、-NR6R7Substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C3-C30Cycloalkyl, substituted or unsubstituted C6-C20Aryl, or substituted or unsubstituted C3-C30(iii) heterocyclyl, wherein the heteroatoms in the heterocyclyl are independently selected from N, O and S, the number of heteroatoms being 1, 2 or 3; wherein R is5、R6And R7Each independently is H, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C3-C30Cycloalkyl, or substituted or unsubstituted C6-C20An aryl group;
R2、R3and R4Each independently of the others being halogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C3-C30Cycloalkyl, or substituted or unsubstituted C6-C20An aryl group;
said "substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C3-C30Cycloalkyl, substituted or unsubstituted C6-C20Aryl, substituted or unsubstituted C3-C30The substituents mentioned for the "heterocyclic group" mean by halogen, C1-C4Alkyl radical, C1-C4One or more of haloalkyl, amino or hydroxy, when a plurality of substituents are present, said substituents are the same or different;
carbon marked with x is chiral carbon or achiral carbon; when the carbon marked is chiral carbon, the configuration is R or S; phosphorus marked with x is chiral phosphorus or achiral phosphorus; when the labeled phosphorus is chiral phosphorus, the configuration is R or S.
In a preferred embodiment of the present inventionWhen said R is1When the halogen is fluorine, chlorine, bromine or iodine.
In a preferred embodiment of the invention, when said R is1Is substituted or unsubstituted C1-C10When alkyl, said C1-C10Alkyl is C1-C4The alkyl group is preferably a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group or a tert-butyl group, and more preferably an isopropyl group.
In a preferred embodiment of the invention, when said R is1Is substituted or unsubstituted C3-C30When there is a cycloalkyl group, said C3-C30Cycloalkyl being C3-C10Cycloalkyl, preferably C3-C6The cycloalkyl group is more preferably a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group.
In a preferred embodiment of the invention, when said R is1Is substituted or unsubstituted C6-C20When aryl, said C6-C20Aryl is C6-C10Aryl, preferably phenyl or naphthyl.
In a preferred embodiment of the invention, when said R is1Is substituted or unsubstituted C3-C30When it is heterocyclic, said C3-C30Heterocyclyl is C3-C10Heterocyclic group, more preferably C3-C6Heterocyclic radical, wherein hetero atom in heterocyclic radical is selected from N and O, the number of hetero atom is preferably 1 or 2; preferably, it is
Figure BDA0001795060830000031
In a preferred embodiment of the invention, when said R is5、R6And R7Each independently is substituted or unsubstituted C1-C10When alkyl, said C1-C10Alkyl is C1-C4The alkyl group is preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group or a tert-butyl group, and more preferably a methyl group or an isopropyl group.
In a preferred embodiment of the invention, when said R is5、R6And R7Each independently is substituted or unsubstituted C3-C30When there is a cycloalkyl group, said C3-C30Cycloalkyl being C3-C10Cycloalkyl, preferably C3-C6The cycloalkyl group is more preferably a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group.
In a preferred embodiment of the invention, when said R is5、R6And R7Each independently is substituted or unsubstituted C6-C20When aryl, said C6-C20Aryl is C6-C10Aryl, preferably phenyl or naphthyl.
In a preferred embodiment of the invention, when said R is2、R3And R4When each is independently halogen, the halogen is fluorine, chlorine, bromine or iodine.
In a preferred embodiment of the invention, when said R is2、R3And R4Each independently is substituted or unsubstituted C1-C10Alkyl radical, said C1-C10Alkyl is C1-C4The alkyl group is preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group or a tert-butyl group, and more preferably a tert-butyl group.
In a preferred embodiment of the invention, when said R is2、R3And R4Each independently is substituted or unsubstituted C3-C30Cycloalkyl radical, said C3-C30Cycloalkyl being C3-C10Cycloalkyl, preferably C3-C6The cycloalkyl group is more preferably a cyclopropyl group, a cyclobutyl group, a cyclopentyl group or a cyclohexyl group.
In a preferred embodiment of the invention, when said R is2、R3And R4Each independently is substituted or unsubstituted C6-C20Aryl radical, said C6-C20Aryl is C6-C10Aryl, preferably phenyl or naphthyl。
In a preferred embodiment of the invention, when said "substituted or unsubstituted C" is1-C10Alkyl, substituted or unsubstituted C3-C30Cycloalkyl, substituted or unsubstituted C6-C20Aryl, substituted or unsubstituted C3-C30When the substituent for said substituent in the heterocyclic group "is halogen, said halogen is fluorine, chlorine, bromine or iodine.
In a preferred embodiment of the invention, when said "substituted or unsubstituted C" is1-C10Alkyl, substituted or unsubstituted C3-C30Cycloalkyl, substituted or unsubstituted C6-C20Aryl, substituted or unsubstituted C3-C30The substituent for said substituent in the heterocyclic group "is C1-C4When alkyl, said C1-C4Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl.
In a preferred embodiment of the invention, when said "substituted or unsubstituted C" is1-C10Alkyl, substituted or unsubstituted C3-C30Cycloalkyl, substituted or unsubstituted C6-C20Aryl, or substituted or unsubstituted C3-C30The substituent for said substituent in the heterocyclic group "is C1-C4When halogenated alkyl, said C1-C4Halogen in the halogenated alkyl is fluorine, chlorine, bromine or iodine, and C is1-C4C in haloalkyl1-C4The alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl, and the C is1-C4The haloalkyl group is further preferably a fluoromethyl group or a pentafluoroethyl group.
In a preferred embodiment of the present invention, R is2、R3And R4The same or different, preferably the same, and more preferably both tert-butyl groups.
In a preferred embodiment of the invention, R1preferably-OR5、-NR6R7、C1-C10Alkyl radical, C6-C20Aryl radical, C3-C30Heterocyclyl, wherein the heteroatoms in the heterocyclyl are independently selected from N and O, the number of heteroatoms is 2; wherein R is5、R6And R7Each independently is C1-C10Alkyl or C6-C20An aryl group;
R2、R3and R4Each independently is C1-C10An alkyl group.
In a preferred embodiment of the invention, R1Is preferably-OCH3、-OPh、-OiPr、-N(CH3)2、-NPh2、-N(iPr)2Isopropyl, phenyl or
Figure BDA0001795060830000051
In a preferred embodiment of the invention, R1preferably-OR5Wherein R is5Is C1-C4An alkyl group; r2、R3And R4Are each independently preferably C1-C4An alkyl group.
In a preferred embodiment of the invention, the carbon marked with x is preferably an achiral carbon; the phosphorus marked with x is preferably achiral phosphorus.
In a preferred embodiment of the present invention, the benzoazaphosphole phosphine oxide ligand shown in formula I is preferably any one of the following compounds:
Figure BDA0001795060830000052
wherein, is as defined above.
The invention also provides a complex, which comprises the benzoazaphosphole phosphine oxide ligand shown in the formula I and transition metal halide.
Wherein the content of the first and second substances,
the transition metal halide may be a transition metal halide conventional in the field of metal catalysis, preferably including a transition metal and a halogen, wherein the transition metal may be a transition metal conventional in the field of metal catalysis, such as one or more of Rh, Ru, Ni, Ir, Pd, Cu, Pt, Co, and Au, preferably Ni; the halogen is preferably chlorine or bromine, and more preferably chlorine. The transition metal halide is further preferably nickel (II) dichloride and/or nickel (II) dichloride in 1.5 hydrate.
The invention also provides a preparation method of the benzoazaphosphole phosphine oxide ligand, which comprises the following steps: under the action of Lewis acid and a reducing agent in an organic solvent under the protection of gas, carrying out the following intra-ring phosphine-oxygen double bond reduction reaction on a compound shown as a formula II to obtain the benzoazaphosphole phosphine-oxygen ligand,
Figure BDA0001795060830000061
wherein the content of the first and second substances,
R1、R2、R3、R4and as defined above.
In the present invention, the organic solvent may be an organic solvent conventional in the art such as an aromatic hydrocarbon solvent and/or an ether solvent. The aromatic hydrocarbon solvent is preferably toluene. The ether solvent is preferably tetrahydrofuran or anhydrous diethyl ether, and more preferably tetrahydrofuran.
In the present invention, the Lewis acid may be a Lewis acid conventional in this type of reaction in the art, such as a titanium-containing Lewis acid, preferably tetraisopropyl titanate (Ti (OiPr))4) Or titanium tetrachloride (TiCl)4) Further preferred is tetraisopropyl titanate.
In the present invention, the reducing agent may be a reducing agent conventional in this type of reaction in the art, such as a siloxane-based reducing agent or a silane-based reducing agent, preferably phenylsilane (PhSiH)3) Trichlorosilane (HSiCl)3) Or Polymethylhydrosiloxane (PMHS), and more preferably polymethylhydrosiloxane.
In the present invention, the reaction temperature may be a temperature conventional in the art, such as 40 to 100 ℃, preferably 50 to 90 ℃, more preferably 60 to 90 ℃ (e.g. 70 ℃).
In the present invention, the reaction time may be a time conventional in the art, such as 3 to 48 hours, preferably 5 to 24 hours, and more preferably 12 to 18 hours (e.g. 12 hours).
In the present invention, the shielding gas may be a shielding gas conventional in the art, such as nitrogen.
In the invention, the molar concentration of the compound shown in the formula II in the organic solvent is the molar concentration conventional in the reaction in the field, and can be 0.05-1.0 mol/L, preferably 0.1-0.6 mol/L, and more preferably 0.1-0.3 mol/L (for example, 0.2 mol/L).
In the invention, the molar ratio of the compound shown in the formula II to the Lewis acid can be 1: 1-1: 10, and preferably 1: 3-1: 7 (for example, 1: 5).
In the invention, the molar ratio of the compound shown as the formula II to the reducing agent can be 1: 1-1: 10, preferably 1: 3-1: 7 (for example, 1: 5).
In a preferred embodiment of the present invention, the reaction further comprises quenching and heating stirring after the reaction is finished.
In a preferred embodiment of the present invention, the solution used for the quenching may be a quenching solution (e.g., sodium hydroxide solution and potassium hydroxide solution) conventional in the art for such reactions. The heating and stirring conditions can be those conventional in the reaction of the type in the art, the heating and stirring temperature can be 40-70 ℃ (for example, 60 ℃), and the heating and stirring time can be 20-40 minutes (for example, 30 minutes).
In a preferred embodiment of the present invention, the reaction further comprises a post-treatment step after the reaction is finished, the post-treatment step may be a post-treatment step conventional in the art, and the post-treatment step may comprise the following operations: one or more of washing, drying, filtering, chromatography steps.
In a preferred embodiment of the invention, the washing solution used may be a washing solution conventional in the art (e.g., a saturated sodium chloride solution). The drying agent used for the drying may be one conventional in the art (e.g., anhydrous sodium sulfate). The chromatographic column used for the chromatography may be a chromatographic column conventional in the art (e.g., a neutral alumina column). The eluent used for the chromatography may be an eluent conventional in the art, such as a mixture of ethyl acetate and methanol, a mixture of n-hexane and ethyl acetate, a mixture of n-hexane and methyl tert-butyl ether, or a mixture of n-hexane and diethyl ether.
The invention also provides a compound shown as a formula II,
Figure BDA0001795060830000071
wherein R is1、R2、R3、R4And as defined above.
The invention also provides a preparation method of the compound shown in the formula II, which comprises the following steps: under the action of alkali and oxidant in organic solvent under the protection of gas, the compound shown in formula VI and the compound shown in formula VII are reacted as shown in the specification to obtain the compound shown in formula II,
Figure BDA0001795060830000081
wherein R is1、R2、R3、R4And as defined above.
In the present invention, the organic solvent may be an organic solvent conventional in the art such as an ethereal solvent, preferably tetrahydrofuran.
In the present invention, the base may be a base conventional in the art such as organolithium, preferably n-butyllithium, t-butyllithium or lithium diisopropylamide, and more preferably lithium diisopropylamide.
In the present invention, the oxidant may be an oxidant conventional in the art, such as a peroxide, and preferably hydrogen peroxide.
In the present invention, the reaction temperature of the first step may be a temperature conventional in this type of reaction in the art, and preferably is a stepwise temperature, the first-stage temperature may be-50 ℃ to-85 ℃ (e.g., -78 ℃), and the second-stage temperature may be 10 ℃ to 40 ℃ (e.g., room temperature).
In the present invention, the reaction time of the first step may be a time conventional in the art, such as 1 to 5 hours, preferably 2 to 4 hours (e.g. 3 hours).
In the present invention, the reaction temperature of the second step may be a temperature conventional in this type of reaction in the art, such as 10 ℃ to 40 ℃ (e.g., room temperature).
In the present invention, the reaction time of the second step can be a time conventional in the art, such as 0.5 to 2 hours, preferably 0.75 to 1.5 hours (e.g. 1 hour).
In the present invention, the shielding gas may be a shielding gas conventional in the art, such as nitrogen.
In the invention, the molar concentration of the compound shown in the formula VI in the organic solvent can be the molar concentration conventional in the reaction in the field, and can be 0.1-1.0 mol/L, preferably 0.1-0.5 mol/L, and more preferably 0.2-0.3 mol/L (for example 0.246 mol/L).
In the invention, the molar ratio of the compound shown in the formula VI to the base can be 1: 1-1: 1.5, and preferably 1: 1-1: 2 (for example, 1: 1.1).
In the invention, the molar ratio of the compound shown in the formula VI to the oxidant can be 1: 10-1: 40, preferably 1: 20-1: 30 (for example, 1: 25.4).
In the invention, the molar ratio of the compound shown in the formula VI to the compound shown in the formula VII can be 1: 1-1: 1.5, and preferably 1: 1-1: 2 (for example, 1: 1.1).
In a preferred embodiment of the present invention, the preparation method of the compound represented by the formula II comprises the following steps: adding the compound shown as the formula IV into a reaction vessel, adding alkali, then adding the compound shown as the formula VII, and finally adding an oxidant for reaction.
In a preferred embodiment of the invention, the oxidant is added dropwise at 0 ℃ in the preparation method of the compound shown in the formula II.
In a preferred embodiment of the present invention, the reaction further comprises a post-treatment step after the reaction is finished, the post-treatment step may be a post-treatment step conventional in the art, and the post-treatment step may comprise the following operations: one or more of the steps of extracting, drying, filtering, and chromatography.
In a preferred embodiment of the present invention, the extractant used for the extraction may be an extractant conventional in the art (e.g., dichloromethane). The drying agent used for the drying may be one conventional in the art (e.g., anhydrous sodium sulfate). The column used for the chromatography may be a column conventional in the art (e.g., silica gel column). The eluent used for the chromatography may be an eluent conventional in the art, such as a mixture of ethyl acetate and methanol, a mixture of n-hexane and ethyl acetate, a mixture of n-hexane and methyl tert-butyl ether, or a mixture of n-hexane and diethyl ether.
The invention also provides a method for synthesizing non-cyclic alkyl aromatic hydrocarbon, which comprises the following steps: under the action of the complex in an organic solvent under the protection of gas, carrying out Kumada coupling reaction on the compounds shown in the formulas III and IV to obtain the compound shown in the formula V,
Figure BDA0001795060830000091
wherein the content of the first and second substances,
a is substituted or unsubstituted C6-C20Aryl, or substituted or unsubstituted C4-C11A nitrogen-containing heteroaryl group, wherein the number of nitrogen atoms in the nitrogen-containing heteroaryl group is 1, 2 or 3; said "substituted or unsubstituted C6-C20Aryl, or substituted or unsubstituted C4-C11Substituted by halogen, C1-C10Alkyl, halogen substituted C1-C10Alkyl, -CN, -OR9、-NO2、-COR10、-NH2、-COOR11-OTf, hydroxy or phenyl, when a plurality of substituents are present, said substitutionThe radicals are identical or different; said halogen substituted C1-C10In the alkyl group, when a plurality of substituents are present, the substituents may be the same or different;
R9is substituted or unsubstituted C1-C10An alkyl group; said substituted or unsubstituted C1-C10The substitution in alkyl means by halogen, C6-C10Aryl and halogen substituted C6-C10One or more substituents of the aryl group, when a plurality of substituents are present, said substituents being the same or different; said halogen substituted C6-C10In the aryl group, when a plurality of substituents are present, the substituents may be the same or different;
R10is hydrogen or C1-C10Alkyl groups of (a);
R11is C1-C10Alkyl groups of (a);
X1is a leaving group;
R8is C1-C10Alkyl or C6-C12Aryl substituted C1-C10An alkyl group; said C6-C12Aryl substituted C1-C10In the alkyl group, when a plurality of substituents are present, the substituents may be the same or different;
X2is halogen.
In a preferred embodiment of the invention, when A is substituted or unsubstituted C6-C20When aryl, said C6-C20Aryl is C6-C14Aryl, preferably phenyl, naphthyl or anthracenyl.
In a preferred embodiment of the invention, when A is substituted or unsubstituted C4-C11When containing nitrogen heteroaryl, said C4-C11The nitrogen-containing heteroaryl is preferably C5-C9Nitrogen-containing heteroaryl, the number of nitrogen atoms is preferably 1; said A is further preferably pyridyl or quinolyl.
In a preferred embodiment of the invention, when said "substituted or unsubstituted C" is6-C20Aryl, or substituted or unsubstituted C4-C11When the substituent substituted in the nitrogen-containing heteroaryl group is halogen, the halogen is fluorine, chlorine, bromine or iodine, and preferably chlorine.
In a preferred embodiment of the invention, when said "substituted or unsubstituted C" is6-C20Aryl, or substituted or unsubstituted C4-C11The substituent in the nitrogen-containing heteroaryl group is C1-C10When alkyl, said C1-C10Alkyl is C1-C4Alkyl, preferably methyl, ethyl or propyl.
In a preferred embodiment of the invention, when said "substituted or unsubstituted C" is6-C20Aryl, or substituted or unsubstituted C4-C11The substituent of the nitrogen-containing heteroaryl group is a halogen-substituted C1-C10When alkyl, said halogen being substituted by C1-C10C in alkyl1-C10Alkyl is C1-C4Alkyl, halogen is fluorine, chlorine, bromine or iodine.
In a preferred embodiment of the invention, when said R is9Is substituted or unsubstituted C1-C10When alkyl, said C1-C10Alkyl is C1-C4Alkyl, preferably methyl.
In a preferred embodiment of the invention, when said R is9Is substituted C1-C10When the substituent is halogen, the halogen is fluorine, chlorine, bromine or iodine.
In a preferred embodiment of the invention, when said R is9Is substituted C1-C10Alkyl, the substituent being C6-C10When aryl, said C6-C10Aryl is phenyl.
In a preferred embodiment of the invention, when said R is9Is substituted C1-C10Alkyl, the substituents being halogen-substituted C6-C10Aryl, said halogen being substituted by C6-C10Aryl radicalsHalogen in (1) is fluorine, chlorine, bromine or iodine, preferably fluorine; said halogen substituted C6-C10C in aryl6-C10Aryl is phenyl.
In a preferred embodiment of the invention, when R is10Is C1-C10When alkyl, said C1-C10Alkyl is C1-C4The alkyl group is preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group or a tert-butyl group, and more preferably a methyl group.
In a preferred embodiment of the present invention, R is11Is C1-C4Alkyl of (a), said C1-C4The alkyl group is preferably a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group or a tert-butyl group, and more preferably a methyl group or an ethyl group.
In a preferred embodiment of the present invention, said X is1Is F, Cl, Br, OTf, OMs, OTs or OPiv, preferably Br, OTf, OMs, OTs or OPiv.
In a preferred embodiment of the invention, when said R is8Is C1-C10When alkyl, said C1-C10Alkyl is C1-C4Alkyl, preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl.
In a preferred embodiment of the invention, when said R is8Is C6-C12Aryl substituted C1-C10When alkyl, said C6-C12Aryl substituted C1-C10C in alkyl1-C10Alkyl is C1-C4Alkyl, preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl; said C is6-C12Aryl substituted C1-C10C in alkyl6-C12Aryl of is C6-C10Aryl of (2), preferably phenyl.
In a preferred embodiment of the present invention, said X is2Is F, Cl, Br or I, preferably Cl.
In a preferred embodiment of the present invention, said A is preferably substituted or unsubstituted C6-C20Aryl, said substitution being by halogen, -CN, -OR9、-COOR11Or phenyl; wherein, R is9Preferably C1-C10An alkyl group; said R11Preferably C1-C10Alkyl groups of (a); said X1Is a leaving group.
In a preferred embodiment of the present invention, R is8Preferably C1-C10An alkyl group; said X2Is halogen.
In a preferred embodiment of the present invention, A is preferably
Figure BDA0001795060830000121
Figure BDA0001795060830000122
Figure BDA0001795060830000131
Figure BDA0001795060830000132
Further preferred is
Figure BDA0001795060830000133
Figure BDA0001795060830000134
In a preferred embodiment of the present invention, said X is1Preferably Br, OTf, OMs, OTs, or OPiv.
In a preferred embodiment of the present invention, the compound represented by formula III is preferably any one of the following compounds:
Figure BDA0001795060830000135
Figure BDA0001795060830000141
in a preferred embodiment of the present invention, the compound shown as IV is preferably any one of the following compounds:
Figure BDA0001795060830000142
in a preferred embodiment of the invention, said compound of formula IV is preferably
Figure BDA0001795060830000143
In a preferred embodiment of the present invention, the compound represented by V is preferably any one of the following compounds:
Figure BDA0001795060830000151
wherein the bold part represents R8A group.
In the present invention, the organic solvent may be an organic solvent conventional in the art such as an aromatic hydrocarbon solvent and/or an ether solvent. The aromatic hydrocarbon solvent is preferably toluene. The ether solvent is preferably tetrahydrofuran or anhydrous diethyl ether, and more preferably tetrahydrofuran.
In a preferred embodiment of the present invention, the reactants of the method for synthesizing acyclic alkylaromatic hydrocarbon may or may not include a base. When a base is included in the reactants, the base can be one conventional in the art for such reactions, such as R12OM or MOH, wherein, R12Is C1-C4Preferably tert-butyl or methyl; m is alkali metal, preferably sodium or potassium. The base is preferably potassium tert-butoxide.
In the present invention, the molar concentration of the benzoazaphosphole phosphine oxide ligand in the organic solvent may be the molar concentration conventional in the reaction in the field, such as 0.001 to 0.1mol/L, preferably 0.015 to 0.5mol/L, and more preferably 0.2 to 0.3mol/L (e.g. 0.025 mol/L).
In the present invention, the molar ratio of the transition metal halide to the benzoazaphosphole phosphine oxide ligand may be 0.5:1 to 1:4, preferably 0.75:1 to 1:2 (e.g., 1: 1).
In the present invention, the molar ratio of the compound represented by formula III to the benzoazaphosphole phosphine oxide ligand may be 100:1 to 1:1, preferably 20:1 to 60:1 (e.g., 40: 1).
In the present invention, the molar ratio of the compound represented by IV to the benzoazaphosphole phosphine oxide ligand may be 300:1 to 50:1, preferably 200:1 to 100:1 (for example, 160: 1).
In the present invention, the protective gas may be a protective gas conventional in this type of reaction in the art, and is preferably nitrogen.
In a preferred embodiment of the present invention, the method for synthesizing acyclic alkylaromatic hydrocarbon comprises the following steps: and sequentially adding the compound shown as the formula III, the compound shown as the formula IV, a transition metal halide and a ligand into a reaction vessel, pumping protective gas, sealing, and adding the organic solvent for reaction.
In the invention, the reaction temperature can be the temperature conventional in the reaction in the field, such as-70-40 ℃, preferably-20 ℃, and more preferably-20-0 ℃ (for example-10 ℃).
In the present invention, the reaction time may be a reaction time conventional in the art, such as 0.5 to 24 hours, preferably 1 to 5 hours, and more preferably 1 to 3 hours (e.g., 1.5 hours).
The above preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention without departing from the common general knowledge in the art.
The reagents and starting materials used in the present invention are commercially available.
The positive progress effects of the invention are as follows: the complex can realize direct coupling of carbon-carbon bonds between alkyl groups with large steric hindrance and aryl groups; the reaction condition is mild; has high catalytic efficiency; the coupling reaction process of the carbon-carbon bond between the alkyl with large steric hindrance and the aryl can be greatly simplified; the method has very high practicability, can obviously reduce the reaction cost and shorten the reaction period; the complexes of the invention are free of other undesirable by-products during the catalytic process.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.
Wherein the abbreviations appearing below refer to all the designations. The room temperature is 20-25 ℃; equiv means equivalent; TLC refers to thin layer chromatography;1h NMR refers to nuclear magnetic resonance hydrogen spectroscopy;13c NMR refers to nuclear magnetic resonance carbon spectroscopy;31PNMR, P spectrum refers to nuclear magnetic resonance phosphorus spectrum; EI-MS refers to electron bombardment mass spectrometry; HRMS (EI) refers to electron bombardment high-resolution mass spectrum, calcd.for refers to the calculated molecular weight of the compound in the high-resolution mass spectrum, and found refers to the actual measured molecular weight of the compound in the high-resolution mass spectrum.
Ligand 1 described below is a racemate.
Example 1
The ligand 1 is prepared by the following reaction scheme:
Figure BDA0001795060830000171
1. synthesis of Compound b
A3L clean three-necked flask was taken, sulfuric acid (3X 210mL,3M), formaldehyde (125mL,1.624mol,4equiv) and tetrahydrofuran (700mL) were added, and then the above mixed system was cooled to-20 ℃ or less, while compound a (50g,406mmol,1.0equiv) and sodium borohydride (90g,2.367mol,5.8equiv) were dissolved in tetrahydrofuran and placed in a 1L clean three-necked flask, and then sulfuric acid was slowly added dropwise to the above mixed system with a tetrafluoroethylene hose, and the temperature of the system was kept below 0 ℃. In this process, the sulfuric acid is added in portions (half is added at the beginning, the remainder is added in portions during the dropwise addition). After the addition of the starting materials was complete, the system was allowed to return to room temperature and stirring was continued for 2 hours. TLC plate monitoring, then use potassium hydroxide aqueous solution to adjust the system to strong alkaline. Dichloromethane was added for extraction and the organic phases were combined and dried over anhydrous sodium sulfate. Column chromatography gave compound b (55g,447.0mmol, 90%) as an oily liquid.
Compound b:1H NMR(500MHz,CDCl3)δ7.17(t,J＝8.2HZ,1H),6.37～6.39(m,1H),6.30～6.32(m,2H),3.81(s,3H),2.95(s,6H)；13C NMR(125MHz,CDCl3)δ158.4,150.6,130.6,118.7,105.1,96.9,55.5,41.2,28.2.EI-MS:m/z 151.2[M]+；HRMS(EI)m/z calcd forC13H23NO2(M):151.0997,found:151.0993.
2. synthesis of Compound c
A3L clean three-necked flask was taken, compound b (57g,376.8mmol,1.0equiv) was added dissolved in cyclohexane (250mL) and tetramethylethylenediamine (28.1mL,188mmol,0.5equiv), and the system was placed in a cooling bath at-5 ℃ and, when the internal temperature of the system was lower than 0 ℃, n-butyllithium (235.5mL,376mmol,1.0equiv) was slowly dropped into the system under nitrogen protection. After the n-butyllithium addition was completed, the reaction was continued for half an hour and the system was heated to 60 ℃ and then reacted for 2 hours. After returning to room temperature, the system was slowly added to a freshly prepared solution of tert-butylphosphine dichloride (0.95equiv) in tetrahydrofuran, reacted at 30 ℃ and monitored by P-spectroscopy. Then, water was added to the system, and the reaction was carried out at 30 ℃ for 3 hours, followed by P spectrum monitoring. To the above system were added aqueous sodium hydroxide (90.4g,3.9mol,9.0equiv) and formaldehyde (275.2mL, 37% aqueous solution), respectively, and monitored by P-spectroscopy. After the reaction was complete, the pH of the system was adjusted to 9 with aqueous hydrogen chloride (6M). Extracting with dichloromethane, concentrating, waiting to obtain white solid, and performing mother liquor column chromatography. Finally, product c (55g,193.0mmol, 51%) was obtained as a white solid.
Compound c:1H NMR(500MHz,CDCl3)δ7.41(t,J＝8.2Hz,1H),6.94(d,J＝5.5Hz,1H),6.66(dd,J＝4.2,4.1Hz,1H),4.26(dd,J＝12.2,1.9Hz,1H),4.07(dd,J＝8.7,5.3Hz,1H),3.75(s,3H),2.71(s,6H),1.12(d,J＝7.6Hz,9H)；13CNMR(125MHz,CDCl3)δ162.1,134.0,115.1(d,J＝7.2Hz),107.3,59.4,58.9,55.4,47.5,35.6,35.1,24.9(d,J＝0.8Hz)；31P NMR(162MHz,CDCl3)δ60.9.EI-MS:m/z 286.32[M]+；HRMS(EI)m/z calcd for C13H23NO2(M):286.1563,found:286.1566.
3. synthesis of Compound d
A500 mL clean three-necked flask was charged with Compound c (15g, 52.5mmol,1.0equiv), nitrogen purged three times and dichloroethane (150mL) added. The reaction was cooled to 0 deg.C (ice-water bath), the nitrogen flush was increased, one port of the three-necked flask was opened, and phosphorus pentachloride (21.9g, 105.0mmol, 2.0equiv) was added to the reaction in portions. The reaction was warmed to 60 ℃ and stirred for 2 h. After the reaction, the reaction system was cooled to 0 ℃ (ice water bath), and quenched by the addition of ice water (20 mL). The aqueous phase was extracted three times with dichloromethane after separation, the organic phases were combined, washed three times with saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate and subjected to spin column chromatography to give product d (7.3g,28.8mmol, 55%) as a yellow solid.
A compound d:1H NMR(500MHz,CDCl3)δ7.31(t,J＝8.1Hz,1H),6.23(d,J＝10.0Hz,2H),3.85(s,3H),3.58(d,J＝13.3Hz,1H),3.31～3.44(m,1H),2.90(s,3H),1.24(d,J＝16.0Hz,9H)；13C NMR(125MHz,CDCl3)δ162.0,158.5,158.3,136.2,102.5(d,J＝8.3Hz),102.0,101.3,99.5(d,J＝5.3Hz),55.3,51.8,51.2,36.7,36.6,34.2,33.6,24.6；31P NMR(162MHz,CDCl3)δ60.9.EI-MS:m/z253.2[M]+；HRMS(EI)m/z calcd for C13H23NO2(M):253.1232,found:253.1225.
4. synthesis of Compound e
A Schlenk tube was taken for drying, the compound d (500mg, 1.95mmol,1.0equiv) was added, nitrogen gas was purged three times, tetrahydrofuran (5mL) was added, the temperature was lowered to-78 deg.C, lithium diisopropylamide (1.10mL,2mol/L (with tetrahydrofuran as a solvent), 1.1equiv) was slowly added dropwise, and the reaction was carried out at-78 deg.C for one hour. Di-tert-butylphosphonium chloride (0.40mL,0.43mmol,1.1equiv) was slowly added to the reaction system, reacted at-78 ℃ for one hour, and then moved to room temperature for one hour. Cooling to 0 deg.c, slowly dropping hydrogen peroxide (5mL, 30%), reacting at room temperature for one hour, adding dichloromethane for demixing, separating organic phase, drying, concentrating and column chromatography (ethyl acetate: methanol 10:1) to obtain compound e (0.63g,1.56mmol, 80%, ee 1.7%).
Compound e:1H NMR(400MHz,CDCl3)δ7.32(t,J＝8.0Hz,1H),6.53(dd,J＝8.1,4.5Hz,1H),6.46(dd,J＝8.2,2.4Hz,1H),4.90(dd,J＝10.0,5.7Hz,1H),2.95(s,6H),1.42(d,J＝13.4Hz,9H),1.40(d,J＝14.3Hz,9H),1.25(d,J＝16.3Hz,9H)；13C NMR(125MHz,CDCl3)δ164.3,157.6(d,J＝2.3Hz),135.5,110.9(d,J＝6.7Hz),106.4(d,J＝5.2Hz),70.1(dd,J＝45.2,5.1Hz),45.0,38.0(d,J＝57.2Hz),37.1(dd,J＝54.5,6.7Hz),36.3(d,J＝77.3Hz),27.6,26.8,25.4；31PNMR(162MHz,CDCl3)δ62.0(d,J＝8.5Hz,1P),61.7(d,J＝8.4Hz,1P)；EI-MS:m/z 413.0[M]+；HRMS(EI)m/z calcd.for C21H37NO3P2(M):413.2246,found:413.2245.
5. synthesis of ligand 1
Compound e (0.41g,1.00mmol,1.0equiv) was placed in a Schlenk tube, and after purging nitrogen three times, tetrahydrofuran (5mL) was added. To this reaction system was added Ti (OiPr)4(0.51mL,5.00mmol,5.0equiv) and PMHS (0.70mL,5.00mmol,5.0 equiv). The reaction system was stirred at 70 ℃ for 12 hours, cooled to room temperature and the tetrahydrofuran was then vacuum-dried. A30% aqueous solution (20mL) of sodium hydroxide was added dropwise to the reaction system, gas was generated during the dropwise addition, the reaction system was heated at 60 ℃ and stirred for 30 minutes, then cooled to room temperature, and dehydrated ether (10 mL. times.6) was added thereto for extraction, and the combined organic phases were dried by adding anhydrous sodium sulfate. Filtration and suction drying through a neutral alumina column afforded product 1 as a white solid (0.38g,0.95mmol, 95%).
Ligand 1:1H NMR(500MHz,CDCl3)δ7.16(t,J＝8.0Hz,1H),6.19(dd,J＝7.7,3.6Hz,1H),6.02(d,J＝8.0Hz,1H),4.26(dd,J＝9.6,1.6Hz,1H),3.75(s,3H),3.11(s,3H),1.40(d,J＝12.7Hz,9H),1.08(d,J＝13.4Hz,9H),0.88(d,J＝11.8Hz,9H)；13C NMR(125MHz,CDCl3)δ161.5,156.5,132.9,102.2,99.5,63.6,63.3,63.1,62.8,55.3,37.8,27.8(d,J＝6.4Hz),27.6(d,J＝4.2Hz),27.0(d,J＝13.7Hz)；31P NMR(162MHz,CDCl3)δ62.3(d,J＝57.4Hz),-9.6(d,J＝57.5Hz).EI-MS:m/z 397.0[M]+；HRMS(EI)m/z calcd.for C21H37NO3P2(M):397.2416,found:397.2445.
example 2
Study of ligand 1 catalysis of different substrates
A10 mL Schlenk tube was dried, compound A (0.10mmol,1.0equiv), tert-butylmagnesium chloride (0.40mmol,4.0equiv), 1.5 hydrated nickel (II) dichloride (2.5% mmol,0.025equiv) and ligand 1 (2.5% mmol,0.025equiv, nickel/ligand molar ratio 1/1) were added, nitrogen was purged three times, and sealed. Tetrahydrofuran (1mL) was added. Cooling the reaction system to-10 ℃ for reaction for 1.5 hours, cooling to room temperature, adding water (10mL) and dichloromethane (10mL), separating liquid, combining organic phases, drying with anhydrous sodium sulfate, concentrating, sampling, detecting the reaction yield by using high performance liquid chromatography, separating by using column chromatography to obtain a colorless oily product, and analyzing the proportion of the product C and the byproduct D by using nuclear magnetic data.
TABLE 1
Figure BDA0001795060830000211
Figure BDA0001795060830000221
[a] Reaction conditions are as follows: under nitrogen atmosphere, with tetrahydrofuran as a solvent, 2.5 mol% of 1.5 hydrated nickel (II) dichloride and 2.5 mol% of ligand 1 were added and reacted at-10 ℃ for 1.5 hours. [b] Total separation yield of C and D.
As can be seen from Table 1, the catalytic system using the catalyst of the present invention has a wide substrate applicability.
Comparative example 1
Different ligands catalyze large steric hindrance aryl alkyl coupling reaction
Figure BDA0001795060830000222
A10 mL Schlenk tube was dried, compound A (0.10mmol,1.0equiv), t-butyl Grignard reagent B (0.40mmol,4.0equiv), 1.5 hydrated nickel (II) dichloride (2.5% mmol,0.025equiv) and ligand (2.5% mmol,0.025equiv, nickel/ligand molar ratio 1/1) were added, nitrogen was purged three times and sealed. Tetrahydrofuran (1mL) was added. Cooling the reaction system to-10 ℃ for reaction for 1.5 hours, cooling to room temperature, adding water (10mL) and dichloromethane (10mL), separating liquid, combining organic phases, drying with anhydrous sodium sulfate, concentrating, sampling, detecting the reaction yield by using high performance liquid chromatography, separating by using column chromatography to obtain a colorless oily product, and analyzing the proportion of the product C and the byproduct D, E by using nuclear magnetic data.
TABLE 2
Figure BDA0001795060830000223
Figure BDA0001795060830000231
Wherein the content of the first and second substances,
in the reaction formula, L is a ligand, N is 1.5 hydrated nickel (II) dichloride,
l1 is
Figure BDA0001795060830000232
L2 is
Figure BDA0001795060830000233
[a] Reaction conditions are as follows: under nitrogen atmosphere, tetrahydrofuran was used as a solvent, and 2.5 mol% of 1.5 hydrated nickel (II) dichloride and 2.5 mol% of a ligand were added to react at-10 ℃ for 1.5 hours. [b] The yield was determined by high performance liquid chromatography on carbon-18. [c] The isolation yield.
As can be seen from Table 2, the catalytic systems using ligands L1 and L2 as ligands have high activity, however, the selectivity of the product to the isomerized by-product is not good, and the debrominated by-product is generated.A ligand 1 of the present invention has high reaction activity, higher reaction selectivity, and inhibition of the β -H elimination pathway and the debromination reduction elimination side reaction pathway.

Claims (21)

1. A benzazaphosphoryl phosphine oxide ligand of formula I:
Figure FDA0002293015970000011
wherein the content of the first and second substances,
R1is-OR5(ii) a Wherein R is5Is C1-C4An alkyl group;
R2is C1-C4An alkyl group; r3And R4Is tert-butyl;
carbon marked with x is chiral carbon or achiral carbon; when the carbon marked is chiral carbon, the configuration is R or S; phosphorus marked with x is chiral phosphorus or achiral phosphorus; when the labeled phosphorus is chiral phosphorus, the configuration is R or S.
2. The benzazaphosphorine oxy ligand of formula I as set forth in claim 1, wherein:
said R5Is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl;
and/or, said R2Is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl.
3. The benzazaphosphorine oxy ligand of formula I as set forth in claim 2, wherein:
said R5Is methyl or isopropyl;
and/or, said R2Is a tert-butyl group.
4. The benzazaphosphorine oxy ligand of formula I as claimed in any of claims 1 to 3, wherein: which is prepared from
Figure FDA0002293015970000012
Wherein, the definition of the compound is as defined in claim 1.
5. A method for preparing the benzazepine phosphole oxygen ligand shown in the formula I according to any one of claims 1 to 4, which is characterized by comprising the following steps: under the action of Lewis acid and a reducing agent in an organic solvent under the protection of gas, carrying out the following intra-ring phosphine-oxygen double bond reduction reaction on a compound shown as a formula II to obtain the benzoazaphosphole phosphine-oxygen ligand,
Figure FDA0002293015970000021
wherein the content of the first and second substances,
R1、R2、R3、R4and is as defined in any one of claims 1 to 4.
6. The process for the preparation of benzazaphosphorine oxygen ligands of formula I as claimed in claim 5, wherein:
the organic solvent is an aromatic hydrocarbon solvent and/or an ether solvent;
and/or the Lewis acid is titanium-containing Lewis acid;
and/or the reducing agent is a siloxane reducing agent or a silane reducing agent;
and/or the reaction temperature is 40-100 ℃;
and/or the reaction time is 3-48 hours;
and/or the protective gas is nitrogen;
and/or the molar concentration of the compound shown as the formula II in the organic solvent is 0.05-1.0 mol/L;
and/or the molar ratio of the compound shown as the formula II to the Lewis acid is 1: 1-1: 10;
and/or the molar ratio of the compound shown as the formula II to the reducing agent is 1: 1-1: 10.
7. The process for the preparation of benzazaphosphorine oxygen ligands of formula I as claimed in claim 6, wherein:
the aromatic hydrocarbon solvent is toluene; and/or the ether solvent is tetrahydrofuran or anhydrous ether;
and/or the Lewis acid is tetraisopropyl titanate or titanium tetrachloride;
and/or the reducing agent is phenyl silane, trichlorosilane or polymethylhydrosiloxane;
and/or the reaction temperature is 50-90 ℃;
and/or the reaction time is 5-24 hours;
and/or the molar concentration of the compound shown as the formula II in the organic solvent is 0.1-0.6 mol/L;
and/or the molar ratio of the compound shown as the formula II to the Lewis acid is 1: 3-1: 7;
and/or the molar ratio of the compound shown as the formula II to the reducing agent is 1: 3-1: 7.
8. The process for the preparation of benzazaphosphorine oxygen ligands of formula I as claimed in claim 7, wherein:
the ether solvent is tetrahydrofuran;
and/or the Lewis acid is tetraisopropyl titanate;
and/or the reducing agent is polymethylhydrosiloxane;
and/or the reaction temperature is 60-90 ℃;
and/or the reaction time is 12-18 hours;
and/or the molar concentration of the compound shown as the formula II in the organic solvent is 0.1-0.3 mol/L.
9. A compound shown as a formula II in the specification,
Figure FDA0002293015970000031
wherein R is1、R2、R3、R4And is as defined in any one of claims 1 to 4.
10. A process for the preparation of a compound according to claim 9 of formula II, comprising the steps of: under the action of alkali and oxidant in organic solvent under the protection of gas, the compound shown in formula VI and the compound shown in formula VII are reacted as shown in the specification to obtain the compound shown in formula II,
Figure FDA0002293015970000041
wherein R is1、R2、R3、R4And is as defined in claim 9.
11. A process according to claim 10 for the preparation of a compound of formula II:
the organic solvent is an ether solvent;
and/or, the alkali is organic lithium;
and/or, the oxidant is peroxide;
and/or the reaction temperature of the first step is a staged temperature, and the temperature of the first stage is-50 ℃ to-85 ℃; the temperature of the second stage is 10-40 ℃;
and/or the reaction time of the first step is 1-5 hours;
and/or the reaction temperature of the second step is 10-40 ℃;
and/or the reaction time of the second step is 0.5-2 hours;
and/or the protective gas is nitrogen;
and/or the molar concentration of the compound shown in the formula VI in the organic solvent is 0.1-1.0 mol/L;
and/or the molar ratio of the compound shown as the formula VI to the alkali is 1: 1-1: 1.5;
and/or the molar ratio of the compound shown as the formula VI to the oxidant is 1: 10-1: 40;
and/or the molar ratio of the compound shown as the formula VI to the compound shown as the formula VII is 1: 1-1: 1.5.
12. A process according to claim 10 for the preparation of a compound of formula II:
the organic solvent is tetrahydrofuran;
and/or the base is n-butyl lithium, tert-butyl lithium or lithium diisopropylamide;
and/or the oxidant is hydrogen peroxide;
and/or, the reaction temperature of the first step is a staged temperature, and the temperature of the first stage is-78 ℃; and/or, the temperature of the second stage is room temperature;
and/or the reaction time of the first step is 2-4 hours;
and/or, the reaction temperature of the second step is room temperature;
and/or the reaction time of the second step is 0.75-1.5 hours;
and/or the molar concentration of the compound shown in the formula VI in the organic solvent is 0.1-0.5 mol/L;
and/or the molar ratio of the compound shown as the formula VI to the alkali is 1: 1-1: 2;
and/or the molar ratio of the compound shown as the formula VI to the oxidant is 1: 20-1: 30;
and/or the molar ratio of the compound shown as the formula VI to the compound shown as the formula VII is 1: 1-1: 2.
13. A process according to claim 12 for the preparation of a compound of formula II:
the alkali is lithium diisopropylamide;
and/or the reaction time of the first step is 3 hours;
and/or the reaction time of the second step is 1 hour;
and/or the molar concentration of the compound shown in the formula VI in the organic solvent is 0.2-0.3 mol/L;
and/or the molar ratio of the compound shown as the formula VI to the alkali is 1: 1.1;
and/or the molar ratio of the compound shown as the formula VI to the oxidant is 1: 25.4;
and/or the molar ratio of the compound shown in the formula VI to the compound shown in the formula VII is 1: 1.1.
14. A complex comprising the benzazaphosphorine oxygen ligand represented by formula I as described in any one of claims 1 to 4 and a transition metal halide comprising a transition metal and a halogen, wherein the transition metal is one or more of Rh, Ru, Ni, Ir, Pd, Cu, Pt, Co and Au.
15. A complex as claimed in claim 14, wherein:
the halogen is chlorine and bromine.
16. A complex as claimed in claim 15, wherein:
the transition metal is Ni; and/or the halogen is chlorine.
17. A complex as claimed in claim 15, wherein: the transition metal halide is 1.5 hydrated nickel (II) dichloride and/or nickel (II) dichloride.
18. A method for synthesizing acyclic alkylaromatic hydrocarbons, comprising the steps of: under the protection gas and the action of the complex compound of any one of claims 14 to 17, subjecting the compounds shown in the formulas III and IV to Kumada coupling reaction as described below in an organic solvent to obtain a compound shown in the formula V,
Figure FDA0002293015970000061
wherein the content of the first and second substances,
a is substituted or unsubstituted C6-C20Aryl, or substituted or unsubstituted C4-C11A nitrogen-containing heteroaryl group, wherein the number of nitrogen atoms in the nitrogen-containing heteroaryl group is 1, 2 or 3; said "substituted or unsubstituted C6-C20Aryl, or substituted or unsubstituted C4-C11Substituted by halogen, C1-C10Alkyl, halogen substituted C1-C10Alkyl, -CN, -OR9、-NO2、-COR10、-NH2、-COOR11-OTf, hydroxy or phenyl, when a plurality of substituents are present, said substituents being the same or different; said halogen substituted C1-C10In the alkyl group, when a plurality of substituents are present, the substituents may be the same or different;
R9is substituted or unsubstituted C1-C10An alkyl group; said substituted or unsubstituted C1-C10The substitution in alkyl means by halogen, C6-C10Aryl and halogen substituted C6-C10One or more substituents of the aryl group, when a plurality of substituents are present, said substituents being the same or different; said halogen substituted C6-C10In the aryl group, when a plurality of substituents are present, the substituents may be the same or different;
R10is hydrogen or C1-C10Alkyl groups of (a);
R11is C1-C10Alkyl groups of (a);
X1is a leaving group;
R8is tert-butyl;
X2is halogen.
19. The method of synthesizing acyclic alkylaromatic hydrocarbons according to claim 18, wherein:
the organic solvent is an aromatic hydrocarbon solvent and/or an ether solvent;
and/or, the non-cyclic alkyl aromatic hydrocarbon synthesis method, reactants also comprise alkali, and the alkali is R12OM or MOH, wherein, R12Is C1-C4Alkyl groups of (a); m is alkali metal;
and/or the molar concentration of the benzoazaphosphole phosphine oxide ligand in the organic solvent is 0.001-0.1 mol/L;
and/or the molar ratio of the transition metal halide to the benzoazaphosphole phosphine oxide ligand is 0.5: 1-1: 4;
and/or the molar ratio of the compound shown as the formula III to the benzoazaphosphole phosphine oxide ligand is 100: 1-1: 1;
and/or the molar ratio of the compound shown as IV to the benzoazaphosphole phosphine oxide ligand is 300: 1-50: 1;
and/or the protective gas is nitrogen;
and/or the reaction temperature is-70-40 ℃;
and/or the reaction time is 0.5-24 hours;
and/or, when A is substituted or unsubstituted C6-C20When aryl, said C6-C20Aryl is C6-C14An aryl group;
and/or, when A is substituted or unsubstituted C4-C11When containing nitrogen heteroaryl, said C4-C11The nitrogen-containing heteroaryl group of (A) is C5-C9A nitrogen-containing heteroaryl group;
and/or, when said "substituted or unsubstituted C6-C20Aryl, or substituted or unsubstituted C4-C11When the substituent in the nitrogen-containing heteroaryl is halogen, the halogen is fluorine, chlorine, bromine or iodine;
and/or, when said "substituted or unsubstituted C6-C20Aryl, or substituted orUnsubstituted C4-C11The substituent in the nitrogen-containing heteroaryl group is C1-C10When alkyl, said C1-C10Alkyl is C1-C4An alkyl group;
and/or, when said "substituted or unsubstituted C6-C20Aryl, or substituted or unsubstituted C4-C11The substituent of the nitrogen-containing heteroaryl group is a halogen-substituted C1-C10When alkyl, said halogen being substituted by C1-C10C in alkyl1-C10Alkyl is C1-C4Alkyl, halogen is fluorine, chlorine, bromine or iodine;
and/or, when said R is9Is substituted or unsubstituted C1-C10When alkyl, said C1-C10Alkyl is C1-C4An alkyl group;
and/or, when said R is9Is substituted C1-C10When the substituent is halogen, the halogen is fluorine, chlorine, bromine or iodine;
and/or, when said R is9Is substituted C1-C10Alkyl, the substituent being C6-C10When aryl, said C6-C10Aryl is phenyl;
and/or, when said R is9Is substituted C1-C10Alkyl, the substituents being halogen-substituted C6-C10Aryl, said halogen being substituted by C6-C10Halogen in aryl is fluorine, chlorine, bromine or iodine; said halogen substituted C6-C10C in aryl6-C10Aryl is phenyl;
and/or, when said R is10Is C1-C10When alkyl, said C1-C10Alkyl is C1-C4An alkyl group;
and/or, said R11Is C1-C4Alkyl groups of (a);
and/or, said X1F, Cl, Br, OTf, OMs, OTs or OPiv;
and/or, X2Is F, Cl, Br or I.
20. The method of synthesizing acyclic alkylaromatic hydrocarbons according to claim 18, wherein:
the organic solvent is an aromatic hydrocarbon solvent and/or an ether solvent; the aromatic hydrocarbon solvent is toluene; and/or the ether solvent is tetrahydrofuran or anhydrous ether;
and/or, the non-cyclic alkyl aromatic hydrocarbon synthesis method, reactants also comprise alkali, and the alkali is R12OM or MOH, wherein, R12Is tert-butyl or methyl; m is sodium or potassium;
and/or the molar concentration of the benzoazaphosphole phosphine oxide ligand in the organic solvent is 0.015-0.5 mol/L;
and/or the molar ratio of the transition metal halide to the benzoazaphosphole phosphine oxide ligand is 0.75: 1-1: 2;
and/or the molar ratio of the compound shown as the formula III to the benzoazaphosphole phosphine oxide ligand is 20: 1-60: 1;
and/or the molar ratio of the compound shown as IV to the benzoazaphosphole phosphine oxide ligand is 200: 1-100: 1;
and/or the reaction temperature is-20 to 20 ℃;
and/or the reaction time is 1-5 hours;
and/or, when A is substituted or unsubstituted C6-C20When aryl, said C6-C20Aryl is phenyl, naphthyl or anthryl;
and/or, when A is substituted or unsubstituted C4-C11When containing nitrogen heteroaryl, said C4-C11The nitrogen-containing heteroaryl group of (A) is C5-C9Nitrogen-containing heteroaryl, wherein the number of nitrogen atoms is 1;
and/or, when said "substituted or unsubstituted C6-C20Aryl, or substituted or unsubstituted C4-C11When the substituent in the nitrogen-containing heteroaryl is halogen, the halogen is chlorine;
and/or, when said "substituted or unsubstituted C6-C20Aryl, or substituted or unsubstituted C4-C11The substituent in the nitrogen-containing heteroaryl group is C1-C10When alkyl, said C1-C10Alkyl is methyl, ethyl or propyl;
and/or, when said R is9Is substituted or unsubstituted C1-C10When alkyl, said C1-C10Alkyl is methyl;
and/or, when said R is9Is substituted C1-C10Alkyl, the substituents being halogen-substituted C6-C10Aryl, said halogen being substituted by C6-C10Halogen in aryl is fluorine;
and/or, when said R is10Is C1-C10When alkyl, said C1-C10Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl;
and/or, said R11Is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl;
and/or, said X1Br, OTf, OMs, OTs or OPiv;
and/or, X2Is Cl.
21. The method of synthesizing acyclic alkylaromatic hydrocarbons according to claim 20, wherein:
the ether solvent is tetrahydrofuran;
and/or the alkali is potassium tert-butoxide;
and/or the molar concentration of the benzoazaphosphole phosphine oxide ligand in the organic solvent is 0.2-0.3 mol/L;
and/or the reaction temperature is-20 to 0 ℃;
and/or the reaction time is 1-3 hours;
and &Or, when A is substituted or unsubstituted C4-C11When containing nitrogen heteroaryl, A is pyridyl or quinolyl;
and/or, when said R is10Is C1-C10When alkyl, said C1-C10Alkyl is methyl;
and/or, said R11Is methyl or ethyl.
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