CN113845550A - Flexible large-steric-hindrance N-heterocyclic carbene palladium complex containing halogenated benzene ring, and preparation method and application thereof - Google Patents
Flexible large-steric-hindrance N-heterocyclic carbene palladium complex containing halogenated benzene ring, and preparation method and application thereof Download PDFInfo
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- CN113845550A CN113845550A CN202111137193.1A CN202111137193A CN113845550A CN 113845550 A CN113845550 A CN 113845550A CN 202111137193 A CN202111137193 A CN 202111137193A CN 113845550 A CN113845550 A CN 113845550A
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- benzene ring
- heterocyclic carbene
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 title claims abstract description 76
- 229910052763 palladium Inorganic materials 0.000 title claims abstract description 38
- ADLVDYMTBOSDFE-UHFFFAOYSA-N 5-chloro-6-nitroisoindole-1,3-dione Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC2=C1C(=O)NC2=O ADLVDYMTBOSDFE-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 100
- 239000003054 catalyst Substances 0.000 claims abstract description 32
- 230000007306 turnover Effects 0.000 claims abstract description 16
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 14
- 150000004982 aromatic amines Chemical group 0.000 claims abstract description 12
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- AFPRJLBZLPBTPZ-UHFFFAOYSA-N acenaphthoquinone Chemical compound C1=CC(C(C2=O)=O)=C3C2=CC=CC3=C1 AFPRJLBZLPBTPZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- -1 N-heterocyclic carbene palladium complexes Chemical class 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
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- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- 230000009471 action Effects 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 229910052751 metal Inorganic materials 0.000 abstract description 24
- 239000000758 substrate Substances 0.000 abstract description 20
- 230000000694 effects Effects 0.000 abstract description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 14
- 229910052799 carbon Inorganic materials 0.000 abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 12
- 125000004054 acenaphthylenyl group Chemical group C1(=CC2=CC=CC3=CC=CC1=C23)* 0.000 abstract description 4
- 238000011065 in-situ storage Methods 0.000 abstract description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 abstract description 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 29
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- 238000001228 spectrum Methods 0.000 description 24
- 150000001875 compounds Chemical class 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 12
- 229910052739 hydrogen Inorganic materials 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
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- 239000007787 solid Substances 0.000 description 6
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- 125000001424 substituent group Chemical group 0.000 description 5
- NIIJLHLBNABUFL-UHFFFAOYSA-N (4-chlorophenyl) trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=C(Cl)C=C1 NIIJLHLBNABUFL-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 4
- 150000001543 aryl boronic acids Chemical class 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 238000013461 design Methods 0.000 description 4
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- 238000000034 method Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
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- 239000012044 organic layer Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- HXGDTGSAIMULJN-UHFFFAOYSA-N acetnaphthylene Natural products C1=CC(C=C2)=C3C2=CC=CC3=C1 HXGDTGSAIMULJN-UHFFFAOYSA-N 0.000 description 2
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- 239000008204 material by function Substances 0.000 description 2
- 239000012454 non-polar solvent Substances 0.000 description 2
- GNWXVOQHLPBSSR-UHFFFAOYSA-N oxolane;toluene Chemical compound C1CCOC1.CC1=CC=CC=C1 GNWXVOQHLPBSSR-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
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- 238000005406 washing Methods 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- KWVPRPSXBZNOHS-UHFFFAOYSA-N 2,4,6-Trimethylaniline Chemical compound CC1=CC(C)=C(N)C(C)=C1 KWVPRPSXBZNOHS-UHFFFAOYSA-N 0.000 description 1
- WKBALTUBRZPIPZ-UHFFFAOYSA-N 2,6-di(propan-2-yl)aniline Chemical compound CC(C)C1=CC=CC(C(C)C)=C1N WKBALTUBRZPIPZ-UHFFFAOYSA-N 0.000 description 1
- PWRBCZZQRRPXAB-UHFFFAOYSA-N 3-chloropyridine Chemical compound ClC1=CC=CN=C1 PWRBCZZQRRPXAB-UHFFFAOYSA-N 0.000 description 1
- 125000006416 CBr Chemical class BrC* 0.000 description 1
- 125000006414 CCl Chemical class ClC* 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001555 benzenes Chemical group 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- FCYRSDMGOLYDHL-UHFFFAOYSA-N chloromethoxyethane Chemical compound CCOCCl FCYRSDMGOLYDHL-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- IRXRGVFLQOSHOH-UHFFFAOYSA-L dipotassium;oxalate Chemical compound [K+].[K+].[O-]C(=O)C([O-])=O IRXRGVFLQOSHOH-UHFFFAOYSA-L 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
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- 229910052740 iodine Inorganic materials 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000006464 oxidative addition reaction Methods 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- ZOUWOGOTHLRRLS-UHFFFAOYSA-N palladium;phosphane Chemical compound P.[Pd] ZOUWOGOTHLRRLS-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
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- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical group 0.000 description 1
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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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System compounds of the platinum group
- C07F15/006—Palladium compounds
-
- 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
- B01J31/22—Organic complexes
- B01J31/2265—Carbenes or carbynes, i.e.(image)
- B01J31/2269—Heterocyclic carbenes
- B01J31/2273—Heterocyclic carbenes with only nitrogen as heteroatomic ring members, e.g. 1,3-diarylimidazoline-2-ylidenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
- C07B37/04—Substitution
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
- C07C303/30—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reactions not involving the formation of esterified sulfo groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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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
- B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
- B01J2231/4211—Suzuki-type, i.e. RY + R'B(OR)2, in which R, R' are optionally substituted alkyl, alkenyl, aryl, acyl and Y is the leaving group
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- 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
- B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
- B01J2231/4211—Suzuki-type, i.e. RY + R'B(OR)2, in which R, R' are optionally substituted alkyl, alkenyl, aryl, acyl and Y is the leaving group
- B01J2231/4227—Suzuki-type, i.e. RY + R'B(OR)2, in which R, R' are optionally substituted alkyl, alkenyl, aryl, acyl and Y is the leaving group with Y= Cl
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- 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 relates to a flexible N-heterocyclic carbene palladium complex with large steric hindrance, which contains a halogenated benzene ring. The complex is characterized in that: (1) the acenaphthylene group is used as a skeleton structure, and the excellent electron donating performance and the rigidity steric hindrance of the acenaphthylene group are utilized, so that the metal center can be stabilized, and the high stability of the catalyst in the presence of air and water vapor is ensured; (2) the aromatic amine part of the N-heterocyclic carbene is introduced with flexible large steric hindrance, so that the metal center has certain openness, the structure of the active center can be changed under different reaction conditions by the metal center, and completely different active species can be generated in situ, thereby realizing the selective turnover of different carbon (pseudo) halogen bonds by only adding one catalyst; (3) the catalyst has wide substrate adaptability range and high activity on heterocyclic poly (pseudo) halogenated aromatic hydrocarbon, and the reaction based on the catalyst does not need to isolate air and water vapor and can realize high reaction activity under mild reaction conditions.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a flexible high-steric-hindrance N-heterocyclic carbene palladium complex containing a halogenated benzene ring, and a preparation method and application thereof.
Background
In the past decades, there have been many C' sAr-CArBond and CArThe compound of the-X bond has been widely used in the fields of medicines, pesticides, functional materials and the like, and the development of chemoselective synthesis reaction is also an important research. Up to now, the palladium-catalyzed Suzuki-Miyaura coupling reaction has become the construction C due to the characteristics of good functional group tolerance, low toxicity and the likeAr-CArBond and CAr-heteroatom bonding efficient methods. However, when the Suzuki-Miyaura reaction catalyzes multi (pseudo) halogenated compounds (such as C-I, C-Br, C-Cl and C-OTf bonds), the defects of poor chemical selectivity, poor substrate adaptability, harsh reaction conditions and the like are often faced, so that the development of a high-efficiency chemical selectivity catalytic system is very important work.
Currently, there are two strategies for achieving chemoselective cross-coupling reactions: one is to use catalysts of different structures to achieve selective reactions by their differences in activity towards the substrate (J)Am. chem soc.2010,132, 2496-2497; nat.chem.2016,8, 610-617; chem.2019,84, 11474-11481; chem.2019,84, 11799-11812; J.am.chem.Soc.2020,142, 15454-15463; ). This strategy is expensive due to the need to design catalysts of different structures, thus limiting the widespread use of this strategy. Yet another strategy is to design a single catalyst, and the shift of the selective reaction can be achieved by merely changing the reaction conditions such as reaction solvent, reaction temperature, or additives. (Angew. chem. int. Ed.2011,50, 8192-. The latter is a significant advantage since it allows the efficient construction of complex functional molecules with only a single catalyst. However, to date, only a few catalytic systems have been available, such as Pd2(dba)3/P(tBu)3And monovalent palladium dimer [ (P)tBu3)PdBr]2"selective inversion" of C-Cl bonds and C-OTf bonds using only a single catalyst is achieved (Angew. chem. int. Ed.2011,50, 8192-. Although the above palladium catalysts containing phosphine ligands exhibit good chemoselectivity, they are sensitive to air and water vapor, unstable in solution, and are very low in activity for nitrogen-containing heterocyclic haloaromatics to react with heterocyclic arylboronic acids. Thus, the use of the above-mentioned catalysts is greatly limited. Based on this problem, there is a need to develop a new catalyst to solve the above-mentioned challenges.
Disclosure of Invention
Aiming at the defects of the catalytic system, the invention designs and synthesizes a flexible N-heterocyclic carbene palladium complex with large steric hindrance and containing a halogenated benzene ring, which has the advantages of convenient synthesis, mild reaction conditions and wide substrate applicability, and can realize the turnover of selective coupling reaction by changing the specific reaction conditions. Therefore, the invention meets the economic requirements of organic chemistry, medicine and material synthesis, and the non-phosphine palladium catalyst developed on the basis provides a new idea for catalyst design.
The invention discloses a flexible large steric hindrance N-heterocyclic carbene palladium complex containing a halogenated benzene ring, which is characterized in that: (1) the electronic effect of the halogen atom is utilized to adjust the nucleophilicity of the metal center, so that the metal center can meet the electronic effect requirement of the metal center on the selectivity of the electrophilic reagent under the reaction condition, and the reaction has excellent selectivity; (2) the acenaphthylene or the derivative thereof is used as a skeleton structure, and the excellent electron donating performance and the rigidity steric hindrance of the acenaphthylene or the derivative thereof are utilized, so that the metal center can be stabilized, and the catalyst is ensured to keep high stability in the presence of air and water vapor; (3) the aromatic amine part of the N-heterocyclic carbene is introduced with flexible large steric hindrance, so that the metal center has certain openness, the structure of the active center can be changed under different reaction conditions by the metal center, and completely different active species can be generated in situ, thereby realizing the selective turnover of different carbon (pseudo) halogen bonds by only adding one catalyst; (4) the catalyst has wide substrate adaptability range and high activity on heterocyclic poly (pseudo) halogenated aromatic hydrocarbon, and the reaction based on the catalyst does not need to isolate air and water vapor and can realize high reaction activity under mild reaction conditions.
In the present invention, the term "Suzuki-Miyaura coupling turnover reaction" refers to the situation where two (pseudo) halogen electrophilic substituent groups (X) with different activities exist in the same electrophile in the Suzuki-Miyaura coupling reaction1And X2) When reacting with arylboronic acid (ester), under certain conditions, one (pseudo) halogen electrophilic substituent group X can promote high selectivity reaction1And another substituent X2Does not participate in the reaction. When the reaction conditions are changed, the selectivity of the coupling reaction is reversed, in which case the (pseudo) halogen electrophilic substituent group X2Coupling with arylboronic acids (esters) to substituents X1It does not participate in the reaction.
One object of the invention is to provide a flexible large steric hindrance N-heterocyclic carbene palladium complex containing a halogenated benzene ring, which is represented by the following structural general formula:
wherein the content of the first and second substances,
R1-R3independently selected from hydrogen atom, halogen, C1-C22 alkyl or C1-C22 alkoxyA group;
R4-R6independently selected from C1-C22, aryl or aryl derivatives;
y is selected from halogen or carboxyl;
X1-X2selected from halogens;
X3selected from hydrogen atoms or halogens.
Further, said X1-X2Is a fluorine atom.
Further, said R4-R6Selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, aryl or aryl derivatives.
Further, said R6Selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or tert-butyl.
Further, R1-R3Is a hydrogen atom.
Further, the flexible large steric hindrance N-heterocyclic carbene palladium complex containing the halogenated benzene ring is selected from the following structures:
the invention also aims to provide a preparation method of the flexible large-steric-hindrance N-heterocyclic carbene palladium complex containing the halogenated benzene ring, which comprises the following steps:
dissolving acenaphthenequinone or derivatives thereof and halogenated arylamine in a solvent, and heating to react under the action of a catalyst to obtain a precursor containing a halogenated benzene ring.
Specifically, under the condition of inert gas, acenaphthenequinone or derivatives thereof and halogenated arylamine are dissolved in a solvent in a catalyst system, then heating reflux reaction is carried out for a specified time, the obtained intermediate product is washed by a solution, reduced pressure distillation is carried out to remove the solvent, and finally a high-purity precursor containing halogenated benzene rings is obtained in a recrystallization mode to obtain the alpha-diimine compound.
Further, the structure of the acenaphthenequinone or the derivative thereof is as follows:
further, the catalyst is a transition metal halide, preferably anhydrous zinc chloride.
The invention also aims to provide the application of the flexible large-steric-hindrance N-heterocyclic carbene palladium complex containing the halogenated benzene ring in Suzuki-Miyaura coupling turnover reaction.
Further, the reaction conditions of the Suzuki-Miyaura coupling turnover reaction are as follows:
reaction conditions A: the solvent is a mixed solvent of THF and DMAc;
or
Reaction conditions B: the solvent is a mixed solvent of THF and toluene.
The invention has the following beneficial effects:
(1) the flexible high-steric-hindrance N-heterocyclic carbene palladium complex containing the halogenated benzene ring is used as a catalyst, is applied to selective Suzuki-Miyaura coupling overturning reaction, and utilizes the electronic effect of halogen atoms to adjust the nucleophilicity of a metal center, so that the metal center can meet the electronic effect requirements of the metal center on different electrophilic reagent selectivities under different reaction conditions, and the reaction has excellent selectivity.
(2) The catalyst of the invention introduces flexible large steric hindrance at the arylamine part of the N-heterocyclic carbene, so that the metal center has good openness, thereby enabling the metal center to change the structure of the active center under different reaction conditions and generating completely different active species in situ. For example, in a polar coordination solvent, due to the flexible large steric hindrance of the metal center, solvent molecules can be allowed to participate in the coordination of the metal center, so that the nucleophilicity of the metal center is increased, and carbon-pseudohalogen bonds (such as C-OTf bonds) can be selectively reacted; in non-polar solvents, however, the electronic effect of the metal center is relatively weak and it can only selectively react carbon-halogen bonds (e.g., C-Cl bonds). Thereby enabling the highly selective inversion of the reaction of C-Cl bonds with arylboronic acids, or of C-OTf bonds with arylboronic acids, simply by adding a single catalyst.
(3) The Suzuki-Miyaura coupling turnover reaction has mild reaction conditions, can be carried out under the conditions of air, water and the like, has higher reaction yield, can be used for preparing and synthesizing polyaryl substituted bioactive molecules and functional materials, and has wide commercial prospect.
Drawings
FIG. 1(a) shows a nuclear magnetic hydrogen spectrum of Compound 7; fig. 1(b) shows the nuclear magnetic carbon spectrum of compound 7.
FIG. 2(a) shows a nuclear magnetic hydrogen spectrum of Compound 8; fig. 2(b) shows the nuclear magnetic carbon spectrum of compound 8.
FIG. 3(a) shows a nuclear magnetic hydrogen spectrum of Compound 9; fig. 3(b) shows the nuclear magnetic carbon spectrum of compound 9.
FIG. 4(a) shows a nuclear magnetic hydrogen spectrum of the complex 10; fig. 4(b) shows the nuclear magnetic carbon spectrum of the complex 10.
FIG. 5(a) shows a nuclear magnetic hydrogen spectrum of complex 11; fig. 5(b) shows the nuclear magnetic carbon spectrum of the complex 11.
FIG. 6(a) shows a nuclear magnetic hydrogen spectrum of complex 12; fig. 6(b) shows the nuclear magnetic carbon spectrum of the complex 12.
FIG. 7 shows a single crystal structural diagram of the complex 10.
Detailed Description
The invention is further described with reference to the drawings and the following detailed description, which are not intended to limit the invention in any way. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated.
In the embodiment of the invention, the preparation methods of the flexible and highly hindered N-heterocyclic carbene palladium complex 10-12 (complex 10-12) containing halogenated benzene rings as the final product are independently carried out without interfering with each other. In this example, for the purpose of simple illustration only, the preparation methods of the N-heterocyclic carbene palladium complex 10-12 with similar preparation conditions are all described in the same example; but not mean that three products of flexible high-steric-hindrance N-heterocyclic carbene palladium complex 10-12 containing halogenated benzene rings can be obtained simultaneously in the same experiment.
Similarly, in the embodiments of the present invention, the reaction substrates and the raw materials in the steps are independently performed without interfering with each other. For example, in the examples, "halogenated aromatic amine 1 to 3" means that in three separate experiments which do not interfere with each other, halogenated aromatic amine 1, halogenated aromatic amine 2 and halogenated aromatic amine 3 are taken as reaction substrates, respectively, and it does not mean that in the same experiment, halogenated aromatic amines 1 to 3 are simultaneously added as reaction substrates.
Example 1
The chemical synthetic route of the flexible large steric hindrance N-heterocyclic carbene palladium complex containing the halogenated benzene ring is shown as follows.
(1) Synthesis of alpha-diimine Compound 4-6 (Compound 4-6)
In the presence of nitrogen protection, acenaphthenequinone (10.0mmol), halogenated arylamine 1-3(20.0mmol) and anhydrous zinc chloride (20.0mmol) are sequentially added into a 100mL flask, 40mL of glacial acetic acid is added, and the reactants are heated and refluxed for 5 hours and then cooled to room temperature. Filtration gave an orange solid which was then washed with a small amount of glacial acetic acid and dried in vacuo. The resulting orange solid was dissolved in 200mL of dichloromethane, and an aqueous potassium oxalate solution was added thereto and stirred for 12 hours. The white solid precipitate was removed, and after separation, the organic layer was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give a crude product, which was then recrystallized from methylene chloride and ethanol to give the product α -diimine compound 4-6 (yield 63-75%).
(2) Synthesis of imidazole salt intermediate 7-9 (Compound 7-9)
Under the protection of nitrogen, 4-6(1mmol) of alpha-diimine compound and 3mL of chloromethyl ethyl ether are added into a thick-wall bottle with a mouth, the mixture is cooled to room temperature after being sealed and reacted for 24 hours at 100 ℃, 20mL of anhydrous ethyl ether is added to be stirred vigorously to generate a large amount of yellow powder, the washing is repeated for three times, and the product, namely the imidazole salt intermediate 7-9, is obtained after the filtration.
The yield of compound 7 was 65%. FIG. 1(a) shows a nuclear magnetic hydrogen spectrum of Compound 7; fig. 1(b) shows the nuclear magnetic carbon spectrum of compound 7.
1H NMR(400MHz,CDCl3)δ12.16(s,1H),7.85(d,J＝8.2Hz,2H),7.41(t,J＝7.5Hz,2H),7.28(s,6H),7.26(s,2H),7.20(s,2H),7.09(d,J＝6.9Hz,2H),6.93(d,J＝6.8Hz,2H),6.82–6.71(m,8H),6.65(dd,J＝14.8,8.0Hz,4H),5.84(s,2H),2.21(s,6H).13C NMR(101MHz,CDCl3)δ164.7,162.2,144.2,140.7,140.5,138.1,136.4,129.8,129.8,129.0,128.9,128.3,127.4,127.2,126.6,122.7,122.6,117.1,116.9,116.7,51.6,18.9.
The yield of compound 8 was 66%. FIG. 2(a) shows a nuclear magnetic hydrogen spectrum of Compound 8; fig. 2(b) shows the nuclear magnetic carbon spectrum of compound 8.
1H NMR(400MHz,CDCl3)δ11.90(s,1H),7.87(dd,J＝18.9,8.3Hz,3H),7.41–7.35(m,3H),7.09(t,J＝7.7Hz,8H),7.00(d,J＝7.7Hz,2H),6.94(d,J＝7.8Hz,2H),6.83(t,J＝6.8Hz,3H),6.71(dd,J＝9.3,2.5Hz,2H),6.63(s,5H),6.47(d,J＝7.8Hz,3H),5.63(s,1H),5.31(s,1H),2.27(d,J＝9.1Hz,12H),2.18(s,3H),1.75(s,3H).13C NMR(101MHz,CDCl3)δ164.7,162.3,162.2,144.9,144.8,144.2,144.1,143.0,138.6,138.5,138.1,138.0,137.8,137.8,137.7,137.5,136.8,136.6,136.6,136.5,136.2,129.8,129.7,129.4,129.2,129.1,128.9,128.9,128.0,127.5,127.2,122.7,122.3,117.3,117.0,116.8,116.6,116.4,116.2,116.0,51.1,21.0,20.9,20.6,20.4,18.7,18.5.
The yield of compound 9 was 74%. FIG. 3(a) shows a nuclear magnetic hydrogen spectrum of Compound 9; fig. 3(b) shows the nuclear magnetic carbon spectrum of compound 9.
1H NMR(400MHz,CDCl3)δ11.52(s,1H),7.31(d,J＝7.5Hz,5H),7.21(d,J＝7.2Hz,4H),7.16(d,J＝7.4Hz,2H),7.04(d,J＝7.6Hz,4H),6.98(s,2H),6.93(d,J＝6.6Hz,4H),6.65(d,J＝9.0Hz,1H),6.60(d,J＝9.1Hz,2H),6.53(s,1H),6.44(s,2H),5.59(s,2H),5.39(s,1H),2.22(d,J＝13.2Hz,12H).13C NMR(101MHz,CDCl3)δ142.3,142.2,141.6,141.4,139.9,139.7,135.1,134.9,131.0,130.7,130.2,129.8,129.6,129.3,128.8,128.6,127.2,127.0,126.9,124.2,51.4,21.4,18.0.
(3) Synthesis of flexible large steric hindrance N-heterocyclic carbene palladium complex 10-12 containing halogenated benzene ring
Imidazole salt intermediate 7-9(1mmol), palladium chloride (1.1mmol), potassium carbonate (10mmol), and 3mL of 3-chloropyridine were sequentially added to a 25mL thick-walled vial. Reacting at 90 ℃ for 24 hours under the protection of nitrogen, and cooling the reaction to room temperature. The obtained reaction solution was subjected to flash dry-column chromatography with dichloromethane, and the solvent was removed under reduced pressure to obtain a solid. The solid obtained was dissolved with dichloromethane and then precipitated with a large amount of n-hexane until a solid powder precipitated. And finally, repeatedly washing the product with normal hexane for three times, and performing suction filtration and drying to obtain the flexible high-steric-hindrance N-heterocyclic carbene-palladium complex 10-12 containing the halogenated benzene ring.
The yield of complex 10 was 48%. FIG. 4(a) shows a nuclear magnetic hydrogen spectrum of the complex 10; fig. 4(b) shows the nuclear magnetic carbon spectrum of the complex 10.
1H NMR(400MHz,CDCl3)δ9.09(d,J＝2.2Hz,1H),8.94(d,J＝4.7Hz,1H),7.78(d,J＝8.2Hz,1H),7.53(d,J＝8.3Hz,2H),7.43(d,J＝6.9Hz,4H),7.32(dd,J＝8.1,5.7Hz,2H),7.27(dd,J＝8.8,5.7Hz,8H),7.17–7.12(m,2H),7.03(dd,J＝8.6,2.8Hz,2H),6.94(d,J＝7.4Hz,4H),6.75(dd,J＝9.6,2.8Hz,2H),6.59(t,J＝7.6Hz,4H),6.48(d,J＝6.9Hz,2H),6.42(t,J＝7.4Hz,2H),2.29(s,6H).13C NMR(101MHz,CDCl3)δ163.9,161.4,154.8,150.7,149.4,145.6,145.5,142.9,140.9,140.2,140.1,138.6,138.0,132.6,132.5,130.0,129.3,128.5,128.4,127.7,127.6,126.5,126.4,124.8,124.6,120.7,116.3,116.1,116.0,115.8,50.9,19.9.
FIG. 7 shows a single crystal structural diagram of the complex 10.
The yield of complex 11 was 46%. FIG. 5(a) shows a nuclear magnetic hydrogen spectrum of complex 11; fig. 5(b) shows the nuclear magnetic carbon spectrum of the complex 11.
1H NMR(400MHz,CDCl3)δ9.05(d,J＝2.2Hz,1H),8.91(dd,J＝5.5,1.1Hz,1H),7.77(ddd,J＝8.2,2.1,1.3Hz,1H),7.54(d,J＝8.2Hz,2H),7.32(d,J＝7.8Hz,5H),7.15(dd,J＝8.2,7.1Hz,2H),7.08(d,J＝7.9Hz,4H),7.02(dd,J＝8.5,2.7Hz,2H),6.97(s,2H),6.79(dd,J＝9.7,2.8Hz,2H),6.75(d,J＝7.9Hz,4H),6.41(d,J＝6.9Hz,2H),6.32(d,J＝7.8Hz,4H),2.38(s,6H),2.33(s,6H),1.58(s,2H),1.56(s,6H).13C NMR(101MHz,CDCl3)δ163.9,161.4,155.1,150.7,149.4,146.5,146.5,140.1,140.0,139.7,138.6,138.1,137.9,135.9,135.3,132.5,132.4,132.4,129.8,129.3,128.4,127.2,126.3,124.8,124.3,120.8,116.1,115.9,115.7,115.4,50.2,21.0,20.3,20.1.
The yield of complex 12 was 39%. FIG. 6(a) shows a nuclear magnetic hydrogen spectrum of complex 12; fig. 6(b) shows the nuclear magnetic carbon spectrum of the complex 12.
1H NMR(400MHz,CDCl3)δ8.83(s,1H),8.71(d,J＝5.5Hz,1H),7.74(dd,J＝15.6,7.8Hz,6H),7.66(d,J＝8.1Hz,1H),7.40(t,J＝7.6Hz,2H),7.26–7.16(m,8H),6.94(d,J＝6.9Hz,2H),6.88(d,J＝7.3Hz,2H),6.50(d,J＝9.5Hz,2H),5.60(d,J＝7.0Hz,2H),2.22(s,6H),1.29(d,J＝7.1Hz,6H).13C NMR(101MHz,CDCl3)δ164.2,161.7,157.4,150.6,149.5,148.6,148.5,143.6,139.8,139.7,139.6,137.9,132.3,131.5,129.8,129.3,129.0,128.7,128.0,127.9,126.5,125.4,124.6,121.1,116.0,115.8,114.4,114.2,38.8,20.7,19.6.
Test example 1
To test the effect of the flexible, highly sterically hindered N-heterocyclic carbene palladium complex 10-12 containing a halogenated benzene ring on the Suzuki-Miyaura coupling inversion reaction, the following experiment was set up.
In parallel reactors, 4-chlorophenyl triflate (1.0mmol), p-methylphenylboronic acid (1.1mmol), a variable substrate (catalytic amount), potassium carbonate (2.0mmol) were added in this order. Wherein, the flexible N-heterocyclic carbene palladium complex with large steric hindrance and containing halogenated benzene rings is provided with a plurality of groups of parallel experiments.
And two different sets of reaction conditions were set:
reaction conditions A: THF DMAc ═ 1: 1; water as additive, reaction temperature: 80 ℃; reaction time: and 4 h.
Reaction conditions B: toluene THF ═ 19: 1; water as additive, reaction temperature: 100 ℃; reaction time: and 4 h.
And (3) post-treatment process: after the reaction time was reached, the reaction was cooled to room temperature, transferred to a separatory funnel, and extracted with ethyl acetate. Drying the organic layer with anhydrous sodium sulfate to remove water, rotary evaporating to remove solvent, separating and purifying with thin layer silica gel plate to determine yield, and purifying the product1H NMR and13c NMR characterization to confirm the coupled product structure.
Wherein, the variable substrates in the reaction are respectively selected from flexible large steric hindrance N-heterocyclic carbene palladium complex 10-12 containing halogenated benzene ring, and commercialized catalysts Pd-PEPSI-IMes (contrast 1) and Pd-PEPSI-IPr (contrast 2). All of the above variable substrates were added to parallel tubes and parallel experiments were performed.
The chemical equation for the parallel experiment is shown below:
the above chemical equation shows that after the 4-chlorophenyl trifluoromethanesulfonate and the p-methylphenylboronic acid are subjected to the Suzuki-Miyaura coupling turnover reaction under the reaction condition A or the reaction condition B, the final product is a mixture which contains both the products M1 and M2. However, the proportions of M1 and M2 produced were different depending on the reaction conditions.
The expected result is that the abovementioned Suzuki-Miyaura coupling turnover reaction is highly selective, i.e. depending on the reaction conditions selected (reaction conditions a/reaction conditions B), wherein one of the products M1 or M2 exhibits a clearly advantageous yield.
In general, it is well known to those skilled in the art that the Suzuki-Miyaura coupling turnover reaction is considered to be highly selective when the molar ratio of the product with a significantly dominant yield to the product with a non-dominant yield is greater than 10:1, out of the two products.
In the above parallel experiment, the molar ratios of M1 and M2 formed for different variables of substrate under reaction conditions A and B, respectively, are shown in Table 1.
TABLE 1 molar ratio of product M1 to M2 (M1/M2) after reaction with reaction conditions A/B under varying substrate conditions
As can be seen from the above table, the reaction results show a high selectivity when complexes 10-12 are used as variable substrates in a Suzuki-Miyaura coupling turnover reaction. Namely: whether reaction condition A or reaction condition B is adopted, the molar ratio of the products M1 and M2 with the dominant yield to the products with the non-dominant yield can be maintained at 10/1 or above, and the individual results are even close to 100/1, so that the reaction selectivity is remarkable. All of the above data meet the criteria of high selectivity.
However, the product obtained did not fully exhibit high selectivity when the reaction conditions were changed, in either case of control 1 or control 2, which acted as variable substrates in the Suzuki-Miyaura conjugate turnover reaction: for example, in control 1, the molar ratio of the product with the predominant yield to the product with the non-predominant yield was only 3/4 for reaction condition B, while in control 2, the molar ratio of the product with the predominant yield to the product with the non-predominant yield was only 59/25 for reaction condition A. The above two results, with highly selective ideal results, are all far apart. This indicates that control 1 and control 2 did not achieve the desired results.
The reason for the above results is that the aromatic amine part in the catalyst in the complex 10-12 has flexibility and great steric hindrance and has good space openness. They allow the solvent molecule DMAc to participate in the coordination under the reaction conditions A of the polar coordinating solvent. Such a dual ligand (L)1L2) Pd active centerThe nucleophilic ability of palladium metal is enhanced, resulting in high selectivity for the oxidative addition of C-OTf. In the case of the reaction condition B of the nonpolar solvent, the electron donating ability of the metal center can be weakened due to the electron withdrawing effect of the fluorine atom, so that the palladium metal center can only selectively react with the C-Cl bond. Therefore, the coupling reaction can be reversed by only using a single catalyst and changing the reaction conditions.
In contrast, since the arylamine moiety of commercial control 1(Pd-PEPPSI-IMes) is 2,4, 6-trimethylaniline, its axial steric hindrance is small, and the degree of protection of the metal center is insufficient, the metal center is susceptible to deactivation under the low-polarity reaction condition B. Whereas for commercial control 2 (Pd-PEPSI-IPr), it is highly sterically hindered in the axial position of the metal center due to its arylamine moiety being 2, 6-diisopropylaniline. When in the polar coordination solvent reaction condition A, the large steric hindrance prevents the solvent molecule from participating in coordination, thereby resulting in low selectivity of C-OTf and C-Cl bonds.
Test example 2
Based on the results of test example 1, we further set up parallel experiments for expanding the screening range of the reaction substrates; and carrying out arrangement statistics on the molar ratio of the product with the dominant yield to the product with the non-dominant yield in the obtained products.
Variable substrate only N-heterocyclic carbene palladium complex 10 was selected and tested for its effect in Suzuki-Miyaura coupled flip reactions. The parallel experimental setup was as follows:
in a parallel reactor, 4-chlorophenyl trifluoromethanesulfonate (1.0mmol), a phenylboronic acid derivative (1.1mmol), N-heterocyclic carbene-palladium complex 10 (catalytic amount), and potassium carbonate (2.0mmol) were added in this order. Among them, the phenylboronic acid derivatives have several specific structures, as shown in table 2.
Two different sets of reaction conditions were set:
reaction conditions A: THF DMAc ═ 1: 1; water as additive, reaction temperature: 80 ℃; reaction time: and 4 h.
Reaction conditions B: toluene THF ═ 19: 1; water as additive, reaction temperature: 100 ℃; reaction time: and 4 h.
And (3) post-treatment process: after the reaction time was reached, the reaction was cooled to room temperature, transferred to a separatory funnel, and extracted with ethyl acetate. Drying the organic layer with anhydrous sodium sulfate to remove water, rotary evaporating to remove solvent, separating and purifying with thin layer silica gel plate to determine yield, and purifying the product1H NMR and13c NMR characterization to confirm the coupled product structure.
The chemical equation for the parallel experiment is shown below:
the above chemical equation shows that after the 4-chlorophenyl trifluoromethanesulfonate and the phenylboronic acid derivative are subjected to Suzuki-Miyaura coupling turnover reaction under the reaction condition A or the reaction condition B, the final product is a mixture which contains the products M3 and M4. However, the proportions of M3 and M4 produced are different depending on the reaction substrate, phenylboronic acid derivative, and the reaction conditions. Table 2 shows the molar ratio of the products M3 to M4 in the total amount of the products obtained by reacting the complex 10 as a catalyst under reaction conditions A/B under different phenylboronic acid derivatives.
Table 2 shows the molar ratios of the products M3 to M4 in the product total indicated in parentheses after reaction of complex 10 as catalyst under different phenylboronic acid derivatives under reaction conditions A/B.
As is clear from Table 2, when the N-heterocyclic carbene palladium complex 10 is used as a catalyst, the final molar ratios of M3 and M4 obtained are both greater than 30/1 or more depending on the reaction substrate. Therefore, the complex 10 has flexibility and large steric hindrance, can realize the selective turnover of a single catalyst to C-OTf bonds and C-Cl bonds by changing reaction conditions, and has high selectivity. Meanwhile, the reaction condition is mild, and the defects of poor substrate adaptability, low yield and the like reported in the literature are overcome.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
Furthermore, it should be understood that although the present description refers to embodiments, not every embodiment may contain only a single embodiment, and such description is for clarity only, and those skilled in the art should integrate the description, and the embodiments may be combined as appropriate to form other embodiments understood by those skilled in the art.
Claims (10)
1. The flexible large steric hindrance N-heterocyclic carbene palladium complex containing a halogenated benzene ring is characterized in that the flexible large steric hindrance N-heterocyclic carbene palladium complex containing the halogenated benzene ring is represented by the following structural general formula:
wherein the content of the first and second substances,
R1-R3independently selected from hydrogen atom, halogen, alkyl of C1-C22 or alkoxy of C1-C22;
R4-R6independently selected from alkyl, aryl or aryl derivatives of C1-C22;
y is selected from halogen or carboxyl;
X1-X2selected from halogens;
X3selected from hydrogen atoms or halogens.
2. The flexible, bulky-hindered N-heterocyclic carbene palladium complex comprising a halogenated benzene ring according to claim 1, wherein X is1-X2Is a fluorine atom.
3. The flexible bulky N-heterocyclic carbene palladium complex containing halogenated benzene ring according to claim 1, wherein R is4-R6Selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, aryl or aryl derivatives.
4. The flexible bulky N-heterocyclic carbene palladium complex containing halogenated benzene ring according to claim 1, wherein R is6Selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or tert-butyl.
5. The flexible, bulky and hindered N-heterocyclic carbene palladium complex comprising a halogenated benzene ring according to claim 1, wherein R is1-R3Is a hydrogen atom.
6. The flexible bulky N-heterocyclic carbene palladium complex comprising a halogenated benzene ring according to claim 5, wherein the flexible bulky N-heterocyclic carbene palladium complex comprising a halogenated benzene ring is selected from the following structures:
7. the preparation method of the flexible large steric hindrance N-heterocyclic carbene palladium complex containing a halogenated benzene ring according to any one of claims 1 to 6, characterized in that the preparation method of the flexible large steric hindrance N-heterocyclic carbene palladium complex containing a halogenated benzene ring comprises the following steps:
dissolving acenaphthenequinone or derivatives thereof and halogenated arylamine in a solvent, and heating to react under the action of a catalyst to obtain a precursor containing a halogenated benzene ring.
8. The preparation method of the flexible large steric hindrance N-heterocyclic carbene palladium complex containing the halogenated benzene ring according to claim 7, wherein the acenaphthenequinone or the derivative thereof has a structure of:
9. use of the flexible, bulky N-heterocyclic carbene palladium complexes containing a halogenated benzene ring as claimed in any of claims 1 to 6 in Suzuki-Miyaura coupling flip reactions.
10. The application of the flexible large steric hindrance N-heterocyclic carbene palladium complex containing the halogenated benzene ring in Suzuki-Miyaura coupling turnover reaction according to claim 9, wherein the reaction conditions of the Suzuki-Miyaura coupling turnover reaction are as follows:
reaction conditions A: the solvent is a mixed solvent of THF and DMAc;
or
Reaction conditions B: the solvent is a mixed solvent of THF and toluene.
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| CN109776422A (en) * | 2017-11-15 | 2019-05-21 | 中国科学院上海有机化学研究所 | Chiral 1,3- diaryl imidazole salt carbene precursor, its synthetic method, metal salt complex and application |
| CN109794295A (en) * | 2019-02-20 | 2019-05-24 | 中国科学院兰州化学物理研究所 | A kind of acenaphthene imidazole base N-heterocyclic carbine metal palladium complex catalyst and its preparation and application |
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| CN109776422A (en) * | 2017-11-15 | 2019-05-21 | 中国科学院上海有机化学研究所 | Chiral 1,3- diaryl imidazole salt carbene precursor, its synthetic method, metal salt complex and application |
| CN109794295A (en) * | 2019-02-20 | 2019-05-24 | 中国科学院兰州化学物理研究所 | A kind of acenaphthene imidazole base N-heterocyclic carbine metal palladium complex catalyst and its preparation and application |
Non-Patent Citations (2)
| Title |
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| EMILY K. REEVES 等: "N Heterocyclic Carbene Ligand-Controlled Chemodivergent Suzuki−Miyaura Cross Coupling", J. ORG. CHEM., no. 84, pages 11799 * |
| JIA-SHENG OUYANG 等: "The Highly Efficient Suzuki–Miyaura Cross-Coupling of (Hetero)aryl Chlorides and (Hetero)arylboronic Acids Catalyzed by "Bulky-yet-Flexible" Palladium–PEPPSI Complexes in Air", CHEMCATCHEM, no. 10, pages 371 - 375 * |
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