CN105541925B - Ferrocene frame having ferrocene frame N, N ligand and its preparation method and application - Google Patents
Ferrocene frame having ferrocene frame N, N ligand and its preparation method and application Download PDFInfo
- Publication number
- CN105541925B CN105541925B CN201610040998.7A CN201610040998A CN105541925B CN 105541925 B CN105541925 B CN 105541925B CN 201610040998 A CN201610040998 A CN 201610040998A CN 105541925 B CN105541925 B CN 105541925B
- Authority
- CN
- China
- Prior art keywords
- ferrocene
- ligand
- frame
- ferrocene frame
- chirality
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 title claims abstract description 44
- 239000003446 ligand Substances 0.000 title claims abstract description 38
- 229910052757 nitrogen Inorganic materials 0.000 title claims description 38
- 238000002360 preparation method Methods 0.000 title claims description 23
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
- -1 nitro, hydroxyl Chemical group 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 5
- 230000000694 effects Effects 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 3
- 238000006884 silylation reaction Methods 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 11
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
- 229910052763 palladium Inorganic materials 0.000 claims description 5
- 230000009471 action Effects 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 3
- GPRSOIDYHMXAGW-UHFFFAOYSA-N cyclopenta-1,3-diene cyclopentanecarboxylic acid iron Chemical compound [CH-]1[CH-][CH-][C-]([CH-]1)C(=O)O.[CH-]1C=CC=C1.[Fe] GPRSOIDYHMXAGW-UHFFFAOYSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- ZPQOPVIELGIULI-UHFFFAOYSA-N 1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1 ZPQOPVIELGIULI-UHFFFAOYSA-N 0.000 claims description 2
- 150000001414 amino alcohols Chemical class 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 235000019256 formaldehyde Nutrition 0.000 claims description 2
- 238000006138 lithiation reaction Methods 0.000 claims description 2
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims 1
- 238000006482 condensation reaction Methods 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 72
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 239000007787 solid Substances 0.000 description 23
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 238000005187 foaming Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 7
- 235000004237 Crocus Nutrition 0.000 description 6
- 241000596148 Crocus Species 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 238000006555 catalytic reaction Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229940125904 compound 1 Drugs 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
- LGZXYFMMLRYXLK-UHFFFAOYSA-N mercury(2+);sulfide Chemical compound [S-2].[Hg+2] LGZXYFMMLRYXLK-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 241000675108 Citrus tangerina Species 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- 229910013594 LiOAc Inorganic materials 0.000 description 1
- 241000736199 Paeonia Species 0.000 description 1
- 235000006484 Paeonia officinalis Nutrition 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- PYHXGXCGESYPCW-UHFFFAOYSA-N alpha-phenylbenzeneacetic acid Natural products C=1C=CC=CC=1C(C(=O)O)C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000037429 base substitution Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940045348 brown mixture Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- AXVOAMVQOCBPQT-UHFFFAOYSA-N triphos Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 AXVOAMVQOCBPQT-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic Table
-
- 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
- B01J31/2282—Unsaturated compounds used as ligands
- B01J31/2295—Cyclic compounds, e.g. cyclopentadienyls
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0261—Complexes comprising ligands with non-tetrahedral chirality
- B01J2531/0263—Planar chiral ligands, e.g. derived from donor-substituted paracyclophanes and metallocenes or from substituted arenes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/842—Iron
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
General structure (1) show novel chiral N, the N ligand based on ferrocene frame having ferrocene frame, wherein R1For the alkyl of C1-C7, aryl or substituted aryl, R2For hydrogen or the alkyl-substituted silylation of C1-C7, R3For hydroxyl or the alkoxy of C1-C7, R4For hydrogen, the alkyl of C1-C7, aryl or substituted aryl, the substituted group is selected from phenyl, benzyl, naphthalene, the alkyl of C1-C7, the alkoxy of C1-C7, halogen, nitro, hydroxyl.The present invention is raw material using ferrocene cheap and easy to get, prepare novel N by easy synthetic route, N ligand, introduces multiple chiral factors in this ligand, and introduce hydrogen-bond donor, the fine structures such as steric hindrance and electronic effect are with good adjustability.
Description
Technical field
Novel chiral N, N ligand the present invention relates to one kind based on ferrocene frame having ferrocene frame belongs to asymmetry catalysis synthesis field.
Background technique
In numerous chiral skeletons for constructing ligand, ferrocene because its high heat stability, chemical stability and easily
It the features such as modification and special electronic effect, spatial chemistry, is widely used in asymmetric catalysis.Two
The type of luxuriant iron ligand is varied, can be subdivided by different the position of substitution, the number of substituent group and coordination atom difference
Different types of ligand.
In developed ferrocene chiral ligand, the overwhelming majority be biphosphine ligand and phosphine-hetero atom bidentate ligand, typically
Example such as Walphos, Chenphos and TriPhos etc..Related ferrocene is the chiral N of skeleton, and the report of N- ligand is but extremely
It is rare.It is well known that N, N- ligand because its stability, it is convieniently synthesized, be widely used the features such as one in asymmetric catalysis field
Directly it is concerned.
Summary of the invention
The purpose of the present invention is to provide a kind of raw materials to be easy to get, convieniently synthesized, catalytic activity is high, chiral induction acts on strong
Ferrocene N, N- ligand, such ligand include multiple chiral factors, and there is also potential hydrogen-bond donors, in the reaction can be the bottom of with
Object forms secondary interaction and further stablizes reaction transition state, is a kind of efficient novel chiral N, N- ligand.
It is a further object of the present invention to provide the preparation methods of above-mentioned ligand.
It is a still further object of the present invention to provide above-mentioned ligands and palladium original position composition catalyst in asymmetry catalysis allyl
Application in base substitution reaction.
Realization process of the invention is as follows:
Ferrocene frame having ferrocene frame chirality N, N ligand shown in general structure (1),
(I)
R1For the alkyl of C1-C7, aryl or substituted aryl；
R2For hydrogen or the alkyl-substituted silylation of C1-C7；
R3For hydroxyl or the alkoxy of C1-C7；
R4 For hydrogen, the alkyl of C1-C7, aryl or substituted aryl；
The substituted group be selected from phenyl, benzyl, naphthalene, the alkyl of C1-C7, the alkoxy of C1-C7, halogen, nitro,
Hydroxyl.
Specifically, R1For methyl, isopropyl, tert-butyl, cyclohexyl, phenyl, 2,4 dichloro benzene base, benzyl, adamantane
Base；R2For trimethylsilyl or hydrogen；R3For methoxyl group or hydroxyl；R4 Middle aryl is selected from phenyl, benzyl, naphthalene, the alkane of C1-C7
The aryl that base, the alkoxy of C1-C7, halogen, nitro, hydroxyl replace.
The inductive structure of typical ferrocene N, the N- ligand in part is as follows:
The preparation method of above-mentioned ferrocene frame having ferrocene frame chirality N, N ligand, comprising the following steps:
(1) using ferrocenecarboxylic acid as raw material, with chiral amino alcohol in the presence of triphenylphosphine, carbon tetrachloride, triethylamine,
Generate ferrocene-oxazoline class compound；
(2) ortho lithiation occurs under that action of n-butyl lithium for above-mentioned ferrocene-oxazoline compound, with trimethylchloro-silicane
Alkane effect generates key intermediate；
(3) pyridine carboxaldehyde or substituted pyridines formaldehydes are added under that action of n-butyl lithium again after lithiumation in above-mentioned intermediate
Compound generates ferrocene class N, N- ligand through column chromatography for separation.
Synthetic route is as follows:
Ferrocene frame having ferrocene frame chirality N, N ligand of the present invention can be applicable in the allyl group alkylated reaction of palladium chtalyst.
Two building blocks of oxazoline and pyridine are dexterously assembled in ferrocene in Catalyst Design of the invention by inventor
On skeleton, a kind of novel ferrocene N, N- ligand is formed, while introducing a potential hydrogen-bond donor, the latter is as Louis
This acid, the hydrogen bond that can be formed between the hydrogen bond receptor in related substrates, this secondary interaction force are living to the catalysis of reaction
Property and stereoselectivity play a crucial role.In addition, by the unique stereoeffect of ferrocene frame having ferrocene frame, in such ligand
In introduce the factor of face chirality, so that such ligand is become structure height adjustable, expand its potential application value.The present invention
Involved in application of ferrocene N, the N- ligand in the allyl substitution reaction of palladium chtalyst, it is high, vertical to show reactivity
The advantages such as body is selectively good, substrate spectrum is extensive, it is shown that its application prospect in asymmetric catalysis field.
Specific embodiment
Embodiment 1: preparation (R)-{2-[(S) -4- isopropyl -4,5- dihydro-oxazole base] -3- (trimethylsilyl) benzene
Base }-(2- pyridyl group)-methanol 1 and (S)-{2-[(S) -4- isopropyl -4,5- dihydro-oxazole base] -3- (trimethylsilyl) benzene
Base }-(2- pyridyl group)-methanol 1 '
Step 1:
Ferrocenecarboxylic acid (3.10g, 13.5 mmol) are added in 250mL single port bottle, after evacuated/inflated with nitrogen circulation,
Dry methylene chloride 25mL is added, draws oxalyl chloride (2.40mL, 27.0 mmol) with syringe and stirs at room temperature, reaction has
Gas is released, and reaction solution becomes peony after 20 m, is continued after stirring 10 m, revolving removes solvent, obtained brown-red solid
Be directly dissolved in 15mL methylene chloride, be added to after long needle aspirate (S)-valerian ammonia alcohol (1.65g, 16.11 mmol) and three
In the dichloromethane solution of ethamine (3.75 mL, 27.0 mmol), under nitrogen protection, it is stirred overnight at room temperature, gained dark-brown
Mixture washes (2 x, 30 mL), anhydrous Na2SO4Dry, gained crude product column chromatographic purifying obtains yellow solid 3.6g, produces
Rate 84%.
In the acetonitrile solution of yellow solid obtained above (2.45 g) and triphenylphosphine (7.47 g) (60 mL), add
Enter triethylamine (4.8 ml) and carbon tetrachloride (6.6mL), gained mixture are stirred overnight at room temperature under nitrogen protection, adds 80mL water
It is quenched, petroleum ether extraction (5 x, 50 mL), merges organic phase, anhydrous MgSO4Dry, crude by column chromatography purifies to obtain phase
Ferrocene-the oxazoline answered is light yellow solid, total 2.04g, yield 89%.
Step 2:
Take the history Nike pipe that ferrocene-oxazoline obtained in step 1 (2.04g, 6.86 mmol) is dry in a 100mL
In, it vacuumizes, inflated with nitrogen, is added dry ether (20mL), is cooled to 0 DEG C, carefully draws n-BuLi (1.6M with long syringe needle
Hexane solution, 4.72 mL, 7.55 mmol) it is slowly added to above-mentioned reaction tube, after stirring 1h at 0 DEG C, drawn with syringe
Trimethylsilyl chloride (0.96mL, 7.55 mmol) is warmed to room temperature naturally after stirring 1h at 0 DEG C, and anhydrous ether dilution is added
Reaction solution, a small amount of water quenching reaction separate organic layer, anhydrous Na2SO4Dry, revolving removes solvent, and column chromatographic purifying there are tangerine
Red solid 2.2g, yield 87%.
Step 3:
It takes the above Chinese red solid powder (2.0g, 5.41 mmol) in one 100 mL dry history Nike pipe, takes out true
Anhydrous THF (15 mL) is added in sky, inflated with nitrogen, be slowly added under -78 °C n-BuLi (1.6M hexane solution, 3.72
ML, 5.95 mmol), at this temperature stir 1h after, in this reaction tube be added 2- pyridine carboxaldehyde (0.57 mL, 5.95
Mmol), after reacting 2h at the same temperature, reaction solution is slowly increased to room temperature and is stirred overnight, and is quenched with 2mL methanol, revolving is removed
Solvent is removed, column chromatographic purifying respectively obtains target product 1, is crocus solid, total 976mg, yield 38%；Obtain target production
Object 1 ' is Chinese red solid, total 1.03g, yield 40%.
Compound 1:[α] D 25 =+367.5° (c=0.5, CH2Cl2); m.p. 114.4-116 ºC; 1H NMR
(400 MHz, CDCl3) δ 8.56 (d, J = 4.5 Hz, 1H), 8.23 (bs, 1H), 7.72-7.67 (m,
1H), 7.19-7.17 (m, 1H), 5.95 (s, 1H), 4.54-4.41 (m, 1H), 4.29 (s, 5H), 4.19
(d, J = 2.2 Hz, 1H), 4.11 (s, 1H), 4.04-3.99 (m, 2H), 1.73 (dq, J = 13.0, 6.5
Hz, 1H), 0.97 (d, J = 6.7 Hz, 3H), 0.88 (d, J = 6.7 Hz, 3H), 0.24 (s, 9H). 13C
NMR (100 MHz, CDCl3) δ 168.99, 162.57, 148.28, 136.29, 122.09, 121.36, 95.28,
77.34, 77.23, 77.03, 76.71, 75.83, 75.42, 73.82, 73.40, 71.75, 70.70, 70.49,
32.86, 18.82, 18.56, 0.76; HRMS m/z calcd for C25H32FeN2O2Si [M+H]+ 477.1582,
found 477.1664.
Compound 1 ': [α] D 25 =+216.7° (c=0.5, CH2Cl2); m.p. 97.6-98.8 ºC; 1H NMR
(400 MHz, CDCl3) δ 8.56 (d, J = 4.4 Hz, 1H), 8.32 (bs, 1H), 7.91 (d, J = 7.8
Hz, 1H), 7.83 (t, J = 7.5 Hz, 1H), 7.23 (d, J = 6.1 Hz, 1H), 5.70 (s, 1H),
4.36 (t, J = 7.5 Hz, 1H), 4.28 (s, 5H), 4.14-4.03 (m, 3H), 3.63 (s, 1H),
1.81-1.68 (m, 1H), 0.99 (d, J = 6.6 Hz, 3H), 0.94 (d, J = 6.7 Hz, 3H), 0.27
(s, 9H). 13C NMR (100 MHz, CDCl3) δ 168.99, 162.37, 148.19, 136.59, 122.16,
121.32, 100.65, 77.25, 74.73, 74.50, 73.76, 71.72, 71.67, 70.50, 70.33,
70.24, 32.99, 18.71, 18.35, 0.57; HRMS m/z calcd for C25H32FeN2O2Si [M+H]+
477.1582, found 477.1664。
Embodiment 2: preparation (R)-{2-[(S) -4- tert-butyl -4,5- dihydro-oxazole base] -3- (trimethylsilyl) benzene
Base }-(2- pyridyl group)-methanol 2 and (S)-{2-[(S) -4- tert-butyl -4,5- dihydro-oxazole base] -3- (trimethylsilyl) benzene
Base }-(2- pyridyl group)-methanol 2 '
For preparation method with embodiment 1, respectively obtaining target product 2 is rufous foaming shape solid, total 1.12g, yield
41%；Obtaining target product 2 ' is crocus solid, total 945mg, yield 37%.
Compound 2:[α] D 25 =+396.3º (c=0.26, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ
8.59 (d, J = 4.7 Hz, 1H), 8.14 (bs, 1H), 7.75-7.69 (m, 2H), 7.21 (td, J =
6.6, 5.8, 2.2 Hz, 1H), 5.98 (s, 1H), 4.46-4.41 (m, 2H), 4.30 (s, 5H), 4.21
(d, J = 2.5 Hz, 1H), 4.15 (t, J = 8.5 Hz, 1H), 4.07-3.99 (m, 2H), 0.9 (s,
9H), 0.27 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 168.88, 162.37, 148.38, 136.20,
122.14, 121.53, 95.00, 75.77, 75.55, 75.31, 73.65, 73.38, 72.49, 70.67,
68.66, 33.67, 25.89, 0.79; HRMS m/z calcd for C26H34FeN2O2Si [M+H]+ 491.1739,
found 491.1816.
Compound 2 ': [α] D 25 =+184.5° (c=0.2, CH2Cl2), m.p. 133.2-134.4ºC; 1H NMR
(400 MHz, CDCl3) δ 8.59 (d, J = 4.1 Hz, 1H), 8.46 (bs, 1H), 7.97-7.95 (m,
1H), 7.86 (td, J = 7.7, 1.7 Hz, 1H), 7.27-7.25 (m, 1H), 5.71 (s, 1H), 4.31
(s, 5H), 4.27-4.16 (m, 2H), 4.11-4.02 (m, 2H), 3.61 (d, J = 2.5 Hz, 1H), 0.95
(s, 9H), 0.29 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 169.05, 162.39, 148.21,
136.56, 122.17, 121.36, 100.80, 75.31, 74.71, 74.64, 73.83, 71.88, 71.60,
70.62, 70.24, 68.53, 33.76, 29.71, 26.37, 25.71, 0.6; HRMS m/z calcd for
C26H34FeN2O2Si [M+H]+ 491.1739, found 491.1816。
Embodiment 3: preparation (R)-{2-[(S) -4- phenyl -4,5- dihydro-oxazole base] -3- (trimethylsilyl) benzene
Base }-(2- pyridyl group)-methanol 3 and (S)-{2-[(S) -4- phenyl -4,5- dihydro-oxazole base] -3- (trimethylsilyl) benzene
Base }-(2- pyridyl group)-methanol 3 '
For preparation method with embodiment 1, respectively obtaining target product 3 is rufous foaming shape solid, total 1.33g, yield
51%；Obtaining target product 3 ' is crocus solid, total 873mg, yield 32%.
Compound 3:[α] D 25 = +336.2° (c=0.21, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ
8.55 (d, J = 4.6 Hz, 1H), 8.04 (d, J = 7.1 Hz, 1H), 7.61-7.48 (m, 2H), 7.35-
7.28 (m, 3H), 7.19-7.14 (m, 2H), 5.91 (d, J = 6.5 Hz, 1H), 5.36 (t, J = 9.0
Hz, 1H), 4.81 (t, J = 9.2 Hz, 1H), 4.36 (s, 5H), 4.34-4.29 (m, 2H), 4.19 (t,J = 8.3 Hz, 1H), 0.30 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 170.51, 162.83,
148.08, 141.64, 136.45, 130.93, 128.72, 127.69, 126.68, 121.97, 121.30,
96.08, 76.27, 75.56, 74.61, 74.54, 73.41, 70.86, 69.18, 65.58, 30.59, 29.72,
13.76, 0.87; HRMS m/z calcd for C28H30FeN2O2Si [M+H]+ 511.1460, found 511.1500.
Compound 3 ': [α] D 25= +289.7º (c=0.5, CH2Cl2); m.p. 168.2-169.8 ºC; 1H NMR
(400 MHz, CDCl3) δ 8.59 (d, J = 4.6 Hz, 1H), 7.93-7.74 (m, 3H), 7.37-7.24 (m,
5H), 5.84 (s, 1H), 5.47-5.38 (m, 1H), 4.75 (t, J = 9.1 Hz, 1H), 4.34 (s, 5H),
4.26 (t, J = 7.8 Hz, 1H), 4.17-4.12 (m, 2H), 3.77 (d, J=1.8 Hz, 1H), 0.31 (s,
9H). 13C NMR (100 MHz, CDCl3) δ 170.43, 162.26, 148.13, 142.12, 136.65,
128.80, 127.62, 126.28, 122.20, 121.37, 100.62, 75.16, 74.62, 74.42, 74.14,
72.05, 71.17, 70.40, 69.13, 29.72, 21.09, 14.23, 0.69; HRMS m/z calcd for
C28H30FeN2O2Si [M+H]+ 511.1460, found 511.1499。
Embodiment 4: preparation (R)-{2-[(S) -4- benzyl -4,5- dihydro-oxazole base] -3- (trimethylsilyl) benzene
Base }-(2- pyridyl group)-methanol 4 and (S)-{2-[(S) -4- benzyl -4,5- dihydro-oxazole base] -3- (trimethylsilyl) benzene
Base }-(2- pyridyl group)-methanol 4 '
For preparation method with embodiment 1, respectively obtaining target product 4 is rufous foaming shape solid, total 1.27g, yield
53%；Obtaining target product 4 ' is crocus solid, total 901mg, yield 33%.
Compound 4:[α] D 25 = +230.5° (c=0.36, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ
8.57 (d, J=4 Hz, 1H), 7.99 (d, J = 5.8 Hz, 1H), 7.78-7.57 (m, 2H), 7.34-7.13
(m, 5H), 5.91 (d, J = 5.6 Hz, 1H), 4.56 (dt, J = 14.9, 8.0 Hz, 1H), 4.40 (t,J = 8.8 Hz, 1H), 4.30 (s, 5H), 4.23 (d, J = 2.1 Hz, 2H), 4.05 (t, J = 8.0 Hz,
1H), 3.12 (dd, J = 13.8, 5.7 Hz, 1H), 2.66 (dd, J = 13.8, 8.1 Hz, 1H), 0.23
(s, 8H). 13C NMR (100 MHz, CDCl3) δ 169.54, 162.83, 148.40, 137.63, 136.18,
129.13, 128.63, 126.61, 122.00, 121.21, 95.69, 75.92, 75.38, 74.14, 74.10,
73.43, 71.85, 71.71, 70.75, 66.91, 41.52, 0.74; HRMS m/z calcd for
C29H32FeN2O2Si [M+H]+ 525.1616, found 525.1653.
Compound 4 ': [α] D 25 = +207.4º (c=0.5, CH2Cl2); m.p. 105.6~106.9 ºC; 1H NMR
(400 MHz, CDCl3) δ 8.60 (d, J = 4.6 Hz, 1H), 7.92-7.80 (m, 3H), 7.34-7.22 (m,
5H), 5.79 (s, 1H), 4.61-4.54 (m, 1H), 4.33-4.31 (m, 1H), 4.29 (s, 5H), 4.17-
4.11 (m, 2H), 4.09 (d, J = 2.0 Hz, 1H), 3.73 (d, J = 2.3 Hz, 1H), 3.13 (dd, J
= 13.7, 5.4 Hz, 1H), 2.72 (dd, J = 13.7, 8.3 Hz, 1H), 0.26 (s, 9H). 13C NMR
(100 MHz, CDCl3) δ 169.47, 162.35, 148.20, 137.69, 136.54, 129.24, 128.57,
126.58, 122.16, 121.34, 100.36, 74.96, 74.41, 73.93, 71.96, 71.37, 70.30,
67.13, 41.84, 0.61; HRMS m/z calcd for C29H32FeN2O2Si [M+H]+ 525.1616, found
525.1660。
Embodiment 5: preparation (R)-{2-[(S) -4- isopropyl -4,5- dihydro-oxazole base] phenyl-(2- pyridyl group)-first
Alcohol 5 and (S)-{2-[(S) -4- isopropyl -4,5- dihydro-oxazole base] phenyl-(2- pyridyl group)-methanol 5 '
It takes above compound 1 (953mg, 2.0 mmol) in the dry history Nike pipe of a 50mL, vacuumizes, inflated with nitrogen,
Anhydrous DMSO (5mL) is added, under nitrogen atmosphere, is added potassium tert-butoxide (538.6mg, 4.8 mmol), stirs at room temperature
Overnight, reaction solution is concentrated under reduced pressure, it is crocus solid, total 663mg, yield 82% that column chromatographic purifying, which obtains target product 5,.
[α] D 25 = +342.1° (c=0.22, CH2Cl2); m.p. 80.1-81.2 ºC; 1H NMR (400 MHz,
CDCl3) δ 8.53 (d, J = 4.7 Hz, 1H), 8.23 (d, J = 6.6 Hz, 1H), 7.70-7.63(m,
2H), 7.14 (ddd, J = 6.7, 4.9, 1.7 Hz, 1H), 5.84 (d, J = 6.1 Hz, 1H), 4.65
(dd, J = 2.4, 1.6 Hz, 1H), 4.50-4.43 (m, 1H), 4.32 (s, 5H), 4.27 (dt, J =
4.0, 2.5 Hz, 2H), 4.08-4.01 (m, 2H), 1.75 (td, J = 13.2, 6.6 Hz, 1H), 0.97
(d, J = 6.7 Hz, 3H), 0.90 (d, J = 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ
168.07, 162.16, 148.05, 136.59, 122.27, 121.49, 95.83, 72.41, 71.96, 70.67,
70.38, 70.19, 69.57, 68.23, 66.44, 33.02, 18.72, 18.57; HRMS m/z calcd for
C22H24FeN2O2 [M+H]+ 405.1221, found 405.1263.
Compound 5 ' is prepared by compound 1 ', and preparation method is same as above.It there are 452mg, yield 67%.
[α] D 25 = +139.1°(c=0.45, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J
= 4.7 Hz, 1H), 8.24 (d, J = 7.9 Hz, 1H), 7.70-7.63 (m, 2H), 7.14 (dd, J =
6.8, 5.0 Hz, 1H), 5.84 (d, J = 7.7 Hz, 1H), 4.65 (dd, J = 2.5, 1.6 Hz, 1H),
4.50-4.43 (m, 1H), 4.32 (s, 5H), 4.28-4.26 (m, 2H), 4.08-4.01 (m, 2H), 1.74
(dt, J = 13.2, 6.6 Hz, 1H), 0.97 (d, J = 6.7 Hz, 3H), 0.90 (d, J = 6.7 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ 168.17, 163.26, 148.45, 136.22, 121.91,
120.84, 92.44, 73.67, 72.38, 71.95, 70.76, 70.70, 70.40, 68.78, 66.94, 32.84,
18.76, 18.60; HRMS m/z calcd for C22H24FeN2O2 [M+H]+ 405.1221, found 405.1261。
Embodiment 6: preparation (R)-{2-[(S) -4- tert-butyl -4,5- dihydro-oxazole base] phenyl-(2- pyridyl group)-first
Alcohol 6 and (S)-{2-[(S) -4- tert-butyl -4,5- dihydro-oxazole base] phenyl-(2- pyridyl group)-methanol 6 '
For preparation method with embodiment 5, respectively obtaining target product 6 is crocus solid, total 763g, yield 73%；?
It is rufous foaming shape solid, total 623mg, yield 63% to target product 6 '.
Compound 6:[α] D 25 = +416.7° (c=0.45, CH2Cl2); m.p. 129.5-130.3 ºC; 1H NMR
(400 MHz, CDCl3) δ 8.58 (d, J = 4.4 Hz, 1H), 8.26 (s, 1H), 7.93 (d, J = 7.8
Hz, 1H), 7.84 (t, J = 7.6 Hz, 1H), 7.26-7.25 (m, 1H), 5.78 (s, 1H), 4.67 (s,
1H), 4.40-4.33 (m, 1H), 4.28 (s, 5H), 4.21-4.15 (m, 2H), 4.05 (dd, J = 9.8,
7.9 Hz, 1H), 3.62 (s, 1H), 0.94 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 168.08,
162.14, 148.07, 136.60, 122.28, 121.50, 96.05, 75.36, 72.54, 70.45, 70.18,
69.49, 68.80, 68.15, 66.42, 33.70, 25.74; HRMS m/z calcd for C23H26FeN2O2 [M+H]+
419.1377, found 419.1416.
Compound 6 ': [α] D 25 = +102.3° (c=0.15, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ
8.52 (d, J = 4.6 Hz, 1H), 8.25 (s, 1H), 7.70-7.63 (m, 2H), 7.15-7.11 (m, 1H),
5.83 (s, 1H), 4.66 (t, J = 2.0 Hz, 1H), 4.39 (dd, J = 9.7, 8.6 Hz, 1H), 4.32
(s, 5H), 4.28-4.27 (m, 2H), 4.11 (t, J = 8.5 Hz, 1H), 4.02 (dd, J = 9.7, 8.7
Hz, 1H), 0.88 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 168.17, 163.23, 148.49,
136.20, 121.92, 120.93, 92.43, 75.47, 73.59, 72.47, 70.70, 70.42, 68.94,
68.77, 66.87, 33.65, 25.87; HRMS m/z calcd for C23H26FeN2O2 [M+H]+ 419.1377,
found 419.1419。
Embodiment 7: preparation (R)-{2-[(S) -4- phenyl -4,5- dihydro-oxazole base] phenyl-(2- pyridyl group)-methanol
7 and (S)-{2-[(S) -4- phenyl -4,5- dihydro-oxazole base] phenyl-(2- pyridyl group)-methanol 7 '
For preparation method with embodiment 5, respectively obtaining target product 7 is rufous foaming shape solid, total 663g, yield
63%；Obtaining target product 7 ' is rufous foaming shape solid, total 513mg, yield 76%.
Compound 7:[α] D 25 = +401.9° (c=0.42, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ
8.59 (t, J = 4.9 Hz, 1H), 7.87-7.84 (m, 1H), 7.78 (td, J = 7.7, 1.6 Hz, 1H),
7.63 (s, 1H), 7.46-7.39 (m, 3H), 7.38-7.35 (m, 1H), 7.31-7.29 (m, 1H), 7.26-
7.23 (m, 1H), 5.90 (d, J = 11.3 Hz, 1H), 5.43-5.32 (m, 1H), 4.83-4.75 (m,
2H), 4.33-4.28 (m, 6H), 4.25-4.21 (m, 1H), 3.83-3.81 (m, 1H). 13C NMR (100
MHz, CDCl3) δ 169.55, 169.49, 162.07, 161.99, 148.02, 142.28, 136.58, 136.54,
128.97, 127.72, 126.43, 122.28, 121.53, 95.61, 74.62, 72.45, 72.29, 70.33,
70.30, 70.20, 70.11, 69.91, 69.34, 69.23, 68.68, 68.60, 66.20, 66.11; HRMS m/
z calcd for C25H22FeN2O2 [M+H]+ 439.1064, found 439.1108.
Compound 7 ': [α] D 25 = +256.7° (c=0.48, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ
8.53 (dd, J = 16.5, 4.7 Hz, 1H), 8.07-7.92 (m, 1H), 7.69-7.66 (m, 1H), 7.57-
7.50 (m, 1H), 7.47-7.40 (m, 2H), 7.38-7.31 (m, 1H), 7.18-7.10 (m, 2H), 5.87
(dd, J = 55.4, 6.2 Hz, 1H), 5.39-5.31 (m, 1H), 4.83-4.72 (m, 2H), 4.43-4.25
(m, 7H), 4.19-4.13 (m, 1H).13C NMR (100 MHz, CDCl3) δ 169.75, 169.69, 163.37,
163.06, 148.40, 142.26, 141.78, 136.44, 136.25, 129.00, 128.65, 127.74,
127.67, 126.67, 126.25, 122.06, 121.82, 120.96, 120.87, 93.07, 92.55, 74.93,
73.77, 73.65, 72.92, 72.45, 70.80, 70.53, 69.25, 69.12, 68.91; HRMS m/z calcd
for C25H22FeN2O2 [M+H]+ 439.1064, found 439.1108。
Embodiment 8: preparation (R)-{2-[(S) -4- benzyl -4,5- dihydro-oxazole base] phenyl-(2- pyridyl group)-methanol
8 and (S)-{2-[(S) -4- benzyl -4,5- dihydro-oxazole base] phenyl-(2- pyridyl group)-methanol 8 '
For preparation method with embodiment 5, respectively obtaining target product 8 is rufous foaming shape solid, total 713g, yield
68%；Obtaining target product 8 ' is rufous foaming shape solid, total 243mg, yield 56%.
Compound 8:[α] D 25 = +316.3° (c=0.32, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ
8.60 (d, J = 4.6 Hz, 1H), 7.87 (d, J = 7.8 Hz, 1H), 7.82 (td, J = 7.7, 1.4
Hz, 1H), 7.72 (s, 1H), 7.35-7.31 (m, 2H), 7.27-7.23 (m, 4H), 5.86 (s, 1H),
4.68-4.67 (m, 1H), 4.57 (dt, J = 14.9, 7.5 Hz, 1H), 4.38 (t, J = 8.8 Hz, 1H),
4.26 (s, 5H), 4.19 (t, J = 2.5 Hz, 1H), 4.13-4.09 (m, 1H), 3.75 (s, 1H), 3.12
(dd, J = 13.7, 5.6 Hz, 1H), 2.78 (dd, J = 13.7, 7.8 Hz, 1H). 13C NMR (100 MHz,
CDCl3) δ 168.61, 162.14, 148.01, 137.71, 136.58, 129.34, 128.57, 126.59,
122.28, 121.52, 95.52, 72.30, 71.67, 70.25, 70.23, 69.79, 68.45, 67.18,
66.28, 41.69, 29.72; HRMS m/z calcd for C26H24FeN2O2 [M+H]+ 453.1221, found
453.1264.
Compound 8 ': [α] D 25 = +146.8° (c=1.0, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ
8.54 (d, J = 4.7 Hz, 1H), 7.98 (d, J = 7.7 Hz, 1H), 7.68-7.61 (m, 2H), 7.34-
7.31 (m, 2H), 7.27-7.25 (m, 1H), 7.23-7.20 (m, 2H), 7.15 (ddd, J = 6.6, 4.9,
1.7 Hz, 1H), 5.82 (d, J = 7.1 Hz, 1H), 4.65-4.64 (m, 1H), 4.56 (dd, J = 15.3,
7.6 Hz, 1H), 4.41 (t, J = 8.8 Hz, 1H), 4.31 (s, 5H), 4.30-4.28 (m, 2H), 4.08-
4.05 (m, 1H), 3.10 (dd, J = 13.8, 6.0 Hz, 1H), 2.70 (dd, J = 13.8, 8.0 Hz,
1H). 13C NMR (100 MHz, CDCl3) δ 168.76, 163.21, 148.46, 137.76, 136.25,
129.12, 128.63, 126.62, 121.92, 120.86, 92.42, 73.64, 72.50, 72.11, 70.73,
70.46, 68.95, 67.06, 66.70, 41.62; HRMS m/z calcd for C26H24FeN2O2 [M+H]+
453.1221, found 453.1266。
Embodiment 9: preparation (S)-{2-[(R) -4- isopropyl -4,5- dihydro-oxazole base] phenyl-(2- pyridyl group)-first
Alcohol 9
For preparation method with embodiment 5, obtaining target product 9 is rufous foaming shape solid, total 826g, yield 80%.
[α] D 25 = -340° (c=0.12, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 8.59 (d, J =
4.3 Hz, 1H), 8.15 (d, J = 1.6 Hz, 1H), 7.91 (d, J = 7.8 Hz, 1H), 7.83 (td, J
= 7.7, 1.7 Hz, 1H), 7.28-7.24 (m, 1H), 5.79 (s, 1H), 4.68-4.67 (m, 1H), 4.47-
4.41 (m, 1H), 4.28 (s, 5H), 4.17 (t, J = 2.6 Hz, 1H), 4.11-4.04 (m, 2H),
3.67-3.66 (m, 1H), 1.79-1.74 (m, 1H), 1.02 (d, J = 6.7 Hz, 3H), 0.96 (d, J =
6.7 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 168.06, 162.18, 148.05, 136.57,
122.25, 121.49, 95.84, 72.42, 71.97, 70.65, 70.38, 70.19, 69.57, 68.22,
66.46, 33.02, 18.71, 18.56; HRMS m/z calcd for C22H24FeN2O2 [M+H]+ 405.1221,
found 405.1264。
Embodiment 10: preparation (S) -4- isopropyl -2- { 2- [(R)-methoxyl group-(2- pyridyl group) methyl] phenyl } -4,
5- dihydro-oxazole 10
It takes compound 5 (202mg, 0.5 mmol) in one 50 mL history Nike pipes, is added dry THF (5 mL), then
It is added NaH (18mg, 0.75 mmol), is stirred at room temperature after ten minutes, is added MeI (60 μ L, 1.0 mmol), gained is mixed
It closes after 10 h are stirred at room temperature in object and is quenched with saturated ammonium chloride, anhydrous ether extracts organic phase (3 × 5 mL), anhydrous Na2SO4It is dry
Dry, column chromatographic purifying, gained target product is rufous foaming shape solid, total 182mg, yield 87%.
[α] D 25 = +51.7° (c=0.12, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J
= 4.7 Hz, 1H), 7.55 (td, J = 7.7, 1.6 Hz, 1H), 7.31 (s, 1H), 7.11 (dd, J =
7.0, 5.3 Hz, 1H), 5.82 (s, 1H), 4.71 (t, J = 2.3 Hz, 2H), 4.34-4.32 (m, 1H),
4.27 (s, 5H), 4.20-4.15 (m, 1H), 4.06-4.02 (m, 1H), 3.96-3.91 (m, 1H), 3.56
(s, 3H), 1.80-1.74 (m, 1H), 0.93 (d, J = 6.8 Hz, 3H), 0.87 (d, J = 6.8 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ 165.46, 161.19, 149.05, 136.21, 122.45,
122.26, 90.67, 81.04, 71.98, 70.48, 69.58, 69.05, 68.83, 57.65, 32.29, 29.73,
18.63, 17.83; HRMS m/z calcd for C23H26FeN2O2 [M+H]+ 419.1377, found 419.1420。
Embodiment 11: ferrocene N involved in the present invention, N ligand answering in the allyl group alkylated reaction of palladium chtalyst
Use example
Shown in following reaction equation, [Pd (C is added in 10mL reaction tube3H5)Cl]2(0.02 mmol), ligand 5
After stirring half an hour under nitrogen atmosphere, (E) -1,3- diphenyl acetic acid alkene is added in (0.06 mmol), methylene chloride 2.0mL
Propyl ester (0.4 mmol), dimethyl malenate (1.2 mmol), BSA (1.2 mmol) and LiOAc (0.034 mmol).
Gained reaction solution reacts 8h at room temperature, and the chemical yield for measuring product is up to 99%, and enantiomeric excess value is up to 98.4%.
。
Claims (7)
1. ferrocene frame having ferrocene frame chirality N, N ligand shown in general structure (1),
R1For methyl, isopropyl, tert-butyl, cyclohexyl, phenyl, 2,4 dichloro benzene base, benzyl, adamantyl；
R2For hydrogen or the alkyl-substituted silylation of C1-C7；
R3For hydroxyl or the alkoxy of C1-C7；
R4 For hydrogen, the alkyl of C1-C7, aryl or substituted aryl, the aryl is selected from phenyl, benzyl, naphthalene, described substituted
Group is selected from phenyl, benzyl, naphthalene, the alkyl of C1-C7, the alkoxy of C1-C7, halogen, nitro, hydroxyl.
2. ferrocene frame having ferrocene frame chirality N, N ligand according to claim 1, it is characterised in that: R2For trimethylsilyl or
Hydrogen.
3. ferrocene frame having ferrocene frame chirality N, N ligand according to claim 1, it is characterised in that: R3For methoxyl group or hydroxyl.
4. ferrocene frame having ferrocene frame chirality N, N ligand according to claim 1, it is characterised in that: R4 For the alkyl of C1-C7, C1-
The alkoxy of C7, halogen, nitro, the aryl that hydroxyl replaces.
5. ferrocene frame having ferrocene frame chirality N, N ligand according to claim 1, it is characterised in that ferrocene frame having ferrocene frame chirality N, N match
Body are as follows:
。
6. the preparation method of ferrocene frame having ferrocene frame chirality N, N ligand described in claim 1, comprising the following steps:
R1、R2And R4 It is identical as substituent group described in claim 1, R5For the alkyl of C1-C7；
(1) using ferrocenecarboxylic acid as raw material, formed after condensation reaction with chiral amino alcohol Aminylferrocene compound again with
In the presence of triphenylphosphine, carbon tetrachloride, triethylamine, ferrocene-oxazoline class compound is generated；
(2) ortho lithiation occurs under that action of n-butyl lithium for above-mentioned ferrocene-oxazoline compound, with R2Cl effect generates crucial
Intermediate；
(3) pyridine carboxaldehyde or substituted pyridines formaldehydes chemical combination is added under that action of n-butyl lithium again after lithiumation in above-mentioned intermediate
Object generates ferrocene class N, N- ligand through column chromatography for separation.
7. application of ferrocene frame having ferrocene frame chirality N, the N ligand in the allyl group alkylated reaction of palladium chtalyst described in claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610040998.7A CN105541925B (en) | 2016-01-22 | 2016-01-22 | Ferrocene frame having ferrocene frame N, N ligand and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610040998.7A CN105541925B (en) | 2016-01-22 | 2016-01-22 | Ferrocene frame having ferrocene frame N, N ligand and its preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105541925A CN105541925A (en) | 2016-05-04 |
| CN105541925B true CN105541925B (en) | 2019-09-24 |
Family
ID=55821528
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610040998.7A Expired - Fee Related CN105541925B (en) | 2016-01-22 | 2016-01-22 | Ferrocene frame having ferrocene frame N, N ligand and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105541925B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112538033B (en) * | 2019-09-20 | 2022-02-11 | 中国科学院大连化学物理研究所 | Resolution method of naphthenic face chiral compound |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804432A (en) * | 2014-02-25 | 2014-05-21 | 中国人民解放军第四军医大学 | Double-functionalized amine-thiourea organic catalyst based on ferrocene and preparation method and application thereof |
-
2016
- 2016-01-22 CN CN201610040998.7A patent/CN105541925B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804432A (en) * | 2014-02-25 | 2014-05-21 | 中国人民解放军第四军医大学 | Double-functionalized amine-thiourea organic catalyst based on ferrocene and preparation method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| 1,1"-Di(heteroatom)-functionalised ferrocenes as [N,N], [O,O] and [S,S] chelate ligands in transition metal chemistry;Ulrich Siemeling et al.;《Chem. Soc. Rev.》;20050420;第34卷;第584-594页 * |
| New P,N-Ferrocenyl Ligands for the Asymmetric Ir-Catalyzed Hydrogenation of Imines;Murthy N. Cheemala et al.;《Org. Lett.》;20070707;第9卷(第16期);第3089-3092页 * |
| Synthesis of Ferrocene Oxazoline N,O ligands and Their Application in Asymmetric Ethyl- and Phenylzinc Additions to Aldehydes;Chris Nottingham et al.;《J. Org. Chem.》;20150901;第80卷;第10163-10176页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105541925A (en) | 2016-05-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9108996B2 (en) | Ruthenium-based metathesis catalysts and precursors for their preparation | |
| CN112321627B (en) | Axis chiral arylethynyl silane compound and preparation method thereof | |
| CN109422684A (en) | A method of synthesis 6- methyl phenanthridines class compound | |
| Chelucci et al. | Enantiomerically pure pyridine and 2, 2′-bipyridine thioethers: new N–S chiral ligands for asymmetric catalysis. Palladium-catalyzed allylic alkylation | |
| CN103408573B (en) | Boric acid derivatives and its preparation method and application | |
| Yuan et al. | Selectfluor-mediated construction of 3-arylselenenyl and 3, 4-bisarylselenenyl spiro [4.5] trienones via cascade annulation of N-phenylpropiolamides with diselenides | |
| Wang et al. | Copper (II)/Palladium (II) catalysed highly selective cross-coupling of terminal alkynes in supercritical carbon dioxide | |
| CN105541925B (en) | Ferrocene frame having ferrocene frame N, N ligand and its preparation method and application | |
| WO2014000455A1 (en) | Chiral five-membered bicyclic guanidine compound, and preparation method and application thereof | |
| JP2007230963A (en) | Method for producing 2,4-disubstituted pyridine | |
| CN108440483B (en) | 3, 4-dihydrooxy-2 (7H) -ketone and preparation method thereof | |
| CN113045530B (en) | Method for preparing naphthopyran compounds by ruthenium catalysis | |
| WO2022104599A1 (en) | N-heterocyclic carbene catalyst and preparation method therefor | |
| CN110437277B (en) | Synthetic method of phosphoalkenyl ester compound | |
| CN111362795B (en) | Preparation method of substituted butyrate derivatives | |
| CN111116465B (en) | Cyanoalkyl substituted nitrogen heterocyclic compound and synthetic method thereof | |
| CN109651404B (en) | Aziridine derivative and preparation method and application thereof | |
| CN102786466B (en) | Synthetic method of chiral Salan ligand | |
| CN106966948A (en) | A kind of synthetic method together with difluoro substituted pyrrolidone compound | |
| CN113024592A (en) | Synthetic method of azetidine silicon precursor compound and method for synthesizing six-membered silicon nitrogen heterocyclic compound by using same | |
| CN112979513A (en) | Chiral sulfoxide containing styrene monomer and preparation method thereof | |
| CN101735241A (en) | Prasugrel intermediate and preparation method thereof | |
| CN110963981A (en) | Benzothiazole aryl compound derivatives and preparation method thereof | |
| JP2005041791A (en) | OPTICALLY ACTIVE QUATERNARY AMMONIUM SALT, METHOD FOR PRODUCING THE SAME AND METHOD FOR PRODUCING OPTICALLY ACTIVE alpha-AMINO ACID DERIVATIVE USING THE SAME | |
| CN115232163B (en) | Silicon center chiral molecular compound and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20190924 Termination date: 20200122 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |