CN113185553A - Chiral phosphoric acid compound with aryl indole carbazole skeleton and preparation method and application thereof - Google Patents
Chiral phosphoric acid compound with aryl indole carbazole skeleton and preparation method and application thereof Download PDFInfo
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 title claims abstract description 39
- -1 phosphoric acid compound Chemical class 0.000 title claims abstract description 32
- 229910000147 aluminium phosphate Inorganic materials 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 27
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000004185 ester group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 6
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- 150000008049 diazo compounds Chemical class 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- SKVVLPFEDFQEPS-UHFFFAOYSA-N Cl.Cl.Cl.[PH3]=O Chemical compound Cl.Cl.Cl.[PH3]=O SKVVLPFEDFQEPS-UHFFFAOYSA-N 0.000 claims description 2
- 229950011260 betanaphthol Drugs 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 238000006880 cross-coupling reaction Methods 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000011914 asymmetric synthesis Methods 0.000 abstract description 4
- 238000011160 research Methods 0.000 abstract description 4
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical class C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 150000005347 biaryls Chemical class 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000004679 31P NMR spectroscopy Methods 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- PPTXVXKCQZKFBN-UHFFFAOYSA-N (S)-(-)-1,1'-Bi-2-naphthol Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3O)=C(O)C=CC2=C1 PPTXVXKCQZKFBN-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- QJTQKPNNQVLHHO-UHFFFAOYSA-N 9h-carbazole;1h-indole Chemical group C1=CC=C2NC=CC2=C1.C1=CC=C2C3=CC=CC=C3NC2=C1 QJTQKPNNQVLHHO-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- UWQPDVZUOZVCBH-UHFFFAOYSA-N 2-diazonio-4-oxo-3h-naphthalen-1-olate Chemical class C1=CC=C2C(=O)C(=[N+]=[N-])CC(=O)C2=C1 UWQPDVZUOZVCBH-UHFFFAOYSA-N 0.000 description 1
- 241000251737 Raja Species 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- FLGMAMYMYDIKLE-UHFFFAOYSA-N chloro hypochlorite;phosphane Chemical compound P.ClOCl FLGMAMYMYDIKLE-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- URQUNWYOBNUYJQ-UHFFFAOYSA-N diazonaphthoquinone Chemical compound C1=CC=C2C(=O)C(=[N]=[N])C=CC2=C1 URQUNWYOBNUYJQ-UHFFFAOYSA-N 0.000 description 1
- VVVPGLRKXQSQSZ-UHFFFAOYSA-N indolo[3,2-c]carbazole Chemical class C1=CC=CC2=NC3=C4C5=CC=CC=C5N=C4C=CC3=C21 VVVPGLRKXQSQSZ-UHFFFAOYSA-N 0.000 description 1
- 229960005544 indolocarbazole Drugs 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000006713 insertion reaction Methods 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
- C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
- C07F9/65848—Cyclic amide derivatives of acids of phosphorus, in which two nitrogen atoms belong to the ring
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0255—Phosphorus containing compounds
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Indole Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The chiral phosphoric acid compound with the aryl indole carbazole skeleton can be used as a catalyst, and the synthesis method is simple and efficient, has high enantioselectivity and high yield, and provides a research basis for asymmetric synthesis of a chiral organic catalyst.
Description
Technical Field
The invention belongs to the technical field of compound synthesis, and relates to a chiral phosphoric acid compound with an aryl indole carbazole skeleton, and a preparation method and application thereof.
Background
Axial chiral biaryls are ubiquitous in many natural products, bioactive molecules and functional materials, and are the core structural motifs that constitute chiral catalysts and ligands for asymmetric transformation reactions. So far, asymmetric reactions promoted by axial chiral biaryl catalysts are widely applied in the field of organic synthesis, such as chiral biaryl catalysts BINOL and H8-BINOL. Wherein the BINOL scaffold-based Chiral Phosphate (CPA) is capable of efficiently inducing significant energy differences between diastereoisomeric transition states in different reactions with high selectivity [ (a) Parmar, D.; sugiono, e.; raja, s.; rueping, m.chem.rev.2014,114,9047, (b) shuugrue, c.r.; miller, S.J.chem.Rev.2017,117,11894 ]. However, chiral biaryl phosphate catalysts have been reported to date in a limited number of classes. In the research of asymmetric catalysis, the design and synthesis of chiral catalysts are of great significance.
Indolocarbazoles are very important high-affinity ligands, can effectively improve the corresponding induction of chiral ligands, and are key active ingredients of anti-cancer, antifungal, antibacterial and antihypertensive drugs. Therefore, the developed novel aryl indole carbazole phosphoric acid catalyst shows better regioselectivity and stereoselectivity in the asymmetric catalysis field compared with a biaryl skeleton by introducing the indole carbazole skeleton with the advantages into chiral phosphoric acid.
In view of the foregoing, there is a need to develop chiral phosphoric acids having novel arylindolocarbazole skeletons for exploring a variety of different types of asymmetric reactions.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a chiral phosphoric acid compound with an arylindole carbazole skeleton, and a preparation method and application thereof.
In order to achieve the purpose, the invention adopts the following technical scheme:
in one aspect, the present invention provides a chiral phosphoric acid compound having an arylindolocarbazole skeleton, the chiral phosphoric acid compound having a structure represented by formula I:
wherein R is1And R3Independently of one another, from hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl or substituted or unsubstituted ester groups, the M radicals being
R2And R4Independently of one another, from hydrogen, halogen, substituted or unsubstituted alkyl, substitutedOr an unsubstituted alkoxy group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted ester group.
Preferably, the substituted or unsubstituted alkyl group is a substituted or unsubstituted alkyl group having 1 to 5 (e.g., 1, 2,3, 4, or 5) carbon atoms.
Preferably, the substituted or unsubstituted alkoxy group is a substituted or unsubstituted alkoxy group having 1 to 5 (e.g., 1, 2,3, 4, or 5) carbon atoms.
Preferably, when the group has a substituent as described above, the substituent is a halogen, an alkyl group having 1 to 5 carbon atoms, or a phenyl group.
Preferably, R1、R2And R3Independently of one another, from hydrogen, methyl, methoxy, fluorine, chlorine, bromine, benzyloxy, tert-butyl, aryl, ester or trifluoromethyl.
Preferably, the aryl group is phenyl,
Wherein the wavy line represents the attachment position of the group.
Preferably, the ester group is-COOCH3、-OC4H8CO2CH3、-COOCH2CH3or-COOBn.
Preferably, the chiral phosphoric acid compound having an arylindolocarbazole skeleton is any one of the following compounds:
in another aspect, the present invention provides a method for preparing a chiral phosphoric acid compound having an arylindolocarbazole skeleton as described above, the method comprising the steps of:
(1) reacting diazo compound with M group shown in formula II with a compound (indole [2,3-a ] carbazole derivative) shown in formula III to obtain an axial chiral aryl indole carbazole derivative shown in formula IV, wherein the reaction formula is as follows:
(2) reacting the axial chiral aryl indole carbazole derivative shown in the formula IV with phosphorus oxychloride to obtain a chiral phosphoric acid compound with an aryl indole carbazole skeleton shown in the formula I, wherein the reaction formula is as follows:
preferably, the molar ratio of the diazo compound of formula II with M groups to the compound of formula III in step (1) is 1:1 to 1:1.8, for example 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7 or 1: 1.8.
Preferably, the reaction of step (1) is carried out in the presence of a catalyst, preferably tetrakis [ (S) - (+) -1-adamantyl) - (N-phthalimido) acetate]Dirhodium (II) (Rh)2(S-PTAD)4)。
Preferably, the catalyst is used in an amount of 0.1 to 0.8%, for example 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7% or 0.8% of the molar amount of the compound of formula III.
Preferably, the reaction of step (1) is carried out at room temperature.
Preferably, the reaction time in step (1) is 1 to 12 hours, such as 1 hour, 3 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours.
Preferably, the molar ratio of the axial chiral arylindolocarbazole derivative of formula IV to the phosphine oxide trichloride in step (2) is 1:2-1:5, such as 1:2, 1:2.2, 1:2.5, 1:2.8, 1:3, 1:3.5, 1:4, 1:4.5 or 1: 5.
Preferably, the solvent for the reaction of step (2) is pyridine.
Preferably, the temperature of the reaction in step (2) is 50-80 ℃, such as 50 ℃, 55 ℃, 58 ℃, 60 ℃, 65 ℃, 68 ℃, 70 ℃, 73 ℃, 75 ℃, 78 ℃ or 80 ℃.
Preferably, the reaction time in step (2) is 1 to 12 hours, such as 1 hour, 3 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours.
The preparation method selectively synthesizes the axial chiral aryl indole carbazole phosphoric acid through Rh (II) catalytic intermolecular N-H insertion reaction axis, has high enantiomer selectivity and high yield, and provides a research basis for asymmetric synthesis of chiral organic catalysts.
In another aspect, the present invention provides the use of the chiral phosphoric acid compound having an arylindolocarbazole skeleton as described above as a catalyst.
Preferably, the catalyst is a catalyst for catalyzing the C-C bond cross-coupling reaction of 2-naphthol and benzoquinone.
Compared with the prior art, the invention has the following beneficial effects:
the chiral phosphate compound with the aryl indole carbazole skeleton can be used as a catalyst, and the synthesis method is simple and efficient, has high enantioselectivity and high yield, and provides a research basis for asymmetric synthesis of chiral organic catalysts.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.
Example 1: synthesis of 3aa
In the first step, 1.0mmol of diazonaphthoquinone and indole [2,3-a ] are added under the protection of argon]Carbazole 1.5mmol and tetrakis [ (S) - (+) -1-adamantyl) - (N-phthalimido) acetate]Dirhodium (II) (Rh)2(S-PTAD)4) Mixing the raw materials in chloroform according to a molar equivalent ratio of 1:1.5: 0.5%, reacting at room temperature for 6h, concentrating under reduced pressure to dryness, and performing column chromatography to obtain the axial chiral arylindolocarbazole derivative shown in 3 aa', wherein the yield is 52%, and the ee 99% is obtained by HPLC analysis, and the reaction formula is as follows:
secondly, adding 3 aa' (0.5mmol) of the arylindolocarbazole derivative into 5ml of pyridine under the protection of argon, then slowly dropwise adding phosphine oxychloride (2.0mmol), reacting at 60 ℃ for 7 hours, cooling to room temperature, concentrating under reduced pressure to dryness, and then obtaining chiral arylindolocarbazole phosphoric acid shown in 3aa through column chromatography, wherein the yield is 88%, ee 99%, and the reaction formula is as follows:
1H NMR(600MHz,CDCl3):δ＝8.28(dd,J＝8.1,1.2Hz,2H),8.12–8.09(m,2H),8.05–7.95(m,4H),7.50–7.45(m,3H),7.42–7.40(m,1H),7.37–7.35(m,1H),7.23–7.21(m,1H),6.90(d,J＝8.1Hz,1H),6.84(d,J＝8.7Hz,1H)。
13C NMR(151MHz,CDCl3):δ＝143.31,143.25,141.46,141.17,133.80,133.79,132.66,132.65,130.87,130.83,130.54,130.52,130.08,130.04,129.50,129.48,129.45,127.73,127.72,127.58,127.22,126.56,126.42,126.38,125.93,125.47,124.70,124.58,121.82,121.64,121.63,120.85,120.56,118.50,118.49,118.35,113.68,113.28。
31P NMR(162MHz,CDCl3):δ＝6.42。
HRMS(ESI):calcd for C28H16O3N2P[M-H]-:459.0904,found 459.0906。
note: 3aa1H-NMR spectrum and13the C-NMR spectrum was obtained by detection with a nuclear magnetic resonance spectrometer (Avance II 400 MHz).31P NMR was measured by a nuclear magnetic resonance spectrometer (Avance II 400MHz) and HRMS was measured by an electrospray mass spectrometer (ESI) (the same applies to the examples below).
Example 2: synthesis of 3ra
In the first step, diazonaphthoquinone derivative (1.0mmol) and indole are added under the protection of argonIndole [2,3-a ]]Carbazole (1.5mmol) and tetrakis [ (S) - (+) -1-adamantyl) - (N-phthalimido) acetate]Dirhodium (II) (Rh)2(S-PTAD)4) Mixing the raw materials in chloroform according to a molar equivalent ratio of 1:1.5: 0.5%, reacting at room temperature for 12h, concentrating under reduced pressure to dryness, and performing column chromatography to obtain an axial chiral arylindolocarbazole derivative shown in 3 ra', wherein the yield is 55%, and the ee is 97% by HPLC analysis, and the reaction formula is as follows:
secondly, under the protection of argon, adding 3 ra' (0.5mmol) of the arylindolocarbazole derivative into 5ml of pyridine, then slowly dropwise adding phosphorus oxychloride (2.0mmol), reacting at 60 ℃ for 7h, cooling to room temperature, concentrating under reduced pressure to dryness, and then obtaining chiral arylindolocarbazole phosphoric acid shown by 3ra through column chromatography, wherein the yield is 79%, ee is 97%, and the reaction formula is as follows:
1H NMR(600MHz,CDCl3):δ＝8.82(dd,J＝8.3,1.1Hz,2H),8.77(d,J＝8.3Hz,1H),8.31–8.29(m,2H),8.08(d,J＝8.0Hz,1H),8.05(d,J＝7.4Hz,1H),7.98(dd,J＝8.1,1.2Hz,1H),7.93–7.87(m,2H),7.62(t,J＝7.6Hz,1H),7.48–7.39(m,3H),7.33–7.29(m,1H),7.24–7.22(m,1H),6.80(d,J＝8.2Hz,1H),6.66(d,J＝8.4Hz,1H)。
13C NMR(151MHz,CDCl3):δ＝142.07,141.60,141.53,141.33,141.33,132.68,132.67,131.58,131.57,130.91,130.87,130.03,129.99,129.13,128.35,127.99,127.68,127.67,127.59,127.58,127.54,126.62,126.13,126.12,125.99,125.75,125.66,125.35,125.34,124.96,124.74,124.70,124.65,123.94,123.23,121.89,120.92,120.52,118.87,118.52,118.51,113.78,113.56。
31P NMR(162MHz,CDCl3):δ＝5.24。
HRMS(ESI):calcd for C32H18O3N2P[M-H]-:509.1065,found 509.1071。
the method is characterized in that a commercially available traditional phosphoric acid catalyst and the chiral phosphoric acid compound 3ra are used as a novel phosphoric acid catalyst to catalyze the reaction of the compounds 4 and 5 to generate the compound 6, the using amount of the catalyst is 10 mol% of the mass of the compound 4, the reaction solvent is DCM, the reaction is carried out for 48h at room temperature, and chiral analysis on the product compound 6 shows that when the chiral phosphoric acid compound 3ra is used as the catalyst, the chiral selectivity of the product 6 reaches 33% ee, and the chiral selectivity of the commercially available traditional phosphoric acid catalyst is only 2% ee. The indole carbazole based phosphoric acid can be widely applied to different types of asymmetric synthesis to achieve better chiral control.
A commercially available phosphoric acid catalyst.
The applicant states that the present invention is illustrated by the above examples, but the present invention is not limited to the above examples, i.e. the present invention is not limited to the above examples, which means that the present invention can be implemented only by relying on the above examples. It should be understood by those skilled in the art that any modification of the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific modes, etc., are within the scope and disclosure of the present invention.
Claims (10)
1. A chiral phosphoric acid compound having an arylindolocarbazole skeleton, wherein the chiral phosphoric acid compound has a structure represented by formula I:
wherein R is1And R3Independently of one another, from hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl or substituted or unsubstituted ester groups, the M radicals being
R2And R4Independently of one another, from hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl or substituted or unsubstituted ester groups, the wavy line representing the attachment site of the radicals.
2. The chiral phosphoric acid compound having an arylindolocarbazole skeleton according to claim 1, wherein the substituted or unsubstituted alkyl group is a substituted or unsubstituted alkyl group having 1 to 5 carbon atoms;
preferably, the substituted or unsubstituted alkoxy group is a substituted or unsubstituted alkoxy group having 1 to 5 carbon atoms;
preferably, when the group has a substituent, the substituent is a halogen, an alkyl group having 1 to 5 carbon atoms, or a phenyl group.
3. The chiral phosphoric acid compound having an arylindolocarbazole skeleton according to claim 1 or 2, wherein R is1、R2And R3Independently of one another, from hydrogen, methyl, methoxy, fluorine, chlorine, bromine, benzyloxy, tert-butyl, aryl, ester or trifluoromethyl.
4. The chiral phosphoric acid compound having an arylindolocarbazole skeleton according to claim 3, wherein the aryl group is a phenyl group,
Wherein the wavy line representsThe attachment position of the group;
preferably, the ester group is-COOCH3、-OC4H8CO2CH3、-COOCH2CH3or-COOBn.
5. The chiral phosphoric acid compound having an arylindolocarbazole skeleton according to any one of claims 1 to 4, wherein the chiral phosphoric acid compound is any one of the following compounds:
6. the method for producing a chiral phosphoric acid compound having an arylindolocarbazole skeleton according to any one of claims 1 to 5, characterized by comprising the steps of:
(1) reacting diazo compound with M group shown in formula II with a compound shown in formula III to obtain the axial chiral arylindolocarbazole derivative shown in formula IV, wherein the reaction formula is as follows:
(2) reacting the axial chiral aryl indole carbazole derivative shown in the formula IV with phosphorus oxychloride to obtain a chiral phosphoric acid compound with an aryl indole carbazole skeleton shown in the formula I, wherein the reaction formula is as follows:
7. the method according to claim 6, wherein the molar ratio of the diazo compound having an M group represented by formula II to the compound of formula III in step (1) is 1:1 to 1: 1.8.
8. The preparation process according to claim 6 or 7, characterized in that the reaction of step (1) is carried out in the presence of a catalyst, preferably tetrakis [ (S) - (+) -1-adamantyl) - (N-phthalimido) acetate ] dirhodium (II);
preferably, the catalyst is used in an amount of 0.1 to 0.8% by mole based on the compound of formula III;
preferably, the reaction of step (1) is carried out at room temperature;
preferably, the reaction time in step (1) is 1 to 12 hours.
9. The preparation method according to any one of claims 6 to 8, wherein the molar ratio of the axial chiral arylindolocarbazole derivative represented by the formula IV to the phosphine oxide trichloride in the step (2) is 1:2 to 1: 5;
preferably, the solvent for the reaction of step (2) is pyridine;
preferably, the temperature of the reaction of the step (2) is 50-80 ℃;
preferably, the reaction time in step (2) is 1 to 12 hours.
10. Use of a chiral phosphoric acid compound having an arylindolocarbazole skeleton according to any one of claims 1 to 5 as a catalyst;
preferably, the catalyst is a catalyst for catalyzing the C-C bond cross-coupling reaction of 2-naphthol and benzoquinone.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107501160A (en) * | 2017-09-07 | 2017-12-22 | 南方科技大学 | Method for synthesizing axial chiral aryl indole through organic catalysis |
| CN107501163A (en) * | 2017-09-07 | 2017-12-22 | 南方科技大学 | Method for synthesizing axial chiral aniline indole under catalysis of chiral phosphoric acid |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107501160A (en) * | 2017-09-07 | 2017-12-22 | 南方科技大学 | Method for synthesizing axial chiral aryl indole through organic catalysis |
| CN107501163A (en) * | 2017-09-07 | 2017-12-22 | 南方科技大学 | Method for synthesizing axial chiral aniline indole under catalysis of chiral phosphoric acid |
Non-Patent Citations (2)
| Title |
|---|
| LIANG-WEN QI等: ""Organocatalytic asymmetric arylation of indoles enabled by azo groups"", 《NATURE CHEMISTRY》, vol. 10, pages 58 - 64 * |
| LIHAN ZHU等: ""Thecontrol effects of different scaffolds in chiral phosphoric acids: a case study of enantioselective asymmetric arylation"", 《CATAL.SCI.TECHNOL.》, vol. 9, pages 6482 - 6491 * |
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