CN113185553B - 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 37
- -1 phosphoric acid compound Chemical class 0.000 title claims abstract description 33
- 229910000147 aluminium phosphate Inorganic materials 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 27
- 238000006243 chemical reaction Methods 0.000 claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 239000010948 rhodium Substances 0.000 claims description 5
- 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
- 150000001989 diazonium salts Chemical class 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
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 2
- 229950011260 betanaphthol Drugs 0.000 claims description 2
- 238000006880 cross-coupling reaction Methods 0.000 claims description 2
- AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229910052703 rhodium Inorganic materials 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
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical class C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 150000005347 biaryls Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 125000004185 ester group Chemical group 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 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
- YNWSXIWHOSSPCO-UHFFFAOYSA-N rhodium(2+) Chemical compound [Rh+2] YNWSXIWHOSSPCO-UHFFFAOYSA-N 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
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 238000004679 31P NMR spectroscopy Methods 0.000 description 2
- 150000001716 carbazoles Chemical class 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 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 2
- 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 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000001424 substituent group Chemical group 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
- QJTQKPNNQVLHHO-UHFFFAOYSA-N 9h-carbazole;1h-indole Chemical compound C1=CC=C2NC=CC2=C1.C1=CC=C2C3=CC=CC=C3NC2=C1 QJTQKPNNQVLHHO-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 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
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000013461 design 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
- 150000002148 esters Chemical class 0.000 description 1
- 229960005544 indolocarbazole Drugs 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000006713 insertion reaction Methods 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 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
- 239000010452 phosphate Substances 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
- 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)
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- 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 invention provides a chiral phosphoric acid compound with an aryl indole carbazole skeleton, a preparation method and application thereof, wherein the chiral phosphoric acid compound has a structure shown in a formula I, the chiral phosphoric acid compound with the aryl indole carbazole skeleton can be used as a catalyst, the synthesis method is simple and efficient, the enantioselectivity is high, the yield is high, and a research foundation is provided for asymmetric synthesis of chiral organic catalysts.
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 biaryl is ubiquitous in many natural products, bioactive molecules and functional materials, and is the core structural motif of chiral catalysts and ligands that constitute asymmetric conversion reactions. So far, the asymmetric reaction promoted by the axial chiral biaryl catalyst is widely applied in the field of organic synthesis, such as chiral biaryl catalysts BINOL and H8-BINOL. Chiral Phosphoric Acid (CPA) based on BINOL bracket can effectively induce remarkable energy difference between diastereoisomer transition states in different reactions, has high-efficiency selectivity [(a)Parmar,D.;Sugiono,E.;Raja,S.;Rueping,M.Chem.Rev.2014,114,9047.(b)Shugrue,C.R.;Miller,S.J.Chem.Rev.2017,117,11894]., but the types of chiral biaryl phosphoric acid catalysts reported so far are limited. In the research of asymmetric catalysis, the design and synthesis of chiral catalysts are of great significance.
Indolocarbazoles are a very important class of high affinity ligands, which can effectively improve the corresponding induction of chiral ligands, and are key active ingredients of anticancer, antifungal, antibacterial and antihypertensive drugs. Therefore, the indolocarbazole skeleton with the advantages is introduced into chiral phosphoric acid, and the novel aryl indolocarbazole phosphoric acid catalyst developed shows better regioselectivity and stereoselectivity in the asymmetric catalysis field compared with biaryl skeleton.
In view of the foregoing, there is a need to develop chiral phosphoric acids having novel aryl indolocarbazole backbones 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 aryl indole carbazole skeleton, and a preparation method and application thereof.
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 aryl indole carbazole skeleton, the chiral phosphoric acid compound having a structure represented by formula I:
Wherein R 1 and R 3 are independently selected from hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl or substituted or unsubstituted ester group, and M is R 2 and R 4 are independently selected from hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl or 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 as described above has a substituent, the substituent is halogen, an alkyl group having 1 to 5 carbon atoms, or a phenyl group.
Preferably, R 1、R2 and R 3 are independently from each other selected from hydrogen, methyl, methoxy, fluoro, chloro, bromo, 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-COOCH 3、-OC4H8CO2CH3、-COOCH2CH3 or-COOBn.
Preferably, the chiral phosphoric acid compound with aryl indole carbazole 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 aryl indole carbazole skeleton as described above, the method comprising the steps of:
(1) The diazonium compound with M group shown in the formula II reacts with the compound shown in the formula III (indole [2,3-a ] carbazole derivative) to obtain the axial chiral aryl indole carbazole derivative shown in the formula IV, wherein the reaction formula is as follows:
(2) The axial chiral aryl indole carbazole derivative shown in the formula IV reacts with phosphorus oxychloride to obtain the chiral phosphoric acid compound shown in the formula I and having an aryl indole carbazole skeleton, wherein the reaction formula is as follows:
Preferably, the molar ratio of the diazonium compound with an M group represented by formula II 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 ] rhodium (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 of step (1) is 1-12 hours, for example 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 of step (2) is 1:2-1:5, e.g. 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 of the reaction of step (2) is pyridine.
Preferably, the temperature of the reaction in step (2) is 50-80 ℃, e.g. 50 ℃, 55 ℃, 58 ℃, 60 ℃, 65 ℃, 68 ℃, 70 ℃, 73 ℃, 75 ℃, 78 ℃ or 80 ℃.
Preferably, the reaction time of step (2) is 1-12 hours, for example 1 hour, 3 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours.
The preparation method of the invention synthesizes the axial chiral aryl indolocarbazole phosphoric acid selectively through the N-H insertion reaction shaft among Rh (II) catalytic molecules, has high enantioselectivity 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 a chiral phosphate compound having an aryl indole carbazole skeleton as described above as a catalyst.
Preferably, the catalyst is a catalyst that catalyzes a 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 phosphoric acid compound with aryl indole carbazole skeleton can be used as a catalyst, and the synthesis method is simple and efficient, high in enantioselectivity and high in yield, and provides a research foundation for asymmetric synthesis of chiral organic catalysts.
Detailed Description
The technical scheme of the invention is further described by the following specific embodiments. It will be apparent to those skilled in the art that the examples are merely to aid in understanding the invention and are not to be construed as a specific limitation thereof.
Example 1: synthesis of 3aa
Firstly, under the protection of argon, 1.0mmol of diazonaphthoquinone, 1.5mmol of indole [2,3-a ] carbazole and 1:1 molar equivalent ratio of tetrakis [ (S) - (+) -1-adamantyl) - (N-phthalimido) acetate ] rhodium (II) (Rh 2(S-PTAD)4) are mixed in chloroform, reacted for 6 hours at room temperature, concentrated to dryness under reduced pressure, and then the axial chiral arylindole carbazole derivative shown as 3aa' is obtained through column chromatography, the yield is 52%, ee 99% is obtained through HPLC analysis, the reaction formula is as follows:
secondly, under the protection of argon, 3aa' (0.5 mmol) of aryl indole carbazole derivative is added into 5ml of pyridine, then phosphorus oxychloride (2.0 mmol) is slowly added dropwise, the mixture is reacted for 7 hours at 60 ℃, cooled to room temperature, concentrated to dryness under reduced pressure, and chiral aryl indole carbazole phosphoric acid shown as 3aa is obtained through column chromatography, and 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 that: the 3aa 1 H-NMR spectrum and 13 C-NMR spectrum were carried out by nuclear magnetic resonance spectroscopy (Avance II 400 MHz). 31 P NMR was performed by nuclear magnetic resonance spectroscopy (Avance II 400 MHz) and HRMS was performed by electrospray mass spectrometer (ESI) (the same applies to the examples below).
Example 2: synthesis of 3ra
Firstly, under the protection of argon, diazonaphthoquinone derivative (1.0 mmol), indole [2,3-a ] carbazole (1.5 mmol) and tetra [ (S) - (+) -1-adamantyl) - (N-phthalimido) acetate ] rhodium (II) (Rh 2(S-PTAD)4) are mixed in chloroform according to the molar equivalent ratio of 1:1.5:0.5%, after the mixture is reacted for 12 hours at room temperature, the mixture is decompressed and concentrated to dryness, and then the axial chiral arylindole carbazole derivative shown as 3ra' is obtained through column chromatography, the yield is 55%, the ee 97% is obtained through HPLC analysis, and the reaction formula is as follows:
Secondly, under the protection of argon, 3ra' (0.5 mmol) of aryl indole carbazole derivative is added into 5ml of pyridine under the protection of argon, then phosphorus oxychloride (2.0 mmol) is slowly added dropwise, the mixture is reacted for 7 hours at 60 ℃, cooled to room temperature, concentrated to dryness under reduced pressure, and chiral aryl indole carbazole phosphoric acid shown as 3ra is obtained through column chromatography, and the yield is 79%, ee 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 chiral phosphoric acid 3ra is used as a novel phosphoric acid catalyst to catalyze the reaction of the compounds 4 and 5 to generate the compound 6, the catalyst dosage is 10mol% of the compound 4, the reaction solvent is DCM, the reaction is carried out for 48 hours at room temperature, and the chiral analysis of the product compound 6 proves that the chiral selectivity of the product 6 reaches 33%ee when the chiral phosphoric acid 3ra is used as the catalyst, and the chiral selectivity of the product 6 only reaches 2%ee when the chiral phosphoric acid 3ra is used as the catalyst. The indole carbazole-based phosphoric acid can be widely applied to asymmetric synthesis of different types, and better chiral control is achieved.
Commercial phosphoric acid catalysts.
The applicant states that the chiral phosphoric acid compound having an aryl indole carbazole skeleton, the preparation method and the application thereof are described by the above examples, but the present invention is not limited to the above examples, i.e. the present invention is not necessarily limited to the above examples. It should be apparent to those skilled in the art that any modification of the present invention, equivalent substitution of raw materials for the product of the present invention, addition of auxiliary components, selection of specific modes, etc., falls within the scope of the present invention and the scope of disclosure.
Claims (12)
1.A chiral phosphoric acid compound with an aryl indole carbazole skeleton, which is characterized by having a structure shown in a formula I:
Wherein R 1 and R 3 are selected from hydrogen and M is R 2 and R 4 are selected from hydrogen, and the wavy line represents the attachment site of the group.
2. The chiral phosphoric acid compound having an arylindole carbazole skeleton according to claim 1, wherein the chiral phosphoric acid compound is any one of the following compounds:
3. the method for producing a chiral phosphoric acid compound having an arylindolocarbazole skeleton according to claim 1 or 2, characterized by comprising the steps of:
(1) The diazonium compound with M group shown in the formula II reacts with the compound shown in the formula III to obtain the axial chiral aryl indole carbazole derivative shown in the formula IV, wherein the reaction formula is as follows:
The reaction in the step (1) is carried out in the presence of a catalyst, wherein the catalyst is tetra [ (S) - (+) -1-adamantyl) - (N-phthalimido) acetate ] rhodium (II);
(2) The axial chiral aryl indole carbazole derivative shown in the formula IV reacts with phosphorus oxychloride to obtain the chiral phosphoric acid compound shown in the formula I and having an aryl indole carbazole skeleton, wherein the reaction formula is as follows:
4. The process according to claim 3, wherein the molar ratio of the diazonium 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.
5. A process according to claim 3, wherein the catalyst is used in an amount of 0.1 to 0.8% of the molar amount of the compound of formula III.
6. A process according to claim 3, wherein the reaction of step (1) is carried out at room temperature.
7. A process according to claim 3, wherein the reaction time in step (1) is 1 to 12 hours.
8. The method according to claim 3, wherein the molar ratio of the axial chiral arylindolocarbazole derivative represented by formula IV in the step (2) to the phosphine oxide is 1:2 to 1:5.
9. A process according to claim 3, wherein the solvent of the reaction of step (2) is pyridine.
10. A process according to claim 3, wherein the temperature of the reaction in step (2) is 50-80 ℃.
11. A process according to claim 3, wherein the reaction time in step (2) is 1 to 12 hours.
12. Use of a chiral phosphoric acid compound having an aryl indole carbazole skeleton according to claim 1 or 2 as a catalyst;
the catalyst is a catalyst for catalyzing the cross-coupling reaction of the C-C bond of the 2-naphthol and the benzoquinone.
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| 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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| 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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