CN109354579A - A kind of biaryl axial chirality benzindole-naphthalene compounds and its synthetic method - Google Patents
A kind of biaryl axial chirality benzindole-naphthalene compounds and its synthetic method Download PDFInfo
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Abstract
The invention discloses a kind of biaryl axial chirality benzindole-naphthalene compounds and its synthetic method, this method to be realized by following steps: 1) R is added into 1 compound represented of structural formula4Cl and 4-dimethylaminopyridine add the first organic solvent and triethylamine after mixing evenly, react under room temperature, and after fully reacting, solvent, column chromatography for separation is removed under reduced pressure, obtains 2 compound represented of structural formula；2) 2 compound represented of structural formula is dissolved in the second organic solvent, add oxidant, it is reacted at 30~50 DEG C, after having reacted, saturated sodium bicarbonate solution washing, liquid separation, drying, solvent is removed under reduced pressure, through column chromatography for separation, obtains biaryl axial chirality benzindole-naphthalene compounds shown in structural formula 3；Operation of the present invention is simple, and reaction condition is mild, at low cost, and the yield of final product obtained is high, enantioselectivity is good.
Description
Technical field
The invention belongs to technical field of medicine synthesis, and in particular to a kind of biaryl axial chirality benzindole-naphthalenes chemical combination
Object and its synthetic method.
Background technique
Biaryl axial chirality compound is suffered from fields such as catalysis, chiral ligand and molecular recognitions and is widely applied.
The pure biaryl axial chirality compound of how succinct, efficient synthesizing optical has not attracted various chemists for it not
Slack effort.Only the synthesis of the biaryl axial chirality compound based on indoles skeleton is reported on a small quantity at present, and the base of these reports
In the biaryl axial chirality compound of indoles skeleton be all with indole nitrogen-aryl, indoles C (3)-aryl axial chirality compound,
Indoles C (2)-constructing for aryl axial chirality compound is not reported still.It is this that there is Yin from the perspective of ligand design
Diindyl C (2)-aryl axial chirality compound has huge development potentiality.Here, the strategy that we are changed using chirality for the first time,
Simple and convenient synthetic method is provided for efficiently constructing for such compound.
Summary of the invention
In view of this, the main purpose of the present invention is to provide a kind of biaryl axial chirality benzindole-naphthalene compounds；
The object of the invention is also to provide it is a kind of it is easy to operate, convenient separation, reaction condition is mild, yield is high, enantioselectivity is good
Biaryl axial chirality benzindole-naphthalene compounds synthetic method.
In order to achieve the above objectives, the technical scheme of the present invention is realized as follows: a kind of biaryl axial chirality benzindole-
Naphthalene compounds, which is characterized in that shown in its chemical structure such as formula (1):
Wherein, R is selected from least one of hydrogen, halogen, phenyl, silicon substrate；R1In hydrogen, halogen, methyl, tert-butyl
It is at least one；R2Selected from benzoyl, methoxy methyl acyl group, ethoxy acetyl, benzyloxy-formyl base, propyl formoxyl, different
At least one of propyl formoxyl；R3Selected from least one of hydrogen, halogen, methyl, phenyl, methoxyl group；R4Selected from fluoroform
At least one of sulfonyl, p-methylphenyl sulfonyl, p-bromophenyl sulfonyl.
Another technical method of the invention is achieved in that a kind of biaryl axial chirality benzindole-naphthalenes chemical combination
The synthetic method of object, this method are realized by following steps:
Step 1, R is added into 1 compound represented of structural formula4Cl and 4-dimethylaminopyridine add again after mixing evenly
Enter the first organic solvent and triethylamine, react under room temperature, after fully reacting, solvent, column chromatography for separation is removed under reduced pressure, obtains
2 compound represented of structural formula；
Step 2,2 compound represented of structural formula is dissolved in the second organic solvent, adds oxidant, 30~50
It is reacted at DEG C, after having reacted, saturated sodium bicarbonate solution washing, liquid separation, drying are removed under reduced pressure solvent, through column chromatography for separation, obtain
Obtain biaryl axial chirality benzindole-naphthalene compounds shown in structural formula 3.
The reaction equation of step 1 is as follows:
The reaction equation of step 2 is as follows:
Wherein, in each compound, R is selected from least one of hydrogen, halogen, phenyl, silicon substrate；R1Selected from hydrogen, halogen,
At least one of methyl, tert-butyl；R2Selected from benzoyl, methoxy methyl acyl group, ethoxy acetyl, benzyloxy-formyl
At least one of base, propyl formoxyl, isopropyl formoxyl；R3In hydrogen, halogen, methyl, phenyl, methoxyl group at least
It is a kind of；R4Selected from least one of trifyl, p-methylphenyl sulfonyl, p-bromophenyl sulfonyl.
Preferably, in the step 1,1 compound represented of structural formula, R4Between Cl, 4-dimethylaminopyridine
Molar ratio is 1:(0.2~1.5): (0.1~0.3).
Preferably, in the step 1, the molar ratio of 1 compound represented of structural formula and triethylamine be 1:(1.3~
1.7)；
Preferably, in the step 1, the R4Cl is TsCl, 4-BrC6H4SO2One of Cl.
Preferably, in the step 1, first organic solvent is selected from methylene chloride, toluene, tetrahydrofuran, acetonitrile, 1,
At least one of 2- dichloroethanes.
Preferably, in the step 2, the molar ratio of 2 compound represented of structural formula and oxidant is 1:(1-3).
Preferably, in the step 2, the oxidant is selected from DDQ, MnO2At least one of.
Preferably, in the step 2, second organic solvent is selected from methylene chloride, toluene, tetrahydrofuran, acetonitrile, 1,
At least one of 2- dichloroethanes.
Compared with prior art, the present invention by select chiral benzindole quinoline derivant be raw material and using DDQ or
MnO2As the synthetic method of oxidant, central chirality is effectively realized to the chiral inversion of axial chirality, has constructed biaryl
Axial chirality compound, and in compound obtained and nitrogen-atoms is adjacent to chiral axis；Operation of the present invention is simple, reaction condition temperature, at
This is low, and the yield of final product obtained is high, enantioselectivity is good.
Detailed description of the invention
Fig. 1 is the hydrogen spectrogram for the compound 3a that the embodiment of the present invention 1 obtains；
Fig. 2 is the carbon spectrogram for the compound 3a that the embodiment of the present invention 1 obtains；
Fig. 3 is the high-efficient liquid phase chromatogram for the compound 3a raceme that the embodiment of the present invention 1 obtains；
Fig. 4 is the high-efficient liquid phase chromatogram for the compound 3a that the embodiment of the present invention 1 obtains.
Specific embodiment
In order to make the objectives, technical solutions, and advantages of the present invention clearer, with reference to the accompanying drawings and embodiments, right
The present invention is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, and
It is not used in the restriction present invention.
The embodiment of the invention provides a kind of biaryl axial chirality benzindole-naphthalene compounds, chemical structure such as formulas
(1) shown in:
Wherein, R is selected from least one of hydrogen, halogen, phenyl, silicon substrate；R1In hydrogen, halogen, methyl, tert-butyl
It is at least one；R2Selected from benzoyl, methoxy methyl acyl group, ethoxy acetyl, benzyloxy-formyl base, propyl formoxyl, different
At least one of propyl formoxyl；R3Selected from least one of hydrogen, halogen, methyl, phenyl, methoxyl group；R4Selected from fluoroform
At least one of sulfonyl, p-methylphenyl sulfonyl, p-bromophenyl sulfonyl.
The embodiment of the invention provides a kind of synthetic method of biaryl axial chirality benzindole-naphthalene compounds, the party
Method is realized by following steps:
Step 1, R is added into 1 compound represented of structural formula4Cl and 4-dimethylaminopyridine (DMAP), stir evenly
After add the first organic solvent and triethylamine, react under room temperature, after fully reacting, be removed under reduced pressure solvent, column chromatography point
From acquisition 2 compound represented of structural formula (intermediate product)；
Step 2,2 compound represented of structural formula is dissolved in the second organic solvent, adds oxidant, 30~50
It is reacted at DEG C, after having reacted, saturated sodium bicarbonate solution washing, liquid separation, drying are removed under reduced pressure solvent, through column chromatography for separation, obtain
Obtain biaryl axial chirality benzindole-naphthalene compounds shown in structural formula 3.
Wherein, in the structure of each reactant, R is selected from least one of hydrogen, halogen, phenyl, silicon substrate；R1Selected from hydrogen, halogen
At least one of element, methyl, tert-butyl；R2Selected from benzoyl, methoxy methyl acyl group, ethoxy acetyl, benzyloxy first
At least one of acyl group, propyl formoxyl, isopropyl formoxyl；R3In hydrogen, halogen, methyl, phenyl, methoxyl group extremely
Few one kind；R4Selected from least one of trifyl, p-methylphenyl sulfonyl, p-bromophenyl sulfonyl.
Further, in step 1,1 compound represented of structural formula, R4Molar ratio between Cl, DMAP be 1:(0.2~
1.5): (0.1~0.3)；1 compound represented of structural formula and the molar ratio of triethylamine are 1:(1.3~1.7)；R4Cl be TsCl,
4-BrC6H4SO2One of Cl；First organic solvent is selected from methylene chloride, toluene, tetrahydrofuran, acetonitrile, 1,2- dichloroethanes
At least one of.
Further, in step 2, the molar ratio of 2 compound represented of structural formula and oxidant is 1:(1-3)；Oxidant
Selected from DDQ, MnO2At least one of, preferably DDQ；Second organic solvent is selected from methylene chloride, toluene, tetrahydrofuran, second
At least one of nitrile, 1,2- dichloroethanes.
The embodiment of the invention also provides 1 compound represented of structural formula (chirality 2,3- diaryl benzindole quinoline classes
Close object) synthetic method, this method are as follows: by 4 compound represented of structural formula, 5 compound represented of structural formula, additive 3A point
Son sieve and catalyst are dissolved in third organic solvent, and 36h is reacted at -36 DEG C, after fully reacting, filters, solvent is removed under reduced pressure,
Through column chromatography for separation, chirality 2 shown in the structural formula 1,3- diaryl benzindole quinoline class compound are obtained.
Wherein, the molar ratio of 4 compound represented of structural formula and 5 compound represented of structural formula is 1.5:1, structural formula 5
Compound represented and the molar ratio of catalyst are 1.0:0.1；Catalyst is further selected from chiral phosphoric acid, loop coil derived from dinaphthol
At least one of class chiral phosphoric acid；Additive is selected from least one of 3A molecular sieve, 4A molecular sieve, 5A molecular sieve, preferably
For 3A molecular sieve；Third organic solvent is selected from methylene chloride, toluene, tetrahydrofuran, acetonitrile, at least one in 1,2- dichloroethanes
Kind, preferably methylene chloride.
Its reaction equation is as follows:
In reaction equation, R is selected from least one of hydrogen, silicon substrate, halogen；R1In hydrogen, halogen, methyl, tert-butyl
It is at least one；R2Selected from benzoyl, methoxy methyl acyl group, ethoxy acetyl, benzyloxy-formyl base, propyl formoxyl, different
At least one of propyl formoxyl；R3Selected from least one of hydrogen, phenyl, methoxyl group, methyl, halogen.
This method specifically: under the protection of inert nitrogen gas or argon gas, by naphthol derivative shown in structural formula 4
2- azo naphthalene derivatives (0.1mmol), catalyst (0.01mmol) shown in (0.15mmol), structural formula 5 and 3A molecular sieve
(100mg) is added in Schlenk bottles, vacuumizes, and displacement nitrogen three times, adds the methylene chloride of 2ml ice-cold (- 30 DEG C) ,-
It is stirred to react 36h at 30 DEG C, after TLC plate monitors fully reacting, restores room temperature, filtering removal molecular sieve, decompression to reaction system
Solvent is boiled off, is chromatographed post separation (petroleum ether: ethyl acetate=6:1), chirality 2 shown in structural formula 1,3- diaryl benzo are obtained
Indoline-like compound.
Table 1 be under the preferred conditions 1 compound represented of preparation structure formula when, raw materials used structural formula and final
Synthesize structural formula and the production of 1 compound represented of structural formula (chirality 2,3- diaryl benzindole quinoline class compound) obtained
Rate；
To structural formula 1a compound represented in table 1 carry out respectively nuclear magnetic resonance, optically-active, infrared, high resolution mass spectrum and
High performance liquid chromatography detection, detection data are as follows:
Magnetic resonance detection result are as follows:1H NMR(400MHz,Chloroform-d)δ9.90(s,1H),8.54(s,1H),
7.89 (d, J=8.2Hz, 1H), 7.82-7.68 (m, 5H), 7.51 (t, J=7.5Hz, 1H), 7.41 (ddd, J=8.2,5.9,
2.0Hz, 1H), 7.38-7.13 (m, 13H), 7.03 (d, J=4.1Hz, 2H), 6.21 (s, 1H), 5.09 (d, J=10.7Hz,
1H)；13C NMR (100MHz, Chloroform-d) δ=166.92,155.12,147.04,141.16,133.55,132.35,
131.85,131.61,130.44,130.22,130.19,129.00,128.94,128.82,128.73,128.65,128.27,
127.26,127.14,126.64,125.98,123.91,122.88,122.80,121.70,114.17,112.82,54.53；
Optically-active testing result are as follows:
Infrared detection testing result are as follows: IR (KBr): 3423,2924,1654,1267,822,746,684cm-1；
High resolution mass spectrum testing result are as follows: HRMS (ESI) calcd for C35H26N2O2Na m/z[M+Na]+:
529.1886；Found:529.1868；
High performance liquid chromatography detection result are as follows: HPLC (Daicel Chiralpak IC, i-PrOH/hexane=15/85,
Flow rate 0.8mL/min, λ=230nm): t1(minor)=14.7min, t2(major)=29.4min.
To structural formula 1b compound represented in table 1 carry out respectively nuclear magnetic resonance, optically-active, infrared, high resolution mass spectrum and
High performance liquid chromatography detection, detection data are as follows:
Magnetic resonance detection result are as follows:1δ=9.82 (s, 1H) H NMR (400MHz, Chloroform-d), 8.40 (s,
1H), 7.82 (d, J=8.2Hz, 1H), 7.75-7.60 (m, 5H), 7.44 (t, J=7.4Hz, 1H), 7.38-7.10 (m, 9H),
7.07-6.90 (m, 7H), 6.10 (s, 1H), 4.98 (d, J=10.6Hz, 1H), 2.30 (s, 3H)；13C NMR (100MHz,
CDCl3): δ=166.86,155.11,146.94,138.16,136.65,133.57,132.33,131.90,131.61,
130.52,130.12,129.47,128.94,128.77,128.65,128.23,127.26,126.57,125.92,123.94,
123.88,123.15,122.75,121.84,114.34,112.85,54.17,21.15；
Optically-active testing result are as follows:
Infrared detection testing result are as follows: IR (KBr): 3238,2924,2852,1518,1265,1022,813,746cm-1；
High resolution mass spectrum testing result are as follows: HRMS (ESI) calcd for C36H28N2O2Na m/z[M+Na]+:
543.2043；Found:543.2023；
High performance liquid chromatography detection result are as follows: HPLC (Daicel Chiralpak IC, i-PrOH/hexane=15/85,
Flow rate 0.8mL/min, λ=230nm): t1(minor)=13.3min, t2(major)=29.1min.
To structural formula 1e compound represented in table 1 carry out respectively nuclear magnetic resonance, optically-active, infrared, high resolution mass spectrum and
High performance liquid chromatography detection, detection data are as follows:
Magnetic resonance detection result are as follows:1δ=9.46 (s, 1H) H NMR (400MHz, Chloroform-d), 7.88 (dd, J
=8.7,4.5Hz, 2H), 7.75 (dd, J=14.3,8.5Hz, 2H), 7.47-7.04 (m, 13H), 7.05-6.90 (m, 1H),
6.86 (d, J=8.8Hz, 2H), 5.86 (s, 1H), 4.94 (d, J=10.8Hz, 1H), 3.68 (s, 3H)；13C NMR (100MHz,
Chloroform-d) δ=155.05,147.06,141.06,133.52,131.69,130.31,128.94,128.87,
128.75,128.34,127.20,126.69,125.97,123.94,122.80,121.52,113.70,112.84,54.09,
52.81；
Optically-active testing result are as follows:
Infrared detection testing result are as follows: IR (KBr): 3251,2924,1517,1267,1225,810,744cm-1；
High resolution mass spectrum testing result are as follows: HRMS (ESI) calcd for C30H24N2O3Na m/z[M+Na]+:
483.1679；Found:483.1669；
High performance liquid chromatography detection result are as follows: HPLC (Daicel Chiralpak IC, i-PrOH/hexane=15/85,
Flow rate 0.8mL/min, λ=250nm): t1(minor)=8.8min, t2(major)=11.4min.
To structural formula 1j compound represented in table 1 carry out respectively nuclear magnetic resonance, optically-active, infrared, high resolution mass spectrum and
High performance liquid chromatography detection, detection data are as follows:
Magnetic resonance detection result are as follows: δ=9.48 (s, 1H) 1H NMR (400MHz, Chloroform-d), 8.04-7.57
(m, 4H), 7.51-6.67 (m, 15H), 4.94 (d, J=10.8Hz, 1H), 4.18-3.95 (m, 2H), 1.60 (td, J=17.4,
16.9,10.2Hz, 2H), 0.87 (t, J=7.4Hz, 3H)；δ=155.06 13C NMR (100MHz, Chloroform-d),
141.10,131.67,130.30,130.22,128.93,128.86,128.74,128.33,127.19,126.68,125.95,
123.98,122.79,121.55,120.20,113.80,112.85,67.46,54.11,22.12,10.16；
Optically-active testing result are as follows:
Infrared detection testing result are as follows: IR (KBr): 3448,2940,2362,1624,1263,1229,809,748cm-1；
High resolution mass spectrum testing result are as follows: HRMS (ESI) calcd for C32H28N2O3Na m/z [M+Na]+:
511.1992；Found:511.1969；
High performance liquid chromatography detection result are as follows: HPLC (Daicel Chiralpak IC, i-PrOH/hexane=15/85,
Flow rate 0.8mL/min, λ=250nm): t1(minor)=7.5min, t2(major)=9.4min.
The related data of compound about the acquisition of serial number 3,4,6,7,8,10 is not enumerated one by one herein.
Table 2 is a kind of biaryl axial chirality of the structural formula of intermediate product and final synthesis acquisition in embodiment 1-10
Benzindole-naphthalene compounds structural formula and yield are made embodiment 1-10 now in conjunction with the structural formula in table 2 further old
It states, particular content is as follows:
Embodiment 1
Compound 3a is synthesized by compound 1a
Step 1, under the protection of inert gas, compound 1a (0.2mmol) is added in the round-bottomed flask of 25ml, is added
TsCl (0.24mmol) and DMAP (0.04mmolq), adds 12mL methylene chloride and triethylamine after mixing evenly
(0.3mmol), reacts under room temperature, and solvent, column chromatography for separation (petroleum ether: second is removed under reduced pressure in TLC plate monitoring, fully reacting
Acetoacetic ester=6:1), obtain intermediate compound 2a；
Step 2, compound 2a (0.2mmol) is added in the three-necked bottle with condenser, 10ml methylene chloride is added, it will
Reaction system is placed in 40 DEG C of oil bath, is slow added into the dichloromethane solution (0.4mmol DDQ, 10ml DCM) of DDQ,
The monitoring of TLC plate, fully reacting are washed with saturated sodium bicarbonate solution, liquid separation, drying, solvent, column chromatography for separation are removed under reduced pressure
(petroleum ether: ethyl acetate=6:1) obtains compound 3a (white solid, 130mg, 94%).
Carry out nuclear magnetic resonance, optically-active, infrared, high resolution mass spectrum and high performance liquid chromatography detection respectively to compound 3a,
Detection data is as follows:
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of compound 3a, and the carbon-13 nmr spectra figure that Fig. 2 is compound 3a is specific to examine
Measured data are as follows:1δ=9.46 (s, 1H) H NMR (400MHz, Chloroform-d), 8.05 (t, J=7.2Hz, 2H), 7.96-
7.82 (m, 3H), 7.79 (d, J=7.9Hz, 1H), 7.66 (d, J=8.8Hz, 1H), 7.57 (d, J=7.6Hz, 1H), 7.55-
7.41 (m, 4H), 7.41-7.24 (m, 6H), 7.25-7.03 (m, 4H), 6.84 (d, J=7.9Hz, 2H), 2.14 (s, 3H)；13C
NMR (100MHz, Chloroform-d) δ=165.52,145.91,145.65,135.54,134.61,134.02,132.56,
132.25,131.79,131.71,131.57,130.58,130.36,130.05,129.56,128.95,128.71,127.66,
127.57,127.30,127.16,126.90,126.81,125.67,125.00,123.49,123.43,121.81,120.62,
120.28,118.95,111.04,21.37；
Optically-active testing result are as follows:
Infrared detection testing result are as follows: IR (KBr): 3442,2922,2360,1630,1385,1173,802,706,
565cm-1；
High resolution mass spectrum testing result are as follows: HRMS (ESI) calcd for C42H31N2O4S m/z[M+H]+: 659.1999；
Found:659.2012；
Fig. 4 is the high-efficient liquid phase chromatogram of compound 3a, specific detection data are as follows: HPLC (DaicelChiralpak IC,
I-PrOH/hexane=20/80, flow rate 0.8mL/min, λ=250nm): t1(minor)=11.7min, t2
(major)=13.3min.
Fig. 3 is the high-efficient liquid phase chromatogram of compound 3a raceme.
Embodiment 2
Compound 3b is synthesized by compound 1b
Step 1, under the protection of inert gas, compound 1b (0.2mmol) is added in the round-bottomed flask of 25ml, is added
TsCl (0.24mmol) and DMAP (0.04mmol), adds 12mL methylene chloride and triethylamine (0.3mmol) after mixing evenly,
React under room temperature, TLC plate monitoring, fully reacting, be removed under reduced pressure solvent, column chromatography for separation (petroleum ether: ethyl acetate=6:
1) intermediate compound 2b, is obtained；
Step 2, compound 2b (0.2mmol) is added in the three-necked bottle with condenser, 10ml methylene chloride is added, it will
Reaction system is placed in 40 DEG C of oil bath, is slow added into the dichloromethane solution (0.4mmol DDQ, 10ml DCM) of DDQ,
The monitoring of TLC plate, fully reacting are washed with saturated sodium bicarbonate solution, liquid separation, drying, solvent, column chromatography for separation are removed under reduced pressure
(petroleum ether: ethyl acetate=6:1) obtains compound 3b (white solid, 129mg, 96%).
Carry out nuclear magnetic resonance, optically-active, infrared, high resolution mass spectrum and high performance liquid chromatography detection respectively to compound 3b,
Detection data is as follows:
Magnetic resonance detection result are as follows:1δ=9.44 (s, 1H) H NMR (400MHz, Chloroform-d), 8.04 (t, J
=6.8Hz, 2H), 7.86 (ddd, J=34.9,16.8,8.7Hz, 4H), 7.70-7.42 (m, 7H), 7.34 (dt, J=12.9,
6.2Hz, 6H), 7.14 (d, J=7.6Hz, 1H), 6.99 (dd, J=23.8,7.2Hz, 3H), 6.82 (d, J=7.8Hz, 2H),
2.29 (s, 3H), 2.14 (s, 3H)；13C NMR (100MHz, Chloroform-d) δ=165.51,145.85,136.37,
132.53,132.23,131.78,131.51,130.54,130.16,129.81,129.53,128.89,128.81,128.71,
127.66,127.56,127.35,127.16,126.81,125.61,124.92,123.47,121.97,120.66,111.03,
21.38 21.24；
Optically-active testing result are as follows:
Infrared detection testing result are as follows: IR (KBr): 3411,2922,2837,1625,1172,955,815cm-1；
High resolution mass spectrum testing result are as follows: HRMS (ESI) calcd for C43H33N2O4S m/z[M+H]+: 673.2156；
Found:673.2169；
High performance liquid chromatography detection result are as follows: HPLC (Daicel Chiralpak IC, i-PrOH/hexane=20/80,
Flow rate 0.8mL/min, λ=250nm): t1(minor)=13.3min, t2(major)=39.8min.
Embodiment 3
Compound 3c is synthesized by compound 1c
Step 1, under the protection of inert gas, compound 1c (0.2mmol) is added in the round-bottomed flask of 25ml, is added
TsCl (0.24mmol) and DMAP (0.04mmol), adds 12mL methylene chloride and triethylamine (0.3mmol) after mixing evenly,
React under room temperature, TLC plate monitoring, fully reacting, be removed under reduced pressure solvent, column chromatography for separation (petroleum ether: ethyl acetate=6:
1) intermediate compound 2c, is obtained；
Step 2, compound 2c (0.2mmol) is added in the three-necked bottle with condenser, 10ml methylene chloride is added, it will
Reaction system is placed in 40 DEG C of oil bath, is slow added into the dichloromethane solution (0.4mmol DDQ, 10ml DCM) of DDQ,
The monitoring of TLC plate, fully reacting are washed with saturated sodium bicarbonate solution, liquid separation, drying, solvent, column chromatography for separation are removed under reduced pressure
(petroleum ether: ethyl acetate=6:1) obtains compound 3c (white solid, 130mg, 94%).
Carry out nuclear magnetic resonance, optically-active, infrared, high resolution mass spectrum and high performance liquid chromatography detection respectively to compound 3c,
Detection data is as follows:
Magnetic resonance detection result are as follows:1δ=9.43 (s, 1H) H NMR (400MHz, Chloroform-d), 8.03 (dd, J
=14.2,8.1Hz, 2H), 7.93 (d, J=9.0Hz, 1H), 7.84 (q, J=8.4,7.5Hz, 3H), 7.65 (d, J=8.9Hz,
1H), 7.56 (d, J=7.6Hz, 5H), 7.48 (d, J=7.8Hz, 3H), 7.37 (td, J=22.3,20.7,11.3Hz, 7H),
7.24-7.07 (m, 3H), 6.85 (d, J=7.9Hz, 2H), 2.16 (s, 3H)；13C NMR (100MHz, Chloroform-d) δ=
165.48,145.87,145.74,134.51,134.11,132.81,132.50,132.30,131.79,131.74,131.61,
131.41,130.60,129.59,129.05,128.88,128.72,128.52,128.31,128.07,127.80,127.66,
127.60,127.15,126.91,125.80,125.18,123.63,123.22,121.51,120.59,118.95,118.72,
111.05,21.39；
Optically-active testing result are as follows:
Infrared detection testing result are as follows: IR (KBr): 3373,2924,1701,1352,1173,941,806,748,
544cm-1；
High resolution mass spectrum testing result are as follows: HRMS (ESI) calcd for C42H30N2O4SCl m/z[M+H]+:
693.1609；Found:693.1629；
High performance liquid chromatography detection result are as follows: HPLC (Daicel Chiralpak IC, i-PrOH/hexane=30/70,
Flow rate 0.8mL/min, λ=250nm): t1(minor)=9.6min, t2(major)=26.5min.
Embodiment 4
Compound 3d is synthesized by compound 1d
Step 1, under the protection of inert gas, (0.2mmol) of compound 1d is added in the round-bottomed flask of 25ml, is added
Enter TsCl (0.2mmol) and DMAP (0.02mmol), adds 12mL methylene chloride and triethylamine after mixing evenly
(0.26mmol), reacts under room temperature, TLC plate monitoring, fully reacting, be removed under reduced pressure solvent, column chromatography for separation (petroleum ether:
Ethyl acetate=6:1), obtain intermediate compound 2d；
Step 2, compound 2d (0.2mmol) is added in the three-necked bottle with condenser, 10ml methylene chloride is added, it will
Reaction system is placed in 50 DEG C of oil bath, is slow added into the dichloromethane solution (0.2mmol DDQ, 10ml DCM) of DDQ,
The monitoring of TLC plate, fully reacting are washed with saturated sodium bicarbonate solution, liquid separation, drying, solvent, column chromatography for separation are removed under reduced pressure
(petroleum ether: ethyl acetate=6:1) obtains compound 3d (white solid, 139mg, 94%).
Carry out nuclear magnetic resonance, optically-active, infrared, high resolution mass spectrum and high performance liquid chromatography detection respectively to compound 3d,
Detection data is as follows:
Magnetic resonance detection result are as follows:1δ=9.53-9.26 (m, 1H) H NMR (400MHz, Chloroform-d),
8.05-7.95 (m, 2H), 7.91 (d, J=9.0Hz, 1H), 7.88-7.75 (m, 3H), 7.63 (dd, J=8.9,2.6Hz, 1H),
7.58-7.50 (m, 2H), 7.47 (tt, J=7.7,3.1Hz, 3H), 7.42-7.27 (m, 8H), 7.23 (d, J=8.3Hz, 1H),
7.09 (d, J=8.3Hz, 1H), 6.92 (s, 1H), 6.83 (d, J=8.0Hz, 2H), 2.14 (s, 3H)；13C NMR (100MHz,
Chloroform-d) δ=165.49,145.86,145.79,134.61,134.51,134.10,132.43,132.34,
131.95,131.79,131.58,131.30,131.23,130.59,129.61,129.10,128.75,128.51,127.85,
127.71,127.61,127.16,127.06,126.95,125.85,125.22,123.68,123.23,121.48,121.10,
120.61,118.94,118.65,111.07,21.43；
Optically-active testing result are as follows:
Infrared detection testing result are as follows: IR (KBr): 3373,2924,1697,1172,801,748,702cm-1；
High resolution mass spectrum testing result are as follows: HRMS (ESI) calcd for C42H30N2O4SBr m/z[M+H]+:
737.1104；Found:737.1119；
High performance liquid chromatography detection result are as follows: HPLC (Daicel Chiralpak IC, i-PrOH/hexane=20/80,
Flow rate 0.8mL/min, λ=230nm): t1(minor)=11.9min, t2(major)=12.6min.
Embodiment 5
Compound 3e is synthesized by compound 1e
Step 1, under the protection of inert gas, compound 1e (0.2mmol) is added in the round-bottomed flask of 25ml, is added
TsCl (0.24mmol) and DMAP (0.04mmol), adds 12mL methylene chloride and triethylamine (0.3mmol) after mixing evenly,
React under room temperature, TLC plate monitoring, fully reacting, be removed under reduced pressure solvent, column chromatography for separation (petroleum ether: ethyl acetate=6:
1) intermediate compound 2e, is obtained；
Step 2, compound 2e (0.2mmol) is added in the three-necked bottle with condenser, 10ml methylene chloride is added, it will
Reaction system is placed in 40 DEG C of oil bath, is slow added into the dichloromethane solution (0.4mmol DDQ, 10ml DCM) of DDQ,
The monitoring of TLC plate, fully reacting are washed with saturated sodium bicarbonate solution, liquid separation, drying, solvent, column chromatography for separation are removed under reduced pressure
(petroleum ether: ethyl acetate=6:1), acquisition compound 3e (white solid, 116mg, 95%).
Carry out nuclear magnetic resonance, optically-active, infrared, high resolution mass spectrum and high performance liquid chromatography detection respectively to compound 3e,
Detection data is as follows:
Magnetic resonance detection result are as follows:1δ=8.15-7.73 (m, 7H) H NMR (400MHz, Chloroform-d), 7.67
(d, J=8.6Hz, 1H), 7.57-7.25 (m, 10H), 7.25-7.01 (m, 5H), 6.84 (s, 2H), 3.56 (s, 3H), 2.13
(s, 3H)；13C NMR (100MHz, Chloroform-d) δ=155.23,145.49,135.47,134.12,132.76,
131.92,131.58,130.55,130.29,129.52,128.99,128.62,128.04,127.59,126.91,126.62,
125.78 124.98,123.50,120.93,120.24,110.62,53.00,21.38；
Optically-active testing result are as follows:
Infrared detection testing result are as follows: IR (KBr): 3378,2925,1725,1156,954,753cm-1；
High resolution mass spectrum testing result are as follows: HRMS (ESI) calcd for C37H29N2O5S m/z[M+H]+: 613.1792；
Found:613.1809；
High performance liquid chromatography detection result are as follows: HPLC (Daicel Chiralpak IC, i-PrOH/hexane=20/80,
Flow rate 0.8mL/min, λ=250nm): t1(minor)=11.5min, t2(major)=22.1min.
Embodiment 6
Compound 3f is synthesized by compound 1f
Step 1, under the protection of inert gas, compound 1f (0.2mmol) is added in the round-bottomed flask of 25ml, is added
TsCl (0.24mmol) and DMAP (0.04mmol), adds 12mL tetrahydrofuran and triethylamine (0.3mmol) after mixing evenly,
React under room temperature, TLC plate monitoring, fully reacting, be removed under reduced pressure solvent, column chromatography for separation (petroleum ether: ethyl acetate=6:
1) intermediate compound 2f, is obtained；
Step 2, compound 2f (0.2mmol) is added in the three-necked bottle with condenser, 10ml tetrahydrofuran is added, it will
Reaction system is placed in 30 DEG C of oil bath, is slow added into the tetrahydrofuran solution (0.6mmol DDQ, 10ml THF) of DDQ,
The monitoring of TLC plate, fully reacting are washed with saturated sodium bicarbonate solution, liquid separation, drying, solvent, column chromatography for separation are removed under reduced pressure
(petroleum ether: ethyl acetate=6:1) obtains compound 3f (white solid, 121mg, 97%).
Carry out nuclear magnetic resonance, optically-active, infrared, high resolution mass spectrum and high performance liquid chromatography detection respectively to compound 3f,
Detection data is as follows:
Magnetic resonance detection result are as follows:1δ=8.05 (d, J=8.2Hz, 1H) H NMR (400MHz, Chloroform-d),
7.89 (dd, J=29.0,9.0Hz, 6H), 7.66 (d, J=8.9Hz, 1H), 7.58-7.26 (m, 9H), 7.18 (s, 3H), 6.81
(d, J=8.0Hz, 2H), 4.03 (s, 2H), 2.11 (s, 3H), 1.04 (d, J=26.5Hz, 3H)；13C NMR (100MHz,
Chloroform-d) δ=154.86,145.43,135.51,134.17,132.77,131.91,131.49,130.54,
130.37,129.47,128.95,128.63,128.12,128.00,127.55,126.86,126.58,125.70,124.89,
123.50,120.93,120.16,118.54,110.68,62.13,21.33,14.18；
Optically-active testing result are as follows:
Infrared detection testing result are as follows:；IR (KBr): 3365,2924,1723,1163,938,731cm-1；
High resolution mass spectrum testing result are as follows: HRMS (ESI) calcd for C38H31N2O5S m/z[M+H]+: 627.1948；
Found:627.1955；
High performance liquid chromatography detection result are as follows: HPLC (Daicel Chiralpak IC, i-PrOH/hexane=20/80,
Flow rate 0.8mL/min, λ=250nm): t1(minor)=10.9min, t2(major)=25.5min.
Embodiment 7
Compound 3g is synthesized by compound 1g
Step 1, under the protection of inert gas, compound 1g (0.2mmol) is added in the round-bottomed flask of 25ml, is added
TsCl (0.24mmol) and DMAP (0.04mmol), adds 12mL methylene chloride and triethylamine (0.3mmol) after mixing evenly,
React under room temperature, TLC plate monitoring, fully reacting, be removed under reduced pressure solvent, column chromatography for separation (petroleum ether: ethyl acetate=6:
1) intermediate compound 2g, is obtained；
Step 2, compound 2g (0.2mmol) is added in the three-necked bottle with condenser, 10ml methylene chloride is added, it will
Reaction system is placed in 40 DEG C of oil bath, is slow added into the dichloromethane solution (0.4mmol DDQ, 10ml DCM) of DDQ,
The monitoring of TLC plate, fully reacting are washed with saturated sodium bicarbonate solution, liquid separation, drying, solvent, column chromatography for separation are removed under reduced pressure
(petroleum ether: ethyl acetate=6:1) obtains compound 3g (white solid, 129mg, 94%).
Carry out nuclear magnetic resonance, optically-active, infrared, high resolution mass spectrum and high performance liquid chromatography detection respectively to compound 3g,
Detection data is as follows:
Magnetic resonance detection result are as follows:1δ=8.14-7.76 (m, 9H) H NMR (400MHz, Chloroform-d), 7.60
(d, J=8.9Hz, 1H), 7.55-7.22 (m, 9H), 7.16 (s ,-1H), 7.07 (d, J=18.0Hz, 3H), 6.79 (d, J=
7.9Hz, 2H), 5.31-4.80 (m, 2H), 2.11 (s, 3H)；13δ=154.69 C NMR (100MHz, Chloroform-d),
145.39,135.43,134.10,132.73,131.86,131.46,130.54,129.44,128.92,128.61,128.45,
128.18,127.94,127.55,126.82,126.61,125.68,124.92,123.48,120.87,120.25,110.60,
67.54 21.32；
Optically-active testing result are as follows:
Infrared detection testing result are as follows: IR (KBr): 3373,2924,1701,1261,1170,943,750cm-1；
High resolution mass spectrum testing result are as follows: HRMS (ESI) calcd for C43H33N2O5S m/z[M+H]+: 689.2105；
Found:689.2131；
High performance liquid chromatography detection result are as follows: HPLC (Daicel Chiralpak IE, i-PrOH/hexane=30/70,
Flow rate 0.8mL/min, λ=250nm): t1(minor)=14.8min, t2(major)=16.9min.
Embodiment 8
Compound 3i is synthesized by compound 1i
Step 1, under the protection of inert gas, compound 1i (0.2mmol) is added in the round-bottomed flask of 25ml, is added
TsCl (0.24mmol) and DMAP (0.04mmol), adds 12mL methylene chloride and triethylamine (0.3mmol) after mixing evenly,
React under room temperature, TLC plate monitoring, fully reacting, be removed under reduced pressure solvent, column chromatography for separation (petroleum ether: ethyl acetate=6:
1) intermediate compound 2i, is obtained；
Step 2, compound 2i (0.2mmol) is added in the three-necked bottle with condenser, 10ml methylene chloride is added, it will
Reaction system is placed in 40 DEG C of oil bath, is slow added into the dichloromethane solution (0.4mmol DDQ, 10ml DCM) of DDQ,
The monitoring of TLC plate, fully reacting are washed with saturated sodium bicarbonate solution, liquid separation, drying, solvent, column chromatography for separation are removed under reduced pressure
(petroleum ether: ethyl acetate=6:1) obtains compound 3i (white solid, 140mg, 95%).
Carry out nuclear magnetic resonance, optically-active, infrared, high resolution mass spectrum and high performance liquid chromatography detection respectively to compound 3i,
Detection data is as follows:
Magnetic resonance detection result are as follows:1H NMR (400MHz, Chloroform-d) δ 9.41 (d, J=18.6Hz, 1H),
8.12-7.75 (m, 4H), 7.72-7.42 (m, 6H), 7.41-7.25 (m, 7H), 7.14-6.88 (m, 3H), 6.81 (d, J=
8.2Hz, 2H), 2.13 (s, 3H)；13C NMR (100MHz, Chloroform-d) δ 165.46,145.74,134.27,132.30,
131.80,131.59,130.62,129.92,129.67,129.06,128.72,128.43,127.83,127.66,127.43,
127.14,127.05,126.91,125.86,125.27,123.67,123.22,121.35,120.80,118.70,111.05,
21.34；
Optically-active testing result are as follows:
Infrared detection testing result are as follows: IR (KBr): 3383,2924,1597,1352,1173,804,683cm-1
High resolution mass spectrum testing result are as follows: HRMS (ESI) calcd for C42H30N2O4SBr m/z[M+H]+:
737.1104；Found:737.1119；
High performance liquid chromatography detection result are as follows: HPLC (Daicel Chiralpak ID, i-PrOH/hexane=30/70,
Flow rate 0.8mL/min, λ=250nm): t1(minor)=11.1min, t2(major)=25.5min.
Embodiment 9
Compound 3j is synthesized by compound 1j
Step 1, under the protection of inert gas, compound 1j (0.2mmol) is added in the round-bottomed flask of 25ml, is added
4-BrC6H4SO2Cl (0.04mmol) and DMAP (0.04mmol), adds 12mL methylene chloride and triethylamine after mixing evenly
(0.3mmol), reacts under room temperature, and solvent, column chromatography for separation (petroleum ether: second is removed under reduced pressure in TLC plate monitoring, fully reacting
Acetoacetic ester=6:1), obtain intermediate compound 2j；
Step 2, compound 2j (0.2mmol) is added in the three-necked bottle with condenser, 10ml methylene chloride is added, it will
Reaction system is placed in 40 DEG C of oil bath, is slow added into the dichloromethane solution (0.4mmol DDQ, 10ml DCM) of DDQ,
The monitoring of TLC plate, fully reacting are washed with saturated sodium bicarbonate solution, liquid separation, drying, solvent, column chromatography for separation are removed under reduced pressure
(petroleum ether: ethyl acetate=6:1) obtains compound 3j (white solid, 140mg, 97%).
Carry out nuclear magnetic resonance, optically-active, infrared, high resolution mass spectrum and high performance liquid chromatography detection respectively to compound 3j,
Detection data is as follows:
Magnetic resonance detection result are as follows:1δ=9.36 (s, 1H) H NMR (400MHz, Chloroform-d), 8.05 (t, J
=7.9Hz, 2H), 7.92 (d, J=9.0Hz, 1H), 7.87 (t, J=7.5Hz, 2H), 7.80 (d, J=8.0Hz, 1H), 7.64
(d, J=8.9Hz, 1H), 7.49 (ddd, J=32.4,16.4,8.3Hz, 5H), 7.41-7.24 (m, 7H), 7.19 (p, J=
10.4,8.2Hz, 5H), 7.09 (d, J=6.4Hz, 1H)；13δ=165.50 C NMR (100MHz, Chloroform-d),
145.56,135.37,134.61,133.97,132.33,132.30,131.87,131.72,130.57,130.36,129.80,
129.05,128.73,128.61,128.17,128.00,127.81,127.60,127.31,127.12,126.99,125.93,
125.28,123.70,123.37,121.88,120.37,118.85,110.85；
Optically-active testing result are as follows:
Infrared detection testing result are as follows: IR (KBr): 3373,2942,1701,1261,1166,944,750,701cm-1；
High resolution mass spectrum testing result are as follows: HRMS (ESI) calcd for C41H28N2O4SBr m/z[M+H]+:
723.0948；Found:723.0962；
High performance liquid chromatography detection result are as follows: HPLC (Daicel Chiralpak IC, i-PrOH/hexane=20/80,
Flow rate 0.8mL/min, λ=250nm): t1(minor)=10.5min, t2(major)=12.2min.
Embodiment 10
Compound 3k is synthesized by compound 1k
Step 1, under the protection of inert gas, compound 1k (0.2mmol) is added in the round-bottomed flask of 25ml, is added
TsCl (0.30mmol) and DMAP (0.06mmol), adds 12mL tetrahydrofuran and triethylamine after mixing evenly
(0.34mmol), reacts under room temperature, TLC plate monitoring, fully reacting, be removed under reduced pressure solvent, column chromatography for separation (petroleum ether:
Ethyl acetate=6:1), obtain intermediate compound 2k；
Step 2, compound 2k (0.2mmol) is added in the three-necked bottle with condenser, 10ml tetrahydrofuran is added, it will
Reaction system is placed in 40 DEG C of oil bath, is slow added into the tetrahydrofuran solution (0.4mmol DDQ, 10ml THF) of DDQ,
The monitoring of TLC plate, fully reacting are washed with saturated sodium bicarbonate solution, liquid separation, drying, solvent, column chromatography for separation are removed under reduced pressure
(petroleum ether: ethyl acetate=6:1) obtains compound 3k (white solid, 125mg, 98%).
Carry out nuclear magnetic resonance, optically-active, infrared, high resolution mass spectrum and high performance liquid chromatography detection respectively to compound 3k,
Detection data is as follows:
Magnetic resonance detection result are as follows:1δ=8.03 (d, J=8.2Hz, 1H) H NMR (400MHz, Chloroform-d),
7.94 (d, J=8.8Hz, 3H), 7.85 (t, J=9.1Hz, 5H), 7.63 (d, J=8.9Hz, 1H), 7.48 (dt, J=16.8,
7.3Hz, 2H), 7.41-7.23 (m, 6H), 7.17 (s, 2H), 7.02 (s, 1H), 6.79 (d, J=8.5Hz, 2H), 3.84 (t, J
=62.8Hz, 2H), 2.11 (s, 3H), 1.34 (m, J=18.2Hz, 2H), 0.69 (t, J=29.0Hz, 3H)；13C NMR
(101MHz, Chloroform-d) δ=154.98,145.44,135.53,134.21,132.76,131.93,131.50,
130.55,130.40,129.48,128.97,128.65,128.13,128.01,127.55,126.87,126.59,125.70,
124.90,123.50,121.43,120.92,120.17,118.54,110.70,67.63,21.96,21.34,9.92；
Optically-active testing result are as follows:
Infrared detection testing result are as follows: IR (KBr): 3362,2924,1733,1165,942cm-1；
High resolution mass spectrum testing result are as follows: HRMS (ESI) calcd for C39H33N2O5S m/z[M+H]+: 641.2105；
Found:641.2126；
High performance liquid chromatography detection result are as follows: HPLC (Daicel Chiralpak IC, i-PrOH/hexane=20/80,
Flow rate 0.8mL/min, λ=250nm): t1(minor)=9.9min, t2(major)=24.8min.
Interpretation of result
The detection data of the product obtained by embodiment 1- embodiment 10 can be seen that the method for the present invention was prepared
H atom and C atom in biaryl axial chirality benzindole-naphthalene compounds in different chemical environments go out peak position and stablize, nothing
Impurity peaks, purity is high, separation property is good, and yield is high.
Table 1 is the structural formula for the compound that each reactant and final synthesis obtain in embodiment 1-10
Note: in table 1, during being respectively synthesized each compound of serial number 1-10, reaction condition is identical.
Table 2 is the structural formula for the compound that each reactant and final synthesis obtain in embodiment 1-10
The present invention is by selecting chiral benzindole quinoline derivant to be raw material and use DDQ or MnO2Conjunction as oxidant
At method, central chirality is effectively realized to the chiral inversion of axial chirality, has constructed biaryl axial chirality compound, and be made
Compound in and nitrogen-atoms adjacent to chiral axis；Operation of the present invention is simple, and reaction condition is mild, at low cost, final production obtained
The yield of object is high, enantioselectivity is good.
The foregoing is only a preferred embodiment of the present invention, is not intended to limit the scope of the present invention.
Claims (9)
1. a kind of biaryl axial chirality benzindole-naphthalene compounds, which is characterized in that shown in its chemical structure such as formula (1):
Wherein, R is selected from least one of hydrogen, halogen, phenyl, silicon substrate；R1In hydrogen, halogen, methyl, tert-butyl at least
It is a kind of；R2Selected from benzoyl, methoxy methyl acyl group, ethoxy acetyl, benzyloxy-formyl base, propyl formoxyl, isopropyl
At least one of formoxyl；R3Selected from least one of hydrogen, halogen, methyl, phenyl, methoxyl group；R4Selected from trifluoro methylsulfonyl
At least one of base, p-methylphenyl sulfonyl, p-bromophenyl sulfonyl.
2. a kind of synthetic method of biaryl axial chirality benzindole-naphthalene compounds, which is characterized in that this method passes through following
What step was realized:
Step 1, it is to structural formulaCompound in R is added4Cl and 4-dimethylaminopyridine, are stirred
The first organic solvent and triethylamine are added after mixing uniformly, reacts under room temperature, after fully reacting, solvent, column is removed under reduced pressure
Chromatography, obtaining structural formula isCompound；
Step 2, it is by the structureCompound be dissolved in the second organic solvent, add oxygen
Agent is reacted at 30~50 DEG C, and after having reacted, solvent is removed under reduced pressure, through column in saturated sodium bicarbonate solution washing, liquid separation, drying
Chromatography, obtaining structural formula isBiaryl axial chirality benzindole-naphthalene compounds.
Wherein, in each compound, R is selected from least one of hydrogen, halogen, phenyl, silicon substrate；R1Selected from hydrogen, halogen, methyl,
At least one of tert-butyl；R2Selected from benzoyl, methoxy methyl acyl group, ethoxy acetyl, benzyloxy-formyl base, propyl
At least one of formoxyl, isopropyl formoxyl；R3Selected from least one of hydrogen, halogen, methyl, phenyl, methoxyl group；R4
Selected from least one of trifyl, p-methylphenyl sulfonyl, p-bromophenyl sulfonyl.
3. a kind of synthetic method of biaryl axial chirality benzindole-naphthalene compounds according to claim 2, feature
It is, in the step 1, the structural formula isCompound, R4Cl, 4-dimethylaminopyridine
Between molar ratio be 1:(0.2~1.5): (0.1~0.3).
4. a kind of synthetic method of biaryl axial chirality benzindole-naphthalene compounds according to claim 2, feature
It is, in the step 1, in the step 1, the structural formula isCompound and triethylamine
Molar ratio be 1:(1.3~1.7).
5. a kind of synthetic method of biaryl axial chirality benzindole-naphthalene compounds according to claim 2, feature
It is, in the step 1, the R4Cl is TsCl, 4-BrC6H4SO2One of Cl.
6. a kind of synthetic method of biaryl axial chirality benzindole-naphthalene compounds according to claim 2, feature
It is, in the step 1, first organic solvent is selected from methylene chloride, toluene, tetrahydrofuran, acetonitrile, 1,2- dichloroethanes
At least one of.
7. a kind of synthetic method of biaryl axial chirality benzindole-naphthalene compounds according to claim 2, feature
It is, in the step 2, the structure isCompound and oxidant molar ratio be 1:(1-
3)。
8. a kind of synthetic method of biaryl axial chirality benzindole-naphthalene compounds according to claim 2, feature
It is, in the step 2, the oxidant is selected from DDQ, MnO2At least one of.
9. a kind of synthetic method of biaryl axial chirality benzindole-naphthalene compounds according to claim 2, feature
It is, in the step 2, second organic solvent is selected from methylene chloride, toluene, tetrahydrofuran, acetonitrile, 1,2- dichloroethanes
At least one of.
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| BO ZHOU等: "Synthesis of Indoles through Palladium-Catalyzed Three-Component Reaction of Aryl Iodides, Alkynes, and Diaziridinone", 《ORG. LETT.》 * |
| JAYNE L. FERGUSON等: "Photochemical and oxidative cyclisation of tetraphenylpyrroles", 《ORG. BIOMOL. CHEM.》 * |
| S. G. P. PLANT等: "C-Acetylation of α,β-naphthindole (4,5-benzindole)", 《JOURNAL OF THE CHEMICAL SOCIETY》 * |
| TIRUMALAI R. KASTURI等: "Reaction of spironaphthalenones with hydroxylamine. Part II. Structure of product in the reaction of 1-substituted spironaphthalenone", 《TETRAHEDRON》 * |
| 李晓静等: "分子内叠氮酰氯的 Schmidt 反应合成(R)-苯并吲哚里西定", 《合成化学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112430207A (en) * | 2020-10-21 | 2021-03-02 | 中山大学 | Indole derivative and preparation method and application thereof |
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