CN103864668A - Preparing method of 3-hydroxyloxoindole derivatives - Google Patents

Preparing method of 3-hydroxyloxoindole derivatives Download PDF

Info

Publication number
CN103864668A
CN103864668A CN201210546796.1A CN201210546796A CN103864668A CN 103864668 A CN103864668 A CN 103864668A CN 201210546796 A CN201210546796 A CN 201210546796A CN 103864668 A CN103864668 A CN 103864668A
Authority
CN
China
Prior art keywords
isatin
diazonium
indole derivatives
hydroxyl oxidize
water
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201210546796.1A
Other languages
Chinese (zh)
Inventor
胡文浩
史滔达
荆常城
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
East China Normal University
Original Assignee
East China Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by East China Normal University filed Critical East China Normal University
Priority to CN201210546796.1A priority Critical patent/CN103864668A/en
Publication of CN103864668A publication Critical patent/CN103864668A/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/32—Oxygen atoms
    • C07D209/38—Oxygen atoms in positions 2 and 3, e.g. isatin

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Indole Compounds (AREA)

Abstract

The invention discloses a preparing method of 3-hydroxyloxoindole derivatives shown as the formula (I). The 3-hydroxyloxoindole derivatives are prepared from isatin, water and diazonium, and are prepared by one-step catalysis. According to the method, the 3-hydroxyloxoindole derivatives are prepared with high yield by utilization of a reaction with high atom economy and through green operation processes.

Description

A kind of preparation method of 3-hydroxyl oxidize indole derivatives
Technical field
The invention belongs to medication chemistry synthesis technical field, be specifically related to a kind of preparation method of 3-hydroxyl oxidize indole derivatives, for synthetic cancer therapy drug molecule TMC-95 provides new potential approach.
Background technology
3-hydroxyl oxidize indole derivatives is the very important structural unit of a class, extensively be present in and there is (as shown in following structural formula) in bioactive compound, for example, alkaloid Convolutamydine A-E (Tetrahedron1995,51,5523), 3 '-Hydroxygluoisatisin (Tetrahedron Lett.2001,42,9015) and cancer therapy drug TMC-95A-D (PNAS, 2004,101,11949) in molecule, all contain 3-hydroxyl oxidize indole derivatives skeleton.
2000, Kohno and the separation and Extraction TMC-95A-D first that works together thereof, TMC-95A-D is a kind of proteinase inhibitor efficiently, has the biological activity (J.Org.Chem.2000 65,990) that anticancer increases.After its separation and Extraction work is in the news, its complete synthesis research be also constantly in the news (Angew.Chem.Int.Ed.2002,41,512; Angew.Chem.Int.Ed.2001,40,1967; Angew.Chem.Int.Ed.2003 42,2654; Org.Lett.2001,3,2863).Development 3-hydroxyl oxidize indoles synthetic method is a focus of organic synthesis workers' extensive concern.In recent years, relevant bibliographical information showed increased.In the methodology of having reported, utilize isatin and containing ketone or the aldehyde of active α-H, Aldol reaction occurs, be simply the most direct method (Green Chem.2009,11,1465; Chem.Eur.J.2009,15,6790; Chem.Asian J.2009,4,1664; Tetrahedron 2010,66,1441).Recently, the M-BH of the asymmetry catalysis of isatin and propenal reaction can obtain 3-hydroxyl oxidize indole derivatives (J.Am.Soc.Chem.2010,132,15176) high enantioselectivity.The aryl boric acid of rhodium catalysis and the addition reaction of isatin can obtain the hydroxyl oxidize indole derivatives that 3-aryl replaces, and the method productive rate is high, but enantioselectivity general (Org.Lett., 2006,8,13).The addition reaction of indoles and isatin, also can be used for building 3-hydroxyl oxidize indole derivatives skeleton (Angew.Chem.Int.Ed.2010,49,744).But there is following shortcoming in above method: one,, with an organic solvent as reaction media, toxicity is large; Two, raw materials cost is high, and three, reaction time is long; Four, product purification process complexity etc.These shortcomings are all unfavorable for the industrial applications of the method.
Summary of the invention
The present invention overcomes the above-mentioned defect of prior art, discloses a kind of raw material cheap and easy to get, and syntheti c route is short, simple to operate, is easy to the production method of industrialized 3-hydroxyl oxidize indole derivatives.Than the synthetic method of having reported, present method embodies the feature of Green Chemistry better at aspects such as reaction solvent, catalyzer and aftertreatments.
To achieve these goals, the present invention adopts three component reaction of diazo ester, water and the isatin of metal catalytic to obtain target compound 3-hydroxyl oxidize indole derivatives.One disclosed by the invention is suc as formula the preparation method of the 3-hydroxyl oxidize indole derivatives shown in (1), and take isatin, water and diazonium as raw material, a step catalysis prepares described 3-hydroxyl oxidize indole derivatives:
Figure BDA00002591995100021
Formula (1)
In formula (1), R 1for methyl, nitro, bromine, fluorine; R 2for bromine; R 3for hydrogen or alkyl;
Comprise the following steps:
Step (1): press diazonium: isatin: catalyst molar ratio=1: 1: 0.0001-10: 1: 10, take raw material, and add water; Wherein, water: diazonium mol ratio is no less than 0.1;
Step (2): described isatin and described catalyst dissolution, in solvent, are made to the mixing solutions of isatin and catalyzer; Described diazonium is dissolved in solvent, makes diazonium solution;
Step (3): the mixing solutions that described diazonium solution is injected to described isatin and catalyzer by peristaltic pump; Stirring at normal temperature 1-2 hour, revolves to boil off and desolventizes, and crude product obtains 3-hydroxyl oxidize indole derivatives sterling through recrystallization.
In the present invention, described solvent is water, methylene dichloride, tetrahydrofuran (THF), 1,2-ethylene dichloride, trichloromethane, toluene, acetonitrile, ether or normal hexane.Preferentially make water as solvent.
In the present invention, described catalyzer is the Lewis acid that the catalysis diazonium such as ruthenium chloride, iron(ic) chloride, Palladous chloride, acetic acid rhodium, copper sulfate are decomposed.
In the present invention, described isatin is substituted or non-substituted isatin.
In the present invention, described isatin is substituted at 4,5,6.
In the present invention, described diazonium is diazo compound derivative, and described diazonium is ethyl diazoacetate, diazonium ethyl propionate, the diazobenzene methyl acetate that ethyl diazoacetate, alkyl replace.
In the present invention, material rate is according to diazonium: isatin: catalyst molar ratio=1: 1: 0.0001-10: 1: 10.Preferably, material rate is according to diazonium: isatin: catalyst molar ratio=1: 1: 0.0001-4: 4: 1.Further preferably, material rate is according to diazonium: isatin: catalyst molar ratio=2: 1: 0.01.In the inventive method, the molar equivalent of the water adding should be no less than diazonium, and water can be directly to add or to add with the form of the solvent that contains water.In the inventive method, the consumption of catalyzer is catalyzer: diazonium mol ratio=0.001 or following.
Preferred preparation method of the present invention, specifically comprise: first take diazonium: water: isatin: catalyzer=2: 2: 1: 0.01 mol ratios, then with solvent by isatin and catalyst dissolution, and water is also added and wherein makes isatin and catalyst mix solution, the consumption of solvent is 50-100 times of diazonium amount; Then, diazonium is evenly made to diazonium solution with another part and the solvent of the same amount of above-mentioned solvent, then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and catalyst mix solution, after stirring at normal temperature 1-2 hour, 40 ℃-60 ℃ revolve to boil off and desolventize, and crude product obtains 3-hydroxyl oxidize indole derivatives sterling through recrystallization.
The present invention has the following advantages and effect: ethyl diazoacetate, isatin, water and solvent that the raw materials used ethyl diazoacetate of the present invention or alkyl replace are cheap and easy to get, and the present invention makes the with low cost of target compound 3-hydroxyl oxidize indole derivatives.Existing report document is made catalyzer with expensive acetic acid rhodium, and the present invention adopts inexpensive copper sulfate to make catalyzer, can greatly save production cost.Reaction conditions gentleness of the present invention, solvent green, simple to operate, especially purge process only needs recrystallization, avoids the column chromatography of wasting time and energy, and is conducive to expand suitability for industrialized production 3-hydroxyl oxidize indole derivatives.Three component reaction of the present invention, have the feature of Atom economy, meet the requirement of Green Chemistry.Reaction required time in the present invention is short, and common 1 hour, whole operation flow process only needed about 2 hours.This is by the production cycle that contributes to shorten after industrialization.
Embodiment
In conjunction with following specific embodiment, the present invention is described in further detail.Implement process of the present invention, condition, experimental technique etc., except the content of mentioning specially below, be universal knowledege and the common practise of this area, the present invention is not particularly limited content.
Embodiment 1
First take isatin (1mmol): copper sulfate=1: 0.01 (mol ratio), be placed in 50mL round-bottomed flask, add 10mL water wherein to make isatin and copper sulfate mixing solutions, then, ethyl diazoacetate (2mmol) is mixed with another part of 10mL water, then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and copper sulfate mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1a sterling through volume ratio.Productive rate: 90%, dr value: 80: 20.
Figure BDA00002591995100041
1h NMR (400MHz, DMSO-d 6): δ (anti-1a) 0.86 (t, J=7.0Hz, 3H), 3.77-3.82 (m, 2H), 4.38 (d, J=5.1Hz, 1H), 5.82 (d, J=5.0Hz, 1H), 6.14 (s, 1H), 6.74 (d, 1H), 6.87-6.93 (m, 1H), 7.15-7.19 (m, 1H), 7.39 (d, 1H), 10.22 (s, 1H); (syn-1a) 1.21 (t, J=7.1Hz, 3H), 4.12-4.18 (m, 2H), 4.34 (d, J=5.9Hz, 1H), 5.57 (d, J=5.9Hz, 1H), 6.12 (s, 1H), 6.76 (d, 1H), 6.87-6.93 (m, 1H), 7.15-7.19 (m, 2H), 10.24 (s, 1H); 13c NMR (100MHz, DMSO-d 6): 13.44,14.04,59.94,60.13,73.35,73.73,75.83,76.51,109.13,109.24,120.94,121.03,125.51,125.76,128.57,129.08,129.15,142.54,143.15,169.90,171.25,176.76,177.73; HRMS (ESI): calculated value: C 12h 13nNaO 5[M+Na] +: 274.0686, actual value: 274.0720.
Embodiment 2
First take 4-bromo-isatin (1mmol): acetic acid rhodium=2: 0.01 (mol ratio), be placed in 50mL round-bottomed flask, add 10mL tetrahydrofuran (THF) (moisture) to make isatin and acetic acid rhodium mixing solutions, then, ethyl diazoacetate (2mmol) is mixed with another part of 10mL tetrahydrofuran (THF) (moisture), then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and acetic acid rhodium mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1b sterling through volume ratio.Productive rate: 40%, dr value: 83: 17.
Figure BDA00002591995100042
1h NMR (400MHz, DMSO-d 6): δ (anti-1b) 1.21 (t, J=7.1Hz, 3H), 4.11-4.16 (m, 2H), 4.77 (s, 1H), 5.52 (s, 1H), 5.91 (s, 1H), 6.76 (d, J=7.4Hz, 1H), 7.07-7.15 (m, 2H), 10.39 (s, 1H); (syn-1b) 0.88 (t, J=7.1Hz, 3H), 3.85-3.87 (m, 2H), 4.77 (s, 1H), 5.45 (s, 1H), 6.34 (s, 1H), 6.76 (d, J=7.4Hz, 1H), 7.07-7.15 (m, 2H), 10.53 (s, 1H); 13c NMR (100MHz, DMSO-d 6): 13.40,14.03,60.21,60.32,70.71,73.23,76.97,78.39,108.75,108.97,118.58,125.35,125.59,128.53,130.99,131.36,144.65,145.23,171.19,175.88,176.42; HRMS (ESI): calculated value: C 12h 12brNNaO 5[M+Na] +: 351.9791, actual value: 351.9810.
Embodiment 3
First take 5-methylisatin (1mmol): ruthenium chloride=2: 0.01 (mol ratio), be placed in 50mL round-bottomed flask, add 10mL 1,2-ethylene dichloride (moisture) is made isatin and ruthenium chloride mixing solutions, then, by ethyl diazoacetate (2mmol) and another part of 10mL 1, 2-ethylene dichloride (moisture) mixes, then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and ruthenium chloride mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1c sterling through volume ratio.Productive rate: 85%, dr value: 89: 11.
Figure BDA00002591995100051
1h NMR (300MHz, DMSO-d 6): δ (anti-1c) 0.85 (t, J=7.2Hz, 3H), 2.20 (s, 1H), 3.75-3.82 (m, 2H), 4.34 (d, J=5.4Hz, 1H), 5.80 (d, J=5.4Hz, 1H), 6.08 (s, 1H), 6.60-6.64 (m, 1H), 6.95-7.00 (m, 1H), 7.20 (s, 1H), 10.10 (s, 1H); (syn-1c) 1.20 (t, J=7.0Hz, 3H), 2.20 (s, 1H), 4.16-4.20 (m, 2H), 4.30 (d, J=6.0Hz, 1H), 5.55 (d, J=6.3Hz, 1H), 6.08 (s, 1H), 6.60-6.64 (m, 1H), 6.95-7.00 (m, 2H), 10.13 (s, 1H); 13c NMR (100MHz, DMSO-d 6): 13.46,14.04,20.65,20.71,59.90,60.10,73.44,73.73,75.93,76.57,108.84,126.15,129.15,129.29,129.63,140.09,169.92,176.76,177.70; HRMS (ESI): calculated value: C 13h 15nNaO 5[M+Na] +: 288.0842, actual value: 288.0846.
Embodiment 4
First take 5-bromoisatin (1mmol): iron(ic) chloride=2: 0.01 (mol ratio), be placed in 50mL round-bottomed flask, add 10mL chloroform (moisture) to make isatin and iron(ic) chloride mixing solutions, then, ethyl diazoacetate (2mmol) is mixed with another part of 10mL chloroform (moisture), then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and iron(ic) chloride mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1d sterling through volume ratio.Productive rate: 65%, dr value: 91: 9.
Figure BDA00002591995100052
1h NMR (300MHz, DMSO-d 6): δ (anti-1d) 0.88 (t, J=7.0Hz, 3H), 3.78-3.85 (m, 2H), 4.35 (d, J=5.7Hz, 1H), 6.03 (d, J=5.7Hz, 1H), 6.35 (s, 1H), 6.69-6.71 (m, 1H), 7.33-7.37 (m, 1H), 7.49-7.50 (d, 1H), 10.38 (s, 1H); 13c NMR (100MHz, DMSO-d 6): 13.48,14.05,60.11,60.30,73.28,73.72,76.62,111.20,112.72,128.31,128.87,131.47,131.81,141.89,142.55,169.77,176.25.HRMS (ESI): calculated value: C 12h 12brNNaO 5[M+Na] +: 351.9791, actual value: 351.9843.
Embodiment 5
First take 5-fluoro indigo red (1mmol): Palladous chloride=2: 0.01 (mol ratio), be placed in 50mL round-bottomed flask, add 10mL toluene (moisture) to make isatin and Palladous chloride mixing solutions, then, ethyl diazoacetate (2mmol) is mixed with another part of 10mL toluene (moisture), then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and Palladous chloride mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1e sterling through volume ratio.Productive rate: 64%, dr value: 69: 31.
Figure BDA00002591995100061
1h NMR (400MHz, DMSO-d 6): δ (anti-1e) 0.77 (t, J=7.0Hz, 3H), 3.68-3.73 (m, 2H), 4.26 (d, J=5.6Hz, 1H), 5.88 (d, J=6.0Hz, 1H), 6.24 (s, 1H), 6.60-6.64 (m, 1H), 6.88-6.93 (m, 1H), 7.08 (d, J=8.4Hz, 1H), 10.17 (s, 1H); (syn-1e) 1.11 (t, J=7.0Hz, 3H), 4.02-4.08 (m, 2H), 4.21 (d, J=6.4Hz, 1H), 5.65 (d, J=6.0Hz, 1H), 6.22 (s, 1H), 6.60-6.64 (m, 1H), 6.88-6.93 (m, 2H), 10.21 (s, 1H); 13c NMR (100MHz, DMSO-d 6) 14.49,15.04,61.10,61.28,74.22,74.70,77.17,77.79,110.88,110.96,114.05,114.30,114.54,114.79,116.28,116.51,131.66,131.74,139.73,140.37,157.30,159.64,170.81,172.19,177.67,178.76; HRMS (ESI): calculated value: C 12h 12fNNaO 5[M+Na] +: 292.0592, actual value: 292.0597.
Embodiment 6
First take 6-bromo-isatin (1mmol): copper sulfate=2: 0.01 (mol ratio), be placed in 50mL round-bottomed flask, add 10mL acetonitrile (moisture) to make isatin and copper sulfate mixing solutions, then, ethyl diazoacetate (4mmol) is mixed with another part of 10mL acetonitrile (moisture), then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and copper sulfate mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1f sterling through volume ratio.Productive rate: 54%, dr value: 72: 28.
1h NMR (400MHz, DMSO-d 6): δ (anti-1f) 0.78 (t, J=7.0Hz, 3H), 3.68-3.73 (m, 2H), 4.24 (d, J=
Figure BDA00002591995100071
4.8Hz, 1H), 5.88 (d, J=5.2Hz, 1H), 6.20 (s, 1H), 6.77 (s, 1H), 6.96-7.00 (m, 1H), 7.19 (d, J=7.6Hz, 1H), 10.28 (s, 1H); (syn-1f) 1.10 (t, J=7.2Hz, 3H), 4.02-4.04 (m, 2H), 4.18 (d, J=6.0Hz, 1H), 5.60 (d, J=6.0Hz, 1H), 6.16 (s, 1H), 6.78 (s, 1H), 6.96-7.00 (m, 2H), 10.29 (s, 1H); 13cNMR (100MHz, DMSO-d 6) 14.50,15.07,16.11,16.25,74.11,74.64,76.56,77.38,112.98,113.06,122.90,124.61,124.74,128.36,128.70,128.90,129.46,145.28,145.91,170.80,172.10,177.59,178.67; HRMS (ESI): calculated value: C 12h 12brNNaO 5[M+Na] +: 351.9791, actual value: 351.9845.
Embodiment 7
First take 6-fluoro indigo red (1mmol): copper sulfate=1: 0.0001 (mol ratio), be placed in 50mL round-bottomed flask, add 10mL ether (moisture) to make isatin and copper sulfate mixing solutions, then, ethyl diazoacetate (8mmol) is mixed with another part of 10mL ether (moisture), then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and copper sulfate mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1g sterling through volume ratio.Productive rate: 66%, dr value: 72: 28. 1h NMR (400MHz, DMSO-d 6): δ (anti-1g) 0.90 (t, J=7.1Hz, 3H), 3.82-3.85 (m, 2H), 4.38 (d, J=5.3Hz, 1H), 5.92 (d, J=5.4Hz, 1H), 6.24 (s, 1H), 6.55-6.58 (m, 1H), 6.69-6.72 (m, 1H), 7.38-7.42 (m, 1H), 10.38 (s, 1H); (syn-1g) 1.23 (t, J=7.1Hz, 3H), 4.15-4.17 (m, 2H), 4.33 (d, J=6.1Hz, 1H), 5.65 (d, J=6.1Hz, 1H), 6.20 (s, 1H), 6.55-6.58 (m, 1H), 6.69-6.72 (m, 1H), 7.19-7.22 (m, 1H), 10.40 (s, 1H); 13c NMR (100MHz, DMSO-d 6) 13.97,14.53,60.54,60.70,73.69,74.22,75.92,76.68,97.67,97.94,107.45,107.67,124.93,125.56,127.52,127.62,144.81,144.93,162.15,164.56,170.35,171.67,177.53,178.56; HRMS (ESI): calculated value: C 12h 12fNNaO 5[M+Na] +: 292.0592, actual value: 292.0585.
Embodiment 8
First take 7-bromo-isatin (1mmol): copper sulfate=2: 0.01 (mol ratio), be placed in 50mL round-bottomed flask, add 10mL normal hexane (moisture) to make isatin and copper sulfate mixing solutions, then, ethyl diazoacetate (10mmol) is mixed with another part of 10mL normal hexane (moisture), then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and copper sulfate mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30 mL ethyl acetate extractions, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1h sterling through volume ratio.Productive rate: 78%, dr value: 80: 20.
Figure BDA00002591995100081
1h NMR (500MHz, DMSO-d 6): δ (anti-1h) 0.87 (t, J=7.0Hz, 3H), 3.78-3.88 (m, 2H), 4.39 (d, J=4.5Hz, 1H), 6.01 (d, J=4.0Hz, 1H), 6.39 (s, 1H), 6.85-6.89 (m, 1H), 7.37-7.41 (m, 2H), 10.58 (s, 1H); (syn-1h) 1.22 (t, J=7.0Hz, 3H), 4.14-4.17 (m, 2H), 4.33 (d, J=5.5Hz, 1H), 5.75 (d, J=5.5Hz, 1H), 6.35 (s, 1H), 6.85-6.89 (m, 1H), 7.19 (d, J=7.0Hz, 1H), 7.37-7.41 (m, 1H), 10.58 (s, 1H); 13c NMR (100MHz, DMSO-d 6) 13.88,14.54,60.58,60.74,73.86,74.25,77.06,77.92,102.14,123.24,123.40,125.00,125.32,131.15,131.60,132.47,134.01,142.02,142.41,170.21,174.45,177.11; HRMS (ESI): calculated value: C 12h 12brNNaO 5[M+Na] +: 351.9791, actual value: 351.9806.
Embodiment 9
First take isatin (1mmol): copper sulfate=1: 0.001 (mol ratio), be placed in 50mL round-bottomed flask, add 10mL water to make isatin and copper sulfate mixing solutions, then, the diazoacetic acid tert-butyl ester is mixed with another part of 10mL water, then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and copper sulfate mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1i sterling through volume ratio.Productive rate: 82%, dr value: 67: 33.
Figure BDA00002591995100082
1h NMR (300MHz, DMSO-d 6): δ (anti-1i) 1.05 (s, 9H), 4.27 (d, J=5.3Hz, 1H), 5.58 (d, J=5.3Hz, 1H), 6.06 (s, 1H), 6.77 (d, J=7.7Hz, 1H), 6.86-6.94 (m, 1H), 7.16-7.22 (m, 1H), 7.38 (d, J=7.2Hz, 1H), 10.24 (s, 1H); (syn-1i) 1.38 (s, 9H), 4.23 (d, J=6.6Hz, 1H), 5.30 (d, J=6.6Hz, 1H), 6.05 (s, 1H), 6.77 (d, J=7.7Hz, 1H), 6.86-6.94 (m, 1H), 7.16-7.22 (m, 1H), 7.25 (d, J=7.3Hz, 1H), 10.24 (s, 1H); 13c NMR (100MHz, DMSO-d 6) 26.95,27.57,73.48,74.14,75.52,76.23,80.40,80.75,109.10,109.25,120.92,120.98,125.74,128.74,129.07,129.13,129.16,142.72,143.02,168.85,170.33,176.79,177.75; HRMS (ESI): calculated value: C 14h 17nNaO 5[M+Na] +: 302.0999, actual value: 302.1005.
Embodiment 10
First take isatin (1mmol): copper sulfate=1: 5 (mol ratios), be placed in 50mL round-bottomed flask, add 10mL water to make isatin and copper sulfate mixing solutions; Then, diazonium ethyl propionate is mixed with another part of 10mL water, then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and copper sulfate mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1j sterling through volume ratio.Productive rate: 92%, dr value: 63: 37.
Figure BDA00002591995100091
1h NMR (400MHz, DMSO-d 6): δ (anti-1j) 0.88 (t, J=7.0Hz, 3H), 1.53 (s, 3H), 3.78-3.82 (m, 2H), 5.40 (s, 1H), 5.91 (s, 1H), 6.69-6.76 (m, 1H), 6.83-6.90 (m, 1H), 7.11-7.18 (m, 1H), 7.46 (d, J=7.6Hz, 1H), 10.13 (s, 1H); (syn-1j) 1.10 (t, J=7.0Hz, 3H), 1.46 (s, 3H), 4.03-4.05 (m, 2H), 5.18 (s, 1H), 6.03 (s, 1H), 6.69-6.76 (m, 1H), 6.83-6.90 (m, 1H), 7.11-7.19 (m, 2H), 10.26 (s, 1H); 13c NMR (100MHz, DMSO-d 6) 13.41,13.75,19.17,20.24,60.20,60.50,76.99,77.27,77.74,108.80,109.30,120.72,121.11,124.99,126.38,129.05,129.21,129.49,129.85,142.40,142.76,172.91,173.00,176.64,177.58; HRMS (ESI): calculated value: C 13h 15nNaO 5[M+Na] +: 288.0842, actual value: 288.0867.
Embodiment 11
First take 5-methylisatin (1mmol): copper sulfate=1: 4 (mol ratios), be placed in 50mL round-bottomed flask, add 10mL water to make isatin and copper sulfate mixing solutions; Then, diazonium ethyl propionate is mixed with another part of 10mL water, then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and copper sulfate mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1k sterling through volume ratio.Productive rate: 67%, dr value: 91: 9.
Figure BDA00002591995100092
1h NMR (400MHz, DMSO-d 6): δ (anti-1k) 0.90 (t, J=6.8Hz, 3H), 1.53 (s, 3H), 2.21 (s, 3H), 3.80-3.85 (m, 2H), 5.33 (s, 1H), 5.83 (s, 1H), 6.59 (d, J=7.6Hz, 1H), 6.96 (d, J=7.6Hz, 1H), 7.29 (s, 1H), 10.03 (s, 1H); 13c NMR (100MHz, DMSO-d 6) 13.44,20.28,20.73,60.19,77.14,77.70,108.53,127.03,129.21,129.28,129.87,139.96,173.04,176.68; HRMS (ESI): calculated value: C 14h 17nNaO 5[M+Na] +: 302.0999, actual value: 302.1004.
Embodiment 12
First take 5-nitro isatin (1mmol): copper sulfate=2: 0.01 (mol ratio), be placed in 50mL round-bottomed flask, add 10mL water to make isatin and copper sulfate mixing solutions; Then, diazonium ethyl propionate is mixed with another part of 10mL water, then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and copper sulfate mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1l sterling through volume ratio.Productive rate: 73%, dr value: 58: 42.
Figure BDA00002591995100101
1h NMR (400MHz, DMSO-d 6): δ (anti-1l) 1.22 (t, J=7.1Hz, 3H), 1.51 (s, 3H), 4.11-4.19 (m, 2H), 5.47 (s, 1H), 6.38 (s, 1H), 6.88-6.96 (m, 1H), 7.87 (s, 1H), 8.26-8.32 (m, 1H), 10.89 (s, 1H); (syn-1l) 0.87 (t, J=7.1Hz, 3H), 1.58 (s, 3H), 3.76-3.84 (m, 2H), 5.83 (s, 1H), 6.33 (s, 1H), 6.88-6.96 (m, 1H), 8.15-8.19 (m, 2H), 10.84 (s, 1H); 13c NMR (100MHz, DMSO-d 6) 13.41,13.93,19.42,19.93,60.39,60.81,76.35,77.52,77.60,78.07,109.14,109.42,120.41,122.13,126.49,126.54,130.85,141.47,149.11,149.79,172.58,172.80,176.73,177.52; HRMS (ESI): calculated value: C 13h 14n 2naO 7[M+Na] +: 333.0693, actual value: 333.0694.
Embodiment 13
First take 5-fluoro indigo red (1mmol): copper sulfate=1: 3 (mol ratios), be placed in 50mL round-bottomed flask, add 10mL water to make 5-fluoro indigo red and copper sulfate mixing solutions; Then, diazonium ethyl propionate is mixed with another part of 10mL water, then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and copper sulfate mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1m sterling through volume ratio.Productive rate: 66%, dr value: 60: 40.
Figure BDA00002591995100102
1h NMR (400MHz, DMSO-d 6): δ (anti-1m) 0.89 (t, J=7.1Hz, 3H), 1.55 (s, 3H), 3.80-3.85 (m, 2H), 5.59 (s, 1H), 6.12 (s, 1H), 6.68-6.71 (m, 1H), 6.98-7.04 (m, 1H), 7.25-7.29 (m, 1H), 10.18 (s, 1H); (syn-1m) 1.15 (t, J=7.1Hz, 3H), 1.44 (s, 3H), 4.05-4.12 (m, 2H), 5.29 (s, 1H), 6.19 (s, 1H), 6.73-6.77 (m, 1H), 6.89-6.77 (m, 1H), 6.98-7.04 (m, 1H), 10.28 (s, 1H); 13c NMR (100MHz, DMSO-d 6) 13.40,13.81,19.27,20.02,60.27,60.59,77.14,77.57,77.83,109.40,109.48,109.94,110.02,112.57,112.82,113.95,114 .20,115.13,115.29,115.36,115.52,131.28,131.36,131.51,131.59,138.54,138.55,138.99,139.01,156.08,156.32,158.42,158.66,172.76,176.44,177.36; HRMS (ESI): calculated value: C 13h 14fNNaO 5[M+Na] +: 306.0748, actual value: 306.0766.
Embodiment 14
First take 6-fluoro indigo red (1mmol): copper sulfate=1: 0.01 (mol ratio), be placed in 50mL round-bottomed flask, add 10mL water to make 6-fluoro indigo red and copper sulfate mixing solutions; Then, diazonium ethyl propionate is mixed with another part of 10mL water, then, reaction soln will be injected by peristaltic pump for for diazonium solution 1 hour, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1n sterling through volume ratio.Productive rate: 60%, dr value: 64: 36.
Figure BDA00002591995100111
a 1h NMR (400MHz, DMSO-d 6): δ (anti-1n) 0.91 (t, J=7.1Hz, 3H), 1.54 (s, 3H), 3.81-3.86 (m, 2H), 5.51 (s, 1H), 6.00 (s, 1H), 6.50-6.72 (m, 2H), 7.46-7.49 (m, 1H), 10.29 (s, 1H); (syn-1n) 1.15 (t, J=7.1Hz, 3H), 1.46 (s, 3H), 4.06-4.11 (m, 2H), 5.20 (s, 1H), 6.07 (s, 1H), 6.50-6.72 (m, 2H), 7.08-7.11 (m, 1H), 10.38 (s, 1H); 13c NMR (100MHz, DMSO-d 6) 13.44,13.83,19.25,20.15,60.25,60.57,76.49,77.10,77.64,77.85,96.73,96.99,97.25,97.52,106.59,106.81,106.95,107.17,125.53,125.56,125.89,125.92,126.43,126.53,127.94,128.04,144.13,144.25,144.59,144.71,161.58,164.00,172.89,176.81,177.69; HRMS (EI): calculated value: C 13h 14fNNaO 5[M+Na] +: 306.0724, actual value: 306.0748.
Embodiment 15
First take isatin (1mmol): copper sulfate=2: 0.01 (mol ratio), be placed in 50mL round-bottomed flask, add 10mL water to make isatin and copper sulfate mixing solutions, then, diazonium isopropyl propionate is mixed with another part of 10mL water, then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and copper sulfate mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1o sterling through volume ratio.Productive rate: 82%, dr value: 56: 44.
Figure BDA00002591995100121
1h NMR (400MHz, DMSO-d 6): δ (anti-1o) 0.90 (m, 6H), 1.54 (s, 3H), 4.59 (m, 1H), 5.34 (s, 1H), 5.89 (s, 1H), 6.69-6.92 (m, 2H), 7.13-7.20 (m, 2H), 7.48-7.49 (d, J=6.8Hz, 1H), 10.13 (s, 1H); (syn-1o) 1.06 (m, 6H), 1.46 (s, 3H), 4.78 (m, 1H), 5.16 (s, 1H), 6.05 (s, 1H), 6.69-6.92 (m, 2H), 7.13-7.20 (m, 2H), 10.33 (s, 1H); 13c NMR (100MHz, DMSO-d 6) 18.98,20.23,20.68,20.99,21.08,21.22,67.82,68.14,76.71,76.94,77.65,77.81,108.78,109.44,120.68,121.21,125.18,126.44,129.03,129.29,129.36,129.91,142.48,142.70,172.23,172.42,176.58,177.87; HRMS (ESI): calculated value: C 14h 17nNaO 5[M+Na] +: 302.0999, actual value: 302.1032.
Embodiment 16
First take isatin (1mmol): copper sulfate=2: 0.01 (mol ratio), be placed in 50mL round-bottomed flask, add 10mL water to make isatin and copper sulfate mixing solutions; Then, diazonium ethyl butyrate is mixed with another part of 10mL water, then, by peristaltic pump by diazonium solution with within 1 hour, injecting isatin and copper sulfate mixing solutions, after stirring at normal temperature 1-2 hour, remove little polar impurity with 30mL petroleum ether extraction, afterwards with three times (10mL/ time) of 30mL ethyl acetate extraction, merge organic layer, after the water washing of 30mL saturated common salt, with anhydrous sodium sulfate drying after 3 hours 40 ℃ revolve and boil off except ethyl acetate, crude product is that 1: 1 sherwood oil and re-crystallizing in ethyl acetate obtain 3-hydroxyl oxidize indole derivatives 1p sterling through volume ratio.Productive rate: 68%, dr value: 50: 50.
Figure BDA00002591995100122
1h NMR (500MHz, DMSO-d 6): δ (anti-1p) 0.75 (t, J=7.0Hz, 3H), 0.96 (t, J=7.0Hz, 3H), 1.90-1.92 (m, 1H), 2.49-2.50 (m, 1H), 4.07-4.14 (m, 2H), 4.60 (s, 1H), 5.87 (s, 1H), 6.88-6.92 (m, 2H), 7.11 (d, J=7.5Hz, 1H), 7.47 (d, J=7.5Hz, 1H), 10.04 (s, 1H); (syn-1p) 0.75 (t, J=7.0Hz, 3H), 1.14 (t, J=7.0Hz, 3H), 2.07-2.08 (m, 2H), 3.87-3.89 (m, 2H), 4.81 (s, 1H), 5.76 (s, 1H), 6.71-6.76 (m, 2H), 7.15-7.18 (m, 2H), 10.10 (s, 1H); 13c NMR (100MHz, DMSO-d 6) 7.50,7.62,13.56,13.93,23.53,24.62,60.34,60.69,77.75,77.94,81.21,81.40,108.85,109.19,120.81,121.04,124.88,126.43,129.15,129.91,142.31,142.89,172.06,172.45,176.84,177.45; HRMS (ESI): calculated value: C 14h 17nNaO 5[M+Na] +: 302.0999, actual value: 302.1029.
Protection content of the present invention is not limited to above embodiment.Do not deviating under the spirit and scope of inventive concept, variation and advantage that those skilled in the art can expect are all included in the present invention, and take appending claims as protection domain.

Claims (6)

1. suc as formula a preparation method for the 3-hydroxyl oxidize indole derivatives shown in (1), it is characterized in that, take isatin, water and diazonium as raw material, a step catalysis makes described 3-hydroxyl oxidize indole derivatives: formula (1)
Wherein, R 1for methyl, nitro, bromine, fluorine; R 2for bromine; R 3for hydrogen or alkyl;
Comprise the following steps:
Step (1): by diazonium: isatin: catalyst molar ratio is 1: 1: 0.0001-10: 1: 10, take raw material, and add water; Wherein, water: diazonium mol ratio is no less than 0.1;
Step (2): described isatin and described catalyst dissolution, in solvent, are made to the mixing solutions of isatin and catalyzer; Described diazonium is dissolved in solvent, makes diazonium solution;
Step (3): the mixing solutions that described diazonium solution is injected to described isatin and catalyzer by peristaltic pump; Stirring at normal temperature 1-2 hour, revolves to boil off and desolventizes, and crude product obtains 3-hydroxyl oxidize indole derivatives sterling through recrystallization.
2. the preparation method of 3-hydroxyl oxidize indole derivatives as claimed in claim 1, is characterized in that, described solvent is methylene dichloride, water, tetrahydrofuran (THF), 1,2-ethylene dichloride, trichloromethane, toluene, acetonitrile, ether or normal hexane.
3. the preparation method of 3-hydroxyl oxidize indole derivatives as claimed in claim 1, is characterized in that, described catalyzer is ruthenium chloride, iron(ic) chloride, Palladous chloride, acetic acid rhodium, copper sulfate.
4. the preparation method of 3-hydroxyl oxidize indole derivatives as claimed in claim 1, is characterized in that, described isatin is substituted or non-substituted isatin.
5. the preparation method of 3-hydroxyl oxidize indole derivatives as claimed in claim 1, is characterized in that, described isatin is substituted at 4,5,6.
6. the preparation method of 3-hydroxyl oxidize indole derivatives as claimed in claim 1, is characterized in that, described diazonium is ethyl diazoacetate, diazonium ethyl propionate, the diazobenzene methyl acetate that ethyl diazoacetate or alkyl replace.
CN201210546796.1A 2012-12-14 2012-12-14 Preparing method of 3-hydroxyloxoindole derivatives Pending CN103864668A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201210546796.1A CN103864668A (en) 2012-12-14 2012-12-14 Preparing method of 3-hydroxyloxoindole derivatives

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201210546796.1A CN103864668A (en) 2012-12-14 2012-12-14 Preparing method of 3-hydroxyloxoindole derivatives

Publications (1)

Publication Number Publication Date
CN103864668A true CN103864668A (en) 2014-06-18

Family

ID=50903742

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201210546796.1A Pending CN103864668A (en) 2012-12-14 2012-12-14 Preparing method of 3-hydroxyloxoindole derivatives

Country Status (1)

Country Link
CN (1) CN103864668A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106478486A (en) * 2016-09-18 2017-03-08 华东师范大学 A kind of β hydroxyl alpha amino acid ester derivant and its synthetic method and application
CN106565683A (en) * 2016-09-30 2017-04-19 江汉大学 Method for synthesizing 3-hydroxyl oxoindole derivative

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101979379A (en) * 2010-09-30 2011-02-23 中国科学院昆明植物研究所 Method for preparing 3-acetonyl-3-hydroxy oxindole (AHO)
CN102070509A (en) * 2011-01-24 2011-05-25 华东师范大学 Method for preparing 3-allyl-3-hydroxy oxindole
CN102127002A (en) * 2011-01-20 2011-07-20 华东师范大学 Method for preparing 3,3-diaryl substituted and 3-alkyl-3-aryl substituted oxoindole derivative

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101979379A (en) * 2010-09-30 2011-02-23 中国科学院昆明植物研究所 Method for preparing 3-acetonyl-3-hydroxy oxindole (AHO)
CN102127002A (en) * 2011-01-20 2011-07-20 华东师范大学 Method for preparing 3,3-diaryl substituted and 3-alkyl-3-aryl substituted oxoindole derivative
CN102070509A (en) * 2011-01-24 2011-05-25 华东师范大学 Method for preparing 3-allyl-3-hydroxy oxindole

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
NUNO R. CANDEIAS,等: "Rh(II)-Catalyzed Intramolecular C-H Insertion of Diazo Substrates in Water: Scope and Limitations", 《THE JOURNAL OF ORGANIC CHEMISTRY》, vol. 71, no. 15, 22 June 2006 (2006-06-22), pages 5489 - 5497 *
SHOU-FEI ZHU,等: "Catalytic Asymmetric Reaction withWater: Enantioselective Synthesis of a-Hydroxyesters by a Copper–Carbenoid O-H Insertion Reaction", 《ANGEW. CHEM. INT. ED.》, vol. 47, 14 December 2007 (2007-12-14), pages 932 - 934 *
李志成,等: "金属催化重氮化合物参与的分子间多组分反应研究进展", 《广东化工》, vol. 34, no. 6, 30 June 2007 (2007-06-30), pages 70 - 74 *
郭鑫,等: "路易斯酸催化苯基重氮乙酸甲酯，苄醇和N-甲基靛红三组分反应", 《合成化学》, vol. 17, no. 2, 28 February 2009 (2009-02-28), pages 196 - 198 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106478486A (en) * 2016-09-18 2017-03-08 华东师范大学 A kind of β hydroxyl alpha amino acid ester derivant and its synthetic method and application
CN106478486B (en) * 2016-09-18 2019-04-30 华东师范大学 A kind of beta-hydroxy-alpha-amino acid ester derivant and its synthetic method and application
CN106565683A (en) * 2016-09-30 2017-04-19 江汉大学 Method for synthesizing 3-hydroxyl oxoindole derivative
CN106565683B (en) * 2016-09-30 2019-03-12 江汉大学 A method of synthesis 3- hydroxyl oxoindole derivative

Similar Documents

Publication Publication Date Title
Lv et al. Asymmetric Dimerization of Disubstituted Ketenes Catalyzed by N‐Heterocyclic Carbenes
Wang et al. Synthesis of chiral ferrocenyl aziridino alcohols and use in the catalytic asymmetric addition of diethylzinc to aldehydes
Singh et al. Rapid access of 2, 3, 4-trisubstituted-2, 3, 4, 9-tetrahydrothiopyrano [2, 3-b] indole derivatives via one-pot three component reaction using organocatalysis
CN101712645B (en) Preparation method for (2R, 4R)-4-substituted-2-piperidine carboxylic acid compound and intermediate thereof
Muthiah et al. Enantioselective synthesis of α-methylene-γ-butyrolactones using chiral Pd (II)-SPRIX catalyst
Yang et al. Asymmetric Michael addition reactions catalyzed by a novel upper-rim functionalized calix [4] squaramide organocatalyst
Liu et al. N-Heterocyclic carbene/palladium cascade catalysis: Construction of 2, 2-disubstitiuted benzofuranones from the reaction of 3-(2-formylphenoxy) propenoates with allylic esters
Soeta et al. An asymmetric intramolecular Stetter reaction catalyzed by a chiral triazolium precatalyst bearing a pyridine moiety
CN103694204B (en) 1,2,4-trisubstituent furan compound and preparation method thereof
CN102432485B (en) Alpha,beta-diamino acid derivative and synthetic method and application thereof
CN103864668A (en) Preparing method of 3-hydroxyloxoindole derivatives
Liu et al. Modular bipyridine ligands coupled with Cinchona alkaloids for Cu (II)-catalyzed asymmetric Henry reactions
Zhang et al. Application of asymmetric aminohydroxylation to heteroaromatic acrylates
Shao et al. Easily accessible chiral dicyclopentadiene ligands for rhodium-catalyzed enantioselective 1, 4-addition reactions
CN106146334A (en) 2,3-diaryl-2-propargyl amide groups-3-arylamino methyl propionate derivant and its preparation method and application
Kumar et al. A simple and efficient enantioselective route to 2, 6-disubstituted piperidines: synthesis of (2R, 6S)-isosolenopsin A and (2S, 6R)-isosolenopsin
CN103232462A (en) Synthetic method of coumarin-pyrrole compound
CN101906445B (en) Synthesis method of 2H-1-benzopyran-2-ketone derivatives
CN103910676B (en) A kind of synthetic method of polysubstituted tetrahydro isoquinoline derivative
CN105732648A (en) Nitrogen heterocyclic ring compound of pyrrolofuran and synthetic method
CN112430183B (en) Preparation method of axial chiral 4-substituted cyclohexylidene aryl acetate compound
CN102329281B (en) C-acyl-dihydro sulfinpyrazone based on catalysis of chiral bicyclic imidazole nucleophilic catalyst and preparation method thereof
CN103467386A (en) Aryl pyrimidine ortho-position monocyano compounds and synthesis method thereof
CN103265545A (en) Method for preparing parazole iso-indole compound
Sun et al. Organocatalytic asymmetric cascade cyclization reaction of o-hydroxy cinnamaldehydes with diphenylphosphine oxide

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C02 Deemed withdrawal of patent application after publication (patent law 2001)
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20140618