CN109096150A - A kind of nonmetal catalyzed method for preparing beta-amino ketones of photoinduction - Google Patents

A kind of nonmetal catalyzed method for preparing beta-amino ketones of photoinduction Download PDF

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CN109096150A
CN109096150A CN201811145401.0A CN201811145401A CN109096150A CN 109096150 A CN109096150 A CN 109096150A CN 201811145401 A CN201811145401 A CN 201811145401A CN 109096150 A CN109096150 A CN 109096150A
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beta
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CN109096150B (en
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傅尧
吴雅楠
尚睿
付明臣
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University of Science and Technology of China USTC
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/04—Systems containing only non-condensed rings with a four-membered ring

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The invention discloses a kind of nonmetal catalyzed methods for preparing beta-amino ketones of photoinduction.The described method includes: realizing the decarboxylation of active carboxylic acid's ester by illumination, and react to obtain beta-amino ketones with silyl enol ether under the conditions of existing for simple salt compounded of iodine, Phosphine ligands and the organic solvent.Method provided by the invention utilizes photocatalysis, realizes efficient catalytic conversion at room temperature, reaction condition is mild, easy to operate.This method avoid the use of metallic catalyst, meet the requirement for developing the friendly chemistry of green environment, substrate spectrum is wide and functional group compatibility is good, provides a kind of new method for the synthesis of Beta-aminoketones compound.Raw materials and reagents are easy to get, and reaction can be amplified to gram-grade gauge mould, and conversion ratio and yield are higher, have good prospects for commercial application.

Description

A kind of nonmetal catalyzed method for preparing beta-amino ketones of photoinduction
Technical field
The present invention relates to compound synthesis fields, and in particular to a kind of photoinduction is nonmetal catalyzed to prepare β-amino ketones Method.
Background technique
Beta-amino ketones are widely used in fine chemistry industry and field of medicaments as intermediate, its bioactivity include it is anti-inflammatory, Anticancer, treating tuberculosis, antibacterial, analgesic and cough-relieving.General synthetic method include using aldehyde, ketone and amine as raw material Mannich reaction, The open loop addition etc. of the pure and mild sulfonyl azide compound of cyclopropyl.Method provided by the invention utilizes photoinduction, realizes at room temperature non- The conversion of metal efficient catalytic, reaction condition is mild, easy to operate.This method avoid the uses of metallic catalyst, meet development The requirement of the friendly chemistry of green environment.
Summary of the invention
The purpose of the present invention is to provide a kind of nonmetal catalyzed methods for preparing beta-amino ketones of photoinduction, and in this hair It does not need that metallic catalyst is added in bright reaction system, and reaction condition is mild, it is preferable to functional group compatibility.
In order to solve the above technical problem, the present invention provides following technical solutions:
<1>the nonmetal catalyzed method for preparing beta-amino ketones of a kind of photoinduction of, the described method comprises the following steps:
At room temperature, existing for simple salt compounded of iodine, Phosphine ligands and the organic solvent under the conditions of, pass through illumination and realize 1 institute of formula Show the decarboxylation of active carboxylic acid's ester compounds, and reacts to obtain beta-amino ketones shown in formula 3 with silyl enol ether compound shown in formula 2 Class compound:
Wherein:
In formula 1, R1For tertbutyloxycarbonyl (Boc) and benzyloxycarbonyl group (Cbz), R2For hydrogen atom or straight chain, branch or ring The C of shape1-20Alkyl, R3For hydrogen atom, C6-20Aryl, straight chain, branch or cricoid C1-20Alkyl, C1-20Sulfanyl, C1-4Alkylbenzene Oxygroup C1-4Alkyl or R3And R2Ring is formed together with their connect N atoms；
In formula 2, aromatic ring is by R4Substituted phenyl ring or thiphene ring, TMS indicate trimethyl silane group, and R4 It is the C of the linear chain or branched chain on different the position of substitution of the aromatic ring1-20Alkyl, C6-20Aryl or ester group；
In formula 3, R1And R2Definition it is identical as the definition in formula 1, R4Definition it is identical as the definition in formula 2.
<2>is according to method as described above, wherein the molar ratio of the formula 2 and formula 1 is 1.0-4.0.
<3>is according to method as described above, wherein the simple salt compounded of iodine is in sodium iodide, potassium iodide and lithium iodide At least one.
<4>is according to method as described above, wherein the Phosphine ligands be selected from triphenylphosphine, three (4- fluorophenyl) phosphines, In three (4- anisyl) phosphines, three (3- anisyl) phosphines, diphenyl-2-pyridyl phosphine and bis- (2- diphenylphosphine phenyl) ethers extremely Few one kind.
<5>is according to method as described above, wherein the mole dosage of the salt compounded of iodine is the mole dosage of the formula 1 1.0-2.0 again.
<6>is according to method as described above, wherein the mole dosage of the Phosphine ligands is the mole dosage of the formula 1 5%-50%.
<7>is according to method as described above, wherein the wave-length coverage of the light source is shone between 365nm to 500nm Penetrating the time is 4-24 hours.
<8>is according to method as described above, wherein the organic solvent is selected from n,N-Dimethylformamide, N, N- diformazan At least one of yl acetamide, acetonitrile, tetrahydrofuran and toluene.
<9>is according to method as described above, wherein active carboxylic acid's ester compounds of formula 1 are selected from:
<10>is according to method as described above, wherein the silyl enol ether compound of formula 2 is selected from:
Method provided by the invention, be by utilize the nonmetal catalyzed active carboxylic acid's ester decarboxylation of photoinduction, and with enol silicon Ether compound reacts to obtain beta-amino ketones.It is mild with reaction condition, easy to operate, and avoid making for metallic catalyst With providing a kind of novel method for the synthesis of beta-amino ketones, meet the requirement for developing the friendly chemistry of green environment.Moreover, This method can be successfully applied to the precursor of synthetic drug molecule Duloxetine, Fluoxetine hydrochloride and atomoxetine.Gram-grade scale There is the high conversion rate of reaction commercial synthesis to be worth prospect.
Specific embodiment
Unless otherwise defined, it anticipates known to all professional and scientific terms as used herein and one skilled in the art Justice is identical.In addition, any method similar to or equal to what is recorded and material can be applied to the method for the present invention.Herein Described in preferred implement methods and materials be for illustrative purposes only.
In the present invention, " nonmetallic " in term " photoinduction is nonmetal catalyzed " refers in catalyst system without using metal Such as metal iridium, ruthenium, palladium etc., thus " photoinduction is nonmetal catalyzed " refer in catalyst system without using metal such as metal The Photocatalysis effect occurred in the case where iridium, ruthenium, palladium etc..
The present invention provides a kind of photoinduction the nonmetal catalyzed method for preparing beta-amino ketones, and chemical equation is as follows:
It can be seen that the method for the present invention from above-mentioned formula to include the following steps:
At room temperature, existing for simple salt compounded of iodine, Phosphine ligands and the organic solvent under the conditions of, formula is realized by illumination The decarboxylation of active carboxylic acid's ester compounds shown in 1, and react to obtain β-ammonia shown in formula 3 with silyl enol ether compound shown in formula 2 Base ketone compounds.
Also, in above-mentioned formula, group R1、R2、R3And R4With following meaning.
In formula 1, R1For tertbutyloxycarbonyl Boc and benzyloxycarbonyl group Cbz, R2For hydrogen atom or straight chain, branch or cricoid C1-20Alkyl, R3For hydrogen atom, C6-20Aryl, straight chain, branch or cricoid C1-20Alkyl, C1-20Sulfanyl, C1-4Alkyl phenoxy C1-4Alkyl or R3And R2Ring is formed together with their connect N atoms.
In formula 1, the straight chain, branch or cricoid C1-20The example of alkyl include methyl, ethyl, propyl, normal-butyl, Sec-butyl, tert-butyl, hexyl, heptyl, octyl, cyclobutyl, cyclohexyl, dodecyl, octadecyl, docosyl, etc..
In formula 1, the C6-20The example of aryl be phenyl, benzyl, phenethyl, etc..
In formula 1, the C1-20The example of sulfanyl include butylthiomethyl, sulfenyl n-propyl, sulfenyl normal-butyl, sulfenyl oneself Base, sulfenyl dodecyl, etc..
In formula 1, " the C1-4Alkyl phenoxy C4The example of alkyl " includes methylphenoxy normal-butyl, n-propylbenzene Oxygroup tert-butyl, ethylpropoxy tert-butyl, etc..
In formula 1, " the R3And R2Form ring with their connect N atoms " example include cyclobutyl, cyclopropyl, ring Hexyl, etc..
In formula 2, aromatic ring is by R4Substituted phenyl ring or thiphene ring, TMS indicate trimethyl silane group, and R4 It is the C of the linear chain or branched chain on different the position of substitution of the aromatic ring1-20Alkyl, C6-20Aryl or ester group.
In formula 3, R1And R2Definition and formula 1 in R1And R2Definition it is identical, R4Definition and formula 2 in R4Definition phase Together.
Inventors have found that in active carboxylic acid's ester decarboxylic reaction conversion, the molar ratio of reasonable formula 1 and formula 2, formula 1 With the molar ratio of salt compounded of iodine, Phosphine ligands, salt compounded of iodine and Phosphine ligands and the type of light source etc. are to carry out the mostly important technique of the reaction Condition.
In the present invention, the molar ratio of formula 2 and formula 1 can be 1.0-4.0, more preferably 1.5-2.0.
In the present invention, term " simple salt compounded of iodine " refers to the iodide of alkali metal.It is suitble to the simple salt compounded of iodine used Example is selected from least one of sodium iodide, potassium iodide and lithium iodide, more preferably sodium iodide.
In the present invention, the Phosphine ligands used is suitble to be selected from triphenylphosphine, three (4- fluorophenyl) phosphines, three (4- methoxy benzene Base) phosphine, three (3- anisyl) phosphines, diphenyl-2-pyridyl phosphine, at least one of bis- (2- diphenylphosphine phenyl) ethers, it is more excellent It is selected as triphenylphosphine.
In the present invention, being suitble to the mole dosage of the salt compounded of iodine used is 1.0-2.0 times of the mole dosage of the formula 1, excellent It is selected as 1.2-1.8 times, more preferably 1.4-1.5 times.
In the present invention, it is suitble to the mole dosage of the Phosphine ligands used for the 5%-50% of the mole dosage of the formula 1, Preferably 10-30%, more preferably 15-25%.
In the present invention, being suitble to the mole dosage of the formula 2 used is 1-4 times of the mole dosage of the formula 1, more preferably It is 2-3 times.
In the present invention, it is suitble to the wave-length coverage of the light source used between 365nm to 500nm, preferably 430- 480nm, more preferably 450-460nm；Irradiation time is 4-24 hours, 8-20 hours, more preferably 12-15 hours.
In the present invention, the organic solvent used is suitble to be selected from n,N-Dimethylformamide, n,N-dimethylacetamide, second At least one of nitrile, tetrahydrofuran and toluene, more preferably acetonitrile.
In the preparation process in accordance with the present invention, the yield of Beta-aminoketones compound shown in formula 3 can be up to about 90%, and And the minimum yield of Beta-aminoketones compound also can achieve 62%.
Embodiment
In order to which the present invention is furture elucidated, the preferred embodiment of the invention is described below with reference to embodiment, still It should be appreciated that these descriptions are intended merely to further illustrate the features and advantages of the present invention, rather than to the claims in the present invention Limitation, every other embodiment obtained by those of ordinary skill in the art without making creative efforts, all Belong to the scope of protection of the invention.
For the nonmetal catalyzed drug difference for preparing beta-amino ketones and using of photoinduction in the following embodiments of the present invention It is bought in following Reagent Company:
Acetonitrile (C2H3N, 99.9%), n,N-Dimethylformamide (C3H7NO, 99.5%), N, N- dimethyl acetamide (C4H9NO, 99.0%) bought from Bellingwell company.
Sodium iodide (NaI, 99.5%) is bought from Aladdin company, triphenylphosphine (PPh3, 99%) and it is purchased from Adamas company It buys.
In addition, r.t indicates room temperature, and blue LED indicates blue-ray LED, and LED indicates hair in the reaction equation of following example Optical diode.
Embodiment 1, preparation (4- oxo -4- phenyl butyl- 2- yl) benzyq carbamate
Reaction equation:
The specific method is as follows:
In Schlenk reaction tube (Beijing Xin Weier glass apparatus Co., Ltd, F891410 reaction tube, the capacity of 10mL 10mL, ground 14/20) in be added sodium iodide (0.3mmol, 45.0mg), triphenylphosphine (0.04mmol (that is, be active carboxylic acid's ester The 20mol% of compound.Meaning same as below), 10.5mg) and benzyloxycarbonyl group Cbz- protection alanine active carboxylic acid's ester (0.2mmol, 73.6 mg).Inner air tube is replaced three times completely with argon gas, and 2mL acetonitrile, trimethyl are then added under argon atmosphere ((1- phenyl vinyl) oxygroup) silane (0.4mmol, 76.8mg).Reaction system room under the illumination condition of 456nm wavelength It is continuously stirred under temperature 15 hours (using IKA magnetic stirring apparatus, RCT basic model, 500 revs/min of mixing speed).End of reaction Afterwards, H is used2O quenching reaction, and reaction solution is extracted with ethyl acetate (3*10mL), then by combined organic phase rotary evaporation (Bu Qi Co., Ltd of Switzerland, BUCHI Rotary Evaporators R-3) is concentrated in mode.Concentrated residue passes through chromatographic column (Beijing Xin Weierbo Glass Instrument Ltd., C383040C tool sand plate storage ball chromatographic column, 35/20,It is effectively long: 500ml) chromatography Obtain product.(product is white solid, totally 60.3 milligrams, yield 76%, and eluant ethyl acetate: petroleum ether=1: 10~1: 5)。
1H NMR (400MHz, CDCl3) δ 7.95 (d, J=7.1Hz, 2H), 7.64-7.54 (m, 1H), 7.51-7.41 (m, 2H), 7.40-7.27 (m, 5H), 5.34 (s, 1H), 5.18-5.00 (m, 2H), 4.31-4.20 (m, 1H), 3.47-2.96 (m, 2H), 1.30 (d, J=6.7Hz, 3H).
13C NMR (101MHz, CDCl3) δ 198.7,155.6,136.9,136.5,133.3,128.7,128.5, 128.1,128.1,128.0,66.6,44.3,44.1,20.4.
Embodiment 2, preparation (1- (4- (tert-butoxy) phenyl) -4- oxo -4- phenyl butane -2- base) carbamic acid uncle Butyl ester
Reaction equation:
In Schlenk reaction tube (Beijing Xin Weier glass apparatus Co., Ltd, F891410 reaction tube, the capacity of 10mL 10mL, ground 14/20) in be added sodium iodide (0.4mmol, 60.0mg), triphenylphosphine (0.04mmol, 10.5mg) and 1,3- bis- Oxoisoindolines -2- base 3- (4- (tert-butoxy) phenyl) -2- ((tert-butoxycarbonyl) amino) propionic ester (0.2mmol, 96.4mg).Inner air tube is replaced three times completely with argon gas, and 2mL acetonitrile, trimethyl ((1- phenyl are then added under argon atmosphere Vinyl) oxygroup) silane (0.4mmol, 76.8mg).The reaction system is continuous at room temperature under the illumination condition of 456 nm wavelength Stirring 18 hours (using IKA magnetic stirring apparatus, RCT basic model, 500 revs/min of mixing speed).After completion of the reaction, H is used2O Quenching reaction, and reaction solution is extracted with ethyl acetate (3*10mL), then the mode of combined organic phase rotary evaporation is concentrated (Bu Qi Co., Ltd of Switzerland, BUCHI Rotary Evaporators R-3).By chromatographic column, (Beijing Xin Weier glass apparatus has concentrated residue Limit company, C383040C tool sand plate storage ball chromatographic column, 35/20,Effectively long: 500ml) chromatography is produced Object.(product is white solid, totally 61.8 milligrams, yield 75%, and eluant ethyl acetate: petroleum ether=1: 10~1: 5).
1H NMR (400MHz, CDCl3) δ 7.85 (d, J=7.8Hz, 2H), 7.59-7.50 (m, 1H), 7.48-7.38 (m, 2H), 7.06 (d, J=8.0Hz, 2H), 6.88 (d, J=8.0Hz, 2H), 5.26 (br, 1H), 4.35-4.14 (m, 1H), 3.24- 2.80 (m, 4H), 1.38 (s, 9H), 1.31 (s, 9H).
13C NMR (101MHz, CDCl3) δ 199.4,155.3,153.9,136.9,133.3,129.7,128.6, 128.1,124.2,79.2,78.3,49.3,40.9,39.4,28.8,28.4.
HRMS (ESI), to C25H34O4N+ [M+H]+calculated value: 412.2482, measured value: 412.2486.
Embodiment 3, preparation 2- (2- oxo -2- phenethyl) pyrrolidines -1- carboxylic acid tert-butyl ester
Reaction equation:
In Schlenk reaction tube (Beijing Xin Weier glass apparatus Co., Ltd, F891410 reaction tube, the capacity of 10mL 10mL, ground 14/20) in be added potassium iodide (0.3mmol, 49.8mg), triphenylphosphine (0.04mmol, 10.5mg) and 2- (1, 3- dioxoisoindolin -2- base) pyrrolidines -1,2- dicarboxylic acids 1- tert-butyl ester (0.2mmol, 72.0mg).It is set completely with argon gas It changes inner air tube three times, 2mL acetonitrile, trimethyl ((1- phenyl vinyl) oxygroup) silane is then added under argon atmosphere (0.4mmol, 76.8mg).The reaction system is continuously stirred 20 hours at room temperature under the illumination condition of 456nm wavelength and (is used IKA magnetic stirring apparatus, RCT basic model, 500 revs/min of mixing speed).After completion of the reaction, H is used2O quenching reaction, and use second Acetoacetic ester (3*10mL) extracts reaction solution, then (the limited public affairs of Switzerland's step fine jade are concentrated in the mode of combined organic phase rotary evaporation Department, BUCHI Rotary Evaporators R-3).Concentrated residue passes through chromatographic column (Beijing Xin Weier glass apparatus Co., Ltd, C383040C Tool sand plate storage ball chromatographic column, 35/20,Effectively long: 500ml) chromatography obtains product.(product is that white is solid Body, totally 44.5 milligrams, yield 77%, eluant ethyl acetate: petroleum ether=1: 10~1: 5).
1H NMR (400MHz, CDCl3) δ 7.99 (d, J=7.4Hz, 2H), 7.59-7.50 (m, 1H), 7.49-7.40 (m, 2H), 4.31 (t, J=8.6Hz, 1H), 3.85-3.21 (m, 3H), 2.92- 2.74 (m, 1H), 2.13-1.98 (m, 1H), 1.92-1.69 (m, 3H), 1.44 (s, 9H).
13C NMR (101MHz, CDCl3) δ 199.0,154.4,136.9,133.1,128.6,128.3,79.5,54.3, 46.5,43.4,29.7,28.6,23.3.
Embodiment 4, preparation (4- oxo-Isosorbide-5-Nitrae-diphenyl butyl- 2- yl) t-butyl carbamate
Reaction equation:
In Schlenk reaction tube (Beijing Xin Weier glass apparatus Co., Ltd, F891410 reaction tube, the capacity of 10mL 10mL, ground 14/20) in be added sodium iodide (0.3mmol, 45.0mg), three (4- fluorophenyl) phosphines (0.04mmol, 12.6mg) and 1,3- dioxoisoindolin -2- base 2- ((tert-butoxycarbonyl) amino) -3- phenylpropionic acid ester (0.2mmol, 82.0mg). Inner air tube is replaced three times completely with argon gas, and 2mL acetonitrile, trimethyl ((1- phenyl vinyl) oxygen are then added under argon atmosphere Base) silane (0.4mmol, 76.8mg).It is small that the reaction system continuously stirs 20 at room temperature under the illumination condition of 456nm wavelength When (use IKA magnetic stirring apparatus, RCT basic model, 500 revs/min of mixing speed).After completion of the reaction, H is used2O quenching reaction, And reaction solution is extracted with ethyl acetate (3*10mL), then (Switzerland's step fine jade is concentrated in the mode of combined organic phase rotary evaporation Co., Ltd, BUCHI Rotary Evaporators R-3).Concentrated residue by chromatographic column (Beijing Xin Weier glass apparatus Co., Ltd, C383040C tool sand plate storage ball chromatographic column, 35/20,Effectively long: 500ml) chromatography obtains product.(product For oily liquids, totally 47.5 milligrams, yield 70%, eluant ethyl acetate: petroleum ether=1: 10~1: 5).
1H NMR (400MHz, CDCl3) δ 7.94-7.81 (m, 2H), 7.64-7.52 (m, 1H), 7.50-7.38 (m, 2H), 7.34-7.12 (m, 5H), 5.26 (br, 1H), 4.55-4.07 (m, 1H), 3.35-2.81 (m, 4H), 1.39 (s, 9H).
13C NMR (101MHz, CDCl3) δ 199.3,155.3,138.3,137.0,133.3,129.4,128.7, 128.5,128.1,126.5,79.3,49.3,40.94,4.12,28.4.
HRMS (ESI), C21H26O3N+ [M+H]+calculated value: 340.1907, measured value: 340.1912.
Embodiment 5, preparation (5- (methyl mercapto) -1- oxo -1- phenyl pentane -3- base) t-butyl carbamate reaction equation:
In Schlenk reaction tube (Beijing Xin Weier glass apparatus Co., Ltd, F891410 reaction tube, the capacity of 10mL 10mL, ground 14/20) in be added sodium iodide (0.3mmol, 45.0mg), three (4- fluorophenyl) phosphines (0.04mmol, 12.6mg) and 1,3- dioxoisoindolin -2- base 2- ((tert-butoxycarbonyl) amino) -4- (methyl mercapto) butyrate (0.2mmol, 78.9mg).Inner air tube is replaced three times completely with argon gas, then under argon atmosphere plus 2mL n,N-Dimethylformamide, three Methyl ((1- phenyl vinyl) oxygroup) silane (0.4mmol, 76.8mg).Illumination condition of the reaction system in 456nm wavelength Under continuously stir at room temperature 20 hours (using IKA magnetic stirring apparatus, RCT basic model, 500 revs/min of mixing speed).It has reacted Bi Hou uses H2O quenching reaction, and reaction solution is extracted with ethyl acetate (3*10mL), then by combined organic phase rotary evaporation Mode (Bu Qi Co., Ltd of Switzerland, BUCHI Rotary Evaporators R-3) is concentrated.Concentrated residue passes through chromatographic column (Beijing Xin Weier Glass apparatus Co., Ltd, C383040C tool sand plate storage ball chromatographic column, 35/20,It is effectively long: 500ml) chromatography point From obtaining product.(product is oily liquids, totally 50.4 milligrams, yield 78%, and eluant ethyl acetate: petroleum ether=1: 10~1 ∶5)。
1H NMR (400MHz, CDCl3) δ 7.98-7.90 (m, 2H), 7.62-7.53 (m, 1H), 7.50-7.43 (m, 2H), 5.18 (br, 1H), 4.20-4.11 (m, 1H), 3.43-2.98 (m, 2H), 2.81-2.39 (m, 2H), 2.08 (s, 3H), 2.01- 1.80 (m, 2H), 1.41 (s, 9H)
13C NMR (101MHz, CDCl3) δ 198.9,155.4,136.8,133.4,128.7,128.1,79.3,47.2, 42.47,33.6,31.0,28.4,15.5.
HRMS (ESI), C17H26O3NS+ [M+H]+calculated value: 324.1628, measured value: 324.1632.
Embodiment 6, preparation (1- (2- oxo -2- phenylethyl) cyclobutyl) t-butyl carbamate
Reaction equation:
For method with example 1, yield is shown in Table 1, is 78%.
In Schlenk reaction tube (Beijing Xin Weier glass apparatus Co., Ltd, F891410 reaction tube, the capacity of 10mL 10mL, ground 14/20) in be added sodium iodide (0.3mmol, 45.0mg), three (4- fluorophenyl) phosphines (0.04mmol, 12.6mg) and 1,3- dioxoisoindolin -2- base 1- ((tert-butoxycarbonyl) amino) cyclobutane-carboxylic acid ester (0.2mmol, 72.0mg).With Argon gas replaces inner air tube three times completely, and 2mL n,N-dimethylacetamide, trimethyl ((1- benzene are then added under argon atmosphere Base vinyl) oxygroup) silane (0.4mmol, 76.8mg).The reaction system connects at room temperature under the illumination condition of 456 nm wavelength Continuous stirring 20 hours (using IKA magnetic stirring apparatus, RCT basic model, 500 revs/min of mixing speed).After completion of the reaction, it uses H2O quenching reaction, and reaction solution is extracted with ethyl acetate (3*10mL), then the mode of combined organic phase rotary evaporation is dense It contracts (Bu Qi Co., Ltd of Switzerland, BUCHI Rotary Evaporators R-3).Concentrated residue passes through chromatographic column (Beijing Xin Weier glass apparatus Co., Ltd, C383040C tool sand plate storage ball chromatographic column, 35/20,Effectively long: 500ml) chromatography obtains Product.(product is white solid, totally 45.1 milligrams, yield 78%, and eluant ethyl acetate: petroleum ether=1: 10~1: 5).
1H NMR (400MHz, CDCl3) δ 7.97 (d, J=7.7Hz, 2H), 7.56 (t, J=7.3 Hz, 1H), 7.46 (t, J =7.6Hz, 2H), 5.22 (br, 1H), 3.56 (s, 2H), 2.42-2.18 (m, 4H), 2.09-1.92 (m, 1H), 1.92-1.78 (m, 1H), 1.38 (s, 9H)
13C NMR (101MHz, CDCl3) δ 199.23,154.47,137.46,133.14,128.58,128.07, 79.04,54.72,44.46,33.43,28.38,15.48.
HRMS (ESI), C17H24O3N+ [M+H]+calculated value: 290.1751, measured value: 290.1755.
Embodiment 7, (3- ([1,1 '-biphenyl] -4- base) -3- oxopropyl) t-butyl carbamate
Reaction equation:
For method with example 1, yield is shown in Table 1, is 84%.
1H NMR (400MHz, CDCl3) δ 8.03 (d, J=8.5Hz, 2H), 7.69 (d, J=8.5 Hz, 2H), 7.66- 7.60 (m, 2H), 7.52-7.45 (m, 2H), 7.44-7.37 (m, 1H), 5.19 (br, 1H), 3.57 (dd, J=11.4, 5.7Hz, 2H), 3.24 (t, J=5.6Hz, 2H), 1.44 (s, 9H)
13C NMR (101MHz, CDCl3) δ 199.0,156.0,146.1,139.7,135.3,129.0,128.6, 128.3,127.3,127.3,79.3,38.7,35.5,28.4.
HRMS (ESI), C20H24O3N+[M+H]+Calculated value: 326.1751, measured value: 326.1754.
Embodiment 8, preparation (3- oxo -3- phenyl propyl) t-butyl carbamate
Reaction equation:
For method with example 1, yield is shown in Table 1.
1H NMR (400MHz, CDCl3) δ 7.82 (d, J=7.2Hz, 2H), 7.43 (t, J=7.3 Hz, 1H), 7.32 (t, J =7.6Hz, 2H), 3.49 (br, 2H), 3.07 (s, 2H), 2.76 (s, 3H), 1.29 (s, 9H).
13C NMR (101MHz, CDCl3) δ 199.0,155.6,136.8,133.3,128.7,128.1,79.6,45.1, 37.2,35.3,34.8,28.4.
Embodiment 9, preparation (3- oxo -3- (thiophene -2- base) propyl) t-butyl carbamate
Reaction equation:
For method with example 1, yield is shown in Table 1.
1H NMR (400MHz, CDCl3) δ 7.75 (br, 1H), 7.66 (d, J=4.8Hz, 1H), 7.22-7.06 (m, 1H), 3.63 (t, J=6.9Hz, 2H), 3.15 (br, 3H), 2.89 (s, 9H)
13C NMR (101MHz, CDCl3) δ 192.1,155.7,144.4,134.1,132.5,128.3,79.8,45.4, 38.3,35.7 and 34.9 (CH2 rotational isomers), 28.5.
HRMS (ESI), C13H20O3NS+[M+H]+Calculated value: 270.1158, measured value: 270.1163.
Embodiment 10, preparation 2- (2- (4- isobutyl phenenyl) -2- oxoethyl) pyrrolidines -1- carboxylic acid tert-butyl ester
Reaction equation:
For method with example 1, yield is shown in Table 1.
1H NMR (400MHz, CDCl3) δ 7.92 (d, J=7.8Hz, 2H), 7.22 (d, J=7.9 Hz, 2H), 4.32 (t, J =8.6Hz, 1H), 3.59 (br, 1H), 3.36 (t, J=6.2Hz, 2H), 2.92-2.70 (m, 1H), 2.51 (d, J=7.2Hz, 2H), 2.10-1.99 (m, 1H), 1.93-1.71 (m, 4H), 1.45 (s, 9H), 0.89 (d, J=6.6Hz, 6H).
13C NMR (101MHz, CDCl3) δ 198.7,154.4,147.7,134.7,129.3,128.3,79.4,54.4, 46.5,45.4,43.4,30.1,28.6,22.3.(two carbon signal overlappings)
HRMS (ESI), C21H32O3N+[M+H]+Calculated value: 346.2377, measured value: 346.2379.
Embodiment 11, preparation (2- (4- (methoxycarbonyl) phenyl) -2- oxoethyl) pyrrolidines -1- carboxylic acid tert-butyl ester
Reaction equation:
For method with example 1, yield is shown in Table 1.
1H NMR (400MHz, CDCl3) δ 8.24-7.96 (m, 4H), 4.39-4.26 (m, 1H), 3.95 (s, 3H), 3.82- 3.54 (m, 1H), 3.48-3.28 (m, 2H), 2.96-2.76 (m, 1H), 2.19-2.02 (m, 1H), 1.98-1.81 (m, 9H), 1.80-1.70 (m, 1H), 1.46 (s, 9H).
13C NMR (101MHz, CDCl3) δ 198.5,166.2,154.4,139.9,134.2,129.9,128.2,79.6, 63.6,54.2,52.5,46.5,29.7,28.5,28.3.
HRMS (ESI), C19H26O5N+[M+H]+Calculated value: 348.1805, measured value: 348.1809.
Embodiment 12[gram-grade reaction], preparation the tertiary fourth of 4- (((benzyloxy) carbonyl) amino) -6- oxo -6- phenyl caproic acid Ester
In Schlenk reaction tube (Beijing Xin Weier glass apparatus Co., Ltd, F891410 reaction tube, the capacity of 100mL 10mL, ground 14/20) in sodium iodide (12mmol, 1.8g), triphenylphosphine (0.8mmol, 209.8mg) and 1- (1,3- bis- is added Oxoisoindolines -2- base) 2- (((benzyloxy) carbonyl) amino) glutaric acid 5- tert-butyl ester (12mmol, 3.86g).It is complete with argon gas Total replacement inner air tube three times, then adds 40mL acetonitrile, trimethyl ((1- phenyl vinyl) oxygroup) silane under argon atmosphere (12mmol, 2.31g).The reaction system continuously stirs 20 hours at room temperature under the illumination condition of 456nm wavelength and (uses IKA Magnetic stirring apparatus, RCT basic model, 500 revs/min of mixing speed).After completion of the reaction, H is used2O quenching reaction, and with acetic acid second Ester (3*30mL) extracts reaction solution, then the mode of combined organic phase rotary evaporation is concentrated (Bu Qi Co., Ltd of Switzerland, BUCHI Rotary Evaporators R-3).Concentrated residue passes through chromatographic column (Beijing Xin Weier glass apparatus Co., Ltd, C383040C tool Sand plate storage ball chromatographic column, 35/20,Effectively long: 500ml) chromatography obtains product.(product is white solid, Totally 2.91 grams, yield 88%, eluant ethyl acetate: petroleum ether=1: 10~1: 5).
1H NMR (400MHz, CDCl3) δ 7.94 (d, J=7.5Hz, 2H), 7.60-7.53 (m, 1H), 7.45 (t, J= 7.6Hz, 2H), 7.37-7.27 (m, 5H), 5.51 (d, J=8.7Hz, 1H), 5.07 (s, 2H), 4.13 (tt, J=14.5, 7.3Hz, 1H), 3.38 (dd, J=17.0,4.3Hz, 1H), 3.14 (dd, J=17.0,6.1Hz, 1H), 2.33 (t, J= 7.3Hz, 2H), 2.09-1.80 (m, 2H), 1.42 (s, 9H).
13C NMR (101MHz, CDCl3) δ 198.6,172.8,156.0,136.8,136.5,133.4,128.7, 128.5,128.1,128.1,128.0,80.6,66.6,48.3,42.8,32.6,29.1,28.1.
HRMS (ESI), C24H30NO5 +[M+H]+Calculated value: 412.2118, measured value: 412.2130.
The preparation of the nonmetal catalyzed beta-amino ketones of 1 photoinduction of table
Industrial applicability
Inventive process avoids the use of metallic catalyst, meet the requirement for developing the friendly chemistry of green environment, substrate Range is wide and functional group compatibility is good, provides a kind of new method for the synthesis of Beta-aminoketones compound.Moreover, of the invention Raw materials and reagents used in method are easy to get, and reaction can be amplified to gram-grade gauge mould, and conversion ratio and yield are higher, have good Prospects for commercial application.

Claims (10)

1. a kind of nonmetal catalyzed method for preparing beta-amino ketones of photoinduction, the described method comprises the following steps:
At room temperature, existing for simple salt compounded of iodine, Phosphine ligands and the organic solvent under the conditions of, pass through illumination realize it is living shown in formula 1 The decarboxylation of property carboxylate compound, and react to obtain Beta-aminoketones shown in formula 3 with silyl enol ether compound shown in formula 2 Close object:
Wherein:
In formula 1, R1For tertbutyloxycarbonyl and benzyloxycarbonyl group, R2For hydrogen atom or straight chain, branch or cricoid C1-20Alkyl, R3 For hydrogen atom, C6-20Aryl, straight chain, branch or cricoid C1-20Alkyl, C1-20Sulfanyl, C1-4Alkyl phenoxy C1-4Alkyl, or Person R3And R2Ring is formed together with their connect N atoms；
In formula 2, aromatic ring is by R4Substituted phenyl ring or thiphene ring, TMS indicate trimethyl silane group, and R4Be The C of linear chain or branched chain on different the position of substitution of the aromatic ring1-20Alkyl, C6-20Aryl or ester group；
In formula 3, R1And R2Definition it is identical as the definition in formula 1, R4Definition it is identical as the definition in formula 2.
2. according to the method described in claim 1, wherein, the molar ratio of the formula 2 and formula 1 is 1.0-4.0.
3. according to the method described in claim 1, wherein, the simple salt compounded of iodine is in sodium iodide, potassium iodide and lithium iodide At least one.
4. according to the method described in claim 1, wherein, the Phosphine ligands are selected from triphenylphosphine, three (4- fluorophenyl) phosphines, three In (4- anisyl) phosphine, three (3- anisyl) phosphines, diphenyl-2-pyridyl phosphine and bis- (2- diphenylphosphine phenyl) ethers at least It is a kind of.
5. according to the method described in claim 1, wherein, the mole dosage of the salt compounded of iodine is the mole dosage of the formula 1 1.0-2.0 again.
6. according to the method described in claim 1, wherein, the mole dosage of the Phosphine ligands is the mole dosage of the formula 1 5%-50%.
7. according to the method described in claim 1, wherein, the wave-length coverage of the light source is between 365nm to 500nm, irradiation Time is 4-24 hours.
8. according to the method described in claim 1, wherein, the organic solvent is selected from n,N-Dimethylformamide, N, N- diformazan At least one of yl acetamide, acetonitrile, tetrahydrofuran and toluene.
9. according to the method described in claim 1, wherein, active carboxylic acid's ester compounds of formula 1 are selected from:
10. according to the method described in claim 1, wherein, the silyl enol ether compound of formula 2 is selected from:
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020063399A1 (en) * 2018-09-26 2020-04-02 中国科学技术大学 Method for light-induced decarboxylation coupling of active carboxylic acid ester under non-metal catalysis
CN111233752A (en) * 2020-03-10 2020-06-05 中国科学技术大学 Decarboxylation in-situ methylation method of alkyl active carboxylic ester
CN111269133A (en) * 2020-03-10 2020-06-12 中国科学技术大学 Method for synthesizing photoinduced anion catalyzed unnatural amino acid
CN114605237A (en) * 2020-12-09 2022-06-10 武汉大学 Preparation method and application of fluoroalkyl ketone compound

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3859303A (en) * 1971-08-09 1975-01-07 Fuji Photo Film Co Ltd Spiro(indoline-2,5'-pyrazoline)derivatives
EP0247378A1 (en) * 1986-04-30 1987-12-02 Kanegafuchi Kagaku Kogyo Kabushiki Kaisha Process for preparing 4-acetoxy-3-hydroxyethylazetidin-2-one derivatives
CN101982455A (en) * 2010-10-09 2011-03-02 苏州大学 Method for synthesizing beta-arylamino ketone and method for synthesizing beta-heterocyclic amino ketone
CN106496114A (en) * 2016-10-18 2017-03-15 中国科学技术大学 A kind of preparation method of aromatic aza cycle compound
CN106699662A (en) * 2015-11-18 2017-05-24 安阳师范学院 Novel method for efficiently preparing beta-aminoketone by utilizing dimethyl sulfoxide

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3859303A (en) * 1971-08-09 1975-01-07 Fuji Photo Film Co Ltd Spiro(indoline-2,5'-pyrazoline)derivatives
EP0247378A1 (en) * 1986-04-30 1987-12-02 Kanegafuchi Kagaku Kogyo Kabushiki Kaisha Process for preparing 4-acetoxy-3-hydroxyethylazetidin-2-one derivatives
CN101982455A (en) * 2010-10-09 2011-03-02 苏州大学 Method for synthesizing beta-arylamino ketone and method for synthesizing beta-heterocyclic amino ketone
CN106699662A (en) * 2015-11-18 2017-05-24 安阳师范学院 Novel method for efficiently preparing beta-aminoketone by utilizing dimethyl sulfoxide
CN106496114A (en) * 2016-10-18 2017-03-15 中国科学技术大学 A kind of preparation method of aromatic aza cycle compound

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
KONG WEIGUANG ET AL: "Photoredox-Catalyzed Decarboxylative Alkylation of Silyl Enol Ethers To Synthesize Functionalized Aryl Alkyl Ketones", 《ORGANIC LETTERS》 *
XIA ZIHAO ET AL: "Switchable Decarboxylative Heck-Type Reaction and Oxo-alkylation of Styrenes with N‑Hydroxyphthalimide Esters under Photocatalysis", 《ORGANIC LETTERS》 *
闫溢哲等: "低价碘催化的氧化偶联反应研究进展", 《有机化学》 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020063399A1 (en) * 2018-09-26 2020-04-02 中国科学技术大学 Method for light-induced decarboxylation coupling of active carboxylic acid ester under non-metal catalysis
CN111233752A (en) * 2020-03-10 2020-06-05 中国科学技术大学 Decarboxylation in-situ methylation method of alkyl active carboxylic ester
CN111269133A (en) * 2020-03-10 2020-06-12 中国科学技术大学 Method for synthesizing photoinduced anion catalyzed unnatural amino acid
CN111269133B (en) * 2020-03-10 2021-04-23 中国科学技术大学 Method for synthesizing photoinduced anion catalyzed unnatural amino acid
CN111233752B (en) * 2020-03-10 2021-07-09 中国科学技术大学 Decarboxylation in-situ methylation method of alkyl active carboxylic ester
CN114605237A (en) * 2020-12-09 2022-06-10 武汉大学 Preparation method and application of fluoroalkyl ketone compound
CN114605237B (en) * 2020-12-09 2023-02-24 武汉大学 Preparation method and application of fluoroalkyl ketone compound

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