CN109096150B - Method for preparing beta-aminoketone by photoinduction nonmetal catalysis - Google Patents
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- C07—ORGANIC CHEMISTRY
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- 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
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- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
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- 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
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- 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
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Abstract
The invention discloses a method for preparing beta-aminoketone by photoinduction nonmetal catalysis. The method comprises the following steps: under the condition of existence of simple iodized salt, phosphine ligand and organic solvent, decarboxylation of active carboxylic ester is realized by illumination, and the decarboxylation reacts with silicon enol ether to obtain beta-aminoketone. The method provided by the invention utilizes photocatalysis to realize high-efficiency catalytic conversion at room temperature, and has mild reaction conditions and simple operation. The method avoids the use of metal catalysts, meets the requirements of developing green environment-friendly chemistry, has wide substrate range and good functional group compatibility, and provides a new method for synthesizing beta-aminoketone compounds. The raw materials and reagents are easy to obtain, the reaction can be amplified to gram-scale, the conversion rate and the yield are high, and the method has a good industrial application prospect.
Description
Technical Field
The invention relates to the field of compound synthesis, in particular to a method for preparing beta-aminoketone by photoinduction nonmetal catalysis.
Background
The beta-aminoketone as intermediate is widely applied to the fields of fine chemical industry and medicine, and the biological activity of the beta-aminoketone comprises anti-inflammatory, anti-cancer, anti-tuberculosis, antibacterial, analgesic and cough relieving. The general synthesis method comprises Mannich reaction using aldehyde, ketone and amine as raw materials, ring-opening addition of cyclopropyl alcohol and sulfonyl azide compounds and the like. The method provided by the invention utilizes light induction to realize high-efficiency catalytic conversion of nonmetal at room temperature, and has mild reaction conditions and simple operation. The method avoids the use of metal catalysts and meets the requirements of developing green environment-friendly chemistry.
Disclosure of Invention
The invention aims to provide a method for preparing beta-aminoketone by photoinduced nonmetal catalysis, and the method does not need to add a metal catalyst in a reaction system, and has mild reaction conditions and better compatibility with functional groups.
In order to solve the technical problems, the invention provides the following technical scheme:
a method for preparing beta-aminoketone by photoinduced nonmetal catalysis, which comprises the following steps:
at room temperature, under the condition of existence of simple iodized salt, phosphine ligand and organic solvent, decarboxylation of the active carboxylic ester compound shown in the formula 1 is realized through illumination, and the decarboxylation reacts with the enol silyl ether compound shown in the formula 2 to obtain the beta-aminoketone compound shown in the formula 3:
wherein:
in formula 1, R1Is tert-butyloxycarbonyl (Boc) and benzyloxycarbonyl (Cbz), R2Is a hydrogen atom or a linear, branched or cyclic C1-20Alkyl radical, R3Is a hydrogen atom, C6-20Aryl, straight, branched or cyclic C1-20Alkyl radical, C1-20Sulfanyl radical, C1-4Alkylphenoxy C1-4Alkyl, or R3And R2Form a ring together with the N atom to which they are attached;
in formula 2, the aromatic ring is substituted by R4A substituted benzene ring, or a thiophene ring, TMS represents a trimethylsilyl group, and R represents4Is a straight-chain or branched C at different substitution positions of the aromatic ring1-20Alkyl radical, C6-20An aryl or ester group;
in formula 3, R1And R2Is as defined in formula 1, R4Is the same as defined in formula 2.
The method according to the above, wherein the molar ratio of the formula 2 to the formula 1 is 1.0 to 4.0.
<3> the method as described above, wherein the simple iodide salt is selected from at least one of sodium iodide, potassium iodide and lithium iodide.
<4> the method as described above, wherein the phosphine ligand is at least one selected from the group consisting of triphenylphosphine, tris (4-fluorophenyl) phosphine, tris (4-methoxyphenyl) phosphine, tris (3-methoxyphenyl) phosphine, diphenyl-2-pyridylphosphine and bis (2-diphenylphosphinophenyl) ether.
<5> the method as described above, wherein the molar amount of the iodide salt is 1.0 to 2.0 times the molar amount of formula 1.
<6> the method as described above, wherein the molar amount of the phosphine ligand is 5% to 50% of the molar amount of the formula 1.
<7> the method as described above, wherein the light source has a wavelength ranging from 365nm to 500nm and an irradiation time ranging from 4 to 24 hours.
The method according to the above, wherein the organic solvent is at least one selected from the group consisting of N, N-dimethylformamide, N-dimethylacetamide, acetonitrile, tetrahydrofuran and toluene.
The method according to the above, wherein the active carboxylate compound of formula 1 is selected from:
the method according to the above, wherein the enolsilyl ether compound of formula 2 is selected from the group consisting of:
the method provided by the invention is to utilize light to induce the decarboxylation of the non-metal catalytic active carboxylic ester and react with the enol silyl ether compound to obtain the beta-aminoketone. The method has the advantages of mild reaction conditions and simple operation, avoids the use of metal catalysts, provides a novel method for synthesizing the beta-aminoketone, and meets the requirements of developing green environment-friendly chemistry. Moreover, the method can be successfully applied to the synthesis of precursors of pharmaceutical molecules duloxetine, fluoxetine hydrochloride and atomoxetine. The gram-scale reaction has high conversion rate and industrial synthesis value prospect.
Detailed Description
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the methods of the present invention. The preferred methods and materials described herein are exemplary only.
In the present invention, "non-metal" in the term "light-induced non-metal catalysis" means that a metal such as metallic iridium, ruthenium, palladium, etc. is not used in the catalytic system, and thus "light-induced non-metal catalysis" means light-induced catalysis that occurs without using a metal such as metallic iridium, ruthenium, palladium, etc. in the catalytic system.
The invention provides a method for preparing beta-aminoketone by photoinduction nonmetal catalysis, which has the following chemical reaction schematic diagram:
as can be seen from the above schematic diagram, the method of the present invention comprises the following steps:
at room temperature, under the condition that simple iodized salt, phosphine ligand and organic solvent exist, decarboxylation of the active carboxylic ester compound shown in the formula 1 is realized through illumination, and the decarboxylation reacts with the enol silyl ether compound shown in the formula 2 to obtain the beta-aminoketone compound shown in the formula 3.
And, in the above schematic, the group R1、R2、R3And R4Has the following meanings.
In formula 1, R1Is Boc and Cbz, R2Is a hydrogen atom or a linear, branched or cyclic C1-20Alkyl radical, R3Is a hydrogen atom, C6-20Aryl, straight, branched or cyclic C1-20Alkyl radical, C1-20Sulfanyl radical, C1-4Alkylphenoxy C1-4Alkyl, or R3And R2 form a ring together with the N atom to which they are attached.
In formula 1, the straight, branched or cyclic C1-20Examples of alkyl groupsIncluding methyl, ethyl, propyl, n-butyl, sec-butyl, tert-butyl, hexyl, heptyl, octyl, cyclobutyl, cyclohexyl, dodecyl, octadecyl, docosyl, and the like.
In formula 1, C6-20Examples of aryl groups are phenyl, benzyl, phenethyl, and the like.
In formula 1, C1-20Examples of thioalkyl groups include thiomethyl, thio-n-propyl, thio-n-butyl, thiohexyl, thiododecyl, and the like.
In formula 1, the term "C" is1-4Alkylphenoxy C4Examples of alkyl groups include methylphenoxy n-butyl, n-propylphenoxy tert-butyl, ethylpropoxy tert-butyl, and the like.
In formula 1, the "R" is3And R2Examples of the ring "forming a ring with the N atom to which they are attached include cyclobutyl, cyclopropyl, cyclohexyl, and the like.
In formula 2, the aromatic ring is substituted by R4A substituted benzene ring, or a thiophene ring, TMS represents a trimethylsilyl group, and R represents4Is a straight-chain or branched C at different substitution positions of the aromatic ring1-20Alkyl radical, C6-20An aryl group or an ester group.
In formula 3, R1And R2Is defined as in formula 11And R2Are as defined for R4Is defined as in formula 24The same definition is applied.
The inventors found that reasonable molar ratio of formula 1 to formula 2, molar ratio of formula 1 to iodide salt and phosphine ligand, kinds of iodide salt and phosphine ligand and light source, etc. are the most important process conditions for carrying out the reaction in the decarboxylation conversion of the active carboxylic ester.
In the present invention, the molar ratio of formula 2 to formula 1 may be 1.0 to 4.0, more preferably 1.5 to 2.0.
In the present invention, the term "simple iodide salt" refers to an iodide of an alkali metal. Examples of simple iodine salts suitable for use are at least one selected from sodium iodide, potassium iodide and lithium iodide, and more preferably sodium iodide.
In the present invention, the phosphine ligand suitably used is at least one selected from the group consisting of triphenylphosphine, tris (4-fluorophenyl) phosphine, tris (4-methoxyphenyl) phosphine, tris (3-methoxyphenyl) phosphine, diphenyl-2-pyridylphosphine, bis (2-diphenylphosphinophenyl) ether, and more preferably triphenylphosphine.
In the present invention, the iodine salt is suitably used in a molar amount of 1.0 to 2.0 times, preferably 1.2 to 1.8 times, more preferably 1.4 to 1.5 times the molar amount of said formula 1.
In the present invention, the phosphine ligand is suitably used in a molar amount of 5 to 50%, preferably 10 to 30%, more preferably 15 to 25% of the molar amount of said formula 1.
In the present invention, the amount of formula 2 used in a molar amount is suitably 1 to 4 times, more preferably 2 to 3 times the amount of formula 1 used in a molar amount.
In the present invention, the wavelength range of the light source suitable for use is 365nm to 500nm, preferably 430-480nm, and more preferably 450-460 nm; the irradiation time is 4 to 24 hours, 8 to 20 hours, and more preferably 12 to 15 hours.
In the present invention, the organic solvent suitably used is at least one selected from the group consisting of N, N-dimethylformamide, N-dimethylacetamide, acetonitrile, tetrahydrofuran and toluene, and more preferably acetonitrile.
In the preparation method of the present invention, the yield of the β -aminoketone compound represented by formula 3 may be as high as about 90%, and the minimum yield of the β -aminoketone compound may also be 62%.
Examples
To further illustrate the present invention, preferred embodiments of the present invention are described below with reference to examples, but it should be understood that these descriptions are only for the purpose of further illustrating the features and advantages of the present invention, and are not intended to limit the claims of the present invention, and all other examples obtained by one of ordinary skill in the art without inventive faculty are within the scope of the present invention.
The drugs used in the following examples of the invention for the photoinduced non-metal catalyzed preparation of beta-aminoketones were purchased from the following reagent companies:
acetonitrile (C)2H3N, 99.9%), N, N-dimethylformamide (C)3H7NO, 99.5%), N, N-dimethylacetamide (C)4H9NO, 99.0%) were purchased from carbofuran corporation.
Sodium iodide (NaI, 99.5%) from Aladdin, triphenylphosphine (PPh)399%) from Adamas corporation.
In addition, in the reaction formulae of the following examples, r.t. represents room temperature, blue LED represents blue LED, and LED represents light emitting diode.
EXAMPLE 1 preparation of benzyl (4-oxo-4-phenylbutan-2-yl) carbamate
The reaction formula is as follows:
the specific method comprises the following steps:
to a 10mL Schlenk reaction tube (Beijing Xinville glass Instrument Co., Ltd., F891410 reaction tube, capacity 10mL, ground 14/20), sodium iodide (0.3mmol, 45.0mg), triphenylphosphine (0.04mmol (i.e., 20 mol% of active carboxylate compound, the same meaning hereinafter), 10.5mg) and benzyloxycarbonyl Cbz-protected alanine active carboxylate (0.2mmol, 73.6mg) were added. The air in the tube was completely replaced with argon three times, and then 2mL of acetonitrile, trimethyl ((1-phenylvinyl) oxy) silane (0.4mmol, 76.8mg) was added under an argon atmosphere. The reaction was stirred continuously at room temperature for 15 hours under light at a wavelength of 456nm (using an IKA magnetic stirrer, RCT basic type, stirring speed 500 rpm). After the reaction is finished, H is used2The reaction was quenched with ethyl acetate (3 x 10mL) and the combined organic phases were concentrated by rotary evaporation (BUCHI rotary evaporator R-3, qi, switzerland). The concentrated residue was purified by column chromatography (beijing xinweil glass instruments ltd, C383040C sand plate storage ball chromatography column, 35/20,
effective length: 500m1) was chromatographed to give the product. (the product is white)60.3 mg of a total of solid, 76% yield, and eluent ethyl acetate and petroleum ether of 1: 10-1: 5).
1H NMR(400MHz，CDCl3)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)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。
Example 2 preparation of tert-butyl (1- (4- (tert-butoxy) phenyl) -4-oxo-4-phenylbutan-2-yl) carbamate
The reaction formula is as follows:
to a 10mL Schlenk reaction tube (Beijing Xinville glass Instrument Co., Ltd., F891410 reaction tube, capacity 10mL, ground 14/20) were added sodium iodide (0.4mmol, 60.0mg), triphenylphosphine (0.04mmol, 10.5mg) and 1, 3-dioxoisoindolin-2-yl 3- (4- (tert-butoxy) phenyl) -2- ((tert-butoxycarbonyl) amino) propionate (0.2mmol, 96.4 mg). The air in the tube was completely replaced with argon three times, and then 2mL of acetonitrile, trimethyl ((1-phenylvinyl) oxy) silane (0.4mmol, 76.8mg) was added under an argon atmosphere. The reaction was stirred continuously at room temperature for 18 hours under light at a wavelength of 456nm (using an IKA magnetic stirrer, RCT basic type, stirring speed 500 rpm). After the reaction is finished, H is used2The reaction was quenched with ethyl acetate (3 x 10mL) and the combined organic phases were concentrated by rotary evaporation (BUCHI rotary evaporator R-3, qi, switzerland). The concentrated residue was purified by column chromatography (beijing xinweil glass instruments ltd, C383040C sand plate storage ball chromatography column, 35/20,
effective length: 500ml) was chromatographed to give the product. (the product was white61.8 mg of solid, 75% yield, eluent ethyl acetate and petroleum ether are 1: 10-1: 5).
1H NMR(400MHz，CDCl3)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)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), for C25H34O4N+[M+H]Calculated value of +: 412.2482, measured value：412.2486。
Example 3 preparation of tert-butyl 2- (2-oxo-2-phenylethyl) pyrrolidine-1-carboxylate
The reaction formula is as follows:
to a 10mL Schlenk reaction tube (Beijing Xinville glass Instrument Co., Ltd., F891410 reaction tube, capacity 10mL, ground 14/20) were added potassium iodide (0.3mmol, 49.8mg), triphenylphosphine (0.04mmol, 10.5mg) and 1-tert-butyl 2- (1, 3-dioxoisoindolin-2-yl) pyrrolidine-1, 2-dicarboxylate (0.2mmol, 72.0 mg). The air in the tube was completely replaced with argon three times, and then 2mL of acetonitrile, trimethyl ((1-phenylvinyl) oxy) silane (0.4mmol, 76.8mg) was added under an argon atmosphere. The reaction was stirred continuously for 20 hours at room temperature under light at a wavelength of 456nm (using an IKA magnetic stirrer, RCT basic type, stirring speed 500 rpm). After the reaction is finished, H is used2The reaction was quenched with ethyl acetate (3 x 10mL) and the combined organic phases were concentrated by rotary evaporation (BUCHI rotary evaporator R-3, qi, switzerland). The concentrated residue was purified by column chromatography (beijing xinweil glass instruments ltd, C383040C sand plate storage ball chromatography column, 35/20,
effective length: 500m1) was chromatographed to give the product. (the product was a white solid, 44.5 mg total, 77% yield, eluent ethyl acetate to petroleum ether 1: 10-1: 5).
1H NMR(400MHz，CDCl3)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)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。
Example 4 preparation of tert-butyl (4-oxo-1, 4-diphenylbutan-2-yl) carbamate
The reaction formula is as follows:
to a 10mL Schlenk reaction tube (Beijing Xinville glass Instrument Co., Ltd., F891410 reaction tube, capacity 10mL, ground 14/20) were added sodium iodide (0.3mmol, 45.0mg), tris (4-fluorophenyl) phosphine (0.04mmol, 12.6mg) and 1, 3-dioxoisoindolin-2-yl 2- ((tert-butoxycarbonyl) amino) -3-phenylpropionate (0.2mmol, 82.0 mg). The air in the tube was completely replaced with argon three times, and then 2mL of acetonitrile, trimethyl ((1-phenylvinyl) oxy) silane (0.4mmol, 76.8mg) was added under an argon atmosphere. The reaction was stirred continuously for 20 hours at room temperature under light at a wavelength of 456nm (using an IKA magnetic stirrer, RCT basic type, stirring speed 500 rpm). After the reaction is finished, H is used2The reaction was quenched with ethyl acetate (3 x 10mL) and the combined organic phases were concentrated by rotary evaporation (BUCHI rotary evaporator R-3, qi, switzerland). The concentrated residue was purified by column chromatography (beijing xinweil glass instruments ltd, C383040C sand plate storage ball chromatography column, 35/20,
effective length: 500ml) was chromatographed to give the product. (the product is an oily liquid, 47.5 mg in total, the yield is 70%, and the eluent ethyl acetate and petroleum ether are 1: 10-1: 5).
1H NMR(400MHz，CDCl3)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)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 of +: 340.1907, measurement: 340.1912.
example 5 preparation of tert-butyl (5- (methylthio) -1-oxo-1-phenylpentan-3-yl) carbamate the reaction scheme:
to a 10mL Schlenk reaction tube (Beijing Xinville glass Instrument Co., Ltd., F891410 reaction tube, capacity 10mL, ground 14/20) were added sodium iodide (0.3mmol, 45.0mg), tris (4-fluorophenyl) phosphine (0.04mmol, 12.6mg) and 1, 3-dioxoisoindolin-2-yl 2- ((tert-butoxycarbonyl) amino) -4- (methylthio) butyrate (0.2mmol, 78.9 mg). The air in the tube was completely replaced with argon three times, and then 2mL of N, N-dimethylformamide, trimethyl ((1-phenylvinyl) oxy) silane (0.4mmol, 76.8mg) was added under an argon atmosphere. The reaction was stirred continuously for 20 hours at room temperature under light at a wavelength of 456nm (using an IKA magnetic stirrer, RCT basic type, stirring speed 500 rpm). After the reaction is finished, H is used2The reaction was quenched with ethyl acetate (3 x 10mL) and the combined organic phases were concentrated by rotary evaporation (BUCHI rotary evaporator R-3, qi, switzerland). The concentrated residue was purified by column chromatography (beijing xinweil glass instruments ltd, C383040C sand plate storage ball chromatography column, 35/20,
effective length: 500ml) was chromatographed to give the product. (the product is oily liquid, 50.4 mg in total, yield is 78%, and eluent ethyl acetate and petroleum ether are 1: 10-1: 5).
1H NMR(400MHz，CDCl3)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)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 of +: 324.1628, measurement: 324.1632.
example 6 preparation of tert-butyl (1- (2-oxo-2-phenylethyl) cyclobutyl) carbamate the reaction scheme:
the procedure is as in example 1, the yield is 78% in Table 1.
To a 10mL Schlenk reaction tube (Beijing Xinville glass Instrument Co., Ltd., F891410 reaction tube, capacity 10mL, ground 14/20) were added sodium iodide (0.3mmol, 45.0mg), tris (4-fluorophenyl) phosphine (0.04mmol, 12.6mg) and 1, 3-dioxoisoindolin-2-yl 1- ((tert-butoxycarbonyl) amino) cyclobutanecarboxylic acid ester (0.2mmol, 72.0 mg). The air in the tube was completely replaced with argon three times, and then 2mL of N, N-dimethylacetamide, trimethyl ((1-phenylvinyl) oxy) silane (0.4mmol, 76.8mg) was added under an argon atmosphere. The reaction was stirred continuously for 20 hours at room temperature under light at a wavelength of 456nm (using an IKA magnetic stirrer, RCT basic type, stirring speed 500 rpm). After the reaction is finished, H is used2The reaction was quenched with ethyl acetate (3 x 10mL) and the combined organic phases were concentrated by rotary evaporation (Swiss Stewqi Co., Ltd.)BUCHI rotary evaporator R-3). The concentrated residue was purified by column chromatography (beijing xinweil glass instruments ltd, C383040C sand plate storage ball chromatography column, 35/20,
effective length: 500ml) was chromatographed to give the product. (the product was a white solid, 45.1 mg total, 78% yield, eluent ethyl acetate to petroleum ether 1: 10-1: 5).
1H NMR(400MHz，CDCl3)7.97(d，J＝7.7Hz，2H)，7.56(t，J＝7.3Hz，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)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 of +: 290.1751, measurement: 290.1755.
example 7 tert-butyl (3- ([1, 1' -biphenyl ] -4-yl) -3-oxopropyl) carbamate
The reaction formula is as follows:
the procedure is as in example 1, the yield is shown in Table 1 and is 84%.
1H NMR(400MHz，CDCl3)8.03(d，J＝8.5Hz，2H)，7.69(d，J＝8.5Hz，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)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]+The calculated value of (a): 326.1751, measurement: 326.1754.
example 8 preparation of tert-butyl (3-oxo-3-phenylpropyl) carbamate
The reaction formula is as follows:
the procedure is as in example 1, the yields are given in Table 1.
1H NMR(400MHz，CDCl3)7.82(d，J＝7.2Hz，2H)，7.43(t，J＝7.3Hz，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)199.0，155.6，136.8，133.3，128.7，128.1，79.6，45.1，37.2，35.3，34.8，28.4。
Example 9 preparation of tert-butyl (3-oxo-3- (thien-2-yl) propyl) carbamate
The reaction formula is as follows:
the procedure is as in example 1, the yields are given in Table 1.
1H NMR(400MHz，CDCl3)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)192.1, 155.7, 144.4, 134.1, 132.5, 128.3, 79.8, 45.4, 38.3, 35.7 and 34.9(CH2 rotamer), 28.5.
HRMS(ESI)，C13H20O3NS+[M+H]+The calculated value of (a): 270.1158, measurement: 270.1163.
example 10 preparation of tert-butyl 2- (2- (4-isobutylphenyl) -2-oxoethyl) pyrrolidine-1-carboxylate
The reaction formula is as follows:
the procedure is as in example 1, the yields are given in Table 1.
1H NMR(400MHz，CDCl3)7.92(d，J＝7.8Hz，2H)，7.22(d，J＝7.9Hz，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)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 signals overlap)
HRMS(ESI)，C21H32O3N+[M+H]+The calculated value of (a): 346.2377, measurement: 346.2379.
example 11 preparation of tert-butyl (2- (4- (methoxycarbonyl) phenyl) -2-oxoethyl) pyrrolidine-1-carboxylate
The reaction formula is as follows:
the procedure is as in example 1, the yields are given in Table 1.
1H NMR(400MHz，CDCl3)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)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]+The calculated value of (a): 348.1805, measurement: 348.1809.
example 12 [ gram-scale reaction ] preparation of tert-butyl 4- (((benzyloxy) carbonyl) amino) -6-oxo-6-phenylhexanoate
To a 100mL Schlenk reaction tube (Beijing Xinville glass Instrument Co., Ltd., F891410 reaction tube, capacity 10mL, ground 14/20) were added sodium iodide (12mmol, 1.8g), triphenylphosphine (0.8mmol, 209.8mg) and 5-tert-butyl 1- (1, 3-dioxoisoindolin-2-yl) 2- (((benzyloxy) carbonyl) amino) glutarate (12mmol, 3.86 g). The air in the tube was completely replaced with argon three times, and then 40mL of acetonitrile, trimethyl ((1-phenylvinyl) oxy) silane (12mmol, 2.31g) was added under an argon atmosphere. The reaction was stirred continuously for 20 hours at room temperature under light at a wavelength of 456nm (using an IKA magnetic stirrer, RCT basic type, stirring speed 500 rpm). After the reaction is finished, H is used2The reaction was quenched with ethyl acetate (3 × 30mL), and the combined organic phases were concentrated by rotary evaporation (BUCHI rotary evaporator R-3, qi, switzerland). The concentrated residue was purified by column chromatography (beijing xinweil glass instruments ltd, C383040C sand plate storage ball chromatography column, 35/20,
effective length: 500ml) was chromatographed to give the product. (the product was a white solid, 2.91 g total, 88% yield, eluent ethyl acetate to petroleum ether 1: 10 to 1: 5).
1H NMR(400MHz，CDCl3)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)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]+The calculated value of (a): 412.2118, measurement: 412.2130.
TABLE 1 preparation of photoinduced non-metal catalyzed beta-aminoketones
Industrial applicability
The method avoids the use of metal catalysts, meets the requirements of developing green environment-friendly chemistry, has wide substrate range and good functional group compatibility, and provides a new method for synthesizing the beta-aminoketone compound. In addition, the raw materials and reagents used by the method are easy to obtain, the reaction can be amplified to gram-scale quantity, the conversion rate and the yield are high, and the method has good industrial application prospect.
Claims (10)
1. A method for preparing beta-aminoketones under photoinduced non-metal catalysis, which comprises the following steps:
at room temperature, under the condition of existence of simple iodized salt, phosphine ligand and organic solvent, decarboxylation of the active carboxylic ester compound shown in the formula 1 is realized through illumination, and the decarboxylation reacts with the enol silyl ether compound shown in the formula 2 to obtain the beta-aminoketone compound shown in the formula 3:
wherein:
R1is tert-butoxycarbonyl and benzyloxycarbonyl, R2Is a hydrogen atom or a linear, branched or cyclic C1-20Alkyl radical, R3Is a hydrogen atom, C6-20Aryl, straight, branched or cyclic C1-20Alkyl radical, C1-20Sulfanyl radical, C1-4Alkylphenoxy C1-4Alkyl, or R3And R2To which they are connectedThe N atoms together form a ring;
TMS represents a trimethylsilyl group, and R4Is a straight chain or branched C at different substituted positions of the benzene ring represented by the formula (2)1-20Alkyl radical, C6-20An aryl or ester group;
wherein the simple iodide salt is selected from at least one of sodium iodide and potassium iodide,
the phosphine ligand is selected from at least one of triphenylphosphine and tris (4-fluorophenyl) phosphine, and
the wavelength range of the light source is 430nm to 480 nm.
2. The method of claim 1, wherein the molar ratio of formula 2 to formula 1 is 1.0-4.0.
3. The method of claim 1, wherein the molar amount of the iodide salt is 1.0-2.0 times the molar amount of formula 1.
4. The method according to claim 1, wherein the molar amount of the phosphine ligand is 5 to 50% of the molar amount of the formula 1.
5. The method of claim 1, wherein the light source has a wavelength in the range of 450nm to 460nm and an illumination time of 4-24 hours.
6. The method according to claim 1, wherein the organic solvent is selected from at least one of N, N-dimethylformamide, N-dimethylacetamide, acetonitrile, tetrahydrofuran, and toluene.
7. The method of claim 1, wherein the active carboxylate compound of formula 1 is selected from the group consisting of:
8. the method of claim 1, wherein the active carboxylate compound of formula 1 is replaced with a compound of:
9. the method of claim 1, wherein the silyl enol ether compound of formula 2 is selected from the group consisting of:
10. the method of claim 1, wherein the silyl enol ether compound is replaced with a compound represented by:
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