阅读说明：本技术 光催化合成1,2-联烯基酮的方法 (Method for photocatalytic synthesis of 1, 2-allenyl ketone ) 是由 金小平 雷宛 方烨汶 于 2021-08-05 设计创作，主要内容包括：本发明提供一种光催化合成1,2-联烯基酮的方法,包括以下步骤：S1、往具有搅拌子的反应管中加入光敏剂、1,3-烯炔类化合物、自由基前体和干燥的溶剂；S2、反应管在氮气保护下置于LED灯下照射,室温搅拌反应24h；S3、萃取、洗涤、干燥、过滤得到有机相溶液经旋转蒸发仪除去溶剂；S4、用石油醚和乙酸乙酯的混合液作为淋洗剂进行柱层析分离,经旋转蒸发仪蒸馏得到目标产物1,2-联烯基酮。本发明首次发展了在可见光促进的催化体系下,通过烷基自由基和1,3-烯炔类化合物的加成/还原/异构化,合成了一系列1,2-联烯基酮,具有反应条件温和、操作简单、反应经济性好、底物普适性好、官能团兼容性强等优点。(The invention provides a method for synthesizing 1, 2-allenyl ketone by photocatalysis, which comprises the following steps: s1, adding a photosensitizer, a 1, 3-eneyne compound, a free radical precursor and a dry solvent into a reaction tube with a stirrer; s2, placing the reaction tube under an LED lamp for irradiation under the protection of nitrogen, and stirring and reacting for 24 hours at room temperature; s3, extracting, washing, drying and filtering to obtain an organic phase solution, and removing the solvent by a rotary evaporator; s4, performing column chromatography separation by using a mixed solution of petroleum ether and ethyl acetate as an eluent, and distilling by using a rotary evaporator to obtain the target product 1, 2-allenyl ketone. The invention develops a series of 1, 2-allenyl ketones by adding/reducing/isomerizing alkyl free radicals and 1, 3-eneyne compounds under a visible light promoted catalytic system for the first time, and has the advantages of mild reaction conditions, simple operation, good reaction economy, good substrate universality, strong functional group compatibility and the like.)

1. A process for the photocatalytic synthesis of 1, 2-allenyl ketones, comprising the steps of:

s1, adding a photosensitizer, a 1, 3-eneyne compound, a free radical precursor and a dry solvent into a reaction tube with a stirrer;

s2, placing the reaction tube under an LED lamp for irradiation under the protection of nitrogen, and stirring and reacting for 24 hours at room temperature;

s3, adding saturated Na into the reaction solution₂CO₃Extracting the aqueous solution with ethyl acetate, mixing the organic phases, washing with saturated saline solution, drying with anhydrous magnesium sulfate, filtering to obtain an organic phase solution, and removing the solvent by a rotary evaporator;

s4, performing column chromatography separation by using a mixed solution of petroleum ether and ethyl acetate as an eluent, and distilling by using a rotary evaporator to obtain the target product 1, 2-allenyl ketone.

2. The photocatalytic synthesis method of 1, 2-allenyl ketone according to claim 1, characterized in that in step S1, the photosensitizer is Ir [ dF (CF)₃)ppy]₂(dtbbpy)PF₆。

3. The photocatalytic synthesis method for 1, 2-allenyl ketone according to claim 2, characterized in that in step S1, the 1, 3-enyne compound is 2-acyl-1, 3-enyne.

4. The photocatalytic synthesis method of 1, 2-allenyl ketone according to claim 3, characterized in that, in step S1, the radical precursor is alkyl bis (catechol) silicate-18-crown-6-potassium.

5. The photocatalytic synthesis method for 1, 2-allenyl ketone according to claim 4, characterized in that in step S1, the solvent is dimethyl sulfoxide.

6. The photocatalytic synthesis method of 1, 2-allenyl ketone according to claim 1, wherein in step S1, the molar ratio of the 1, 3-enyne compound to the radical precursor is 1: 2-4.

7. The photocatalytic synthesis method of 1, 2-allenyl ketone as recited in claim 6, wherein in step S1, the molar ratio of 1, 3-enyne compound to the solvent is 1: 400-450.

8. The photocatalytic synthesis method of 1, 2-allenyl ketone as claimed in claim 1, wherein in step S2, the LED lamp is a 9W blue LED lamp.

9. The photocatalytic synthesis method of 1, 2-allenyl ketone according to claim 1, wherein in step S4, the volume ratio of petroleum ether to ethyl acetate in the mixed solution of petroleum ether and ethyl acetate is 25-100: 1.

10. The photocatalytic synthesis method of 1, 2-allenyl ketone according to claim 9, characterized in that the length of the silica gel column used for column chromatographic separation in step S4 is 20 cm.

Technical Field

The invention relates to the technical field of photocatalytic synthesis, in particular to a method for catalytically synthesizing 1, 2-allenyl ketone.

Background

The allene skeleton widely exists in molecular structures of natural products, drug molecules and advanced functional materials, and is also a very practical organic synthon in organic synthesis. Therefore, the development of a new method for efficiently constructing the allene, particularly the polysubstituted allene, has good research prospect and application value.

Among the numerous synthetic methods, functionalization of 1, 3-enynes is a common strategy for the synthesis of allenes. For example, in the ionic pathway, an alkyl zinc reagent and a 1, 3-enyne compound can react at low temperature to give a trisubstituted 1, 2-dienyl ketone. The reaction formula is as follows:

in addition, the reaction of 1, 3-eneyne compounds and free radicals becomes a new method for synthesizing allenes. Under copper catalysis conditions, besides alkyl free radicals can participate in the reaction, nitrogen-centered free radicals can also synthesize tetra-substituted allenes under similar conditions. The reaction formula is as follows:

although nucleophiles can react with 1, 3-eneyne compounds efficiently in the ionic pathway, the reaction is limited by the application of metal reagents and low temperature conditions, which are not favorable for the operation and atom economy of the reaction. Under the free radical path, the copper-catalyzed reaction of the 1, 3-eneyne compounds and the free radicals has better substrate universality, but the reaction is not reported to be used for 1, 2-allenyl ketone at present, and the reaction is limited by the participation of the allenyl free radicals as intermediates in the reaction. Therefore, under the visible light catalysis condition, the 1, 3-eneyne compounds and carbon-centered free radicals react to synthesize the 1, 2-allenyl ketone, so that the defects of the existing method are hopefully overcome, and a new strategy and method are provided for synthesis of polysubstituted allene.

Disclosure of Invention

The technical problem to be solved by the invention is to overcome the defect that the prior art only has a single ion path and a single free radical path, provide a novel free radical-ion staggered approach and a novel method for synthesizing 1, 2-allenyl ketone under the photocatalysis condition.

The invention provides a method for synthesizing 1, 2-allenyl ketone by photocatalysis, which comprises the following steps:

s1, adding a photosensitizer, a 1, 3-eneyne compound, a free radical precursor and a dry solvent into a reaction tube with a stirrer;

s2, placing the reaction tube under an LED lamp for irradiation under the protection of nitrogen, and stirring and reacting for 24 hours at room temperature;

s3, adding saturated Na into the reaction solution₂CO₃Extracting the aqueous solution with ethyl acetate, mixing the organic phases, washing with saturated saline solution, drying with anhydrous magnesium sulfate, filtering to obtain an organic phase solution, and removing the solvent by a rotary evaporator;

s4, performing column chromatography separation by using a mixed solution of petroleum ether and ethyl acetate as an eluent, and distilling by using a rotary evaporator to obtain the target product 1, 2-allenyl ketone.

In a preferred or alternative embodiment, the photosensitizer in step S1 is Ir [ dF (CF)₃)ppy]₂(dtbbpy)PF₆。

In a preferred or alternative embodiment, in said step S1, the 1, 3-enyne compound is a 2-acyl-1, 3-enyne.

In a preferred or alternative embodiment, the radical precursor in step S1 is alkyl bis (catechol) silicate-18-crown-6-potassium acetate.

In a preferred or alternative embodiment, in said step S1, the solvent is dimethyl sulfoxide.

In a preferred or alternative embodiment, in step S1, the molar ratio of the 1, 3-enyne compound to the radical precursor is 1: 2-4.

In a preferred or alternative embodiment, the molar ratio of the 1, 3-enyne compound to the solvent in step S1 is 1: 400-450.

In a preferred or alternative embodiment, in the step S2, the LED lamp is a 9W blue LED lamp.

In a preferred or alternative embodiment, in step S4, the volume ratio of the petroleum ether to the ethyl acetate in the mixed solution of the petroleum ether and the ethyl acetate is 25-100: 1.

In a preferred or alternative embodiment, the length of the silica gel column used in the step S4 is 20 cm.

The method for photocatalytic synthesis of 1, 2-allenyl ketone has the following general reaction formula in step S2:

compared with the prior art, the invention has the following beneficial effects:

the invention develops a series of 1, 2-allenyl ketones by adding/reducing/isomerizing alkyl free radicals and 1, 3-eneyne compounds under a visible light promoted catalytic system for the first time;

the method has the advantages of mild reaction conditions, simple operation, good reaction economy, good substrate universality, strong functional group compatibility and the like.

Detailed Description

In order to make the aforementioned objects, features and advantages of the present invention comprehensible, specific embodiments thereof are described in detail below. It should be noted that the following examples are only used to illustrate the implementation method and typical parameters of the present invention, and are not used to limit the scope of the parameters of the present invention, so that reasonable variations can be made and still fall within the protection scope of the claims of the present invention.

It is noted that the endpoints of the ranges and any values disclosed herein are not limited to the precise range or value, and that such ranges or values are understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein.

The present invention will be described in detail below by way of specific examples.

Example 1

This example provides a method for photocatalytic synthesis of 1, 2-allenyl ketone, comprising the steps of:

s1 ExampleAdding magneton, adding Ir [ dF (CF)₃)ppy]₂(dtbbpy)PF₆(4.5mg,0.004 mmol,0.02equiv), 2-benzoyl-1, 3-enyne (59.6mg,0.2mmol,1.0 equiv); the reaction tube was placed in a glove box, and methoxymethyl bis (catechol) silicate-18-crown ether-6-potassium complex (237.1mg,0.4mmol,2.0equiv) was weighed in the glove box; after weighing, the reaction tube was stoppered with a rubber stopper, and dried dimethylsulfoxide DMSO (6mL) was added to the reaction tube under nitrogen, and the rubber stopper was sealed with a sealing film.

And S2, placing the reaction tube under a 9W blue LED lamp for irradiation, stirring at room temperature for reaction for 24 hours, and stopping the irradiation reaction. The reaction formula is as follows:

s3, 6mL of saturated Na was added to the reaction mixture₂CO₃The solution was stirred for 30min, the separated aqueous phases were extracted with ethyl acetate (4X 10mL), the combined organic phases were washed with 5mL of saturated brine and the organic phase was MgSO₄Drying for 15min, filtering, and removing solvent from the filtrate by rotary evaporation.

S4, mixed solution of petroleum ether and ethyl acetate (V)_{Petroleum ether}：V_{Ethyl acetate}25:1) as eluent, column chromatography was carried out using a 20cm length silica gel column and distillation on a rotary evaporator gave 46.1 mg with a yield of 69% (dr 50: 50).

The product analysis data is as follows:

isomer 1 colorless oily liquid.¹H NMR(500MHz,CDCl₃)δ7.69-7.66(m,2H), 7.46-7.43(m,1H),7.37-7.28(m,6H),7.22-7.18(m,1H),5.46(d,J＝1.9Hz,1H), 4.48-4.45(m,1H),3.77-3.71(m,2H),3.35(s,3H),0.80(s,9H).¹³C NMR(126 MHz,CDCl₃)δ211.4,194.5,140.8,138.8,131.4,128.7,128.3,128.2,127.5, 126.7,111.6,108.6,74.8,58.7,43.1,33.0,29.5.HRMS(ESI)[M+H]⁺:calculated for C₂₃H₂₇O₂:335.2011,found 335.2013.

Isomer 2 white solid.¹H NMR(500MHz,CDCl₃)δ7.65-7.63(m,2H), 7.45-7.41(m,1H),7.36-7.28(m,6H),7.22-7.19(m,1H),5.51(d,J＝1.8Hz,1H), 4.47-4.44(m,1H),3.78-3.65(m,2H),3.34(s,3H),0.96(s,9H).¹³C NMR(126 MHz,CDCl₃)δ211.2,194.4,141.1,138.6,131.4,128.7,128.3,128.1,127.5, 126.7,111.2,108.8,75.4,58.5,42.9,33.2,29.6.HRMS(ESI)[M+H]⁺:calculated for C₂₃H₂₇O₂:335.2011,found 335.2015.

Example 2

This example provides a method for photocatalytic synthesis of 1, 2-allenyl ketone, comprising the steps of:

s1, adding magnetons into the reaction tube, and adding Ir [ dF (CF)₃)ppy]₂(dtbbpy)PF₆(4.5mg,0.004 mmol,0.02equiv), 2-benzoyl-1, 3-enyne (58.9mg,0.2mmol,1.0 equiv); the reaction tube was placed in a glove box, and cyclohexylbis (catechol) silicate-18-crown-6-potassium complex (252.4mg,0.4mmol,2.0equiv) was weighed in the glove box; after weighing, the reaction tube was stoppered with a rubber stopper, dried dimethylsulfoxide DMSO (6mL,0.033M) was added to the reaction tube under nitrogen, and the rubber stopper was sealed with a sealing film.

And S2, placing the reaction tube under a 9W blue LED lamp for irradiation, stirring at room temperature for reaction for 24 hours, and stopping the irradiation reaction. The reaction formula is as follows:

s3, 6mL of saturated Na was added to the reaction mixture₂CO₃The solution was stirred for 30min, the aqueous phase after separation was extracted with ethyl acetate (4X 10mL), the organic phase was washed once with 5mL of saturated brine, and the combined organic phases were MgSO₄Drying for 15min, filtering, and removing the solvent from the filtrate by rotary evaporation.

S4, mixed solution of petroleum ether and ethyl acetate (V)_{Petroleum ether}：V_{Ethyl acetate}100: 1) column chromatography was performed as eluent using a silica gel column of 20cm in length and distilled using a rotary evaporator to obtain 52.9mg of the objective product at a yield of 70%.

The product analysis data is as follows:

¹H NMR(500MHz,CDCl₃)δ7.69-7.66(m,2H),7.46-7.42(m,1H), 7.37-7.34(m,2H),5.35(s,1H),2.69(m,1H),1.82-1.73(m,10H),1.30-0.96(m, 12H),0.89(s,9H).¹³C NMR(126MHz,CDCl₃)δ212.6,196.3,139.0,131.0, 128.7,127.5,111.9,107.9,46.5,39.3,39.1,33.4,32.3,31.2,29.9,28.0,26.9(3), 26.9(0),26.8,26.7,26.6,26.4.HRMS(ESI)[M+H]⁺:calculated for C₂₇H₃₉O: 379.3001,found 379.2991.

example 3

This example provides a method for photocatalytic synthesis of 1, 2-allenyl ketone, comprising the steps of:

s1, adding magnetons into the reaction tube, and adding Ir [ dF (CF)₃)ppy]₂(dtbbpy)PF₆(4.5mg,0.004 mmol,0.02equiv), 2-p-chlorobenzoyl-1, 3-enyne (64.6mg,0.2mmol,1.0 equiv); the reaction tube was placed in a glove box, and methoxymethyl bis (catechol) silicate-18-crown ether-6-potassium complex (237.1mg,0.4mmol,2.0equiv) was weighed in the glove box; after weighing, the reaction tube was stoppered with a rubber stopper, dried dimethylsulfoxide DMSO (6mL,0.033M) was added to the reaction tube under nitrogen, and the rubber stopper was sealed with a sealing film.

And S2, placing the reaction tube under a 9W blue LED lamp for irradiation, stirring at room temperature for reaction for 24 hours, and stopping the irradiation reaction. The reaction formula is as follows:

s3, adding 6mL of saturated NaCl solution into the reaction solution, stirring for 5min, extracting the separated aqueous phase with ethyl acetate (4X 10mL), combining the organic phases, and MgSO₄Drying for 15min, filtering, and removing the solvent from the filtrate by rotary evaporation.

S4, mixed solution of petroleum ether and ethyl acetate (V)_{Petroleum ether}：V_{Ethyl acetate}25:1) as eluent, the column chromatography was carried out using a silica gel column of 20cm length and the distillation was carried out on a rotary evaporator to give the desired product 36.8mg in 50% yield (dr-37: 63))。

The product analysis data is as follows:

isomer 1 white solid.¹H NMR(500MHz,CDCl₃)δ7.62-7.59(m,2H), 7.34-7.28(m,6H),7.22-7.19(m,1H),5.55(d,J＝1.8Hz,1H),4.44-4.41(m,1H), 3.77-3.63(m,2H),3.33(s,3H),0.98(s,9H).¹³C NMR(126MHz,CDCl₃)δ210.9, 193.0,140.9,137.7,136.8,130.2,128.4,128.1,127.8,126.8,111.1,109.1,75.3, 58.5,43.0,33.3,29.7.HRMS(ESI)[M+H]⁺:calculated for C₂₃H₂₆O₂Cl:369.1621, found 369.1616.

Isomer 2 white solid.¹H NMR(500MHz,CDCl₃)δ7.66-7.63(m,2H), 7.34-7.28(m,6H),7.22-7.19(m,1H),5.50(d,J＝2.0Hz,1H),4.45-4.42(m,1H), 3.76-3.70(m,2H),3.34(s,3H),0.81(s,9H).¹³C NMR(126MHz,CDCl₃)δ211.1, 193.0,140.7,137.7,137.0,130.2,128.3(2),128.2(8),127.9,126.8,111.6,108.9, 74.8,58.7,43.2,33.1,29.5.HRMS(ESI)[M+H]⁺:calculated for C₂₃H₂₆O₂Cl: 369.1621,found 369.1617.

Although the present invention is disclosed above, the present invention is not limited thereto. Various changes and modifications may be effected therein by one skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.