Method for synthesizing cyclopentane compound through bromine ion / visible light concerted catalysis

Abstract

The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing cyclopentane compounds through [3 + 2] cycloaddition reaction of aryl cyclopropane and olefin under the synergistic catalysis of bromide ions / visible light. The method comprises the following steps: in a nitrogen atmosphere, sequentially adding aryl cyclopropane, a benzyl malononitrile derivative, pyridine tribromide and a photocatalyst into a reaction solvent to obtain a mixture, stirring the mixture at the temperature of 40 DEG C under the irradiation of a 12W blue light LED lamp until the reaction is complete, and performing concentration and column chromatography purification to obtain the cyclopentane compound. The method has the advantages of mild reaction conditions, simple operation, simple and easily available raw materials and low cost.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to a method for preparing substituted cyclopentane compounds by ring-opening [3+2] cycloaddition reactions of arylcyclopropane and olefins under synergistic catalytic conditions of bromide ions and photo-redox. Background Technology

[0002] Cyclopropanes are widely found in natural products and bioactive synthetic chemical entities, making them a preferred structure for drug and agrochemical development. Furthermore, cyclopropanes possess unique bond structures and high ring strain, allowing them to undergo ring cleavage and subsequent functionalization under specific conditions. As a versatile building block in modern organic synthesis, cyclopropanes can undergo various types of ring-opening functionalization reactions, among which cycloaddition reactions are a hot research area.

[0003] Currently, there are several main strategies for the ring-opening of cyclopropane and the cycloaddition of alkenes. One, as disclosed in Reference 1 (H. Xiong, H. Xu, S. Liao, Z. Xie, Y. Tang. J Am. Chem. Soc. 2013, 135, 7851-7854), uses cyclopropane with electron-donating and electron-withdrawing groups, and performs a [3+2] cycloaddition reaction with indole via Lewis acid activation. The specific reaction process is shown below:

[0004]

[0005] Secondly, as disclosed in Reference 2 (AGAmador, EMSherbrook, TPYoon. J. Am. Chem. Soc. 2016, 138, 4722-4725), cyclopropyl ketone is used as a raw material to undergo a cycloaddition reaction with an olefin under the synergistic catalysis of a photocatalyst and a Lewis acid. The specific reaction process is as follows:

[0006]

[0007] Thirdly, in the method disclosed in Reference 3 (S. Maity, M. Zhu, R.S. Shinabery, N. Zheng. Angew. Chem. Int. Ed., 2012, 51, 222-226.), cyclopropylamine is used as a raw material to undergo a cycloaddition reaction with an olefin under photocatalytic oxidation conditions. The specific reaction process is as follows:

[0008]

[0009] Fourth, in the method disclosed in Reference 4 (Q.-Q. Zhao, X.-S. Zhou, S.-H. Xu, Y.-L. Wu, W.-J. Xiao, J.-R. Chen. Org. Lett. 2020, 22, 2470-2475.), alkenylcyclopropane is used as a raw material to undergo a cycloaddition reaction with an olefin under photocatalytic conditions. The specific reaction process is as follows:

[0010]

[0011] However, the above strategies all require the cyclopropane to have an activated group (ester, carbonyl, amino, alkenyl, etc.), and the reactions are generally only applicable to electron-rich alkenes, which greatly limits the application of constructing cyclopentane derivatives using the [3+2] cycloaddition reaction of cyclopropane with alkenes. Therefore, developing a more general and efficient method to realize the cycloaddition reaction of other types of unactivated cyclopropanes is of great significance. Summary of the Invention

[0012] The purpose of this invention is to provide a mild and simple method for preparing cyclopentane derivatives by utilizing bromide ion / visible light synergistic catalysis of the [3+2] cycloaddition reaction of arylcyclopropane and alkenes, aiming to solve the difficulties such as the limitation of substrate types for cyclopropane and alkenes under existing methods.

[0013] The solution adopted by the present invention to achieve the objective includes the following steps: under a nitrogen atmosphere, arylcyclopropane, olefin, bromide ion catalyst and photocatalyst are added sequentially to the reaction solvent to obtain a mixture. The mixture is stirred at a suitable temperature and under blue LED light irradiation until the reaction is complete. After concentration and column chromatography purification, cyclopentane compounds can be obtained.

[0014] The reaction formula of the method of the present invention can be expressed as follows:

[0015]

[0016] Formula 1 represents arylcyclopropane, Formula 2 represents olefins, and Formula 3 represents cyclopentane compounds.

[0017] In Equations 1 and 3, Ar 1 Selected from any of the following groups: 4-methoxyphenyl, 2-methoxyphenyl, 4-phenylphenyl, 2-naphthyl, 4-tert-butylphenyl, 3-fluoro-4-methoxyphenyl, benzodihydrofuran-4-one, dibenzofuran-2-yl, 6-benzothiophene, 4-trimethylsilylphenyl, 4-tert-butylcarbamate-phenyl, 4-methylpropionate-phenyl, 3-methyl ester-4-methoxyphenyl, 2,3-dihydrobenzo[b][1,4]dioxane, 4-phenylacetate;

[0018] In Equations 2 and 3, Ar 2Selected from any of the following groups: phenyl, 4-phenylphenyl, methyl 3-benzoate phenyl, 4-chlorophenyl, 4-bromophenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-cyanophenyl;

[0019] The bromide ion catalyst is pyridine tribromide;

[0020] The photocatalyst is 3,6-di-tert-butyl-9-trimethyl-10-phenylacridin-10-onium tetrafluoroborate.

[0021] The reaction solvent is one of tetrahydrofuran, dichloromethane, and acetonitrile, preferably acetonitrile; the concentration of the reaction mixture is 0.1M-1.0M, preferably 0.2M;

[0022] The molar ratio of arylcyclopropane 1, olefin 2, bromide ion catalyst, and photocatalyst is 1.5:1:0.02:0.02;

[0023] The reaction temperature is room temperature or 20-60℃, preferably 40℃;

[0024] The reaction time is 10-40 hours, preferably 24 hours;

[0025] The blue light wavelength is 420-470nm, preferably 456nm, and the LED power is 5-40W, preferably 12W.

[0026] Beneficial effects of this invention:

[0027] (1) This invention provides a method for preparing polysubstituted cyclopentanes from arylcyclopropane, using low-cost and readily available raw materials; and the entire process does not require the use of precious metal catalysts and equivalent oxidants.

[0028] (2) This invention provides a novel arylcyclopropane activation method using bromide ion / visible light catalysis for the first time, and develops a completely new method for preparing cyclopentane compounds. This method eliminates the cumbersome prefunctionalization steps, simplifies the process, and optimizes the solvent, stoichiometry, and catalyst to achieve the best product yield. Attached Figure Description

[0029] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. Wherein:

[0030] Figure 1 This is the hydrogen NMR spectrum of embodiment 3a of the present invention;

[0031] Figure 2 This is the carbon NMR spectrum of embodiment 3a of the present invention;

[0032] Figure 3 This is the 1H NMR spectrum of 3p in this embodiment of the invention;

[0033] Figure 4 This is the carbon NMR spectrum of 3p in the embodiment of the present invention; Detailed Implementation

[0034] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the examples in the specification.

[0035] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0036] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.

[0037] Example 1:

[0038]

[0039] (1) Under a nitrogen atmosphere, 4-cyclopropyl-1-methoxybenzene 1a (0.3 mmol), benzylmalonium 2a (0.2 mmol), pyridine tribromide (0.004 mmol), and 3,6-di-tert-butyl-9-trimethyl-10-phenylacridin-10-onium tetrafluoroborate (0.004 mmol) were sequentially added to 1.0 mL of acetonitrile to obtain a mixture;

[0040] (2) Under a nitrogen atmosphere, the mixture was stirred at 40°C for 24 hours. After the reaction solution was concentrated under reduced pressure, it was purified by silica gel column chromatography to obtain 3-(4-methoxyphenyl)-2-phenylcyclopentane-1,1-dionitrile 3a (57.4 mg, 0.190 mmol, colorless oil), with a yield of 95%. 1H NMR (400MHz, CDCl3): δ7.47-7.40(m, 2H), 7.40-7.32(m, 3H), 7.26-7.19(m, 3H), 7 .16-7.05(m, 2H), 6.99-6.89(m, 2H), 6.87-6.74(m, 4H), 6.70-6.65(m, 2H), 4.09- 3.93 (m, 2H), 3.85-3.74 (m, 1H), 3.73 (s, 3H), 3.72 (s, 3H), 3.68 (d, J=12.2Hz, 1H) ,2.94-2.82(m,2H),2.81-2.70(m,2H),2.66-2.40(m,3H),2.21-2.07(m,1H).13C NMR (100MHz, CDCl3): δ158.7, 158.5, 133.9, 133.3, 131.7, 129.6, 129.6, 129.3, 129.1, 129.1, 128.6, 128.6, 128.4, 12 8.3, 117.7, 116.2, 115.2, 115.0, 114.4, 113.6, 62.0, 60.5, 55.3, 55.2, 47.8, 46.6, 42.2, 39.9, 37.6, 37.5, 32.0, 28.3.

[0041] Examples 2-15 are basically the same as Example 1, except that:

[0042]

[0043]

[0044] Example 16:

[0045]

[0046] (1) Under a nitrogen atmosphere, 4-cyclopropyl-1-methoxybenzene (0.3 mmol), 2-([1,1′-biphenyl]-4-ylmethylene)malonium (0.2 mmol), pyridine tribromide (0.004 mmol), and PC1 (0.004 mmol) were added sequentially to 1.0 mL of acetonitrile to obtain a mixture;

[0047] (2) Under a nitrogen atmosphere, the mixture was stirred at 40°C for 24 hours. After the reaction solution was concentrated under reduced pressure, it was purified by silica gel column chromatography to obtain 2-([1,1′-biphenyl]-4-yl)-3-(4-methoxyphenyl)cyclopentane-1,1-dionitrile 3p (56.9 mg, 0.15 mmol, colorless oil), with a yield of 75%.

[0048] 1H NMR (400MHz, CDCl3): δ7.62-7.53(m, 6H), 7.53-7.39(m, 8H), 7.39-7.32(m, 2H), 7.17-7.09 (m, 2H), 7.05-6.99 (m, 2H), 6.92-6.84 (m, 2H), 6.84-6.76 (m, 2H), 6.74-6.65 (m, 2H), 4.09 (d , J=7.5Hz, 1H), 4.01 (dt, J=10.9, 8.1Hz, 1H), 3.91-3.74 (m, 2H), 3.73 (s, 3H), 3.72 (s, 3H), 2 .96-2.85 (m, 2H), 2.78 (tdd, J=13.9, 9.3, 6.2Hz, 2H), 2.67-2.44 (m, 3H), 2.23-2.08 (m, 1H). 13 C NMR (100MHz, CDCl3): δ158.8, 158.6, 141.9, 141.0, 140.3, 140.1, 132.8, 132.2, 131.7, 130.1, 129.6, 129.4, 129.1, 128.9, 128.3, 12 7.8, 127.7, 127.7, 117.7, 116.2, 115.2, 115.1, 114.4, 113.7, 61.7, 60.2, 55.3, 55.3, 47.8, 46.7, 42.3, 40.0, 37.5, 32.1, 28.4, 14.3.

[0049] Examples 17-22 are basically the same as Example 16, except that:

[0050] Table 2 Examples 17-22

[0051]

[0052] The above description is only a partial embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing cyclopentane compounds, characterized in that: Under the synergistic catalysis of bromide ion catalyst and photocatalyst, arylcyclopropane and olefins undergo a [3+2] cycloaddition reaction under blue light irradiation to obtain cyclopentane compounds; The structure of the arylcyclopropane is shown in Formula 1. The structure of the olefin is shown in Formula 2. The structure of the cyclopentane compounds is shown in Formula 3. In Equations 1 and 3, Ar 1 Selected from any of the following groups: 4-methoxyphenyl, 2-methoxyphenyl, 4-phenylphenyl, 2-naphthyl, 4-tert-butylphenyl, 3-fluoro-4-methoxyphenyl, benzodihydrofuran-4-one, dibenzofuran-2-yl, 6-benzothiophene, 4-trimethylsilylphenyl, 4-tert-butylcarbamate-phenyl, 4-methylpropionate-phenyl, 3-methyl ester-4-methoxyphenyl, 2,3-dihydrobenzo[b][1,4]dioxane, 4-phenylacetate; In Equations 2 and 3, Ar 2 Selected from any of the following groups: phenyl, 4-phenylphenyl, methyl 3-benzoate phenyl, 4-chlorophenyl, 4-bromophenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-cyanophenyl; The bromide ion catalyst is pyridine tribromide; The photocatalyst is 3,6-di-tert-butyl-9-trimethyl-10-phenylacridin-10-onium tetrafluoroborate.

2. The method for preparing cyclopentane compounds according to claim 1, characterized in that, The method includes the following steps: (1) Under a nitrogen atmosphere, arylcyclopropane 1, olefin 2, bromide ion catalyst and photocatalyst are added to the reaction solvent in sequence to obtain a mixture; The molar ratio of arylcyclopropane 1, olefin 2, bromide ion catalyst, and photocatalyst is 1.5:1:0.02:0.

02. (2) The mixture described in step (1) was stirred under a suitable temperature and a blue LED light until the reaction was complete. The crude product was concentrated and purified by column chromatography to obtain cyclopentane compounds; The mixture was stirred and reacted at 40 degrees Celsius for 20 hours, and the blue light used had a wavelength of 456nm and a power of 12W.

3. The method for preparing cyclopentane compounds according to claim 2, characterized in that, In step (1), the reaction solvent is acetonitrile.

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