Axial chiral BODIPY olefin compound and synthesis method thereof

Abstract

The invention provides an axially chiral BODIPY olefin compound and a synthesis method thereof, the structure of the axially chiral BODIPY olefin compound is # imgabs0 #, the synthesis method provided by the invention can obtain a relatively high enantiomer excess value, and the axially chiral BODIPY olefin compound has an obvious red shift phenomenon; therefore, the compounds have potential application prospects in the aspects of fluorescent probes, biological imaging, macromolecular markers, photoelectric materials and the like.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and mainly relates to an axially chiral BODIPY olefin compound and a synthesis method thereof. Background Art

[0002] Fluoroboron dipyrrole compounds (4,4-difluoro-boradiazaindacene, abbreviated as BODIPY) are one of the very excellent emerging dyes. Its parent structure is as shown in the formula. The two pyrrole rings on the left and right are connected by a methine bridge bond, and there is a boron-nitrogen six-membered heterocyclic ring in the middle. The three rings form a very good rigid conjugated planar structure, and the two fluorine atoms connected to the boron atom are located at both ends of the BODIPY core plane.

[0003]

[0004] BODIPY-based fluorescent dyes have very excellent photochemical and physical properties, mainly including the following points: (1) They have a very high molar extinction coefficient, which is beneficial to improving the photosensitizing performance of the dyes. (2) They have a relatively high fluorescence quantum yield, generally reaching more than 0.6, and the quantum yields of many dyes can reach 1. They still maintain a very high quantum yield in solution and do not undergo quenching phenomena, and can be applied to the field of biological analysis. (3) The spectral properties of the dyes are quite stable and are not easily affected by the solvent polarity and pH value. They can be applied to biological molecule labeling such as the DNA field. (4) The fluorescence spectral peak width of the dyes is relatively small, and this advantage makes the dyes have higher detection sensitivity when applied to the analysis field. (5) The dyes have good photothermal stability and chemical stability, avoiding rapid photodegradation due to external interference and ensuring the stability of the optical signal.

[0005] These excellent properties have led to the rapid development of the application of this type of dye, and it has currently become one of the most concerned fluorescent dyes. Various organic fluorescent materials based on BODIPY have gradually become the focus of research due to their high excitation rate, high fluorescence quantum yield, and their stability to light and chemical reactions. Modifying BODIPY-based fluorescent compounds to broaden their applications and enrich the types of organic fluorescent dyes is still a hot topic in scientific research.

[0006] Although BODIPY-based functional dyes have been efficiently and intelligently applied in the fields of fluorescence sensing, phototherapy, photocatalysis, etc., there are still some problems to be solved. At present, researchers tend to modify or regulate the BODIPY mother nucleus more, and only a few studies focus on chiral BODIPY. Among them, there are few studies on axially chiral BODIPYs compounds in enantiomerically enriched forms, and the synthesis of axially chiral BODIPYs with structural diversity is still underdeveloped. Based on the excellent spectral and photophysical properties of BODIPY-based fluorescent dyes, the present invention synthesizes an axially chiral BODIPY olefin derivative in one step through the Heck reaction, which is expected to be used in the material field or as an organic reaction catalyst and ligand to improve chemical reactivity. Summary of the Invention

[0007] Aiming at the deficiencies existing in the prior art, the purpose of the present invention is to provide an axially chiral BODIPY olefin compound and its synthesis method.

[0008] In the first aspect of the present invention, it lies in providing an axially chiral BODIPY olefin compound, the structural general formula of which is shown in formula (Ⅰ): Through the above structure, the axially chiral structure of the compound of formula (Ⅰ) can be clearly seen. This axially chiral structure enables the compound of formula (Ⅰ) to be further applied to the development of biological and material research, provides new structural design strategies, enriches the types of azaborine dyes and enriches the types of organic catalysts and ligands.

[0009] The benzene ring structure in the above compound of formula (Ⅰ) is selected from One of them. It can be seen that the benzene ring structure can be designed with electron-donating groups or electron-withdrawing groups. Through the above design, the prepared compound of formula (Ⅰ) has controllable optical properties, thereby expanding the application scenarios of these compounds.

[0010] R in the above compound of formula (Ⅰ) 1 is selected from one of methyl, p-trifluoromethylphenyl and 3,5-dimethylphenyl; similarly, electron-withdrawing groups and electron-donating groups are also set to regulate the optical properties in the compound of formula (Ⅰ).

[0011] R in the above compound of formula (Ⅰ) 2 is selected from One of them.

[0012] In a preferred embodiment, the enantiomeric excess value ee of the compound of formula (Ⅰ) is 85-98%.

[0013] In a preferred embodiment, the fluorescence quantum yield Φf of the compound of formula (I) is in the range of 0.90 - 0.98. This indicates that these chiral compounds all have very good fluorescence quantum yields and excellent luminescence properties. Therefore, they have good application prospects in the fields of display imaging, biomedicine, and energy.

[0014] The second aspect of the present invention provides a method for synthesizing the above-mentioned axially chiral BODIPY olefin compound, which includes the following steps:

[0015] (1) Place compound M and pyrrole in a reactor and react at room temperature for 20 - 60 minutes to form compound N.

[0016] (2) Place compound N and a solvent in a reactor, add tetrachlorobenzoquinone and react at room temperature for 6 - 10 hours. Then add N,N - diisopropylethylamine and react further for 20 - 40 minutes. Next, dropwise add an ether solution of boron trifluoride dissolved therein within 5 - 10 minutes and react for 0.5 - 2 hours to form compound L.

[0017] (3) Under an inert gas protection atmosphere, place compound L, olefin compound K, (MeCN) 2 PdCl 2 , ligand compound H, NaBO 3 ·4H 2 O, CuMeSal, CsF and CuF 2 in a reactor, then add trifluoroethanol and react at 30 °C for 24 - 48 hours to obtain the compound of formula (I).

[0018] Among them, the structure of compound M is The structure of compound N is The structure of compound L is The benzene ring structure therein is selected from one of; R 1 is selected from one of methyl, p - trifluoromethylphenyl, and 3,5 - dimethylphenyl.

[0019] Among them, the structural formula of the olefin compound K is R 2 is selected from one of.

[0020] In a preferred embodiment, the structural formula of the ligand compound H is

[0021] In a preferred embodiment, compound L, olefin compound K, (MeCN) 2 PdCl 2 , ligand compound H, NaBO 3 ·4H2 O, CuMeSal, CsF, and CuF 2 The input molar ratio is 1:(2 - 4):(0.05 - 0.2):(0.1 - 0.3):(1 - 3):(0.1 - 0.3):(0.1 - 0.3):(0.1 - 0.3).

[0022] Compared with the prior art, the beneficial technical effects of the present invention are that an axially chiral BODIPY olefin compound can be obtained with relatively simple steps and high yield, and it can be compatible with a variety of substituents, all having high yields and excellent enantioselectivity. This compound has great potential for development and can be derived into many axially chiral BODIPY olefins with excellent enantioselectivity. These axially chiral BODIPY olefins all show obvious red-shift phenomena. Therefore, they have potential application values in fluorescence probes, bioimaging, macromolecule labeling, and optoelectronic materials, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 is the 1H NMR spectrum of compound BDP-1.

[0024] Figure 2 is the 19F NMR spectrum of compound BDP-1.

[0025] Figure 3 is the 13C NMR spectrum of compound BDP-1.

[0026] Figure 4 is the single crystal diffraction pattern of compound BDP-1.

[0027] Figure 5 is the UV-Vis absorption spectra of chiral compound BDP-1, its racemate, and compound M 3 and

[0028] Figure 6 is the UV-Vis absorption spectra of chiral compound BDP-1, its racemate, and compound M 3 and

[0029] Figure 7 is the 1H NMR spectrum of compound BDP-5.

[0030] Figure 8 is the 19F NMR spectrum of compound BDP-5.

[0031] Figure 9 is the 13C NMR spectrum of compound BDP-5.

[0032] Figure 10 is the UV-Vis absorption spectra of compounds BDP-1 to BDP-8.

[0033] Figure 11It is the fluorescence emission spectra of BDP-1 to BDP-8.

[0034] Figure 12 They are the maximum absorption wavelength and maximum emission wavelength of BDP-1 to BDP-8. Specific embodiments

[0035] The present invention will be described in detail below with reference to the embodiments shown in the drawings, but this does not limit the scope of the claims of the present invention.

[0036] Example 1

[0037] Take a round-bottom flask and dissolve compound M 1 (10 mmol, 1.5 g, 1 equiv.) in pyrrole (110 mmol, 7.4 g, 11 equiv.), add 1.5 ml of trifluoroacetic acid (TFA), react at room temperature for 30 minutes. After the reaction is completed, remove pyrrole with a rotary evaporator, dissolve the residue in 30 ml of dichloromethane, wash and separate with 30 ml of deionized water, and dry the organic phase with 5 g of anhydrous MgSO 4 Filter to remove the solid, and purify the filtrate with a silica gel column to obtain compound M 2 ; Dissolve compound M 2 (5.2 mmol, 1.4 g, 1 equiv.) in 40 ml of dry dichloromethane, add tetrachlorobenzoquinone (6.24 mmol, 1.5 g, 1.2 equiv.), react at room temperature for 8 hours, then add N,N-diisopropylethylamine (DIPEA) (7.8 mmol, 1.4 ml, 1.5 equiv.) to the system. After stirring for 30 minutes, slowly dropwise add an ether solution (1.5 ml) of boron trifluoride (7.8 mmol, 1.5 equiv.). The dropping process can be completed within 5 - 10 minutes, and then react at room temperature for 1 hour. After the reaction is completed, quench the reaction with 2 ml of saturated sodium bicarbonate, then wash and separate with 40 ml of deionized water, and dry the organic phase with 5 g of anhydrous MgSO 4 Filter to remove the solid, remove the solvent from the filtrate with a rotary evaporator, and purify with a silica gel column to obtain M 3 (942 mg, yield 58%). Compound M 1 -M 3 in the above reaction is shown as follows:

[0038]

[0039] Take a dry reaction tube and place it in a nitrogen environment. Put compound M 3 (0.1 mmol, 31.4 mg, 1 equiv.), n-butyl acrylate (0.3 mmol, 41 μL, 3 equiv.), (MeCN)2 PdCl 2 (0.01 mmol, 2.6 mg), ligand (0.02 mmol, 3.8 mg), NaBO 3 ·4H 2 O (0.18 mmol, 27.7 mg, 1.8 equiv.), CuMeSal (0.02 mmol, 4.3 mg) and CsF (0.02 mmol, 3.0 mg) and CuF 2 (0.02 mmol, 2.0 mg) were separately placed into a reaction tube, and then 3 ml of trifluoroethanol was added dropwise. The reaction tube was reacted at 30 °C for 36 hours. After the reaction was completed, the solvent was removed by a rotary evaporator and purified by a silica gel column to obtain the target product BDP-1 (36.1 mg, 80% yield, 91% ee), and its fluorescence quantum yield Φf = 0.95. The structure of the target product BDP-1 is attached Figures 1-3 1H NMR, 19F NMR and 13C NMR spectra of compound BDP-1 are shown. From the above figures, it can be known that the target compound BDP-1 was successfully prepared. Attached Figure 4 shows the single crystal diffraction pattern of compound BDP-1, which clearly shows the axial chirality structure of compound BDP-1.

[0040] In addition, attached Figure 5 shows the UV-Vis absorption spectra of chiral compound BDP-1, its racemate and compound M 3 . The maximum absorption wavelengths of the racemate and the single enantiomer are the same. The maximum absorption spectrum of BDP-1 shows an obvious red shift compared with that of the precursor compound M 3 . Figure 6 is the fluorescence emission spectra of chiral compound BDP-1, its racemate and compound M 3 . It also shows that the maximum absorption spectrum of BDP-1 shows an obvious red shift compared with that of the precursor compound M 3 . In addition, the fluorescence quantum yield of BDP-1 (Φf = 0.95) is increased compared with that of the raw material compound M 3 (Φf = 0.93). Therefore, chiral compound BDP-1 can be used to design long-wavelength fluorescence probes, which are suitable for bioimaging and detection. In addition, the obvious red shift property also enables BDP-1 to be used for labeling biomolecules for applications such as cell and tissue imaging.

[0041] Example 2

[0042] For the specific experimental procedure, refer to Example 1. The difference is that n-butyl acrylate is replaced by 1-penten-3-one to obtain the target product BDP-2 with a yield of 70%, an enantiomeric excess value of 90% ee, and a fluorescence quantum yield Φf = 0.93; the structure of the target product BDP-2 is

[0043] Example 3

[0044] For the specific experimental procedure, refer to Example 1. The difference is that n-butyl acrylate is replaced by 1-penten-3-one to obtain the target product BDP-3 with a yield of 73%, an enantiomeric excess value of 91% ee, and a fluorescence quantum yield Φf = 0.94; the structure of the target product BDP-3 is

[0045] Example 4

[0046] For the specific experimental procedure, refer to Example 1. The difference is that n-butyl acrylate is replaced by 1-penten-3-one to obtain the target product BDP-4 with a yield of 65%, an enantiomeric excess value of 97% ee, and a fluorescence quantum yield Φf = 0.92; the structure of the target product BDP-4 is

[0047] Example 5

[0048] Take a round-bottom flask and dissolve compound M 4 (10 mmol, 2.4 g, 1 equiv.) in pyrrole (110 mmol, 7.4 g, 11 equiv.), add 1.5 ml of trifluoroacetic acid (TFA), react at room temperature for 30 minutes. After the reaction is completed, remove pyrrole using a rotary evaporator. Dissolve the residue in 30 ml of dichloromethane, wash and separate with 30 ml of deionized water. The organic phase is dried with 5 g of anhydrous MgSO 4 and filtered to remove the solid. After removing the solvent from the filtrate using a rotary evaporator, purify it using a silica gel column to obtain compound M 5 ; Dissolve compound M 5 (5.5 mmol, 1.9 g, 1 equiv.) in 40 ml of dry dichloromethane, add tetrachlorobenzoquinone (6.6 mmol, 1.6 g, 1.2 equiv.), react at room temperature for 8 hours. Then add N,N-diisopropylethylamine (DIPEA) (8.3 mmol, 1.5 ml, 1.5 equiv.) to the system, stir for 30 minutes, and then slowly dropwise add an ether solution (1.6 ml) of boron trifluoride (8.3 mmol, 1.5 equiv.). The dropping process can be completed within 5 - 10 minutes, and then react at room temperature for 1 hour. After the reaction is completed, quench with 2 ml of saturated sodium bicarbonate, then wash and separate with 40 ml of deionized water. The organic phase is dried with 5 g of anhydrous MgSO4 Dry, filter to remove solids. After removing the solvent from the filtrate using a rotary evaporator, purify it using a silica gel column to obtain compound M. 6 (1.4 g, yield 62%). Compound M in the above reaction 4 -M 6 is as shown in the following formula:

[0049]

[0050] Place a dry reaction tube in a nitrogen environment, and add M 4 (0.1 mmol, 40.4 mg, 1 equiv.), n-butyl acrylate (0.3 mmol, 41 μL, 3 equiv.), (MeCN) 2 PdCl 2 (0.02 mmol, 2.6 mg), ligand (0.02 mmol, 3.8 mg), NaBO 3 ·4H 2 O (0.18 mmol, 27.7 mg, 1.8 equiv.), CuMeSal (0.02 mmol, 4.3 mg), CsF (0.02 mmol, 3.0 mg, 20%), and CuF 2 (0.02 mmol, 2.0 mg) into the reaction tube respectively. Then add 3 ml of trifluoroethanol to the reaction tube, and react the reaction tube at 30 °C for 36 hours. After the reaction is completed, remove the solvent using a rotary evaporator, and then purify it using a silica gel column to obtain the target product BDP-5 (48.9 mg, 92% yield, 89% ee), and its fluorescence quantum yield Φf = 0.95. The structural formula of BDP-5 is Attached Figures 7-9 Show the 1H NMR, 19F NMR, and 13C NMR spectra of compound BDP-5. From the above figures, it can be known that the target compound BDP-5 has been successfully prepared.

[0051] Example 6

[0052] The specific experimental procedure is referred to Example 5. The difference is that compound M 7 is used to replace M 4 , to obtain the target product BDP-6, with a yield of 60% and an enantiomeric excess value of 89% ee, and its fluorescence quantum yield Φf = 0.95; where compound M 7 and the target product BDP-6 are as shown in the following formula.

[0053]

[0054] Example 7

[0055] The specific experimental procedure is referred to Example 5. The difference is that compound M8 Replace M 4 , to obtain the target product BDP-7, with a yield of 74% and an enantiomeric excess value of 88% ee, and its fluorescence quantum yield Φf = 0.94; wherein compound M 8 and the structure of the target product BDP-7 are shown in the following formulae.

[0056]

[0057] Example 8

[0058] For the specific experimental procedure, refer to Example 5. The difference is that compound M 9 is used to replace M 4 , to obtain the target product BDP-8, with a yield of 62% and an enantiomeric excess value of 91% ee, and its fluorescence quantum yield Φf = 0.91; wherein compound M 9 and the structure of the target product BDP-8 are shown in the following formulae.

[0059]

[0060] Appendix Figure 10 shows the ultraviolet-visible absorption spectra of BDP-1 to BDP-8. The maximum absorption wavelengths of all compounds are basically the same. Among them, the maximum absorption wavelength is that of BDP-8, and the minimum is that of BDP-7. It can be seen that by modifying the groups on the chiral compound structure, the corresponding ultraviolet absorption wavelength can be effectively controlled. Furthermore, potential application exploration can be carried out based on the controllable ultraviolet absorption wavelength. Figure 11 shows the fluorescence emission spectra of BDP-1 to BDP-8. As can be seen from the attached figure, the chiral compound BDP-3 has the maximum emission wavelength. It can be seen that by modifying the groups on the chiral compound structure, the corresponding fluorescence emission wavelength can be effectively controlled. Furthermore, potential application exploration can be carried out based on the controllable fluorescence emission wavelength. Appendix Figure 12 summarizes the maximum absorption wavelengths and maximum emission wavelengths of BDP-1 to BDP-8. Providing accurate data of these absorption wavelengths and emission wavelengths lays a good foundation for fully developing the applications of these axially chiral compounds.

[0061] The above has introduced the technical solutions provided by the present invention in detail. For those of ordinary skill in the art, according to the idea of the embodiments of the present invention, there will be changes in the specific implementation manners and application scopes. In summary, the content of this specification should not be construed as a limitation to the present invention.

Claims

1. An axially chiral BODIPY olefin compound, characterized in that: The general structural formula is shown in formula (I): Among them, the benzene ring structure in formula (Ⅰ) Selected from One of; Wherein, R1 is selected from one of methyl, p-trifluoromethylphenyl and 3,5-dimethylphenyl; Wherein R2 is selected from One of them.

2. The axially chiral BODIPY olefin compound according to claim 1, characterized in that The enantiomeric excess (ee) value of the compound of formula (I) is 85-98%.

3. The axially chiral BODIPY olefin compound according to claim 1, characterized in that The fluorescence quantum yield Φf of the compound of formula (I) is between 0.90 and 0.

98.

4. The method for synthesizing an axially chiral BODIPY olefin compound according to claim 1-2, characterized in that: Includes the following: (1) placing compound M and pyrrole in a reactor and reacting at room temperature for 20-60 minutes to generate compound N; (2) Compound N and a solvent are placed in a reactor, tetrachlorobenzoquinone is added and reacted at room temperature for 6-10 hours, then N,N-diisopropylethylamine is added and reacted for further 20-40 minutes, and then an ether solution containing boron trifluoride is added dropwise over 5-10 minutes, and reacted for 0.5-2 hours to generate compound L; (3) Under an inert gas atmosphere, compound L, olefin compound K, (MeCN)2PdCl2, ligand compound H, NaBO3·4H2O, CuMeSal, CsF and CuF2 are placed in a reactor, and then trifluoroethanol is added to react at 30° C. for 24-48 hours to obtain a compound of formula (I); Among them, the structure of compound M is The structure of compound N is The structure of compound L is The benzene ring structure Selected from One of; R1 is selected from one of methyl, p-trifluoromethylphenyl and 3,5-dimethylphenyl; Wherein, the structural formula of the olefin compound K is R2 is selected from One of them.

5. The method for synthesizing an axially chiral BODIPY olefin compound according to claim 4, characterized in that: The structural formula of ligand compound H is 6. The method for synthesizing an axially chiral BODIPY olefin compound according to claim 4-5, characterized in that: The input molar ratio of L compound, olefin compound K, (MeCN)2PdCl2, ligand compound H, NaBO3·4H2O, CuMeSal, CsF and CuF2 is 1:(2-4):(0.05-0.2):(0.1-0.3):(1-3):(0.1-0.3):(0.1-0.3):(0.1-0.3).

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