CN118406033A - Preparation method of chroman compound - Google Patents

Preparation method of chroman compound Download PDF

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CN118406033A
CN118406033A CN202410881398.8A CN202410881398A CN118406033A CN 118406033 A CN118406033 A CN 118406033A CN 202410881398 A CN202410881398 A CN 202410881398A CN 118406033 A CN118406033 A CN 118406033A
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chroman
nmr
benzene
chroman compound
photosensitizer
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CN118406033B (en
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张鸽
汪越
张前
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Northeast Normal University
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Northeast Normal University
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Abstract

The invention relates to the technical field of organic synthetic chemistry, and discloses a preparation method of a chroman compound, which comprises the following steps: under anaerobic condition, cobalt catalyst, bronsted acid and photosensitizer are generatedSpecies, intercalated into 1-benzene-1, 3-butadiene derivatives, and oxidized to form alkyl Co 4+ cationic intermediates, followed by phenol derivative pairsKey progression classNucleophilic substitution to obtain allyl aryl ether intermediate product, and under the catalysis of cobalt, making intramolecular hydroarylation produce reaction to make constructionThe bond finally obtains the chroman compound. The invention provides a preparation method of a chroman compound with high diastereoselectivity, which can prepare the chroman compound no matter the raw material used is phenol with electron donating groups or electron withdrawing groups, and expands the application range of the reaction and the diversity of the chroman structure.

Description

Preparation method of chroman compound
Technical Field
The invention belongs to the technical field of organic synthetic chemistry, and particularly relates to a preparation method of a chroman compound.
Background
The chroman structure is the core backbone of many bioactive compounds, including a large number of natural products and many synthetic compounds that are bioactive. Because these compounds exhibit different biological activities, synthetic chemists have developed a number of effective methods for obtaining the chroman backbone: (1) Intramolecular Friedel-Crafts cyclization using aryl allyl ethers is described in detail in reference J.Org. chem.2021, 86, 21, 14290-14310; (2) Intramolecular orthoallylic phenol cyclisation, specific reference J.Org. chem.2017, 82, 6, 3192-3222; (3) Catalyzing [4+2] cycloaddition, specifically referred to by Angew, chem, int, ed., 2015, 54, 5460-5464; (4) The functionalization of the existing chromans and related backbones can be referred to in particular as org. Chem. Front. 2019,6,3523-3529. As can be seen, most attention is focused on the formation of the pyran ring from functionalized phenols. The direct use of phenol is very attractive for the step economy of such routes.
The prior art uses phenol directly to synthesize chromans, see reference ANGEWANDTE CHEMIE International edition 2015, 54, 8203-8207; org. Lett.2015, 17 (23), 5812-5815, because of involving Friedel-Crafts and oxa-Michael addition reactions, the electrophilic reaction mostly requires the use of electron-rich phenol as a raw material, i.e. the phenol needs to be connected with an electron donating group for reaction, so that electron withdrawing groups cannot be compatible with the phenol, and then the phenol with the electron withdrawing group cannot be used as the raw material for synthesizing the chromans, thereby greatly limiting the application range of the reaction and the diversity of chroman structures. Therefore, there is an urgent need to develop a method for synthesizing chromans which is compatible with phenols having electron withdrawing groups and phenols having electron donating groups as raw materials.
Disclosure of Invention
The invention provides a preparation method of a chroman compound, which solves the problem that the prior art cannot be compatible with a method for synthesizing the chroman compound by taking phenol with an electron withdrawing group and phenol with an electron donating group as raw materials.
A method for preparing a chroman compound, comprising the following steps: under the anaerobic condition, the cobalt catalyst, the Bronsted acid and the photosensitizer generate Co 3+ -H species, the Co 3+ -H species is inserted into 1-benzene-1, 3-butadiene derivatives, and then the Co 4+ cation intermediate is formed by oxidation, and then the phenol derivative pairNucleophilic substitution of S N -like 2 is carried out on the bond to obtain an allyl aryl ether intermediate product, and intramolecular hydroarylation is carried out under the catalysis of cobalt to obtain the chroman compound.
Preferably, the preparation method of the chroman compound specifically comprises the following steps:
Under the anaerobic condition, dissolving a cobalt catalyst, bronsted acid and a photosensitizer in dichloromethane or acetonitrile, reacting with a phenol derivative and a 1-benzene-1, 3-butadiene derivative for 24-48 hours under blue light irradiation, quenching, and separating and purifying an organic phase to obtain the chroman compound.
Preferably, the molar ratio of cobalt catalyst, photosensitizer, bronsted acid, phenol derivative and 1-benzene-1, 3-butadiene derivative is 0.03:0.01:0.2:1.0:2.0.
Preferably, the cobalt catalyst is Salen chelated Co 2+ catalyst, preferably:
。
Preferably, the photosensitizer is an iridium photosensitizer, and specifically is terpyridyl iridium.
Preferably, the bronsted acid is 2,4, 6-trimethylpyridine-trifluoromethanesulfonic acid.
Since the catalytic cycle involves two electron transfer steps: single electron reduction of Co 2+, E red = -1.31V vs SCE, and single electron oxidation of alkyl Co 3+, E ox =0.39V vs SCE, the catalytic efficiency of the reaction can be affected by the choice of photo-redox catalyst. In order to satisfy this condition, it is critical to select a suitable photooxidation-reduction catalyst having high reducing power in the form of radical cations having an excited state and medium oxidizing power, so that the reaction system is preferably such that the photosensitizer is iridium terpyridyl.
The effect on reactivity is very pronounced since the pyridinium salt is also the counter anion of the photosensitizer cationic radical and the counter anion of the alkyl Co 4+ during the reaction catalysis. For example, when the trifluoroacid salt anion is replaced with tetrafluoroborate or hexafluorophosphate ion, a drastic decrease in reaction yield is observed. The reaction system is therefore preferably 2,4, 6-trimethylpyridine-trifluoromethanesulfonic acid with pka=15 in acetonitrile.
The reaction solvent is selected from dichloromethane or acetonitrile because dichloromethane not only has good solubility, but also can provide good reaction yield in condition screening. Other solvents such as 1, 1-dichloroethane, as well as diethyl ether, tetrahydrofuran, can lead to Z/E isomerization and reduction of diolefins, and the desired target product is not obtained. Acetonitrile is reactive as a solvent, but the yield of the target product is reduced, so that the solvent of the reaction system is preferably methylene chloride.
Preferably, the structural general formula of the phenol derivative is:
；
Wherein R 2 is heteroalkyl, alkoxy, phenoxy, ester, borate or halogen.
Preferably, the phenol derivative includes any one of the following:
。
Preferably, the structural general formula of the 1-benzene-1, 3-butadiene derivative is as follows:
；
Wherein R 1 is hydrogen, alkyl, alkoxy, ester group or halogen.
Preferably, the 1-benzene-1, 3-butadiene derivative includes any one of the following:
。
Preferably, the structural general formula of the chroman compound is as follows:
formula 2;
wherein R 1 is hydrogen, alkyl, alkoxy, ester group, or halogen; r 2 is heteroalkyl, alkoxy, phenoxy, ester, borate or halogen.
Preferably, the R 1 is C 1~C3 alkoxy or C 1~C3 alkyl; r 2 is C 1~C3 heteroalkyl, C 1~C3 substituted alkoxy or benzoate.
The halogen is Cl or Br. R 1 is-H, -CH 3 and-Br. R 2 is-H, -Br, -CH 2CN、-Bpin、-OCF3, -Cl, -COOMe and-OPh.
The chroman compound comprises any one of the following compounds:
。
Compared with the prior art, the invention has the beneficial effects that:
1. The invention firstly provides a preparation method of the chroman compound with high diastereoselectivity, which can prepare the chroman compound no matter the raw material used is phenol with electron donating groups or electron withdrawing groups, thereby expanding the application range of the reaction and the diversity of the chroman structure. Co 3+ -H species are generated by cobalt catalyst, bronsted acid and photosensitizer, co 3+ -H species are inserted into 1-benzene-1, 3-butadiene derivatives, and are oxidized to form alkyl Co 4+ cation intermediate, then phenol derivative pair The bond undergoes a nucleophilic substitution process of class S N 2 to formLinkage, yields the key allyl aryl ether intermediate. Subsequently, the allyl aryl ether is subjected to intramolecular hydroarylation under the catalysis of cobalt, namely formal intramolecular Friedel-crafts alkylation, and the reaction is constructedThe bond ultimately gives chromans with high diastereoselectivity.
2. The preparation method of the chroman compound with high diastereoselectivity directly uses industrial raw material phenol as an oxygen nucleophilic reagent and a hydrogen donor, has the advantages of simple operation, easily obtained raw material reagent, mild condition, environment-friendly reaction system, easy separation and purification of products, suitability for synthesizing various chroman compounds with high diastereoselectivity, and derivative conversion of the chroman compounds with further three-dimensional retention by halogen atoms on aromatic rings, and synthesis of other important compounds. In addition, a large number of experiments prove that the method is suitable for large-scale industrial production, and can be used for preparing the chroman compounds with high purity with high efficiency.
3. The method uses the cobalt catalyst, and the cobalt light combined catalysis conjugated diene and phenol hydrogen functionalization reaction has the advantages of environmental friendliness, low price, atom economy, practicality and high efficiency. To date, continuous construction by the free radical process one-pot methodBond and method of making the sameThe synthesis of chromans by bonding is not reported.
4. The catalytic reaction of cobalt is of great interest due to its inexpensive, high yield characteristics. Particularly, the cobalt hydrogen-mediated hydrogen atom transfer hydrogenation functionalization reaction has the characteristics of wide functional group tolerance, air and water tolerance and simple operation, so that the method becomes an important supplement for synthesizing the chroman derivatives.
Drawings
FIG. 1 is a nuclear magnetic resonance spectrum of 1 H-NMR of chroman 2a prepared in example 1;
FIG. 2 is a nuclear magnetic resonance spectrum of 13 C-NMR of chroman 2a prepared in example 1;
FIG. 3 is a nuclear magnetic resonance spectrum of 1 H-NMR of chroman 2b prepared in example 2;
FIG. 4 is a nuclear magnetic resonance spectrum of 13 C-NMR of chroman 2b prepared in example 2;
FIG. 5 is a nuclear magnetic resonance spectrum of 1 H-NMR of chroman 2c prepared in example 3;
FIG. 6 is a nuclear magnetic resonance spectrum of 13 C-NMR of chroman 2C prepared in example 3;
FIG. 7 is a nuclear magnetic resonance spectrum of 1 H-NMR of chroman 2d prepared in example 4;
FIG. 8 is a nuclear magnetic resonance spectrum of 13 C-NMR of chroman 2d prepared in example 4;
FIG. 9 is a nuclear magnetic resonance spectrum of 19 F-NMR of chroman 2d prepared in example 4;
FIG. 10 is a Noesy nuclear magnetic resonance spectrum of chroman 2d prepared in example 4;
FIG. 11 is a nuclear magnetic resonance spectrum of 1 H-NMR of chroman 2e prepared in example 5;
FIG. 12 is a nuclear magnetic resonance spectrum of 13 C-NMR of chroman 2e prepared in example 5;
FIG. 13 is a nuclear magnetic resonance spectrum of 1 H-NMR of chroman 2f prepared in example 6;
FIG. 14 is a nuclear magnetic resonance spectrum of 13 C-NMR of chroman 2f prepared in example 6;
FIG. 15 is a nuclear magnetic resonance spectrum of 1 H-NMR of 2g of chroman obtained in example 7;
FIG. 16 is a nuclear magnetic resonance spectrum of 13 C-NMR of 2g of chroman obtained in example 7;
FIG. 17 is a nuclear magnetic resonance spectrum of 1 H-NMR of chroman 2H prepared in example 8;
FIG. 18 is a nuclear magnetic resonance spectrum of 13 C-NMR of chroman 2h prepared in example 8;
FIG. 19 is a synthetic route for the preparation of chromans 2 a-2 h of examples 1-8.
Detailed Description
The following description of the embodiments of the present invention will be made in detail, but not necessarily with reference to the specific embodiments of the present invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The methods described in the various embodiments of the present invention, unless otherwise specified, are all conventional. The materials, reagents and the like used, unless otherwise specified, are all commercially available.
The 1-benzene-1, 3-butadiene derivatives according to the invention can be prepared and synthesized according to methods known in the art, and reference is specifically made to the literature (J. Am. chem. Soc. 2023, 145, 3909). The bronsted acids may be prepared and synthesised according to methods known in the art, and reference is made in particular to (j. Am. chem. Soc. 2022, 144, 7953).
The cobalt catalyst used in the embodiment of the invention is。
Example 1
Under the protection of nitrogen, adding a cobalt catalyst of 3.6 mg, iridium terpyridyl of 1.3 mg and 2,4, 6-trimethylpyridine-trifluoromethanesulfonic acid of 10.8 mg into a 10 mL pressure-resistant seal pipe with a stirrer, and adding dichloromethane of 1.0 mL. Subsequently, 2-bromophenol 0.2 mmol, 36.4: 36.4 mg, and then 1-benzene-1, 3-butadiene 1a 0.4 mmol,52.0 mg were added to the system. The reaction was irradiated with blue light and stirred at room temperature for 24 h. After the TLC detection reaction is finished, adding 10 mL water for quenching, extracting with dichloromethane for 3 times, 10 mL each time, combining organic phases, drying with anhydrous sodium sulfate, suction-filtering, distilling off the organic solvent under reduced pressure, and finally separating by silica gel column chromatography to obtain the chroman 2a with the yield of 70%, dr > 15:1. The eluent of column chromatography is petroleum ether and ethyl acetate, and the volume ratio is 100-98:0-2. The synthetic route is shown in FIG. 19.
FIG. 1 is a nuclear magnetic resonance spectrum of 1 H-NMR of chroman 2a prepared in example 1; FIG. 2 is a nuclear magnetic resonance spectrum of 13 C-NMR of chroman 2a prepared in example 1; spectrogram analysis data:
yellow oil. NMR Spectroscopy: 1H NMR (500 MHz, CDCl3) δ 7.38-7.31 (m, 3H), 7.29 – 7.24 (m, 1H), 7.17 (d, J = 7.0 Hz, 2H), 6.69 – 6.58 (m, 2H), 4.41-4.33 (m, 1H), 4.22-4.15 (m, 1H), 2.26-2.19 (m, 1H), 2.02-1.92 (m, 1H), 1.51 (d, J = 6.0 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 152.0, 144.4, 131.3, 129.1, 128.7, 128.5, 127.5, 126.8, 120.8, 110.8, 73.4, 43.3, 39.7, 21.4. HRMS (ESI-TOF) (m/z): calcd for C16H15BrNaO ([M+Na]+), 325.0198, found, 325.0195.
Example 2
Under the protection of nitrogen, adding a cobalt catalyst of 3.6 mg, iridium terpyridyl of 1.3 mg and 2,4, 6-trimethylpyridine-trifluoromethanesulfonic acid of 10.8 mg into a 10 mL pressure-resistant seal pipe with a stirrer, and adding dichloromethane of 1.0 mL. Subsequently, to the system was added 26.6 mg of parahydroxyphenylacetonitrile, followed by 52.0 mg of 1-benzene-1, 3-butadiene 1 a. The reaction was irradiated with blue light and stirred at room temperature for 36 hours. After TLC detection reaction is completed, adding water 10 mL for quenching, extracting with dichloromethane for 3 times, 10 mL each time, combining organic phases, drying with anhydrous sodium sulfate, suction-filtering, removing the organic solvent by reduced pressure distillation, and finally separating by silica gel column chromatography to obtain the chroman 2b, wherein the yield is 84%, and dr is more than 15:1. The eluent of column chromatography is petroleum ether and ethyl acetate, and the volume ratio is 95-90:5-10. The synthetic route is shown in FIG. 19.
FIG. 3 is a nuclear magnetic resonance spectrum of 1 H-NMR of chroman 2b prepared in example 2; FIG. 4 is a nuclear magnetic resonance spectrum of 13 C-NMR of chroman 2b prepared in example 2; spectrogram analysis data:
yellow oil. NMR Spectroscopy: 1H NMR (500 MHz, CDCl3) δ 7.33 (t, J = 7.0 Hz, 2H), 7.27 (d, J = 6.5 Hz, 1H), 7.16 (d, J = 7.5 Hz, 2H), 7.05 (d, J = 8.0 Hz, 1H), 6.84 (d, J = 8.5 Hz, 1H), 6.60 (s, 1H), 4.34-4.24 (m, 1H), 4.18-4.08 (m, 1H), 3.53-3.42 (m, 2H), 2.24 – 2.14 (m, 1H), 1.96-1.86 (m, 1H), 1.42 (d, J = 6.0 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 155.2, 144.3, 129.4, 128.7, 128.4, 127.2, 126.9, 126.4, 121.3, 118.2, 117.4, 72.5, 42.9, 39.8, 22.8, 21.5. HRMS (ESI-TOF) (m/z): calcd for C18H17NNaO ([M+Na]+), 286.1202, found, 286.1201.
Example 3
Under the protection of nitrogen, adding a cobalt catalyst of 3.6 mg, iridium terpyridyl of 1.3 mg and2, 4, 6-trimethylpyridine-trifluoromethanesulfonic acid of 10.8 mg into a 10 mL pressure-resistant seal pipe with a stirrer, and adding dichloromethane of 1.0 mL. Subsequently, 4-hydroxyphenylboronic acid pinacol ester 44.0 mg was added to the system, followed by the addition of 52.0 mg of 1-benzene-1, 3-butadiene 1 a. The reaction was irradiated with blue light and stirred at room temperature for 48 hours. After TLC detection reaction is completed, adding water 10 mL for quenching, extracting with dichloromethane for 3 times, 10 mL each time, combining organic phases, drying with anhydrous sodium sulfate, suction-filtering, distilling off the organic solvent under reduced pressure, and finally separating rapidly by silica gel column chromatography to obtain chroman 2c with the yield of 90%, dr > 15:1. The eluent of column chromatography is petroleum ether and ethyl acetate, and the volume ratio is 95-90:5-10. The synthetic route is shown in FIG. 19.
FIG. 5 is a nuclear magnetic resonance spectrum of 1 H-NMR of chroman 2c prepared in example 3; FIG. 6 is a nuclear magnetic resonance spectrum of 13 C-NMR of chroman 2C prepared in example 3; spectrogram analysis data:
yellow oil. NMR Spectroscopy: 1H NMR (500 MHz, CDCl3) δ 7.57 (d, J = 8.0 Hz, 1H), 7.31 (t, J = 7.0 Hz, 2H), 7.26 – 7.22 (m, 2H), 7.17 (d, J = 7.5 Hz, 2H), 6.85 (d, J = 8.5 Hz, 1H), 4.31-4.22 (m, 1H), 4.20-4.13 (m, 1H), 2.25-2.15 (m, 1H), 1.92-1.80 (m, 1H), 1.41 (d, J = 6.5 Hz, 3H), 1.24 (s, 12H). 13C NMR (151 MHz, CDCl3) δ 158.4, 145.1, 136.7, 134.6, 128.6, 128.5, 126.5, 124.8, 116.3, 83.3, 72.4, 42.8, 40.9, 24.8, 24.7, 21.5. HRMS (ESI-TOF) (m/z): calcd for C22H27BNaO3 ([M+Na]+), 373.2542, found, 373.2543.
Example 4
Under the protection of nitrogen, adding a cobalt catalyst of 3.6 mg, iridium terpyridyl of 1.3 mg and 2,4, 6-trimethylpyridine-trifluoromethanesulfonic acid of 10.8 mg into a 10 mL pressure-resistant seal pipe with a stirrer, and adding dichloromethane of 1.0 mL. Subsequently, 35.6 mg of 4-trifluoromethoxyphenol was added to the system, followed by 52.0 mg of 1-benzene-1, 3-butadiene 1 a. The reaction was irradiated with blue light and stirred at room temperature for 48 hours. After TLC detection reaction is completed, adding water 10 mL for quenching, extracting 3 times with dichloromethane, 10 mL each time, combining organic phases, drying with anhydrous sodium sulfate, suction-filtering, removing the organic solvent by reduced pressure distillation, and finally obtaining the chroman 2d by silica gel column chromatography and rapid separation, wherein the yield is 83%, dr is more than 15:1. The eluent of column chromatography is petroleum ether and ethyl acetate, and the volume ratio is 100-98:0-2. The synthetic route is shown in FIG. 19.
FIG. 7 is a nuclear magnetic resonance spectrum of 1 H-NMR of chroman 2d prepared in example 4; FIG. 8 is a nuclear magnetic resonance spectrum of 13 C-NMR of chroman 2d prepared in example 4; FIG. 9 is a nuclear magnetic resonance spectrum of 19 F-NMR of chroman 2d prepared in example 4; FIG. 10 is a nuclear magnetic resonance spectrum of Noesy of chroman 2d prepared in example 4; spectrogram analysis data:
yellow oil. NMR Spectroscopy: 1H NMR (500 MHz, CDCl3) δ 7.33 (t, J = 7.5 Hz, 2H), 7.27 (d, J = 7.0 Hz, 1H), 7.16 (d, J = 7.0 Hz, 2H), 6.95 (d, J = 10.5 Hz, 1H), 6.83 (d, J = 9.0 Hz, 1H), 6.56 (s, 1H), 4.34-4.25 (m, 1H), 4.18-4.10 (m, 1H), 2.25-2.15 (m, 1H), 1.95-1.85 (m, 1H), 1.42 (d, J = 6.0 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 154.0, 143.9, 142.1 (d, J = 1.8 Hz), 128.8, 128.4, 127.0, 126.8, 122.6, 120.7, 120.4 (q, J = 255.9Hz), 117.5, 72.7, 43.1, 39.6, 21.5. 19F NMR (565 MHz, CDCl3) δ = -58.43 (s, 1OCF3). HRMS (ESI-TOF) (m/z): calcd for C17H15F3NaO2 ([M+Na]+), 331.0916, found, 331.0920.
Example 5
Under the protection of nitrogen, adding a cobalt catalyst of 3.6 mg, iridium terpyridyl of 1.3 mg and 2,4, 6-trimethylpyridine-trifluoromethanesulfonic acid of 10.8 mg into a 10mL pressure-resistant seal pipe with a stirrer, and adding dichloromethane of 1.0 mL. Subsequently, methyl 4-hydroxybenzoate 30.4 mg was added to the system, followed by the addition of 52.0 mg of 1-benzene-1, 3-butadiene 1 a. The reaction was irradiated with blue light and stirred at room temperature for 48 hours. After TLC detection reaction is completed, adding water 10mL for quenching, extracting with dichloromethane for 3 times, 10mL each time, combining organic phases, drying with anhydrous sodium sulfate, suction-filtering, removing the organic solvent by reduced pressure distillation, and finally separating by silica gel column chromatography to obtain the chroman 2e with the yield of 75%, dr > 15:1. The eluent of the column chromatography is petroleum ether and ethyl acetate, and the volume ratio is 98-95:2-5. The synthetic route is shown in FIG. 19.
FIG. 11 is a nuclear magnetic resonance spectrum of 1 H-NMR of chroman 2e prepared in example 5; FIG. 12 is a nuclear magnetic resonance spectrum of 13 C-NMR of chroman 2e prepared in example 5; spectrogram analysis data:
yellow oil. NMR Spectroscopy: 1H NMR (600 MHz, CDCl3) δ 7.79 (dd, J = 8.4, 1.8 Hz, 1H), 7.45 – 7.43 (m, 1H), 7.34-7.31 (m, 2H), 7.28 – 7.24 (m, 2H), 7.16 (d, J = 7.2 Hz, 2H), 6.86 (d, J = 8.4 Hz, 1H), 4.40-4.30 (m, 1H), 4.18-4.13 (m, 1H), 3.76 (s, 3H), 2.24-2.18 (m, 1H), 1.97 – 1.88 (m, 1H), 1.44 (d, J = 6.6 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 166.9, 159.5, 144.1, 131.9, 129.4, 128.8, 128.4, 126.9, 125.5, 122.1, 116.7, 73.0, 51.7, 42.9, 39.8, 21.4. HRMS (ESI-TOF) (m/z): calcd for C18H18NaO3 ([M+Na]+), 305.1148, found, 305.1147.
example 6
Under the protection of nitrogen, adding a cobalt catalyst of 3.6 mg, iridium terpyridyl of 1.3 mg and2, 4, 6-trimethylpyridine-trifluoromethanesulfonic acid of 10.8 mg into a 10 mL pressure-resistant seal pipe with a stirrer, and adding dichloromethane of 1.0 mL. Subsequently, 2-chlorophenol 30.4 mg was added to the system, followed by addition of 57.6 mg of 1- (3-methylphenyl) -1, 3-butadiene 1 f. The reaction was irradiated with blue light and stirred at room temperature for 48 hours. After TLC detection reaction is completed, adding water 10 mL for quenching, extracting with dichloromethane for 3 times, 10 mL each time, combining organic phases, drying with anhydrous sodium sulfate, suction-filtering, removing the organic solvent by reduced pressure distillation, and finally separating by silica gel column chromatography to obtain the chroman 2f with the yield of 80%, dr > 15:1. The eluent of column chromatography is petroleum ether and ethyl acetate, and the volume ratio is 100-98:0-2. The synthetic route is shown in FIG. 19.
FIG. 13 is a nuclear magnetic resonance spectrum of 1 H-NMR of chroman 2f prepared in example 6; FIG. 14 is a nuclear magnetic resonance spectrum of 13 C-NMR of chroman 2f prepared in example 6; spectrogram analysis data:
yellow oil. NMR Spectroscopy: 1H NMR (500 MHz, CDCl3) δ 7.23 – 7.15 (m, 2H), 7.07 (d, J = 7.5 Hz, 1H), 6.96 (d, J = 10.5 Hz, 2H), 6.68-6.59 (m, 2H), 4.40-4.30 (m, 1H), 4.16-4.11 (m, 1H), 2.32 (s, 3H), 2.24-2.17 (m, 1H), 2.01-1.91 (m, 1H), 1.50 (d, J = 6.5 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 151.2, 144.4, 138.3, 129.2, 128.5, 128.3, 128.1, 127.6, 127.6, 125.6, 121.3, 120.1, 73.3, 43.1, 39.7, 21.4. HRMS (ESI-TOF) (m/z): calcd for C17H18Na ([M+Na]+), 261.1250, found, 261.1250.
Example 7
Under the protection of nitrogen, adding a cobalt catalyst of 3.6 mg, iridium terpyridyl of 1.3 mg and 2,4, 6-trimethylpyridine-trifluoromethanesulfonic acid of 10.8 mg into a 10 mL pressure-resistant seal pipe with a stirrer, and adding dichloromethane of 1.0 mL. Subsequently, 2-chlorophenol 30.4 mg was added to the system, followed by 1g of 1- (4-bromophenyl) -1, 3-butadiene 82.8 mg. The reaction was irradiated with blue light and stirred at room temperature for 48 hours. After TLC detection reaction is completed, adding water 10 mL for quenching, extracting with dichloromethane 3 times, 10 mL each time, combining organic phases, drying with anhydrous sodium sulfate, suction-filtering, removing the organic solvent by reduced pressure distillation, and finally separating by silica gel column chromatography to obtain 2g of chroman with the yield of 81%, dr > 15:1. The eluent of column chromatography is petroleum ether and ethyl acetate, and the volume ratio is 100-98:0-2. The synthetic route is shown in FIG. 19.
FIG. 15 is a nuclear magnetic resonance spectrum of 1 H-NMR of 2g of chroman obtained in example 7; FIG. 16 is a nuclear magnetic resonance spectrum of 13 C-NMR of 2g of chroman obtained in example 7; spectrogram analysis data:
yellow oil. NMR Spectroscopy: 1H NMR (500 MHz, CDCl3) δ 7.44 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 8.0 Hz, 1H), 7.04 (d, J = 8.5 Hz, 2H), 6.66 (t, J = 8.0 Hz, 1H), 6.57 (d, J = 8.0 Hz, 1H), 4.38-4.30 (m, 1H), 4.18-4.11 (m, 1H), 2.24-2.16 (m, 1H), 1.94-1.84 (m, 1H), 1.50 (d, J = 6.0 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 151.2, 143.5, 131.8, 130.2, 128.4, 128.1, 126.8, 121.6, 120.6, 120.2, 73.2, 42.7, 39.6, 21.4. HRMS (ESI-TOF) (m/z): calcd for C16H14BrClNaO ([M+Na]+), 358.9809, found, 359.9811.
Example 8
Under the protection of nitrogen, adding a cobalt catalyst of 3.6 mg, iridium terpyridyl of 1.3 mg and 2,4, 6-trimethylpyridine-trifluoromethanesulfonic acid of 10.8 mg into a 10mL pressure-resistant seal pipe with a stirrer, and adding dichloromethane of 1.0 mL. Subsequently, 4-phenoxyphenol 37.2 mg was added to the system, followed by the addition of 52.0 mg of 1-benzene-1, 3-butadiene 1 a. The reaction was irradiated with blue light and stirred at room temperature for 48 hours. After the TLC detection reaction is finished, adding water 10mL for quenching, extracting with dichloromethane for 3 times, 10mL each time, combining organic phases, drying with anhydrous sodium sulfate, suction-filtering, distilling off the organic solvent under reduced pressure, and finally separating by silica gel column chromatography to obtain the chroman 2h with the yield of 98%, dr=2.4:1. The eluent of column chromatography is petroleum ether and ethyl acetate, and the volume ratio is 100-98:0-2. The synthetic route is shown in FIG. 19.
FIG. 17 is a nuclear magnetic resonance spectrum of 1 H-NMR of chroman 2H prepared in example 8; FIG. 18 is a nuclear magnetic resonance spectrum of 13 C-NMR of chroman 2h prepared in example 8; spectrogram analysis data:
yellow oil. NMR Spectroscopy: 1H NMR (500 MHz, CDCl3) δ 7.31-7.26 (m, 2.84H), 7.26 – 7.24 (m, 1H), 7.23 – 7.18 (m, 3.68H), 7.17 – 7.15 (m, 2H), 7.08 (d, J = 7.5 Hz, 1H), 7.01-6.93 (m, 1.42H), 6.91 – 6.87 (m, 1.42H), 6.84 – 6.81 (m, 2.84H), 6.78 (dd, J = 8.5, 2.5 Hz, 1H), 6.68 (d, J = 2.5 Hz, 0.42H), 6.48-6.46 (m, 1H), 4.33-4.25 (m, 1H), 4.19 – 4.08 (m, 1.84H), 2.20-2.15 (m, 1H), 2.12 – 2.06 (m, 0.42H), 2.01-1.96 (m, 0.42H), 1.96-1.87 (m, 1H), 1.42 (d, J = 6.5 Hz, 3H), 1.32 (d, J = 6.5 Hz, 1.26H). 13C NMR (151 MHz, CDCl3) δ 158.6, 151.9, 151.89, 149.39, 149.09, 146.3, 144.5, 129.5, 129.5, 128.6, 128.5, 128.4, 128.3, 126.8, 126.7, 126.3, 123.9, 122.1, 122.0, 121.8, 121.4, 120.0, 119.6, 117.8, 117.5, 117.3, 117.0, 72.4, 67.5, 43.2, 40.3, 40.0, 37.6, 21.5, 21.1. HRMS (ESI-TOF) (m/z): calcd for C22H20NaO2 ([M+Na]+), 339.1356, found, 339.1351.
since the chroman structure is the core backbone of many bioactive compounds, including a large number of natural products and many bioactive compounds. Such as vitamin E (I), antiestrogens (II), and crotamarind (III). Therefore, the chroman compound prepared by the invention can be used as a core skeleton of the medicine.
While preferred embodiments of the present invention have been described, additional variations and modifications in those embodiments may occur to those skilled in the art once they learn of the basic inventive concepts. It is therefore intended that the following claims be interpreted as including the preferred embodiments and all such alterations and modifications as fall within the scope of the invention.
It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention also include such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.

Claims (10)

1. The preparation method of the chroman compound is characterized by comprising the following steps of: under the anaerobic condition, the cobalt catalyst, the Bronsted acid and the photosensitizer generate Co 3+ -H species, the Co 3+ -H species is inserted into 1-benzene-1, 3-butadiene derivatives, and then the Co 4+ cation intermediate is formed by oxidation, and then the phenol derivative pairNucleophilic substitution of S N -like 2 is carried out on the bond to obtain an allyl aryl ether intermediate product, and intramolecular hydroarylation is carried out under the catalysis of cobalt to obtain the chroman compound.
2. The method for preparing the chroman compound according to claim 1, which is characterized by comprising the following steps:
Under the anaerobic condition, dissolving a cobalt catalyst, bronsted acid and a photosensitizer in dichloromethane or acetonitrile, reacting with a phenol derivative and a 1-benzene-1, 3-butadiene derivative for 24-48 hours under blue light irradiation, quenching, and separating and purifying an organic phase to obtain the chroman compound.
3. The method for preparing the chroman compound according to claim 2, wherein the molar ratio of the cobalt catalyst, the photosensitizer, the bronsted acid, the phenol derivative and the 1-benzene-1, 3-butadiene derivative is 0.03:0.01:0.2:1.0:2.0.
4. A process for the preparation of chromans according to claim 3, wherein the cobalt catalyst is Salen chelated Co 2+ catalyst.
5. The method for preparing chroman compounds according to claim 4, wherein the photosensitizer is an iridium photosensitizer.
6. The method for producing chromans according to claim 5, wherein the bronsted acid is 2,4, 6-trimethylpyridine-trifluoromethanesulfonic acid.
7. The method for preparing a chroman compound according to claim 1, wherein the phenol derivative has a general structural formula:
；
Wherein R 2 is heteroalkyl, alkoxy, phenoxy, ester, borate or halogen.
8. The method for producing a chroman-based compound according to claim 7, wherein the phenol derivative comprises any one of:
。
9. The method for preparing a chroman compound according to claim 8, wherein the 1-benzene-1, 3-butadiene derivative has a general structural formula:
；
Wherein R 1 is hydrogen, alkyl, alkoxy, ester group or halogen.
10. The method for producing a chroman-based compound according to claim 9, wherein the 1-benzene-1, 3-butadiene derivative comprises any one of the following:
。
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