A method for selectively synthesizing para-pinacol boryl ester-substituted anisole compounds

Abstract

The invention provides a method for selectively synthesizing anisole compounds substituted with a pinacol boron ester, the synthesis method comprising: reacting anisole compounds with a pinacol boron ester under the catalysis of an organic boron catalyst and a noble metal catalyst. The method can selectively replace the anisole compounds substituted with a pinacol boron ester at a limited para position, the product has high selectivity, mild reaction conditions and simple operation.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis and relates to a method for synthesizing anisole compounds substituted with pinacol borate, in particular to a method for selectively synthesizing anisole compounds substituted with para-pinacol borate. Background Art

[0002] Since Milton R. Smith III first reported the transition metal Ir-catalyzed CH bond borylation reaction of aromatic hydrocarbons in 2001 (Cho, JY; Tse, MK; Holmes, D.; Maleczka Jr, RE; Smith III, MR Science, 2002, 295, 305.), chemists have developed a variety of transition metal-catalyzed CH bond functionalization reactions (including aromatization, alkaneization, olefination, alkyneization and amination, etc.) (Kalyani, D.; Deprez, NR; Desai, LV; Sanford, MSJ Am. Chem. Soc. 2005, 127, 7330; Chen, X.; Goodhue, CE; Yu, JQJ Am. Ch em.Soc.2006,128,12634; Shabashov, D.; Daugulis, OJAm.Chem.Soc.2010,132,3965; Rouquet, G.; Chatani , N. Angew. Chem. Int. Ed. 2013, 52, 11726; Daugulis, O.; Roane, J.; Tran, LDAcc. Chem. Res. 2015, 48, 1053). However, most transition metal-catalyzed CH bond functionalization reactions currently adopt a directing group strategy, using functional groups with complexing ability in the molecule (such as pyridyl, amide, imine, alkoxy, carboxyl, etc.) to form a five-membered / six-membered cyclometal intermediate (such as Palladacycle) with a complex metal catalyst to achieve CH bond cleavage, and then react with other reactants through oxidative addition and reduction elimination to achieve CH bond functionalization. This makes the activated CH bonds in the substrate molecule very limited, and only the sites that can form cyclometal intermediates can be activated, limiting the applicability of the reaction. The most typical example is the CH functionalization reaction of 2-phenylpyridine, where only the two ortho positions of the directing group pyridine can be functionalized, while the activation of the distal meta (-m) / para (-p) position is very difficult.

[0003] Recently, chemists have developed a new catalytic concept that uses the non-covalent bond interaction between the ligand and the substrate to achieve distal position selective CH bond activation reactions. Most of these ligands have a special skeleton structure, which includes a recognition center, a catalytic center and an appropriate connecting group. The recognition center in the ligand interacts with the functional group in the substrate through non-covalent bonds (such as hydrogen-bonding interaction; Lewis acid-base interaction; electrostatic interaction, etc.), so that the catalytic center is spatially close to the distal meta- or para-CH bond to achieve distal position selectivity (Biedermann, F.; Schneider, H.-J. Chem. Rev. 2016, 116, 5216; Schneider, Acc.Chem.Res.2015,48,1815). This method can not only get rid of the limitation of substrate molecules, but also greatly improve the applicability of the reaction. Summary of the invention

[0004] In view of the problems existing in the prior art, the present invention provides a method for selectively synthesizing anisole compounds substituted with a para-pinacol boron ester. The method can selectively replace the para position in anisole compounds substituted with a pinacol boron ester, has high product selectivity, mild reaction conditions and simple operation.

[0005] In order to achieve the above technical effects, the present invention adopts the following technical solutions:

[0006] The present invention provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, the synthesis method comprising:

[0007] The phenyl ether compound represented by Formula 1 and the pinacol boron ester are reacted under the catalysis of the organic boron catalyst represented by Formula 2 and the noble metal catalyst;

[0008]

[0009] Wherein, R is any one of hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, ester, cyano, amido or silicon; R1 is a C1-C5 straight-chain alkyl; R2 is a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aryloxy or C4-C12 alkoxy; the substituent in R2 includes alkyl, alkoxy, aryloxy or perfluoroaryl.

[0010] Wherein, the halogen includes any one of fluorine, chlorine, bromine or iodine;

[0011] The substituted or unsubstituted alkyl group includes C1-C12 alkyl groups, preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl or n-dodecyl, etc.;

[0012] The substituted or unsubstituted alkoxy group includes C1-C12 alkoxy groups, preferably methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentyloxy, n-hexyloxy, n-heptyloxy, n-octyloxy, n-nonyloxy, n-decyloxy, n-undecyloxy or n-dodecyloxy, etc.;

[0013] The ester group includes C1-C6 ester groups, preferably formate, acetate, propionate, isopropionate, butyrate, valerate or hexanoate, etc.;

[0014] The acylamino group includes C1 to C6 acylamino groups, preferably formamide, acetamide, propionamide, butyramide, valeramide or hexanamide, etc.;

[0015] The silicon group includes trimethylsilyl, triethylsilyl, trimethoxysilyl or triethoxysilyl.

[0016] The C1-C5 straight-chain alkyl group is preferably methyl, ethyl, n-propyl, n-butyl or n-pentyl;

[0017] The substituted or unsubstituted aryl group includes a substituted or unsubstituted C3-C12 aryl group, preferably a substituted or unsubstituted phenyl or naphthyl group;

[0018] The substituted or unsubstituted heteroaryl group includes substituted or unsubstituted C5-C12 heteroaryl groups, preferably substituted or unsubstituted furyl, pyranyl, thienyl, pyrimidinyl or quinolyl, etc.;

[0019] The substituted or unsubstituted aryloxy group includes a substituted or unsubstituted C3-C12 aryloxy group, preferably a substituted or unsubstituted phenoxy group or naphthoxy group;

[0020] The C4-C12 alkoxy group is preferably n-butoxy, isobutoxy, tert-butoxy, n-pentyloxy, n-hexyloxy, n-heptyloxy, n-octyloxy, n-nonyloxy, n-decyloxy, n-undecyloxy or n-dodecyloxy, etc.;

[0021] The alkyl group in the substituent in R2 includes a C1-C12 alkyl group, preferably a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a tert-butyl group, a n-pentyl group, a n-hexyl group, a n-heptyl group, a n-octyl group, a n-nonyl group, a n-decyl group, a n-undecyl group or a n-dodecyl group;

[0022] The alkoxy group in the substituent in R2 includes C1-C12 alkoxy groups, preferably methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentyloxy, n-hexyloxy, n-heptyloxy, n-octyloxy, n-nonyloxy, n-decyloxy, n-undecyloxy or n-dodecyloxy, etc.;

[0023] The aryloxy group in the substituent in R2 includes C3-C12 aryloxy groups, preferably substituted or unsubstituted phenoxy or naphthoxy, etc.;

[0024] The perfluoroaryl group in the substituent in R2 includes perfluorophenyl group or perfluoronaphthyl group.

[0025] In the present invention, the organic boron catalyst shown in Formula 2 is introduced into the reaction, and the organic boron catalyst has an empty p orbital perpendicular to the sp2 hybrid orbital, so it tends to combine with the electron pair; and the phenyl ether compound shown in Formula 1 has an alkoxy group, and the oxygen atom of the alkoxy group has a lone electron pair, which can form a Lewis acid-base non-covalent interaction with the organic boron catalyst. Since the organic boron catalyst used in the present invention is trisubstituted, and the substituent is mainly substituted or substituted aryl or heteroaryl, etc., it has a large steric hindrance. When the phenyl ether compound forms a Lewis acid-base non-covalent interaction with the organic boron catalyst, the ortho and meta positions of the phenyl ether substrate are blocked, so at this time, the noble metal catalyst is more inclined to activate the para position with less steric hindrance, thereby controlling the remote para selectivity.

[0026] As a preferred technical solution of the present invention, the pinacol borate includes biboric acid pinacol borate or isopropyl pinacol borate.

[0027] As a preferred technical solution of the present invention, the molar ratio of the phenyl ether compound to the pinacol borate is 1:0.4-0.6, such as 1:0.42, 1:0.45, 1:0.48, 1:0.5, 1:0.52, 1:0.55 or 1:0.58.

[0028] As a preferred technical solution of the present invention, the molar ratio of the phenyl ether compound to the organic boron catalyst is 1:1-2, such as 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8 or 1:1.9.

[0029] As a preferred technical solution of the present invention, the noble metal catalyst includes an Ir complex generated by the reaction of [Ir(COD)OMe]2 and 4,4'-di-tert-butylbipyridine, and the molar ratio of [Ir(COD)OMe]2 to 4,4'-di-tert-butylbipyridine is 1:2.

[0030] In the present invention, in addition to the above-mentioned noble metal catalysts, an Ir complex generated by the reaction of metal iridium catalysts such as [Ir(COD)Cl]2, [Ir(COD)BF4]2 with 4,4'-di-tert-butylbipyridine can also be used, wherein the molar ratio of [Ir] to 4,4'-di-tert-butylbipyridine is 1:2.

[0031] As a preferred technical solution of the present invention, the molar ratio of the phenyl ether compound to the precious metal catalyst is 1:0.02-0.04, such as 1:0.022, 1:0.025, 1:0.028, 1:0.03, 1:0.032, 1:0.035 or 1:0.038, etc.

[0032] As a preferred technical solution of the present invention, the reaction is carried out in an organic solvent, and the organic solvent includes any one of p-xylene, cyclohexane, petroleum ether, ethyl acetate, dichloromethane, toluene or diethyl ether, or a combination of at least two thereof.

[0033] As a preferred technical solution of the present invention, the reaction temperature is 50-55°C, such as 50.5°C, 51°C, 51.5°C, 52°C, 52.5°C, 53°C, 53.5°C, 54°C or 54.5°C.

[0034] As a preferred technical solution of the present invention, the reaction time is 8 to 24 hours, such as 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours or 23 hours.

[0035] As a preferred technical solution of the present invention, after the reaction is completed, the product is separated by recrystallization, thin layer chromatography or column chromatography under reduced pressure distillation.

[0036] In the present invention, as in the recrystallization method, the recommended solvent is a mixed solvent of a polar solvent and a non-polar solvent. The recommended solvent may be dichloromethane-n-hexane, ethyl acetate-n-hexane. In thin layer chromatography and column chromatography, the developing solvent used is a mixed solvent of a polar solvent and a non-polar solvent. The recommended solvent may be dichloromethane-n-hexane, ethyl acetate-n-hexane. The volume ratios thereof may be respectively: polar solvent: non-polar solvent = 10:1 to 20:1. For example, dichloromethane:n-hexane = 10:1 to 20:1; ethyl acetate:n-hexane = 10:1 to 20:1.

[0037] In the present invention, the values ​​listed in the numerical ranges of various conditions are only preferred values, but are not limited to the listed values, and other values ​​not listed in the numerical ranges are also applicable.

[0038] Compared with the prior art solutions, the present invention has at least the following beneficial effects:

[0039] The invention provides a method for selectively synthesizing anisole compounds substituted with a para-pinacol boron ester. The method can selectively replace the para position in anisole compounds substituted with a pinacol boron ester, and the product has high selectivity, a yield of generally 60-82%, mild reaction conditions and simple operation. DETAILED DESCRIPTION

[0040] To better illustrate the present invention and facilitate understanding of the technical solution of the present invention, typical but non-limiting embodiments of the present invention are as follows:

[0041] Example 1

[0042] This embodiment provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, wherein the reaction is shown in Formula 3 and the main conditions are shown in Table 1:

[0043]

[0044] Table 1

[0045]

[0046] Example 2

[0047] This embodiment provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, the method comprising:

[0048] In a dry reaction tube, anisole (0.2 mmol), B2Pin2 (0.2 mmol),

[0049] [Ir(COD)OMe]2 (0.0006mmol), dtbpy (0.0012mmol), BPh3 (0.2mmol), and then 2mL of p-xylene was added as solvent. The reaction was carried out at 55°C for 12 hours. After the reaction, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain 2-(4-methoxyphenyl)-pinacol boron ester, the chemical structure of which is shown in Formula 4.

[0050]

[0051] The total yield of the borylation product is 70%, the ratio of the meta-isomer to the para-isomer is greater than 15, and the product is a white solid.

[0052] 1 H NMR (400MHz, CDCl3) δ1.38 (s, 12H), 2.53 (s, 3H), 7.26-7.28 (d, J = 8.2Hz, 2H), 7.74 (d, J = 8.2Hz, 2H); 13C NMR (100MHz, CDCl3) δ15.2, 25.1, 83.9, 125.2, 135.3, 142.8.

[0053] Example 3

[0054] This embodiment provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, the method comprising:

[0055] In a dry reaction tube, phenyl ether (0.2 mmol), B2Pin2 (0.2 mmol), [Ir(COD)OMe]2 (0.0006 mmol), dtbpy (0.0012 mmol), BPh3 (0.2 mmol) were added in sequence, and then 2 mL of p-xylene was added as a solvent. The reaction was carried out at 55°C for 12 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain 2-(4-ethoxy)-pinacol boron ester, the chemical structure of which is shown in Formula 5.

[0056]

[0057] The total yield of the borylation product is 66%, the ratio of the meta-isomer to the para-isomer is greater than 15, and the product is a white solid.

[0058] 1 H NMR (400MHz, CDCl3) δ1.24 (s, 12H), 1.41 (t, J = 4.8, 6.4Hz, 3H), 4.01-4.05 (m, 2H), 6.87 (d, J = 8.2Hz, 2H), 7.78 (d, J = 8.2Hz, 2H); 13 C NMR (100MHz, CDCl3) δ14.7, 24.8, 63.6, 84.0, 114.2, 130.5, 136.5, 160.9.

[0059] Example 4

[0060] This embodiment provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, the method comprising:

[0061] 2-Methylanisole (0.2mmol), B2Pin2 (0.2mmol), [Ir(COD)OMe]2 (0.0006mmol), dtbpy (0.0012mmol), BPh3 (0.2mmol) were added to a dry reaction tube in sequence, and then 2mL of p-xylene was added as a solvent. The reaction was carried out at 55°C for 12 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain 2-(4-methoxy-3-methylphenyl) pinacol boron ester, the chemical structure of which is shown in Formula 6.

[0062]

[0063] The total yield of the borylation product is 63%, the ratio of the meta-isomer to the para-isomer is greater than 15, and the product is a white solid.

[0064] 1 H NMR (500MHz, CDCl3) δ1.24 (s, 12H), 2.21 (s, 3H), 3.83 (s, 3H), 6.75 (d, J = 8.9Hz, 1H), 7.36-7.38 (m, 1H), 7.65 (dd, J = 9.0, 1.8Hz, 1H); 13 C NMR (100MHz, CDCl3) δ16.1,24.8,55.6,83.6,111.9,127.8,132.1,133.9,135.1,158.3.

[0065] Example 5

[0066] This embodiment provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, the method comprising:

[0067] 2-phenylanisole (0.2mmol), B2Pin2 (0.2mmol), [Ir(COD)OMe]2 (0.0006mmol), dtbpy (0.0012mmol), BPh3 (0.2mmol) were added to a dry reaction tube in sequence, and then 2mL of p-xylene was added as a solvent. The reaction was carried out at 55°C for 12 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain 2-(6-methoxy-[1,1'-biphenyl]-3-pinacol boron ester, the chemical structure of which is shown in Formula 7.

[0068]

[0069] The total yield of the borylation product is 74%, the ratio of the meta-isomer to the para-isomer is greater than 15, and the product is a white solid.

[0070] 1 H NMR (500MHz, CDCl3) δ1.24 (s, 12H), 3.90 (s, 3H),, 6.69 (d, J = 8.8Hz, 1H), 7.3 5–7.40(m,1H),7.42–7.46(m,4H),7.67(d,J=2.0Hz,1H),7.73–7.77(m,1H); 13 C NMR (125MHz, CDCl3) δ24.8,55.0,83.6,111.4,127.9,128.7,129.1,130.7,132.0,133.3,135.5,138.8,156.0.

[0071] Example 6

[0072] This embodiment provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, the method comprising:

[0073] 2-Fluoroanisole (0.2 mmol), B2Pin2 (0.2 mmol), [Ir(COD)OMe]2 (0.0006 mmol), dtbpy (0.0012 mmol), BPh3 (0.2 mmol) were added in sequence to a dry reaction tube, and then 2 mL of p-xylene was added as a solvent. The reaction was carried out at 55° C. for 12 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate=10 / 1) to obtain 2-(3-fluoro-4-methoxyphenyl)-pinacol boron ester, the chemical structure of which is shown in Formula 8.

[0074]

[0075] The total yield of the borylation product was 59%, the ratio of the meta-isomer to the para-isomer was greater than 15, and the product was a colorless oil.

[0076] 1 H NMR (500MHz, CDCl3) δ1.24(s,12H),3.90(s,3H),6.92(dd,J=9.9,4.9Hz,1H),7.40(dd,J=8.0,1.9Hz,1H),7.57(dd,J=9.9,2.0Hz,1H); 13C NMR (125MHz, CDCl3) δ24.8,56.5(d,J=2.5Hz),83.6,114.8(d,,J=8.8Hz),123.35(d, J=20Hz),131.7(d,J=2.5Hz),133.5(d,J=7.5Hz),148.70(d,J=20Hz),150.2,152.2.

[0077] Example 7

[0078] This embodiment provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, the method comprising:

[0079] 2-Chloroanisole (0.2 mmol), B2Pin2 (0.2 mmol), [Ir(COD)OMe]2 (0.0006 mmol), dtbpy (0.0012 mmol), BPh3 (0.2 mmol) were added to a dry reaction tube in sequence, and then 2 mL of p-xylene was added as a solvent. The reaction was carried out at 55° C. for 12 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate=10 / 1) to obtain 2-(3-chloro-4-methoxyphenyl)-pinacol boron ester, the chemical structure of which is shown in Formula 9.

[0080]

[0081] The total yield of the borylation product is 68%, the ratio of the meta-isomer to the para-isomer is greater than 15, and the product is a white solid.

[0082] 1 H NMR (500MHz, CDCl3) δ1.24 (s, 12H), 3.91 (s, 3H),, 6.94 (d, J = 8.8Hz, 1H), 7.58 (d, J = 2.0Hz, 1H), 7.67 (d, J = 8.8Hz, 1H); 13 C NMR (125MHz, CDCl3) δ24.8,56.6,83.6,113.7,121.9,133.4,134.5,135.1,157.0.

[0083] Example 8

[0084] This embodiment provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, the method comprising:

[0085] In a dry reaction tube, o-phenyl dimethyl ether (0.2 mmol), B2Pin2 (0.2 mmol), [Ir(COD)OMe]2 (0.0006 mmol), dtbpy (0.0012 mmol), BPh3 (0.2 mmol) were added in sequence, and then 2 mL of p-xylene was added as a solvent. The reaction was carried out at 55°C for 12 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain 2-(3,4-dimethoxyphenyl)-pinacol boron ester, the chemical structure of which is shown in Formula 10.

[0086]

[0087] The total yield of the borylation product is 81%, the ratio of the meta-isomer to the para-isomer is greater than 15, and the product is a white solid.

[0088] 1 H NMR (500MHz, CDCl3) δ1.24 (s, 12H), 3.82 (s, 6H),, 6.87 (d, J = 8.9Hz, 1H), 7.15 (d, J = 1.9Hz, 1H), 7.15 (d, J = 1.9Hz, 1H); 13 C NMR (125MHz, CDCl3) δ24.8,55.9,56.1,83.6,113.4,120..7,130.1,130.3,149.1,151.4.

[0089] Example 9

[0090] This embodiment provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, the method comprising:

[0091] In a dry reaction tube, 2-methoxybenzoic acid methyl ester (0.2mmol), B2Pin2 (0.2mmol), [Ir(COD)OMe]2 (0.0006mmol), dtbpy (0.0012mmol), BPh3 (0.2mmol) were added in sequence, and then 2mL of p-xylene was added as solvent. The reaction was carried out at 55°C for 12 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain 2-methoxy-5-pinacol boron ester-benzoic acid methyl ester, the chemical structure of which is shown in Formula 11.

[0092]

[0093] The total yield of the borylation product was 74%, the ratio of the meta-isomer to the para-isomer was greater than 15, and the product was a colorless oil.

[0094] 1 H NMR (500MHz, CDCl3) δ1.24 (s, 12H), 3.86 (s, 3H), 3.87 (s, 3H), 6.96 (d, J = 9.1Hz, 1H), 7.85 (dd, J = 9.0, 2.0Hz, 1H), 8.14 (d, J = 1.9Hz, 1H); 13 C NMR (125MHz, CDCl3) δ24.8,52.3,56.3,83.6,113.4,119.1,130.9,,136.7,139.3,158.5,167.1.

[0095] Example 10

[0096] This embodiment provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, the method comprising:

[0097] 2-methoxybenzamide (0.2mmol), B2Pin2 (0.2mmol), [Ir(COD)OMe]2 (0.0006mmol), dtbpy (0.0012mmol), BPh3 (0.2mmol) were added to a dry reaction tube in sequence, and then 2mL of p-xylene was added as a solvent. The reaction was carried out at 55°C for 12 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain 2-methoxy-5-pinacol boron ester-benzamide, the chemical structure of which is shown in Formula 12.

[0098]

[0099] The total yield of the borylation product was 62%, the ratio of the meta-isomer to the para-isomer was greater than 15, and the product was a colorless oil.

[0100] 1 H NMR (500MHz, CDCl3) δ1.24 (s, 12H), 2.91 (d, J=5.0Hz, 3H), 3.88 (s, 3H), 6.94 (d, J= 9.1Hz,1H),7.71-7.75(m,1H),7.89(dd,J=9.0,2.0Hz,1H),8.02(d,J=1.9Hz,1H); 13 C NMR (125MHz, CDCl3) δ24.8,26.3,56.5,83.6,113.2,120.9,131.5,134.3,139.0,157.6,168.4.

[0101] Embodiment 11

[0102] This embodiment provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, the method comprising:

[0103] In a dry reaction tube, (2-methoxyphenyl)trimethylsilane (0.2mmol), B2Pin2 (0.2mmol), [Ir(COD)OMe]2 (0.0006mmol), dtbpy (0.0012mmol), BPh3 (0.2mmol) were added in sequence, and then 2mL of p-xylene was added as a solvent. The reaction was carried out at 55°C for 12 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain 2-methoxy-5-pinacol boron ester-phenyltrimethylsilane, the chemical structure of which is shown in Formula 13.

[0104]

[0105] The total yield of the borylation product is 79%, the ratio of the meta-isomer to the para-isomer is greater than 15, and the product is a white solid.

[0106] 1 H NMR (500MHz, CDCl3) δ0.39 (s, 9H), 1.24 (s, 12H), 3.65 (s, 3H), 6.97 (d, J = 8.6Hz, 1H), 7.69 (d, J = 2.0Hz, 1H), 7.76 (dd, J = 8.5, 1.9Hz, 1H); 13 C NMR (125MHz, CDCl3) δ-0.58, 24.8, 56.4, 83.6, 101.6, 113.0, 115.7, 131.2, 138.0, 139.2, 161.51.

[0107] Example 12

[0108] This embodiment provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, the method comprising:

[0109] 2-Methoxybenzonitrile (0.2 mmol), B2Pin2 (0.2 mmol), [Ir(COD)OMe]2 (0.0006 mmol), dtbpy (0.0012 mmol), BPh3 (0.2 mmol) were added to a dry reaction tube in sequence, and then 2 mL of p-xylene was added as a solvent. The reaction was carried out at 55° C. for 12 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate=10 / 1) to obtain 2-methoxy-5-pinacol boron ester-benzonitrile, the chemical structure of which is shown in Formula 14.

[0110]

[0111] The total yield of the borylation product is 72%, the ratio of the meta-isomer to the para-isomer is greater than 15, and the product is a white solid.

[0112] 1 H NMR (500MHz, CDCl3) δ1.24 (s, 12H), 3.90 (s, 3H),, 7.03 (d, J = 8.8Hz, 1H), 7.85 (d, J = 1.9Hz, 1H), 7.89 (dd, J = 8.8, 2.0Hz, 1H); 113 C NMR (125MHz, CDCl3) δ24.8,56.4,83.6,101.6,113.0,115.7,131.2,138.0,139.2,161.5.

[0113] Example 13

[0114] This embodiment provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, the method comprising:

[0115] 1-(2-methoxyphenyl)pyrrole (0.2mmol), B2Pin2 (0.2mmol), [Ir(COD)OMe]2 (0.0006mmol), dtbpy (0.0012mmol), BPh3 (0.2mmol) were added to a dry reaction tube in sequence, and then 2mL of p-xylene was added as a solvent. The reaction was carried out at 55°C for 12 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain 1-(2-methoxy-5-pinacol boroyl)phenyl)pyrrole, the chemical structure of which is shown in Formula 15.

[0116]

[0117] The total yield of the borylation product was 72%, the ratio of the meta-isomer to the para-isomer was greater than 15, and the product was a colorless oil.

[0118] 1 H NMR (400MHz, CDCl3) δ1.24(s,12H),1.98(s,4H),3.53-3.57(m,4H),3.87(s,3 H), 6.76 (d, J = 9.3Hz, 1H), 7.30 (d, J = 1.9Hz, 1H), 7.44 (dd, J = 9.2, 1.9Hz, 1H); 13C NMR (100MHz, CDCl3) δ24.8,25.4,51.8,55.0,83.6,114.2,121.0,129.1,131.0,140.6,151.8.

[0119] Embodiment 14

[0120] This embodiment provides a method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, the method comprising:

[0121] 4-(2-methoxyphenyl)morpholine (0.2mmol), B2Pin2 (0.2mmol), [Ir(COD)OMe]2 (0.0006mmol), dtbpy (0.0012mmol), BPh3 (0.2mmol) were added to a dry reaction tube in sequence, and then 2mL of p-xylene was added as a solvent. The reaction was carried out at 55°C for 12 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product was separated by column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain 4-(2-methoxy-5-pinacol boroyl)phenyl)morpholine, the chemical structure of which is shown in Formula 16.

[0122]

[0123]

[0124] The total yield of the borylation product was 55%, the ratio of the meta-isomer to the para-isomer was greater than 15, and the product was a colorless oil.

[0125] 1 H NMR (400MHz, CDCl3) δ1.24(s,12H),3.18(dd,J=6.0,3.3Hz,2H),3.27(dd,J=6.1,3.4Hz,2H),3.78–3.84(m,4H) , 3.87(s,3H),6.76(d,J=9.3Hz,1H),7.26(d,J=1.9Hz,1H),7.44(dd,J=9.2,1.9Hz,1H); 13 C NMR (100MHz, CDCl3) δ24.8,50.2,55.0,66.7,83.6,114.0,122.1,129.2,131.0,140.7,152.7.

[0126] Comparative Example 1

[0127] Except that BPh3 is not added, the other conditions of this comparative example are the same as those of Example 2.

[0128] The total yield of the prepared borylation product is 80%, and the ratio of the meta-isomer to the para-isomer is 2:1.

[0129] Comparative Example 2

[0130] In this comparative example, except that BPh3 is replaced by perfluorotriphenylboron, the other conditions are the same as those in Example 2.

[0131] The total yield of the prepared borylation product is 15%, and only the para-isomer is generated.

[0132] Comparative Example 3

[0133] Except that BPh3 is replaced by boric acid, the other conditions in this comparative example are the same as those in Example 2.

[0134] The reaction could not proceed.

[0135] The applicant declares that the present invention illustrates the detailed structural features of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned detailed structural features, that is, it does not mean that the present invention must rely on the above-mentioned detailed structural features to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of the components selected by the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

[0136] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0137] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

[0138] In addition, various embodiments of the present invention may be arbitrarily combined, and as long as they do not violate the concept of the present invention, they should also be regarded as the contents disclosed by the present invention.

Claims

1. A method for selectively synthesizing anisole compounds substituted with para-pinacol boronate, characterized in that: The synthesis method comprises: The phenyl ether compound shown in Formula 1 and pinacol boron ester are reacted under the catalysis of an organic boron catalyst and a noble metal catalyst; Wherein, R is any one of hydrogen, halogen, C1-C12 alkyl, C1-C12 alkoxy, ester, cyano, amido, trimethylsilyl, triethylsilyl, trimethoxysilyl or triethoxysilyl; R1 is a C1-C5 straight-chain alkyl; The pinacol borate is selected from biboric acid pinacol borate or isopropyl pinacol borate; The molar ratio of the phenyl ether compound to the organic boron catalyst is 1:1-2; The organic boron catalyst is selected from triphenylboron or perfluorotriphenylboron; The noble metal catalyst is selected from an Ir complex formed by the reaction of [Ir(COD)OMe]2 and 4,4'-di-tert-butylbipyridine, and the molar ratio of [Ir(COD)OMe]2 to 4,4'-di-tert-butylbipyridine is 1:

2.

2. The method according to claim 1, characterized in that The molar ratio of the phenyl ether compound to the pinacol boron ester is 1:0.4-0.

6.

3. The method according to claim 1, characterized in that The molar ratio of the phenyl ether compound to the noble metal catalyst is 1:0.02-0.

04.

4. The method according to claim 1, characterized in that: The reaction is carried out in an organic solvent, and the organic solvent includes any one of p-xylene, cyclohexane, petroleum ether, ethyl acetate, dichloromethane, toluene or diethyl ether, or a combination of at least two thereof.

5. The method according to claim 1, characterized in that The reaction temperature is 50-55°C.

6. The method according to claim 1, characterized in that The reaction time is 8 to 24 hours.

7. The method according to claim 1, characterized in that After the reaction is completed, the product is separated by recrystallization, thin layer chromatography or column chromatography under reduced pressure distillation.

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