3-amino-1-indanone derivatives and processes for their preparation

Abstract

This invention discloses a 3-amino-1-indanone derivative and its preparation method, belonging to the field of organic synthesis technology. The preparation method includes the following steps: under the presence of a base, the o-cyanopropargyl ether substrate shown in Formula II and the arylating agent shown in Formula III are added to a solvent and reacted at room temperature to carry out the cyclization and coupling reaction as shown below, to obtain the 3-amino-1-indanone derivative shown in Formula I. This invention realizes a mild and efficient cyclization and coupling reaction of the o-cyanopropargyl ether substrate in the presence of a base and an arylating agent, and has the advantages of readily available raw materials, mild conditions, high reaction efficiency, functional group compatibility and good substrate universality.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and specifically relates to a method for preparing aryl difluoroalkyl compounds. Background Technology

[0002] Indanones are ubiquitous structural units with wide applications in medicine, pesticides, and materials science, and are also important structural units in dyes. Among them, 3-aminoindanone is an important class of indanone derivatives. Some molecules based on this core skeleton exhibit unique biological activities, such as compound A with antibacterial activity, topoisomerase I inhibitor B, and bispecific phosphatase inhibitor C. Representative 3-aminoindanone bioactive molecules are shown below. Furthermore, 3-aminoindanone can undergo various derivatization reactions, leading to important subsequent transformation applications. For example, it can undergo photochemical rearrangement to yield phthalamides, and can be hydrolyzed under acidic conditions to yield important organic synthetic intermediates such as 1,3-indanedione.

[0003]

[0004] Due to the unique advantages and important roles of 3-aminoindanone derivatives, the synthesis of functionalized 3-aminoindanone compounds has attracted widespread attention from organic chemists. Traditional methods for synthesizing 3-aminoindanone derivatives require saturated amounts of metal reagents or catalysts, and these reactions are often multi-step processes. The harsh reaction conditions result in poor substrate universality, low regioselectivity, and low yields. Therefore, developing mild and efficient methods for synthesizing 3-aminoindanone derivatives is of great significance for biomedicine, advanced materials, and other related fields.

[0005] Organoboron compounds possess advantages such as chemical stability, unique reactivity, low toxicity, good functional group tolerance, and the ability to undergo various transformation reactions, leading to their increasingly widespread application in organic synthesis. Boron, located in Group IIIA of the second period of the periodic table, has three valence electrons in its outermost shell. Neutral boron atoms have six valence electrons and an empty p orbital, making them relatively electron-deficient and exhibiting Lewis acidity, allowing them to accept lone pairs of electrons to form complexes. Organoboron reagents can be used as functional group transfer agents to achieve structural modification of various skeletal fragments, or to directly introduce boron-containing groups into active molecules, thereby obtaining a series of active molecular analogs through diverse transformation reactions. Therefore, applying organoboron compounds to methodological research is of great significance for the mild and efficient synthesis of complex drug structural fragments.

[0006] Triarylboranes are an important class of organoboron compounds, widely used in organic synthesis, olefin polymerization, and optoelectronic materials. Due to the electron deficiency of the boron center, triarylboranes have strong Lewis acidity and can effectively activate unsaturated compounds such as alkenes / alkynes, carbonyl compounds, imines, and nitriles, initiating a variety of tandem reactions. In these reactions, triarylboranes can not only participate in the reaction as an arylating agent in stoichiometric form, but also as a catalyst, which to some extent avoids the heavy metal pollution problem that may exist in the traditional method of using transition metal catalysts, and plays an increasingly important role in organic synthesis. However, there are some problems in this field: for example, (1) most reactions are currently limited to the application of B(C6F5)3, which is more expensive and has a stronger Lewis acidity, while the relatively inexpensive BPh3 is less studied due to its low reactivity. (2) The reaction modes are relatively limited. For example, a large part of the current reactions are based on the tandem reaction of alkenes, alkynes, and carbonyl compounds, while the use of triarylboranes to activate nitriles is limited. 1 No coordination-activated tandem cyclization reactions have been reported to date. We discovered that triarylborane compounds can coordinate with cyano groups to form tetracoordinate organoboron complexes. These complexes exhibit high reactivity, enabling the cyclization and coupling reactions of o-cyanopropyne ethers without the involvement of transition metals.

[0007] In summary, traditional methods for preparing 3-aminoindanone derivatives are still very limited, with previous reports often requiring transition metals and harsh reaction conditions. Based on existing research, we found that triarylboron can act as a mild and stable Lewis acid to activate the cyano group, promoting the addition of allenol silyl ether fragments to the cyano carbon and achieving a cyclization reaction. Since tetracoordinated boron can act as a bridging unit between the aryl and imine groups, facilitating 1,5-aryl migration, this method can be developed into a simple and efficient approach for preparing 3-aminoindanone compounds. Because transition metal catalysis often leaves behind toxic transition metal residues, requiring cumbersome post-processing and purification steps in drug development, this project utilizes the mild chemical properties of organoboron compounds to achieve a method for preparing 3-aminoindanone derivatives without the presence of transition metals. Summary of the Invention

[0008] This invention provides a 3-aminoindanone derivative and its preparation method. The proposed method does not require the use of transition metals, making it greener, more environmentally friendly, simpler, and more efficient. It will provide a more effective method for the diversified synthesis of 3-aminoindanone heterocyclic skeletons with potential pharmaceutical value. It also realizes a mild and efficient cyclization reaction of o-cyanopropynyl ether without the participation of transition metals.

[0009] To achieve the above-mentioned objectives, the technical solution of this invention is as follows:

[0010] A method for preparing a 3-amino-1-indanone derivative includes the following steps: under the presence of a base, adding the o-cyanopropargyl ether substrate shown in Formula II and the arylating agent shown in Formula III to a solvent, reacting at room temperature, and carrying out the cyclization and coupling reaction as shown below to obtain the 3-amino-1-indanone derivative shown in Formula I;

[0011]

[0012] In the o-cyanopropargyl ether derivatives as shown in Formula II: R1 may be the same or different, and each is independently selected from hydrogen atoms and halogens; R2 is independently selected from one or more of hydrogen atom, aryl, C1-C4 straight-chain or branched alkyl, C1-C4 straight-chain or branched alkoxy, carbocyclic, aryl, and unsaturated aryl. Among them, in the arylating reagents shown in Formula III: Ar is selected from one of the following: hydrogen atom, alkyl group, or halogen-substituted benzene ring.

[0013] In the preparation method described above: And / or, when any of the substituents in R1 and R2 is a halogen, the halogen is preferably fluorine, chlorine, or bromine; And / or, when any of the substituents in R1 and R2 is a straight-chain or branched alkyl group of C1-C6, the straight-chain or branched alkyl group of C1-C6 is a straight-chain or branched alkyl group of C1-C4. And / or, when any of R2 is a C1-C6 straight-chain or branched alkoxy group, the C1-C6 straight-chain or branched alkoxy group is a C1-C3 straight-chain or branched alkoxy group. And / or, when R2 is any carbon ring, the carbon ring is selected from 3- to 6-membered rings; The reaction equations for the coupling reaction are shown in any of the following examples: ;

[0014] Wherein, the alkali is potassium tert-butoxide ( t BuOK).

[0015] The arylating agent shown in Formula III is a triarylboron derivative.

[0016] The cyclization and coupling reactions are carried out under the protection of an inert gas, which is either nitrogen or argon. The molar ratio of the o-cyanopropargyl ether as shown in Formula II to the arylating agent is 1:1.1; The solvent is one of tetrahydrofuran and toluene; The molar volume ratio of the o-cyanopropyne ether as shown in Formula II to the solvent is 0.3 mmol / mL; The reaction time for the coupling reaction is 1-24 h; A 3-amino-1-indanone derivative is prepared by the above-described preparation method.

[0017] Compared with the prior art, the present invention has the following beneficial effects: This invention uses triarylboron derivatives as activating agents to activate the cyano group in the substrate of o-cyanopropynyl ether derivatives to form a tetracoordinated boron intermediate, which can serve as a bridging unit between aryl and imine groups via 1,5-aryl migration, thus realizing a mild and efficient method for preparing 3-aminoindanone derivatives.

[0018] This invention utilizes an inexpensive reaction system to prepare various functionally substituted 3-aminoindanone derivatives, offering advantages such as readily available raw materials, mild conditions, high reaction efficiency, functional group compatibility, and good substrate universality. This preparation method provides better application prospects and practical value for the industrial synthesis of functionally substituted 3-aminoindanone derivatives. Detailed Implementation

[0019] The technical solution of the present invention will be clearly and completely described below with reference to specific embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0020] Example 1: Screening for optimal reaction conditions:

[0021]

[0022] Table 1 Screening of conditions for the synthesis of 3-aminoindanone derivatives via triarylboron-promoted cyclization reactions. [a]

[0023] [a]: Reaction conditions: 1a (0.2 mmol), BAr3 (0.22 mmol), base (0.02 mmol), solvent (1.0 mL); [b]: Yield: NMR yield; [c]: Raw material recovery yield; [d]: Potassium tert-butoxide and triphenylborone were added to the reaction solution simultaneously.

[0024] We selected 1a as the template substrate, BPh3 as the arylation reagent, and toluene as the solvent to screen for bases. When using DBU as the base, the reaction time was 36 hours, and the target product was obtained in 50% yield. t When Buok is used as a base, the target product can be obtained in 80% yield. When CH3CN, 1,4-dioxane, and THF are used as bases, the target product can be obtained in 79% yield after 1 hour of reaction. However, the target product cannot be obtained when B(C6F5)3 is used as the arylating agent. Therefore, we use potassium tert-butoxide as a base, stir in tetrahydrofuran solvent for 2 minutes, then add triarylboron as the arylating agent, and react at room temperature for 1 hour as the optimal reaction conditions.

[0025] Example 2: ;

[0026] Under an argon atmosphere, o-cyanophenylpropargyl ether substrate 1a (104.3 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 4:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2a, which was a red solid with a yield of 80%. 1 H NMR (400 MHz, CDCl3) δ 7.36-7.34(m, 1H), 7.29-7.19 (m, 12H), 7.04-7.03 (m, 1H), 5.49 (s, 1H), 4.88 (bs, 2H). 13 IR (film): 3442, 3323, 3192,2920, 2845, 1705, 1630, 1606, 1553, 1425, 1213, 725 cm -1 HRMS (ESI) calcd for C22 H 18 NO [M+H] + : 312.1383, found 312.1384.

[0027] Example 3: ;

[0028] In a nitrogen-filled glove box, o-cyanophenylpropyne substrate (1 h, 124.7 mg, 0.3 mmol), toluene (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 24 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2a, which was a red solid with a yield of 77%. 1 H NMR (400 MHz, CDCl3) δ7.51-7.53 (m, 2H), 7.08-7.34 (m, 11H), 5.52 (s, 1H), 5.08 (bs, 2H). 13 C NMR (100 MHz, CDCl3) δ 192.90, 160.82, 146.28, 141.44, 138.51, 133.87, 131.10,130.18, 129.12, 128.81, 128.74 (q, J = 32.3 Hz), 128.68, 126.89, 125.44 (q, J = 3.8 Hz), 124.15 (q, J = 271.4 Hz), 120.52, 116.68, 107.19, 44.40. IR(film): 3334, 3201, 1708, 1632, 1552, 1424, 1322, 1162, 1107, 1066, 1018, 723cm -1 HRMS (ESI) calcd for C 23 H 17 F3NO [M+H] +380.1257, found 380.1258.

[0029] Example 4: ;

[0030] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1b (108.5 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to an 8 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2b, which was a red solid with a yield of 83%. 1 H NMR (400 MHz, CDCl3) δ7.30-7.17 (m, 8H), 7.08-7.06 (m, 5H), 5.42 (s, 1H), 5.16 (bs, 2H), 2.28 (s,3H). 13 C NMR (100 MHz, CDCl3) δ 193.1, 161.0, 142.4, 139.1, 138.7, 136.0,134.2, 130.9, 129.8, 129.2, 128.7, 128.6, 128.5, 126.4, 120.2, 116.7, 108.1,44.1, 20.9. IR (film): 3442, 3328, 3195, 2920, 1709, 1629, 1552, 1422, 1361,1219, 770, 718, 699 cm -1 HRMS (ESI) calcd for C 23 H 20 NO [M+H] + : 326.1539, found326.1542.

[0031] Example 5: ;

[0032] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1c (113.3 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at 100 °C for 0.1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2c, which was a red solid with a yield of 78%. 1 H NMR (400 MHz, CDCl3)δ 7.33-7.31 (m, 1H), 7.28-7.18 (m, 7H), 7.10 (d, J = 8.8 Hz, 2H), 7.06-7.04(m, 1H), 6.80 (d, J = 8.4 Hz, 2H), 5.42 (s, 1H), 5.03 (bs, 2H), 3.74 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 193.0, 160.7, 158.1, 142.6, 138.8, 134.1, 130.9,129.9, 129.7, 128.7, 128.5, 126.4, 120.3, 120.3, 116.5, 113.9, 108.4, 55.2,43.6. IR (film): 3445, 3326, 3198, 1708, 1629, 1607, 1552, 1508, 1442, 1246,1177, 1030, 719 cm -1 HRMS (ESI) calcd for C 23 H 20 NO2[M+H] + : 342.1489, found342.1492.

[0033] Example 6: ;

[0034] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1d (109.7 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness before column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2d, which was a red solid with a yield of 75%. 1 H NMR (400 MHz, CDCl3) δ7.35-7.15 (m, 10H), 7.07-7.06 (m, 1H), 6.95 (t, J = 8.8 Hz, 2H), 5.45 (s,1H), 4.96 (bs, 2H). 13 C NMR (100 MHz, CDCl3) δ 192.9, 161.5 (d, J = 243.8 Hz),160.3, 142.2, 138.7, 137.7 (d, J = 3.1 Hz), 133.9, 131.0, 130.3, 130.2,130.1, 128.7 (d, J = 3.5 Hz), 126.7, 120.5, 116.5, 115.3 (d, J = 21.3 Hz),108.1, 43.8. IR (film): 3445, 3326, 3195, 1705, 1628, 1605, 1549, 1505, 1423,1220, 1158, 855, 718, 699 cm -1 HRMS (ESI) calcd for C 22 H 17 FNO [M+H] + :330.1289, found 330.1291.

[0035] Example 7: ;

[0036] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1e (114.6 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2e, which was a red solid with a yield of 67%. 1 H NMR (400 MHz, DMSO-d6) δ7.89 (bs, 2H), 7.56 (d, J = 6.8 Hz, 2H), 7.39-7.25 (m, 10H), 7.20-7.16 (m, 1H), 5.30 (s, 1H). 13 C NMR (100 MHz, DMSO-d6) δ 190.2, 162.9, 143.1, 142.6,138.1, 135.1, 130.7, 130.5, 130.3, 130.1, 128.7, 128.1, 127.9, 125.9, 119.0,118.3, 105.1, 43.5. IR (film): 3450, 3317, 3190, 2920, 1705, 1627, 1608,1553, 1488, 1422, 1086, 1010, 766 cm -1 HRMS (ESI) calcd for C 22 H 17 ClNO [M+H] + :346.0993, found 346.0995.

[0037] Example 8: ;

[0038] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1f (104.3 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 6:1:1 (add 1% v / v Et3N) to give product 2f, which was a red solid with a yield of 65%. 1 H NMR (400 MHz, CDCl3) δ 7.90 (bs, 2H), 7.55 (d, J = 7.2 Hz, 1H), 7.46-7.43 (m, 2H), 7.39- 7.29 (m, 2H), 7.27-7.24 (m, 4H), 7.21-7.15 (m, 4H), 5.27(s, 1H). 13 C NMR (100 MHz, Chloroform- d ) δ 190.2, 162.9, 143.0(5), 143.0(1),138.1, 135.1, 130.9, 130.8, 130.7, 130.1, 128.7, 128.1, 125.9, 119.0, 118.8,118.3, 105.0, 43.5. IR (film): 3454, 3315, 3213, 1628, 1608, 1557, 1484,1424, 1010, 782, 731, 711 cm -1 .HRMS (ESI) calcd for C 22 H 17 BrNO [M+H] + : 390.0488, found 390.0490.

[0039] Example 9: ;

[0040] In a nitrogen-filled glove box, 1 g (129.5 mg, 0.3 mmol) of o-cyanophenylpropyne substrate, 1 mL of THF, and 3.4 mg (0.03 mmol) of potassium tert-butoxide were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 6:1:1 (add 1% v / v Et3N). 2 g of the product was obtained as a red solid, with a yield of 71%. 1 H NMR (400 MHz, CDCl3) δ 7.39-7.36 (m, 1H), 7.32-7.20 (m, 7H), 7.17-7.12 (m, 4H), 7.06- 7.04 (m, 1H), 5.49 (s, 1H), 4.9 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 192.9, 160.4, 147.8, 141.8, 140.7, 138.6, 133.8, 131.1, 130.2, 130.1, 128.8, 128.7, 126.8, 121.0, 120.6, 116.4, 115.4, 107.9, 43.9. 19 F NMR (376 MHz, CDCl3) δ -57.8. IR (film): 3356, 3193, 1634, 1609, 1553, 1453,1436, 1097, 1077, 740, 728, 697 cm -1 .HRMS (ESI) calcd for C 23 H 16 F3NNaO2[M+Na] + :418.1025, found 418.1035.

[0041] Example 10: ;

[0042] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate (124.7 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 24 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2a, which was a red solid with a yield of 77%. 1 H NMR (400 MHz, CDCl3) δ7.51-7.53 (m, 2H), 7.08-7.34 (m, 11H), 5.52 (s, 1H), 5.08 (bs, 2H). 13 C NMR (100 MHz, CDCl3) δ 192.90, 160.82, 146.28, 141.44, 138.51, 133.87, 131.10,130.18, 129.12, 128.81, 128.74 (q, J = 32.3 Hz), 128.68, 126.89, 125.44 (q, J = 3.8 Hz), 124.15 (q, J = 271.4 Hz), 120.52, 116.68, 107.19, 44.40. IR(film): 3334, 3201, 1708, 1632, 1552, 1424, 1322, 1162, 1107, 1066, 1018, 723cm -1 HRMS (ESI) calcd for C 23 H 17 F3NO [M+H] + 380.1257, found 380.1258.

[0043] Example 11: ;

[0044] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1i (125.9 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2i, which was a red solid with a yield of 64%. 1 H NMR (400 MHz, CDCl3) δ7.94 (d, J = 8.0 Hz, 2H), 7.33-7.34 (m, 1H), 7.21-7.29 (m, 7H), 7.15-7.16 (m,2H), 7.09-7.10 (m, 1H), 5.52 (s, 1H), 5.14 (bs, 2H), 4.33 (q, J = 7.2 Hz, 2H), 1.36 (t, J = 7.2 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 192.82, 166.45,160.83, 147.58, 141.50, 138.55, 133.92, 131.01, 130.06, 129.76, 128.77,128.69, 128.67, 128.64, 126.74, 120.40, 116.69, 107.25, 60.86, 44.50, 14.25.IR (film): 3445, 3334, 3200, 1713, 1632, 1608, 1553, 1426, 1277, 1104, 726cm -1 HRMS (ESI) calcd for C 25 H 22 NO3[M+H] + : 384.1594, found 384.1596.

[0045] Example 12: ;

[0046] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1j (104.3 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2j, which was a red solid with a yield of 87%. 1 H NMR (400 MHz, CDCl3) δ7.05-7.29 (m, 12H), 6.96-6.97 (m, 1H), 5.52 (s, 1H), 5.09 (bs, 2H), 2.23 (s,3H). 13 C NMR (100 MHz, CDCl3) δ 192.97, 161.29, 141.93, 140.60, 138.76,137.30, 133.95, 130.93, 130.75, 129.86, 128.71, 128.56, 127.84, 126.64,126.46, 125.92, 120.19, 116.63, 106.64, 41.99, 19.53. IR (film): 3434, 3312,3176, 1629, 1608, 1552, 1425, 1205, 1116, 853cm -1 HRMS (ESI) calcd for C 23 H 20 NO [M+H] + : 326.1539, found 326.1543.

[0047] Example 13: ;

[0048] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1k (116.9 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 3 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2k, which was a red solid with a yield of 73%. 1 H NMR (400 MHz, CDCl3) δ7.22-7.29 (m, 5H), 7.12-7.18 (m, 3H), 6.99-7.00 (m, 1H), 6.83 (s, 2H), 5.76(s, 1H), 4.77 (bs, 2H), 2.24 (s, 3H), 2.14 (s, 6H). 13 C NMR (100 MHz, CDCl3) δ193.89, 159.70, 141.17, 139.25, 137.36, 135.91, 135.28, 133.74, 130.88,130.17, 129.67, 128.50, 128.34, 125.99, 119.95, 116.35, 105.40, 41.23, 21.54,20.72. IR (film): 3462, 3320, 3206, 2918, 1707, 1622, 1560, 1544, 1424, 868,720cm -1 HRMS (ESI) calcd for C 25 H 24 NO [M+H] + : 354.1852, found 354.1855.

[0049] Example 14: ;

[0050] In a nitrogen-filled glove box, 1 L of o-cyanophenylpropyne substrate (119.3 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 4:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain 2 L of product, which was a red solid with a yield of 83%. 1 H NMR (400 MHz, CDCl3) δ7.95 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H),7.02-7.40 (m, 12H), 6.92 (d, J = 7.2 Hz, 1H), 6.05 (s, 1H), 5.10 (bs, 2H). 13 CNMR (100 MHz, CDCl3) δ 192.78, 161.93, 141.91, 138.86, 138.55, 133.90,133.83, 131.85, 130.90, 129.86, 128.91, 128.54, 128.50, 127.62, 126.52,126.32, 125.85, 125.54, 124.96, 124.18, 120.19, 116.67, 107.23, 41.32. IR(film): 3439, 3320, 3190, 3059, 1709, 1628, 1606, 1556, 1423, 1219, 774 cm -1 .HRMS (ESI) calcd for C 26 H 20 NO [M+H] + : 362.1539, found 362.1541.

[0051] Example 15: ;

[0052] In a nitrogen-filled glove box, 1m of o-cyanophenylpropyne substrate (106.1 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2m, which was a red solid with a yield of 49%. 1 H NMR (400 MHz, CDCl3) δ7.17-7.36 (m, 9H), 7.10-7.12 (m, 1H), 6.90 (s, 1H), 6.74 (s, 1H), 5.65 (s,1H), 5.21 (bs, 2H). 13 C NMR (100 MHz, CDCl3) δ 192.40, 160.67, 146.62, 142.09,138.54, 133.99, 131.02, 130.09, 128.58, 128.20, 126.88, 126.66, 125.88,124.69, 120.52, 116.73, 108.18, 39.78. IR (film): 3426, 3309, 3176, 1627,1606, 1427, 1227, 1058, 698 cm -1 HRMS (ESI) calcd for C 20 H 16 NOS [M+H] + :318.0947, found 318.0950.

[0053] Example 16: ;

[0054] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1n (104.6 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 24 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2n, which was a red solid with a yield of 33%. 1 H NMR (400 MHz, CDCl3) δ8.49-8.50 (m, 1H), 7.65-7.69 (m, 1H), 7.42-7.46 (m, 2H), 7.14-7.30 (m, 8H), 7.08-7.09 (m, 1H), 5.60 (s, 1H). 13 C NMR (100 MHz, CDCl3) δ 192.13, 162.71,162.63, 148.54, 141.84, 138.35, 137.41, 135.04, 130.61, 129.98, 128.09,128.01, 126.07, 124.39, 121.56, 120.27, 116.60, 105.65, 46.30. IR (film): 3317, 3145, 2920, 1709, 1627, 1590, 1541, 1430, 1355, 1219, 865, 717cm -1 .HRMS (ESI) calcd for C 21 H 17 N2O [M+H] + : 313.1335, found 313.1340.

[0055] Example 17: ;

[0056] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1o (109.7 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 6:1:1 (add 1% v / v Et3N) to give product 2o, which was a red solid with a yield of 71%. 1 H NMR (400 MHz, DMSO- d 6) δ 7.77 (bs, 2H), 7.46 (dd, J = 8.8, 2.4 Hz,1H), 7.28-7.23 (m, 8H), 7.20-7.14 (m, 3H), 7.11-7.06 (m, 1H), 5.29 (s, 1H). 13 C NMR (100 MHz, DMSO- d 6) δ 189.2, 164.3 (d, J = 245.1 Hz), 160.7(d, J = 1.8Hz), 143.2, 141.5 (d, J = 9.5 Hz), 130.9 (d, J = 2.7 Hz), 128.7, 128.0,125.8, 120.6 (d, J = 9.4 Hz), 115.1(d, J = 22.4 Hz), 107.3 (d, J = 26.2 Hz), 106.7, 44.1. 19 F NMR (376 MHz, Chloroform- d ) δ -108.4. IR (film): 3462, 3315,3216, 3054, 1629, 1566, 1478, 1409, 1211, 746, 698, 656 cm -1 HRMS (ESI) calcd for C 22 H 17 FNO [M+H] + : 330.1289, found 330.1284.

[0057] Example 18: ;

[0058] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1p (127.9 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 6:1:1 (add 1% v / v Et3N) to give product 2p, which was a red solid with a yield of 62%. 1 H NMR (400 MHz, DMSO- d 6) δ 7.95 (bs, 2H), 7.61 (dd, J = 7.6, 2.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.26-7.24 (m, 9H), 7.19-7.14 (m, 2H), 5.29 (s,1H). 13 C NMR (100 MHz, DMSO- d 6) δ 188.4, 162.5, 143.2, 137.5, 137.1, 133.0,128.7, 128.0, 125.8, 123.2, 121.9, 120.2, 106.2, 44.1. IR (film): 3456, 3215,1629, 1600, 1559, 1428, 740, 719, 700 cm -1 HRMS (ESI) calcd for C 22 H 17 BrNO [M+H] + : 390.0488, found 390.0483.

[0059] Example 19: ;

[0060] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1q (94.1 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2q, which was a red solid with a yield of 76%. 1 H NMR (400 MHz, C6D6) δ7.39-7.42 (m, 3H), 7.14 (t, J = 7.6 Hz, 2H), 7.03 (t, J = 7.2 Hz, 1H), 6.86-6.96 (m, 3H), 5.41 (s, 2H), 3.99–4.03 (m, 1H), 2.15–2.25 (m, 1H), 1.96–2.05(m, 1H), 1.35–1.48 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H). 13 C NMR (100 MHz, C6D6)δ 193.61, 161.48, 144.82, 139.17, 135.39, 130.94, 130.05, 128.83, 128.19,126.29, 120.39, 117.19, 108.99, 39.66, 35.35, 21.92, 14.45. IR (film): 3351,3203, 2954, 2926, 1705, 1627, 1607, 1545, 1422, 1219, 1088, 771, 721 cm -1 .HRMS (ESI) calcd for C 19 H 20 NO [M+H] + : 278.1539, found 278.1543.

[0061] Example 20: ;

[0062] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1r (98.3 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N) to give product 2r, which was a red solid with a yield of 93%. 1 H NMR (400 MHz, CDCl3) δ 7.35 (t, J = 7.6 Hz, 3H), 7.22-7.30 (m, 4H), 7.17 (t, J = 7.4 Hz, 1H), 7.02–7.04 (m, 1H), 5.13 (s, 2H), 3.88 (t, J = 7.8Hz, 1H), 2.00-2.08 (m, 2H), 1.32-1.37 (m, 4H), 0.86 (t, J = 6.8 Hz, 3H). 13 CNMR (100 MHz, CDCl3) δ 193.44, 160.12, 143.88, 138.58, 134.32, 130.77,129.76, 128.53, 127.65, 126.09, 120.17, 116.09, 109.36, 39.00, 32.14, 30.30,22.74, 14.03. IR (film): 3351, 3212, 2956, 2923, 2856, 1707, 1629, 1608,1548, 1423, 1222, 1089, 772, 722cm -1 HRMS (ESI) calcd for C 20 H 22 NO [M+H] + :292.1696, found 292.1699.

[0063] Example 21: ;

[0064] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1a (93.5 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2s, which was a red solid with a yield of 62%. 1 H NMR (400 MHz, C6D6) δ7.40-7.46 (m, 3H), 7.14 (t, J = 7.4 Hz, 2H), 7.04 (t, J = 7.4 Hz, 1H), 6.86-6.97 (m, 3H), 5.30 (s, 2H), 3.58 (d, J = 9.2 Hz, 1H), 1.31-1.36 (m, 1H), 0.39-0.53 (m, 3H), 0.22-0.27 (m, 1H). 13 C NMR (100 MHz, C6D6) δ 193.45,161.15, 144.06, 139.37, 135.28, 130.97, 130.06, 128.78, 126.42, 120.49,117.28, 109.28, 43.31, 14.40, 5.86, 4.54. IR (film): 3326, 3195, 1706, 1606,1549, 1422, 1220, 771, 721, 698 cm -1 HRMS (ESI) calcd for C 19 H 18 NO [M+H] + :276.1383, found 276.1386.

[0065] Example 22: ;

[0066] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1v (117.5 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 6:1:1 (add 1% v / v Et3N) to give product 2v, which was a red solid with a yield of 72%. 1 H NMR (400 MHz, CDCl3) δ 7.38-7.34 (m, 3H), 7.30-7.22 (m, 7H), 7.20-7.15 (m, 3H), 7.06-7.04 (m, 1H), 6.07 (s, 2H), 4.49 (s, 2H), 4.31 (t, J = 4.0Hz, 1H), 4.15 (dd, J = 9.6, 4.0 Hz, 1H), 3.96 (dd, J = 9.6, 3.6 Hz, 1H). 13 CNMR (400 MHz, CDCl3) δ 192.9, 161.7, 141.2, 138.6, 137.6, 134.7, 130.7,129.9, 128.4, 128.2, 128.0, 127.7, 127.6, 126.1, 120.22, 116.3, 107.1, 73.5,73.5, 39.1. IR (film): 3317, 3192, 3060, 3027, 2858, 1629, 1607, 1552, 1493,1475, 1431, 1362, 1207, 1097, 1076, 723, 698 cm -1 HRMS (ESI) calcd for C 24 H 22 NO2[M+H] + : 356.1645, found 356.1646.

[0067] Example 23: ;

[0068] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1x (117.2 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2u, which was a red solid with a yield of 48%. 1 H NMR (400 MHz, C6D6) δ7.43 (d, J = 7.6 Hz, 3H), 7.22 (t, J = 7.6 Hz, 2H), 7.11 (t, J = 7.6 Hz, 2H), 7.03 (t, J = 7.4 Hz, 1H), 6.87-6.89 (m, 2H), 6.74 (t, J = 7.2 Hz, 1H), 6.68 (d, J = 8.4 Hz, 2H), 6.62-6.64 (m, 1H), 4.77 (s, 2H), 4.32-4.38 (m, 1H), 4.10-4.20 (m, 2H), 2.58 (s, 3H). 13 C NMR (100 MHz, C6D6) δ 193.56, 161.87,149.16, 143.22, 138.64, 135.29, 130.83, 130.29, 129.64, 128.87, 128.72,126.73, 120.60, 116.85, 116.34, 112.58, 106.94, 56.07, 39.50, 39.09. IR(film): 3356, 3209, 1706, 1631, 1598, 1548, 1506, 1426, 1355, 1255, 748, 722cm -1 HRMS (ESI) calcd for C 24 H 23 N2O [M+H] +: 355.1805, found 355.1807.

[0069] Example 24: ;

[0070] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1v (104.4 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 24 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 5:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2v, which was a red solid with a yield of 65%. 1 H NMR (400 MHz, C6D6) δ7.34-7.43 (m, 3H), 7.11-7.16 (m, 2H), 7.01-7.05 (m, 1H), 6.84-6.91 (m, 3H),5.19 (s, 2H), 3.90 (t, J = 7.8 Hz, 1H), 3.20-3.23 (m, 2H), 2.09-2.24 (m, 2H), 1.66 (s, 2H). 13 C NMR (100 MHz, C6D6) δ 193.40, 161.31, 144.12, 138.94,135.20, 131.00, 130.23, 128.95, 128.06, 126.53, 120.52, 117.09, 108.20,45.36, 39.16, 31.60, 30.30. IR (film): 3356, 3212, 2926, 1702, 1629, 1548,1424, 759, 722, 699 cm -1 HRMS (ESI) calcd for C 19 H 19 ClNO [M+H] + : 312.1150, found 312.1151.

[0071] Example 25: ;

[0072] In a nitrogen-filled glove box, 1w of o-cyanophenylpropargyl ether substrate (104.3 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 6:1:1 (add 1% v / v Et3N), yielding 2w of product, which was a red solid with a yield of 60%. 1 H NMR (400 MHz, CDCl3) δ 7.42-7.40 (m, 1H), 7.33-7.25 (m, 6H), 7.22-7.18 (m, 1H), 7.07- 7.04 (m, 1H), 5.24 (s, 2H), 5.07-5.06 (m, 1H), 4.65 (d, J = 26.0 Hz, 2H), 1.88 (d, J = 0.8 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 193.0,160.2, 147.5, 141.1, 138.8, 134.0, 130.9, 129.9, 128.7, 128.4, 126.4, 120.6,116.0, 113.6, 106.4, 46.3, 23.0. IR (film): 3432, 3197, 1629, 1606, 1557,1474, 1452, 1427, 773, 723, 700 cm -1 HRMS (ESI) calcd for C 19 H 18 NO [M+H] + :276.1383, found 276.1385.

[0073] Example 26: ;

[0074] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1x (105.5 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 6:1:1 (add 1% v / v Et3N) to give product 2x, which was a red solid with a yield of 67%. 1 H NMR (400 MHz, CDCl3) δ 7.29-7.26 (m, 1H), 7.21-7.15 (m, 6H), 7.11-7.07 (m, 1H),, 7.03- 7.01 (m, 1H), 5.41 (s, 2H), 5.21 (q, J = 2.0 Hz, 1H), 4.51 (s, 1H), 1.99-1.90 (m, 4H), 1.58-1.46 (m, 4H). 13 C NMR (100 MHz, CDCl3) δ193.2, 160.9, 141.5, 139.4, 138.8, 134.2, 130.8, 129.8, 128.7, 128.3, 126.2,124.2, 120.2, 116.3, 106.8, 46.3, 28.9, 25.3, 23.0, 22.4. IR (film): 3431, 3203, 2925, 1629, 1607, 1556, 1425, 716, 700 cm -1 HRMS (ESI) calcd for C 22 H 22 NO [M+H] + : 316.1696, found 316.1700.

[0075] Example 27: ;

[0076] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1y (81.4 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of BPh3 (79.9 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 4:2:1 (add 1% v / v Et3N). The crude product was then washed with a mixed solvent of n-hexane / diethyl ether and dried to obtain product 2y, which was a red solid with a yield of 49%. 1 H NMR (400 MHz, CDCl3) δ7.37-7.39 (m, 1H), 7.24-7.26 (m, 6H), 7.17-7.19 (m, 1H), 7.05-7.07 (m, 1H), 5.14 (s, 2H), 3.63 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 193.36, 161.02, 139.44,138.49, 134.64, 130.83, 129.87, 128.62, 128.36, 126.17, 120.34, 116.23,105.41, 27.32. IR (film): 3328, 3195, 1706, 1629, 1548, 1434, 1073, 943, 771,719 cm -1 HRMS (ESI) calcd for C 16 H 14 NO [M+H] + : 236.1070, found 236.1074.

[0077] Example 28: ;

[0078] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1a (104.3 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of tris(4-methyl-phenyl)borane BPh3 (93.8 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 6:1:1 (add 1% v / v Et3N) to give product 2z, which was a red solid with a yield of 71%. 1 H NMR (400 MHz, CDCl3) δ 7.41-7.36 (m, 1H), 7.30-7.25 (m, 4H), 7.22-7.19 (m, 3H), 7.09 (s, 4H), 7.01-6.97 (m, 1H), 5.47 (s,1H), 4.70 (s, 2H), 2.31 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 192.9, 159.9,142.4, 139.2, 139.0, 136.1, 134.0, 130.9, 129.9, 129.3, 128.8, 128.7, 128.6,126.5, 120.6, 115.9, 108.8, 44.1, 21.0.

[0079] Example 29: ;

[0080] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1a (104.3 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of tris(4-fluorophenyl)borane (97.7 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 6:1:1 (add 1% v / v Et3N) to give product 2za, which was a red solid with a yield of 65%. 1H NMR (400 MHz, CDCl3) δ 7.42-7.38 (m, 1H), 7.32-7.28 (m,4H), 7.25- 7.16 (m, 5H), 7.03-6.95 (m, 3H), 5.49 (s, 1H), 4.67 (s, 2H). 13 CNMR (101 MHz, CDCl3) δ 192.8, 161.5 (d, J = 243.7 Hz), 159.8, 142.2, 138.8,137.7 (d, J = 3.4 Hz), 133.8, 131.0, 130.3, 130.2, 130.1, 128.7 (d, J = 2.3Hz), 126.7, 120.7, 116.0, 115.5 (d, J = 21.2 Hz), 108.5, 43.8.

[0081] Example 30: ;

[0082] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1a (104.3 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of tris(3,5-dimethyl-phenyl)borane (107.7 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 6:1:1 (add 1% v / v Et3N) to give product 2zb, which was a red solid with a yield of 58%. 1 H NMR (400 MHz, CDCl3) δ 7.31-7.15 (m, 8H), 7.06-7.04 (m, 1H), 6.82 (s, 1H), 6.79 (s, 2H), 5.39 (s, 1H), 5.13 (s, 2H), 2.21(s, 6H). 13C NMR (101 MHz, CDCl3) δ 193.0, 160.9, 142.3, 142.1, 138.8, 138.0,134.2, 130.9, 129.8, 128.8, 128.4, 128.2, 126.5, 126.3, 120.2, 116.6, 108.2,44.4, 21.3.

[0083] Example 31: ;

[0084] In a nitrogen-filled glove box, o-cyanophenylpropargyl ether substrate 1e (114.6 mg, 0.3 mmol), THF (1 mL), and potassium tert-butoxide (3.4 mg, 0.03 mmol) were added sequentially to a 4 mL vial sealed with a PTFE gasket. The mixture was stirred at room temperature for 2 min, followed by the addition of tris(4-chlorophenyl)borane (114.0 mg, 0.33 mmol). The system was sealed and removed from the glove box, and stirred at room temperature for 1 h. The reaction solution was filtered through a short silica gel column, and the filtrate was evaporated to dryness and then separated by column chromatography. The eluent was petroleum ether / ethyl acetate / dichloromethane = 6:1:1 (add 1% v / v Et3N), yielding product 2zc, which was a red solid with a yield of 56%. 1 H NMR (400 MHz, CDCl3) δ 7.45-7.42 (m, 1H), 7.34-7.32(m, 2H), 7.29- 7.26 (m, 4H), 7.16-7.12 (m, 4H), 7.02-7.00 (m, 1H), 5.45 (s,1H), 4.62 (s, 2H). 13 C NMR (100 MHz, CDCl3) δ 192.7, 160.1, 140.2, 138.5,133.7, 132.5, 131.1, 130.3, 130.0, 128.8, 120.7, 116.4, 107.5, 43.33.

[0085] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit them. Although the preferred embodiments have been described in detail, those skilled in the art can still make appropriate modifications or equivalent substitutions to the solutions of the present invention, and such modifications or substitutions should be considered to still fall within the spirit and scope of the technical solutions of the present invention.

Claims

1. A method for preparing a 3-amino-1-indanone derivative, characterized in that... The process includes the following steps: In the presence of a base, the o-cyanopropyne substrate shown in Formula II and the arylating agent shown in Formula III are added to a solvent and reacted at room temperature to carry out the cyclization and coupling reactions as shown below, to obtain the 3-amino-1-indanone derivative shown in Formula I. ； In the o-cyanopropargyl ether derivatives as shown in Formula II: R1 may be the same or different, and each is independently selected from hydrogen atoms and halogens; R2 is independently selected from one or more of hydrogen atom, aryl, C1-C4 straight-chain or branched alkyl, C1-C4 straight-chain or branched alkoxy, carbocyclic, aryl, and unsaturated aryl. In the arylating reagents shown in Formula III: Ar is selected from one of the following: hydrogen atom, alkyl group, or halogen-substituted benzene ring.

2. The preparation method according to claim 1, characterized in that: And / or, when any of the substituents in R1 and R2 is a halogen, the halogen is preferably fluorine, chlorine, or bromine; And / or, when any of the substituents in R1 and R2 is a straight-chain or branched alkyl group of C1-C6, the straight-chain or branched alkyl group of C1-C6 is a straight-chain or branched alkyl group of C1-C4. And / or, when any of R2 is a C1-C6 straight-chain or branched alkoxy group, the C1-C6 straight-chain or branched alkoxy group is a C1-C3 straight-chain or branched alkoxy group. And / or, when R2 is any carbon ring, the carbon ring is selected from 3- to 6-membered rings.

3. The preparation method according to claim 1, characterized in that: The reaction equations for the coupling reaction are shown in any of the following: ； 。 4. The preparation method according to claim 1, characterized in that: The alkali is potassium tert-butoxide.

5. The preparation method according to claim 1, characterized in that: The arylating agent shown in Formula III is a triarylboron derivative.

6. The preparation method according to claim 1, characterized in that: The cyclization and coupling reactions are carried out under the protection of an inert gas, which is either nitrogen or argon. The molar ratio of the o-cyanopropargyl ether as shown in Formula II to the arylating agent is 1:1.1; The solvent is one of tetrahydrofuran and toluene; The molar volume ratio of the o-cyanopropyne ether as shown in Formula II to the solvent is 0.3 mmol / mL; The reaction time for the coupling reaction is 1-24 h.

7. A 3-amino-1-indanone derivative, prepared by the method described in any one of claims 1-6.

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