A method for the visible light-catalyzed synthesis of 3-fluoroindole compounds

Abstract

This invention relates to the field of organic synthesis and discloses a method for the visible-light photocatalytic synthesis of 3-fluoroindole oxides. This method utilizes a benzothiazole-substituted sulfone group as the leaving group, achieving efficient preparation of 3-fluoro-3-alkyl-N-methylindole oxides with a fluorine-containing quaternary carbon center under excited-state photocatalytic redox conditions. Compared with traditional methods for synthesizing 3-fluoroindole oxides, this invention has the following advantages: convenient substrate preparation; mild reaction conditions; and good functional group compatibility.

Description

Technical Field

[0001] This invention relates to the field of organic chemical synthesis, and specifically to a novel method for synthesizing 3-fluoro-oxidized indole compounds via visible light catalysis. Background Technology

[0002] Fluorinated organic compounds play an irreplaceable role in many fields such as medicine, pesticides, and materials science. Therefore, the precise and efficient selective synthesis of fluorinated compounds has always been a popular research direction in organic chemistry. Among the many fluorinated organic compounds, the 3-fluoro-oxidized indole structure with a fluorine-containing quaternary carbon center has received increasing attention in recent years due to its potential applications in medicinal chemistry (Bioorg. Med. Chem. Lett. 2002, 12, 1023; Nat. Med. 2001, 7, 471.).

[0003] Currently, the preparation of 3-fluoroindole structures with fluorine-containing quaternary carbon centers mainly relies on transition metal-catalyzed coupling reactions, electrochemical oxidative coupling reactions, rearrangement reactions involving difluorocarbenes, and fluoroaromatization reactions of carbenes. Examples of these reactions will be provided below. Reference 1 (Angew. Chem. Int. Ed. 2012, 511, 2870) discloses a method for enantioselectively synthesizing 3-fluoroindole using α-arylation catalyzed by chiral monodentate N-heterocyclic carbene (NHC) ligands. The specific reaction process is shown below:

[0004]

[0005] Reference 2 (Angew. Chem. Int. Ed. 2017, 56, 4734) discloses a method for the intramolecular C(sp) of fluoromalonic acid amide under electrochemical conditions. 3 )-H and C(sp 2 The method for synthesizing 3-fluoroindole via a dehydrogenation coupling reaction between H bonds is shown below:

[0006]

[0007] Reference 3 (CCS Chem. 2022, 4, 1671) discloses a method for the rapid synthesis of 3-fluoroindole via intramolecular rearrangement of in-situ generated difluorocarbene reacting with 2-aminoaryl ketones. The specific reaction process is shown below:

[0008]

[0009] Reference 4 (J.Org.Chem.2016, 81, 6887) discloses a method for synthesizing 3-fluoroindole via in-situ denitrification and fluoroarylation of N-aryl α-diazoamide and N-fluorobenzenesulfonylimide. The specific reaction process is as follows:

[0010]

[0011] However, the above strategies all have some shortcomings, such as difficulty in raw material preparation, inconvenience in operation, and the need to use unstable diazo compounds. Therefore, developing a new strategy to achieve convenient and efficient construction of this potential bioactive framework structure is still of great value. Summary of the Invention

[0012] This invention provides a novel method for the visible light-catalyzed synthesis of 3-fluoro-oxidized indole compounds, which has the advantages of mild reaction conditions, high separation yield, and broad functional group compatibility.

[0013] To solve the technical problem of this invention, the proposed technical solution is: a novel method for synthesizing 3-fluoroindole compounds via photocatalysis, comprising the following steps:

[0014] Step 1: Under a nitrogen atmosphere, the photocatalyst and the α-fluoro-α-sulfonyl-N-arylamide compound (Formula 1) are added to the solvent, and the resulting mixture is stirred under the irradiation of a blue light lamp with a wavelength of 450-460 nm and a power of 8W.

[0015] Step 2: Quench the mixture obtained in Step 1 with a saturated ammonium chloride aqueous solution. Extract the aqueous phase with ethyl acetate, wash the combined organic phases with water and saturated brine successively, dry the organic phases with anhydrous sodium sulfate, concentrate and purify by silica gel column chromatography to obtain the 3-fluoroindole compound (Formula 2).

[0016] The specific reaction route is as follows:

[0017]

[0018] Where R 1 It is: hydrogen, 4-phenyl, 4-fluoro, 4-chloro, 3-chloro, 4-bromo, 4-trifluoromethyl, 4-methyl, 4-methoxy, 4-methyl ester, 3-tert-butyl, and other alkyl groups; R 2 The following are alkyl groups: methyl, ethyl, allyl, 3-bromopropyl, 3-cyanopropyl, benzyl, 4-fluorobenzyl, 4-bromobenzyl, 3-trifluoromethylbenzyl, 4-methylbenzyl, 4-methoxybenzyl, 4-methyl esterbenzyl, 1-methylnaphthyl and other alkyl groups.

[0019] Preferably, the photocatalyst is tris(2-phenylpyridine)iridium, fac-Ir(ppy)3.

[0020] Preferably, the solvent is anhydrous N,N-dimethylformamide.

[0021] Preferably, the reaction temperature is 25°C and the reaction time is 12 hours.

[0022] Preferably, the reaction molar ratio is α-fluoro-α-sulfonyl-N-arylamide compound: tris(2-phenylpyridine)iridium = 1:0.01.

[0023] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0024] 1. This invention provides a novel method for synthesizing 3-fluoro-oxidized indole compounds, making the entire synthesis process more direct and easier to operate.

[0025] 2. The reaction system of the present invention is clean, has a high conversion rate, and the products are easy to separate.

[0026] 3. By optimizing reaction conditions, this invention can obtain the target compound in high yield, thereby reducing costs and improving efficiency.

[0027] 4. The method in this invention is compatible with various functional groups such as halogen, ester, cyano, and methoxy groups, providing possibilities for further structural modification.

[0028] 5. This invention is carried out under relatively mild reaction conditions, which helps to reduce potential environmental impact and may reduce the requirements for reaction equipment. Attached Figure Description

[0029] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below.

[0030] Figure 1 The nuclear magnetic resonance of 3-fluoro-1,3-dimethylindololin-2-one provided in Example 1 of this invention. 1 H spectrum;

[0031] Figure 2 The nuclear magnetic resonance of 3-fluoro-1,3-dimethylindololin-2-one provided in Example 1 of this invention. 19 F-spectrum;

[0032] Figure 3 The nuclear magnetic resonance of 3-fluoro-1,3-dimethylindololin-2-one provided in Example 1 of this invention. 13 C spectrum; Detailed Implementation

[0033] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0034] The method of this invention can synthesize various types of 3-fluoroindole compounds through the same mechanism, depending on the structure of the reaction substrate. The specific structural formula of the target product is as follows:

[0035]

[0036] 3-fluoro-1,3-dimethylindolin-2-one(2a):

[0037]

[0038] 1 H NMR (400MHz, CDCl3): δ7.47-7.34 (m, 2H), 7.12 (t, J=7.5Hz, 1H), 6.85 (d, J=7.8Hz, 1H), 3.20 (s, 3H), 1.76 (d, J=22.1Hz, 3H). 13 C NMR (101MHz, CDCl3): δ173.26 (d, J=22.0Hz), 143.65 (d, J=4.9Hz), 131.18 (d, J=2.6Hz), 127.34 (d, J =18.4Hz), 124.18, 123.38 (d, J = 2.3Hz), 108.80, 91.00 (d, J = 183.6Hz), 26.32, 21.29 (d, J = 29.5Hz). 19 F NMR (376MHz, CDCl3): δ-152.60 (q, J=22.1Hz). HRMS (ESI, m / z): calcd.for C 10 H 11 FNO[M+H] + :180.0819, found:180.0816.

[0039] 3-fluoro-1,3-dimethyl-5-phenylindolin-2-one(2b):

[0040]

[0041] 1H NMR(400MHz,CDCl3):δ7.66(t,J=1.9Hz,1H),7.62-7.60(m,1H),7.57-7.55(m,2H),7.47-7.43(m,2H),7.38-7.34(m,1H),6.92(d,J=8.2Hz,1H),3.24(s,3H),1.81(d,J=22.2Hz,3H). 13 C NMR(101MHz,CDCl3):6173.28(d,J=21.8Hz),142.91(d,J=4.9Hz),140.34,136.96(d,J=2.1Hz),129.89(d,J=2.5Hz),129.03,128.00,127.82,127.46,127.17,126.90,123.15,109.12,91.11(d,J=184.3Hz),26.47,21.38(d,J=29.5Hz). 19 FNMR(376MHz,CDCl3):δ-152.30(q,J=22.8Hz).HRMS(ESI,m / z):calcd.for C 16 H 15 FNO[M+H] + :256.1132,found:256.1133.

[0042] 3,5-difluoro-1,3-dimethylindolin-2-one(2c):

[0043]

[0044] 1 H NMR(400MHz,CDCl3):δ7.17-7.14(m,1H),7.11-7.05(m,1H),6.79-6.76(m,1H),3.19(s,3H),1.74(d,J=22.1Hz,3H). 13 C NMR(101MHz,CDCl3):δ172.94(d,J=21.6Hz),159.53(dd,J=242.7,2.8Hz),139.50(d,J=5.16Hz),128.68(dd,J=18.5,7.8Hz),117.40(dd,J=23.6,2.3Hz),112.46(d,J=25.0Hz),109.57(d,J=7.9Hz),90.88(d,J=185.5Hz),26.48,21.29(d,J=29.0Hz). 19F NMR(376MHz,CDCl3):δ-119.13(t,J=9.3Hz),-153.31(q,J=21.9Hz).HRMS(ESI,m / z):calcd.for C 10 H 10 F2NO[M+H] + :198.0725,found:198.0728.

[0045] 5-chloro-3-fluoro-1,3-dimethylindolin-2-one(2d):

[0046]

[0047] 1 H NMR(400MHz,CDCl3):δ7.38(t,J=1.8Hz,1H),7.37-7.32(m,1H),6.77(d,J=8.1Hz,1H),3.18(s,3H),1.74(d,J=22.1Hz,3H). 13 C NMR(101MHz,CDCl3):δ172.75(d,J=21.5Hz),142.14(d,J=5.2Hz),131.05(d,J=2.8Hz),128.88,128.83(d,J=3.1Hz),128.69,109.89,90.69(d,J=185.8Hz),26.48,21.26(d,J=29.1Hz). 19 F NMR(376MHz,CDCl3):δ-153.11(q,J=22.3Hz).HRMS(ESI,m / z):calcd.for C 10 H 10 ClFNO[M+H] + :214.0429,found:214.0433.

[0048] 4-chloro-3-fluoro-1,3-dimethylindolin-2-one(2e):

[0049]

[0050] 1 H NMR(400MHz,CDCl3):δ7.33-7.27(m,1H),7.08-6.99(m,1H),6.78-6.68(m,1H),3.19(s,3H),1.92(d,J=21.9Hz,3H).13 C NMR(101MHz,CDCl3):δ172.62(d,J=21.4Hz),145.29(d,J=4.5Hz),132.32,132.11(d,J=2.2Hz),124.48(d,J=1.4Hz),123.91(d,J=17.8Hz),107.28,91.33(d,J=188.5Hz),26.57,19.37(d,J=28.6Hz). 19 F NMR(376MHz,CDCl3):δ-159.49(q,J=21.9Hz).HRMS(ESI,m / z):calcd.for C 10 H 10 ClFNO[M+H] + :214.0429,found:214.0433

[0051] 5-bromo-3-fluoro-1,3-dimethylindolin-2-one(2f):

[0052]

[0053] 1 H NMR(400MHz,CDCl3):δ7.58-7.43(m,2H),6.73(t,J=7.0Hz,1H),3.17(d,J=6.5Hz,3H),1.77-1.67(m,3H). 13 C NMR(101MHz,CDCl3):δ172.62(d,J=21.6Hz),142.64(d,J=4.9Hz),133.97(d,J=2.7Hz),129.11(d,J=18.7Hz),127.55(d,J=0.8Hz),115.96(d,J=3.0Hz),110.39(d,J=1.0Hz),90.64(dd,J=185.8,1.4Hz),26.46(d,J=1.2Hz),21.26(d,J=29.2Hz). 19 F NMR(376MHz,CDCl3):δ-152.98(q,J=22.2Hz).HRMS(ESI,m / z):calcd.for C 10 H 10 BrFNO[M+H] + :257.9924,found:257.9925.

[0054] 3-fluoro-1,3-dimethyl-5-(trifluoromethyl)indolin-2-one(2g):

[0055]

[0056] 1 H NMR(400MHz,CDCl3):δ7.77-7.58(m,2H),6.94(d,J=8.0Hz,1H),3.24(s,3H),1.79(d,J=22.1Hz,3H). 13 C NMR(101MHz,CDCl3):δ173.04(d,J=21.6Hz),146.62(d,J=4.0Hz),128.91,127.84(d,J=19.0Hz),125.78(dd,J=33.2,2.1Hz),124.05(d,J=271.6Hz),121.44(d,J=3.5Hz),108.74,90.29(d,J=185.8Hz),26.55,21.16(d,J=29.2Hz). 19 F NMR(376MHz,CDCl3):δ-61.69,-153.30(q,J=22.2Hz).HRMS(ESI,m / z):calcd.for C 11 H 10 F4NO[M+H] + :248.0693,found:248.0698.

[0057] 3-fluoro-1,3,5-trimethylindolin-2-one(2h):

[0058]

[0059] 1 H NMR(400MHz,CDCl3):δ7.22(s,1H),7.16(d,J=8.5Hz,1H),6.72(d,J=7.9Hz,1H),3.17(s,3H),2.34(s,3H),1.73(d,J=22.1Hz,3H). 13C NMR(101MHz,CDCl3):δ173.24(d,J=21.6Hz),141.21(d,J=5.0Hz),133.08(d,J=2.4Hz),131.34(d,J=2.7Hz),127.29(d,J=18.4Hz),124.97,108.58,91.21(d,J=183.6Hz),26.35,21.32(d,J=29.3Hz),21.10. 19 F NMR(376MHz,CDCl3);δ-152.38(q,J=22.1Hz).HRMS(ESI,m / z):calcd.forC 11 H 13 FNO[M+H] + :194.0976,found:194.0978.

[0060] 3-fluoro-5-methoxy-1,3-dimethylindolin-2-one(2i):

[0061]

[0062] 1 H NMR(400MHz,CDCl3):δ7.02(t,J=2.2Hz,1H),6.90-6.86(m,1H),6.74(d,J=8.5Hz,1H),3.79(s,3H),3.16(s,3H),1.73(d,J=22.2Hz,3H). 13 C NMR(101MHz,CDCl3):δ173.01(d,J=21.7Hz),156.55,136.85(d,J=5.2Hz),128.43(d,J=18.3Hz),115.45(d,J=2.8Hz),111.36(d,J=0.9Hz),109.34(d,J=1.2Hz),91.33(d,J=184.5Hz),55.98,26.40,21.42(d,J=29.2Hz). 19 F NMR(376MHz,CDCl3):δ-152.84(q,J=22.2Hz).HRMS(ESI,m / z):calcd.for C 11 H 13 FNO2[M+H] + :210.0925,found:210.0930.

[0063] methyl-3-fluoro-1,3-dimethyl-2-oxoindoline-5-carboxylate(2j):

[0064]

[0065] 1 H NMR(400MHz,CDCl3):δ8.12-8.09(m,1H),8.07-8.06(m,1H),6.88(d,J=8.2Hz,1H),3.90(s,3H),3.22(s,3H),1.76(d,J=22.1Hz,3H). 13 C NMR(101MHz,CDCl3):δ173.39(d,J=21.7Hz),166.36,147.64(d,J=4.6Hz),133.73(d,J=1.9Hz),127.26(d,J=19.0Hz),125.58,125.41(d,J=1.8Hz),108.50,90.36(d,J=185.2Hz),52.34,26.56,21.13(d,J=29.4Hz). 19 F NMR(376MHz,CDCl3):δ-152.81(q,J=22.1Hz).HRMS(ESI,m / z):calcd.for C 12 H 13 FNO3[M+H] + :238.0874,found:238.0876.

[0066] 4-(tert-butyl)-3-fluoro-1,3-dimethylindolin-2-one(2k):

[0067]

[0068] 1 H NMR(400MHz,CDCl3):δ7.32-7.26(m,1H),7.21(d,J=8.3Hz,1H),6.74-6.68(m,1H),3.18(s,3H),1.91(d,J=19.6Hz,3H),1.44(s,9H). 13C NMR(101MHz,CDCl3):δ174.11(d,J=23.6Hz),150.65,144.10,144.04,130.39,124.43,124.23,123.02,107.14,93.09(d,J=192.6Hz),36.62,32.60(d,J=4.6Hz),26.52,24.81(d,J=26.3Hz). 19 F NMR(376MHz,CDCl3):δ-156.14(q,J=19.6Hz).HRMS(ESI,m / z):calcd.for C 14 H 19 FNO[M+H] + :236.1445,found:236.1447.

[0069] 3-ethyl-3-fluoro-1-methylindolin-2-one(21):

[0070]

[0071] 1 H NMR(400MHz,CDCl3):δ7.39-7.35(m,2H),7.14-7.06(m,1H),6.88-6.78(m,1H),3.19(s,3H),2.22-2.13(m,2H),0.83(t,J=7.5Hz,3H). 13 C NMR(101MHz,CDCl3):δ173.12(d,J=21.5Hz),144.27(d,J=5.1Hz),131.08(d,J=2.6Hz),125.96(d,J=18.8Hz),124.57,123.26(d,J=2.0Hz),108.68,94.07(d,J=186.2Hz),28.25(d,J=27.8Hz),26.26,7.08(d,J=8.2Hz). 19 F NMR(376MHz,CDCl3):δ-157.23(t,J=14.2Hz).HRMS(ESI,m / z):calcd.for C 12 H 13 FNO[M+H] + :206.0976,found:206.0979.

[0072] 3-allyl-3-fluoro-1-methylindolin-2-one(2m):

[0073]

[0074] 1 H NMR(400MHz,CDCl3):δ7.46-7.31(m,2H),7.09(t,J=7.5Hz,1H),6.82(d,J=7.8Hz,1H),5.64-5.53(m,1H),5.14-5.08(m,2H),3.17(s,3H),3.01-2.93(m,1H),2.82-2.72(m,1H). 13 C NMR(101MHz,CDCl3):δ172.63(d,J=21.4Hz),144.05(d,J=5.3Hz),131.22(d,J=2.9Hz),129.04(d,J=8.4Hz),125.72,125.53,125.02(d,J=0.9Hz),123.21,123.19,92.44(d,J=188.9Hz),39.48(d,J=28.1Hz),26.29. 19 F NMR(376MHz,CDCl3):δ-156.87(dd,J=18.7,11.4Hz).HRMS(ESI,m / z):calcd.for C 12 H 13 FNO[M+H] + :206.0976,found:206.0979.

[0075] 3-(3-bromopropyl)-3-fluoro-1-methylindolin-2-one(2n):

[0076]

[0077] 1 H NMR(400MHz,CDCl3):δ7.41-7.36(m,2H),7.11(t,J=7.5Hz,1H),6.84(d,J=8.1Hz,1H),3.37(t,J=6.8Hz,2H),3.18(s,3H),2.31-2.22(m,2H),1.97-1.83(m,2H). 13CNMR(101MHz,CDCl3):δ172.67(d,J=21.6Hz),143.99(d,J=5.2Hz),131.42(d,J=2.9Hz),125.79(d,J=18.7Hz),124.61(d,J=1.2Hz),123.47(d,J=2.7Hz),108.91,92.65(d,J=187.6Hz),34.02(d,J=27.8Hz),32.94,26.37,25.94(d,J=6.3Hz). 19 F NMR(376MHz,CDCl3):δ-157.13(t,J=16.0Hz).HRMS(ESI,m / z):calcd.for C 12 H 14 BrFNO[M+H] + :286.0237,found:286.0241.

[0078] 4-(3-fluoro-1-methyl-2-oxoindolin-3-yl)butanenitriIe(2o):

[0079]

[0080] 1 H NMR(400MHz,CDCl3):δ7.44-7.38(m,2H),7.13(t,J=7.6Hz,1H),6.86(d,J=8.3Hz,1H),3.20(s,3H),2.43-2.36(m,2H),2.35-2.14(m,2H),1.86-1.74(m,2H). 13 C NMR(101MHz,CDCl3):δ172.37(d,J=21.7Hz),143.89(d,J=5.1Hz),131.62(d,J=2.6Hz),125.56(d,J=18.6Hz),124.53,123.59(d,J=2.0Hz),119.07,109.05,92.36(d,J=188.3Hz),34.24(d,J=28.0Hz),26.40,18.96(d,J=5.9Hz),17.26. 19 F NMR(376MHz,CDCl3):δ-158.29(t,J=16.8Hz).HRMS(ESI,m / z):calcd.for C 13 H 14 FN2O[M+H] +:233.1085,found:233.1086.

[0081] 3-benzyl-3-fluoro-1-methylindolin-2-one(2p):

[0082]

[0083] 1 H NMR(400MHz,CDCl3):δ7.33-7.28(m,1H),7.22-7.15(m,3H),7.10-7.03(m,2H),7.03-6.96(m,2H),6.70(d,J=7.8Hz,1H),3.58(dd,J=13.4,10.4Hz,1H),3.20(dd,J=22.6,13.4Hz,1H),3.07(s,3H). 13 C NMR(101MHz,CDCl3):δ172.84(d,J=21.1Hz),143.94(d,J=5.5Hz),132.79(d,J=6.9Hz),131.12(d,J=2.5Hz),130.66,128.16,127.33,125.49,125.21(d,J=19.1Hz),122.93(d,J=2.2Hz),108.60,93.32(d,J=190.6Hz),41.27(d,J=27.8Hz),26.19. 19 F NMR(376MHz,CDCl3):δ-156.24(dd,J=22.7,10.4Hz).HRMS(ESI,m / z):calcd.for C 16 H 15 FNO[M+H] + :256.1132,found:256.1131.

[0084] 3-fluoro-3-(4-fluorobenzyl)-1-methylindolin-2-one(2q):

[0085]

[0086] 1H NMR(400MHz,CDCl3):δ7.34-7.26(m,1H),7.03-6.95(m,4H),6.91-6.80(m,2H),6.70(d,J=7.7Hz,1H),3.51(dd,J=13.5,10.2Hz,1H),3.17(dd,J=21.8,13.5Hz,1H),3.05(s,3H). 13 C NMR(101MHz,CDCl3):δ172.65(d,J=21.0Hz),162.18(d,J=245.7Hz),143.93(d,J=5.4Hz),132.17(d,J=8.0Hz),131.25(d,J=2.5Hz),128.49(d,J=4.1Hz),125.32,125.03(d,J=19.2Hz),123.01(d,J=2.3Hz),115.07(d,J=21.2Hz),108.71,93.18(d,J=190.8Hz),40.43(d,J=28.1Hz),26.19. 19 F NMR(376MHz,CDCl3):δ-115.12(tt,J=9.2,5.3Hz),-156.43(dd,J=21.7,10.1Hz).HRMS(ESI,m / z):calcd.for C 16 H 14 F2NO[M+H] + :274.1038,foand:274.1036.

[0087] 3-(4-bromobenzyl)-3-fluoro-1-methylindolin-2-one(2r):

[0088]

[0089] 1 H NMR(400MHz,CDCl3):δ7.34-7.26(m,3H),7.04-6.97(m,2H),6.91(d,J=8.2Hz,2H),6.71(d,J=7.9Hz,1H),3.49(dd,J=13.4,10.2Hz,1H),3.15(dd,J=21.8,13.5Hz,1H),3.06(s,3H). 13C NMR(101MHz,CDCl3):δ172.53(d,J=21.0Hz),143.93(d,J=5-4Hz),132.34,132.33,131.80(d,J=7.2Hz),131.34,131.33,125.33(d,J=0.9Hz),124.91(d,J=19.1Hz),123.07(d,J=2.7Hz),108.80,92.93(d,J=190.9Hz),40.61(d,J=28.3Hz),26.25. 19 F NMR(376MHz,CDCl3):δ-155.97(dd,J=21.9,10.2Hz).HRMS(ESI,m / z):calcd.for C 16 H 14 BrFNO[M+H] + :334.0237,foand:334.0235.

[0090] 3-fluoro-1-methyl-3-(3-(trifluoromethyl)benzyl)indolin-2-one(2s):

[0091]

[0092] 1 H NMR(400MHz,CDCl3):δ7.45(d,J=7.4Hz,1H),7.34-7.26(m,3H),7.25(s,1H),7.06-6.92(m,2H),6.69(d,J=7.9Hz,1H),3.59(dd,J=13.4,10.3Hz,1H),3.25(dd,J=21.5,13.4Hz,1H),3.04(s,3H). 13 C NMR(101MHz,CDCl3):δ172.42(d,J=21.0Hz),143.79(d,J=5.4Hz),134.10,133.84(d,J=7.1Hz),131.42(d,J=2.1Hz),130.44(d,J=32.2Hz),128.65,127.29(d,J=3.3Hz),125.33,125.26,124.70(d,J=19.0Hz),124.20(d,J=3.7Hz),123.08(d,J=1.8Hz),108.79,92.94(d,J=191.9Hz),41.12(d,J=28.2Hz),26.15. 19F NMR(376MHz,CDCl3):δ-62.63,-157.33(dd,J=21.4,10.3Hz).HRMS(ESI,m / z):calcd.for C 17 H 14 F4NO[M+H] + :324.1006,foand:324.1005.

[0093] 3-fluoro-1-methyl-3-(4-methylbenzyl)ind0lin-2-one(2t):

[0094]

[0095] 1 H NMR(400MHz,CDCl3):δ7.34-7.26(m,1H),7.03-6.96(m,4H),6.93(d,J=8.0Hz,2H),6.69(d,J=7.8Hz,1H),3.52(dd,J=13.4,10.5Hz,1H),3.15(dd,J=22.7,13.5Hz,1H),3.06(d,J=1.1Hz,3H),2.26(s,3H). 13 C NMR(101MHz,CDCl3):δ172.92(d,J=21.1Hz),143.97(d,J=5.5Hz),136.88,131.04(d,J=2.4Hz),130.52,129.60(d,J=6.9Hz),128.87,125.51,125.35(d,J=19.2Hz),122.89(d,J=2.3Hz),108.58,93.32(d,J=190.0Hz),40.79(d,J=28.8Hz),26.19,21.20. 19 F NMR(376MHz,CDCl3):δ-155.89(dd,J=22.6,10.4Hz).HRMS(ESI,m / z):calcd.for C 17 H 17 FNO[M+H] + :270.1289,found:270.1293.

[0096] 3-fluoro-3-(4-methoxybenzyl)-1-methylindolin-2-one(2u):

[0097]

[0098] 1 H NMR(400MHz,CDCl3):δ7.33-7.27(m,1H),7.00(d,J=4.9Hz,2H),6.96(d,J=8.6Hz,2H),6.73-6.67(m,3H),3.74(s,3H),3.51(dd,J=13.5,10.2Hz,1H),3.14(dd,J=22.3,13.5Hz,1H),3.06(s,3H). 13 C NMR(101MHz,CDCl3):δ172.92(d,J=21.1Hz),158.79,143.96(d,J=5.4Hz),131.68,131.06(d,J=2.5Hz),125.45,125.24,124.67(d,J=7.4Hz),122.91(d,J=2.1Hz),113.53,108.61,93.38(d,J=190.0Hz),55.23,40.36(d,J=27.8Hz),26.19. 19 F NMR(376MHz,CDCl3):δ-156.19(dd,J=22.4,10.2Hz).HRMS(ESI,m / z):calcd.for C 17 H 17 FNO2[M+H] + :286.1238,found:286.1242.

[0099] methyl-4-((3-fluoro-1-methyl-2-oxoindolin-3-yl)methyl)benzoate(2v):

[0100]

[0101] 1 H NMR(400MHz,CDCl3):δ7.87-7.83(m,2H),7.33-7.27(m,1H),7.13(d,J=8.1Hz,2H),7.03-6.94(m,2H),6.69(d,J=7.8Hz,1H),3.87(s,3H),3.65-3.53(m,1H),3.31-3.17(m,1H),3.06(s,3H). 13C NMR(101MHz,CDCl3):δ172.47(d,J=21.1Hz),167.01,143.86(d,J=5.3Hz),138.18(d,J=6.9Hz),131.36(d,J=2.2Hz),130.72,129.42,129.20,125.35,124.80(d,J=18.9Hz),123.08(d,J=1.8Hz),108.77,92.98(d,J=191.4Hz),52.25,41.21(d,J=28.1Hz),26.24. 19 F NMR(376MHz,CDCl3):δ-155.89(dd,J=21.7,10.3Hz).HRMS(ESI,m / z):calcd.for C 18 H 17 FNO3[M+H] + :314.1187,found:314.1190.

[0102] 3-fluoro-1-methyl-3-(naphthalen-1-ylmethyl)indolin-2-one(2w):

[0103]

[0104] 1 H NMR(400MHz,CDCl3):δ7.98(d,J=8.6Hz,1H),7.83-7.75(m,2H),7.44-7.34(m,3H),7.30-7.20(m,2H),6.83-6.66(m,2H),6.59(d,J=7.5Hz,1H),4.11(dd,J=14.6,11.6Hz,1H),3.53(dd,J=29.3,14.6Hz,1H),3.13(s,3H). 13C NMR (101MHz, CDCl3): δ173.39 (d, J=21.3Hz), 143.75 (d, J=5.5Hz), 133.81, 132. 94, 130.97 (d, J = 2.8Hz), 129.79 (d, J = 1.0Hz), 129.61 (d, J = 3.3Hz), 128.57, 128. 33, 126.20, 125.94, 125.69, 125.19 (d, J = 19.3Hz), 125.02, 124.71 (d, J = 2.8Hz), 122.68 (d, J=2.6Hz), 108.58, 93.32 (d, J=191.8Hz), 37.37 (d, J=27.6Hz), 26.37. 19 F NMR (376MHz, CDCl3): δ-157.15 (dd, J=29.3, 11.6Hz). HRMS (ESI, m / z): calcd.for C 20 H 17 FNO[M+H] + :306.1289, found:306.1292.

[0105] Example 1

[0106] This embodiment describes the preparation of 3-fluoro-1,3-dimethylindolin-2-one. The specific procedures are as follows:

[0107]

[0108] Tris(2-phenylpyridine)iridium (0.002 mmol, 0.01 eq.) and 2-(benzo[d]thiazolyl-2-ylsulfinyl)-2-fluoro-N-methyl-N-phenylpropionamide (0.2 mmol, 1.0 eq.) were added to the reaction tube. The mixture was purged three times with nitrogen, and then anhydrous N,N-dimethylformamide (3 mL) was added under a nitrogen atmosphere. The mixture was stirred at room temperature for 12 h under blue LED light (450-460 nm, 8 W). The reaction was monitored by TLC. After completion, the reaction was quenched with saturated ammonium chloride aqueous solution (10 mL). The aqueous phase was extracted with ethyl acetate (3 × 5 mL). The combined organic phases were washed with water (10 mL) and saturated brine (10 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was then purified by column chromatography to obtain the final target product. The product was a white solid with a yield of 90%.

[0109] The results of the 1H NMR spectrum determination of 3-fluoro-1,3-dimethylindoline-2-one are as follows: 1¹H NMR (400MHz, CDCl₃): δ 7.47–7.34 (m, 2H), 7.12 (t, J = 7.5 Hz, 1H), 6.85 (d, J = 7.8 Hz, 1H), 3.20 (s, 3H), 1.76 (d, J = 22.1 Hz, 3H). The results of the fluorine NMR spectrum determination of 3-fluoro-1,3-dimethylindoline-2-one were as follows: 19 FNMR (376 MHz, CDCl3): δ -152.60 (q, J = 22.1 Hz). The results of the carbon NMR spectrum determination for 3-fluoro-1,3-dimethylindoline-2-one are as follows: 13 C NMR (100MHz, CDCl3): δ173.26 (d, J=22.0Hz), 143.65 (d, J=4.9Hz), 131.18 (d, J=2.6Hz), 127.34 (d, J =18.4Hz), 124.18, 123.38 (d, J = 2.3Hz), 108.80, 91.00 (d, J = 183.6Hz), 26.32, 21.29 (d, J = 29.5Hz).

[0110] The 1H NMR spectrum, fluorine NMR spectrum, and 3C NMR spectrum of compound 2a are as follows: Figure 1 , Figure 2 and Figure 3 As shown.

[0111] Examples 2-23

[0112] Examples 2-23 are basically the same as Example 1, except that the substituent R in the α-fluoro-α-sulfone-N-arylamide compound is... 1 and R 2 The specific structures of the α-fluoro-α-sulfone-N-arylamide compounds vary and are detailed in the table below:

[0113] Table 1 Examples 2-23

[0114]

[0115]

[0116]

[0117] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for the visible light-catalyzed synthesis of 3-fluoroindole compounds, characterized in that, Under excited-state photocatalyst redox conditions, the solution of α-fluoro-α-sulfone-N-arylamide compound undergoes a desulfonation intramolecular cyclization reaction to give 3-fluoro-oxidized indole compound; The molecular structure of the α-fluoro-α-sulfone-N-aryl amide is shown in Formula 1 below: The molecular structure of the 3-fluoroindole oxide is shown in Formula 2 below: In Equations 1 and 2, R 1 Selected from hydrogen, 4-phenyl, 4-fluoro, 4-chloro, 3-chloro, 4-bromo, 4-trifluoromethyl, 4-methyl, 4-methoxy, 4-methyl ester, 3-tert-butyl; R 2 Selected from methyl, ethyl, allyl, 3-bromopropyl, 3-cyanopropyl, benzyl, 4-fluorobenzyl, 4-bromobenzyl, 3-trifluoromethylbenzyl, 4-methylbenzyl, 4-methoxybenzyl, 4-methyl esterbenzyl; The photocatalyst is fac -Ir(ppy)3, where ppy is 2-phenylpyridine; The solvent is N,N-dimethylformamide.

2. The method for synthesizing 3-fluoroindole compounds by visible light catalysis according to claim 1, characterized in that, The method includes the following steps: (1) Under a nitrogen atmosphere, the photocatalyst and α-fluoro-α-sulfone-N-arylamide compound formula I are added to a solvent, and the resulting mixture is stirred under a blue light lamp with a wavelength of 450-460 nm and a power of 8 W until the reaction is complete. The photocatalyst is fac -Ir(ppy)3, where ppy is 2-phenylpyridine; the solvent is N,N-dimethylformamide; the molar ratio of α-fluoro-α-sulfonyl-N-arylamide compound to photocatalyst is 1.0:0.01; the reaction temperature is 25°C. o C; The reaction time is 12 hours; (2) Quench the mixture obtained in step (1) with a saturated ammonium chloride aqueous solution; extract the aqueous phase with ethyl acetate; wash the combined organic phase with water and saturated brine successively; dry the organic phase with anhydrous sodium sulfate; concentrate and then separate and purify by silica gel column chromatography to obtain 3-fluoro-oxidized indole compound formula II.

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