Method for synthesizing 3-fluoro oxoindole compound through visible light catalysis

Abstract

The invention relates to the technical field of organic synthesis, and discloses a method for synthesizing a 3-fluoro oxoindole compound through visible light catalysis. According to the method, benzothiazole is used for replacing sulfuryl to serve as a leaving group, and efficient preparation of the 3-fluoro-3-alkyl-N-methyl oxoindole with the fluorine-containing quaternary carbon center is achieved under the condition of oxidation-reduction of the excited-state photocatalyst. Compared with a traditional 3-fluoro oxoindole compound synthesis method, the method has the following advantages that a substrate is convenient to prepare; the reaction conditions are mild; and the functional group compatibility is good.

Description

Technical Field

[0001] The invention relates to the field of organic chemical synthesis, and in particular to a new method for synthesizing 3-fluorooxidindole compounds by visible light catalysis. Background Art

[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 hot research direction in organic chemistry. Among the many fluorinated organic compounds, the 3-fluoroindole structure with a fluorinated quaternary carbon center has received increasing attention in recent years due to its potential application value in medicinal chemistry (Bioorg. Med. Chem. Lett. 2002, 12, 1023; Nat. Med. 2001, 7, 471.).

[0003] At present, the preparation of 3-fluoroindole with fluorine-containing quaternary carbon center mainly depends on transition metal catalyzed coupling reaction, electrochemical oxidative coupling reaction, rearrangement reaction involving difluorocarbene and fluoroaromatization reaction of carbene, which will be described by examples below. Document 1 (Angew.Chem.Int.Ed.2012,511,2870) discloses a method for enantioselectively synthesizing 3-fluoroindole by α-arylation reaction catalyzed by chiral monodentate N-heterocyclic carbene (NHC) ligand, and the specific reaction process is as follows:

[0004]

[0005] Document 2 (Angew.Chem.Int.Ed.2017, 56, 4734) discloses a method for preparing a novel nanostructured carbonyl fluoride by electrochemical reaction of the nanostructured carbonyl fluoride with fluoromalonamide. 3 )-H and C(sp 2 )-H bond dehydrogenation and hydrogenation coupling reaction to synthesize 3-fluoroindole, the specific reaction process is as follows:

[0006]

[0007] Document 3 (CCS Chem. 2022, 4, 1671) discloses a method for rapidly synthesizing 3-fluorooxindole by reacting in situ generated difluorocarbene with 2-aminoaryl ketone through intramolecular rearrangement. The specific reaction process is as follows:

[0008]

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

[0010]

[0011] However, the above strategies all have some shortcomings, such as difficulty in preparing raw materials, inconvenient operation, and the need to use unstable diazo compounds. Therefore, it is still of great value to develop a new strategy to achieve the convenient and efficient construction of this potential bioactive skeleton structure. Summary of the invention

[0012] The invention provides a new method for synthesizing 3-fluoroindole oxide compounds by visible light catalysis. The method has the advantages of mild reaction conditions, high separation yield, wide functional group compatibility, and the like.

[0013] In order to solve the technical problem of the present invention, a technical solution is proposed: a new method for synthesizing 3-fluoroindole compounds by photocatalysis, comprising the following steps:

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

[0015] Step 2: The mixture obtained in step 1 is quenched with a saturated aqueous solution of ammonium chloride. The aqueous phase is extracted with ethyl acetate, the combined organic phase is washed with water and saturated brine, the organic phase is dried with anhydrous sodium sulfate, concentrated, and separated and purified by silica gel column chromatography to obtain a 3-fluoroindole oxide compound (Formula 2).

[0016] The specific reaction route is as follows:

[0017]

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

[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 12h.

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

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] 1. The present invention provides a new method for synthesizing 3-fluoroindole compounds, which makes the entire synthesis process more direct and easy to operate.

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

[0026] 3. The present invention can obtain the target compound with a higher yield by optimizing the reaction conditions, thereby reducing costs and improving efficiency.

[0027] 4. The method of the present invention is compatible with various functional groups such as halogen, ester, cyano, methoxy, etc., providing the possibility for further structural modification.

[0028] 5. The present invention is carried out under relatively mild reaction conditions, which helps to reduce potential impacts on the environment and may reduce requirements for reaction equipment. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art are briefly introduced below.

[0030] Figure 1 The nuclear magnetic resonance of 3-fluoro-1,3-dimethylindolin-2-one provided in Example 1 of the present invention is 1 H spectrum;

[0031] Figure 2 The nuclear magnetic resonance of 3-fluoro-1,3-dimethylindolin-2-one provided in Example 1 of the present invention is 19 F spectrum;

[0032] Figure 3 The nuclear magnetic resonance of 3-fluoro-1,3-dimethylindolin-2-one provided in Example 1 of the present invention is 13 C spectrum; DETAILED DESCRIPTION

[0033] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0034] The method of the present invention can synthesize various types of 3-fluoroindole oxide compounds through the same mechanism according to the different structures of the reaction substrates. 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 example is used to prepare 3-fluoro-1,3-dimethylindolin-2-one. The specific operation is as follows:

[0107]

[0108] Tris(2-phenylpyridine)iridium (0.002mmol, 0.01eq.) and 2-(benzo[d]thiazol-2-ylsulfinyl)-2-fluoro-N-methyl-N-phenylpropionamide (0.2mmol, 1.0eq.) were added to the reaction tube. The nitrogen atmosphere was replaced three times, and anhydrous N,N-dimethylformamide (3mL) was added under nitrogen atmosphere. Stir at room temperature for 12h under the irradiation of a blue LED lamp (450-460nm, 8W). TLC spot plate monitoring, when the reaction is complete, quench with saturated ammonium chloride aqueous solution (10mL), extract the aqueous phase with ethyl acetate (3×5mL), wash the combined organic phase with water (10mL) and saturated brine (10mL), dry over anhydrous sodium sulfate, and concentrate under reduced pressure. The crude product is separated and purified by column chromatography to obtain the final target product. The product is a white solid with an isolation yield of 90%.

[0109] The results of the H NMR spectrum of 3-fluoro-1,3-dimethylindolin-2-one are as follows: 1H 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). The results of the determination of the nuclear magnetic resonance fluorine spectrum of 3-fluoro-1,3-dimethylindolin-2-one are as follows: 19 FNMR (376MHz, CDCl3): δ-152.60 (q, J = 22.1Hz). The results of the determination of the carbon nuclear magnetic resonance spectrum of 3-fluoro-1,3-dimethylindolin-2-one are: 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 H NMR, F NMR and C NMR spectra of compound 2a are shown in Figure 1 , Figure 2 and Figure 3 shown.

[0111] Embodiments 2 to 23

[0112] Examples 2 to 23 are substantially 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 α-fluoro-α-sulfone-N-arylamide compounds are shown in the following table:

[0113] Table 1 Examples 2 to 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 in the protection scope of the present invention.

Claims

1. A method for synthesizing 3-fluoroindole compounds by visible light catalysis, characterized in that: Under the redox condition of excited-state photocatalyst, the α-fluoro-α-sulfone-N-arylamide compound undergoes a desulfonation intramolecular cyclization reaction to obtain a 3-fluoroindole oxide compound.

2. The method for synthesizing 3-fluoroindole compounds by photocatalysis according to claim 1, characterized in that: The following steps are involved: Step 1: Under a nitrogen atmosphere, add a photocatalyst and an α-fluoro-α-sulfone-N-arylamide compound (Formula 1) into a solvent, and stir the resulting mixture under irradiation with a blue light having a wavelength of 450-460 nm and a power of 8 W until the reaction is complete. Step 2: The mixture obtained in step 1 is quenched with a saturated aqueous solution of ammonium chloride. The aqueous phase is extracted with ethyl acetate, the combined organic phase is washed with water and saturated brine, the organic phase is dried with anhydrous sodium sulfate, concentrated, and separated and purified by silica gel column chromatography to obtain a 3-fluoroindole oxide compound (Formula 2). The specific reaction route is as follows:

3. The method for synthesizing 3-fluoroindole compounds by photocatalysis according to claim 1, characterized in that: The photocatalyst is tris(2-phenylpyridine)iridium, fac-Ir(ppy)3.

4. The method for synthesizing 3-fluoroindole compounds by photocatalysis according to claim 1, characterized in that: The solvent is anhydrous N,N-dimethylformamide.

5. The method for synthesizing 3-fluorooxindole compounds by photocatalysis according to claim 1, characterized in that: The reaction temperature is 25°C; the reaction time is 12h.

6. The method for synthesizing 3-fluoroindole compounds by photocatalysis according to claim 1, characterized in that: The reaction molar ratio is α-fluoro-α-sulfone-N-arylamide compound: tris(2-phenylpyridine)iridium=1:0.

01.

7. The method for synthesizing 3-fluoroindole compounds by photocatalysis according to claim 1, characterized in that: The specific reaction route is as follows: Where R 1 R2 is: hydrogen, 4-phenyl, 4-fluoro, 4-chloro, 3-chloro, 4-bromo, 4-trifluoromethyl, 4-methyl, 4-methoxy, 4-carbomethoxy, 3-tert-butyl and other alkyl groups; R2 is: methyl, ethyl, allyl, 3-bromopropyl, 3-cyanopropyl, benzyl, 4-fluorobenzyl, 4-bromobenzyl, 3-trifluoromethylbenzyl, 4-methylbenzyl, 4-methoxybenzyl, 4-carbomethoxybenzyl, 1-methylnaphthyl and other alkyl groups.

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