Supporting Information Wiley-VCH 2013 69451 Weinheim, Germany Highly Enantioselective Construction of 3-Hydroxy xindoles through a Decarboxylative Aldol Addition of Trifluoromethyl a-fluorinated gem-diols to N-Benzyl Isatins** Ibrayim Saidalimu, Xiang Fang,* Xiao-Peng He, Jing Liang, Xueyan Yang, and Fanhong Wu* anie_201301443_sm_miscellaneous_information.pdf
Table of Contents 1. General... 2 2. General procedure and product characterization data for Table 1... 2 2.1 1,3-Dione substrates characterization data... 2 2.1.1 Product characterization data... 3 2.2 Synthesis of α-fluorinated gem-diols... 3 2.2.1 Product characterization data (Table 1)... 3 3. X-ray crystallography data for the 1a... 8 4. General procedure for asymmetric decarboxylative aldol reaction... 9 4.1 Product characterization data (Table 4)... 9 4.2 Product characterization data (Table 5)... 18 5. X-ray crystallography data for the major diastereomer of 3aa... 25 6. HPLC traces... 25 6.1 HPLC traces for Table 4... 25 6.2 HPLC traces for Table 5... 38 7. NMR spectra... 49 7.1 1 H NMR and 19 F NMR spectra for 1,3-dione... 49 7.2 1 H NMR, 13 C NMR and 19 F NMR spectra for α-fluorinated gem-diols (Table 1)... 50 7.3 1 H NMR, 19 F NMR and 13 C NMR spectra for Table 4... 68 7.4 1 H NMR, 19 F NMR and 13 C NMR spectra for Table 5... 86 8. 19 F NMR spectra for diastereoselectivities... 103
1. General All chemicals used in this study were obtained from commercial sources and used without further purification. The chromatographic purification of the products was conducted by flash chromatography using Merck silica gel 60 (200 300 mesh). IR spectra were measured on a Nicolet Magna IR-550 spectrometer using potassium bromide pellet. High resolution mass spectra were carried out on a Finnigan GC-MS-4021 spectrometer. 1 H NMR (400 MHz) and 13 C NMR (100.6 MHz) spectra were recorded on a Brucker AM-400 spectrometer with Me 4 Si as internal standard. 19 F NMR spectra were obtained on Brucker AM-400 (367.5 MHz) spectrometer in CDCl 3 with CFCl 3 as external standard, downfield shifts being designated as negative. All chemical shifts (δ) are expressed in ppm, coupling constants (J) are given in Hz. HPLC analysis was performed on a Waters 510 instrument with a 2487 detector using a Daicel Chiralpak D-H, AS-H or Chiralpak AD-H column. 2. General procedure and product characterization data for Table 1 2.1 1,3 Dione substrates characterization data To a stirred solution of sodium methoxide (60 mmol) in diethyl ether (25 ml) was added dropwise the solution of trifluoromethyl ethyl acetate (30 mmol) and acetophenone (30 mmol) in diethyl ether (25 ml), the mixture stirred for overnight at room temperature. Then resulting mixture was diluted with 1M HCl solution (PH=3) and extracted with ether, organic layer was dried over MgS 4. The solvent was removed under reduced pressure, and then purified by distillation or recrystallization
to afford the 4,4,4-trifluoro-3-hydroxy-1-phenylbut-2-en-1-one. 2.1.1 Product characterization data 4,4,4-trifluoro-3-hydroxy-1-phenylbut-2-en-1-one 1 H NMR (CDCl 3, 400 MH Z ) δ: 14.47 (s, 1H), 7.95 (d, 2 H, J = 7.2 H Z ), 7.63 (t, 1 H, J = 7.4 H Z ), 7.51 (t, 2 H, J = 7.8 H Z ), 6.58 (s, 1H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -76.48 (d, 3 F). 2.2 Synthesis of α fluorinated gem diols H R CF 3 a- l + Cu(N 3 ) 2.3H 2 H H Selectfluor R CF 3 CH 3 CN / H 2-20 o C F 1a-1l To a stirred solution of the 4,4,4-trifluoro-3-hydroxy-1-aryl(alkyl)-but-2-en-1-one (10 mmol) in the acetonitrile (50 ml) was added Cu(N 3 ) 2 3H 2 (20 mmol%). The mixture was stirred for 2h at room temperature, dropwise added selectfluoro (10 mmol) with the acetonitrile and water (50:4 ml) at -20 o C, keeping stirred for 6h, warmed to room temperature. The resulting solution was evaporated, extracted with ethyl acetate, dried over MgS 4. The solvent was removed under reduced pressure, and then purified by distillation or recrystallization to afford products (1a-1l). 2.2.1 Product characterization data (Table 1) 2,4,4,4-tetrafluoro-3,3-dihydroxy-1-phenylbutan-1-one (1a)
White solid. m.p.: 99.8-100.2. 1 H NMR (CDCl 3, 400 MH Z ) δ: 8.03 (d, 2 H, J = 8.4 H Z ), 7.69 (t, 1 H, J = 7.4 H Z ), 7.54 (t, 2 H, J = 8.0 H Z ), 5.72 (d, 1H, J = 47.6 H Z ), 4.78 (s, 1H), 4.52 (s, 1H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -83.72 (s, 3 F), -195.03 (q, 1 F, J = 11.2 H Z ). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 196.6 (d, J = 19.4 H Z ), 135.2, 129.7, 129.6, 128.9, 121.8 (q, J = 287.5 H Z ), 93.4 (dd, J = 26.3 H Z, J = 15.3 H Z ), 85.1 (d, J = 194.7 H Z ). EI-MS (m/z): 252 [M] +, 234, 106, 105 (100), 77. HRMS Calcd. for [C 10 H 7 F 3 2 ]: 252.0410; Found: 252.0409. 2,4,4,4-tetrafluoro-3,3-dihydroxy-1-m-tolylbutan-1-one (1b) White solid. m.p.: 86.6-87.3. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.83 (d, 2 H, J = 5.6 H Z ), 7.51 (d, 1 H, J = 8.0 H Z ), 7.42 (t, 1 H, J = 8.0 H Z ), 5.72 (d, 1H, J = 47.6 H Z ), 4.83 (s, 1H), 4.45 (s, 1H), 2.44 (s, 3H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -83.78 (s, 3 F), -194.84 (q, 1 F, J = 11.0 H Z ). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 196.7 (d, J = 18.8 H Z ), 138.9, 136.1, 134.6, 129.9, 128.8, 126.9, 121.6 (q, J = 287.0 H Z ), 93.0 (dd, J = 32.9 H Z, J = 22.2 H Z ), 84.8 (d, J = 193.9 H Z ), 21.3. 2,4,4,4-tetrafluoro-1-(4-fluorophenyl)-3,3-dihydroxybutan-1-one (1c) White solid. m.p.: 88.2-88.9. 1 H NMR (CDCl 3, 400 MH Z ) δ: 8.11-8.07 (m, 2 H), 7.21 (t, 2 H, J = 8.6 H Z ), 5.67 (d, 1H, J = 48.0 H Z ), 4.62 (s, 1H), 4.57 (s, 1H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -83.67 (s, 3 F), -100.44 (s, 1 F), -194.85 (q, 1 F, J = 11.6 H Z ). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 195.1 (d, J = 19.8 H Z ), 166.9 (d, J = 259.1 H Z ),
132.7 (dd, J = 9.6 H Z, J = 4.5 H Z ), 131.0, 121.4 (q, J = 269.1 H Z ), 116.3 (d, J = 22.1 H Z ), 93.0 (dd, J = 32.9 H Z, J = 22.1 H Z ), 85.9 (d, J = 195.8 H Z ). 1-(3,4-difluorophenyl)-2,4,4,4-tetrafluoro-3,3-dihydroxybutan-1-one (1d) Yellow oil. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.89-7.85 (m, 2 H), 7.34-7.29 (m, 1 H), 5.64 (d, 1H, J = 47.6 H Z ), 5.01 (s, 2H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -83.57 (s, 3 F), -125.54 (d, 1 F, J = 24.2 H Z ), -135.10 (d, 1 F, J = 24.2 H Z ), -195.48 (q, 1 F, J = 11.4 H Z ). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 194.1 (d, J = 20.9 H Z ), 154.8 (dd, J = 261.2 H Z, J = 13.3 H Z ), 150.4 (dd, J = 252.3 H Z, J = 13.9 H Z ), 131.4, 127.3, 121.6 (q, J = 287.7 H Z ), 119.0 (d, 1H, J = 21.5 H Z ), 117.9 (d, J = 18.1 H Z ), 92.7 (dd, J = 31.9 H Z, J = 21.6 H Z ), 86.9 (d, J = 196.3 H Z ). 2,4,4,4-tetrafluoro-3,3-dihydroxy-1-(4-methoxyphenyl)butan-1-one (1e) Yellow oil. 1 H NMR (CDCl 3, 400 MH Z ) δ: 8.02 (d, 2 H, J = 8.4 H Z ), 6.97 (d, 2 H, J = 9.2 H Z ), 5.68 (d, 1H, J = 47.6 H Z ), 5.20 (s, 1H), 4.90 (s, 1H), 3.89 (s, 3H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -83.66 (s, 3 F), -194.73 (q, 1 F, J = 12.3 H Z ). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 194.4 (d, J = 18.8 H Z ), 165.3, 132.4 (d, J = 3.8 H Z ), 127.5, 121.7 (q, J = 287.5 H Z ), 114.2, 93.0 (dd, J = 32.8 H Z, J = 22.4 H Z ), 85.0 (d, J = 193.7 H Z ), 55.6. 2,4,4,4-tetrafluoro-3,3-dihydroxy-1-o-tolylbutan-1-one (1f)
White solid. m.p.: 86.4-87.3. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.73-7.70(m, 1 H), 7.50-7.46 (m, 1 H), 7.34-7.30 (m, 2 H), 5.56 (d, 1H, J = 48.0 H Z ), 4.93 (s, 1H), 4.69 (s, 1H), 2.50 (s, 3H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -83.65 (s, 3 F), -193.13 (q, 1 F, J = 11.4 H Z ). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 201.1 (d, J = 21.2 H Z ), 139.6, 133.2, 132.1, 129.9, 129.8, 125.7, 121.6 (q, J = 295.3 H Z ), 93.2 (dd, J = 32.9 H Z, J = 21.9 H Z ), 86.1 (d, J = 196.8 H Z ), 20.8. 2,4,4,4-tetrafluoro-1-(furan-2-yl)-3,3-dihydroxybutan-1-one (1g) White solid. m.p.: 68.3-69.6. 1 H NMR (CDCl 3, 400 MH Z ) δ: 8.12-8.10 (m, 1 H), 7.89 (d, 1 H, J = 4.8 H Z ), 7.24 (t, 1 H, J = 4.4 H Z ), 5.48 (d, 1H, J = 47.6 H Z ), 4.89 (s, 1H), 4.42 (s, 1H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -83.33 (s, 3 F), -195.88 (q, 1 F, J = 11.9 H Z ). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 189.2 (d, J = 21.6 H Z ), 138.1 (d, J = 2.6 H Z ), 137.1, 137.0, 129.1 (d, J = 1.6 H Z ), 121.6 (q, J = 286.9 H Z ), 93.0 (dd, J = 32.9 H Z, J = 21.1 H Z ), 88.0 (d, J = 200.1 H Z ). 2,4,4,4-tetrafluoro-3,3-dihydroxy-1-(thiophen-2-yl)butan-1-one (1h) White solid. m.p.: 74.2-75.7. 1 H NMR (CDCl 3, 400 MH Z ) δ: 8.12-8.10 (m, 1 H), 7.90 (d, 1 H, J = 4.8 H Z ), 7.24 (t, 1 H, J = 4.6 H Z ), 5.48 (d, 1H, J = 47.6 H Z ), 5.32 (s, 1H), 4.47 (s, 1H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -83.36 (s, 3 F), -195.89 (q, 1 F, J = 12.1 H Z ). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 189.1 (d, J = 21.4 H Z ), 138.0 (d, J = 2.4 H Z ), 137.0, 136.9, 129.0 (d, J = 1.7 H Z ), 121.6 (q, J = 287.5 H Z ), 93.1 (dd, J = 32.9 H Z, J = 11.9 H Z ), 88.1 (d, J = 199.8 H Z ).
1-(4-bromophenyl)-2,4,4,4-tetrafluoro-3,3-dihydroxybutan-1-one (1i) H H Br F CF 3 White solid. m.p.: 73.2-74.3. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.88 (d, 2 H, J = 8.0 H Z ), 7.66 (d, 2 H, J = 8.8 H Z ), 5.67 (d, 1H, J = 47.6 H Z ), 4.63 (s, 2H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -83.63 (s, 3 F), -195.38 (q, 1 F, J = 11.4 H Z ). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 195.8 (d, J = 20.1 H Z ), 133.2, 132.3, 131.0 (d, J = 4.3 H Z ), 130.9, 121.5 (q, J = 287.4 H Z ), 92.9 (dd, J = 32.9 H Z, J = 22.3 H Z ), 86.1 (d, J = 195.8 H Z ). 1-(4-chlorophenyl)-2,4,4,4-tetrafluoro-3,3-dihydroxybutan-1-one (1j) H H Cl F CF 3 White solid. m.p.: 76.5-77.4. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.97 (d, 2 H, J = 8.0 H Z ), 7.66 (d, 2 H, J = 8.4 H Z ), 5.67 (d, 1H, J = 47.6 H Z ), 4.63 (s, 2H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -83.61 (s, 3 F), -195.24 (q, 1 F, J = 11.3 H Z ). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 195.6 (d, J = 19.9 H Z ), 142.0, 132.8, 131.1 (d, J = 4.4 H Z ), 129.3, 121.5 (q, J = 287.7 H Z ), 92.9 (dd, J = 33.1 H Z, J = 22.1 H Z ), 86.1 (d, J = 195.9 H Z ). 3,5,5,5-tetrafluoro-4,4-dihydroxypentan-2-one (1k) Yellow oil. 1 H NMR (CDCl 3, 400 MH Z ) δ: 5.53 (s, 1 H), 5.03 (s, 1 H), 4.86 (d, 1H, J = 48.4 H Z ), 2.44 (d, 1H, J = 5.2 H Z ). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -83.28 (s, 3 F), -198.83 (q, 1 F, J = 12.3 H Z ). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 209.6 (d, J = 26.4 H Z ), 121.5 (q, J = 287.6 H Z ), 92.6 (dd, J = 33.0 H Z, J = 20.3 H Z ), 90.2 (d, J = 200.7 H Z ), 27.7.
1-cyclopropyl-2,4,4,4-tetrafluoro-3,3-dihydroxybutan-1-one (1l) H F H CF 3 Yellow oil. 1 H NMR (CDCl 3, 400 MH Z ) δ: 5.72 (s, 1 H), 4.97 (d, 1H, J = 48.0 H Z ), 3.85 (s, 1 H), 2.66-2.58 (m, 1 H), 1.34-1.26 (m, 2 H), 1.24-1.18 (m, 2 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -83.27 (s, 3 F), -200.73 (q, 1 F, J = 13.3 H Z ). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 210.7 (d, J = 24.4 H Z ), 121.5 (q, J = 289.0 H Z ), 92.7 (dd, J = 32.7 H Z, J = 20.3 H Z ), 90.0 (d, J = 201.6 H Z ), 18.1 (d, J = 4.5 H Z ), 14.5, 14.4. 3. X-ray crystallography data for the 1a RTEP drawing of 1a
4. General procedure for asymmetric decarboxylative aldol reaction 4.1 Product characterization data (Table 4) H H R 1 CF 3 F 1a-1l + N Bn 2a Cat 6 (10 mol%) AcH(20 mol %) iprh/dmf (4:1) r t H F N Bn 3aa-3la R 1 The solution of N-benzyl isatin (2a) (0.200 mmol) and Cat 6 (10 mol%) in iprh/dmf (2.5 ml, 4:1) was stirred for 20 min at room temperature, the 2,4,4,4-tetrafluoro-3,3-dihydroxy-1-aryl(alkyl)butane-1-ones (1a-1l) (0.300 mmol) and AcH (20 mol %) was added. Upon consumption of N-benzyl isatin (monitored by TLC), the reaction mixture was concentrated and purified by column chromatography to afford the decarboxylative aldol products (3aa-3la). 1-benzyl-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxyindolin-2-one (3aa) H F N Bn White solid. m.p.: 161.5-162.2. 1 H NMR (CDCl 3, 400 MH Z ) δ: 8.00 (d, 2 H, J = 8.0 H Z ), 7.86 (d, 2 H, J = 8.4 H Z ), 7.63-7.55 (m, 2 H), 7.51-7.40 (m, 6 H), 7.33-7.28 (m, 10 H), 7.24-7.19 (m, 2 H), 7.04-6.97 (m, 2 H), 6.68 (dd, 2 H, J = 7.6 H Z, J = 2.0 H Z ), 6.03 (d, 1 H, J = 46.0 H Z ), 5.89 (d, 1 H, J = 47.2 H Z ), 5.11 (d, 1 H, J = 16.0 H Z ), 4.90 (d, 1 H, J = 16.0 H Z ), 4.80 (d, 1 H, J = 16.0 H Z ), 4.73 (d, 1 H, J = 16.0 H Z ), 4.35 (s, 1 H), 4.21 (s, 1 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -192.07 (s, 1 F), -197.10 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 196.0 (d, J = 20.0 Hz), 195.9 (d, J = 21.9 Hz), 174.3, 143.7, 143.6, 135.1, 135.0, 134.9, 134.5, 134.0, 130.7, 130.6, 129.6, 129.5,
129.4, 129.3, 128.9, 128.8, 128.7, 128.4, 127.7, 127.6, 127.2, 127.0, 126.4, 125.8, 125.6, 124.8, 123.3, 123.2, 109.9, 109.8, 94.7 (d, J = 194.8 Hz), 91.4 (d, J = 191.3 Hz), 76.7 (d, J = 27.5 Hz), 76.2 (d, J = 24.9 Hz), 44.1, 44.0. IR (KBr) ν: 3401, 3329, 1711, 1686, 1615, 1386, 1077, 764, 695 cm 1. EI-MS (m/z): 375 [M] +, 238, 237 (100), 180, 146, 105, 91, 77. HRMS Calcd. for [C 23 H 18 FN 3 ]: 375.1271; Found: 375.1269. 1-benzyl-3-(1-fluoro-2-oxo-2-m-tolylethyl)-3-hydroxyindolin-2-one (3ba) H F N Bn Yellow solid. m.p.: 118.4-119.8. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.71 (d, 2 H, J = 6.8 H Z ), 7.55 (d, 2 H, J = 8.4 H Z ), 7.37 (d, 1 H, J = 7.6 H Z ), 7.30-7.17 (m, 10 H), 7.15-7.12 (m, 4 H), 7.07 (t, 2 H, J = 7.8 H Z ), 7.03-6.95 (m, 1 H), 6.90-6.85 (m, 2H), 6.55 (dd, 2 H, J = 8.0 H Z, J = 3.6 H Z ), 5.99 (d, 1 H, J = 46.0 H Z ), 5.85 (d, 1 H, J = 46.8 H Z ), 4.98 (d, 1 H, J = 16.0 H Z ), 4.77 (d, 1 H, J = 16.0 H Z ), 4.65 (d, 1 H, J = 15.6 H Z ), 4.57 (d, 1 H, J = 15.6 H Z ). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -192.17 (s, 1 F), -197.22 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 194.8 (d, J = 20.1 Hz), 194.7 (d, J = 21.9 Hz), 173.5, 173.4, 142.6, 142.5, 137.5, 137.2, 134.2, 134.0, 133.8, 133.7, 129.5, 129.4, 128.8, 128.7, 127.8, 127.7, 127.5, 127.2, 126.7, 126.6, 126.1, 126.0, 125.8, 125.6 124.7, 124.6, 123.9, 122.2, 122.1, 108.8, 108.7, 93.8 (d, J = 194.8 Hz), 90.2 (d, J = 190.4 Hz), 75.4 (d, J = 21.5 Hz), 75.2 (d, J = 25.4 Hz), 43.0, 42.9, 20.3, 20.2. IR (KBr) ν: 3347, 3025, 1688, 1583, 1393, 1075, 766, 692 cm 1. EI-MS (m/z): 389 [M] +, 238, 237, 180, 152, 146, 105, 91 (100), 77, 65. HRMS Calcd. for [C 24 H 20 FN 3 ]: 389.1427; Found: 389.1425. 1-benzyl-3-(1-fluoro-2-(4-fluorophenyl)-2-oxoethyl)-3-hydroxyindolin-2-one (3ca)
H F N Bn F White solid. m.p.: 161.1-161.4. 1 H NMR (CDCl 3, 400 MH Z ) δ: 8.04 (dd, 2 H, J = 8.4 H Z, J = 5.6 H Z ), 7.93 (dd, 2 H, J = 7.6 H Z, J = 5.2 H Z ), 7.33-7.27 (m, 12 H), 7.24-7.20 (m, 2 H), 7.17-7.11 (m, 3 H), 7.09-6.98 (m, 3 H), 6.70 (d, 2 H, J = 7.6 H Z ), 5.97 (d, 1 H, J = 46.0 H Z ), 5.82 (d, 1 H, J = 46.8 H Z ), 5.10 (d, 1 H, J = 16.0 H Z ), 4.93 (d, 1 H, J = 15.6 H Z ), 4.80 (d, 1 H, J = 15.6 H Z ), 4.73 (d, 1 H, J = 15.6 H Z ), 4.19 (s, 2 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -101.87 (s, 1 F), -102.67 (s, 1 F), -191.85 (s, 1 F), -196.55 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 194.4 (d, J = 22.0 Hz), 194.1 (d, J = 20.0 Hz), 174.4, 174.3, 166.5 (d, J = 257.9 Hz), 166.2 (d, J = 262.2 Hz), 143.6, 135.0, 134.8, 132.6, 132.5, 132.4, 132.3, 131.4 (d, J = 10.1 Hz), 131.2 (d, J = 8.8 Hz), 130.7, 130.6, 128.9, 128.8, 127.8, 127.7, 127.2, 127.0, 126.4, 125.7, 125.6, 124.8, 123.4, 123.2, 116.0 (d, J = 22.2 Hz), 115.7 (d, J = 16.2 Hz), 109.9, 109.8, 94.9 (d, J = 195.3 Hz), 91.7 (d, J = 191.5 Hz), 76.5 (d, J = 22.1 Hz), 76.2 (d, J = 25.1 Hz), 44.1, 44.0. IR (KBr) ν: 3404, 1709, 1684, 1596, 1386, 1079, 762, 697 cm 1. EI-MS (m/z): 393 [M] +, 238, 237 (100), 180, 146, 110, 91, 77. HRMS Calcd. for [C 23 H 17 F 2 N 3 ]: 393.1176; Found: 393.1177. 1-benzyl-3-(2-(3,4-difluorophenyl)-1-fluoro-2-oxoethyl)-3-hydroxyindolin-2-one (3da) H F N Bn F F White solid. m.p.: 156.4-157.3. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.89-7.82 (m, 2 H), 7.74-7.70 (m, 2 H), 7.46 (d, 1 H, J = 7.6 H Z ), 7.32-7.26 (m, 11 H), 7.23-7.15 (m, 4 H), 7.05-6.98 (m, 2 H), 6.71 (d, 2 H, J = 8.0 H Z ), 5.96 (d, 1 H, J = 46.0 H Z ), 5.80 (d, 1 H,
J = 47.2 H Z ), 5.09 (d, 1 H, J = 15.6 H Z ), 4.94 (d, 1 H, J = 16.0 H Z ), 4.79 (d, 1 H, J = 15.6 H Z ), 4.71 (d, 1 H, J = 16.0 H Z ), 4.30 (s, 2 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -126.65 (d, 1 F, J = 20.1 H Z ), -127.32 (d, 1 F, J = 20.5 H Z ), -135.34 (d, 1 F, J = 21.2 H Z ), -135.71 (d, 1 F, J = 20.1 H Z ), -192.33 (s, 1 F), -196.79 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 193.4 (d, J = 21.0 Hz), 192.8 (d, J = 18.7 Hz), 174.5, 173.3, 154.4 (dd, J = 259.7 Hz, J = 13.5 Hz), 154.1 (dd, J = 259.0 Hz, J = 12.7 Hz), 150.3 (dd, J = 253.7 Hz, J = 15.1 Hz), 150.1 (dd, J = 250.5 Hz, J = 12.7 Hz), 143.6, 143.5, 134.9, 134.7, 132.0, 131.6, 130.9, 130.7, 128.9, 128.8, 127.9, 127.8, 127.2, 127.0, 126.2, 125.5, 125.4, 124.9, 123.4, 123.3, 119.0 (d, J = 19.3 Hz), 118.9 (d, J = 19.1 Hz), 117.8, 117.6, 117.4, 110.0, 109.9, 95.2 (d, J = 195.5 Hz), 91.8 (d, J = 191.7 Hz), 76.5 (d, J = 21.9 Hz), 76.1 (d, J = 25.4 Hz), 44.1. IR (KBr) ν: 3392, 3131, 1723, 1674, 1613, 1350, 1074, 760, 697 cm 1. EI-MS (m/z): 411 [M] +, 238, 237 (100), 180, 146, 141, 91. HRMS Calcd. for [C 23 H 16 F 3 N 3 ]: 411.1082; Found: 411.1085. 1-benzyl-3-(1-fluoro-2-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxyindolin-2-one (3ea) H F N Bn CH 3 Yellow oil. m.p.: 68-70. 1 H NMR (CDCl 3, 400 MH Z ) δ: 8.02 (d, 2 H, J = 8.8 H Z ), 7.88 (d, 2 H, J = 8.0 H Z ), 7.47 (d, 1 H, J = 7.2 H Z ), 7.29-7.21 (m, 11 H), 7.15 (t, 2 H, J = 7.8 H Z ), 6.96 (q, 2 H, J = 8.6 H Z ), 6.88 (d, 2 H, J = 9.2 H Z ), 6.84 (d, 2 H, J = 8.8 H Z, ), 6.64 (dd, 2 H, J = 7.6 H Z, J = 4.4 H Z ), 6.03 (d, 1 H, J = 46.0 H Z ), 5.92 (d, 1 H, J = 46.8 H Z ), 5.07 (d, 1 H, J = 16.0 H Z ), 4.94-4.86 (m, 3 H), 4.73 (d, 1 H, J = 15.6 H Z ), 4.66 (d, 1 H, J = 16.0 H Z ), 3.80 (s, 3 H), 3.79 (s, 3 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -191.72 (s, 1 F), -196.71 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 193.7 (d, J = 19.1 Hz), 193.3 (d, J = 20.8 Hz),
174.8, 174.6, 171.3, 164.6, 164.2, 143.6, 143.5, 135.2, 135.0, 132.2, 132.1, 132.0, 128.8, 128.2, 127.7, 127.6, 127.2, 127.0, 126.8, 126.0, 125.8, 125.0, 123.3, 123.2, 113.9, 113.7, 109.8, 109.7, 95.0 (d, J = 194.4 Hz), 91.4 (d, J = 190.0 Hz), 76.5 (d, J = 21.5 Hz), 76.4 (d, J = 25.7 Hz), 55.6, 55.5, 44.0. IR (KBr) ν: 3379, 3063, 1714, 1647, 1372, 1077, 752 cm 1. HRMS (ESI) Calcd. for C 24 H 20 FNNa 4 [M+Na] + :428.1274; Found:428.1271. 1-benzyl-3-(1-fluoro-2-oxo-2-o-tolylethyl)-3-hydroxyindolin-2-one (3fa) H F N Bn Yellow solid. m.p.: 139.6-140.2. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.62 (d, 1 H, J = 7.6 H Z ), 7.44-7.27 (m, 13 H), 7.24-7.15 (m, 8 H), 7.00 (t, 2 H, J = 7.4 H Z ), 7.67 (d, 1 H, J = 8.0 H Z ), 6.63 (d, 1 H, J = 7.6 H Z, ), 5.94 (d, 1 H, J = 46.0 H Z ), 5.83 (d, 1 H, J = 47.6 H Z ), 5.26 (s, 1 H), 5.08 (d, 1 H, J = 16.0 H Z ), 4.78 (s, 2 H), 4.69 (d, 1 H, J = 16.0 H Z ), 4.59 (s, 1 H), 2.48 (s, 3 H), 2.02 (s, 3 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -190.50 (s, 1 F), -197.57 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 200.1 (d, J = 24.0 Hz), 199.8 (d, J = 21.0 Hz), 174.5, 174.4, 143.6, 139.4, 138.4, 135.0, 134.9, 132.7, 132.1, 131.9, 131.4, 130.7, 130.6, 130.1, 130.0, 129.1, 129.0, 128.9, 128.8, 127.2, 127.1, 126.4, 126.0, 125.6, 125.5, 125.2, 125.1, 123.4, 123.2, 110.0, 109.9, 94.6 (d, J = 195.9 Hz), 91.3 (d, J = 192.3 Hz), 76.8 (d, J = 19.7 Hz), 76.6 (d, J = 21.3 Hz), 44.0, 21.0, 19.7. IR (KBr) ν: 3338, 3029, 1720, 1615, 1391, 1105, 759, 659 cm 1. EI-MS (m/z): 389 [M] +, 238, 237, 180, 146, 119, 91 (100), 77, 65. HRMS Calcd. for [C 24 H 20 FN 3 ]: 389.1427; Found: 389.1430. 1-benzyl-3-(2-(4-bromophenyl)-1-fluoro-2-oxoethyl)-3-hydroxyindolin-2-one (3ga)
H F N Bn Br White solid. m.p.: 109.0-109.5. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.86 (d, 2 H, J = 8.0 H Z ), 7.74 (d, 2 H, J = 7.6 H Z ), 7.61 (d, 2 H, J = 8.8 H Z ), 7.57 (d, 2 H, J = 8.4 H Z ), 7.46 (d, 1 H, J = 7.2 H Z ), 7.34-7.27 (m, 11 H), 7.24-7.21 (m, 2 H), 7.09-6.98 (m, 2 H), 6.70 (d, 2 H, J = 7.6 H Z ), 5.95 (d, 1 H, J = 46.0 H Z ), 5.80 (d, 1 H, J = 47.2 H Z ), 5.10 (d, 1 H, J = 15.6 H Z ), 4.93 (d, 1 H, J = 15.6 H Z ), 4.80 (d, 1 H, J = 16.0 H Z ), 4.73 (d, 1 H, J = 16.0 H Z ), 4.04 (s, 2 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -192.27 (s, 1 F), -196.76 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 195.0 (d, J = 22.0 Hz), 194.6 (d, J = 19.8 Hz), 174.5, 174.4, 174.3, 143.5, 134.9, 134.8, 133.8, 133.6, 132.0, 131.8, 131.1, 131.0, 130.9, 130.8, 130.7, 130.0, 129.4, 128.9, 128.8, 127.8, 127.7, 127.2, 127.0, 126.3, 125.6, 124.9, 123.4, 123.2, 110.0, 109.9, 95.0 (d, J = 195.2 Hz), 91.6 (d, J = 191.4 Hz), 76.5 (d, J = 21.8 Hz), 76.2 (d, J = 25.4 Hz), 44.1. IR (KBr) ν: 3391, 1698, 1614, 1398, 1071, 753, 696 cm 1. EI-MS (m/z): 455 [M+2] +, 453 [M] +, 238, 237 (100), 184, 182, 180, 146, 91. HRMS Calcd. for [C 23 H 17 BrFN 3 ]: 453.0376; Found: 453.0380. 1-benzyl-3-(2-(4-chlorophenyl)-1-fluoro-2-oxoethyl)-3-hydroxyindolin-2-one (3ha) H F N Bn Cl White solid. m.p.: 117.5-118.1. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.94 (d, 2 H, J = 8.4 H Z ), 7.82 (d, 2 H, J = 7.6 H Z ), 7.47-7.38 (m, 5 H), 7.33-7.27 (m, 11 H), 7.24-7.20 (m, 2 H), 7.06-6.98 (m, 2 H), 6.70 (d, 2 H, J = 8.0 H Z ), 5.97 (d, 1 H, J = 46.0 H Z ), 5.82 (d, 1 H, J = 47.2 H Z ), 5.10 (d, 1 H, J = 15.6 H Z ), 4.92 (d, 1 H, J = 15.6 H Z ), 4.80 (d, 1 H, J = 15.6 H Z ), 4.72 (d, 1 H, J = 16.0 H Z ), 4.26 (s, 2 H).
19 F NMR (CDCl 3, 367.5 MH Z ) δ: -192.27 (s, 1 F), -196.85 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 194.9 (d, J = 22.1 Hz), 194.5 (d, J = 19.8 Hz), 174.4, 174.3, 174.2, 143.6, 141.1, 140.6, 134.9, 134.8, 133.4, 133.1, 131.0, 130.9, 130.8, 130.7, 129.0, 128.8, 128.6, 127.8, 127.7, 127.2, 127.0, 126.3, 125.6, 124.8, 123.4, 123.2, 110.0, 109.9, 94.9 (d, J = 195.4 Hz), 91.7 (d, J = 191.5 Hz), 76.5 (d, J = 22.0 Hz), 76.2 (d, J = 25.3 Hz), 44.1, 44.0. IR (KBr) ν: 3430, 1688, 1614, 1400, 1080, 753, 698 cm 1. EI-MS (m/z): 411 [M+2] +, 409 [M] +, 238, 237 (100), 180, 146, 138, 91. HRMS Calcd. for [C 23 H 17 ClFN 3 ]: 409.0881; Found: 409.0883. 1-benzyl-3-(1-fluoro-2-(furan-2-yl)-2-oxoethyl)-3-hydroxyindolin-2-one (3ia) H F N Bn White solid. m.p.: 143.8-144.3. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.99-7.97 (m, 1H), 7.96-7.94 (m, 1H), 7.78 (d, 1 H, J = 4.8 H Z ), 7.73 (d, 1 H, J = 4.8 H Z ), 7.49 (d, 1 H, J = 7.6 H Z ), 7.33-7.27 (m, 9 H), 7.23-7.18 (m, 3 H), 7.13 (q, 2 H, J = 4.6 H Z ), 7.06-7.02 (m, 1 H), 6.97-6.93 (m, 1 H, ), 6.68 (t, 2 H, J = 7.4 H Z ), 5.79 (d, 1 H, J = 46.0 H Z ), 5.63 (d, 1 H, J = 47.2 H Z ), 5.11 (d, 1 H, J = 15.6 H Z ), 4.96 (d, 1 H, J = 16.0 H Z ), 4.78 (d, 1 H, J = 15.6 H Z ), 4.72 (d, 1 H, J = 16.0 H Z ), 4.56 (s, 2 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -192.05 (s, 1 F), -196.85 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 188.8 (d, J = 21.7 Hz), 188.5 (d, J = 23.1 Hz), 174.3, 174.2, 174.0, 143.6, 141.0, 140.4, 140.3, 136.8, 136.4, 136.3, 136.2, 135.7, 135.5, 135.0, 134.9, 130.7, 128.9, 128.8, 128.5, 127.7, 127.2, 127.0, 126.1, 125.7, 125.4, 124.8, 123.3, 123.2, 109.9, 109.8, 94.8 (d, J = 197.0 Hz), 92.7 (d, J = 194.2 Hz), 76.8 (d, J = 18.1 Hz), 76.3 (d, J = 24.9 Hz), 44.1, 44.0. IR (KBr) ν: 3390, 3109, 1707, 1664, 1613, 1350, 1082, 763, 698 cm 1. EI-MS (m/z): 365 [M] +, 238, 237(100), 180, 146, 110, 91. HRMS Calcd. for [C 21 H 16 FN 4 ]: 365.1063; Found: 365.1059.
1-benzyl-3-(1-fluoro-2-oxo-2-(thiophen-2-yl)ethyl)-3-hydroxyindolin-2-one (3ja) H F N Bn S White solid. m.p.: 141.3-142.8. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.98-7.97 (m, 1H), 7.96-7.94 (m, 1H), 7.79 (d, 1 H, J = 4.8 H Z ), 7.72 (d, 1 H, J = 4.8 H Z ), 7.49 (d, 1 H, J = 7.6 H Z ), 7.33-7.29 (m, 6 H), 7.25-7.17 (m, 7 H), 7.13 (q, 2 H, J = 4.6 H Z ), 7.03 (t, 1 H, J = 7.4 H Z ), 6.95 (t, 1 H, J = 7.4 H Z ), 6.67 (t, 2 H, J = 7.4 H Z ), 5.79 (d, 1 H, J = 46.0 H Z ), 5.64 (d, 1 H, J = 47.2 H Z ), 5.10 (d, 1 H, J = 16.0 H Z ), 4.96 (d, 1 H, J = 16.0 H Z ), 4.78 (d, 1 H, J = 16.0 H Z ), 4.72 (d, 1 H, J = 16.0 H Z ), 4.62 (s, 1 H), 4.57 (s, 1 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -192.03 (s, 1 F), -196.87 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 188.8 (d, J = 21.7 Hz), 188.4 (d, J = 23.1 Hz), 174.3, 174.2, 174.1, 143.6, 141.0, 140.3, 136.8, 136.3, 136.2, 135.7, 135.5, 135.0, 134.9, 130.7, 128.9, 128.8, 128.5, 127.8, 127.7, 127.2, 127.0, 126.1, 125.7, 125.4, 124.8, 123.3, 123.2, 109.9, 109.8, 94.9 (d, J = 197.1 Hz), 92.8 (d, J = 194.1 Hz), 76.8 (d, J = 17.7 Hz), 76.3 (d, J = 25.1 Hz), 44.1, 44.0. IR (KBr) ν: 3393, 3111, 1715, 1649, 1613, 1082, 762, 698 cm 1. EI-MS (m/z): 381 [M] +, 238, 237(100), 180, 146, 110, 91. HRMS Calcd. for [C 21 H 16 FN 3 S]: 381.0835; Found: 381.0837. 1-benzyl-3-(1-fluoro-2-oxopropyl)-3-hydroxyindolin-2-one (3ka) H F N Bn Yellow oil. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.38 (d, 1 H, J = 7.2 H Z ), 7.28-7.24 (m, 2 H), 7.21-7.14 (m, 10 H), 7.09-7.07 (m, 1 H), 7.02-6.98 (m, 1 H), 6.97-6.93 (m, 1 H), 6.62 (d, 1 H, J = 8.0 H Z ), 6.59 (d, 1 H, J = 8.0 H Z ), 5.39 (s, 1 H), 5.16 (d, 1 H, J = 46.4 H Z ), 5.02 (d, 1 H, J = 16.0 H Z ), 5.00 (d, 1 H, J = 48.0 H Z ), 4.89 (d, 1 H, J = 16.0
H Z ), 4.71 (d, 1 H, J = 15.6 H Z ), 4.65-4.57 (m, 2 H), 2.26 (d, 3 H, J = 4.8 H Z ), 2.18 (d, 3 H, J = 5.6 H Z ). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -194.38 (s, 1 F), -198.59 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 208.2 (d, J = 23.5 Hz), 207.9 (d, J = 21.3 Hz), 174.5, 174.0, 143.6, 143.5, 134.8, 134.7, 130.9, 130.8, 128.9, 127.8, 127.1, 127.0, 125.8, 125.5, 124.6, 124.5, 123.6, 123.4, 110.2, 110.1, 94.2 (d, J = 195.1 Hz), 93.1 (d, J = 192.8 Hz), 76.6 (d, J = 22.6 Hz), 76.0 (d, J = 25.0 Hz), 44.1, 44.0, 28.3, 27.4. IR (KBr) ν: 3307, 1704, 1614, 1383, 1183, 758, 696 cm 1. HRMS (ESI) Calcd. for C 18 H 16 FNNa 3 [M+Na] + : 336.1012; Found:336.1012. 1-benzyl-3-(2-cyclopropyl-1-fluoro-2-oxoethyl)-3-hydroxyindolin-2-one (3la) H F N Bn Yellow oil. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.50 (d, 1 H, J = 7.2 H Z ), 7.33-7.20 (m, 12 H), 7.16 (d, 1 H, J = 6.8 H Z ), 6.69 (d, 1 H, J = 7.6 H Z ), 6.65 (d, 1 H, J = 7.6 H Z ), 5.46 (s, 1 H), 5.36 (d, 1 H, J = 46.8 H Z ), 5.18 (d, 1 H, J = 48.4 H Z ), 5.11 (d, 1 H, J = 15.6 H Z ), 4.94 (d, 1 H, J = 15.6 H Z ), 4.80 (d, 1 H, J = 16.0 H Z ), 4.74 (s, 1 H), 4.70 (d, 1 H, J = 15.6 H Z ), 2.45-2.35 (m, 2 H), 1.27-1.15 (m, 4 H), 1.10-0.90 (m, 4 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -196.02 (s, 1 F), -201.13 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 209.4 (d, J = 23.4 Hz), 208.8 (d, J = 24.9 Hz), 174.3, 174.1, 143.6, 143.4, 134.9, 134.8, 130.7, 128.9, 128.8, 127.8, 127.7, 127.1, 127.0, 126.1, 125.7, 124.8, 124.7, 123.4, 123.2, 110.0, 109.9, 94.7 (d, J = 196.2 Hz), 93.3 (d, J = 193.5 Hz), 76.6 (d, J = 21.3 Hz), 76.0 (d, J = 25.1 Hz), 44.1, 44.0, 18.4, 17.4, 17.3, 14.9, 14.5, 13.7, 13.5, 13.4. IR (KBr) ν: 3364, 2927, 1698, 1614, 1392, 753, 697 cm 1. HRMS (ESI) Calcd. for C 20 H 18 FNNa 3 [M+Na] + : 362.1168; Found:362.1172.
4.2 Product characterization data (Table 5) H H CF 3 R 1 + R2 R 2 F N iprh/dmf (4:1) r t N Bn Bn R 1 1a 1c 1e 2b-2i Cat 6 (10 mol%) AcH(20 mol %) H F 3ab-3ai 3cb 3eb To a solution of N-benzyl isatins (2b-2i) (0.200 mmol) and Cat 6 (10 mol%) in iprh/dmf (2.5 ml, 4:1) was stirred for 20 min at room temperature, the 2,4,4,4-tetrafluoro-3,3-dihydroxy-1-arylbutane-1-ones (1a, 1c, 1e) (0.300 mmol) and AcH (20 mol %) was added. Upon consumption of N-benzyl isatins (monitored by TLC), the reaction mixture was concentrated and purified by column chromatography to afford the decarboxylative aldol products (3ab-3ai, 3cb, 3eb). 1-benzyl-5-fluoro-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxyindolin-2-one (3ab) F H F N Bn White solid. m.p.: 138.4-138.9. 1 H NMR (CDCl 3, 400 MH Z ) δ: 8.02 (d, 2 H, J = 8.4 H Z ), 7.87 (d, 2 H, J = 8.4 H Z ), 7.65-7.56 (m, 2 H), 7.50-7.41 (m, 4 H), 7.33-7.26 (m, 10 H), 7.22 (dd, 1 H, J = 6.0 H Z, J = 3.6 H Z ), 7.09 (dd, 1 H, J = 7.6 H Z, J = 2.4 H Z ), 6.92-6.87 (m, 2 H), 6.60-6.57 (m, 2 H), 6.04 (d, 1 H, J = 45.6 H Z ), 5.92 (d, 1 H, J = 46.8 H Z ), 5.10 (d, 1 H, J = 15.6 H Z ), 4.89 (d, 1 H, J = 15.6 H Z ), 4.78 (d, 1 H, J = 16.0 H Z ), 4.70 (d, 1 H, J = 16.0 H Z ), 4.55 (s, 1 H), 4.38 (s, 1 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -118.95 (s, 1 F), -119.07 (s, 1 F), -191.73 (s, 1 F), -197.36 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 195.9 (d, J = 19.9 Hz), 195.4 (d, J = 21.5 Hz), 174.2, 174.1, 159.3 (d, J = 242.5 Hz), 159.2 (d, J = 242.2 Hz), 139.5, 134.9, 134.7, 134.6, 134.5, 134.2, 129.6, 129.5, 129.4, 129.0, 128.9, 128.8, 128.5, 128.0 (d, J = 8.1 Hz), 127.8, 127.4 (d, J = 7.8 Hz), 127.2, 127.0, 116.9 (d, J = 23.4 Hz), 116.8 (d, J = 23.4 Hz), 114.2, 114.0, 110.6, 110.5, 94.7 (d, J = 195.0 Hz), 91.0 (d, J = 191.4 Hz),
76.5 (d, J = 21.3 Hz), 76.3 (d, J = 25.4 Hz), 44.2. IR (KBr) ν: 3338, 1717, 1675, 1493, 1088, 876, 692 cm 1. HRMS (ESI) Calcd. for C 23 H 17 F 2 NNa 3 [M+Na] + : 416.1074; Found:416.1073. 1-benzyl-6-bromo-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxyindolin-2-one (3ac) H F Br N Bn White solid. m.p.: 169.8-170.3. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.99 (d, 2 H, J = 8.4 H Z ), 7.85 (d, 2 H, J = 8.4 H Z ), 7.63-7.55 (m, 2 H), 7.48-7.40 (m, 4 H), 7.34-7.28 (m, 9 H), 7.26-7.25 (m, 2 H), 7.16-7.10 (m, 3 H), 6.82 (s, 2 H), 6.02 (d, 1 H, J = 45.6 H Z ), 5.90 (d, 1 H, J = 46.8 H Z ), 5.07 (d, 1 H, J = 16.0 H Z ), 4.87 (d, 1 H, J = 16.0 H Z ), 4.74 (d, 1 H, J = 16.0 H Z ), 4.66 (d, 1 H, J = 16.0 H Z ), 4.51 (s, 1 H), 4.35 (s, 1 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -191.48 (s, 1 F), -196.93 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 195.7 (d, J = 19.8 Hz), 195.4 (d, J = 21.4 Hz), 174.4, 174.3, 174.2, 145.0, 134.9, 134.7, 134.6, 134.5, 134.3, 134.2, 129.6, 129.5, 129.4, 129.0, 128.9, 128.8, 128.5, 128.0, 127.9, 127.1, 127.0, 126.2, 126.1, 125.7, 124.8, 124.6, 124.4, 113.3, 113.2, 94.7 (d, J = 194.7 Hz), 91.1 (d, J = 191.1 Hz), 76.0 (d, J = 21.6 Hz), 75.9 (d, J = 25.5 Hz), 44.1. IR (KBr) ν: 3326, 1693, 1609, 1382, 1068, 768, 691 cm 1. HRMS (ESI) Calcd. for C 23 H 17 BrFNNa 3 [M+Na] + : 476.0274; Found:476.0279. 1-benzyl-5-bromo-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxyindolin-2-one (3ad) Br H F N Bn Yellow solid. m.p.: 135.6-136.3. 1 H NMR (CDCl 3, 400 MH Z ) δ: 8.00 (d, 2 H, J = 8.4 H Z ), 7.88 (d, 2 H, J = 8.0 H Z ), 7.65-7.57 (m, 3 H), 7.50-7.42 (m, 5 H), 7.33-7.27 (m, 10 H), 7.25-7.24 (m, 2 H), 6.54 (d, 2 H, J = 8.4 H Z ), 6.01 (d, 1 H, J = 46.0 H Z ),
5.90 (d, 1 H, J = 46.8 H Z ), 5.08 (d, 1 H, J = 15.6 H Z ), 4.90 (d, 1 H, J = 16.0 H Z ), 4.78 (d, 1 H, J = 15.6 H Z ), 4.70 (d, 1 H, J = 15.6 H Z ), 4.51 (s, 1 H), 4.33 (s, 1 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -191.48 (s, 1 F), -196.70 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 195.7 (d, J = 20.1 Hz), 195.4 (d, J = 21.8 Hz), 173.9, 173.8, 142.7, 134.8, 134.7, 134.6, 134.4, 134.2, 133.4, 133.3, 129.6, 129.5, 129.4, 129.0, 128.9, 128.8, 128.6, 128.2, 128.1, 127.9, 127.8, 127.2, 127.0, 116.0, 115.9, 113.4, 113.3, 94.6 (d, J = 194.9 Hz), 91.1 (d, J = 191.7 Hz), 76.2 (d, J = 21.5 Hz), 76.1 (d, J = 25.3 Hz), 44.1. IR (KBr) ν: 3373, 1699, 1612, 1434, 1174, 729, 691 cm 1. HRMS (ESI) Calcd. for C 23 H 17 BrFNNa 3 [M+Na] + : 476.0274; Found:476.0271. 1-benzyl-7-chloro-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxyindolin-2-one (3ae) H F Cl N Bn White solid. m.p.: 129.7-130.9. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.98 (d, 2 H, J = 8.8 H Z ), 7.84 (d, 2 H, J = 8.4 H Z ), 7.61-7.54 (m, 2 H), 7.46-7.38 (m, 5 H), 7.30-7.17 (m, 13 H), 6.98-6.91 (m, 2 H), 6.01 (d, 1 H, J = 45.6 H Z ), 5.86 (d, 1 H, J = 46.8 H Z ), 5.37 (d, 1 H, J = 16.0 H Z ), 5.28 (d, 1 H, J = 16.8 H Z ), 5.25 (s, 2 H), 4.62 (s, 1 H), 4.51 (s, 1 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -192.04 (s, 1 F), -196.79 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 195.9 (d, J = 21.8 Hz), 195.6 (d, J = 19.7 Hz), 175.2, 175.1, 139.8, 139.7, 136.8, 136.7, 135.0, 134.7, 134.6, 134.1, 133.3, 133.1, 129.6, 129.5, 129.4, 128.7, 128.6, 128.5, 127.3, 127.2, 126.4, 126.2, 124.4, 124.3, 124.2, 123.5, 116.1, 116.0, 113.4, 113.3, 94.6 (d, J = 195.4 Hz), 91.3 (d, J = 191.8 Hz), 75.7 (d, J = 22.0 Hz), 75.6 (d, J = 25.2 Hz), 45.3, 45.2. IR (KBr) ν: 3374, 1698, 1622, 1375, 1078, 734, 695 cm 1. HRMS (ESI) Calcd. for C 23 H 17 ClFNNa 3 [M+Na] + : 432.0779; Found:432.0779.
1-benzyl-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxy-5-methylindolin-2-one (3af) H 3 C H F N Bn White solid. m.p.: 112.7-113.9. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.99 (d, 2 H, J = 7.6 H Z ), 7.86 (d, 2 H, J = 8.0 H Z ), 7.62-7.54 (m, 2 H), 7.47-7.39 (m, 4 H), 7.31-7.27 (m, 9 H), 7.25-7.22 (m, 2 H), 7.10 (s, 1 H), 7.00-6.98 (m, 2 H), 6.55 (dd, 2 H, J = 8.0 H Z, J = 2.8 H Z ), 6.08-5.96 (m, 1 H), 5.95-5.82 (m, 1 H), 5.07 (d, 1 H, J = 16.0 H Z ), 4.86 (d, 1 H, J = 16.0 H Z ), 4.75 (d, 1 H, J = 15.6 H Z ), 4.70 (d, 1 H, J = 16.0 H Z ), 4.35 (s, 1 H), 4.28 (s, 1 H), 2.24 (s, 3 H), 2.21 (s, 3 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -192.24 (s, 1 F), -197.13 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 195.9 (d, J = 20.7 Hz), 195.8 (d, J = 22.5 Hz), 174.4, 174.3, 141.1, 135.1, 135.0, 134.9, 134.4, 134.0, 133.0, 132.8, 130.9, 130.8, 129.6, 129.5, 129.4, 128.8, 128.6, 128.4, 127.7, 127.6, 127.2, 127.1, 125.8, 125.7, 109.7, 109.6, 94.7 (d, J = 195.8 Hz), 91.4 (d, J = 191.1 Hz), 76.6 (d, J = 22.4 Hz), 76.3 (d, J = 25.1 Hz), 44.1, 44.0, 21.1, 21.0. IR (KBr) ν: 3365, 1698, 1622, 1377, 1090, 758, 695 cm 1. HRMS (ESI) Calcd. for C 24 H 20 FNNa 3 [M+Na] + : 412.1325; Found:412.1322. 1-benzyl-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxy-5-methoxyindolin-2-one (3ag) H F N Bn Yellow solid. m.p.: 167.2-168.4. 1 H NMR (CDCl 3, 400 MH Z ) δ: 8.01 (d, 2 H, J = 8.0 H Z ), 7.85 (d, 2 H, J = 8.0 H Z ), 7.61-7.53 (m, 2 H), 7.46-7.38 (m, 4 H), 7.31-7.27 (m, 8 H), 7.25-7.22 (m, 2 H), 7.09 (d, 1 H, J = 2.4 H Z ), 6.90 (d, 1 H, J = 2.4 H Z ), 6.71-6.68 (m, 2 H), 6.55 (dd, 2 H, J = 8.4 H Z, J = 3.2 H Z ), 6.05 (d, 1 H, J = 46.0 H Z ), 5.92 (d, 1 H, J = 46.8 H Z ), 5.07 (d, 1 H, J = 16.0 H Z ), 4.85 (d, 1 H, J = 16.0 H Z ), 4.74 (d, 1 H, J = 15.6 H Z ), 4.67 (s, 1 H), 4.66 (d, 1 H, J = 15.6 H Z ), 4.57 (s, 1 H), 3.67 (s, 3
H), 3.65 (s, 3 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -192.36 (s, 1 F), -197.63 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 195.7 (d, J = 19.6 Hz), 195.5 (d, J = 21.5 Hz), 174.3, 174.2, 156.3, 156.1, 136.7, 135.2, 135.1, 134.9, 134.8, 134.4, 134.0, 129.6, 129.5, 129.4, 128.9, 128.8, 128.7, 128.4, 127.7, 127.6, 127.2, 127.1, 125.9, 115.2, 112.8, 111.9, 110.5, 110.4, 94.8 (d, J = 194.9 Hz), 91.4 (d, J = 191.2 Hz), 76.7 (d, J = 21.4 Hz), 76.6 (d, J = 25.4 Hz), 55.8, 55.7, 44.2, 44.1. IR (KBr) ν: 3462, 3307, 1731, 1699, 1394, 1089, 751, 696 cm 1. HRMS (ESI) Calcd. for C 24 H 20 FNNa 4 [M+Na] + : 428.1274; Found:428.1271. 1-benzyl-4-bromo-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxyindolin-2-one (3ah) Br H F N Bn (Minor): Yellow solid. m.p.: 172.4-173.1. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.98 (d, 2 H, J = 8.4 H Z ), 7.60 (t, 1 H, J = 7.6 H Z ), 7.46 (t, 2 H, J = 7.8 H Z ), 7.33-7.27 (m, 2 H), 7.25-7.19 (m, 4 H), 7.10 (t, 1 H, J = 8.0 H Z ), 6.62 (d, 1 H, J = 7.6 H Z ), 6.32 (d, 1 H, J = 46.0 H Z ), 5.04 (s, 1 H), 4.89 (d, 1 H, J = 16.0 H Z ), 4.73 (d, 1 H, J = 16.0 H Z ). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -192.04 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 199.2 (d, J = 21.8 Hz), 173.8, 145.8, 135.7, 134.5, 134.0, 132.0, 129.6, 129.5, 128.9, 128.5, 127.8, 127.6, 127.0, 124.5, 119.8, 108.9, 90.2 (d, J = 194.0 Hz), 78.7 (d, J = 26.4 Hz), 44.0. (Major): Yellow solid. m.p.: 158.7-159.6. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.85 (d, 2 H, J = 8.4 H Z ), 7.56-7.51 (m, 1 H), 7.38 (t, 2 H, J = 7.8 H Z ), 7.34-7.27 (m, 5 H), 7.04-6.95 (m, 2 H), 6.57 (d, 1 H, J = 46.8 H Z ), 6.55 (dd, 1 H, J = 7.6 H Z, J = 1.2 H Z ), 4.98 (d, 1 H, J = 15.6 H Z ), 4.71 (d, 1 H, J = 16.0 H Z ), 4.05 (s, 1 H),. 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -198.88 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 193.3 (d, J = 19.6 Hz), 173.9, 145.6, 134.6, 134.2, 132.1, 129.2, 129.1, 128.8, 128.6, 127.8, 127.4, 127.3, 123.9, 119.8, 108.9, 91.6 (d, J = 195.8 Hz), 76.6 (d, J = 21.2 Hz), 44.2.
IR (KBr) ν: 3356, 1716, 1694, 1378, 1096, 777, 696 cm 1. HRMS (ESI) Calcd. for C 23 H 17 BrFNNa 3 [M+Na] + : 476.0274; Found:476.0269. 1-benzyl-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxy-5,7-dimethylindolin-2-one (3ai) H F H 3 C N Bn CH 3 Yellow oil. 1 H NMR (CDCl 3, 400 MH Z ) δ: 8.00 (d, 2 H, J = 8.0 H Z ), 7.84 (d, 2 H, J = 8.0 H Z ), 7.57-7.51 (m, 2 H), 7.42-7.35 (m, 4 H), 7.28-7.25 (m, 4 H), 7.21-7.16 (m, 7 H), 6.92 (s, 1 H), 6.77 (d, 2 H, J = 6.0 H Z ), 6.06 (d, 1 H, J = 46.4 H Z ), 5.89 (d, 1 H, J = 46.8 H Z ), 5.23 (d, 1 H, J = 16.8 H Z ), 5.07-4.97 (m, 3 H), 4.74 (s, 1 H), 4.70 (s, 1 H), 2.20 (s, 3 H), 2.16 (s, 3 H), 2.13 (s, 6 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -192.49 (s, 1 F), -197.11 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 196.1 (d, J = 21.8 Hz), 195.4 (d, J = 19.6 Hz), 175.9, 175.6, 139.0, 137.0, 136.8, 135.4, 135.1, 135.0, 134.9, 134.2, 133.9, 133.1, 132.8, 129.6, 129.5, 129.4, 128.9, 128.8, 128.6, 128.4, 127.4, 127.2, 127.1, 126.5, 125.7, 125.6, 124.3, 123.6, 120.3, 120.1, 94.8 (d, J = 194.7 Hz), 91.8 (d, J = 190.7 Hz), 75.9 (d, J = 22.3 Hz), 75.7 (d, J = 26.1 Hz), 45.4, 45.2, 20.7, 18.6, 18.5. IR (KBr) ν: 3361, 1685, 1598, 1359, 1081, 755 cm 1. HRMS (ESI) Calcd. for C 25 H 22 FNNa 3 [M+Na] + : 426.1481; Found:426.1478. 1-benzyl-5-fluoro-3-(1-fluoro-2-(4-fluorophenyl)-2-oxoethyl)-3-hydroxyindolin-2- one (3cb) F H F N Bn F Yellow oil. 1 H NMR (CDCl 3, 400 MH Z ) δ: 8.07 (dd, 2 H, J = 8.4 H Z, J = 5.2 H Z ), 7.90 (dd, 2 H, J = 7.6 H Z, J = 5.6 H Z ), 7.30-7.27 (m, 7 H), 7.25-7.20 (m, 4 H), 7.13-7.03 (m, 5 H), 6.90-6.84 (m, 2 H), 6.59-6.56 (m, 2 H), 6.04 (d, 1 H, J = 45.6 H Z ), 5.93 (d, 1 H, J = 46.8 H Z ), 5.07 (d, 1 H, J = 16.0 H Z ), 4.92-4.88 (m, 3 H), 4.75 (d, 1 H, J = 15.6 H Z ),
4.66 (d, 1 H, J = 16.0 H Z ). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -101.55 (s, 1 F), -102.25 (s, 1 F), -118.75 (s, 1 F), -118.90 (s, 1 F), -191.94 (s, 1 F), -197.35 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 193.5 (d, J = 19.7 Hz), 193.4 (d, J = 21.5 Hz), 174.6, 174.4, 166.5 (d, J = 257.9 Hz), 166.2 (d, J = 257.3 Hz), 159.3 (d, J = 242.7 Hz), 159.2 (d, J = 242.7 Hz), 139.4, 134.7, 134.5, 132.7, 132.6, 132.5, 132.4, 132.3, 131.4, 130.9, 129.0, 128.9, 128.1 (d, J = 8.1 Hz), 127.9, 127.8, 127.3 (d, J = 8.1 Hz), 127.2, 127.0, 117.1, 116.9, 116.6, 116.1, 115.9, 115.7, 114.1 (d, J = 25.4 Hz), 113.4 (d, J = 25.3 Hz), 113.3 (d, J = 25.1 Hz), 110.7, 110.6, 95.1 (d, J = 194.9 Hz), 91.3 (d, J = 190.8 Hz), 76.5 (d, J = 21.2 Hz), 76.4 (d, J = 25.5 Hz), 44.2. IR (KBr) ν: 3365, 1718, 1685, 1374, 1078, 731 cm 1. HRMS (ESI) Calcd. for C 23 H 16 F 3 NNa 3 [M+Na] + : 434.0980; Found:434.0980. 1-benzyl-5-fluoro-3-(1-fluoro-2-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxyindolin -2-one (3eb) F H F N Bn Yellow oil. 1 H NMR (CDCl 3, 400 MH Z ) δ: 7.94 (d, 2 H, J = 8.8 H Z ), 7.79 (d, 2 H, J = 8.4 H Z ), 7.22-7.13 (m, 11 H), 6.99 (dd, 1 H, J = 8.0 H Z, J = 2.4 H Z ), 6.83-6.73 (m, 6 H), 6.48-6.44 (m, 2 H), 5.94 (d, 1 H, J = 45.6 H Z ), 5.86 (d, 1 H, J = 47.2 H Z ), 5.00 (d, 1 H, J = 16.0 H Z ), 4.94 (s, 1 H), 4.86 (s, 1 H), 4.80 (d, 1 H, J = 16.0 H Z ), 4.63 (d, 1 H, J = 16.0 H Z ), 4.57 (d, 1 H, J = 16.0 H Z ), 3.73 (s, 3 H), 3.72 (s, 3 H). 19 F NMR (CDCl 3, 367.5 MH Z ) δ: -118.98 (s, 1 F), -119.15 (s, 1 F), -191.31 (s, 1 F), -196.94 (s, 1 F). 13 C NMR (CDCl 3, 100.6 MH Z ) δ: 192.5 (d, J = 19.5 Hz), 191.7 (d, J = 20.7 Hz), 173.5, 173.4, 163.7, 163.3, 158.2 (d, J = 242.1 Hz), 158.1 (d, J = 242.3 Hz), 138.4, 133.7, 133.5, 131.2 (d, J = 4.2 Hz), 131.0 (d, J = 5.9 Hz), 127.9, 127.8, 127.3, 126.8, 126.7, 126.5, 126.4, 126.3, 126.1, 125.9, 115.8, 115.6, 115.4, 113.2 113.0, 112.7,
112.3 (d, J = 25.5 Hz), 112.2 (d, J = 23.8 Hz), 109.5, 109.3, 93.9 (d, J = 194.4 Hz), 89.9 (d, J = 190.2 Hz), 75.6 (d, J = 18.0 Hz), 75.4 (d, J = 22.2 Hz), 54.5, 54.4, 43.1. IR (KBr) ν: 3365, 2253, 1715, 1597, 1376, 1029, 768, 693 cm 1. HRMS (ESI) Calcd. for C 24 H 19 F 2 NNa 4 [M+Na] + : 446.1180; Found:446.1176. 5. X-ray crystallography data for the major diastereomer of 3aa Figure 2 : RTEP drawing of 3aa 6. HPLC traces 6.1 HPLC traces for Table 4 1-benzyl-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxyindolin-2-one (3aa) ptical rotation: [α] 20 D -10.8 (c 0.5, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak AD-H column (Hexane: iprh = 75:25, 1.0 ml / min, 254 nm 7, t R (major) = 16.6 min, t R (minor) = 21.1 min; 92% ee). dr (99:1) determined by 19 F NMR analysis of unpurified reaction products.
归一化 175 150 125 100 75 16.512 20.206 23.436 25.662 50 25 0 0 5 10 15 20 25 min 归一化 400 16.644 300 200 100 0 0 5 10 15 20 25 21.158 min 1-benzyl-3-(1-fluoro-2-oxo-2-m-tolylethyl)-3-hydroxyindolin-2-one (3ba) ptical rotation: [α] 20 D -33.0 (c 0.62, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak D-H column (Hexane: iprh = 90:10, 1.0 ml / min, 254 nm, t R (major)=22.2 min, t R (minor)=28.1 min; 93% ee. dr (99:1) determined
by 19 F NMR analysis of unpurified reaction products. 归一化 175 150 125 100 75 1 8. 3 2 3 1 9. 5 4 3 2 1. 7 4 5 2 7. 3 5 6 50 25 0 0 5 10 15 20 25 min 归一化 175 150 125 100 2 2. 2 3 6 75 50 25 0 2 8. 1 9 6 0 5 10 15 20 25 30 min
1-benzyl-3-(1-fluoro-2-(4-fluorophenyl)-2-oxoethyl)-3-hydroxyindolin-2-one (3ca) ptical rotation: [α] 20 D -30.7 (c 0.57, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak AD-H column (Hexane: iprh = 75:25, 1.2 ml / min, 254 nm, t R (major)=18.6 min, t R (minor)=23.2 min; 91% ee. dr (99:1) determined by 19 F NMR analysis of unpurified reaction products.
1-benzyl-3-(2-(3,4-difluorophenyl)-1-fluoro-2-oxoethyl)-3-hydroxyindolin-2-one (3da) ptical rotation: [α] 20 D -23.9 (c 0.48, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak AD-H column (Hexane: iprh = 75:25, 1.0 ml / min, 254 nm, t R (major)=16.6 min, t R (minor)=21.1 min; 83% ee. dr (99:1) determined by 19 F NMR analysis of unpurified reaction products. 归一化 600 500 400 300 1 7. 7 5 3 2 0. 7 1 0 2 3. 7 9 6 2 5. 6 4 6 200 100 0 0 5 10 15 20 25 min
归一化 350 300 250 200 1 7. 7 8 6 150 100 50 2 0. 7 4 6 0 0 5 10 15 20 25 min 1-benzyl-3-(1-fluoro-2-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxyindolin-2-one (3ea) ptical rotation: [α] 20 D -23.9 (c 0.73, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak AD-H column (Hexane: iprh=80:20, 1.0 ml/min, 254 nm, t R (major)=34.8 min, t R (minor)=50.0 min; 95% ee. dr (99:1) determined by 19 F NMR analysis of unpurified reaction products.
峰号 保留时间峰高 峰面积 含量 1 35.043 88987.289 5495844.000 24.583 2 50.417 63079.746 5489980.000 24.557 3 60.857 54170.875 5687971.500 25.443 4 65.965 50219.348 5682324.500 25.417 峰号保留时间峰高峰面积含量 1 34.862 143699.359 8740403.000 97.278 2 50.058 3245.538 244546.906 2.722 1-benzyl-3-(1-fluoro-2-oxo-2-o-tolylethyl)-3-hydroxyindolin-2-one (3fa) ptical rotation: [α] 20 D -18.9 (c 0.37, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak AD-H column (Hexane: iprh=80:20, 1.0 ml/min,
254 nm, t R (major)=22.2 min, t R (minor)=25.3 min; 93% ee. dr (99:1) determined by 19 F NMR analysis of unpurified reaction products. 峰号 峰名 保留时间 峰高 峰面积 含量 1 22.173 74453.680 2638018.750 6.866 2 25.107 65503.430 2593331.500 6.750 3 26.907 361974.281 16502600.000 42.951 4 30.373 328274.719 16687642.000 43.433 峰号 保留时间 峰高 峰面积 含量 1 22.287 290994.781 10432552.000 96.245 2 25.310 10923.204 407055.719 3.755 1-benzyl-3-(2-(4-bromophenyl)-1-fluoro-2-oxoethyl)-3-hydroxyindolin-2-one (3ga) ptical rotation: [α] D 20-41.4 (c 0.41, CH 2 Cl 2 ). The enantiomeric ratio was determined
by HPLC with a Daicel Chiralpak AD-H column (Hexane: iprh=75:25, 1.2 ml/min, 254 nm, t R (major)=21.9 min, t R (minor)=26.2 min; 88% ee. dr (99:1) determined by 19 F NMR analysis of unpurified reaction products. 归一化 1200 34.639 1000 800 600 22.567 27.031 400 200 0 10 15 20 25 30 35 40 min 归一化 350 300 250 200 21.937 150 100 50 0 5 10 15 20 25 30 35 40 26.231 min 1-benzyl-3-(2-(4-chlorophenyl)-1-fluoro-2-oxoethyl)-3-hydroxyindolin-2-one (3ha) ptical rotation: [α] D 20-29.0 (c 0.62, CH 2 Cl 2 ). The enantiomeric ratio was determined
by HPLC with a Daicel Chiralpak D-H column (Hexane: iprh=75:25, 1.2 ml/min, 254 nm, t R (major)=20.6 min, t R (minor)=24.9 min; 91% ee. dr (99:1) determined by 19 F NMR analysis of unpurified reaction products. 归一化 700 600 500 400 20.793 25.156 300 200 30.342 32.476 100 0 0 5 10 15 20 25 30 35 min 归一化 350 300 250 200 20.600 150 100 50 0 0 5 10 15 20 25 30 24.950 min 1-benzyl-3-(1-fluoro-2-(furan-2-yl)-2-oxoethyl)-3-hydroxyindolin-2-one (3ia) ptical rotation: [α] 20 D -26.8 (c 0.67, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak D-H column (Hexane: iprh=90:10, 1.0 ml/min, 254 nm, t R (major)=30.6 min, t R (minor)=40.6 min; 92% ee. dr (99:1) determined by
19 F NMR analysis of unpurified reaction products. 峰号 峰名 保留时间 峰高 峰面积 含量 1 24.115 182794.688 11068686.000 30.942 2 27.048 97786.070 6725082.000 18.800 3 30.382 140763.094 11340282.000 31.701 4 34.648 74646.281 6638529.500 18.558 峰号 保留时间 峰高 峰面积 含量 1 30.613 201524.391 17003948.000 95.534 2 40.633 12724.000 794850.375 4.466 3-fluoro-4-nitro-3-phenyl-1-(thiophen-2-yl)butan-1-one (3ja) ptical rotation: [α] 20 D -34.0 (c 0.50, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak D-H column (Hexane: iprh=90:10, 1.0 ml/min, 254 nm, t R (major)=30.0 min, t R (minor)=40.1 min; 98% ee. dr (99:1) determined by 19 F NMR analysis of unpurified reaction products.
峰号 保留时间 峰高 峰面积 含量 1 29.773 94729.781 9470173.000 22.594 2 33.973 108774.016 11317253.000 27.001 3 38.707 73733.719 9861062.000 23.527 4 43.707 81863.664 11265348.000 26.877 峰号 保留时间 峰高 峰面积 含量 1 30.025 240152.438 17958198.000 98.803 2 40.168 5728.000 217593.813 1.197 1-benzyl-3-(1-fluoro-2-oxopropyl)-3-hydroxyindolin-2-one (3ka) ptical rotation: [α] 20 D -37.5 (c 0.4, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak AD-H column (Hexane: iprh=90:10, 1.0 ml/min, 254 nm, t R (minor)=33.9 min, t R (major)=38.0 min; 83% ee. dr (1:99) determined by 19 F NMR analysis of unpurified reaction products.
峰号 保留时间 峰高 峰面积 含量 1 30.765 76160.078 3917035.250 29.049 2 33.832 56363.715 2880912.750 21.365 3 37.965 50277.738 2951156.750 21.886 4 54.365 43617.406 3735190.750 27.700 峰号 保留时间 峰高 峰面积 含量 1 33.922 3527.881 137715.688 8.883 2 38.035 24817.947 1412537.250 91.117 1-benzyl-3-(2-cyclopropyl-1-fluoro-2-oxoethyl)-3-hydroxyindolin-2-one (3la) ptical rotation: [α] 20 D -31.9 (c 0.36, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak AD-H column (Hexane: iprh=80:20, 1.0 ml/min, 254 nm, t R (minor)=18.2 min, t R (major)=19.8 min; 85% ee. dr (1:99) determined by 19 F NMR analysis of unpurified reaction products.
峰号 保留时间 峰高 峰面积 含量 1 16.573 219494.328 5968100.000 28.681 2 18.523 141551.422 4336113.500 20.838 3 20.307 130403.430 4455674.500 21.413 4 41.315 88830.742 6048633.000 29.068 峰号 保留时间 峰高 峰面积 含量 1 18.230 7203.479 217521.281 7.753 2 19.897 81340.742 2587975.500 92.247 6.2 HPLC traces for Table 5 1-benzyl-5-fluoro-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxyindolin-2-one (3ab) ptical rotation: [α] 20 D -10.0 (c 0.5, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak AD-H column (Hexane: iprh = 80:20, 1.0 ml / min, 254 nm, t R (major)=20.4 min, t R (minor)=31.2 min; 92% ee. dr (99:1) determined by 19 F NMR analysis of unpurified reaction products.
峰号 保留时间 峰高 峰面积 含量 1 20.182 817638.625 29774606.000 28.080 2 30.715 566738.750 31015736.000 29.251 3 33.248 372648.750 22501578.000 21.221 4 64.315 192583.422 22741444.000 21.447 峰号 保留时间 峰高 峰面积 含量 1 20.435 544381.000 19583962.000 95.558 2 31.280 17211.100 910291.250 4.442 1-benzyl-6-bromo-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxyindolin-2-one (3ac) ptical rotation: [α] 20 D -15.7 (c 0.54, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak AD-H column (Hexane: iprh = 80:20, 1.0 Ml / min, 254 nm, t R (major)=19.6 min, t R (minor)=29.1 min; 91% ee. dr (99:1) determined by 19 F NMR analysis of unpurified reaction products.
峰号 保留时间 峰高 峰面积 含量 1 20.048 183771.953 6229106.000 20.011 2 29.982 122111.820 6292196.000 20.213 3 36.782 145209.219 9289163.000 29.841 4 38.715 138425.578 9318298.000 29.935 峰号 保留时间 峰高 峰面积 含量 1 19.675 613632.250 20802324.000 95.153 2 29.182 21864.230 1059735.500 4.847 1-benzyl-5-bromo-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxyindolin-2-one (3ad) ptical rotation: [α] 20 D -13.6 (c 0.44, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak AD-H column (Hexane: iprh = 80:20, 1.0 ml / min, 254 nm, t R (major)=25.8 min, t R (minor)=37.4 min; 92% ee. dr (99:1) determined by 19 F NMR analysis of unpurified reaction products.
峰号 保留时间 峰高 峰面积 含量 1 27.065 206577.344 9818364.000 19.563 2 39.665 143111.281 9912351.000 19.750 3 42.932 197078.109 15127138.000 30.140 4 91.398 94325.844 15331529.000 30.547 峰号 保留时间 峰高 峰面积 含量 1 25.883 257727.672 11346634.000 95.561 2 37.437 8579.856 527060.000 4.439 1-benzyl-7-chloro-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxyindolin-2-one (3ae) ptical rotation: [α] 20 D -12.8 (c 0.5, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak AD-H column (Hexane: iprh = 80:20, 1.0 ml / min, 254 nm, t R (major)=22.6 min, t R (minor)=31.2 min; 86% ee. dr (99:1) determined by 19 F NMR analysis of unpurified reaction products.
峰号 保留时间 峰高 峰面积 含量 1 22.765 438113.281 17715246.000 20.168 2 31.265 322728.313 17701046.000 20.152 3 38.148 383933.031 26195198.000 29.823 4 49.732 296341.969 26224772.000 29.856 峰号 保留时间 峰高 峰面积 含量 1 22.682 452147.656 18300132.000 92.924 2 31.215 26290.555 1393474.875 7.076 1-benzyl-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxy-5-methylindolin-2-one (3af) ptical rotation: [α] 20 D -26.5 (c 0.47, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak AD-H column (Hexane: iprh = 80:20, 1.0 ml / min, 254 nm, t R (major)=21.6 min, t R (minor)=29.0 min; 92% ee. dr (99:1) determined by 19 F NMR analysis of unpurified reaction products.
峰号 保留时间 峰高 峰面积 含量 1 21.732 553665.000 21542932.000 18.854 2 29.132 421037.000 21913598.000 19.178 3 38.832 503264.313 35208852.000 30.813 4 47.098 411975.531 35599000.000 31.155 峰号保留时间峰高峰面积含量 1 21.630 623997.500 24432728.000 95.640 2 29.097 22866.035 1113838.750 4.360 1-benzyl-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxy-5-methoxyindolin-2-one (3ag) ptical rotation: [α] 20 D -20.2 (c 0.47, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak AD-H column (Hexane: iprh = 80:20, 1.0 ml / min, 254 nm, t R (major)=34.8 min, t R (minor)=41.7 min; 98% ee. dr (99:1) determined by 19 F NMR analysis of unpurified reaction products.
峰号 保留时间 峰高 峰面积 含量 1 35.165 96812.000 6104612.000 27.596 2 42.065 81637.555 5985802.500 27.059 3 67.998 45155.039 5105151.500 23.078 4 78.698 38507.543 4925404.000 22.266 峰号 保留时间 峰高 峰面积 含量 1 34.818 232947.094 14180180.000 98.599 2 41.715 4667.507 201540.047 1.401 1-benzyl-4-bromo-3-(1-fluoro-2-oxo-2-phenylethyl)-3-hydroxyindolin-2-one (3ah) ptical rotation: [α] 20 D -25.4 (c 0.59, CH 2 Cl 2 ). The enantiomeric ratio was determined by HPLC with a Daicel Chiralpak D-H column (Hexane: iprh = 80:20, 1.0 ml / min, 254 nm, t R (major)=13.1 min, t R (minor)=35.0 min; 90% ee. dr (99:1) determined by 19 F NMR analysis of unpurified reaction products.