3. Materials and Methods
All reagents were purchased from commercial sources and used without any further purification. All solvents were dried before use by the standard procedure [
34]. Melting points (m.p.) were measured with a Büchi B-545 melting point apparatus (Büchi, Flawil, Switzerland). Microwave activated reactions were conducted in Monowave 200 (Anton Paar, Graz, Austria). NMR (
1H,
13C and
19F) spectra were obtained with the Bruker AVANCE 400 (Bruker Corp., Karlsruhe, Germany) and Agilent 400-MR spectrometers (Agilent Technologies, Santa Clara, CA, USA) using deuterated chloroform (CDCl
3). Chemical shifts for the
1H NMR spectroscopic data were referenced to the internal tetramethylsilane (δ = 0.0 ppm) and the residual solvent resonance (δ = 7.26 ppm); chemical shifts for the
13C NMR spectroscopic data were referenced to the residual solvent resonance (δ = 77.16 ppm); chemical shifts for the
19F NMR spectroscopic data were referenced to PhCF
3 (δ = −63.72 ppm) or C
6F
6 (δ = −164.90 ppm). Data were reported as follows: chemical shift; integration multiplicity (s = singlet, d = doublet, t = triplet, q = quadruplet, qui = quintet, sext = sextet, sept = septet, br = board, m = multiplet, dd = doublet of doublets and ddd = doublet of doublet of doublets) and coupling constants (Hz). Starting β-fluoro-β-nitrostyrenes were prepared according to the described procedures [
22,
35]. All nitrostyrenes are known compounds [
22,
23,
24,
25,
26,
27,
28,
29,
30].
General procedure for the conjugate addition of 1H-pyrrole to β-fluoro-β-nitrostyrenes.
In a typical experiment, β-fluoro-β-nitrostyrene (0.5 mmol) and pyrrole (0.5 mL) were successively loaded into a vial. The reaction mixture was stirred at room temperature for 25–30 h. After completion of the reaction (TLC monitoring), the excess of pyrrole was evaporated under vacuum. The desired product was isolated by column chromatography on silica gel as a mixture of diastereomers.
2-(2-Fluoro-2-nitro-1-phenylethyl)-1H-pyrrole (3a). Eluent: Hex/DCM 1:1, DCM; 107 mg (88 %); dr = 42:58; colorless oil. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 7.99 (br s, 1H), 7.46–7.23 (m, 5H), 6.78–6.71 (m, 1H), 6.33–6.28 (m, 1H), 6.28 (dd, 2JHF = 50.0, 3.5 Hz, 1H), 6.20 (t, J = 2.3 Hz, 1H), 4.97 (dd, 3JHF = 28.5, 3.4 Hz, 1H) ppm; (minor isomer) δ = 8.11 (br s, 1H), 7.46–7.23 (m, 5H), 6.78–6.71 (m, 1H), 6.26–6.23 (m, 1H), 6.20 (t, J = 2.3 Hz, 1H), 6.19 (dd, 2JHF = 50.0, 3.4 Hz, 1H), 4.99 (dd, 3JHF = 28.0, 4.0 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 133.2, 129.2, 129.1, 128.4, 125.7, 118.9, 111.5 (d, 1JCF = 245.4 Hz), 109.0, 107.6, 47.9 (d, 2JCF = 18.7 Hz) ppm; (minor isomer) δ = 135.1 (d, 3JCF = 1.6 Hz), 129.4, 128.8, 128.6, 123.8, 119.2, 112.4 (d, 1JCF = 243.7 Hz), 109.2 (d, 4JCF = 0.8 Hz), 108.9, 48.0 (d, 2JCF = 18.6 Hz) ppm; 19F NMR (376 MHz, CDCl3): (major isomer) δ = −153.26 (dd, J = 50.0, 28.5 Hz) ppm; (minor isomer) δ = −151.19 (dd, J = 50.0, 28.0 Hz) ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C12H10FN2O2 233.0732; found 233.0735.
2-(2-Fluoro-1-(4-methoxyphenyl)-2-nitroethyl)-1H-pyrrole (3b). Eluent: Hex/DCM 1:1, DCM; 67 mg (>99%); dr = 40:60; colorless oil. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 7.99 (br s, 1H), 7.16 (d, J = 8.5 Hz, 2H), 6.86 (d, J = 8.7 Hz, 2H), 6.77–6.69 (m, 1H), 6.27 (dd, 2JHF = 50.2, 3.2 Hz, 1H), 6.26 (s, 1H), 6.24–6.14 (m, 1H), 4.92 (dd, 3JHF = 29.0, 3.5 Hz, 1H), 3.78 (s, 3H) ppm; (minor isomer) δ = 8.11 (br s, 1H), 7.23 (d, J = 8.6 Hz, 2H), 6.91 (d, J = 8.7 Hz, 2H), 6.77–6.69 (m, 1H), 6.14 (dd, 2JHF = 50.1, 3.8 Hz, 1H), 6.24–6.13 (m, 2H), 4.91 (dd, 3JHF = 27.0, 4.3 Hz, 1H), 3.81 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 159.9, 130.4, 126.1, 125.0, 118.7, 114.5, 111.5 (d, 1JCF = 244.9 Hz), 109.0, 107.3, 55.4, 47.2 (d, 2JCF = 18.9 Hz) ppm; (minor isomer) δ = 159.7, 129.7, 126.8 (d, 3JCF = 2.3 Hz), 124.3, 119.0, 114.7, 112.7 (d, 1JCF = 243.5 Hz), 108.9 (d, 4JCF = 0.8 Hz), 108.9, 55.4, 47.3 (d, 2JCF = 18.7 Hz) ppm. 19F NMR (376 MHz, CDCl3): (major isomer) δ = −153.92 (dd, J = 50.2, 29.0 Hz) ppm; (minor isomer) δ = −150.63 (dd, J = 50.1, 27.0 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C13H14FN2O3 265.0983; found 265.0986.
2-(1-(4-(Tert-butyl)phenyl)-2-fluoro-2-nitroethyl)-1H-pyrrole (3c). Eluent: Hex/DCM 1:1, DCM; 131 mg (85 %); dr = 42:58; yellowish oil. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 7.96 (br s, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.2 Hz, 2H), 6.75–6.71 (m, 1H), 6.29 (br s, 1H), 6.24 (dd, J = 5.8, 3.2 Hz, 1H), 6.27 (dd, 2JHF = 50.1, 3.6 Hz, 1H), 4.96 (dd, 3JHF = 28.3, 3.5 Hz, 1H), 1.33 (s, 9H) ppm; (minor isomer) δ = 8.09 (br s, 1H), 7.44 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 9.0 Hz, 2H), 6.75–6.71 (m, 1H), 6.17–6.21 (m, 2H), 6.18 (dd, 2JHF = 50.1, 3.7 Hz, 1H), 4.99 (dd, 3JHF = 28.4, 3.8 Hz, 1H), 1.36 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 151.7, 130.1, 128.9, 126.1, 125.9 (d, 4JCF = 0.9 Hz), 118.7, 111.6 (d, 1JCF = 245.1 Hz), 109.0, 107.4, 47.5 (d, 2JCF = 18.9 Hz), 34.6, 31.3 ppm; (minor isomer) δ = 151.8, 132.1 (d, 3JCF = 1.3 Hz), 128.1, 126.3, 123.9, 119.0, 112.4 (d, 1JCF = 243.9 Hz), 109.1, 108.9, 47.5 (d, 2JCF = 18.4 Hz), 34.7, 31.3 ppm.19F NMR (376 MHz, CDCl3): (major isomer) δ = −152.75 (dd, J = 50.1, 28.3 Hz) ppm; (minor isomer) δ = −151.15 (ddd, J = 50.1, 28.4, 5.0 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C16H20FN2O2 291.1509; found 291.1503.
2-(2-Fluoro-2-nitro-1-(p-tolyl)ethyl)-1H-pyrrole (3d). Eluent: Hex/DCM 1:1; 122 mg (99 %); dr = 44:56; yellowish oil. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 8.09 (br s, 1H), 7.20–7.12 (m, 4H), 6.77–6.70 (m, 1H), 6.31–6.27 (m, 1H), 6.27 (dd, 2JHF = 50.1, 3.5 Hz, 1H), 6.25 (dd, J = 5.7, 2.5 Hz, 1H), 4.94 (dd, 3JHF = 28.4, 3.4 Hz, 1H), 2.36 (s, 3H) ppm; (minor isomer) δ = 7.97 (br s, 1H), 7.22 (s, 4H), 6.77–6.70 (m, 1H), 6.21–6.17 (m, 2H), 6.17 (dd, 2JHF = 50.1, 4.2 Hz, 1H), 4.95 (dd, 3JHF = 27.6, 4.3 Hz, 1H), 2.39 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 138.7, 130.1, 129.8, 129.1, 125.9, 118.7, 111.5 (d, 1JCF = 245.3 Hz), 109.0, 107.4 (d, 4JCF = 1.0 Hz), 47.6 (d, 2JCF = 18.9 Hz), 21.2 ppm; (minor isomer) δ = 138.6 ppm, 131.9 (d, 3JCF = 2.1 Hz), 130.0, 128.3, 124.1, 119.0, 112.6 (d, 1JCF = 243.5 Hz), 109.0, 108.8, 47.6 (d, 2JCF = 18.9 Hz), 21.2 ppm. 19F NMR (376 MHz, CDCl3): (major isomer) δ = −153.31 (dd, J = 50.1, 28.4 Hz) ppm; (minor isomer) δ = −150.74 (dd, J = 50.1, 27.6 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C13H14FN2O2 249.1039; found 249.1054.
2-(2-Fluoro-1-(4-fluorophenyl)-2-nitroethyl)-1H-pyrrole (3e). Eluent: Hex/DCM 1:1, DCM; 118 mg (94%); dr = 44:56; yellowish oil. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 8.01 (br s, 1H), 7.22 (dd, J = 8.5, 5.2 Hz, 2H), 7.06 –6.98 (m, 2H), 6.80–6.72 (m, 1H), 6.29 (br s, 1H), 6.28 (dd, 2JHF = 50.0, 3.2 Hz, 1H), 6.26–6.15 (m, 1H), 4.97 (dd, 3JHF = 28.8, 3.1 Hz, 1H) ppm; (minor isomer) δ = 8.14 (br s, 1H), 7.30 (dd, J = 8.5, 5.2 Hz, 2H), 7.05–7.13 (m, 2H), 6.72–6.80 (m, 1H), 6.15–6.26 (m, 2H), 6.16 (dd, 2JHF = 50.0, 3.5 Hz, 1H), 4.97 (dd, 3JHF = 27.6, 3.1 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 162.9 (d, 1JCF = 248.2 Hz), 131.0 (d, 3JCF = 8.2 Hz), 129.0 (d, 3JCF = 3.1 Hz), 125.5, 119.0, 116.1 (d, 2JCF = 21.4 Hz), 111.2 (d, 1JCF = 245.4 Hz), 109.1, 107.7, 47.2 (d, 2JCF = 18.8 Hz) ppm; (minor isomer) δ = 162.7 (d, 1JCF = 248.2 Hz), 130.9 (t, 3JCF = 2.6 Hz), 130.2 (d, 3JCF = 8.2 Hz), 123.6, 119.3, 116.3 (d, 2JCF = 21.3 Hz), 47.3 (d, 2JCF = 18.6 Hz), 109.0, 109.3, 112.3 (d, 1JCF = 243.7 Hz) ppm. 19F NMR (376 MHz, CDCl3): (major isomer) δ = −113.92 (tt, J = 8.5, 5.2 Hz), −154.01 (dd, J = 50.0, 28.8 Hz) ppm; (minor isomer) δ = −114.10 (tt, J = 8.5, 5.2 Hz), −151.24 (dd, J = 50.0, 27.6 Hz) ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C12H9F2N2O2 251.0638; found 251.0644.
2-(1-(4-Bromophenyl)-2-fluoro-2-nitroethyl)-1H-pyrrole (3f). Eluent: Hex/DCM 1:1; 133 mg (84 %); dr = 44:56; yellowish oil; 1H NMR (400 MHz, CDCl3): (major isomer) δ = 8.01 (br s, 1H), 7.49–7.44 (m, 2H), 7.11 (d, J = 8.3 Hz, 2H), 6.76 (ddd, J = 4.1, 2.8, 1.5 Hz, 1H), 6.31–6.27 (m, 1H), 6.27 (dd, 2JHF = 49.9, 3.3 Hz, 1H), 6.24 (dd, J = 6.1, 2.8 Hz, 1H), 4.94 (dd, 3JHF = 28.6, 3.5 Hz, 1H) ppm; (minor isomer) δ = 8.13 (br s, 1H), 7.55–7.50 (m, 2H), 7.19 (d, J = 8.5 Hz, 2H), 6.76 (ddd, J = 4.1, 2.8, 1.5 Hz, 1H), 6.16 (dd, 2JHF = 50.0, 4.0 Hz, 1H), 6.14–6.20 (m, 2H), 4.95 (dd, 3JHF = 28.2, 5.2 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 134.1 (d, 3JCF = 1.8 Hz), 132.5, 132.3, 132.2, 130.1, 125.1, 123.1, 122.8, 119.4, 119.1, 111.9 (d, 1JCF = 244.0 Hz), 111.0 (d, 1JCF = 245.7 Hz), 109.5, 109.1, 109.0, 107.9 (d, 4JCF = 1.2 Hz), 47.4 (d, 2JCF = 18.7 Hz), 47.3 (d, 2JCF = 18.7 Hz) ppm.19F NMR (376 MHz, CDCl3): (major isomer) δ = −153.62 (dd, J = 49.9, 28.6 Hz) ppm; (minor isomer) δ = −151.36 (dd, J = 50.0, 28.2 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H1180BrFN2O2 312.9982; found 312.9951.
2-(1-(4-Chlorophenyl)-2-fluoro-2-nitroethyl)-1H-pyrrole (3g). Eluent: Hex/DCM 1:1, DCM; 131 mg, (97 %); dr = 42:58; yellowish oil. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 8.02 (br s, 1H), 7.32 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 8.4 Hz, 2H), 6.76 (s, 1H), 6.29 (br s, 1H), 6.27 (dd, J = 50.0, 3.3 Hz, 1H), 6.25 (dd, J = 5.8, 2.8 Hz, 1H), 4.95 (dd, 3JHF = 28.6, 3.2 Hz, 1H) ppm; (minor isomer) δ = 8.14 (br s, 1H), 7.37 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.4 Hz, 1H), 6.76 (s, 1H), 6.16 (dd, 2JHF = 50.0, 4.0 Hz, 2H), 6.21–6.15 (m, 2H), 4.97 (dd, 3JHF = 27.9, 5.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): (major isomer) δ = 134.9, 131.7, 130.5, 129.3, 125.1, 119.1, 111.1 (d, 1JCF = 245.6 Hz), 109.1, 107.8 (d, 4JCF = 1.1 Hz), 47.2 (d, 2JCF = 18.7 Hz) ppm; (minor isomer) δ = 134.6, 133.6 (d, 3JCF = 1.5 Hz), 129.8, 129.5, 123.2, 119.4, 112.0 (d, 1JCF = 244.0 Hz), 109.4, 109.0, 47.3 (d, 2JCF = 18.8 Hz) ppm; 19F NMR (376 MHz, CDCl3): (major isomer) δ = −153.65 (dd, J = 50.0, 28.6 Hz) ppm; (minor isomer) δ = −151.35 (dd, J = 50.0, 27.9 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H1135ClFN2O2 269.0493; found 269.0485.
2-(1-(2,4-Dichlorophenyl)-2-fluoro-2-nitroethyl)-1H-pyrrole (3h). Eluent: Hex/DCM 1:1; 145 mg, (96 %); dr = 48:52; yellowish oil; 1H NMR (400 MHz, CDCl3): δ = 8.21 (br s, 1H) ppm, 8.11 (br s, 1H), 7.51–7.47 (m, 1H), 7.46–7.41 (m, 2H), 7.29–7.22 (m, 3H), 6.78–6.73 (m, 2H), 6.31 (dd, 2JHF = 50.0, 3.8 Hz, 1H), 6.29–6.24 (m, 2H), 6.21 (td, J = 6.3, 2.8 Hz, 2H), 6.19 (dd, 2JHF = 49.9, 3.3 Hz, 1H), 5.59 (dd, 3JHF = 26.5, 4.0 Hz, 1H), 5.57 (dd, 3JHF = 30.8, 3.2 Hz, 1H) ppm.13C NMR (100 MHz, CDCl3): δ = 135.3, 135.2, 134.9, 134.0, 131.8, 131.5 (d, JCF = 1.0 Hz), 131.1 (d, JCF = 4.1 Hz), 130.5, 130.0, 129.9, 128.1, 128.0, 124.3 (d, JCF = 1.8 Hz), 121.8, 119.3, 119.2, 110.8 (d, 1JCF = 246.1 Hz), 110.1 (d, 1JCF = 244.1 Hz), 110.1 (d, 4JCF = 2.0 Hz), 109.3, 109.2, 108.3, 44.2 (d, 2JCF = 18.4 Hz), 42.9 (d, 2JCF = 18.7 Hz) ppm. 19F NMR (376 MHz, CDCl3): (major isomer) δ = −155.07 (dd, J = 49.8, 30.7 Hz) ppm; (minor isomer) δ = −151.19 (dd, J = 49.8, 26.3 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H1035Cl2FN2O2 303.0098; found 303.0095.
2-(2-Fluoro-2-nitro-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-pyrrole (3i). Eluent: Hex/DCM 1:1, DCM; 142 mg (94%); dr = 38:62; yellow solid; M.p. = 68–72 ºC. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 8.04 (br s, 1H), 7.61 (d, J = 8.1 Hz, 2H), 7.39 (d, J = 8.1 Hz, 2H), 6.81–6.75 (m, 1H), 6.31 (dd, 2JHF = 49.8, 3.4 Hz, 1H), 6.35–6.30 (m, 1H), 6.21 (t, J = 2.4 Hz, 1H), 5.05 (dd, 3JHF = 28.3, 3.3 Hz, 1H) ppm; (minor isomer) δ = 8.17 (br s, 1H), 7.67 (d, J = 8.2 Hz, 2H), 7.46 (d, J = 8.1 Hz, 2H), 6.75–6.81 (m, 1H), 6.22–6.30 (m, 1H), 6.22 (dd, 2JHF = 49.9, 3.7 Hz, 1H), 6.21 (t, J = 2.4 Hz, 1H), 5.08 (dd, 3JHF = 28.6, 3.7 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 137.4, 131.0 (q, 2JCF = 32.8 Hz), 129.7, 126.1 (q, 3JCF = 3.7 Hz), 124.7, 123.9 (q, 1JCF = 272.2 Hz), 119.4, 111.1 (d, 1JCF = 245.9 Hz), 109.3, 108.2 (d, 4JCF = 1.1 Hz), 47.6 (d, 2JCF = 18.8 Hz) ppm; (minor isomer) δ = 139.2, 130.9 (q, 2JCF = 32.6 Hz), 128.9, 126.3 (q, 3JCF = 3.6 Hz), 123.9 (q, 1JCF = 272.2 Hz), 122.7, 119.7, 111.8 (d, 1JCF = 244.2 Hz), 109.8, 109.1, 47.7 (d, 2JCF = 18.6 Hz) ppm; 19F NMR (376 MHz, CDCl3): (major isomer) δ = −65.89 (s, 1F), −155.34 (dd, J = 49.8, 28.3 Hz, 3F) ppm; (minor isomer) δ = −65.86 (s, 1F), -153.71 (dd, J = 49.9, 28.6 Hz, 3F) ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C13H10F4N2O2 301.0606; found 301.0612.
Methyl 4-(2-fluoro-2-nitro-1-(1H-pyrrol-2-yl)ethyl)benzoate (3j). Eluent: Hex/DCM 1:1, DCM; 138 mg (95%), dr = 42:58); yellowish oil; 1H NMR (400 MHz, CDCl3): (major isomer) δ = 8.46 (br s, 1H), 7.93 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.2 Hz, 2H), 6.78–6.74 (m, 1H), 6.31 (dd, 2JHF = 49.8, 3.4 Hz, 1H), 6.27–6.31 (m, 1H), 6.23 (dd, J = 5.9, 2.8 Hz, 1H), 5.03 (dd, 3JHF = 28.2, 3.4 Hz, 1H), 3.88 (s, 3H) ppm; (minor isomer) δ = 8.46 (br s, 1H), 8.00 (d, J = 8.3 Hz, 2H), 7.37 (d, J = 8.2 Hz, 2H), 6.78–6.74 (m, 1H), 6.22 (dd, 2JHF = 49.9, 3.9 Hz, 1H), 6.20–6.16 (m, 2H), 5.05 (dd, 3JHF = 28.3, 3.8 Hz, 1H), 3.91 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): (major isomer) δ = 166.8, 138.51, 130.32, 130.17, 129.27, 124.84, 119.22, 111.14 (d, 1JCF = 245.8 Hz), 109.04, 108.02 (d, 4JCF = 1.1 Hz), 52.38, 47.69 (d, 2JCF = 18.7 Hz) ppm; (minor isomer) δ = 166.7, 140.3 (d, 3JCF = 0.9 Hz), 130.4, 130.3, 128.5, 122.9, 119.5, 111.8 (d, 1JCF = 244.1 Hz), 109.5, 108.9, 52.4, 47.8 (d, 2JCF = 18.8 Hz) ppm. 19F NMR (376 MHz, CDCl3): (major isomer) δ = −153.04 (dd, J = 49.8, 28.2 Hz) ppm; (minor isomer) δ = −151.51 (dd, J = 49.9, 28.3 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C14H14FN2O4 293.0932; found 293.0936.
4-(2-Fluoro-2-nitro-1-(1H-pyrrol-2-yl)ethyl)benzonitrile (3k). Eluent: Hex/DCM 1:1, DCM; 130 mg (85 %); dr = 38:62; yellowish oil; 1H NMR (400 MHz, CDCl3): (major isomer) δ = 8.36 (br s, 1H), 7.61–7.55 (m, 2H), 7.37 (d, J = 8.2 Hz, 2H), 6.81–6.76 (m, 1H), 6.31 (dd, 2JHF = 49.7, 3.3 Hz, 1H), 6.32–6.28 (m, 1H), 6.23 (dd, J = 6.0, 2.8 Hz, 1H), 5.06 (dd, 3JHF = 28.4, 3.2 Hz, 1H) ppm; (minor isomer) δ = 8.36 (br s, 1H), 7.67–7.62 (m, 2H), 7.45 (d, J = 8.3 Hz, 2H), 6.81–6.76 (m, 1H), 6.22 (dd, 2JHF = 49.8, 3.7 Hz, 1H), 6.22–6.17 (m, 2H), 5.09 (dd, 3JHF = 28.6, 3.6 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 138.9, 132.7, 130.0, 124.2, 119.5, 118.4, 112.4, 110.8 (d, 1JCF = 246.2 Hz), 109.2, 108.4 (d, 4JCF = 1.3 Hz), 47.6 (d, 2JCF = 18.5 Hz) ppm; (minor isomer) δ = 140.7, 133.0, 129.3, 122.2, 119.7, 118.3, 112.2, 111.3 (d, 1JCF = 244.5 Hz), 109.8, 109.1, 47.8 (d, 2JCF = 17.1 Hz) ppm. 19F NMR (376 MHz, CDCl3): (major isomer) δ = −153.37 (dd, J = 49.7, 28.4 Hz) ppm; (minor isomer) δ = −151.89 (dd, J = 49.8, 28.6 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C13H11FN3O2 260.0830; found 260.0829.
2-(2-Fluoro-2-nitro-1-(4-nitrophenyl)ethyl)-1H-pyrrole (3l). Eluent: Hex/DCM 1:1, DCM; 428 mg (>99% yield), scaled-up 1303 mg (99%); dr = 40:60; brown waxy solid. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 8.24 (br s, 1H), 8.14 (d, J = 8.6 Hz, 2H), 7.43 (d, J = 8.6 Hz, 1H), 6.84–6.79 (m, 1H), 6.33 (dd, 2JHF = 49.7, 3.2 Hz, 2H), 6.35–6.29 (m, 1H), 6.24 (dd, J = 5.7, 2.8 Hz, 1H), 5.12 (dd, 3JHF = 28.2, 3.1 Hz, 1H) ppm; (minor isomer) δ = 8.31 (br s, 1H), 8.21 (d, J = 8.7 Hz, 1H), 6.84–6.79 (m, 1H), 6.25 (dd, 2JHF = 49.9, 3.7 Hz, 3H), 6.22–6.17 (m, 2H), 5.13 (dd, 3JHF = 28.4, 3.7 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 148.0, 140.7, 130.3, 124.1, 124.1, 119.7, 110.9 (d, 1JCF = 246.1 Hz), 109.4, 108.6 (d, 4JCF = 1.3 Hz), 47.5 (d, 2JCF = 18.9 Hz) ppm; (minor isomer) δ = 147.9, 142.5, 129.5, 124.4, 122.1, 119.9, 111.3 (d, 1JCF = 244.4 Hz), 110.1, 109.3, 47.7 (d, 2JCF = 19.2 Hz) ppm. 19F NMR (376 MHz, CDCl3): (major isomer) δ = −153.27 (dd, J = 49.7, 28.2 Hz) ppm; (minor isomer) δ = −151.61 (dd, J = 49.9, 28.4 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H11FN3O4 280.0728; found 280.0728.
2-(2-Fluoro-2-nitro-1-(3-nitrophenyl)ethyl)-1H-pyrrole (3m). Eluent: Hex/DCM 1:1, DCM; 117 mg (85%); dr = 39:61; yellow oil. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 8.37 (br s, 1H), 8.24–8.09 (m, 2H), 7.61 (d, J = 7.7 Hz, 1H), 7.51 (t, J = 7.9 Hz, 1H), 6.83–6.78 (m, 1H), 6.34 (s, 1H), 6.34 (dd, 2JHF = 49.6, 3.3 Hz, 1H), 6.26–6.21 (m, 1H), 5.13 (dd, 3JHF = 28.4, 3.2 Hz, 1H) ppm; (minor isomer) δ = 8.37 (br s, 1H), 8.24–8.09 (m, 2H), 7.68 (d, J = 7.8 Hz, 1H), 7.57 (t, J = 8.0 Hz, 1H), 6.83–6.78 (m, 1H), 6.26 (dd, 2JHF = 49.8, 3.6 Hz, 1H), 6.26–6.16 (m, 2H), 5.15 (dd, 3JHF = 28.8, 3.6 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 148.3, 135.4, 134.7, 130.2, 124.2, 124.1, 123.8, 119.6, 110.9 (d, 1JCF = 245.9 Hz), 109.3, 108.5 (d, 4JCF = 1.6 Hz), 47.3 (d, 2JCF = 18.6 Hz) ppm; (minor isomer) δ = 148.5, 137.5, 135.7, 130.4, 123.6, 123.3, 122.2, 119.9, 111.4 (d, 1JCF = 244.3 Hz), 109.9, 109.2, 47.5 (d, 2JCF = 18.9 Hz) ppm. 19F NMR (376 MHz, CDCl3): (major isomer) δ = −153.52 (dd, J = 49.6, 28.4 Hz) ppm; (minor isomer) δ = −152.26 (dd, J = 49.8, 28.8 Hz) ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C12H9FN3O4 278.0583; found 278.0587.
2-(2-Fluoro-2-nitro-1-(2-nitrophenyl)ethyl)-1H-pyrrole (3n). Eluent: Hex/DCM 1:1, DCM; 126 mg (89%); dr = 56:44; pale brown oil. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 8.58 (br s, 1H), 7.85 (d, J = 8.1 Hz, 1H), 7.69 (d, J = 7.9 Hz, 1H), 7.42–7.64 (m, 2H), 6.79 (s, 1H), 6.34 (br s, 1H), 6.34 (dd, 2JHF = 49.5, 4.3 Hz, 1H), 6.21 (dd, J = 5.4, 2.6 Hz, 1H), 5.83 (dd, 3JHF = 26.6, 3.8 Hz, 1H) ppm; (minor isomer) δ = 8.38 (br s, 1H), 8.01 (d, J = 8.1 Hz, 1H), 7.42–7.64 (m, 3H), 6.74 (s, 1H), 6.34 (br s, 1H), 6.42 (dd, J = 50.0, 3.0 Hz, 1H), 6.17 (dd, J = 5.4, 2.6 Hz, 1H), 5.83 (dd, J = 30.2, 3.8 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 149.5, 133.5, 131.0 (d, 4JCF = 4.2 Hz), 129.5, 128.6, 125.1, 124.2 (d, 3JCF = 1.1 Hz), 119.3, 111.0 (d, 1JCF = 242.4 Hz), 109.1, 108.0 (d, 4JCF = 1.7 Hz), 41.1 (d, 2JCF = 18.2 Hz) ppm; (minor isomer) δ = 148.6, 134.0, 132.0, 130.4, 129.5, 125.3, 122.4, 119.3, 110.7 (d, 1JCF = 244.1 Hz), 109.8, 109.1, 42.9 (d, 2JCF = 18.1 Hz) ppm. 19F NMR (376 MHz, CDCl3): (major isomer) δ = −151.14 (dd, J = 49.5, 26.6 Hz) ppm; (minor isomer) δ = −155.79 (dd, J = 50.0, 30.2 Hz) ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C12H9FN3O4 278.0583; found 278.0587.
1,3-Bis(2-fluoro-2-nitro-1-(1H-pyrrol-2-yl)ethyl)benzene (3o). Eluent: Hex/DCM 1:1, DCM; 191 mg (>99%); mixture of four isomers dr = 41:59 (two pair of isomers); greenish oil. 1H NMR (400 MHz, CDCl3): δ = 8.15 (s, 1H), 8.11 (s, 1H), 8.05 (s, 3H), 8.02 (br s, 1H), 7.96 (br s, 2H), 7.12–7.44 (m, 15H), 7.07 (s, 1H), 6.65–6.76 (m, 8H), 6.23 (dd, 2JHF = 49.5, 3.6 Hz, 1H), 6.04–6.34 (m, 21H), 6.08 (dd, 2JHF = 50.1, 4.2 Hz, 1H), 6.06 (dd, 2JHF = 49.8, 4.2 Hz, 1H), 4.95 (dd, J = 28.5, 4.6 Hz, 1H), 4.80–5.03 (m, 5H), 4.91 (dd, 3JHF = 28.1, 4.6 Hz, 1H), 4.90 (dd, 3JHF = 28.5, 3.1 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 136.2, 136.2, 136.1, 136.1, 135.9, 135.9, 135.8, 135.8, 134.4, 134.3, 134.0, 134.0, 130.2, 130.1, 130.0, 130.0, 129.8, 129.8, 129.7, 129.4, 129.3, 128.8, 128.8, 128.7, 128.5, 128.4, 128.3, 125.0, 124.9, 123.3, 123.2, 119.4, 119.4, 119.2, 119.2, 119.1, 119.1, 112.1 (d, 1JCF = 244.2 Hz), 112.0 (d, 1JCF = 244.1 Hz), 111.3 (d, 1JCF = 245.9 Hz), 111.2 (d, 1JCF = 245.8 Hz), 109.3, 109.2, 109.0, 109.0, 108.9, 108.9, 108.8, 107.9, 107.9, 107.8, 47.8 (d, 2JCF = 18.0 Hz), 47.7 (d, 2JCF = 18.0 Hz), 47.7 (d, 2JCF = 18.7 Hz), 47.6 (d, 2JCF = 18.5 Hz), 47.5 (d, 2JCF = 18.5 Hz) ppm (the other signals are overlapped). 19F NMR (376 MHz, CDCl3): δ = −151.12 (dd, J = 49.4, 27.7, 2F Hz), −151.12–−151.41 (m, 2F), −153.23–−153.76 (m, 4F) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C18H17F2N4O4 391.1212; found 391.1206.
General procedure for the conjugate addition of 1-substituted 1H-pyrroles to β-fluoro-β-nitrostyrenes.
In a typical experiment, a mixture of β-fluoro-β-nitrostyrene (0.5 mmol) and pyrrole (0.4–0.5 g) was loaded into a 4-mL vial (vial G4, Anton Paar). The reaction mixture was placed into a microwave reactor and heated at 150–200 °C with stirring until completion (15–24 h). The reaction progress was monitored by TLC or 19F NMR analysis. After completion of the reaction, the resulting mixture was separated by column chromatography on silica gel.
2-(1-(4-Chlorophenyl)-2-fluoro-2-nitroethyl)-1-methyl-1H-pyrrole (3p). Eluent: Hex/DCM 3:1, Hex/DCM 1:1; 114 mg (76%); dr = 36:51; yellow oil. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 7.33–7.27 (m, 2H), 7.10 (d, J = 8.4 Hz, 2H), 6.66–6.61 (m, 1H), 6.37–6.32 (m, 1H), 6.18 (t, J = 3.2 Hz, 1H), 6.11 (dd, 2JHF = 49.8, 4.7 Hz, 1H), 4.93 (dd, 3JHF = 27.1, 2.9 Hz, 1H), 3.33 (s, 3H) ppm; (minor isomer) δ = 7.38–7.32 (m, 2H), 7.22 (d, J = 8.5 Hz, 2H), 6.62–6.58 (m, 1H), 6.40–6.36 (m, 1H), 6.29 (dd, J = 49.4, 3.0 Hz, 1H), 6.14 (t, J = 3.2 Hz, 1H), 4.96 (dd, J = 25.6, 4.7 Hz, 1H), 3.36 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 134.8, 131.3, 130.7, 129.3, 126.3, 123.6, 111.2 (d, 1JCF = 245.6 Hz), 108.1 (d, 4JCF = 3.4 Hz), 107.4, 46.0 (d, 2JCF = 19.1 Hz), 34.0 ppm; (minor isomer) δ = 134.6, 133.3 (d, 3JCF = 1.9 Hz), 130.1, 129.5, 124.4, 123.5, 112.2 (d, 1JCF = 246.7 Hz), 108.8 (d, 4JCF = 3.3 Hz), 107.4, 46.0 (d, 2JCF = 19.1 Hz), 33.9 ppm. 19F NMR (282 MHz, CDCl3): (major isomer) δ = −153.51 (dd, J = 49.8, 27.1 Hz) ppm; (minor isomer) δ = −152.56 (dd, J = 49.4, 25.6 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C13H13ClFN2O2 283.0644; found 283.0961.
2-(1-(4-Chlorophenyl)-2-fluoro-2-nitroethyl)-1-phenyl-1H-pyrrole (3q). Eluent: Hex/DCM 3:1, Hex/DCM 1:1, DCM; 62 mg (35%); dr = 55:45; yellow oil. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 7.31–7.42 (m, 3H), 7.22–7.17 (m, 2H), 7.02–6.94 (m, 2H), 6.92 (d, J = 8.4 Hz, 2H), 6.81 (dd, J = 2.8, 1.7 Hz, 1H), 6.49–6.53 (m, 1H), 6.34–6.31 (m, 1H), 6.19 (dd, J = 50.0, 3.7 Hz, 1H), 4.76 (dd, J = 27.1, 3.5 Hz, 1H) ppm; (minor isomer) δ = 7.42–7.31 (m, 3H), 7.29–7.22 (m, 2H), 7.05 (d, J = 8.5 Hz, 2H), 7.02–6.94 (m, 2H), 6.77 (dd, J = 2.8, 1.7 Hz, 1H), 6.28–6.31 (m, 1H), 6.58 (dd, J = 4.3, 3.7 Hz, 1H), 5.97 (dd, J = 49.6, 4.4 Hz, 1H), 4.83 (dd, J = 28.7, 3.3 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 139.0, 134.6, 132.0, 130.6, 129.4, 129.0, 128.5, 127.0, 127.0, 124.0, 111.6 (d, 1JCF = 244.9 Hz), 109.2 (d, 4JCF = 3.2 Hz), 108.8, 46.0 (d, 2JCF = 19.1 Hz) ppm; (minor isomer) δ = 139.0, 134.4, 133.9 (d, 3JCF = 1.4 Hz), 130.1, 129.4, 129.3, 128.4, 127.1, 125.1, 123.8, 112.0 (d, 1JCF = 247.0 Hz), 109.7 (d, 4JCF = 3.6 Hz), 108.9, 45.8 (d, 2JCF = 18.4 Hz) ppm. 19F NMR (282 MHz, CDCl3): (major isomer) δ = −152.19 (dd, J = 50.0, 27.1 Hz), (minor isomer) δ = −153.32 (dd, J = 49.6, 28.7 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C18H15ClFN2O2 345.0801; found 345.0799.
2-(1-(4-Chlorophenyl)-2-fluoro-2-nitroethyl)-1-(4-ethylphenyl)-1H-pyrrole (3r). Eluent: Hex/DCM 5:1, Hex/DCM 3:1; Hex/DCM 1:1; 51 mg (28%); dr = 52:32; yellow oil. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 7.31–7.14 (m, 4H), 6.94 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 6.8 Hz, 2H), 6.79 (dd, J = 2.8, 1.7 Hz, 1H), 6.53–6.45 (m, 1H), 6.33–6.30 (m, 1H), 6.18 (dd, J = 50.0, 3.6 Hz, 1H), 4.76 (dd, J = 27.5, 3.7 Hz, 1H), 2.70 (q, J = 7.6 Hz, 2H), 1.28 (t, J = 7.6 Hz, 3H) ppm; (minor isomer) δ = 7.31–7.14 (m, 4H), 7.07 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 6.9 Hz, 2H), 6.75 (dd, J = 2.8, 1.7 Hz, 1H), 6.60–6.54 (m, 1H), 6.30–6.26 (m, 1H), 5.97 (dd, J = 49.7, 4.4 Hz, 1H), 4.83 (dd, J = 28.8, 4.1 Hz, 1H), 2.70 (q, J = 7.7 Hz, 2H), 1.28 (t, J = 7.6 Hz, 3H) ppm.13C NMR (100 MHz, CDCl3): (major isomer) δ = 144.8, 136.5, 134.5, 132.1, 130.7, 128.9, 128.7, 127.1, 126.8, 124.0, 111.6 (d, 1JCF = 245.1 Hz), 109.0 (d, 4JCF = 3.1 Hz), 108.5, 45.9 (d, 2JCF = 19.0 Hz), 28.6, 15.6 ppm; (minor isomer) δ = 144.6, 136.6, 134.3, 134.0, 130.1, 129.3, 128.7, 126.9, 125.2, 123.8, 112.0 (d, 1JCF = 246.7 Hz), 109.4 (d, 4JCF = 3.6 Hz), 108.6, 45.8 (d, 2JCF = 18.5 Hz), 15.6 ppm. 19F NMR (376 MHz, CDCl3): (major isomer) δ = −152.34 (ddd, J = 50.0, 27.5, 2.3 Hz) ppm; (minor isomer) δ = −153.34 (ddd, J = 49.7, 28.8, 2.5 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C20H19ClFN2O2 373.1114; found 373.1116.
2-(1-(4-Chlorophenyl)-2-fluoro-2-nitroethyl)-1-(p-tolyl)-1H-pyrrole (3s). Eluent: Hex/DCM 5:1, Hex/DCM 4:1, Hex/DCM 1:1; 92 mg (51%); dr =48:47; yellow oil. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 7.25–7.19 (m, 2H), 7.16 (d, J = 7.3 Hz, 2H), 6.96 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 6.4 Hz, 2H), 6.78 (dd, J = 2.6, 1.7 Hz, 1H), 6.53–6.47 (m, 1H), 6.33–6.30 (m, 1H), 6.17 (dd, J = 50.0, 3.6 Hz, 1H), 4.75 (dd, J = 27.5, 3.3 Hz, 1H), 2.40 (s, 3H) ppm; (minor isomer) δ = 7.27 (d, J = 8.6 Hz, 2H), 7.17 (d, J = 7.0 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 6.86 (d, J = 6.5 Hz, 2H), 6.74 (dd, J = 2.6, 1.7 Hz, 1H), 6.60–6.54 (m, 1H), 6.30–6.26 (m, 1H), 5.97 (dd, J = 49.7, 4.3 Hz, 1H), 4.83 (dd, J = 28.3, 3.5 Hz, 1H), 2.40 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 138.5, 136.3, 134.5, 132.1, 130.7, 129.9, 128.9, 127.0, 126.8, 124.0, 111.6 (d, 1JCF = 245.0 Hz), 109.0 (d, 4JCF = 3.1 Hz), 108.6, 45.8 (d, 2JCF = 18.9 Hz), 21.2 ppm; (minor isomer) δ = 138.38, 136.41, 134.34, 133.94 (d, 3JCF = 1.6 Hz), 130.08, 129.89, 129.26, 126.86, 125.12, 123.76, 111.96 (d, 1JCF = 246.7 Hz), 109.48 (d, J = 3.7 Hz), 108.66, 45.74 (d, 2JCF = 18.4 Hz), 21.21 ppm. 19F NMR (376 MHz, CDCl3): (major isomer) δ = −152.30 (ddd, J = 50.0, 27.5, 2.0 Hz) ppm; (minor isomer) δ = −153.45 (ddd, J = 49.7, 28.3, 2.2 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C19H17ClFN2O2 359.0957; found 359.0949.
1-(3-Chloro-4-methoxyphenyl)-2-(1-(4-chlorophenyl)-2-fluoro-2-nitroethyl)-1H-pyrrole (3t). Eluent: Hex/DCM 5:1, Hex/DCM 4:1, Hex/DCM 1:1; 97 mg (46%); dr = 53:43; yellow oil. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 7.26–7.21 (m, 2H), 6.98–6.92 (m, 3H), 6.87–6.84 (m, 2H), 6.74 (dd, J = 2.8, 1.7 Hz, 1H), 6.51–6.46 (m, 1H), 6.31–6.28 (m, 1H), 6.19 (dd, J = 49.9, 3.6 Hz, 1H), 4.68 (dd, J = 27.2, 3.5 Hz, 1H), 3.93 (s, 3H) ppm; (minor isomer) δ = 7.32–7.27 (m, 2H), 7.09 (d, J = 8.5 Hz, 2H), 6.98 (d, J = 1.7 Hz, 1H), 6.90–6.87 (m, 2H), 6.70 (dd, J = 2.8, 1.7 Hz, 1H), 6.58–6.52 (m, 1H), 6.26 (dd, J = 4.8, 3.6 Hz, 1H), 5.97 (dd, J = 49.6, 4.3 Hz, 1H), 4.77 (dd, J = 28.9, 4.2 Hz, 1H), 3.94 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 155.1, 134.7, 131.9, 131.9, 130.6, 129.1, 127.3, 126.4, 124.1, 122.7, 111.8, 111.4 (d, 1JCF = 245.0 Hz), 109.1 (d, 4JCF = 3.1 Hz), 108.8, 56.5, 45.9 (d, 2JCF = 19.0 Hz) ppm; (minor isomer) δ = 155.1, 134.5, 133.7 (d, 3JCF = 1.1 Hz), 132.0, 130.1, 129.4, 126.5, 125.4, 123.8, 122.7, 111.9, 111.8 (d, 1JCF = 247.0 Hz), 109.6 (d, 4JCF = 3.6 Hz), 108.9, 56.4, 45.8 (d, 2JCF = 18.4 Hz) ppm. 19F NMR (376 MHz, CDCl3): (major isomer) δ = −152.40 (ddd, J = 49.9, 27.2, 2.4 Hz) ppm; (minor isomer) δ = −153.78 (ddd, J = 49.6, 28.9, 2.5 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C19H16Cl2FN2O3 409.0517; found 409.0522.
2-(1-(4-Chlorophenyl)-2-fluoro-2-nitroethyl)-1-(3-methoxyphenyl)-1H-pyrrole (3u). Eluent: Hex/DCM 3:1, Hex/DCM 1:1; 153 mg (74%); dr = 53:47; yellow oil. 1H NMR (400 MHz, CDCl3): (major isomer) δ = 7.33–7.19 (m, 3H), 6.99 (d, J = 8.4 Hz, 2H), 6.98–6.91 (m, 1H), 6.83 (dd, J = 2.7, 1.7 Hz, 1H), 6.67–6.59 (m, 1H), 6.56–6.50 (m, 1H), 6.49 (t, J = 2.1 Hz, 1H), 6.36–6.32 (m, 1H), 6.21 (dd, J = 50.0, 3.6 Hz, 1H), 4.84 (dd, J = 27.2, 3.6 Hz, 1H), 3.70 (s, 3H) ppm; (minor isomer) δ = 7.33–7.19 (m, 3H), 7.12 (d, J = 8.4 Hz, 2H), 6.98–6.91 (m, 1H), 6.80 (dd, J = 2.7, 1.7 Hz, 1H), 6.67–6.59 (m, 2H), 6.56–6.50 (m, 1H), 6.32–6.29 (m, 1H), 6.00 (dd, J = 49.5, 4.2 Hz, 1H), 4.92 (dd, J = 29.2, 4.2 Hz, 1H), 3.72 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): (major isomer) δ = 160.1, 139.9, 134.4, 132.1, 130.6, 130.0, 128.9, 126.9, 123.8, 119.0, 114.5, 112.3, 111.5 (d, 1JCF = 244.9 Hz), 109.2 (d, 4JCF = 3.1 Hz), 108.7, 55.3, 45.8 (d, 2JCF = 19.1 Hz) ppm; (minor isomer) δ = 160.1, 140.0, 134.3, 133.9, 130.1, 130.0, 129.2, 124.9, 123.6, 119.1, 114.6, 112.3, 111.8 (d, 1JCF = 246.9 Hz), 109.7 (d, 4JCF = 3.7 Hz), 108.8, 55.3, 45.7 (d, 2JCF = 18.4 Hz). 19F NMR (376 MHz, CDCl3) (major isomer) δ = −152.33 (dd, J = 50.0, 27.2 Hz) ppm; (minor isomer) δ = −153.66 (dd, J = 49.5, 29.2 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C19H17ClFN2O3 375.0906; 375.0893.
General procedure for base-induced nitrous acid elimination.
In a typical experiment, the selected adduct 3 (0.4–0.5 mmol, 1 mol equiv.) was treated with a solution of DBU (2.0–6.0 mol equiv.) in acetonitrile (3 mL) with vigorous stirring at room temperature overnight (15–18 h). After completion of the reaction (TLC monitoring), the reaction mixture was concentrated under vacuum. The residue was separated by column chromatography.
Elimination for 3a. Purification by column chromatography on silica gel with Hex/DCM 1:1 gave 59 mg (76%) of the target product 4a as a mixture of diastereomers (Z:E = 46:54) and 11 mg (13 %) of the side product 5a as a mixture of diastereomers (Z:E = 57:43).
(Z)-2-(2-Fluoro-1-phenylvinyl)-1H-pyrrole (Z-4a). Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 8.90 (br s, 1H), 7.50–7.32 (m, 5H), 6.91 (dd, J = 4.1, 2.6 Hz, 1H), 6.69 (d, 2JHF = 84.3 Hz, 1H), 6.31–6.27 (m, 1H), 6.16–6.10 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 143.7 (d, 1JCF = 265.6 Hz), 134.6 (d, 3JCF = 10.0 Hz), 129.8, 129.7 (d, 4JCF = 3.7 Hz), 128.6, 127.0 (d, 3JCF = 3.1 Hz), 119.4 (d, 6JCF = 4.8 Hz), 118.9 (d, 2JCF = 3.6 Hz), 111.1 (d, 4JCF = 4.6 Hz), 108.9 ppm; 19F NMR (376 MHz, CDCl3) δ = −132.04 (dd, J = 84.3, 6.3 Hz) ppm; HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H11FN 188.0870; found 188.0867.
(E)-2-(2-Fluoro-1-phenylvinyl)-1H-pyrrole (E-4a). Colorless oil. 1H NMR (400 MHz, CDCl3) δ = 7.90 (br s, 1H), 7.50–7.32 (m, 5H), 7.12 (d, 2JHF = 83.2 Hz, 1H), 6.82–6.77 (m, 1H), 6.26 (dd, J = 5.7, 2.9 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 144.7 (d, 1JCF = 267.3 Hz), 133.8, 129.8, 128.6, 128.3 (d, 4JCF = 3.5 Hz), 127.2 (d, 3JCF = 9.4 Hz), 119.0 (d, 6JCF = 2.4 Hz), 118.9 (d, 2JCF = 10.5 Hz), 109.3, 107.6 (d, 4JCF = 2.6 Hz) ppm. 19F NMR (376 MHz, CDCl3): δ = −133.82 (d, 2JHF = 83.2 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H11FN 188.0870; found 188.0867.
(Z)-2-(2-Nitro-1-phenylvinyl)-1H-pyrrole (Z-5a). Yellow oil. 1H NMR (400 MHz, CDCl3): δ = 11.93 (br s, 1H), 7.51–7.36 (m, 4H), 7.34–7.24 (m, 2H), 6.97 (s, 1H), 6.38–6.32 (m, 1H), 6.31–6.26 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 138.4, 138.4, 134.1, 129.6, 129.4, 128.8, 128.3, 126.6, 124.8, 112.0 ppm; HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H11N2O2 215.0815; found 215.0819.
(E)-2-(2-Nitro-1-phenylvinyl)-1H-pyrrole (E-5a). Yellow oil. 1H NMR (400 MHz, CDCl3): δ = 11.93 (br s, 1H), 7.58 (s, 1H), 7.51–7.36 (m, 4H), 7.34–7.28 (m, 1H), 7.00 (td, J = 2.7, 1.4 Hz, 1H), 6.67–6.61 (m, 1H), 6.38–6.32 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 142.8, 141.7, 129.6 129.1, 128.5, 128.4, 127.8, 125.0, 114.8, 112.3 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H11N2O2 215.0815; found 215.0819.
Elimination for 3b. Purification by column chromatography on silica gel with gradient elution (Hex/DCM 1:1, DCM) gave 23 mg (43%) of the target product 4b as a mixture of diastereomers (Z:E = 48:52) and 6 mg (10%) of the side product 5b as a mixture of diastereomers (Z:E = 75:25).
(Z)-2-(2-Fluoro-1-(4-methoxyphenyl)vinyl)-1H-pyrrole (Z-4b). Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 8.88 (br s, 1H), 7.35 (d, J = 8.5 Hz, 2H), 6.94–6.91 (m, 2H), 6.89 (dd, J = 4.1, 2.7 Hz, 1H), 6.64 (d, 2JHF = 84.7 Hz, 1H), 6.27–6.24 (m, 1H), 6.12–6.07 (m, 1H), 3.84 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ =159.5, 143.4 (d, 1JCF = 265.3 Hz), 131.0 (d, 4JCF = 2.9 Hz), 127.4 (d, 3JCF = 3.1 Hz), 126.8 (d, 3JCF = 10.2 Hz), 119.30 (d, 6JCF = 4.8 Hz), 118.26 (d, 2JCF = 3.4 Hz), 113.98, 110.99 (d, 4JCF = 4.8 Hz), 108.93, 55.44 ppm.19F NMR (376 MHz, CDCl3): δ = −132.54 (dd, J = 84.7, 6.3 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C13H13FNO 218.0976; found 218.0973.
(E)-2-(2-Fluoro-1-(4-methoxyphenyl)vinyl)-1H-pyrrole (E-4b). Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 7.97 (br s, 1H), 7.34–7.30 (m, 2H), 7.05 (d, 2JHF = 83.5 Hz, 1H), 6.94–6.91 (m, 2H), 6.79 (dd, J = 4.2, 2.6 Hz, 1H), 6.23 (dd, J = 5.8, 2.9 Hz, 2H), 3.84 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 159.7, 144.3 (d, 1JCF = 266.1 Hz), 130.9 (d, 4JCF = 4.0 Hz), 127.5 (d, 3JCF = 9.9 Hz), 126.0, 118.9 (d, 6JCF = 2.1 Hz), 118.4 (d, 2JCF = 9.7 Hz), 114.0, 109.2, 107.6 (d, 4JCF = 2.7 Hz), 55.4 ppm. 19F NMR (376 MHz, CDCl3): δ = −134.90 (d, J = 83.5 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C13H13FNO 218.0976; found 218.0973.
(Z)-2-(1-(4-Methoxyphenyl)-2-nitrovinyl)-1H-pyrrole (Z-5b). 1H NMR (400 MHz, CDCl3): δ = 11.87 (br s, 1H), 7.39–7.33 (m, 2H), 7.29–7.22 (m, 1H), 7.03–6.90 (m, 3H), 6.38–6.32 (m, 2H), 3.87 (br s, 3H). 13C NMR (100 MHz, CDCl3) δ = 161.0, 141.6, 131.3, 130.6, 128.0, 126.3, 124.8, 113.8, 111.8, 55.6 ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for 243.0770; found 243.0752.
Elimination for 3c. Purification by column chromatography on silica gel with gradient elution (Hex/DCM 3:1; Hex/DCM 2:1; DCM) gave 73 mg (77%) of the target product 4c as a mixture of diastereomers (Z/E = 42:58).
(Z)-2-(1-(4-(Tert-butyl)phenyl)-2-fluorovinyl)-1H-pyrrole (E-4c). Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 8.86 (br s, 1H), 7.49–7.41 (m, 2H), 7.41–7.33 (m, 2H), 6.93–6.87 (m, 1H), 6.69 (d, 2JHF = 84.5 Hz, 1H), 6.32– 6.28 (m, 1H), 6.26–6.16 (m, 1H), 1.39 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3): δ = 151.3, 143.6 (d, 1JCF = 265.5 Hz), 131.6 (d, 4JCF = 10.0 Hz), 129.4 (d, 4JCF = 2.6 Hz), 127.1 (d, 3JCF = 3.2 Hz), 125.5, 119.2 (d, 6JCF = 4.7 Hz), 118.6 (d, 2JCF = 3.7 Hz), 111.1 (d, 4JCF = 5.0 Hz), 109.0, 34.7, 31.4 ppm; 19F NMR (376 MHz, CDCl3): δ = −131.10 (dd, J = 84.5, 6.1 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C16H19FN 244.1496; found 244.1500.
(E)-2-(1-(4-(Tert-butyl)phenyl)-2-fluorovinyl)-1H-pyrrole (E-4c). Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 7.92 (br s, 1H), 7.49–7.41 (m, 2H), 7.41–7.33 (m, 2H), 7.10 (d, 2JHF = 83.4 Hz, 1H), 6.82–6.76 (m, 1H), 6.28–6.22 (m, 2H), 1.40 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3): δ = 151.4, 144.7 (d, 1JCF = 267.0 Hz), 130.8, 129.4 (d, 4JCF = 3.8 Hz), 127.4 (d, 3JCF = 9.9 Hz), 125.5, 118.9 (d, 6JCF = 2.1 Hz), 118.7 (d, 2JCF = 9.8 Hz), 109.2, 107.4 (d, 4JCF = 2.4 Hz), 34.8, 31.5 ppm. 19F NMR (376 MHz, CDCl3): δ = −132.94 (d, 2JHF = 83.4 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C16H19FN 244.1496; found 244.1500.
Elimination for 3d. Purification by column chromatography on silica gel with gradient elution (Hex; Hex/DCM 5:1; Hex/DCM 2:1; Hex/DCM 1:1) gave 29 mg (40%) of the Z-isomer and 31 mg (42%) of the E-isomer of the target product 4d and 13 mg (15%) of the side product 5d as a mixture of diastereomers (Z/E = 49:51).
(Z)-2-(2-Fluoro-1-(p-tolyl)vinyl)-1H-pyrrole (Z-4d). Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 8.87 (br s, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 7.9 Hz, 2H), 6.90–6.86 (m, 1H), 6.64 (d, 2JHF = 84.6 Hz, 1H), 6.24–6.20 (m, 1H), 6.12–6.06 (m, 1H), 2.39 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 2.39 (s, 3H), 143.5 (d, 1JCF = 265.2 Hz), 138.2, 131.6 (d, 3JCF = 10.0 Hz), 129.7 (d, 4JCF = 2.5 Hz), 129.3, 127.2 (d, 3JCF = 3.3 Hz), 119.3 (d, 6JCF = 4.8 Hz), 118.6 (d, 2JCF = 3.3 Hz), 111.0 (d, 4JCF = 4.7 Hz), 108.9, 21.4 ppm. 19F NMR (376 MHz, CDCl3): δ = −132.35 (dd, J = 84.6, 6.3 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C13H13FN 202.1027; found 202.1024.
(E)-2-(2-Fluoro-1-(p-tolyl)vinyl)-1H-pyrrole (E-4d). Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 7.92 (br s, 1H), 7.31 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 7.9 Hz, 2H), 7.08 (d, 2JHF = 83.4 Hz, 1H), 6.79 (dd, J = 3.9, 2.5 Hz, 1H), 6.28–6.24 (m, 1H), 6.23 (dd, J = 5.7, 2.8 Hz, 1H), 2.39 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 144.5 (d, 1JCF = 266.4 Hz), 138.2, 130.8, 129.6 (d, 4JCF = 3.6 Hz), 129.3, 127.4 (d, 3JCF = 9.6 Hz), 118.9 (d, 6JCF = 1.9 Hz), 118.8 (d, 2JCF = 10.0 Hz), 109.2, 107.4 (d, 4JCF = 2.6 Hz), 21.4 ppm. 19F NMR (376 MHz, CDCl3): δ = −134.25 (d, 2JHF = 83.4 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C13H13FN 202.1027; found 202.1024.
2-(2-Nitro-1-(p-tolyl)vinyl)-1H-pyrrole (5d). Pale brown oil. 1H NMR (400 MHz, CDCl3): δ = 11.91 (br s, 1H), 8.21 (br s, 1H), 7.56 (s, 1H), 7.34–7.09 (m, 8H), 7.01–6.96 (m, 1H), 6.97 (s, 1H), 6.80–6.71 (m, 1H), 6.70–6.62 (m, 1H), 6.39–6.29 (m, 3H), 2.43 (s, 3H), 2.42 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.4, 21.6, 111.9, 111.9, 112.2, 114.4, 124.6, 125.0, 126.4, 127.9, 128.3, 128.6, 129.0, 129.5, 129.7, 129.9, 135.5, 139.7, 139.9, 141.9 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for 229.0972; found 229.0972.
Elimination for 3e. Purification by column chromatography on silica gel with Hex/DCM 1:1 gave 63 mg (70%) of the target product 4e as a mixture of diastereomers (Z/E = 42:58) and 10 mg (10 %) of the side product 5e as a mixture of diastereomers (Z/E = 91:9).
(Z)-2-(2-Fluoro-1-(4-fluorophenyl)vinyl)-1H-pyrrole (Z-4e). Colorless oil. 1H NMR (400 MHz, CDCl3): (Z-isomer) δ = 8.93 (br s, 1H), 7.44–7.35 (m, 2H), 7.14–7.06 (m, 2H), 6.94–6.89 (m, 1H), 6.65 (d, J = 84.1 Hz, 1H), 6.25–6.22 (m, 1H), 6.06–6.02 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): (Z-isomer) δ = 162.5 (d, 1JCF = 248.1 Hz), 143.5 (d, 1JCF = 265.4 Hz), 131.5 (dd, 3JCF = 6.0, 4JCF = 3.2 Hz), 130.5 (dd, 3JCF = 10.4, 4JCF = 3.3 Hz), 127.1 (d, 3JCF = 3.1 Hz), 119.7 (d, 6JCF = 5.0 Hz), 118.0 (d, 2JCF = 4.1 Hz), 115.5 (d, 2JCF = 21.5 Hz), 111.1 (d, 4JCF = 4.3 Hz), 109.0 ppm. 19F NMR (376 MHz, CDCl3): δ = −114.24 (tt, J = 8.6, 5.4 Hz, 1F), −131.98 (dd, J = 84.1, 6.5 Hz, 1F) ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C12H8F2N 204.0630; found 204.0638.
(E)-2-(2-Fluoro-1-(4-fluorophenyl)vinyl)-1H-pyrrole (E-4e). Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 7.92 (s, 1H), 7.44–7.35 (m, 2H), 7.14–7.06 (m, 2H), 7.08 (d, 2JHF = 83.1 Hz, 1H), 6.81 (dd, J = 4.6, 2.3 Hz, 1H), 6.25–6.22 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 162.53 (d, 1JCF = 248.1 Hz), 144.67 (d, 1JCF = 267.6 Hz), 131.4 (dd, 3JCF = 8.3, 4JCF = 3.9 Hz), 129.73 (d, 3JCF = 3.3 Hz), 127.02 (d, 3JCF = 12.7 Hz), 119.14 (d, 6JCF = 2.0 Hz), 118.05 (d, 2JCF = 9.7 Hz), 115.56 (d, 2JCF = 21.5 Hz), 109.39, 108.06 (d, 4JCF = 2.8 Hz) ppm. 19F NMR (376 MHz, CDCl3): δ = −114.75–−114.85 (m), −133.82 (d, 2JHF = 83.1 Hz) ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C12H8F2N 204.0630; found 204.0638.
(Z)-2-(1-(4-Fluorophenyl)-2-nitrovinyl)-1H-pyrrole (Z-5e). Pale brown oil. 1H NMR (400 MHz, CDCl3): δ = 11.89 (br s, 1H), 7.45–7.37 (m, 2H), 7.30–7.24 (m, 1H), 7.17–7.08 (m, 2H), 6.93 (s, 1H), 6.38–6.32 (m, 1H), 6.28–6.24 (m, 1H). 13C NMR (100 MHz, CDCl3): δ = 163.5 (d, 1JCF = 249.8 Hz), 140.6, 134.4 (d, 4JCF = 3.5 Hz), 131.6 (d, 3JCF = 8.3 Hz), 128.4, 127.7, 126.7, 124.9, 115.5 (d, 2JCF = 21.8 Hz), 112.1 ppm. 19F NMR (376 MHz, CDCl3) δ = −112.21 (tt, J = 8.5, 5.2 Hz) ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C12H8FN2O2 231.0575; found 231.0572.
Elimination for 3f. Purification by column chromatography on silica gel with gradient elution (Hex; Hex/DCM 6:1; Hex/DCM 4:1; Hex/DCM 1:1) gave 43 mg (40%) of the Z-isomer and 49 mg (45%) of the E-isomer of the target product 4f and 18 mg (15%) of the side product 5f as a mixture of diastereomers (Z/E = 92:8).
(Z)-2-(1-(4-Bromophenyl)-2-fluorovinyl)-1H-pyrrole (Z-4f). Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 8.92 (br s, 1H), 7.56–7.49 (m, 2H), 7.32–7.26 (m, 2H), 6.94–6.89 (m, 1H), 6.64 (d, 2JHF = 83.9 Hz, 1H), 6.26–6.20 (m, 1H), 6.06–6.00 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 143.5 (d, 1JCF = 266.0 Hz), 133.6 (d, 3JCF = 10.3 Hz), 131.8, 131.4 (d, 4JCF = 2.6 Hz), 126.6 (d, 3JCF = 3.1 Hz), 122.5, 119.8 (d, 6JCF = 5.0 Hz), 118.1 (d, 2JCF = 4.2 Hz), 111.2 (d, 4JCF = 4.2 Hz), 109.0 ppm. 19F NMR (376 MHz, CDCl3): δ = −131.66 (dd, J = 83.9, 6.3 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H1079BrFN 265.9975; found 265.9971.
(E)-2-(1-(4-Bromophenyl)-2-fluorovinyl)-1H-pyrrole (E-4f). Bluish oil. 1H NMR (400 MHz, CDCl3): δ = 7.91 (br s, 1H), 7.57–7.54 (m, 2H), 7.29 (d, J = 8.4 Hz, 2H), 7.07 (d, 2JHF = 82.8 Hz, 1H), 6.81 (dd, J = 4.5, 2.3 Hz, 1H), 6.24 (t, J = 2.3 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 145.0 (d, 1JCF = 268.9 Hz), 132.7, 131.8, 131.3 (d, 4JCF = 4.0 Hz), 126.6 (d, 3JCF = 9.3 Hz), 122.4, 119.3 (d, 6JCF = 2.0 Hz), 118.1 (d, 2JCF = 9.4 Hz), 108.3 (d, 4JCF = 2.8 Hz), 109.4 ppm. 19F NMR (376 MHz, CDCl3): δ = −132.42 (d, J = 82.8 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H1081BrFN 267.9955; found 267.9953.
(Z)-2-(1-(4-Bromophenyl)-2-nitrovinyl)-1H-pyrrole (Z-5f). Yellow oil. 1H NMR (400 MHz, CDCl3): (Z-isomer) δ = 11.90 (br s, 1H), 7.60–7.53 (m, 2H), 7.32–7.24 (m, 3H), 6.92 (s, 1H), 6.38–6.32 (m, 1H), 6.29–6.24 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): (Z-isomer) δ = 140.4, 137.3, 131.6, 131.2, 128.2, 127.4, 126.9, 124.9, 124.0, 112.1 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H1079BrN2O2 292.9920; found 292.9914.
Elimination for 3g. Purification by column chromatography on silica gel with gradient elution (Hex; Hex/DCM 6:1; Hex/DCM 4:1; Hex/DCM 1:1) gave 36 mg (34%) of the Z-isomer and 47 mg (45 %) of the E-isomer of the target product 4g and 13 mg (11%) of the side product 5g as a mixture of diastereomers (Z/E = 87:13).
(Z)-2-(1-(4-Chlorophenyl)-2-fluorovinyl)-1H-pyrrole (Z-4g). Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 8.93 (br s, 1H), 7.42–7.30 (m, 4H), 6.94–6.90 (m, 1H), 6.65 (d, 2JHF = 83.9 Hz, 1H), 6.26–6.21 (m, 1H), 6.06–6.02 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 143.5 (d, 1JCF = 265.8 Hz), 134.3, 133.1 (d, 3JCF = 10.3 Hz), 131.1 (d, 4JCF = 2.7 Hz), 128.8, 126.7 (d, 3JCF = 3.2 Hz), 119.8 (d, 6JCF = 5.0 Hz), 118.1 (d, 2JCF = 4.2 Hz), 111.2 (d, 4JCF = 4.3 Hz), 109.0 ppm. 19F NMR (376 MHz, CDCl3) δ = −131.75 (dd, J = 83.9, 6.3 Hz) ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C12H835ClFN 220.0335; found 220.0343.
(E)-2-(1-(4-chlorophenyl)-2-fluorovinyl)-1H-pyrrole (E-4g). Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 7.92 (br s, 1H), 7.41–7.33 (m, 4H), 7.07 (d, 2JHF = 82.8 Hz, 1H), 6.81 (dd, J = 4.6, 2.3 Hz, 1H), 6.24 (t, J = 2.4 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 145.0 (d, 1JCF = 268.8 Hz), 134.1, 132.3, 131.0 (d, 4JCF = 4.0 Hz), 128.8, 126.7 (d, 3JCF = 9.4 Hz), 119.2 (d, 6JCF = 1.9 Hz), 118.0 (d, 2JCF = 9.4 Hz), 109.4, 108.2 (d, 4JCF = 2.8 Hz) ppm. 19F NMR (376 MHz, CDCl3): δ = −132.62 (d, J = 82.9 Hz) ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C12H835ClFN 220.0335; found 220.0343.
(Z)-2-(1-(4-Chlorophenyl)-2-nitrovinyl)-1H-pyrrole (Z-5g). Orange solid. M.p. = 122–124 °C (Hex). 1H NMR (400 MHz, CDCl3): δ = 11.90 (br s, 1H), 7.44–7.38 (m, 2H), 7.38–7.33 (m, 2H), 7.30–7.24 (m, 1H), 6.92 (s, 1H), 6.38–6.32 (m, 1H), 6.30–6.22 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 140.4, 136.8, 135.9, 131.0, 130.0, 128.7, 128.3, 126.9, 124.9, 112.1 ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C12H1035ClN2O2 249.0425; found 249.0421.
Elimination for 3h. Purification by column chromatography on silica gel with gradient elution (Hex; Hex/DCM 4:1; Hex/DCM 1:1; DCM) gave 70 mg (60%) of the Z-isomer and 4 mg (3%) of the E-isomer of the target product 4h and 14 mg (11%) of the side product 5h as a mixture of diastereomers (Z/E = 35:65).
(Z)-2-(1-(2,4-Dichlorophenyl)-2-fluorovinyl)-1H-pyrrole (Z-4h). Yellowish oil. 1H NMR (400 MHz, CDCl3): δ = 8.91 (br s, 1H), 7.50 (s, 1H), 7.33–7.28 (m, 2H), 6.94–6.89 (m, 1H), 6.60 (d, 2JHF = 83.2 Hz, 1H), 6.23–6.18 (m, 1H), 5.83–5.79 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 144.4 (d, 1JCF = 267.6 Hz), 136.3 (d, 4JCF = 3.1 Hz), 135.2, 133.6 (d, 4JCF = 2.5 Hz), 131.6 (d, 3JCF = 11.8 Hz), 129.9, 127.2, 126.1 (d, 3JCF = 3.4 Hz), 119.9 (d, 6JCF = 5.3 Hz), 115.4 (d, 2JCF = 6.2 Hz), 110.8 (d, 4JCF = 4.2 Hz), 109.1 ppm.19F NMR (376 MHz, CDCl3): δ = −130.76 (dd, J = 83.2, 6.2 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H935Cl2FN 256.0091; found 256.0101.
(E)-2-(1-(2,4-Dichlorophenyl)-2-fluorovinyl)-1H-pyrrole (E-4h). Yellowish oil. 1H NMR (400 MHz, CDCl3): δ = 7.88 (br s, 1H), 7.51 (d, J = 2.1 Hz, 1H), 7.31 (dd, J = 8.3, 2.0 Hz, 1H), 7.27 (s, 1H), 7.15 (d, 2JHF = 82.0 Hz, 1H), 6.79–6.75 (m, 1H), 6.21 (dd, J = 6.0, 2.8 Hz, 1H), 6.15–6.10 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 144.8 (d, 1JCF = 264.1 Hz), 135.1, 135.1 (d, 4JCF = 1.4 Hz), 132.7 (d, 4JCF = 1.6 Hz), 131.1, 130.0, 127.5, 126.02 (d, 3JCF = 7.5 Hz), 119.1 (d, 6JCF = 2.3 Hz), 116.2 (d, 2JCF = 13.2 Hz), 109.8, 107.2 (d, 4JCF = 3.8 Hz) ppm. 19F NMR (376 MHz, CDCl3): δ = −130.75 (d, J = 82.0 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H935Cl37ClFN 258.0061; found 258.0069.
2-(1-(2,4-Dichlorophenyl)-2-nitrovinyl)-1H-pyrrole (5h). Red-brown solid; M.p. = 52–54 °C (DCM) with decomposition. 1H NMR (400 MHz, CDCl3): (Z-isomer) δ = 11.87 (br s, 1H), 7.50 (d, J = 2.0 Hz, 1H), 7.41–7.22 (m, 3H), 6.82 (s, 1H), 6.40–6.30 (m, 1H), 6.14–6.07 (m, 1H) ppm; (E-isomer) δ = 8.49 (br s, 1H), 7.62 (s, 1H), 7.54 (d, J = 2.0 Hz, 1H), 7.39–7.32 (m, 1H), 7.18 (d, J = 8.2 Hz, 1H), 7.07–7.02 (m, 1H), 6.52–6.46 (m, 1H), 6.38–6.31 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 138.4, 137.0, 135.9, 135.7, 135.2, 134.5, 133.6, 132.1, 131.8, 130.3, 130.0, 129.9, 128.6, 127.5, 127.3, 127.1, 126.9, 126.5, 125.6, 124.2, 116.6, 112.7, 112.5 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H935Cl2N2O2 283.0036; found: 283.0038.
Elimination for 3i. Purification by column chromatography on silica gel with gradient elution (Hex; Hex/DCM 3:1; Hex/DCM 1:1; DCM) gave 42 mg (36%) of the Z-isomer and 47 mg (41%) of the E-isomer of the target product 4i and 12 mg (7%) of the side product 5i as a mixture of diastereomers (Z/E = 85:15).
(Z)-2-(2-Fluoro-1-(4-(trifluoromethyl)phenyl)vinyl)-1H-pyrrole (Z-4i). Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 8.95 (br s, 1H), 7.66 (d, J = 8.2 Hz, 2H), 7.54 (d, J = 8.0 Hz, 2H), 6.93 (dd, J = 4.1, 2.7 Hz, 1H), 6.68 (d, 2JHF = 83.5 Hz, 1H), 6.26–6.21 (m, 1H), 6.04–5.99 (m, 1H). 13C NMR (100 MHz, CDCl3): δ = 143.9 (d, 1JCF = 266.5 Hz), 138.6 (d, 3JCF = 10.2 Hz), 130.6 (q, 2JCF = 32.5 Hz), 130.2 (d, 4JCF = 2.6 Hz), 126.4 (d, 3JCF = 2.7 Hz), 125.5 (q, 3JCF = 3.8 Hz), 124.2 (q, 1JCF = 272.9 Hz), 120.0 (d, 6JCF = 5.1 Hz), 118.3 (d, 2JCF = 4.4 Hz), 111.3 (d, 4JCF = 4.1 Hz), 109.1 ppm. 19F NMR (376 MHz, CDCl3) δ = −65.78 (s, 3F), −133.27 (dd, J = 83.5, 6.5 Hz, 1F). HRMS (ESI-TOF) m/z: [M − H]− calcd. for C13H8F4N 254.0598; found 254.0601.
(E)-2-(2-Fluoro-1-(4-(trifluoromethyl)phenyl)vinyl)-1H-pyrrole (E-4i). Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 7.92 (br s, 1H), 7.66 (d, J = 8.2 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.12 (d, 2JHF = 82.5 Hz, 1H), 6.82 (dd, J = 4.6, 2.3 Hz, 1H), 6.25 (t, J = 2.4 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ = 145.6 (d, 1JCF = 270.4 Hz), 137.6, 130.3 (q, 2JCF = 32.5 Hz), 130.0 (d, 4JCF = 4.0 Hz), 126.3 (d, 3JCF = 9.3 Hz), 125.5 (q, 3JCF = 3.7 Hz), 124.1 (d, 1JCF = 270.6 Hz), 119.5 (d, 6JCF = 1.9 Hz), 118.1 (d, 2JCF = 9.3 Hz), 109.6, 108.6 (d, J = 2.9 Hz) ppm. 19F NMR (376 MHz, CDCl3) δ = δ − 65.87 (s, 3F), −133.67 (d, J = 82.5 Hz, 1F) ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C13H8F4N 254.0598; found 254.0601.
(Z)-(2-Nitro-1-(4-(trifluoromethyl)phenyl)vinyl)-1H-pyrrole (5i). Orange waxy solid. 1H NMR (400 MHz, CDCl3): δ = 11.92 (br s, 1H), 7.71 (d, J = 8.1 Hz, 2H), 7.55 (d, J = 8.0 Hz, 2H), 7.31–7.27 (m, 1H), 6.91 (s, 1H), 6.38–6.33 (m, 1H), 6.23–6.18 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 141.9, 139.9, 131.7 (q, 2JCF = 33.0 Hz), 130.0, 128.3, 127.1, 125.4 (q, 3JCF = 3.7 Hz), 124.9, 123.9 (q, 1JCF = 272.4 Hz), 112.3, 112.3 ppm.19F NMR (376 MHz, CDCl3) δ = −65.96 ppm. HRMS (ESI-TOF) m/z: [M-H]− calcd. for C13H8F3N2O2 281.0543; found 281.0548.
Elimination for 3j. Purification by column chromatography on silica gel with gradient elution (Hex; Hex/DCM 3:1; Hex/DCM 2:1; Hex/DCM 1:2; DCM) gave 43 mg (38%) of the Z-isomer and 45 mg (39%) of the E-isomer of the target product 4j and 12 mg (9%) of the side product 5j as a mixture of diastereomers (Z/E = 68:32).
(Z)-Methyl 4-(2-fluoro-1-(1H-pyrrol-2-yl)vinyl)benzoate (Z-4j). Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 8.95 (br s, 1H), 8.09–8.02 (m, 2H), 7.52–7.45 (m, 2H), 6.95–6.89 (m, 1H), 6.69 (d, 2JHF = 83.6 Hz, 1H), 6.27–6.19 (m, 1H), 6.07–6.00 (m, 1H), 3.94 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.9, 143.9 (d, 1JCF = 266.6 Hz), 139.6 (d, 3JCF = 10.3 Hz), 130.1, 129.8, 129.8 (d, 4JCF = 2.6 Hz), 126.3 (d, 3JCF = 2.9 Hz), 119.8 (d, 6JCF = 5.0 Hz), 118.6 (d, 2JCF = 4.3 Hz), 111.2 (d, 3JCF = 4.2 Hz), 109.0, 52.4 ppm.19F NMR (376 MHz, CDCl3): δ = −131.15 (dd, J = 83.6, 6.4 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C14H13FNO2 246.0925; found 246.0921.
(E)-Methyl 4-(2-fluoro-1-(1H-pyrrol-2-yl)vinyl)benzoate (E-4j). Yellowish oil. 1H NMR (400 MHz, CDCl3): δ = 8.11 (br s, 1H), 7.97–8.05 (m, 2H), 7.48 (d, J = 8.2 Hz, 2H), 7.11 (d, 2JHF = 82.6 Hz, 1H), 6.82 (dd, J = 4.4, 2.4 Hz, 1H), 6.21–6.27 (m, 2H), 3.92 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.9, 145.6 (d, 1JCF = 270.7 Hz), 138.7, 129.8, 129.7, 129.6 (d, 4JCF = 4.0 Hz), 126.4 (d, 3JCF = 9.4 Hz), 119.4 (d, 6JCF = 2.0 Hz), 118.4 (d, 2JCF = 9.0 Hz), 109.4, 108.5 (d, 3JCF = 2.7 Hz), 52.3 ppm. 19F NMR (376 MHz, CDCl3): δ = −130.88 (d, 2JHF = 82.6 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C14H13FNO2 246.0925; found 246.0921.
Methyl 4-(2-nitro-1-(1H-pyrrol-2-yl)vinyl)benzoate (5j). Red-orange solid. M.p. = 153–155 °C with decomposition. 1H NMR (400 MHz, CDCl3): (Z-isomer) δ = 11.93 (br s, 1H), 8.12–8.06 (m, 2H), 7.53–7.45 (m, 2H), 7.30–7.26 (m, 1H), 6.93 (s, 1H), 6.37–6.32 (m, 1H), 6.23–6.19 (m, 1H), 3.96 (s, 3H) ppm; (E-isomer) δ = 8.41 (s, 1H), 8.17–8.12 (m, 2H), 7.57 (s, 1H), 7.41–7.36 (m, 2H), 7.05–7.01 (m, 1H), 6.56–6.52 (m, 1H), 6.37–6.32 (m, 1H), 3.96 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 52.5, 52.6, 112.2, 112.5, 116.1, 124.9, 125.3, 127.0, 127.3, 127.5, 128.2, 128.5, 129.1, 129.6, 129.7, 130.0, 130.9, 131.2, 139.1, 140.5, 141.8, 142.8, 166.5, 166.7 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C14H13N2O4 273.0870; found 273.0873.
Elimination for 3k. Purification by column chromatography on silica gel with gradient elution (Hex/DCM 1:1; DCM) gave 88 mg (81%) of the target product 4k as a mixture of diastereomers (Z/E = 47:53) and 11 mg (9%) of the side product 5k as a mixture of diastereomers (Z/E = 40:60).
(Z)-4-(2-Fluoro-1-(1H-pyrrol-2-yl)vinyl)benzonitrile (Z-4k). Greenish solid. M.p. = 97–99 °C (Hex:DCM 1:1). 1H NMR (400 MHz, CDCl3): δ = 9.00 (br s, 1H), 7.71–7.63 (m, 2H), 7.57–7.48 (m, 2H), 6.96–6.91 (m, 1H), 6.68 (d, 2JHF = 83.0 Hz, 1H), 6.26–6.18 (m, 1H), 6.00–5.95 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 143.9 (d, 1JCF = 267.5 Hz), 139.8 (d, 3JCF = 10.4 Hz), 132.3, 130.4 (d, 4JCF = 2.6 Hz), 125.7 (d, 3JCF = 2.9 Hz), 120.2 (d, 6JCF = 4.9 Hz), 118.6, 118.2 (d, 2JCF = 5.0 Hz), 112.1, 111.2 (d, 4JCF = 3.9 Hz), 109.0 ppm. 19F NMR (376 MHz, CDCl3): (Z-isomer) δ = −129.86 (dd, 2JHF = 82.2, 6.0 Hz) ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C13H8FN2 211.0677; found 211.0674.
(E)-4-(2-Fluoro-1-(1H-pyrrol-2-yl)vinyl)benzonitrile (E-4k). Greenish solid. M.p. = 97–99 °C (Hex:DCM 1:1). 1H NMR (400 MHz, CDCl3): δ = 8.11 (br s, 1H), 7.71–7.63 (m, 2H), 7.56–7.49 (m, 2H), 7.11 (d, 2JHF = 82.2 Hz, 1H), 6.86–6.82 (m, 1H), 6.28–6.17 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 145.9 (d, 1JCF = 272.2 Hz), 138.9, 132.2, 130.31 (d, 4JCF = 4.3 Hz), 125.6 (d, 3JCF = 9.3 Hz), 119.7 (d, 6JCF = 1.3 Hz), 118.7, 117.9 (d, 2JCF = 8.5 Hz), 111.6, 109.4, 109.1 (d, 4JCF = 3.0 Hz) ppm. 19F NMR (376 MHz, CDCl3): δ = −130.34 (d, 2JHF = 83.0 Hz) ppm.
4-(2-Nitro-1-(1H-pyrrol-2-yl)vinyl)benzonitrile (5k). Yellow oil. 1H NMR (400 MHz, CDCl3): (Z-isomer) δ = 11.90 (br s, 1H), 7.80–7.72 (m, 2H), 7.58–7.51 (m, 2H), 7.33–7.28 (m, 1H), 6.88 (s, 1H), 6.39–6.33 (m, 1H), 6.18–6.14 (m, 1H) ppm; (E-isomer) δ = 8.52 (br s, 1H), 7.80–7.72 (m, 2H), 7.54 (s, 1H), 7.47–7.40 (m, 2H), 7.09–7.05 (m, 1H), 6.48–6.41 (m, 1H), 6.39–6.33 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 142.9, 140.9, 139.4, 139.4, 132.4, 132.2, 130.4, 129.3, 129.0, 128.2, 127.4, 127.0, 126.8, 125.8, 124.8, 118.4, 118.2, 117.4, 113.6, 112.7, 112.4, 112.4, ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C13H10N3O2 240.0768; found 240.0771.
Elimination for 3l. Purification by column chromatography on silica gel with gradient elution (Hex; Hex/DCM 5:1; Hex/DCM 2:1; Hex/DCM 1:1) gave 25 mg (29%) of the Z-isomer and 18 mg (21%) of the E-isomer of the target product 4l.
(Z)-2-(2-Fluoro-1-(4-nitrophenyl)vinyl)-1H-pyrrole (Z-4l). Yellow solid. M.p. = 114–115 °C (Hex/DCM 5:1) with decomposition. 1H NMR (400 MHz, CDCl3): δ = 8.99 (br s, 1H), 8.25 (d, J = 8.5 Hz, 2H), 7.59 (d, J = 8.4 Hz, 2H), 6.97–6.92 (m, 1H), 6.71 (d, 2JHF = 82.8 Hz, 1H), 6.26–6.21 (m, 1H), 6.00–5.95 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.0, 144.0 (d, 1JCF = 267.7 Hz), 141.8 (d, 3JCF = 10.5 Hz), 130.6 (d, 4JCF = 2.4 Hz), 125.8 (d, 3JCF = 3.0 Hz), 123.8, 120.3 (d, 6JCF = 5.0 Hz), 118.1 (d, 2JCF = 5.3 Hz), 111.4 (d, 4JCF = 3.7 Hz), 109.2 ppm. 19F NMR (376 MHz, CDCl3): δ = −130.01 (dd, J = 82.8, 6.5 Hz) ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C12H8FN2O2 231.0575; found 231.0584.
(E)-2-(2-fluoro-1-(4-nitrophenyl)vinyl)-1H-pyrrole (E-4l). Pale brown oil. 1H NMR (400 MHz, CDCl3): δ = 8.23 (d, J = 8.7 Hz, 2H), 8.00 (br s, 1H), 7.59 (d, J = 8.6 Hz, 2H), 7.13 (d, 2JHF = 82.0 Hz, 1H), 6.80–6.89 (m, 1H), 6.20–6.28 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.5, 146.3 (d, 1JCF = 273.8 Hz), 140.8, 130.5 (d, 4JCF = 4.5 Hz), 125.6 (d, 3JCF = 8.8 Hz), 123.8, 119.8 (d, 6JCF = 1.4 Hz), 117.7 (d, 2JCF = 8.5 Hz), 109.7, 109.4 (d, 4JCF = 3.1 Hz) ppm. 19F NMR (376 MHz, CDCl3): δ = −128.64 (d, 2JHF = 82.0 Hz) ppm. HRMS (ESI-TOF) m/z: [M − H]− calcd. for C12H8FN2O2 231.0575; found 231.0584.
Elimination for 3m. Purification by column chromatography on silica gel with gradient elution (Hex; Hex/DCM 3:1; Hex/DCM 1:1; DCM) gave 31 mg (32%) of the Z-isomer and 44 mg (46%) of the E-isomer of the target product 4m and 11.6 mg (11%) of the side product 5m as a mixture of diastereomers (Z/E = 62:38).
(Z)-2-(2-Fluoro-1-(3-nitrophenyl)vinyl)-1H-pyrrole (Z-4m). Yellow oil. 1H NMR (400 MHz, CDCl3) δ = 9.02 (br s, 1H), 8.33–8.22 (m, 2H), 7.78–7.73 (m, 1H), 7.58 (t, J = 7.9 Hz, 1H), 6.96 (dd, J = 4.0, 2.6 Hz, 1H), 6.71 (d, 2JHF = 82.9 Hz, 1H), 6.29–6.17 (m, 1H), 5.94 (s, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.4, 144.0 (d, 1JCF = 266.9 Hz), 136.6 (d, 3JCF = 10.8 Hz), 135.9 (d, 4JCF = 2.6 Hz), 129.6, 126.10 (d, 3JCF = 3.0 Hz), 124.7 (d, 4JCF = 2.7 Hz), 123.4, 120.4 (d, 6JCF = 5.2 Hz), 117.8 (d, 2JCF = 5.4 Hz), 111.4 (d, 4JCF = 3.6 Hz), 109.2 ppm. 19F NMR (376 MHz, CDCl3) δ = −130.64 (dd, J = 82.9, 6.6 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H10FN2O2 233.0721; found 233.0730.
(E)-2-(2-Fluoro-1-(3-nitrophenyl)vinyl)-1H-pyrrole (E-4m). Yellow oil. 1H NMR (400 MHz, CDCl3): δ = 8.29 (br s, 1H), 8.18 (dd, J = 8.2, 1.3 Hz, 1H), 8.07 (s, 1H), 7.74 (d, J = 7.7 Hz, 1H), 7.56 (t, J = 8.0 Hz, 1H), 7.13 (d, 2JHF = 82.1 Hz, 1H), 6.85 (dd, J = 4.0, 2.6 Hz, 1H), 6.25 (dd, J = 5.8, 2.9 Hz, 1H), 6.22 (s, 1H). 13C NMR (100 MHz, CDCl3): δ = 148.4, 145.8 (d, 1JCF = 271.4 Hz), 135.8, 135.7 (d, 4JCF = 4.0 Hz), 129.5, 125.7 (d, 3JCF = 8.9 Hz), 124.5 (d, 4JCF = 4.4 Hz), 123.1, 119.8 (d, 6JCF = 1.8 Hz), 117.4 (d, 2JCF = 8.8 Hz), 109.7, 109.3 (d, 4JCF = 3.4 Hz) ppm. 19F NMR (376 MHz, CDCl3) δ = −130.84 (d, 2JHF = 82.1 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H10FN2O2 233.0721; found 233.0730.
2-(2-Nitro-1-(3-nitrophenyl)vinyl)-1H-pyrrole (5m). Yellow oil. 1H NMR (400 MHz, CDCl3) (Z-isomer) δ = 11.91 (br s, 1H), 8.41–8.32 (m, 1H), 8.33–8.27 (m, 1H), 7.71–7.61 (m, 1H), 7.34–7.30 (m, 1H), 6.92 (s, 1H), 6.40–6.34 (m, 1H), 6.21–6.10 (m, 1H) ppm; (E-isomer) δ = 8.52 (br s, 1H), 8.41–8.32 (m, 1H), 8.23–8.16 (m, 1H), 7.80–7.73 (m, 2H), 7.56 (s, 1H), 7.12–7.07 (m, 1H), 6.46–6.40 (m, 1H), 6.40–6.34 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.3, 148.1, 140.2, 139.9, 138.7, 136.1, 135.4, 134.6, 129.7, 129.6, 129.2, 128.4, 127.5, 127.2, 127.0, 126.0, 124.9, 124.6, 124.5, 124.2, 123.7, 117.8, 112.9, 112.5 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C12H10N3O4 260.0666; found 260.0662.
Elimination for 3o. Purification by column chromatography on silica gel with gradient elution (Hex; Hex/DCM 3:1; Hex/DCM 1:1; Hex/DCM 1:2; DCM) gave 21 mg (15%) of the Z,Z-isomer, 42 mg (29%) of the E,Z-isomer and 24 mg (17 %) of the E,E-isomer of the target product 4o and 13 mg (8 %) of the mixture of (Z-NO2-Z-F)/(E-NO2-Z-F) = 73:27 and 11 mg (7%) of the mixture of (Z-NO2-E-F)/(E-NO2-E-F) = 81:19 of the side product 5o.
1,3-Bis((Z)-2-fluoro-1-(1H-pyrrol-2-yl)vinyl)benzene (Z,Z-4o). Colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.93 (br s, 2H), 7.47–7.37 (m, 4H), 6.91 (dd, J = 4.0, 2.6 Hz, 2H), 6.68 (d, 2JHF = 84.1 Hz, 2H), 6.23 (dd, J = 5.3, 2.6 Hz, 2H), 6.10–6.05 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 143.8 (d, 1JCF = 265.7 Hz), 135.0 (d, 3JCF = 10.2 Hz), 131.0 (d, 4JCF = 2.7 Hz), 129.7 (d, 4JCF = 2.6 Hz), 128.7, 126.9 (d, 3JCF = 3.1 Hz), 119.6 (d, 6JCF = 5.0 Hz), 118.6 (d, 2JCF = 3.6 Hz), 111.2 (d, 4JCF = 4.3 Hz), 109.0. 19F NMR (376 MHz, CDCl3): δ = −131.92 (dd, J = 84.1, 6.5 Hz). HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C18H15F2N2 297.1198; found 297.1197.
1-((E)-2-Fluoro-1-(1H-pyrrol-2-yl)vinyl)-3-((Z)-2-fluoro-1-(1H-pyrrol-2-yl)vinyl)benzene (E,Z-4o). Colorless oil. 1H NMR (400 MHz, CDCl3) δ = 8.92 (br s, 1H), 7.95 (br s, 1H), 7.48 (s, 1H), 7.46–7.35 (m, 3H), 7.10 (d, 2JHF = 83.0 Hz, 1H), 6.91 (dd, J = 4.0, 2.6 Hz, 1H), 6.80 (dd, J = 4.0, 2.5 Hz, 1H), 6.68 (d, 2JHF = 84.1 Hz, 1H), 6.29–6.20 (m, 3H), 6.15–6.09 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 144.9 (d, 1JCF = 267.9 Hz), 143.8 (d, 1JCF = 265.7 Hz), 134.9 (d, 3JCF = 10.2 Hz), 134.1, 130.8 (t, 4JCF = 3.2 Hz), 129.7 (d, 4JCF = 2.5 Hz), 129.5 (d, 4JCF = 3.5 Hz), 128.7, 126.9 (d, 3JCF = 9.6 Hz), 126.9 (d, 3JCF = 3.3 Hz), 119.6 (d, 6JCF = 5.0 Hz), 119.2 (d, 6JCF = 2.0 Hz), 118.7 (d, 2JCF = 9.2 Hz), 118.6 (d, 2JCF = 3.5 Hz), 111.1 (d, 4JCF = 4.5 Hz), 109.4, 109.0, 108.0 (d, 4JCF = 2.7 Hz). 19F NMR (376 MHz, CDCl3) δ −131.77 (dd, J = 84.1, 6.5 Hz), −133.23 (d, 2JHF = 83.0 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C18H15F2N2 297.1198; found 297.1197.
1,3-Bis((E)-2-fluoro-1-(1H-pyrrol-2-yl)vinyl)benzene (E,E-4o). Colorless solid. M.p. = 140-141 ºC with decomposition. 1H NMR (400 MHz, CDCl3): δ = 7.96 (br s, 2H), 7.52–7.33 (m, 4H), 7.10 (d, 2JHF = 83.1 Hz, 2H), 6.79 (dd, J = 4.1, 2.6 Hz, 2H), 6.27–6.23 (m, 2H), 6.22 (dd, J = 5.9, 2.8 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 144.82 (d, 1JCF = 267.3 Hz), 133.99, 130.81 (t, 4JCF = 3.8 Hz), 129.54 (d, 4JCF = 3.4 Hz), 128.75, 126.92 (d, 3JCF = 9.4 Hz), 119.14 (d, 6JCF = 2.1 Hz), 118.74 (d, 2JCF = 9.8 Hz), 109.38, 107.71 (d, 4JCF = 2.6 Hz) ppm. 19F NMR (376 MHz, CDCl3) δ = −133.77 (d, 2JHF = 83.1 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C18H15F2N2 297.1198; found 297.1197.
2-((Z)-1-(3-((Z)-2-fluoro-1-(1H-pyrrol-2-yl)vinyl)phenyl)-2-nitrovinyl)-1H-pyrrole (Z-NO2-Z-F-5o) and 2-((E)-1-(3-((Z)-2-fluoro-1-(1H-pyrrol-2-yl)vinyl)phenyl)-2-nitrovinyl)-1H-pyrrole (E-NO2-Z-F-5o). Yellow oil. 1H NMR (400 MHz, CDCl3): (major) δ = 11.93 (br s, 1H), 8.98 (br s, 1H), 7.55–7.48 (m, 2H), 7.48–7.42 (m, 2H), 7.29–7.24 (m, 1H), 6.98 (s, 1H), 6.93 (dd, J = 4.1, 2.7 Hz, 1H), 6.69 (d, 2JHF = 83.8 Hz, 1H), 6.39–6.33 (m, 1H), 6.34–6.28 (m, 1H), 6.26–6.19 (m, 1H), 6.06–5.98 (m, 1H) ppm; (minor) δ = 8.87 (br s, 1H), 8.34 (br s, 1H), 7.56 (s, 1H), 7.48–7.42 (m, 2H), 7.39–7.37 (s, 1H), 7.34–7.29 (m, 1H), 7.03 (dd, J = 3.9, 2.7 Hz, 1H), 6.90 (dd, J = 4.1, 2.7 Hz, 1H), 6.71 (d, 2JHF = 83.6 Hz, 1H), 6.64–6.59 (m, 1H), 6.39–6.33 (m, 1H), 6.26–6.19 (m, 1H), 6.18–6.14 (m, 1H). 13C NMR (100 MHz, CDCl3) δ = 145.2, 143.8 (d, 1JCF = 266.1 Hz), 142.6, 142.4, 141.1, 139.9 (d, 1JCF = 245.0 Hz), 135.1 (d, 3JCF = 10.4 Hz), 134.9 (d, 3JCF = 10.4 Hz), 134.3, 130.9, 130.8 (d, 4JCF = 2.7 Hz), 130.6 (d, 4JCF = 2.1 Hz), 130.0 (d, 4JCF = 2.9 Hz), 129.5, 129.1, 129.0, 128.5, 128.4, 128.2, 128.9, 127.7, 126.7, 126.7, 126.5 (d, 3JCF = 2.9 Hz), 125.1, 124.9, 119.9 (d, 6JCF = 5.1 Hz), 119.7 (d, 2JCF = 4.7 Hz), 118.4 (d, 2JCF = 3.9 Hz), 115.7, 112.5, 112.1, 111.3 (d, 4JCF = 5.1 Hz), 111.2 (d, 4JCF = 4.0 Hz), 109.2, 109.0 ppm. 19F NMR (376 MHz, CDCl3): (major) δ = −131.57 (dd, J = 83.8, 6.7 Hz) ppm; (minor) δ = −131.01 (dd, J = 83.6, 5.9 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C18H15FN3O2 324.1143; found 324.1140.
2-((Z)-1-(3-((E)-2-fluoro-1-(1H-pyrrol-2-yl)vinyl)phenyl)-2-nitrovinyl)-1H-pyrrole (Z-NO2-E-F-5o) and 2-((E)-1-(3-((E)-2-fluoro-1-(1H-pyrrol-2-yl)vinyl)phenyl)-2-nitrovinyl)-1H-pyrrole (E-NO2-E-F-5o). Yellow oil. 1H NMR (400 MHz, CDCl3): (major) δ = 11.92 (br s, 1H), 8.01 (br s, 1H), 7.54–7.47 (m, 2H), 7.45 (t, J = 7.6 Hz, 1H), 7.39 (dt, J = 7.6, 1.5 Hz, 1H), 7.30–7.25 (m, 1H), 7.10 (d, 2JHF = 82.7 Hz, 1H), 6.97 (s, 1H), 6.84–6.78 (m, 1H), 6.39–6.31 (m, 2H), 6.23 (t, J = 2.3 Hz, 1H), 6.20 (dd, J = 6.0, 2.7 Hz, 1H) ppm; (minor) δ = 8.38 (br s, 1H), 8.08 (br s, 1H), 7.59 (d, J = 7.8 Hz, 1H), 7.56 (s, 1H), 7.54–7.47 (m, 1H), 7.35–7.30 (m, 1H), 7.30–7.25 (m, 1H), 7.14 (d, 2JHF = 83.2 Hz, 1H), 7.05–7.00 (m, 1H), 6.84–6.78 (m, 1H), 6.67 (ddd, J = 3.9, 2.7, 1.3 Hz, 1H), 6.39–6.31 (m, 1H), 6.31–6.26 (m, 1H), 6.23 (t, J = 2.3 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 146.3, 145.2 (d, 1JCF = 269.1 Hz), 143.7, 139.9 (d, 1JCF = 261.7 Hz), 134.2 (d, 3JCF = 5.1 Hz), 134.0, 131.0, 130.9, 130.7 (d, 4JCF = 4.1 Hz), 130.7 (d, 4JCF = 3.5 Hz), 129.6, 129.6, 129.4, 129.1, 129.0, 128.4, 128.4, 128.1, 127.8, 127.7, 126.7, 126.6 (d, 3JCF = 9.0 Hz), 125.3, 125.0, 119.6 (d, 6JCF = 2.5 Hz), 119.4 (d, 6JCF = 2.0 Hz), 118.3 (d, 2JCF = 9.1 Hz), 115.3, 112.5, 112.1, 109.5, 109.2, 108.6 (d, 4JCF = 3.0 Hz), 107.5 (d, 4JCF = 2.0 Hz). 19F NMR (376 MHz, CDCl3) (major) δ = −132.42 (d, 2JHF = 82.7 Hz) ppm; (minor) δ = −133.65 (d, 2JHF = 83.2 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C18H15FN3O2 324.1143; found 324.1140.
Elimination for 3p. Purification by column chromatography on silica gel with gradient elution (Hex/DCM 2:1; DCM) gave 58 mg (63%) of the target product 4p as a mixture of diastereomers (Z/E = 32:54) and 15 mg (15%) of the side product 5p as a mixture of diastereomers (Z/E = 37:63).
2-(1-(4-Chlorophenyl)-2-fluorovinyl)-1-methyl-1H-pyrrole(4p). Colorless oil. 1H NMR (400 MHz, CDCl3): (E-isomer) δ = 7.34–7.28 (m, 2H), 7.20–7.15 (m, 2H), 7.04 (d, 2JHF = 82.9 Hz, 1H), 6.75–6.71 (m, 1H), 6.24–6.21 (m, 1H), 6.20 (dd, J = 3.6, 1.8 Hz, 1H), 3.36 (d, J = 0.8 Hz, 3H) ppm; (Z-isomer) δ = 7.38–7.26 (m, 4H), 6.92 (d, 2JHF = 83.6 Hz, 1H), 6.72–6.69 (m, 1H), 6.25–6.21 (m, 1H), 6.18–6.15 (m, 1H), 3.22 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.5 (d, 1JCF = 278.6 Hz), 146.6 (d, 1JCF = 267.6 Hz), 135.2 (d, 3JCF = 6.7 Hz), 133.9, 133.6 (d, 4JCF = 1.9 Hz), 133.2 (d, 4JCF = 3.6 Hz), 130.1 (d, 4JCF = 5.9 Hz), 129.0, 128.8, 128.6 (d, J = 3.4 Hz), 127.4 (d, 3JCF = 12.6 Hz), 125.5, 124.3 (d, 6JCF = 1.0 Hz), 123.7, 118.1 (d, 2JCF = 8.6 Hz), 116.6 (d, 2JCF = 6.2 Hz), 111.5 (d, 4JCF = 2.5 Hz), 111.3 (d, 4JCF = 1.3 Hz), 108.0, 107.4, 34.9 (d, 5JCF = 2.7 Hz), 34.6 ppm. 19F NMR (282 MHz, CDCl3): (E-isomer) δ = −124.05 (d, 2JHF = 82.9 Hz) ppm; (Z-isomer) δ = −122.67 (d, 2JHF = 83.6 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C13H12ClFN 236.0637; found 236.0640.
2-(1-(4-Chlorophenyl)-2-nitrovinyl)-1-methyl-1H-pyrrole (5p). Yellow oil. 1H NMR (400 MHz, CDCl3) (E-isomer) δ = 7.42–7.37 (m, 2H), 7.35 (s, 1H), 7.31–7.27 (m, 2H), 6.91–6.88 (m, 1H), 6.26 (dd, J = 3.8, 2.6 Hz, 1H), 6.22 (dd, J = 3.8, 1.7 Hz, 1H), 3.38 (s, 3H) ppm; (Z-isomer) δ = 7.42–7.37 (m, 2H), 7.32 (s, 1H), 7.25–7.19 (m, 2H), 6.88–6.84 (m, 1H), 6.28 (dd, J = 3.9, 1.7 Hz, 1H), 6.19 (dd, J = 3.9, 2.7 Hz, 1H), 3.41 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 141.8, 140.7, 137.8, 135.9, 133.9, 133.1, 131.3, 131.1, 130.8, 130.7, 130.7, 129.3, 128.9, 128.5, 127.7, 127.1, 119.1, 116.2, 109.7, 109.4, 36.7, 35.0 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C13H12ClN2O2 263.0582; found 263.0583.
Elimination for 3q. Purification by column chromatography on silica gel with gradient elution (Hex/DCM 3:1; Hex/DCM 1:1) gave 19 mg (57%) of the target product 4q as a mixture of diastereomers (Z/E = 61:31).
2-(1-(4-Chlorophenyl)-2-fluorovinyl)-1-phenyl-1H-pyrrole (4q). Colorless oil. 1H NMR (400 MHz, CDCl3) (Z-isomer) δ = 7.26–7.06 (m, 7H), 7.04–6.97 (m, 2H), 6.97–6.93 (m, 1H), 6.83 (d, 2JHF = 82.4 Hz, 1H), 6.41 (dd, J = 3.6, 1.8 Hz, 1H), 6.38 (dd, J = 3.5, 2.9 Hz, 1H) ppm; (E-isomer) δ = 7.26–7.06 (m, 7H), 7.04–6.97 (m, 2H), 6.97–6.93 (m, 1H), 6.94 (d, 2JHF = 83.4 Hz, 1H), 6.36 (dd, J = 3.5, 1.8 Hz, 1H), 6.33–6.30 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.3 (d, 1JCF = 275.6 Hz), 146.65 (d, 1JCF = 268.1 Hz), 140.3, 140.0, 134.8 (d, 3JCF = 6.6 Hz), 133.5, 133.1, 133.0 (d, 3JCF = 2.9 Hz), 130.2 (d, 4JCF = 5.1 Hz), 128.9, 128.9, 128.6 (d, 4JCF = 3.3 Hz), 128.5, 128.1, 127.7 (d, 3JCF = 11.8 Hz), 126.9, 126.8, 125.4, 125.3, 124.9, 124.5 (d, 6JCF = 1.0 Hz), 123.9, 118.5 (d, 2JCF = 8.6 Hz), 117.6 (d, 2JCF = 7.4 Hz), 113.4 (d, 4JCF = 2.6 Hz), 113.04 (d, 4JCF = 1.5 Hz), 109.3, 108.7. 19F NMR (282 MHz, CDCl3) (Z-isomer) δ = −124.11 (d, 2JHF = 82.4 Hz) ppm; (E-isomer) δ = −124.83 (d, 2JHF = 83.3 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C18H14ClFN 298.0793; found 298.0786.
Elimination for 3r. Purification by column chromatography on silica gel with gradient elution (Hex/DCM 5:1; Hex/DCM 1:1) gave 27 mg (63%) of the target product 4q as a mixture of diastereomers (Z/E = 53:32).
2-(1-(4-Chlorophenyl)-2-fluorovinyl)-1-(4-ethylphenyl)-1H-pyrrole (4r). Yellowish oil. 1H NMR (400 MHz, CDCl3) (Z-isomer) δ = 7.14–6.95 (m, 8H), 6.94–6.90 (m, 1H), 6.82 (d, 2JHF = 82.4 Hz, 1H), 6.40 (dd, J = 3.6, 1.7 Hz, 1H), 6.39–6.36 (m, 1H), 2.59 (q, J = 7.7 Hz, 2H), 1.19 (t, J = 7.5 Hz, 3H) ppm; (E-isomer) δ = 7.14–6.95 (m, 8H), 6.94–6.90 (m, 1H), 6.92 (d, 2JHF = 83.5 Hz, 1H), 6.34 (dd, J = 3.4, 1.8 Hz, 1H), 6.32–6.28 (m, 1H), 2.57 (q, J = 7.7 Hz, 2H), 1.17 (t, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 147.2 (d, 1JCF = 275.0 Hz), 146.6 (d, 1JCF = 268.1 Hz), 143.2, 143.0, 138.0, 137.7, 134.9 (d, 3JCF = 6.7 Hz), 133.4, 133.1 (d, 3JCF = 2.8 Hz), 133.06 (d, 3JCF = 1.3 Hz), 130.3 (d, 4JCF = 5.0 Hz), 129.1 (d, 4JCF = 2.2 Hz), 128.7 (d, 4JCF = 3.3 Hz), 128.4, 128.2, 128.2, 128.0, 125.5, 125.4, 125.0, 124.5 (d, 6JCF = 1.1 Hz), 123.8, 118.5 (d, 2JCF = 8.4 Hz), 117.6 (d, 2JCF = 7.5 Hz), 113.0 (d, 4JCF = 2.6 Hz), 112.6 (d, 4JCF = 1.8 Hz), 109.1, 108.5, 28.5, 28.5, 15.7, 15.7 ppm. 19F NMR (376 MHz, CDCl3) (Z-isomer) δ = −124.17 (d, 2JHF = 82.5 Hz) ppm; (E-isomer) δ = −125.20 (d, 2JHF = 83.4 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C20H18ClFN 326.1106; found 326.1097.
Elimination for 3s. Purification by column chromatography on silica gel with gradient elution (Hex/DCM 4:1; Hex/DCM 1:1) gave 47 mg (72%) of the target product 4s as a mixture of diastereomers (Z/E = 57:35) and 13 mg (18%) of the side product 5s as a mixture of diastereomers (Z/E = 41:59).
2-(1-(4-Chlorophenyl)-2-fluorovinyl)-1-(p-tolyl)-1H-pyrrole (4s). Yellowish oil. 1H NMR (400 MHz, CDCl3) (Z-isomer) δ = 7.18–6.98 (m, 8H), 6.96–6.90 (m, 1H), 6.83 (d, 2JHF = 82.3 Hz, 1H), 6.41–6.36 (m, 2H), 2.31 (s, 3H) ppm; (E-isomer) δ = 7.18–6.98 (m, 8H), 6.96–6.90 (m, 1H), 6.91 (d, 2JHF = 82.1 Hz, 1H), 6.34 (dd, J = 3.3, 1.8 Hz, 1H), 6.31 (t, J = 3.1 Hz, 1H), 2.28 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.3 (d, 1JCF = 275.6 Hz), 146.6 (d, 1JCF = 267.9 Hz), 137.9, 137.5, 136.7, 136.6, 134.9 (d, 3JCF = 6.7 Hz), 133.5, 133.1, 133.1, 130.2 (d, 4JCF = 5.1 Hz), 129.5, 129.4, 128.6 (d, 4JCF = 3.4 Hz), 128.5, 128.1, 127.7 (d, 3JCF = 12.4 Hz), 125.4, 125.1, 124.7, 124.5 (d, 6JCF = 1.0 Hz), 123.9, 118.5 (d, 2JCF = 8.7 Hz), 117.5 (d, 2JCF = 7.3 Hz), 113.0 (d, 4JCF = 2.3 Hz), 112.9 (d, 4JCF = 1.8 Hz), 109.1, 108.5, 21.1, 21.1 ppm. 19F NMR (376 MHz, CDCl3) (Z-isomer) δ = −123.99 (d, 2JHF = 82.4 Hz) ppm; (E-isomer) δ = −124.76 (d, 2JHF = 83.4 Hz) ppm. HRMS (ESI-TOF) m/z: [M + O + H]+ calcd. for C19H15ClFNO (adduct with oxygen) 328.0899; found 328.0890.
2-(1-(4-Chlorophenyl)-2-nitrovinyl)-1-(p-tolyl)-1H-pyrrole (5s). Yellow oil. 1H NMR (400 MHz, CDCl3) (E-isomer) δ = 7.33–7.16 (m, 4H), 7.14–6.96 (m, 5H), 6.75 (s, 1H), 6.32 (dd, J = 3.9, 2.7 Hz, 1H), 6.28 (dd, J = 3.9, 1.7 Hz, 1H), 2.39 (s, 3H) ppm; (Z-isomer) δ = 7.33–7.16 (m, 4H), 7.07 (s, 1H), 7.14–6.96 (m, 5H), 6.42 (d, J = 2.2 Hz, 2H), 2.30 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 140.9, 140.7, 138.6, 137.4, 137.3, 137.1, 136.8, 135.6, 135.3, 134.0, 133.5, 132.2, 131.3, 130.6, 130.5, 130.4, 129.9, 129.2, 129.1, 128.4, 127.4, 126.2, 125.9, 124.6, 121.1, 117.3, 110.6, 110.4, 21.2, 21.1 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C19H16ClN2O2 339.0895; found 339.0895.
Elimination for 3t. Purification by column chromatography on silica gel with gradient elution (Hex/DCM 5:1; Hex/DCM 4:1) gave 46 mg (65%) of the target product 4t as a mixture of diastereomers (Z/E = 62:32) and 10 mg (10%) of the side product 5t as a mixture of diastereomers (Z/E = 39:61).
1-(3-Chloro-4-methoxyphenyl)-2-(1-(4-chlorophenyl)-2-fluorovinyl)-1H-pyrrole (4t). Colorless oil. 1H NMR (400 MHz, CDCl3): (Z-isomer) δ = 7.19–7.09 (m, 3H), 7.07–6.91 (m, 3H), 6.89–6.85 (m, 1H), 6.84 (d, 3JHF = 82.4 Hz, 1H), 6.75 (d, J = 6.8 Hz, 1H), 6.40 (dd, J = 3.5, 1.7 Hz, 1H), 6.38–6.33 (m, 1H), 3.86 (s, 3H) ppm; (E-isomer) δ = 7.19–7.09 (m, 3H), 7.07–6.91 (m, 3H), 6.95 (d, 3JHF = 83.2 Hz, 1H), 6.89–6.85 (m, 1H), 6.71 (d, J = 8.8 Hz, 1H), 6.38–6.33 (m, 1H), 6.29 (t, J = 3.2 Hz, 1H), 3.84 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 153.9, 153.8, 147.3 (d, 1JCF = 276.0 Hz), 146.8 (d, 1JCF = 268.6 Hz), 134.7 (d, 3JCF = 6.6 Hz), 133.7, 133.6, 133.3, 133.3, 132.9 (d, 3JCF = 3.0 Hz), 130.2 (d, 4JCF = 5.0 Hz), 128.6, 128.6, 128.2, 127.4, 127.2, 125.6, 124.6, 124.5, 124.3, 123.8, 122.3, 122.3, 118.2 (d, 2JCF = 8.4 Hz), 117.4 (d, 2JCF = 7.7 Hz), 113.3 (d, 4JCF = 2.7 Hz), 112.8 (d, 4JCF = 1.3 Hz), 111.7, 109.4, 108.8, 56.5, 56.5. 19F NMR (376 MHz, CDCl3): (Z-isomer) δ = −123.66 (d, 3JHF = 82.4 Hz), (E-isomer) δ = −124.46 (d, 3JHF = 83.2 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C19H1535Cl2FNO 362.0509; found 362.0504.
1-(3-Chloro-4-methoxyphenyl)-2-(1-(4-chlorophenyl)-2-nitrovinyl)-1H-pyrrole (5t). Yellow oil. 1H NMR (400 MHz, CDCl3) (E-isomer) δ = 7.33–7.27 (m, 2H), 7.20–7.16 (m, 2H), 7.13 (d, J = 2.6 Hz, 1H), 7.11 (s, 1H), 7.06–6.95 (m, 2H), 6.79 (d, J = 8.8 Hz, 1H), 6.45 (dd, J = 3.8, 1.7 Hz, 1H), 6.41 (dd, J = 3.8, 2.8 Hz, 1H), 3.87 (s, 3H) ppm; (Z-isomer) δ = 7.26–7.22 (m, 2H), 7.16 (d, J = 2.6 Hz, 1H), 7.06–6.95 (m, 4H), 6.94 (s, 1H), 6.84 (d, J = 8.7 Hz, 1H), 6.39 (dd, J = 3.9, 1.7 Hz, 1H), 6.32 (dd, J = 3.9, 2.8 Hz, 1H), 3.92 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 155.0, 154.3, 141.0, 140.4, 137.5, 135.4, 135.3, 133.9, 133.6, 132.6, 132.3, 131.0, 130.5, 130.4, 129.7, 129.2, 128.4, 128.1, 127.3, 126.9, 126.4, 125.5, 124.3, 123.2, 122.7, 120.0, 117.2, 112.2, 112.0, 110.7, 110.6, 56.6, 56.5 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C19H1535Cl2N2O3 389.0454; found 389.0451.
Elimination for 3u. Purification by column chromatography on silica gel with gradient elution (Hex/DCM 2:1; Hex/DCM 1:1; DCM) gave 81 mg (65%) of the target product 4u as a mixture of diastereomers (Z/E = 55:35) and 20 mg (15%) of the side product 5u as a mixture of diastereomers (Z/E = 44:56).
2-(1-(4-Chlorophenyl)-2-fluorovinyl)-1-(3-methoxyphenyl)-1H-pyrrole (4u). Yellowish oil. 1H NMR (400 MHz, CDCl3) (Z-isomer) δ = 7.20–7.05 (m, 4H), 7.02 (d, J = 8.5 Hz, 1H), 7.00–6.94 (m, 1H), 6.87 (d, 2JHF = 82.4 Hz, 1H), 6.80–6.65 (m, 3H), 6.44 (dd, J = 3.4, 1.6 Hz, 1H), 6.42–6.36 (m, 1H), 3.73 (s, 3H) ppm; (E-isomer) δ = 7.20–7.05 (m, 4H), 7.00–6.94 (m, 2H), 6.97 (d, 2JHF = 83.4 Hz, 1H), 6.80–6.65 (m, 3H), 6.42–6.36 (m, 1H), 6.36–6.31 (m, 1H), 3.71 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 159.8, 147.2 (d, 1JCF = 275.7 Hz), 146.7 (d, 1JCF = 268.2 Hz), 141.4, 141.0, 134.7 (d, 3JCF = 6.6 Hz), 133.4, 133.1, 133.0 (d, 3JCF = 2.9 Hz), 130.2 (d, 4JCF = 5.2 Hz), 129.6, 129.6, 128.8 (d, 3JCF = 3.5 Hz), 128.6 (d, 4JCF = 3.2 Hz), 128.5, 128.1, 127.7 (d, 3JCF = 4.1 Hz), 125.3, 124.4, 123.8, 118.5 (d, 2JCF = 8.4 Hz), 117.6, 117.6 (d, 2JCF = 7.2 Hz), 117.3, 113.4 (d, 4JCF = 2.5 Hz), 113.1 (d, 4JCF = 1.3 Hz), 112.5, 112.4, 111.1, 110.9, 109.3, 108.7, 55.4, 55.4 ppm. 19F NMR (376 MHz, CDCl3) (Z-isomer) δ = −124.12 (d, J = 82.4 Hz) ppm; (E-isomer) δ = −124.80 (d, 2JHF = 83.3 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C19H1635ClFNO 328.0899; found 328.0893 ppm.
2-(1-(4-chlorophenyl)-2-nitrovinyl)-1-(3-methoxyphenyl)-1H-pyrrole (5u). Yellow oil. 1H NMR (400 MHz, CDCl3): δ = 7.32–7.22 (m, 3H), 7.21–7.06 (m, 4H), 7.11 (s, 1H), 6.79–6.65 (m, 2H), 6.47 (dd, J = 3.8, 1.7 Hz, 1H), 6.45–6.40 (m, 1H), 3.73 (s, 3H) ppm; δ = 7.32–7.22 (m, 1H), 7.21–7.06 (m, 3H), 7.04 (dd, J = 2.5, 2.0 Hz, 1H), 6.91–6.85 (m, 1H), 6.86 (s, 1H), 6.79–6.65 (m, 3H), 6.37–6.31 (m, 2H), 3.80 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 160.5, 160.1, 140.9, 140.6, 140.6, 140.4, 137.3, 135.4, 135.3, 133.8, 133.7, 132.2, 130.9, 130.6, 130.5, 130.4, 130.0, 129.3, 129.0, 128.3, 127.1, 126.2, 120.6, 118.4, 117.4, 117.1, 113.7, 112.8, 112.2, 110.9, 110.6, 110.4, 55.6, 55.5 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C19H16ClN2O3 355.0844; found 355.0831.
5,5′-((4-Chlorophenyl)methylene)bis(2-(2-fluoro-2-nitro-1-(4-nitrophenyl)ethyl)-1H-pyrrole) (6). A solution of adduct 3l (90 mg, 2.3 mol. equiv.) and 4-chlorobenzaldehyde (23 mg, 1 mol. equiv.) in DCM (1 mL) was loaded into a vial. Next, TFA (1 drop) was added to the solution. The reaction mixture was stirred overnight at room temperature. After completion of the reaction (TLC monitoring), the reaction mixture was concentrated under vacuum. The product was isolated as a mixture of isomers by column chromatography on silica using DCM as the eluent. Pale brown oil. 1H NMR (400 MHz, CDCl3) δ = 8.21–8.06 (m, 4H), 8.03–7.85 (m, 2H), 7.52–7.34 (m, 4H), 7.27–7.20 (m, 2H), 7.07–7.00 (m, 2H), 6.41–6.03 (m, 4H), 5.87–5.69 (m, 2H), 5.37–5.30 (m, 1H), 5.13–4.89 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3) δ = 148.0, 147.8, 142.3, 142.2, 142.2, 140.7, 140.7, 139.5, 139.5, 139.4, 139.4, 133.8, 133.8, 133.7, 133.6, 133.6, 133.3, 133.3, 133.3, 130.2, 130.2, 130.1, 129.7, 129.7, 129.7, 129.4, 129.4, 129.0, 129.0, 129.9, 124.4, 124.2, 124.1, 124.1, 122.2, 122.1, 122.0, 112.3, 111.1 (d, 1JCF = 246.1 Hz), 111.1 (d, 1JCF = 244.8 Hz), 110.9 (d, 1JCF = 246.7 Hz), 110.8, 110.8 (d, 1JCF = 246.4 Hz), 110.8, 110.7, 110.7, 110.6, 110.6, 109.1, 109.1, 109.0, 108.8, 108.8, 108.7, 47.7 (d, 2JCF = 17.5 Hz), 47.6 (d, 2JCF = 17.0 Hz), 47.6 (d, 2JCF = 18.3 Hz), 47.5 (d, 2JCF = 19.2 Hz), 43.3, 43.3 (the other signals are overlapped) ppm. 19F NMR (376 MHz, CDCl3) δ = −150.39–−150.95 (m), −151.00–−151.72 (m) ppm.