The Journal of Organic Chemistry
Article
2
1
(C−F, d, JC−F = 21.2 Hz), 75.2 (C−F, d, JC−F = 242.5 Hz), 62.6
(tdd, J = 8.4, 2.6, 0.9 Hz, 1H), 6.93 (ddt, J = 7.7, 1.7, 0.8 Hz, 1H),
6.86 (dt, J = 9.3, 2.2 Hz, 1H), 4.94 (ddd, J = 61.5, 6.4, 4.4 Hz, 1H),
4.58 (ddd, J = 6.2, 5.3, 0.7 Hz, 1H), 3.94 (dt, J = 22.7, 4.8 Hz, 1H).
(C−F, d, 2JC−F = 13.7 Hz), 29.2 (C−F, dd, 2,3JC−F = 9.2, 4.0 Hz). 19
NMR (376 MHz, CDCl3): δ −115.52 to −115.64 (m), −216.02
(dddd, J = 61.1, 13.3, 8.8, 2.6 Hz). Anal. Calcd for C9H7F2NO2: C,
54.28; H, 3.54; N, 7.03. Found: C, 55.26; H, 3.77; N 6.60.
F
1
13C{1H} NMR (101 MHz, CDCl3): δ 163.2 (C−F, d, JC−F = 248.3
3,3
3
Hz), 134.8 (C−F, dd,
J
= 7.7, 1.1 Hz), 131.1 (C−F, d, JC−F
=
C−F
8.4 Hz), 123.0 (C−F, d, 4JC−F = 3.1 Hz), 115.6 (C−F, d, 2JC−F = 21.0
1-Fluoro-2-((1S*,2R*,3R*)-2-fluoro-3-nitrocyclopropyl)benzene
1
2
1
(3f′). Second fraction (5.5 mg, 0.028 mmol, 14%) a yellow oil. H
Hz), 114.5 (C−F, d, JC−F = 22.5 Hz), 74.4 (C−F, d, JC−F = 247.9
2
2,4
NMR (400 MHz, CDCl3): δ 7.38−7.27 (m, 2H), 7.16 (td, J = 7.6, 1.3
Hz, 1H), 7.07 (ddd, J = 9.5, 8.4, 1.1 Hz, 1H), 5.69 (ddd, J = 59.6, 5.2,
1.4, 0.5 Hz, 2H), 5.03 (ddd, J = 11.9, 10.2, 1.5 Hz, 1H), 3.40 (ddd, J =
21.8, 10.2, 5.3 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3): δ 161.9
Hz), 63.7 (C−F, d, JC−F = 10.7 Hz), 31.7 (C−F, dd,
J
= 10.4,
C−F
2.2 Hz). 19F NMR (376 MHz, CDCl3): δ −111.26 (td, J = 8.9, 6.0
Hz), −215.38 (dd, J = 61.5, 22.8 Hz).
1-Bromo-4-(2-fluoro-3-nitrocyclopropyl)benzene (3h). The prod-
uct was obtained following general procedure C, using (E)-1-bromo-
4-(2-nitrovinyl)benzene(1h) (45.9 mg, 0.201 mmol, 1 equiv), (2,3-
dichlorophenyl)(2,4-dimethylphenyl)(fluoromethyl)sulfonium tetra-
fluoroborate (2y) (162.1 mg, 0.4023 mmol, 2 equiv), NaH (60%
dispersion in mineral oil, 24.1 mg, 0.604 mmol, 3 equiv), and THF (8
mL) to give the crude product 3h (74%, dr = 69:22:9, determined by
1H NMR, using EtOAc as an internal standard). After purification, 3h
(36.9 mg, 0.142 mmol, 71%, dr = 69:20:11) was obtained as a yellow
oil. For separation of diastereomers a preparative TLC was used,
eluting with PE/Et2O 7:1.
1,4
3
(C−F, dd,
J
= 248.4, 1.6 Hz), 130.7 (C−F, d, JC−F = 8.2 Hz),
C−F
3
4
130.5 (C−F, d, JC−F = 2.8 Hz), 124.6 (C−F, d, JC−F = 3.8 Hz),
2
2
116.5 (C−F, d, JC−F = 14.4 Hz), 116.0 (C−F, d, JC−F = 21.0 Hz),
1,4
74.8 (C−F, dd,
(C−F, dd,
J
= 239.8, 2.5 Hz), 63.1−62.9 (C−F, m), 31.2
C−F
2,3
J
= 11.6, 2.8 Hz). 19F NMR (376 MHz, CDCl3): δ
C−F
−115.64 to −115.72 (m), −205.91 (ddd, J = 60.1, 21.8, 12.1 Hz).
1-Fluoro-2-((1S*,2R*,3S*)-2-fluoro-3-nitrocyclopropyl)benzene
1
(3f′′). Third fraction (4.6 mg, 0.023 mmol, 12%) a yellow oil. H
NMR (400 MHz, CDCl3): δ 7.36−7.28 (m, 1H), 7.18−7.06 (m, 3H),
5.09 (ddd, J = 61.7, 6.2, 4.5 Hz, 1H), 4.69 (ddd, J = 6.2, 5.5, 0.6 Hz,
1H), 3.93 (ddd, J = 23.1, 5.5, 4.5 Hz, 1H). 13C{1H} NMR (101 MHz,
1-Bromo-4-((1R*,2R*,3R*)-2-fluoro-3-nitrocyclopropyl)benzene
CDCl3): δ 161.3 (C−F, d, 1JC−F = 247.5 Hz), 130.3 (C−F, d, 3JC−F
=
1
(3h). First fraction (24.5 mg, 0.0942 mmol, 47%) a yellow oil. H
3
4
8.3 Hz), 129.2 (C−F, d, JC−F = 3.4 Hz), 124.8 (C−F, d, JC−F = 3.8
NMR (400 MHz, CDCl3): δ 7.53−7.49 (m, 2H), 7.18−7.14 (m, 2H),
5.46 (ddd, J = 61.2, 7.7, 1.3 Hz, 1H), 4.82 (ddd, J = 13.3, 5.4, 1.3 Hz,
1H), 3.41 (ddd, J = 8.8, 7.6, 5.4 Hz, 1H). 13C{1H} NMR (101 MHz,
Hz), 119.9 (C−F, dd, 2,3JC−F = 13.8, 1.1 Hz), 116.3 (C−F, d, 2JC−F
=
21.1 Hz), 74.1 (C−F, dd, 1,4JC−F = 247.0, 4.0 Hz), 63.2 (C−F, d, 2JC−F
2,3
= 6.1 Hz), 27.7 (C−F, dd,
J
= 11.5, 2.5 Hz). 19F NMR (376
4
C−F
CDCl3): δ 132.2, 130.5 (C−F, d, JC−F = 1.5 Hz), 128.9 (C−F, d,
MHz, CDCl3): δ −117.21 to −117.31 (m), −215.82 (ddd, J = 62.2,
3JC−F = 2.7 Hz), 122.7, 75.5 (C−F, d, 1JC−F = 242.5 Hz), 63.3 (C−F,
23.1, 1.5 Hz).
2
2
d, JC−F = 13.4 Hz), 34.5 (C−F, d, JC−F = 9.2 Hz). 19F NMR (376
MHz, CDCl3): δ −216.55 (ddd, J = 61.2, 13.2, 9.0 Hz). Anal. Calcd
for C9H7BrFNO2: C, 41.57; H, 2.71; N, 5.39. Found: C, 42.97; H,
3.08; N 4.87.
1-Fluoro-3-(2-fluoro-3-nitrocyclopropyl)benzene (3g). The prod-
uct was obtained following general procedure C, using (E)-1-fluoro-3-
(2-nitrovinyl)benzene (1g) (33.6 mg, 0.201 mmol, 1 equiv), (2,3-
dichlorophenyl)(2,4-dimethylphenyl)(fluoromethyl)sulfonium tetra-
fluoroborate (2y) (162.1 mg, 0.4023 mmol, 2 equiv), NaH (60%
dispersion in mineral oil, 24.1 mg, 0.604 mmol, 3 equiv) and THF (8
mL) to give the crude product 3g (69%, dr = 62:16:22, determined by
1H NMR, using EtOAc as an internal standard). After purification, 3g
(29.3 mg, 0.147 mmol, 73%, dr = 65:16:19) was obtained as a slightly
yellow oil. For separation of diastereomers a preparative TLC was
used, eluting with PE/Et2O 7:1. Three separate diastereomers were
obtained.
1-Bromo-4-((1S*,2R*)-2-fluoro-3-nitrocyclopropyl)benzene
(3h′+3h′′). Second fraction (10.7 mg, 0.0411 mmol, 21%, dr =
1
67:33) a yellow oil. H NMR (400 MHz, CDCl3): δ 7.53−7.45 (m,
4H), 7.18−7.13 (m, 2H), 7.06−6.99 (m, 2H), 5.68 (ddd, J = 59.8,
5.2, 1.5 Hz, 1H), 4.96 (ddd, J = 11.9, 10.4, 1.5 Hz, 1H), 4.92 (ddd, J =
61.5, 6.3, 4.4 Hz, 1H), 4.55 (ddd, J = 6.2, 5.3, 0.5 Hz, 1H), 3.90 (dt, J
= 22.7, 4.8 Hz, 1H), 3.40 (ddd, J = 22.0, 10.4, 5.2 Hz, 1H). 13C{1H}
NMR (101 MHz, CDCl3): δ 132.5, 132.3, 131.4 (C−F, d, 3JC−F = 1.0
Hz), 130.6 (C−F, d, 4JC−F = 1.3 Hz), 129.0 (C−F, d, 4JC−F = 0.6 Hz),
1-Fluoro-3-((1R*,2R*,3*)-2-fluoro-3-nitrocyclopropyl)benzene
(3g). First fraction (16.7 mg, 0.0838 mmol, 42%) a slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ 7.35 (td, J = 8.0, 6.0 Hz, 1H), 7.12−
1
127.9, 123.1, 122.6, 74.7 (C−F, d, JC−F = 239.4 Hz), 74.4 (C−F, d,
2
1JC−F = 247.9 Hz), 63.9−63.4 (C−F, m), 36.0 (C−F, d, JC−F = 11.1
Hz), 31.6 (C−F, d, 2JC−F = 10.5 Hz). 19F NMR (376 MHz, CDCl3): δ
−206.60 (ddd, J = 59.9, 22.0, 12.2 Hz), −215.45 (dd, J = 61.5, 22.4
Hz).
7.05 (m, 1H), 7.08−7.01 (m, 1H), 7.02−6.98 (m, 1H), 5.46 (ddd, J =
61.1, 7.7, 1.3 Hz, 1H), 4.84 (ddd, J = 13.4, 5.4, 1.3 Hz, 1H), 3.45 (td,
J = 8.8, 7.7, 5.5 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3): δ 162.9
1
3,3
2-(2-Fluoro-3-nitrocyclopropyl)naphthalene (3i). The product
was obtained following general procedure C, using (E)-2-(2-
nitrovinyl)naphthalene (1i) (40.1 mg, 0.201 mmol, 1 equiv), (2,3-
dichlorophenyl)(2,4-dimethylphenyl)(fluoromethyl)sulfonium tetra-
fluoroborate (2y) (162.1 mg, 0.4023 mmol, 2 equiv), NaH (60%
dispersion in mineral oil, 24.1 mg, 0.604 mmol, 3 equiv), and THF (8
mL) to give the crude product 3i (80%, dr = 66:22:12, determined by
1H NMR, using EtOAc as an internal standard). After purification, 3i
(35.5 mg, 0.154 mmol, 76%, dr = 72:18:10) was obtained as a slightly
yellow oil. For separation of the major diastereomer a silica gel
column chromatography was used, eluting with PE/EtOAc 10:1.
2-((1R*,2R*,3R*)-2-Fluoro-3-nitrocyclopropyl)naphthalene (3i).
First fraction (12.8 mg, 0.0554 mmol, 28%) white solid. Mp: 107−
109 °C. 1H NMR (400 MHz, CDCl3): δ 7.88−7.81 (m, 3H), 7.78 (s,
1H), 7.57−7.47 (m, 2H), 7.36 (dd, J = 8.5, 1.9 Hz, 1H), 5.54 (ddd, J
= 61.3, 7.7, 1.3 Hz, 1H), 4.98 (ddd, J = 13.3, 5.4, 1.3 Hz, 1H), 3.63
(ddd, J = 9.0, 7.6, 5.2 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3): δ
(C−F, d, JC−F = 247.5 Hz), 132.2 (C−F, dd,
J
= 8.2, 2.8 Hz),
C−F
3
4,4
130.6 (C−F, d, JC−F = 8.4 Hz), 124.7 (C−F, dd,
J
= 3.1, 1.4
C−F
Hz), 116.0 (C−F, dd, 2,4JC−F = 22.8, 1.7 Hz), 115.6 (C−F, d, 2JC−F
=
=
1
2
21.0 Hz), 75.5 (C−F, d, JC−F = 242.8 Hz), 63.4 (C−F, d, JC−F
13.5 Hz), 34.6 (C−F, d, 2,4JC−F = 9.2, 2.3 Hz). 19F NMR (376 MHz,
CDCl3): δ −111.81 (td, J = 9.0, 6.0 Hz), −216.63 (ddd, J = 61.2,
13.1, 8.9 Hz). HRMS calcd for [M + H]+: C9H8NO2F2 200.0523,
found 200.0511.
1-Fluoro-3-((1S*,2R*,3R*)-2-fluoro-3-nitrocyclopropyl)benzene
(3g′). Second fraction (4.4 mg, 0.0221 mmol, 11%) a slightly yellow
1
oil. H NMR (400 MHz, CDCl3): δ 7.33 (td, J = 8.0, 5.9 Hz, 1H),
7.08−7.04 (m, 1H), 7.04−6.98 (m, 2H), 5.70 (ddd, J = 59.8, 5.2, 1.5
Hz, 1H), 4.97 (ddd, J = 11.9, 10.4, 1.5 Hz, 1H), 3.45 (ddd, J = 21.9,
10.4, 5.2 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3): δ 163.0 (C−F,
d, 1JC−F = 247.7 Hz), 131.2 (C−F, d, 3JC−F = 8.0 Hz), 130.7 (C−F, d,
3JC−F = 8.4 Hz), 124.7 (C−F, dd, 4,4JC−F = 3.0, 1.2 Hz), 116.2 (C−F,
2,4
2
dd,
J
= 22.5, 1.0 Hz), 116.1 (C−F, d, JC−F = 21.0 Hz), 74.7
C−F
4
1
2
133.3, 133.0, 128.9, 128.2 (C−F, d, JC−F = 1.5 Hz), 127.9, 127.9,
(C−F, d, JC−F = 239.4 Hz), 63.7 (C−F, d, JC−F = 13.7 Hz), 36.0
127.2 (C−F, d, 3JC−F = 2.6 Hz), 126.9, 126.8, 126.2 (C−F, d, 4JC−F
=
2,4
(C−F, d,
J
= 11.1, 2.3 Hz). 19F NMR (376 MHz, CDCl3): δ
C−F
1.2 Hz), 75.9 (C−F, d, 1JC−F = 242.5 Hz), 63.6 (C−F, d, 2JC−F = 13.5
Hz), 35.5 (C−F, d, 2JC−F = 9.2 Hz). 19F NMR (376 MHz, CDCl3): δ
−216.14 (ddd, J = 61.3, 13.1, 9.0 Hz). HRMS calcd for [M + H]+:
C13H11NO2F 232.0778, found 232.0774.
−111.73 to −111.84 (m), −206.67 (ddd, J = 59.9, 21.9, 12.0 Hz).
1-Fluoro-3-((1S*,2R*,3S*)-2-fluoro-3-nitrocyclopropyl)benzene
(3g′′). Third fraction (5.8 mg, 0.029 mmol, 15%) a slightly yellow oil.
1H NMR (400 MHz, CDCl3): δ 7.34 (td, J = 8.1, 5.9 Hz, 1H), 7.03
3206
J. Org. Chem. 2021, 86, 3196−3212