The Journal of Organic Chemistry
Page 18 of 30
rac-(2S,5S)-5-([1,1'-Biphenyl]-2-yl)-1-(tert-butyl)-3,3-difluoropyrrolidine-2-carbonitrile (4j). Yield:
106.5 mg, 78%, dr > 20:1; yellow oil, Rf = 0.30 (PE:EA = 30:1); 1H NMR (CDCl3, 400 MHz) δ 7.94 (d,
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1H, J = 7.9 Hz), 7.48–7.37 (m, 4H), 7.28 (t, 1H, J = 7.1 Hz), 7.21 (d, 2H, J = 6.7 Hz), 7.12 (d, 1H, J =
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7.4 Hz), 4.32–4.18 (m, 2H), 2.56 (td, 1H, J = 14.0, 6.9 Hz), 2.43–2.22 (m, 1H), 0.88 (s, 9H); C{1H}
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NMR (CDCl3, 101 MHz) δ 142.3, 140.8, 139.79, 129.6, 128.8, 128.5, 128.4, 127.5, 127.0, 126.9, 124.1
(dd, J = 263.7, 250.3 Hz), 117.4 (d, J = 14.4 Hz), 57.1 (dd, J = 38.4, 23.1 Hz), 56.8 (d, J = 7.4 Hz), 56.3,
43.9 (dd, J = 22.6, 19.0 Hz), 27.0; 19F NMR (CDCl3, 471 MHz) δ -100.9 (ddt, 1F, J = 227.3, 31.0, 15.3
Hz), -106.6 (dd, 1F, J = 227.4, 7.3 Hz); HRMS (ESI) m/z: [M + H]+ Calcd for C21H23F2N2 341.1829;
Found 341.1831; IR (film): 2971, 1478, 1439, 1373, 1252, 1220, 1197, 1164, 1083, 1026, 981 cm-1.
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rac-(2S,5S)-1-(tert-Butyl)-5-(3-chlorophenyl)-3,3-difluoropyrrolidine-2-carbonitrile (4k). Yield: 92.8
mg, 78%, dr > 20:1; pale yellow oil; Rf = 0.24 (PE:EA = 30:1); 1H NMR (400 MHz, CDCl3) δ 7.37 (d,
2H, J = 7.3 Hz), 7.26 (t, 2H, J = 7.5 Hz), 7.17 (t, 1H, J = 7.3 Hz), 4.29–4.21 (m, 2H), 2.58 (td, 1H, J =
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13.8, 6.7 Hz), 2.23 (dddd, 1H, J = 31.3, 14.0, 10.0, 7.0 Hz), 0.95 (s, 9H); C{1H} NMR (CDCl3, 101
MHz) δ 147.2, 134.6, 130.2, 127.7, 126.2, 124.3, 123.9 (dd, J = 263.9, 250.5 Hz), 117.2 (d, J = 13.9 Hz),
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60.1 (d, J = 7.3 Hz), 57.0 (dd, J = 38.2, 23.2 Hz), 56.5, 43.9 (dd, J = 22.7, 19.4 Hz), 27.15; F NMR
(CDCl3, 471 MHz) δ -101.2 (ddt, J = 228.1, 30.2, 14.7 Hz), -106.9 (dd, J = 228.3, 7.2 Hz); HRMS (ESI)
m/z: [M + H]+ Calcd for C15H18ClF2N2 299.1127; Found 299.1122; IR (film): 2975, 1598, 1475, 1434,
1373, 1349, 1328, 1220, 1202, 1130, 1035, 983 cm-1.
rac-(2S,5S)-1-(tert-Butyl)-3,3-difluoro-5-(3-nitrophenyl)pyrrolidine-2-carbonitrile (4l). Yield: 111.2
mg, 90%, dr > 20:1; pale yellow oil, Rf = 0.09 (PE:EA = 30:1); 1H NMR (CDCl3, 400 MHz) δ 8.23 (s,
1H), 8.14 (d, 1H, J = 8.0 Hz), 7.96 (d, 1H, J = 7.7 Hz), 7.60 (t, 1H, J = 7.9 Hz), 4.52–4.46 (m, 1H), 4.40
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(d, 1H, J = 15.4 Hz), 2.84–2.71 (m, 1H), 2.41–2.22 (m, 1H), 1.06 (s, 9H); C{1H} NMR (CDCl3, 101
MHz) δ 148.4, 147.3, 132.4, 130.2, 123.8 (dd, J = 263.7, 251.0 Hz), 122.8, 121.0, 117.1 (d, J = 13.3 Hz),
59.9 (d, J = 7.0 Hz), 56.9 (dd, J = 37.8, 23.2 Hz), 56.7, 43.7 (t, J = 20.3, 19.7 Hz), 27.2; 19F NMR
(CDCl3, 471 MHz) δ -101.5 (ddt, 1F, J = 228.8, 28.8, 14.3 Hz), -106.4 (ddd, 1F, J = 228.9, 7.3, 3.1 Hz);
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