6
Y. Yamamoto et al. / Tetrahedron xxx (2018) 1e10
(0.95H, dt, J ¼ 15.7, 7.0), 6.44 (0.95H, d, J ¼ 15.7), 6.51 (0.05H, d,
J ¼ 11.7), 7.20e7.35 (5H, m). 13C NMR: 28.67 (CH2), 28.72 (CH2), 37.3
(CH3), 69.3 (CH2), 125.9 (CH), 127.2 (CH), 128.2 (CH), 128.5 (CH),
131.3 (CH), 137.2 (C). IR (neat): 1350, 1171. HRMS-ESI (m/z):
[MþNa]þ calcd for C12H16NaO3S, 263.0718; found, 263.0722.
4.16. tert-Butyl 2-fluoro-5-(trifluoromethyl)benzyl(6-phenylhex-5-
eny1-yl)carbamate (13d)
Synthesized from 12d (1.05 g, 3.6 mmol) by the same procedure
as 13a. Column chromatography (SiO2 40 g, hexane/EtOAc 10/0 to 8/
2) gave 13d (1.21 g, 74%) as a colorless oil. 1H NMR: 1.38e1.60 (13H,
m), 2.22 (1.8H, dt, J ¼ 7.0, 7.0), 2.33 (0.2H, dt, J ¼ 7.0, 7.0), 3.10e3.35
(2H, m), 4.40e4.60 (2H, m), 5.61 (0.1H, dt, J ¼ 12.0, 7.0), 6.17 (0.9H,
dt, J ¼ 15.8, 7.0), 6.36 (0.9H, d, J ¼ 15.8), 6.41 (0.1H, d, J ¼ 12.0),
7.10e7.33 (6H, m), 7.46e7.56 (2H, m). 13C NMR (ꢁ20 ꢀC): 26.2 (CH2),
26.3 (CH2), 27.4 (CH2), 27.6 (CH2), 28.1 (CH3), 28.2 (CH3), 32.6 (CH2),
32.7 (CH2), 43.1 (CH2), 43.8 (CH2), 46.8 (CH2), 47.0 (CH2), 80.1 (C),
80.2 (C), 115.8 (d, J ¼ 17.7, CH), 123.6 (q, J ¼ 272.9, C), 125.8 (CH),
126.0 (CH), 126.3 (d, J ¼ 15.6, C), 126.4 (CH), 126.7 (q, J ¼ 16.8, C),
126.8 (CH), 126.9 (CH), 128.1 (CH), 128.41 (CH), 128.44 (CH), 128.6
(CH),129.8 (CH),129.9 (CH),130.2 (CH),130.4 (CH),132.4 (CH),132.6
(CH), 137.3 (C), 137.4 (C), 155.3 (C), 155.9 (C), 162.1 (d, J ¼ 251.3, C),
162.3 (d, J ¼ 251.3, C). IR (neat): 1698. ESIMS m/z: 474 [MþNa]þ.
HRMS-ESI (m/z): [MþNa]þ calcd for C25H29F4NNaO2, 474.2032;
found, 474.2053. The E/Z ratio was determined based on integration
area of 1H NMR signals at 6.17 ppm (dt, J ¼ 15.8, 7.0) for (E)-isomer
and 5.61 ppm (dt, J ¼ 12.0, 7.0) for (Z)-isomer. Most of 13C NMR
peaks were broadened at room temperature, and two rotamers (ca.
1/1 ratio) were clearly observed at ꢁ20 ꢀC.
4.13. tert-Butyl 2-fluorobenzyl(5-phenylpent-4-eny1-yl)carbamate
(13c)
Synthesized from 10c (1.06 g, 4.4 mmol, E/Z 95/5) and 12a
(901 mg, 4 mmol) by the same procedure as 13a. Column chroma-
tography (SiO2 70 g, hexane/EtOAc 10/1 to 2/1) gave 13c (902 mg,
61%, E/Z 95/5) as a yellow oil. 1H NMR: 1.40e1.50 (9H, m), 1.71 (2H,
m), 2.19 (1.9H, br s), 2.30 (0.1H, br s), 3.21e3.31 (2H, m), 4.40e4.55
(2H, m), 5.61 (0.05H, m), 6.19 (0.95H, m), 6.37 (0.95H, d, J ¼ 16.0),
6.42 (0.05H, d, J ¼ 11.3), 7.02 (1H, m), 7.10 (1H, m), 7.18e7.33 (6H,
m). 13C NMR (ꢁ20 ꢀC) 27.4 (CH2), 27.6 (CH2), 28.2 (CH3), 28.3 (CH3),
30.2 (CH2), 30.4 (CH2), 43.1 (d, J ¼ 3.6, CH2), 43.9 (d, J ¼ 3.6, CH2),
46.2 (CH2), 46.4 (CH2), 79.7 (C), 79.8 (C), 115.1 (d, J ¼ 21.6, CH), 124.0
(CH), 124.2 (CH), 125.0 (d, J ¼ 14.4, C), 125.3 (d, J ¼ 14.4, C), 125.7
(CH), 125.8 (CH), 126.8 (CH), 126.9 (CH), 128.40 (CH), 128.44 (CH),
128.58 (CH), 128.67 (CH), 128.72 (CH), 129.4 (CH), 129.7 (CH), 129.8
(CH), 129.9 (CH), 130.1 (CH), 137.2 (C), 137.3 (C), 155.5 (C), 155.9 (C),
160.4 (d, J ¼ 247.8, C), 160.7 (d, J ¼ 245.4, C). IR (neat): 1694. ESIMS
m/z: 392 [MþNa]þ. HRMS-ESI (m/z): [MþNa]þ calcd for
4.17. N-(2-Fluoro-5-(trifluoromethyl)benzyl)-6-phenylhex-5-
enylamine (4d)
C
23H28FNNaO2, 392.2002; found, 392.1994. The E/Z ratio was
determined based on integration area of 1H NMR signals at 6.19 (m)
for (E)-isomer and 5.61 (m) for (Z)-isomer. Most of 13C NMR peaks
were broadened at room temperature, and two rotamers (ca. 1/1
ratio) were clearly observed at ꢁ20 ꢀC.
Synthesized from 13d (1.04 g, 2.2 mmol) by the same procedure
as 4a. Column chromatography (amino-SiO2, 20 g, hexane/EtOAc 9/
1) gave 4d (709 mg, 92%) as a yellow oil. 1H NMR: 1.40e1.62 (5H,
m), 2.23 (1.8H, dt, J ¼ 7.0, 7.0), 2.35 (dt, 0.2H, J ¼ 7.2, 7.2), 2.62 (0.2H,
t, J ¼ 7.0), 2.66 (1.8H, t, J ¼ 7.0), 3.86 (0.2H, s), 3.89 (1.8H, s), 5.65
(0.1H, dt, J ¼ 11.5, 7.2), 6.21 (0.9H, dt, J ¼ 15.8, 7.0), 6.38 (0.9H, d,
J ¼ 15.8), 6.42 (0.1H, d, J ¼ 11.5), 7.10e7.34 (6H, m), 7.51 (1H, m),
7.66e7.70 (1H, m). 13C NMR: 26.9 (CH2), 27.5 (CH2), 28.3 (CH2), 29.5
(CH2), 32.8 (CH2), 46.8 (CH2), 49.2 (CH2), 115.7 (d, JCF ¼ 22.5, CH),
123.8 (q, J ¼ 270.6, C), 125.9 (CH), 126.4 (CH), 126.5 (d, J ¼ 3.6, C),
126.8 (CH), 127.0 (q, J ¼ 3.6, C), 127.6 (CH), 128.1 (CH), 128.4 (CH),
128.7 (CH), 129.0 (CH), 130.0 (CH), 130.5 (CH), 132.6 (CH), 137.6 (C),
137.7 (C), 162.8 (d, JCF ¼ 250.5, C). IR (neat): 2754, 2932. ESIMS m/z:
352 [MþH]þ. HRMS-ESI (m/z): [MþH]þ calcd for C20H22F4N,
352.1688; found, 352.1685.
4.14. (E)-N-(2-Fluorobenzyl)-5-phenylpent-4-enylamine (4c)
Synthesized from 13c (902 mg, 2.4 mmol, E/Z 95/5) by the same
procedure as 4a. Column chromatography (SiO2 30 g, EtOAc only)
gave 4c (570 mg, 88%, E/Z 95/5) as a yellow oil. 1H NMR: 1.50 (1H,
brs), 1.70 (2H, quintet, J ¼ 7.0), 2.26 (1.9H, q, J ¼ 7.0), 2.38 (0.1H, q,
J ¼ 7.0), 2.64 (0.1H, t, J ¼ 7.0), 2.68 (1.9H, t, J ¼ 7.0), 3.82 (0.1H, s),
3.85 (1.9H, s), 5.65 (0.05H, dt, J ¼ 11.0, 7.0), 6.20 (0.95H, dt, J ¼ 16.0,
7.0), 6.38 (0.95H, d, J ¼ 16.0), 6.42 (0.05H, d, J ¼ 11.0), 7.02 (1H, t,
J ¼ 9.0), 7.09 (1H, t, J ¼ 7.5), 7.16e7.34 (7H, m). 13C NMR: 29.6 (CH2),
30.7 (CH2), 47.4 (d, JCF ¼ 2.5, CH2), 48.7 (CH2), 115.1 (d, JCF ¼ 21.5,
CH), 124.0 (d, JCF ¼ 3.5, CH), 125.9 (CH), 126.8 (CH), 127.3 (d,
JCF ¼ 15.5, C), 128.4 (CH), 128.6 (d, JCF ¼ 8.5, CH), 130.1 (CH), 130.33
(CH), 130.35 (d, JCF ¼ 5.0, CH), 137.7 (C), 160.1(d, JCF ¼ 243.0, C). IR
(neat): 2924. FABMS m/z: 270 [MþH]þ. HRMS-FAB (m/z): [MþH]þ
calcd for C18H21FN, 270.1658; found, 270.1664. The E/Z ratio was
determined based on integration area of 1H NMR signals at 6.20 (dt,
J ¼ 16.0, 7.0) for (E)-isomer and 5.65 (dt, J ¼ 11.0, 7.0) for (Z)-isomer.
4.18. tert-Butyl 2,6-difluorobenzylcarbamate (12e)
Synthesized from 11e (715 mg, 5 mmol) by the same procedure
as 12a to give 12e (1.3 g, quant) as colorless needles of mp 83e84 ꢀC
(EtOH). 1H NMR: 1.44 (9H, s), 4.3e4.5 (2H, m), 4.65e4.95 (1H, m),
6.88 (2H, m), 7.23 (1H, m). 13C NMR: 27.1 (CH3), 32.2 (CH2), 79.2 (C),
111.0 (dd, JCF ¼ 19.0, 5.0, CH), 114.3 (t, JCF ¼ 19.0, C), 129.1 (t,
JCF ¼ 11.0, CH), 146.5 (C), 155.2 (C), 161.0 (dd, JCF ¼ 248, 8.5). IR
(neat): 1697. ESIMS m/z: 266 [MþNa]þ. HRMS-ESI (m/z): [MþNa]þ
calcd for C12H15F2NNaO2, 266.0969; found, 266.0974.
4.15. tert-Butyl 2-fluoro-5-(trifluoromethyl)benzylcarbamate (12d)
4.19. tert-Butyl (2,6-difluorobenzyl) (6-phenylhex-5-en-1-yl)
carbamate (13e)
Synthesized from 11d (773 mg, 4 mmol) by the same procedure
as 12a to give 12d (1.21 g, quant) as a colorless oil. 1H NMR: 1.46
(9H, brs), 4.26e4.45 (2H, m), 4.70e5.0.3 (1H, m), 7.15 (1H, t, J ¼ 9.0),
7.54 (1H, m), 7.62 (1H, dd, J ¼ 2.0, 6.5). 13C NMR: 27.4 (CH3), 28.3
(CH3), 38.2 (CH2), 80.0 (C), 85.2 (C), 115.9 (d, JCF ¼ 22.7, CH), 123.7 (q,
JCF ¼ 270.5, C), 126.4 (dq, JCF ¼ 8.0, 4.0, CH), 126.8 (CH), 127.2 (d,
JCF ¼ 14.5, C), 146.7 (C), 155.8 (C), 162.5 (d, JCF ¼ 251.5, C). IR (neat):
1697. ESIMS m/z: 316 [MþNa]þ. HRMS-ESI (m/z): [MþNa]þ calcd for
Synthesized from 12e (487 mg, 2 mmol) and 10a (560 mg,
2.2 mmol) by the same procedure as 13a. Column chromatography
(SiO2 40g, hexane/EtOAc 10/1 to 2/1) gave 13e (613 mg, 76%, E/Z 92/
8) as a colorless oil. 1H NMR: 1.35e1.68 (13H, m), 2.22 (1.8H, dt,
J ¼ 7.0, 7.0), 2.31 (0.2H, dt, J ¼ 7.0, 7.0), 3.0e3.3 (2H, m), 4.4e4.7 (2H,
m), 5.61 (0.1H, m), 6.17 (0.9H, dt, J ¼ 16.0, 7.0), 6.36 (0.9H, d,
J ¼ 16.0), 6.40 (0.1H, d, J ¼ 11.5), 6.82e6.87 (2H, m), 7.16e7.33 (6H,
C
13H15F4NNaO2, 316.0937; found, 316.0940.
Please cite this article in press as: Yamamoto Y, et al., Aminolithiationearylation consecutive cyclization of N-(2-fluorophenyl)