O. Bassas, J. Huuskonen, K. Rissanen, A. M. P. Koskinen
FULL PAPER
H), 2.42–2.37 (m, 1 H), 1.66–1.64 (m, 3 H), 1.28–1.19 (m, 1 H), δ = 8.45 (d, J = 4.6 Hz, 1 H), 7.91 (d, J = 9.2 Hz, 1 H), 7.82 (dd,
1.12–1.03 (m, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 181.6, J = 12.2, 7.4 Hz, 2 H), 7.61 (m, 3 H), 7.49 (m, 3 H), 7.41–7.24 (m,
2
158.6, 147.3, 146.8, 144.1, 142.1, 140.6, 131.7 (q, JC-F = 33.0 Hz),
130.2, 129.2, 123.5 (q, 1JC-F = 271.0 Hz), 123.0, 122.7, 119.7, 116.9,
114.4, 103.0, 60.5, 55.6, 54.4, 49.2, 47.6, 39.0, 27.6, 25.4 ppm.
7 H), 7.20 (br. s, 1 H), 6.05 (br. s, 1 H), 5.81 (ddd, J = 17.0, 9.0,
6.0 Hz, 1 H), 5.25 (d, J = 10.0 Hz, 1 H), 5.05 (m, 2 H), 3.95 (s, 3
H), 2.45 (m, 1 H), 2.36–2.20 (m, 3 H), 2.12–1.98 (m, 2 H), 1.48 (m,
1 H), 1.37 (m, 1 H), 1.30–1.15 (m, 2 H), 0.60 (m, 1 H) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 181.1, 157.2, 147.2, 146.6, 146.2,
144.0, 142.5, 140.3, 139.7, 139.4, 131.1, 129.3, 129.1, 128.8, 128.5,
128.2, 125.1, 125.1, 121.7, 120.8, 120.3, 118.1, 114.3, 101.4, 71.8,
61.7, 55.2, 48.9, 45.9, 38.6, 26.8, 26.4, 24.6 ppm. C42H40N4OS
(622.3): calcd. C 77.74, H 6.21, N 8.63, S 4.94; found C 77.79, H
6.16, N 9.12, S 5.46.
N-tert-Butyl-NЈ-[(9R)-6Ј-methoxycinchonan-9-yl]thiourea (9): Thio-
urea 9 (578 mg, 70%) was obtained after flash column chromatog-
raphy as an amorphous solid from amine 7 (626 mg, 1.94 mmol)
and tert-butyl isothiocyanate (20) (245 mg, 2.13 mmol). Rf = 0.40
(15% MeOH in EtOAc); visualization: KMnO4. [α]2D0 = +314 (c =
0.62, CHCl ). IR (film): ν = 3683, 3620, 3426, 3019, 2976, 2896,
˜
3
1622, 1590, 1510, 1475, 1431, 1392, 1215, 1046 cm–1. 1H NMR
(CDCl3, 400 MHz): δ = 8.68 (d, J = 4.8 Hz, 1 H), 8.02 (br. s, 1 H),
7.95 (d, J = 9.2 Hz, 1 H), 7.51 (d, J = 4.8 Hz), 7.45 (dd, J = 9.2,
2.6 Hz, 1 H), 6.15 (d, J = 10 Hz, 1 H), 6.00 (ddd, J = 17.0, 10.5,
6.0 Hz, 1 H), 5.26 (dd, J = 17.0, 1.4 Hz, 1 H), 5.18 (dd, J = 10.5,
1.4 Hz, 1 H), 4.90 (br. s, 2 H), 4.07 (s, 3 H), 3.32–3.25 (m, 1 H),
3.25–3.18 (m, 1 H), 3.06–3.00 (m, 1 H), 2.42–2.39 (m, 1 H), 1.65–
1.57 (m, 3 H), 1.45 (s, 9 H), 1.32–1.25 (m, 1 H), 0.98–0.94 (m, 1
H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 181.3, 157.6, 147.5,
144.5, 140.0, 131.9, 131.6, 128.1, 121.9, 119.2, 114.9, 101.6, 61.8,
55.4, 52.9, 48.8, 46.7, 46.0, 38.8, 29.2, 27.1, 26.4, 25.1 ppm.
N-[(9R)-6Ј-Methoxycinchonan-9-yl]-NЈ-tritylthiourea (13): Thiourea
13 (2.17 g, 79%) was obtained as a white solid after flash column
chromatography (5 % MeOH in DCM) from amine 7 (1.43 g,
4.41 mmol) and commercially available trityl isothiocyanate (19)
(1.33 g, 4.41 mmol); crystallization from MeOH/CHCl3 (5:1) gave
needle-like crystals. M.p. 189–190 °C (dec.). Rf = 0.5 (10% MeOH
in DCM). [α]2D0 = +177.4 (c = 1.5, CHCl ). IR (film): ν = 3415,
˜
3
3258, 3155, 2981, 2941, 2874, 1816, 1793, 1622, 1511, 1475,
1
1382 cm–1. H NMR (CDCl3, 400 MHz): δ = 8.45 (d, J = 4.6 Hz,
1 H), 7.92 (d, J = 9.2 Hz, 1 H), 7.58 (d, J = 2.4 Hz, 1 H), 7.38–
7.28 (m, 16 H), 6.73 (d, J = 2.4 Hz, 1 H), 6.02 (d, J = 4.6 Hz, 1
H), 5.87 (ddd, J = 17.0, 10.6, 6.3 Hz, 1 H), 5.47 (d, J = 10.6 Hz, 1
H), 5.13–5.09 (m, 2 H), 3.98 (s, 3 H), 2.77–2.72 (m, 1 H), 2.64–2.58
(m, 1 H), 2.50–2.46 (m, 2 H), 2.24–2.16 (m, 2 H), 1.52–1.51 (m, 1
H), 1.39–1.37 (m, 1 H), 1.32–1.17 (m, 2 H), 0.74–0.68 (m, 1 H)
ppm. 13C NMR (CDCl3, 100 MHz): δ = 179.9, 157.3, 147.0, 145.8,
144.0, 142.8, 140.2, 131.1, 128.6, 128.4, 128.2, 127.4, 121.7, 118.0,
114.4, 101.4, 72.2, 61.3, 55.4, 55.1, 48.5, 46.7, 38.9, 26.9, 26.3,
24.5 ppm. C40H40N4OS (624.3): calcd. C 76.89, H 6.45, N 8.97, S
5.13; found C 76.08, H 6.37, N 9.37, S 5.30.
N-Benzhydryl-NЈ-[(9R)-6Ј-methoxycinchonan-9-yl]thiourea (10):
Thiourea 10 (700 mg, 55 %) was obtained after flash column
chromatography as an amorphous solid from amine 7 (750 mg,
2.32 mmol) and benzhydryl isothiocyanate 22 (522 mg, 2.32 mmol).
Rf = 0.5 (5% MeOH in DCM); visualization: KMnO4. [α]2D0 = +271
(c = 0.5, CHCl ). IR (film): ν = 3684, 3418, 3019, 2976, 2895, 1710,
˜
3
1622, 1521, 1476, 1421, 1364, 1215 cm–1 1H NMR (CDCl3,
.
400 MHz): δ = 8.61 (d, J = 4.0 Hz, 1 H), 7.95 (br. s, 1 H), 7.91 (d,
J = 8.0 Hz, 1 H), 7.41 (m, 2 H), 7.28–7.11 (m, 11 H), 6.5 (br. s, 1
H), 6.16 (d, J = 8.0 Hz), 5.94 (ddd, J = 16.0, 8.0, 4.0 Hz, 1 H), 5.20
(d, J = 16.0 Hz, 1 H), 5.11 (d, J = 8.0 Hz, 1 H), 3.95 (s, 3 H), 3.31–
3.18 (m, 2 H), 2.97–2.95 (m, 3 H), 2.34–2.32 (m, 1 H), 1.61–1.59
(m, 3 H), 1.24–1.19 (m, 1 H), 0.99–0.94 (m, 1 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 181.6, 157.8, 147.4, 144.5, 140.0, 131.8,
131.6, 128.7, 128.5, 127.6, 127.3, 127.1, 122.1, 119.3, 114.6, 101.1,
62.4, 61.0, 57.8, 55.4, 48.5, 46.3, 38.6, 27.1, 26.2, 24.7 ppm.
N-[(9R)-6Ј-Methoxycinchonan-9-yl]-NЈ-[tris(3,5-dimethylphenyl)-
methyl]thiourea (14): Thiourea 14 (868 mg, 72%) was obtained as
a white foam after flash column chromatography (2% MeOH in
Et2O) from amine 7 (550 mg, 1.54 mmol) and isothiocyanate 29
(596 mg, 1.54 mmol); crystallization from MeOH/CHCl3 (5:1) gave
needle-like crystals. M.p. 131–133 °C (dec.). Rf = 0.28 (2% MeOH
in Et2O). [α]2D0 = +114 (c = 0.63, CHCl ). IR (film): ν = 3415, 3155,
˜
N-[Bis(1-naphthyl)methyl]-NЈ-[(9R)-6Ј-methoxycinchonan-9-yl]-
thiourea (11): Thiourea 11 (732 mg, 89%) was obtained after flash
column chromatography as a white foam from amine 18 (411 mg,
1.27 mmol) and isothiocyanate 27 (413 mg, 1.27 mmol). Rf = 0.27
(5% MeOH in DCM); visualization: KMnO4. [α]2D0 = +188 (c =
3
2941, 1793, 1622, 1595, 1510, 1474, 1381, 1226, 1216, 1169, 1095,
1
910 cm–1. H NMR (CDCl3, 400 MHz): δ = 8.45 (d, J = 4.6 Hz, 1
H), 7.92 (d, J = 9.0 Hz, 1 H), 7.66 (d, J = 2.4 Hz, 1 H), 7.31 (dd,
J = 9.0, 2.4 Hz, 1 H), 7.20 (br. s, 1 H), 6.90 (s, 3 H), 6.89 (s, 6 H),
6.54 (d, J = 3.6 Hz, 1 H), 6.10 (d, J = 4.6 Hz, 1 H), 5.86 (ddd, J =
17.0, 10.4, 6.2 Hz, 1 H), 5.56 (dd, J = 10.6, 3.7 Hz, 1 H), 5.10 (m,
2 H), 3.99 (s, 3 H), 2.81 (m, 1 H), 2.64–2.49 (m, 3 H), 2.26 (s, 18
H), 2.25 (m, 1 H), 1.51 (m, 1 H), 1.39 (m, 1 H), 1.26 (m, 1 H), 1.16
(m, 1 H), 0.86 (m, 1 H), 0.70 (m, 1 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 180.0, 157.5, 147.3, 146.4, 144.3, 143.3, 140.5, 137.6,
131.2, 129.1, 128.7, 126.5, 122.0, 118.0, 114.6, 101.9, 72.3, 61.5,
55.7, 55.4, 49.0, 47.3, 39.2, 27.2, 26.6, 25.0, 21.6 ppm.
1.04, CHCl ). IR (film): ν = 3944, 3757, 3691, 3396, 3054, 2987,
˜
3
2685, 2521, 2410, 2126, 1622, 1598, 1550, 1508, 1421, 1267,
1158 cm–1. 1H NMR (CDCl3, 400 MHz): δ = 8.60 (br. s, 1 H), 8.01–
7.75 (m, 10 H), 7.46–7.17 (m, 8 H), 7.01 (br. s, 1 H), 6.12 (br. s, 1
H), 5.95 (m, 1 H), 5.17 (m, 2 H), 3.93 (s, 3 H), 3.25 (br. s, 2 H),
2.95 (br. s, 3 H), 2.34 (br. s, 1 H), 1.60 (br. s, 3 H), 1.25 (m, 1 H),
0.98 (br. s, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 182.5,
158.0, 147.3, 144.4, 139.6, 136.7, 133.8, 131.9, 131.1, 131.0, 128.6,
127.4, 126.7, 125.8, 125.1, 125.0, 124.4, 123.7, 122.1, 114.7, 99.9,
61.7, 56.5, 55.3, 47.9, 45.9, 38.3, 29.5, 27.0, 25.7, 24.5 ppm.
N-[(9R)-6Ј-Methoxycinchonan-9-yl]-NЈ-[(1R)-1-naphthylethyl]-
thiourea (15): Thiourea 15 (484 mg, 81%) was obtained after flash
N-[(9R)-6Ј-Methoxycinchonan-9-yl]-NЈ-(9-phenylfluoren-9-yl)- column chromatography as an amorphous solid from amine 7
thiourea (12): Thiourea 12 (805 mg, 72%) was obtained after flash
column chromatography (10% MeOH in EtOAc) as a crystalline
solid from amine 7 (586 mg, 1.81 mmol) and isothiocyanate 24
(362 mg, 1.12 mmol) and (1R)-1-(1-naphthyl)ethyl isothiocyanate
(21) (238 mg, 1.12 mmol). Rf = 0.29 (15% MeOH in EtOAc); visu-
alization: KMnO4. [α]2D0 = +195 (c = 2.16, CHCl ). IR (film): ν =
˜
3
(543 mg, 1.81 mmol); recrystallization from EtOAc gave cube-like 3684, 3620, 3411, 3019, 2975, 1710, 1622, 1512, 1475, 1419,
1
crystals. M.p. 201–202 °C (dec.). Rf = 0.38 (10% MeOH in EtOAc);
1363 cm–1. H NMR (CDCl3, 400 MHz): δ = 8.72 (d, J = 4.0 Hz,
1 H), 8.12 (d, J = 8.0 Hz, 1 H), 8.00 (d, J = 8.0 Hz, 1 H), 7.92–
7.90 (d, J = 8.0 Hz, 1 H), 7.81 (dd, J = 8.0 Hz, 1 H), 7.58–7.29 (m,
9 H), 5.77–5.69 (m, 1 H), 5.23 (br. s, 1 H), 5.06–5.00 (m, 2 H), 3.88
visualization: KMnO4. [α]2D0 = +362 (c = 1.0, CHCl ). IR (film): ν
˜
3
= 3944, 3757, 3691, 3402, 3054, 2987, 2685, 2521, 2410, 2126, 2054,
1622, 1507, 1475, 1421, 1264 cm–1. 1H NMR (CDCl3, 400 MHz):
1348
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Eur. J. Org. Chem. 2009, 1340–1351