8
L. ADAM ET AL.
was removed under reduced pressure. The residue was purified by column chromatog-
raphy on silica gel (CH2Cl2/MeOH, 15:1) to give the corresponding thiourea product.
1-[3,5-Bis(trifluoromethyl)phenyl]-3-[(2S,3R,4S,5S)-4-hydroxy-2,5-bis(hydroxyl-methyl)-
6,6-dimethyltetrahydro-2H-pyran-3-yl]thiourea (15)
According to the general procedure 1, pyran derivative 9 (282 mg, 1.38 mmol), and iso-
thiocyanate 14 (374 mg, 1.38 mmol) in methanol (7 mL) were used. The crude product
was purified by column chromatography to give 15 (305 mg, 46%) as colorless crystals,
mp. 83–86 ꢀC, and 18 (160 mg, 38%) as colorless wax. Product 15: [aD20] þ 45.0 (c 0.5,
MeOH). 1 H NMR (CD3OD, 500 MHz): d ¼ 1.27, 1.46 (2 s, 3 H each, Me), 1.78 (q,
J ¼ 5.3 Hz, 1 H, 500-H), 3.56 (dd, J ¼ 11.6, 7.1 Hz, 1 H, 200-CH2), 3.66-3.72 (m, 2 H, 200-
CH2, 500-CH2), 3.75 (dd, J ¼ 11.1, 5.7 Hz, 1 H, 500-CH2), 4.05 (t, J ¼ 4.7 Hz, 1 H, 400-H),
4.19-4.25 (m, 1 H, 200-H), 4.63-4.66 (m, 1 H, 300-H), 7.63 (s, 1 H, 40-H), 8.21 ppm (s, 2 H,
13
20-H). C NMR (CD3OD, 125.8 MHz): d ¼ 26.5, 27.6 (2 q, Me), 49.4 (d, C-500), 58.0 (d,
C 300), 62.8 (t, 200-CH2), 63.2 (t, 500-CH2), 70.8 (d, C-200), 72.6 (d, C-400), 75.8 (s, C-600),
1
2
117.8 (d, C-40), 123.7 (d, C-20), 124.7 (q, JCF ¼ 271.9 Hz, CF3), 132.6 (q, JCF ¼ 32.9 Hz,
C-30), 141.5 (s, C-10), 182.8 ppm (s, C-2). 19 F NMR (CD3OD, 376 MHz): d ¼ ꢁ60.4 ppm
(s, CF3). IR (ATR): m ¼ 3500-3100 (OH, NH), 3100-2895 (¼C-H, C-H), 1275 cmꢁ1
(C ¼ S). HRMS (ESI-TOF) calcd for C18H23F6N2O5S [M þ H]þ: 477.1277, found:
477.1325. Elemental analysis calc (%) for C18H22F6N2O5S (476.4): C 45.38, H 4.65, N
5.88, S 6.73; found: C 45.38, H 4.66, N 5.92, S 7.24. Product 18: 1 H NMR (CD3OD,
400 MHz): d ¼ 4.07 (s, 3 H, OMe), 7.69 (s, 1 H, 4-H), 8.30 ppm (br s, 2 H, 2-H).
13 C NMR (CD3OD, 125.8 MHz): d ¼ 56.4 (q, OMe), 117.0 (d, C-4), 121.1 (d, C-2), 123.3
1
2
(q, JCF ¼ 277.2 Hz, CF3), 131.7 (q, JCF ¼ 37.4 Hz, C-30), 189.5 ppm (s, C ¼ S); the signal
of C-10 could not be detected. IR (ATR): m ¼ 3300-3200 (N-H), 3100-2900 (¼C-H,
C-H), 1280 cmꢁ1 (C ¼ S). Elemental analysis calc (%) for C10H7F6NOS (303.2): C 39.61,
H 2.33, N 4.62, S 10.57; found: C 39.64, H 2.54, N 4.69, S 10.04.
1-[3,5-Bis(trifluoromethyl)phenyl]-3-[(2S,3S,4R,5S,6S)-3,5-dihydroxy-2,6-bis-(hydroxy-
methyl)-7,7-dimethyloxepan-4-yl]thiourea (17)
According to the general procedure 1, oxepane derivative 13 (353 mg, 1.50 mmol), and
isothiocyanate 14 (407 mg, 1.50 mmol) in methanol (8 mL) were used. The crude prod-
uct was purified by column chromatography to give 17 (605 mg, 80%) as pale pink solid,
1
mp. 165 ꢀC, [aD20] -20.5 (c 0.7, MeOH). H NMR (CD3OD, 500 MHz, 300 K): d ¼ 1.35
(2 s, 3 H each, Me), 2.00-2.08 (m, 1 H, 600-H), 3.53–3.72 (m, 5 H, 200-H, 200-CH2, 600-CH2),
3.85 (dd, J ¼ 7.8, 2.9 Hz, 1 H, 500-H), 3.95 (mc, 1 H, 300-H), 4.58–4.70 (m, 1 H, 400-H), 7.56
(s, 1 H, 40-H), 8.07 ppm (s, 2 H, 20-H). 13 C NMR (CD3OD, 125.8 MHz, 300 K): d ¼ 21.2,
00
00
00
00
ꢂ
31.6 (2 q, Me), 59.8 (d, C-6 ), 63.6 (t, 2 -CH2, 6 -CH2), 67.7 (d, C-4 ), 73.7, 74.9 (2 d,
1
C-200, C-500), 77.4 (s, C-700), 118.1 (d, C-40), 124.4 (d, C-20), 124.7 (q, JCF ¼ 273.5 Hz,
2
0
0
ꢂ
CF3), 132.8 (q, JCF ¼ 40.9 Hz, C-3 ), 143.0 (s, C-1 ), 184.2 ppm (s, C-2); intensity of the
peak corresponds to two C atoms. 19 F NMR (CD3OD, 376 MHz): d ¼ ꢁ64.3 ppm (s,
CF3). IR (ATR): m ¼ 3500–3100 (O-H, N-H), 3100–2850 (¼C-H, C-H), 1275 cmꢁ1
(C ¼ S). HRMS (ESI–TOF): calcd for C19H25F6N2O5S [M þ H]þ: 507.1400, found:
507.1383. Elemental analysis calc (%) for C19H24F6N2O5S (506.5): C 45.06, H 4.78, N
5.53, S 6.33; found: C 45.00, H 4.79, N 5.46, S 6.48.