Total Syntheses of (+)-Valiolamine and (–)-1-epi-Valiolamine
and filtered. Concentration of the filtrate followed by flash
chromatography (EtOAc/hexane, 1:4) afforded 11a (1.473 g,
2.719 mmol, 92%) as a colorless oil. [α]2D0 = –39.7 (c = 1.00,
11.4 Hz, 1 H, CHHOAc), 4.00 (d, J = 11.4 Hz, 1 H, CHHOAc),
4.24–4.29 (m, 1 H, 1-H), 5.06 (d, J = 10.2 Hz, 4-H), 5.08 (dd, J =
10.3, 3.8 Hz, 1 H, 2-H), 5.69 (dd, J = 10.3, 10.2 Hz, 1 H, 3-H) ppm.
CHCl3). 1H NMR(CDCl3): δ = 1.08 [s, 9 H, C(CH3)3], 1.43 (s, 3 13C NMR (CDCl3): δ = 170.22 (CH3COO), 169.97 (CH3COO),
H, CH3COO), 1.80 (dd, J = 15.5, 3.6 Hz, 1 H, 6-H), 1.93 (dd, J =
169.85 (CH3COO), 169.70 (CH3COO), 73.36 (C-5), 73.14 (C-4),
15.5, 3.2 Hz, 1 H, 6-H), 2.10 (s, 3 H, CH3COO), 2.35 (br. s, 1 H, 71.83 (C-3), 68.51 (C-2), 65.55 (CH2OAc), 58.35 (C-1), 33.30 (C-
OH), 3.02 (br. s, 1 H, OH), 3.50–3.58 (m, 1 H, 1-H), 3.89 (d, J =
11.1 Hz, 1 H, CHHOAc), 4.03 (d, J = 11.1 Hz, 1 H, CHHOAc),
6), 20.77 (CH3COO), 20.58 (CH3COO), 20.54 (CH3COO), 20.42
(CH3COO) ppm. HRMS (ESI): calcd. for C15H21N3O9Na [M +
4.06–4.18 (m, 2 H, 3-H and 4-H), 4.89 (dd, J = 9.9, 3.5 Hz, 1 H, Na]+ 410.1175; found 410.1174. IR (neat): ν = 3349 (O–H), 2926,
˜
2-H), 7.35–7.50 (m, 6 H, Ph-H), 7.60–7.65 (m, 2 H, Ph-H), 7.77–
2111 (N3), 1743 (C=O), 1425, 1375, 1236, 1038, 917, 814, 745, 627,
7.84 (m, 2 H, Ph-H) ppm. 13C NMR (CDCl3): δ = 170.64 602, 531 cm–1.
(CH3COO), 170.59 (CH3COO), 136.15 (Ar), 135.52 (Ar), 134.50
(1R,2S,3R,4S,5S)-5-Acetoxymethyl-1-azido-5-hydroxy-2,3,4-tri-
(Ar), 132.18 (Ar), 130.17 (Ar), 129.56 (Ar), 127.88 (Ar), 127.63
(Ar), 76.09 (C-5), 74.35 (C-2), 73.27 (C-4), 71.66 (C-3), 66.38
(CH2OAc), 58.37 (C-1), 32.36 (C-6), 27.01 (CH3COO), 20.96
(CH3COO), 20.02 [C(CH3)3], 19.73 [C(CH3)3] ppm. HRMS (ESI):
calcd. for C27H35N3O7SiNa [M + Na]+ 564.2142; found 564.2144.
acetoxycyclohexane (12b): The same procedure described for the
preparation of 12a was followed, and compound 12b was obtained
from 11b in 71% yield as off-white crystals, m.p. 113.1–114.5 °C.
[α]2D0 = –11.0 (c = 1.00, CHCl3). H NMR(CDCl3): δ = 1.68 (dd, J
1
= 14.0, 12.7 Hz, 1 H, 6-H), 1.99 (s, 3 H, CH3COO), 2.08 (s, 3 H,
CH3COO), 2.10 (s, 3 H, CH3COO), 2.10 (s, 3 H, CH3COO), 2.19
(dd, J = 14.0, 4.8 Hz, 1 H, 6-H), 2.68 (br. s, 1 H, OH), 3.88 (d, J
= 11.4 Hz, 1 H, CHHOAc), 3.93–4.05 (m, 2 H, 1-H and
CHHOAc), 5.07 (dd, J = 10.0, 9.8 Hz, 1 H, 2-H), 5.11 (d, J =
10.1 Hz, 1 H, 4-H), 5.40 (dd, J = 10.1, 10.0 Hz, 1 H, 3-H) ppm.
13C NMR (CDCl3): δ = 170.58 (CH3COO), 170.11 (CH3COO),
169.88 (CH3COO), 169.26 (CH3COO), 73.97 (C-5), 72.15 (C-4),
72.12 (C-3), 71.22 (C-2), 66.23 (CH2OAc), 57.22 (C-1), 35.09 (C-
6), 20.71 (CH3COO), 20.65 (CH3COO), 20.55 (CH3COO), 20.49
(CH3COO) ppm. HRMS (ESI): calcd. for C15H21N3O9Na [M +
IR (neat): ν = 3496 (O–H), 2933, 2858, 2117 (N ), 1735 (CH COO),
˜
3
3
1429, 1374, 1231, 1113, 1043, 978, 887, 823, 743, 706, 609,
514 cm–1.
(1R,2S,3S,4S,5S)-2-Acetoxy-1-azido-3-(tert-butyldiphenylsilyloxy)-
4,5-dihydroxycyclohex-5-yl Methyl Acetate (11b): The same pro-
cedure described for the preparation of 11a was followed, and com-
pound 11b was obtained from 10b in 91% yield as a colorless oil.
[α]2D0 = –26.2 (c = 1.10, CHCl3). H NMR (CDCl3): δ = 1.02 [s, 9
1
H, C(CH3)3], 1.59 (dd, J = 13.8, 12.0 Hz, 1 H, 6-H), 1.81 (s, 3 H,
CH3COO), 2.04 (dd, J = 13.8, 8.9 Hz, 1 H, C-6), 2.10 (s, 3 H,
CH3COO), 2.33 (br. s, 1 H, OH), 2.43 (br. s, 1 H, OH), 3.49 (d, J
= 8.8 Hz, 1 H, 4-H), 3.53–3.62 (m, 1 H, 1-H), 3.83 (d, J = 11.2 Hz,
1 H, CHHOAc), 3.91 (dd, J = 8.8, 9.2 Hz, 1 H, 3-H), 4.01 (d, J =
11.2 Hz, 1 H, CHHOAc), 5.02 (dd, J = 9.2, 9.6 Hz, 1 H, 2-H),
7.36–7.49 (m, 6 H, Ph-H), 7.65–7.72 (m, 4 H, Ph-H) ppm. 13C
NMR (CDCl3): δ = 171.14 (CH3COO), 170.46 (CH3COO), 135.90
(Ar), 135.61 (Ar), 133.39 (Ar), 132.83 (Ar), 130.11 (Ar), 129.90
(Ar), 128.04 (Ar), 127.77 (Ar), 75.66 (C-5), 74.36 (C-2), 73.67 (C-
4), 72.03 (C-3), 66.91 (CH2OAc), 57.91 (C-1), 34.20 (C-6), 26.94
(CH3COO), 20.91 (CH3COO), 20.88 [C(CH3)3], 19.55 [C(CH3)
3] ppm. HRMS (ESI): calcd. for C27H35N3O7SiK [M + K]+
Na]+ 410.1175; found 410.1176. IR (neat): ν = 3409 (O–H), 2926,
˜
2106 (N3), 1748 (C=O), 1381, 1238, 1048, 915, 829, 606 cm–1.
(1S,2S,3R,4S,5S)-1-Azido-5-hydroxymethyl-2,3,4,5-tetrahydroxy-
cyclohexane (13a): Compound 12a (500.0 mg, 1.291 mmol) was dis-
solved in a mixed solvent of methanol (10 mL) and ammonia hy-
drate (25% w/w, 2 mL), and the mixture was heated to reflux for
approximately 25 h. The solution was then concentrated under vac-
uum to give an oily residue, which was dissolved in pure water
(0.5 mL). The aqueous solution was washed with diethyl ether (2ϫ
10 mL), and the ether phase was decanted each time. The aqueous
solution was concentrated under vacuum to remove water. Com-
pound 13a (274.5 mg, 1.252 mmol, 97%) was thus obtained as a
580.1881; found 580.1877. IR (neat): ν = 3483 (O–H), 2957, 2103
˜
(N3), 1742 (C=O), 1428, 1374, 1238, 1112, 1041, 742, 706, 609,
1
colorless oil. [α]2D0 = +6.5 (c = 0.9, CH3OH). H NMR (CDCl3): δ
514 cm–1.
= 1.71 (dd, J = 15.7, 3.0 Hz, 1 H, 6-H), 1.92 (dd, J = 15.7, 2.6 Hz,
1 H, 6-H), 3.26 (d, J = 10.0 Hz, 1 H, CHHOAc), 3.28 (d, J =
10.0 Hz, 1 H, CHHOAc), 3.40 (d, J = 10.3 Hz, 1 H, 4-H), 3.53 (dd,
J = 9.8, 3.4 Hz, 1 H, 2-H), 3.66 (dd, J = 10.3, 9.8 Hz, 1 H, 3-H),
3.95–4.02 (m, 1 H, 1-H) ppm. 13C NMR (D2O): δ = 74.52 (C-5),
73.16 (C-4), 72.76 (C-3), 70.77 (C-2), 65.16 (C-1), 60.97 (CH2OH),
31.57 (C-6) ppm. HRMS (ESI): calcd. for C7H13N3O5Na [M +
(1S,2S,3R,4S,5S)-5-Acetoxymethyl-1-azido-5-hydroxy-2,3,4-tri-
acetoxycyclohexane (12a): Compound 11a (1.300 g, 2.400 mmol)
was dissolved in tetrahydrofuran (15 mL), and TBAF (2.820 g,
10.79 mmol) was added. After stirring was continued at room tem-
perature for approximate 5 h, the mixture was cooled to 0 °C. Tri-
ethylamine (1.215 g, 12.01 mmol), acetic anhydride (1.225 g,
12.00 mmol) and DMAP (30.0 mg, 0.245 mmol) were added in
turn, then the mixture was further stirred at 0 °C for 1 h. The reac-
tion solution was concentrated under vacuum and the residue was
partitioned between ethyl acetate (50 mL) and aqueous HCl (2 M,
20 mL). The phases were separated, the aqueous phase was ex-
tracted with ethyl acetate (2ϫ 25 mL), and the organic extracts
Na]+ 242.0753; found 242.0753. IR (neat): ν = 3302 (O–H), 2924,
˜
2113 (N3), 1662, 1401, 1347, 1096, 1045 cm–1.
(1R,2S,3R,4S,5S)-1-Azido-5-hydroxymethyl-2,3,4,5-tetrahydroxycy-
clohexane (13b): The same procedure described for the preparation
of 13a was followed, and compound 13b was obtained from 12b in
were combined, washed successively with potassium carbonate 96% yield as a colorless oil. [α]2D0 = –9.3 (c = 1.5, CH3OH). 1H
aqueous solution (10 % w/w, 10 mL), water (10 mL) and brine NMR (CDCl3): δ = 1.39 (dd, J = 14.0, 12.0 Hz, 1 H, 6-H), 1.89
(10 mL), and dried with anhydrous MgSO4. Evaporation of the
solvent under vacuum gave a crude product, which was purified by
flash chromatography (EtOAc/hexane, 1:6) to afford 12a (745.5 mg,
1.925 mmol, 80%) as off-white crystals, m.p. 122.8–124.2 °C. [α]2D0
(dd, J = 14.0, 4.4 Hz, 1 H, 6-H), 3.22 (dd, J = 10.0, 9.8 Hz, 1 H,
2-H), 3.28 (d, J = 9.6 Hz, 1 H, 4-H), 3.35 (d, J = 11.5 Hz,
CHHOH), 3.44 (d, J = 11.5 Hz, 1 H, CHHOH), 3.45–3.52 (m, 2
H, 1-H and 3-H) ppm. 13C NMR (D2O): δ = 75.90 (C-5), 73.65 (C-
4), 73.51 (C-3), 72.49 (C-2), 65.23 (C-1), 59.99 (CH2OH), 33.87 (C-
6) ppm. HRMS (ESI): calcd. for C7H13N3O5Na [M + Na]+
1
= –13.2 (c = 2.00, CHCl3). H NMR (CDCl3): δ = 1.97 (dd, J =
16.0, 3.6 Hz, 1 H, 6-H), 2.00 (s, 3 H, CH3 in Ac), 2.05 (s, 3 H, CH3
in Ac), 2.06 (s, 3 H, CH3 in Ac), 2.10 (s, 3 H, CH3 in Ac), 2.11
(dd, J = 16.0, 3.0 Hz, 1 H, 6-H), 3.40 (s, 1 H, OH), 3.70 (d, J =
242.0753; found 242.0753. IR (neat): ν = 3377 (O–H), 2938, 2105
˜
(N3), 1663, 1430, 1258, 1087, 824, 623 cm–1.
Eur. J. Org. Chem. 2013, 6389–6396
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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