H.-J. Lo, C.-Y. Chen, W.-L. Zheng, S.-M. Yeh, T.-H. Yan
FULL PAPER
= 0.6 (silica gel; hexane/EtOAc, 9:1). [α]2D5 = –64.3 (c = 4.9, CHCl3).
until the blue color persisted. The mixture was stirred for 3 h at
–60 °C, and a small amount of H2O (0.5 mL) was then carefully
IR (film): ν = 2986, 1635, 1584, 1494, 1452, 1372, 1230, 1168, 1094,
˜
850 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.35–7.29 (m, 4 H), added to destroy the excess amount of lithium. The reaction mix-
7.24–7.20 (m, 1 H), 6.16 (d, J = 10.0, Hz, 1 H), 5.93 (d, J = 8.8 Hz,
1 H), 5.82 (d, J = 10.0, Hz, 1 H), 5.17 (s, 1 H), 5.06 (s, 1 H), 4.43
(s, 2 H), 4.18 (d, J = 10.0 Hz, 1 H), 3.80 (dd, J = 8.8, 8.8 Hz, 1 H),
2.42 (s, 3 H), 1.50 (s, 3 H), 1.49 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 156.2, 140.2,140.3, 129.2, 128.2, 128.1, 127.3, 126.5,
ture was warmed to room temperature, at which point a solution
of LiOH (24 mg, 1.0 mmol) in ethanol/H2O (3:7, 3 mL) was added.
The mixture was stirred at 80 °C for 1 h, and a solution of HOAc/
H2O (4:1, 1 mL) was then added. After stirring for 18 h at 50 °C,
the reaction mixture was allowed to cool to room temperature and
111.6, 109.3, 79.7, 76.8, 76.0, 52.6, 27.1, 27.0, 13.4 ppm. HRMS concentrated in vacuo to gave 1. To crude product 1 was added
(EI): calcd for C19H23NO3S [M]+ 345.1398; found 345.1400.
acetic anhydride (1 mL), pyridine (2 mL), and DMAP (5 mg) se-
quentially. After stirring overnight at room temperature, the reac-
tion mixture was concentrated in vacuo, diluted with EtOAc, and
filtered through Celite. The eluate was washed with saturated so-
dium carbonate and brine, dried (MgSO4), filtered, and evaporated
in vacuo. The residue was purified by flash chromatography
(EtOAc) to give valiolamine pentaacetate (45 mg, 0.11 mmol,
53%). Rf = 0.56 (silica gel; methanol/EtOAc, 2:1). [α]2D5 = –19.6 (c
(Z)-(3aR,4S,7S,7aS)-O-[5,6-(Isopropylidenedioxy)-4-hydroxy-4-
(hydroxymethyl)cyclohex-2-enyl] S-Methyl N-Benzylcarbonimido-
thioate (10): To a solution of carbonimidothioate 9 (947 mg,
2.7 mmol) in tBuOH (15 mL) and H2O (15 mL) at 0 °C was added
K3Fe(CN)6 (2.72 g, 8.2 mmol), K2CO3 (1.14 g, 8.2 mmol),
(DHQD)2-AQN (24 mg, 0.027 mmol), K2OsO4·2H2O(9 mg,
0.027 mmol), and MeSO2NH2(262 mg, 2.7 mmol). The mixture
was stirred for 48 h at 0 °C, and then 20% aqueous sodium thio-
sulfate (5 mL) was added at 0 °C. The resulting mixture was then
extracted with EtOAc (4ϫ20 mL). The combined organic layer was
washed with brine (5 mL). Flash chromatography (hexane/EtOAc,
1:2) gave dihydroxycarbonimidothioate 10a (978 mg, 2.6 mmol,
94 %). The title compound was obtained as a mixture of dia-
stereomers (Ͼ18:1), and the ratio was determined by NMR integra-
tion of the olefinic protons (1 H in total): δ = 6.01 (dd, ≈0.948 H,
10a) and 5.48 (dd, ≈0.052 H, 10b) ppm. Rf = 0.5 (silica gel; hexane/
= 0.2, CHCl3) {ref.[15] [α]2D0 = –18.0 (c = 1.0, CHCl3), ref.[4c] [α]2D0
–17.8 (c = 2.0, CHCl3), ref.[2b] [α]2D5 = –14.8 (c = 1.0, CHCl3)}. IR
(film): ν = 3356, 1747, 1662, 1227 cm–1 1H NMR (400 MHz,
=
.
˜
CDCl3): δ = 6.98 (d, J = 8.8 Hz, 1 H), 5.49 (dd, J = 10.0, 10.0 Hz,
1 H), 5.06 (d, J = 10.0 Hz, 1 H), 4.90 (dd, J = 4.4, 10.8 Hz, 1 H),
4.75–4.70 (m, 1 H), 3.93 (d, J = 11.6 Hz, 1 H, ABq), 3.82 (d, J =
11.6 Hz, 1 H, ABq), 3.00 (s, 1 H), 2.07 (s, 3 H), 2.06 (s, 3 H), 1.99
(s, 3 H), 1.97 (s, 3 H), 1.96 (s, 3 H), 1.94–1.93 (m, 2 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 170.5 (C), 170.3 (C), 170.2 (C), 169.9
(C), 169.2 (C), 74.9 (CH), 72.9 (CH), 71.9 (CH), 68.8 (CH), 66.3
(CH2), 44.9 (C), 32.7 (CH2), 23.5 (CH3), 20.7 (2 C, CH3,CH3), 20.6
(CH3), 20.4 (CH3) ppm. 13C NMR (100 MHz, CD3OD): δ = 172.7
(C), 172.1 (C), 171.8 (C), 171.7 (C), 171.5 (C), 75.2 (CH), 74.0
(CH), 73.8 (CH), 70.4 (CH), 67.0 (CH2), 46.9 (C), 33.8 (CH3), 33.1
(CH3), 20.7 (CH3), 20.6 (2 C, CH3,CH3), 20.5 (CH3) ppm. HRMS
(EI): calcd for C17H25NO10 [M]+ 403.1479; found 403.1476.
EtOAc, 1:2). [α]2D5 = +77.4 (c = 2.3, CHCl ). IR (film): ν = 3422,
˜
3
1634, 1495, 1453, 1431, 1373, 1229, 1168, 1114, 1047, 980, 868,
1
792, 734 cm–1. H NMR (400 MHz, CDCl3): δ = 7.33–7.28 (m, 4
H), 7.23–7.19 (m, 1 H), 6.01 (dd, J = 10.0, 1.6 Hz, 1 H), 5.78 (d, J
= 10.0 Hz, 1 H), 5.71 (dd, J = 10.0, 1.6 Hz, 1 H), 4.40 (s, 2 H),
4.20 (dd, J = 9.6, 9.6 Hz, 1 H), 3.73 (d, J = 10.8 Hz, 1 H), 3.57
(dd, J = 9.6, 9.6 Hz, 1 H), 3.52 (d, J = 10.8 Hz, 1 H), 2.88 (s, 1 H),
2.42 (s, 3 H), 1.99 (d, J = 9.6 Hz, 1 H), 1.46 (s, 6 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 156.2, 140.3, 131.6, 128.5, 128.2,
127.3, 126.5, 111.9, 78.5, 75.3, 74.9, 71.5, 68.6, 52.7, 27.2, 26.7,
13.4 ppm. HRMS (EI): calcd for C19H25NO5S [M]+ 379.1454;
found 379.1459.
(3aS,6R,7S,7aS)-3-Benzyl-3a,6,7,7a-tetrahydro-5-iodomethyl-
6,7-(isopropylidenedioxy)benzoxazol-2-one (12): Potassium carbon-
ate (623 mg, 4.5 mmol) and iodine (577 mg, 2.3 mmol) were added
sequentially to a solution of carbonimidothioate 9 (519 mg,
1.5 mmol) in THF (5 mL) at room temperature. After 18 h of stir-
ring at room temperature, saturated aqueous sodium sulfite
(10 mL) was added. The mixture was extracted with EtOAc
(3ϫ20 mL). The combined organic layer was dried, filtered, and
evaporated. The residue was purified by flash chromatography
(hexane/EtOAc, 3:1) to give tetrahydrobenzoxazolin-2-one 12
(577 mg, 1.3 mmol, 87%). Rf = 0.7 (silica gel; hexane/EtOAc, 1:1).
(3aS,4R,5R,6S,7R,7aS)-3-Benzyl-4,5-epoxy-5-hydroxymethyl-
6,7-(isopropylidenedioxy)hexahydrobenzoxazol-2-one (11): Potas-
sium carbonate (106 mg, 0.69 mmol) and iodine (195 mg,
0.69 mmol) were added sequentially to a solution of 10 (146 mg,
0.38 mmol) in THF (4 mL) at room temperature. After 24 h of stir-
ring at room temperature, saturated aqueous sodium sulfite (5 mL)
was added. The mixture was extracted with EtOAc (4ϫ10 mL).
The combined organic layer was dried, filtered, and evaporated.
The residue was purified by flash chromatography (hexane/EtOAc,
1:2) to give epoxy carbonate 11 (95 mg, 0.27 mmol, 72%). Rf = 0.5
(silica gel; hexane/EtOAc, 1:2). [α]2D5 = +56.7 (c = 0.3, CHCl3). IR
[α]2D5 = +33.5 (c = 6.8, CHCl ). IR (film): ν = 2985, 1731, 1495,
˜
3
1449, 1411, 1336, 1230, 1170, 1099, 1057, 1022, 836, 730, 699 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.37–7.24 (m, 5 H), 5.66 (s, 1
H), 4.85 (d, J = 15.2 Hz, 1 H), 4.71 (dd, J = 10.4,10.4 Hz, 1 H),
4.21 (d, J = 8.8 Hz, 1 H), 4.16 (d, J = 8.8 Hz, 1 H), 4.11 (d, J =
15.2 Hz, 1 H), 4.08 (d, J = 9.6 Hz, 1 H), 3.85–3.79 (m, 2 H), 1.48
(s, 3 H), 1.45 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
156.6, 139.7, 134.9, 129.0, 128.2, 128.0, 118.0, 113.7, 79.9, 73.4,
72.4, 54.8, 46.4, 26.7, 26.6, –0.1 ppm. HRMS (EI): calcd for
C18H20INO4 [M]+ 441.0437; found 441.0439.
(film): ν = 2987, 1746, 1542, 1500, 1453, 1228, 1098, 1065, 913,
˜
745 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.38–7.29 (m, 5 H),
5.00 (d, J = 15.2 Hz, 1 H), 4.57 (dd, J = 9.6, 9.6 Hz, 1 H), 4.22–
4.15 (m, 2 H), 4.07 (dd, J = 9.6, 2.4 Hz, 1 H), 4.01 (dd, J = 12.8,
4.0 Hz, 1 H), 3.90 (dd, J = 12.8, 9.2 Hz, 1 H), 3.84 (d, J = 9.2 Hz
1 H), 3.36 (d, J = 2.4 Hz, 1 H), 1.71 (dd, J = 4.0, 9.2 Hz, 1 H),
1.43 (s, 3 H), 1.41 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 156.8, 134.7, 129.1, 128.3, 128.2, 112.9, 76.1, 74.3, 73.9, 62.3,
59.5, 54.1, 53.4, 46.6, 26.7, 26.5 ppm. HRMS (EI): calcd for
C18H21NO6 [M]+ 347.1368; found 347.1372.
(3aS,6R,7S,7aS)-3-Benzyl-3a,6,7,7a-tetrahydro-5-hydroxymethyl-
6,7-(isopropylidenedioxy)benzoxazol-2-one (13): NaOAc (293 mg,
1.2 mmol) was added to a solution of 7-iodooxazolidinone 12
(526 mg, 1.2 mmol) in DMF (2.0 mL) at room temperature. After
18 h of stirring at room temperature, LiOH (428 mg, 17.9 mmol)
and H2O (3 drops) were added sequentially. After stirring for 2 h
at 60 °C, the reaction was cooled and H2O (10 mL) was added.
The mixture was extracted with EtOAc (3ϫ20 mL). The combined
organic layer was washed with brine, dried (MgSO4), and evapo-
(+)-Valiolamine (1) and Its Pentaacetate: Small pieces of lithium
were added to a solution of N-benzyl epoxycarbamate 11 (73 mg,
0.21 mmol) in THF (2 mL) and liquid ammonia (10 mL) at –78 °C
2784
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Eur. J. Org. Chem. 2012, 2780–2785