Claisen Rearrangement of Carbohydrate-Derived Precursors
FULL PAPER
syrup. C11H18O5, M = 230.3. [α]2D0 = +2.0 (c = 1, methanol). 1H
6.65, 7.08–7.21, 7.30–7.32, 7.74–7.77 (4 m, 9 H, Ar) ppm. 13C
NMR (400 MHz, CD3OD): δ = 1.37, 1.50 (2 s, 2×3 H, Me), 3.46 NMR (100 MHz, C6D6): δ = 21.13 (1 C, Ts-Me), 25.54, 27.69 (2
3
3
3
(ddd, J6,7 = 9.7, J7,8a = 5.7, J7,8b = 2.8 Hz, 1 H, 7-H), 3.67–3.71
C, Me), 69.81 (1 C, C-8), 71.10 (1 C, C-7), 72.95 (1 C, OCH2),
73.92 (1 C, C-3), 75.60 (1 C, C-6), 76.69 (1 C, C-4), 78.85 (1 C, C-
5), 109.40 (1 C, CMe2), 117.48 (1 C, C-1), 127.70–129.80
(12 C, Ar), 135.28 (1 C, C-2) ppm. MALDI-TOF-MS: m/z = 497
[M+Na]+, 513 [M+K]+.
3
3
3
3
2
("m", J5,6 = 7.5, J6,7 = 9.7, J7,8a = 5.7, J7,8b = 2.8, J8a,8b
=
3
2
12.0 Hz, 2 H, 6-H, 8a-H), 3.79 (dd, J7,8b = 2.8, J8a,8b = 12.0 Hz,
1 H, 8b-H), 4.06 (dd, J4,5 = 6.4, J5,6 = 7.5 Hz, 1 H, 5-H), 4.24
3
3
3
3
4
(dd, J3,4 = 4.5, J4,5 = 6.4 Hz, 1 H, 4-H), 4.41–4.44 ("m", J1a,3
=
4J1b,3 = 1.8, J2,3 = 4.8, J3,4 = 4.5 Hz, 1 H, 3-H), 5.30 (ddd, J1a,1b
3
3
3,7-Anhydro-6-O-benzyl-1,2,8-trideoxy-4,5-O-isopropylidene-D-talo-
= 1.5, J1b,2 = 10.9, J1b,3 = 1.8 Hz, 1 H, 1b-H), 5.42 (ddd, J1a,1b
=
oct-1,7-dienitol (23): Tetrabutylammonium iodide (TBAI, 4.7 mg,
13 µmol), sodium iodide (26.0 mg, 173 µmol) and 1,8-diazabicy-
clo[5.4.0]undec-7-ene (DBU, 0.5 µL) were added to a solution of
22 (12.0 mg, 25 µmol) in dry DMSO (0.5 mL). After stirring for
1.5 h at 80 °C more DBU (13.0 µL, 13.2 mg, 87 µmol) was added
and stirring was continued for 6 h. When TLC control (petroleum
ether/ethyl acetate, 3:1) showed complete conversion of the starting
material the solution was diluted with water and extracted twice
with dichloromethane. Column chromatography (petroleum ether/
ethyl acetate, 5:1) of the residue gave 23 (6.0 mg, 20 µmol, 78%) as
a colourless syrup. C18H22O4, M = 302.4. [α]2D0 = +13.8 (c = 0.25,
1.5, J1a,2 = 17.5, J1a,3 = 1.8 Hz, 1 H, 1a-H), 5.94 (ddd, J1a,2 = 17.5,
J1b,2 = 10.9, J2,3 = 4.8 Hz, 1 H, 2-H) ppm. 13C NMR (100 MHz,
CD3OD): δ = 26.01, 28.14 (2 C, Me), 62.81 (1 C, C-8), 70.08 (1 C,
C-6), 74.81 (1 C, C-3), 75.69 (1 C, C-7), 77.64 (1 C, C-4), 79.87 (1
C, C-5), 110.21 (1 C, CMe2), 118.08 (1 C, C-1), 136.81 (1 C, C-
2) ppm. MALDI-TOF-MS: m/z = 253 [M+Na]+, 269 [M+K]+;
C11H18O5 (230.3): calcd. C 57.37, H 7.89; found C 56.06, H 7.72
(hygroscopic compound).
3,7-Anhydro-1,2-dideoxy-4,5-O-isopropylidene-8-O-(4-tolylsulfonyl)-
-glycero-D-talo-oct-1-enitol (21): p-Toluenesulfonyl chloride
D
1
chloroform). H NMR (400 MHz, C6D6): δ = 1.07, 1.36 (2 s, 2×3
(308 mg, 1.62 mmol) and a catalytic amount of 4-(dimethylamino)
pyridine was added to a solution of 20 (162 mg, 703 µmol) in dry
pyridine (10 mL) was added at 0 °C. The solution was stirred at
room temperature for two days and the reaction terminated by the
addition of water. Evaporation of the solvent and column
chromatography of the residue (petroleum ether/ethyl acetate, 3:1)
gave 21 (228 mg, 593 µmol, 84%) as a colourless syrup. C18H24O7S,
M = 384.5. [α]2D0 = +3.4 (c = 0.5, chloroform). 1H NMR (400 MHz,
CDCl3): δ = 1.36, 1.50 (2 s, 2×3 H, Me), 2.44 (s, 3 H, Ts-Me), 3.62
3
3
H, Me), 3.83 (dd, J4,5 = 7.4, J5,6 = 8.7 Hz, 1 H, 5-H), 4.17–4.24
3
3
3
("m", J2,3 = 5.6, J4,5 = 7.4, J5,6 = 8.7 Hz, 3 H, 3-H, 4-H, 6-H),
4.68, 4.72 (2 d, 2×1 H, OCH2), 4.71 (s, 1 H, 8b-H), 4.81 (s, 1 H,
2
3
4
8a-H), 5.11 (ddd, J1a,1b = 1.3, J1b,2 = 10.7, J1b,3 = 1.5 Hz, 1 H,
2
3
4
1b-H), 5.42 (ddd, J1a,1b = 1.3, J1a,2 = 17.3, J1a,3 = 1.5 Hz, 1 H,
1a-H), 5.96 (ddd, 3J1a,2 = 17.3, 3J1b,2 = 10.7, 3J2,3 = 5.6 Hz, 1 H, 2-
H), 7.08–7.21, 7.37–7.39 (2 m, 5 H, Ar) ppm. 13C NMR (100 MHz,
C6D6): δ = 24.62, 27.15 (2 C, Me), 72.29 (1 C, OCH2), 75.90, 76.28,
76.81, 78.31 (4 C, C-3, C-4, C-5, C-6), 88.08 (1 C, C-8), 110.02 (1
C, CMe2), 117.39 (1 C, C-1), 127.69–128.63 (6 C, Ar), 135.35 (1 C,
C-2), 155.22 (1 C, C-7) ppm. MALDI-TOF-MS: m/z = 325
[M+Na]+, 341 [M+K]+.
3
3
3
(ddd, J6,7 = 9.9, J7,8a = 4.1, J7,8b = 2.3 Hz, 1 H, 7-H), 3.87 (dd,
3J5,6 = 7.7, J6,7 = 9.9 Hz, 1 H, 6-H), 4.08 (dd, J4,5 = 6.6, J5,6
=
3
3
3
3
3
7.7 Hz, 1 H, 5-H), 4.16 (dd, J3,4 = 5.3, J4,5 = 6.6 Hz, 1 H, 4-H),
4.21 (dd, 3J7,8b = 2.3, 2J8a,8b = 10.9 Hz, 1 H, 8b-H), 4.31–4.36 ("m",
3J2,3 = 5.0, J3,4 = 5.32, J7,8a = 4.1, J8a,8b = 10.9 Hz, 2 H, 8a-H,
3
3
2
cis-(2S,3R,4R)-2-Benzyloxy-3,4-(isopropylidenedioxy)cyclooct-5-en-
one (24): A solution of 23 (8.0 mg, 26 µmol) in a n-decane/toluene
mixture (ratio 4:1, 5 mL) with one drop of triethylamine was heated
at 185 °C under microwave irradiation for 1 h (300 W). After evap-
oration of the solvents the residue was purified by column
chromatography (petroleum ether/ethyl acetate, 8:1) to give 24
(6.4 mg, 21 µmol, 80%) as a white solid. Colourless crystals were
obtained by recrystallization from ethanol. C18H22O4, M = 302.4;
m.p. 143.7–145 °C. [α]2D0 = –16.0 (c = 0.2, chloroform). 1H NMR
(400 MHz, C6D6): δ = 1.24, 1.47 (2 s, 2×3 H, Me), 1.55–1.60 (m,
2 H, 7a/b-H), 1.80–1.87 (m, 1 H, 8b-H), 2.12–2.17 (m, 1 H, 8a-H),
2
3
3
3-H), 5.28–5.36 ("m", J1a,1b = 1.3, J1a,2 = 17.5, J1b,2 = 10.7 Hz,
3
3
3
2 H, 1a/b-H), 5.79 (ddd, J1a,2 = 17.5, J1b,2 = 10.7, J2,3 = 5.01, 1
H, 2-H), 7.34, 7.80 (2 d, 2×2 H, Ar) ppm. 13C NMR (100 MHz,
CDCl3): δ = 21.80 (1 C, Ts-Me), 25.62, 27.76 (2 C, Me), 68.83 (1
C, C-6), 69.37 (1 C, C-8), 71.73 (1 C, C-7), 74.14 (1 C, C-3), 76.24
(1 C, C-4), 78.24 (1 C, C-5), 109.95 (1 C, CMe2), 118.51 (1 C, C-
1), 128.14, 130.03, 132.87, 145.11 (4 C, Ar), 134.76 (1 C, C-2) ppm.
MALDI-TOF-MS: m/z = 407 [M+Na]+, 423 [M+K]+.
3,7-Anhydro-6-O-benzyl-1,2-dideoxy-4,5-O-isopropylidene-8-O-(4-
tolylsulfonyl)-D-glycero-D-talo-oct-1-enitol (22): Benzyl bromide
3
3
3
4.06 (d, J2,3 = 8.6 Hz, 1 H, 2-H), 4.31 (dd, J2,3 = 8.6, J3,4
=
=
=
(90 µL, 129 mg, 757 µmol) and NaH (60 % in paraffin, 28 mg,
700 µmol) was added to a solution of 21 (205 mg, 533 µmol) in
dry DMF (12 mL). The solution was stirred for two days at room
temperature. During this time extra benzyl bromide (50 µL, 72 mg,
420 µmol) and NaH (8 mg, 200 µmol) were added to effect com-
plete conversion of the starting material. The solution was diluted
with ethyl acetate and the solvent evaporated. Chromatography of
the residue (petroleum ether/ethyl acetate, 5:1) gave 22 (194 mg,
409 µmol, 77 %) as a colourless syrup. C25H30O7S, M = 474.6.
3
3
3
5.4 Hz, 1 H, 3-H), 4.45–4.48 ("m", J3,4 = 5.4, J4,5 = 6.1, J4,6
2.0 Hz, 3 H, 4-H, OCH2), 5.27–5.35 ("m", J4,6 = 2.0, J5,6
4
3
3
3
11.3 Hz, 1 H, 6-H), 5.60 (dd, J4,5 = 6.1, J5,6 = 11.3 Hz, 1 H, 5-
H), 7.02–7.12, 7.30–7.32 (2 m, 5 H, Ar) ppm. 13C NMR (100 MHz,
C6D6): δ = 23.65 (1 C, C-7), 26.26, 28.33 (2 C, Me), 44.29 (1 C, C-
8), 72.45 (1 C, OCH2), 74.02 (1 C, C-4), 78.87 (1 C, C-3), 82.74 (1
C, C-2), 127.67–128.73 (6 C, Ar), 128.60 (1 C, C-6), 133.71 (1 C,
C-5) ppm. MALDI-TOF-MS: m/z = 325 [M+Na]+, 341 [M+K]+.
1
[α]2D0 = +7.2 (c = 1, chloroform). H NMR (400 MHz, C6D6): δ =
Crystal Data: C18H22O4, M = 302.4, monoclinic, a = 7.7078(7), b
= 9.8849(10), c = 10.6599(10) Å, U = 808.4(13) Å3, T = 153 K,
space group P21, Z = 2, µ(Mo-Kα) = 0.087 mm–1, 9845 reflections
measured, 1971 unique (Rint = 0.1410).
3
1.16, 1.38 (2 s, 2×3 H, Me), 1.79 (s, 3 H, Ts-Me), 3.62 (ddd, J6,7
3
3
3
= 9.9, J7,8a = 4.3, J7,8b = 2.6 Hz, 1 H, 7-H), 3.75 (dd, J5,6 = 7.0,
3J6,7 = 9.9 Hz, 1 H, 6-H), 3.87 (dd, J3,4 = 5.6, J4,5 = 6.8 Hz, 1 H,
3
3
4-H), 4.02 (dd, 3J4,5 = 6.8, 3J5,6 = 7.0 Hz, 1 H, 5-H), 4.27 (dd, 3J7,8b
cis-(1S,2R,3R,4S)-2,3,4-Tris(benzyloxy)cyclooct-5-en-1-ol (25)
Starting from Compound 11: Triisobutylaluminium (1 in hexane,
2
3
2
= 2.6, J8a,8b = 10.4 Hz, 1 H, 8b-H), 4.31 (dd, J7,8a = 4.3, J8a,8b
= 10.4 Hz, 1 H, 8a-H), 4.31–4.35 ("m", 3J2,3 = 4.8, 3J3,4 = 5.6, 4J1a,3
4
= J1b,3 = 1.5 Hz, 1 H, 3-H), 4.53, 4.90 (2 d, 2×1 H, OCH2), 5.01 0.08 mL, 80 µmol) was added to a solution of precursor 11 (7 mg,
2
3
4
(ddd, J1a,1b = 1.5, J1b,2 = 10.9, J1b,3 = 1.5 Hz, 1 H, 1b-H), 5.22
16 µmol) in dry DCM (0.4 mL) under argon. The solution was
2
3
4
(ddd, J1a,1b = 1.5, J1a,2 = 17.6, J1a,3 = 1.5 Hz, 1 H, 1a-H), 5.63 stirred at room temperature overnight. After dilution with DCM
3
3
3
(ddd, J1a,2 = 17.6, J1b,2 = 10.9, J2,3 = 4.8 Hz, 1 H, 2-H), 6.63– and hydrolysis the organic phase was washed with 1 HCl, filtered
Eur. J. Org. Chem. 2006, 4451–4462
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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