F. Charmantray, L. Hecquet et al.
FULL PAPER
4.32 (m, 2 H, 4-H, X, Y) ppm. 13C NMR (100 MHz, CD3OD): δ 6.87 mmol) as a pale oil in 36% yield (based on 9). Rf (cyclohexane/
1
= 31.2, 35.9, 66.8, 67.5, 77.0, 79.0, 79.8, 83.9, 89.7, 96.0 ppm.
AcOEt, 7:3) = 0.4. H NMR (400 MHz, CDCl3): δ = 1.41 (s, 3 H,
HRMS (ESI): calcd. for C5H10O4NaS [M + Na]+ 189.0198; found 1ЈЈ-H), 1.45 (s, 3 H, 3ЈЈ-H3), 1.83 (m, 2 H, 6-H), 2.32 (s, 3 H, 2Ј-
189.0192.
H), 2.97–3.09 (m, 2 H, 5-H), 3.92 (m, 1 H, 4-H), 4.00 (d, 1 H, J =
17.4 Hz, 1a-H), (dd, 1 H, J = 6.4, 1.2 Hz, 3-H), 4.23 (dd, 1 H, J =
17.4, 1.2 Hz, 1b-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 23.6
(C-3ЈЈ), 23.8 (C-1ЈЈ), 25.0 (C-5), 30.7 (C-2Ј), 32.3 (C-6), 66.7 (C-1),
69.2 (C-4), 75.9 (C-3), 101.1 (C-2ЈЈ), 196.3 (C-1Ј), 210.7 (C-2Ј) ppm.
HRMS (ESI): calcd. for C11H18O5NaS [M + Na]+ 285.0773; found
285.0771.
2,2-Dimethyl-1,3-dioxan-5-one (4): Following the reaction described
by Enders et al.,[34] 2-amino-2-hydroxymethyl-1,3-propanediol
(25.0 g, 159.0 mmol) afforded crude (5-amino-2,2-dimethyl-1,3-di-
oxan-5-yl)methanol (31.0 g), which was dissolved in DCM
(100 mL) and added dropwise to an ice-cold suspension of NaIO4–
SiO2 (45.3 g, 212.0 mmol, 2 equiv.) in DCM (750 mL). The mixture
was stirred vigorously for 3 h at 4 °C. The mixture was filtered. The
precipitate was washed with DCM (3ϫ 100 mL), and the filtrate
was combined with the washings and evaporated under reduced
pressure (250 Torr, 18 °C) to afford 4 as a colorless oil (19.4 g,
149 mmol) in 94% yield over two steps. Rf (cyclohexane/AcOEt,
6-S-Acetyl-5-deoxy-6-thio-L-psicose (11): Following general pro-
cedure C, 11 (760 mg, 3.4 mmol) was recovered in 70% yield from
10 (1.3 g, 5 mmol). Rf (DCM, MeOH, 9:1) = 0.45. [α]2D1 = –36 (c =
1
1.7, MeOH). H NMR (400 MHz, CD3OD): δ = 1.75 (m, 2 H, 5-
H), 2.31 (s, 3 H, 2Ј-H), 2.90 (m, 1 H, 6a-H), 3.07 (m, 1 H, 6b-H),
3.79 (m, 1 H, 4-H), 4.07 (d, J = 5.6 Hz, 1 H, 3-H), 4.40 (d, J =
19.2 Hz, 1 H, 1a-H), 4.50 (d, J = 19.2 Hz, 1 H, 1b-H) ppm. 13C
NMR (100 MHz, CD3OD): δ = 26.5 (C-5), 30.5 (C-2Ј), 33.6 (C-6),
68.1 (C-1), 72.8 (C-4), 79.5 (C-3), 197.6 (C-1Ј), 212.9 (C-2) ppm.
HRMS (ESI): calcd. for C16H8O10NaS2 [2M + Na]+ 467.1022;
found 467.1015.
1
7:3) = 0.6. H NMR (400 MHz, CDCl3): δ = 1.45 (s, 6 H, 7-H and
8-H), 4.15 (s, 4 H, 1-H and 5-H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 23.4 (C-7 and C-8), 66.7 (C-1 and C-5), 100.0 (C-3),
207.9 (C-6) ppm.
5-S-Acetyl-1,3-O-isopropylidene-5-thio-
tyl-1,3-O-isopropylidene-5-thio- -ribulofuranose (7): Following ge-
neral procedure B, the reaction between 4 (10.95 g, 84.3 mmol,
5 equiv.) and 5 (2 g, 16.85 mmol, 1 equiv.) afforded 6 along with its
isomer 7 in 29% global yield (4.9 mmol).
L-ribulose (6) and 4-O-Ace-
L
5-Chloro-5-deoxy-1,3-O-isopropylidene-L-ribulose (13): Following
general procedure B, the reaction between 4 (7.8 g, 60 mmol,
5 equiv.) and 12 (5.5 m, 2.2 mL, 12 mmol, 1 equiv.) afforded 13
(1.75 g, 8.4 mmol) in 70% yield (based on 12). Rf (cyclohexane/
6: Rf (cyclohexane/AcOEt, 3:7) = 0.3.1H NMR (400 MHz, CDCl3):
δ = 1.42 (s, 3 H, 1ЈЈ-H), 1.43 (s, 3 H, 1ЈЈ-H3), 2.33 (s, 3 H, 2Ј-H),
3.15 (m, 1 H, 5a-H), 3.26 (m, 1 H, 5b-H), 4.02 (d, J = 17.2 Hz, 1
H, 1a-H), 4.07 (m, 1 H, 4-H), 4.20 (m, 1 H, 3-H), 4.26 (d, J =
17.2 Hz, 1 H, 1b-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 23.6
(C-1ЈЈ), 23.7 (C-3ЈЈ), 28.5 (C-2Ј), 31.7 (C-5), 66.7 (C-1), 69.6 (C-4),
74.9 (C-3), 101.4 (C-2ЈЈ), 198.2 (C-1Ј), 210.5 (C-2) ppm.
1
AcOEt, 7:3) = 0.4. H NMR (400 MHz, CDCl3): δ = 1.43 (s, 3 H,
3Ј-H), 1.50 (s, 3 H, 1Ј-H), 3.35 (s. wide, 1 H, OH), 3.76 (d, J =
3.6 Hz, 2 H, 5-H), 4.06 (d, J = 17.6 Hz, 1 H, 1a-H), 4.12 (m, 1 H,
4-H), 4.28 (dd, J = 17.6, 1.2 Hz, 1 H, 1b-H), 4.38 (dd, J = 7.6;
1.2 Hz, 1 H, 4-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 23.5 (C-
3Ј), 23.7 (C-1Ј), 45.5 (C-5), 66.9 (C-1), 69.8 (C-4), 72.9 (C-3), 101.6
(C-2Ј), 211.2 (C-2) ppm. HRMS (ESI): calcd. for C8H14ClO4 [M +
H]+ 209.0581; found 209.0598. dr 9:1. ee: Ͼ 98%.
7: Rf (cyclohexane/AcOEt, 3:7) = 0.25. 1H NMR (400 MHz,
CDCl3) δ = 1.44 (s, 3 H, 1ЈЈ-H), 1.46 (s, 3 H, 3ЈЈ-H), 2.09 (s, 3 H,
2Ј-H), 3.21 (m, 2 H, 5a-H, 5b-H), 3.77 (d, 1 H, J = 12.5 Hz, 1a-
H), 3.95 (d, 1 H, J = 12.5 Hz, 1b-H), 4.24 (m, 1 H, 3-H), 5.48 (m,
1 H, 4-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 19.3 (C-3ЈЈ),
21.0 (C-2Ј), 28.3 (C-1ЈЈ), 31.7 (C-5), 65.9 (C-1), 74.7 (C-3), 76.8 (C-
4), 82.9 (C-2), 98.4 (C-2ЈЈ), 171.0 (C-1Ј) ppm.
5-Chloro-5-deoxy-L-ribulose (14): Following general procedure C,
14 (540 mg, 3.2 mmol) was recovered in 71% yield from 13 (0.94 g,
4.5 mmol). Rf (DCM, MeOH, 9:1) = 0.5. [α]2D1 = 13.5 (c = 1.1,
MeOH). 1H NMR (400 MHz, CD3OD): δ = 3.63 (dd, J = 11.3,
6.2 Hz, 1 H, 5a-H), 3.73 (dd, J = 11.3, 4.2 Hz, 1 H; 5b-H), 3.92
(m, 1 H, 4-H), 4.20 (d, J = 6.0 Hz, 1 H, 3-H), 4.43 (d, J = 19.4 Hz,
1 H, 1a-H), 4.54 (d, J = 19.4 Hz, 1 H, 1b-H) ppm. 13C NMR
(100 MHz, CD3OD): δ = 46.9 (C-5), 68.1 (C-1), 74.3 (C-4), 76.4
(C-3), 212.5 (C-2) ppm. HRMS (ESI): calcd. for C5H9ClNaO4 [M
+ Na]+ 191.0087; found 191.0071.
1,3-O-Isopropylidene-5-thio-L-ribulofuranose (8): The mixture of 6
and 7 (1.15 g, 4.63 mmol, 1 equiv.) was dissolved in anhydrous
MeOH (20 mL) under argon. The solution was diluted with a
freshly prepared solution of sodium methoxide in MeOH (0.5 m,
1 mL, 1.85 mmol, 0.4 equiv.) by dropwise addition. The resulting
mixture was stirred at room temperature for 2 h. The reaction was
stopped by addition of solid NH4Cl (123 mg, 2.31 mmol,
0.5 equiv.) followed by MeOH removal by evaporation under vac-
uum. The residue was purified by flash column chromatography
(cyclohexane/AcOEt, 5:5) to afford 8 (0.54 g, 2.63 mmol) as a pale
yellow solid in 57% yield. Rf (cyclohexane/AcOEt, 3:7) = 0.5.
[α]2D3 = 22.3 (c = 1.4, MeOH). 1H NMR (400 MHz, CDCl3): δ =
1.46 (s, 3 H, 3Ј-H), 1.49 (s, 3 H, 1Ј-H), 2.57 (d, J = 9.6 Hz, 1 H,
OH), 2.77 (s, 1 H, OH), 3.07 (dd, J = 10, 9.6 Hz, 1 H, 5a-H), 3.18
(dd, J = 10, 6.8 Hz, 1 H, 5b-H), 3.75 (d; J = 12.4 Hz, 1 H, 1a-H),
3.93 (d, J = 12.4 Hz, 1 H, 1b-H), 4.06 (d, J = 3.2 Hz, 1 H, 3a-H),
4.63 (m, 1 H, 4-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 19.6
(C-3Ј), 28.3 (C-1Ј), 35.8 (C-5), 66.3 (C-1), 75.0 (C-3), 78.2 (C-4),
83.4 (C-2), 98.8 (C-2Ј) ppm.
5-Bromo-5-deoxy-1,3-O-isopropylidene-L-ribulose (16): Following
general procedure B, the reaction between 4 (1.86 g, 14.3 mmol,
5 equiv.) and 15 (1.85 m, 1.54 mL, 2.86 mmol, 1 equiv.) in ethanol
afforded 16 (340 mg, 1.35 mmol) in 47% yield (based on 15). Rf
(cyclohexane/AcOEt, 7:3) = 0.4. [α]2D1 = –136 (c = 1.75, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 1.43 (s, 3 H, 3Ј-H), 1.51 (s, 3 H, 1Ј-
H), 3.63 (d, J = 4 Hz, 1 H, 5-H), 4.04 (m, 1 H, 4-H), 4.07 (d, J =
17.6 Hz, 1 H, 1a-H), 4.28 (dd, J = 17.6, 1.6 Hz, 1 H, 1b-H), 4.38
(dd, J = 7.6, 1.6 Hz, 1 H, 3-H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 23.5 (C-3Ј), 23.8 (C-1Ј), 34.8 (C-5), 66.5 (C-1), 69.2 (C-4), 73.6
(C-3), 101.5 (C-2Ј), 211.2 (C-2) ppm. HRMS (ESI): calcd. for
C8H13BrNaO4 [M + Na]+ 274.9895; found 274.9910. dr 19:1.
5-Bromo-5-deoxy-L-ribulose (17): Following general procedure C,
17 (210 mg, 0.99 mmol) was recovered in 77% yield from 16
(330 mg, 1.3 mmol). Rf (DCM, MeOH, 9:1) = 0.5. [α]2D1 = 7.7 (c =
1.55, MeOH). 1H NMR (400 MHz, CD3OD): δ = 3.51 (dd, J =
10.4, 6.4 Hz, 1 H, 5a-H), 3.63 (dd, J = 10.8, 4 Hz, 1 H, 5b-H), 3.91
(m, 1 H, 4-H), 4.19 (d, J = 6.4 Hz, 1 H, 3-H), 4.45 (d, J = 19.2 Hz,
1 H, 1a-H), 4.53 (d, J = 19.2 Hz, 1 H, 1b-H) ppm. 13C NMR
6-S-Acetyl-5-deoxy-1,3-O-isopropylidene-6-thio-L-psicose (10): Fol-
lowing general procedure B, except that the aldehyde addition was
performed over 24h with a shoot-syringe system, the reaction be-
tween 4 (12.3 g, 94.7 mmol, 5 equiv.) and S-(3-oxopropyl)ethane-
thioate (9, 2.2 g, 18.95 mmol, 1 equiv.) afforded 10 (1.8 g,
208
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Eur. J. Org. Chem. 2012, 203–210