PAPER
C–C-Linked Carbohydrate Dimers via Claisen Rearrangement
2119
(R/S)-(Methyl-6-O-tert-butyldiphenylsilyl-2,3-dideoxy-a-D-
erythro-hex-2-enopyranos-4-yl)-3,4,6-tri-O-benzyl-2¢-deoxy-2¢-
phenylselenoxyl-a-D-mannopyranosides (7a/b)
Within a synthetic sequence of six steps starting from pro-
tected D-glucal derivatives a mixture of diastereomeric
target compounds 9a/b could be isolated in an overall
yield of 26%. These novel compounds exhibit a direct C–
C bond between two pyranose rings and hence belong to
a new class of C–C-disaccharides that are of particular in-
terest with respect to saccharide mimetics and carbohy-
drate-based pharmaceuticals.
A stirred solution of 6 (47 mg, 48 mmol) in CH2Cl2 (3 mL) was treat-
ed with 30% H2O2 (15 mL, 5.0 mg, 147 mmol) at –30 °C and the stir-
ring was continued at –25 °C overnight. The next day, a second
portion of 30% H2O2 (10 mL, 3.3 mg, 98 mmol) was added at –25 °C
and the solution was allowed to warm to r.t. After evaporation of the
solvent, the residue was purified by column chromatography (petro-
leum ether–EtOAc, 1:3) to give 7a/b (mixture of diastereomers, 40
mg, 84%) as a colourless syrup; diastereomeric ratio: a/b = 3:1;
Rf 0.22, 0.26 (petroleum ether–EtOAc, 1:3).
Anhyd solvents were purchased from the manufacturers Fluka and
Merck. The protected D-glucal derivatives were purchased from
Fluka and Sigma-Aldrich. Phenylselenyl chloride was purchased
from Lancaster Synthesis. TLC was performed on silica gel 60-
coated aluminum sheets (Merck or Macherey-Nagel), with detec-
tion by UV at 254 nm and by heating with H2SO4 (10% in EtOH).
Flash chromatography was carried out on silica gel 60 (0.04–0.063
mm; Merck, Macherey-Nagel or ICN). Petroleum ether used refers
to the fraction with bp 50–70 °C. The microwave experiments were
performed in a CEM microwave system (Discover, 300 W maxi-
mum power output) by using sealed tubes with temperature control
via infrared sensor. NMR spectra were recorded on a Bruker AMX-
400 and DRX-500 NMR spectrometer (1H: 400/500 MHz; 13C: 100
MHz) and analysed with the respective solvent peaks as references.
Mass spectra were recorded with a Bruker Biflex III (MALDI-TOF,
positive reflection mode, matrix: 2,5-dihydroxybenzoic acid). IR
spectra were recorded on a Bruker Vector 22 FT-IR spectrometer.
The optical rotations were measured on a Perkin-Elmer 243 or 341
polarimeter at 20 °C.
IR (film): 3031, 2928, 2857, 1454, 1428, 1112, 1046, 967, 742, 700
cm–1.
1H NMR (400 MHz, C6D6): d = 1.15, 1.20 (2 s, 2 × 9 H, 2 × tert-
3
C4H9), 3.30, 3.31 (2 s, 2 × 3 H, 2 × CH3), 3.56 (dd, J1¢,2¢ = 1.3,
3
3
3J2¢,3¢ = 4.8 Hz, 1 H, H-2¢a), 3.65 (dd, J1¢,2¢ = 3.3, J2¢,3¢ = 4.8 Hz, 1
H, H-2¢b), 5.35 (d, 3J1¢,2¢ = 3.3 Hz, 1 H, H-1¢b), 5.55–5.61 (m,
3
3J2,3 = 10.4 Hz, 2 H, H-2a/b), 5.74 (d, J2,3 = 10.4 Hz, 1 H, H-3b),
6.06 (d, 3J2,3 = 10.4 Hz, 1 H, H-3a), 6.17 (s, 1 H, H-1¢a).
13C NMR (100 MHz, C6D6): d = 27.07 [3 C, C(CH3)3b], 27.16 [3 C,
C(CH3)3a], 55.49 (2 × 1 C, CH3a/b), 64.13 (1 C, C-6b), 64.25 (1 C,
C-6a), 65.83 (1 C, C-2¢b), 67.72 (1 C, C-2¢a), 68.93 (1 C, C-6¢b),
69.02 (1 C, C-6¢a), 71.07, 72.26, 72.56, 72.96, 73.18, 73.25, 74.24,
74.91, 75.32, 76.65, 78.02, 79.53, 79.56 (16 C, C-4a/b, C-5a/b
,
C-3¢a/b, C-4¢a/b, C-5¢a/b, PhCH2a/b), 93.28 (1 C, C-1¢a), 93.32 (1 C, C-
1¢b), 95.72 (2 × 1 C, C-1a/b), 127.44–130.75, 136.02, 136.05, 136.31
(2 × 38 C, C-2a/b, C-3a/b, Ara/b).
MALDI-TOF: m/z = 1009.4 [M + Na]+.
(Methyl-6-O-tert-butyldiphenylsilyl-2,3-dideoxy-a-D-erythro-
hex-2-enopyranos-4-yl)-3,4,6-tri-O-benzyl-2¢-deoxy-2¢-phenyl-
selenyl-a-D-mannopyranoside (6)
Anal. Calcd for C56H62O9SeSi (986.23): C, 68.20; H, 6.35. Found:
C, 68.07; H, 6.93.
Under argon, a stirred solution of 5 (106 mg, 254 mmol) in MeCN
(3 mL) was treated at 0 °C with PhSeCl (73 mg, 381 mmol) and
2,4,6-collidine (50 mL, 46 mg, 375 mmol). Subsequently a solution
of 4 (71 mg, 178 mmol) in MeCN (2 mL) was added and stirring
continued overnight. When TLC confirmed the complete conver-
sion of 4, the solvent was evaporated and the residue purified by
column chromatography (petroleum ether–EtOAc, 7:1) to give 6
(145 mg, 84%) as a colourless syrup; [a]546 +79.2 (c = 0.50,
CHCl3); Rf 0.4 (petroleum ether–EtOAc, 3:1).
IR (film): 3030, 2930, 1454, 1428, 1112, 1049, 966, 753, 700 cm–1.
2-Deoxy-2-[(3¢Z)-methyl-6¢-O-tert-butyldiphenylsilyl-2¢,3¢,4¢-
trideoxy-a-D-ribo- or -D-xylo-hex-3¢-enopyranos-2¢-yl]-D-man-
nono-1,5-lactone (9a) and 2-Deoxy-2-[(3¢Z)-methyl-6¢-O-tert-
butyldiphenylsilyl-2¢,3¢,4¢-trideoxy-a-D-ribo- or -D-xylo-hex-3¢-
enopyranos-2¢-yl]-D-glucono-1,5-lactone (9b)
A solution of 7a/b (40 mg, 41 mmol) in toluene (6 mL) was stirred
with molecular sieves 4 Å for 10 min. After addition of i-Pr2NH
(243 mmol, 24.7 mg, 34 mL), the solution was heated to 130 °C for
1 h. Evaporation of the solvent and column chromatography of the
residue (petroleum ether–EtOAc, 12:1) gave a diastereomeric mix-
ture of 9a/b (30.0 mg, 91%) as a colourless syrup; diastereomeric
ratio 9a/9b (2S/2R) = 10:3; Rf 0.34 (petroleum ether–EtOAc, 3:1).
20
1H NMR (400 MHz, C6D6): d = 1.20 (s, 9 H, t-C4H9), 3.30 (s, 3 H,
CH3), 3.55 (dd, 2J6¢a,6¢b = 10.9, 3J5¢,6¢b = 1.5 Hz, 1 H, H-6¢b), 3.74 (dd,
2J6¢a,6¢b = 10.9, 3J5¢,6¢a = 3.8 Hz, 1 H, H-6¢a), 3.93 (dd, 3J1¢,2¢ = 1.8 Hz,
IR (film): 2927, 2856, 1457, 1114 cm–1.
3
3
3J2¢,3¢ = 4.3 Hz, 1 H, H-2¢), 3.96–3.99 (m, J4¢,5¢ = 9.4, J5¢,6¢a = 3.8,
3J5¢,6¢b = 1.5 Hz, 1 H, H-5¢), 4.03–4.10 (m, 2 H, H-6a/b), 4.11–4.15
2S-Diastereomer
1H NMR (500 MHz, C6D6): d = 1.21 (s, 9 H, t-C4H9), 2.92 (dd,
3J2,2¢ = 11.0, 3J2,3 = 2.2 Hz, 1 H, H-2), 3.10 (s, 3 H, CH3), 3.47–3.51
(m, 3J1¢,2¢ = 4.4, 3J2,2¢ = 11.0 Hz, 1 H, H-2¢), 3.91–3.97 (m, 3J2,3 = 2.2
3
3
3
(m, J4,5 = 9.2, J5,6a = 2.3, J5,6b = 4.8 Hz, 1 H, H-5), 4.24 (dd,
3J2¢,3¢ = 4.3, 3J3¢,4¢ = 8.4 Hz, 1 H, H-3¢), 4.28–4.36 (m, 3J4¢,5¢ = 9.4 Hz,
3 H, PhCH2, H-4¢), 4.42–4.48 (m, 3J4,5 = 9.2 Hz, 2 H, PhCH2, H-4),
4.56–4.60 (m, 2 H, PhCH2), 4.72 (d, 3J1,2 = 2.0 Hz, 1 H, H-1), 4.95
(d, 1 H, PhCH2), 5.49 (d, 3J1¢,2¢ = 1.8 Hz, 1 H, H-1¢), 5.56–5.60 (m,
3J1,2 = 2.0, 3J2,3 = 10.4 Hz, 1 H, H-2), 5.68 (d, 3J2,3 = 10.4 Hz, 1 H,
H-3), 6.91–6.96, 7.06–7.35, 7.60–7.62, 7.85–7.90 (4 m, 30 H, Ar).
3
Hz, 1 H, H-3), 4.35 (d, J1¢,2¢ = 4.4 Hz, 1 H, H-1¢), 5.85, 6.35 (2 d,
3J3¢,4¢ = 10.4 Hz, 2 × 1 H, H-3¢, H-4¢).
13C NMR (100 MHz, C6D6): d = 27.12 [3 C, C(CH3)3], 35.41 (1 C,
C-2¢), 44.28 (1 C, C-2), 54.85 (1 C, CH3), 66.95, 69.01, 70.23,
71.70, 73.60 (C-6, C-6¢, PhCH2), 69.29, 74.43, 75.59, 78.38 (4 C, C-
3, C-4, C-5, C-5¢), 97.97 (1 C, C-1¢), 126.24–130.02, 136.08–
136.18 (32 C, C-3¢, C-4¢, Ar), 170.56 (1 C, C-1).
13C NMR (100 MHz, C6D6): d = 19.64 (1 C, CMe3), 27.17 [3 C,
C(CH3)3], 49.80 (1 C, C-2¢), 55.48 (1 C, CH3), 64.18 (1 C, C-6),
67.23 (1 C, C-4), 69.43 (1 C, C-6¢), 71.11 (1 C, C-5), 71.66 (1 C,
PhCH2), 73.44 (1 C, C-5¢), 73.71, 75.17 (2 C, PhCH2), 75.90 (1 C,
C-4¢), 79.72 (1 C, C-3¢), 95.67 (1 C, C-1), 97.71 (1 C, C-1¢), 127.61–
130.01, 135.18, 136.07, 136.32 (38 C, Ar).
2R-Diastereomer
1H NMR (500 MHz, C6D6): d = 1.18 (s, 9 H, t-C4H9), 3.00 (dd,
3J2,2¢ = 3J2,3 = 6.3 Hz, 1 H, H-2), 3.17–3.21 (m, 3J1¢,2¢ = 4.1,
3J2,2¢ = 6.3 Hz, 1 H, H-2¢), 3.24 (s, 3 H, CH3), 3.80 (dd, 3J2,3 = 6.3,
3J3,4 = 10.1 Hz, 1 H, H-3), 4.81 (d, 3J1¢,2¢ = 4.1 Hz, 1 H, H-1¢), 5.81–
5.91 (m, 2 H, H-3¢, H-4¢).
MALDI-TOF: m/z = 993.1 [M + Na]+, 1009.1 [M + K]+.
Anal. Calcd for C56H62O8SeSi (970.23): C, 69.32; H, 6.45. Found:
C, 68.64; H, 6.71.
Synthesis 2006, No. 13, 2117–2120 © Thieme Stuttgart · New York