Induction of a Preferred Sense of Twist
J . Org. Chem., Vol. 66, No. 26, 2001 8791
1
Varian Gemini 2000 spectrometer. Chemical shifts are re-
ported in part per million (δ) relative to CHCl3 (7.26 ppm) for
spectra run in CDCl3. 13C NMR spectra were obtained at 50
MHz on a Varian Gemini 2000 and are reported in δ relative
to CDCl3 (77.0 ppm). Melting points are uncorrected. High
performance liquid chromatography (HPLC) was performed
on a Gilson HPLC system using an Alltech Silica Sp Berisorb
5 µm column. Optical rotations were determined at 25 °C with
a J ASCO DIP-370 polarimeter (1 dm cell). Elemental analyses
were performed on a Perkin-Elmer elemental analyzer 2400
II. Absorption and CD spectra were recorded on a J ASCO J 600
spectropolarimeter at room temperature in THF (c ∼ 6 ×
10-3M) in 0.1 and 1.0 mm cells. During the measurement the
instrument was thoroughly purged with N2.
Meth yl r,â-L-Rh a m n op yr a n osid e (6). To a solution of 300
mg (1.65 mmol) of L-rhamnose monohydrate in 5 mL of MeOH
was added 150 mg of Amberlist IR-120 (H+). The reaction
mixture was refluxed for 48 h and then filtered over Celite
and purified by flash chromatography on silica gel (CH2Cl2/
MeOH, 5:1) to give 287.8 mg (98%) of methyl derivative 6 as
a yellow syrup.
tion: mp 101-102 °C; [R]D -69.4° (c 0.16, CHCl3); H NMR
(200 MHz, CDCl3) δ 1.36 (d, J ) 6.2 Hz, 3H); 2.22 (bs, 2H,
OH), 3.28-3.37 (m, 1H, H-4), 3.35 (s, 3H), 3.65-3.85 (m, 1H,
H-5), 3.86-3.93 (m, 2H, H-2, H-3), 4.66 (s, 1H, H-1), 4.74 (s,
2H), 7.30-7.38 (m, 5H); 13C NMR (50 MHz, CDCl3) δ 17.92,
54.75, 66.98, 71.03, 71.44, 74.91, 81.55, 100.36 (C-1), 127.89,
128.56, 138.28. Anal. Calcd for C14H20O5: C, 62.67; H, 7.51.
Found: C, 62.73; H, 7.50.
Meth yl 4-O-Ben zyl-2,3-O-d ip h en oyl-r-L-r h a m n op yr a -
n osid e (1). To a solution of 92.4 mg (0.3 mmol) of 4 in CH2Cl2
(17.6 mL) was added 252.9 mg (2.1 mmol) of DMAP. The
reaction mixture was cooled to 0 °C, and a solution of 95.9 mg
(0.3 mmol) of diphenoyl chloride in CH2Cl2 (15 mL) was added
in 1 h. After 30 min at 0 °C, the mixture was warmed at rt,
stirred for 1 h, diluted with CH2Cl2 (15 mL), and washed with
H2O (2 × 10 mL). The organic layer was dried (Na2SO4), and
the crude product obtained after concentration (390 mg) was
purified by flash column chromatography on silica gel (eluant
hexane/EtOAc, 2:1) to give the white solid diphenoyl deriva-
tives 1 (33 mg, 23%), as an inseparable 1.8:1 atropdiastero-
meric mixture, and the inseparable open chain diphenoyl
derivatives 8-10 (7.8%). 1: 1H NMR (200 MHz, CDCl3) δ 1.20
(d, J ) 6.4 Hz, 3H, minor diast), 1.36 (d, J ) 6.2 Hz, 3H, major
diast), 2.56 (at, J ) 9.2 Hz, 1H, H-4, minor diast), 2.94 (at, J
) 9.6 Hz, 1H, H-4 major diast), 3.25 (s, 3H, minor diast), 3.28
(s, 3H, major diast), 3.51-3.72 (m, 1H, H-5), 3.94 (dd, J ) 3.6
Hz, J ) 9.2 Hz, 1H, H-3, minor diast), 4.02 (dd, J ) 4.0 Hz, J
) 9.4 Hz, 1H, H-3, major diast), 4.49-4.88 (m, 3H), 5.07 (dd,
Met h yl 2,3-O-Isop r op ylid en e-r-L-r h a m n op yr a n osid e
(7). To a suspension of 1.33 g (7.5 mmol) of methyl R,â-L-
rhamnopyranoside (6) in 10 mL of acetone was added 1.56 mL
(12.8 mmol) of dimethoxypropane. The mixture was cooled to
0 °C, and 138.4 µL (1.1 mmol) of BF3·Et2O was added. After
30 min, the reaction mixture was warmed to room temperature
and stirred for 12 h. Then the reaction mixture was neutralized
with Py (155 µL, 2.0 mmol) and after removal of solvent, the
crude product obtained (2.1 g, R:â ) 11:1) was purified by flash
column chromatography on silica gel (eluant EtOAc/hexane,
3:1) to give 7 (R diastereoisomer, 1.4 g, 86%) as a yellowish oil
[130 mg (8%) of the â diastereoisomer was also isolated]. R-7:
[R]D -290.7° (c 0.22, CHCl3); 1H NMR (200 MHz, CDCl3) δ 1.29
(d, J ) 6.2 Hz, 3H), 1.34 (s, 3H), 1.51 (s, 3H), 2.51 (bs, 1H,
OH), 3.30-3.41 (m, 1H, H-4), 3.37 (s, 3H), 3.59-3.66 (m, 1H,
H-5), 4.02-4.13 (m, 2H, H-2, H-3), 4.83 (s, 1H, H-1);13C NMR
(50MHZ, CDCl3) δ 17.34, 26.02, 27.88, 54.79, 65.57, 74.32,
75.71, 78.46, 98.06 (C-1), 109.41. Anal. Calcd for C10H18O5: C,
55.02; H, 8.32. Found: C, 54.82; H, 8.30. â-7: 1H NMR (200
MHz, CDCl3) δ 1.32 (d, J ) 5.8 Hz, 3H), 1.35 (s, 3H), 1.53 (s,
3H), 3.24-3.35 (m, 1H, H-5), 3.41-3.50 (m, 1H, H-4), 3.56 (s,
3H), 4.01 (at, J ) 5.4 Hz, 1H, H-3), 4.23 (dd, J ) 2.2 Hz, J )
5.4 Hz, 1H, H-2), 4.62 (d, J ) 2.2 Hz, 1H, H-1); 13C NMR (50
MHz, CDCl3) δ 17.55, 26.08, 27.80, 57.45, 70.88, 74.41, 74.60,
80.08, 99.50 (C-1), 110.64.
Meth yl 4-O-Ben zyl-r-L-r h a m n op yr a n osid e (4). To a
solution of 500 mg (2.3 mmol) of methyl 2,3-O-isopropylidene-
R-L-rhamnopyranoside (7) in DMF (4 mL) was added 0.545 mL
(4.6 mmol) of benzyl bromide. The reaction mixture was cooled
to 0 °C and treated with 137.4 mg (4.6 mmol) of NaH (80%),
and the suspension obtained was warmed to rt and stirred for
6 h. After this time, the reaction was diluted with CH2Cl2 (10
mL) and washed with saturated NH4Cl (3 × 5 mL). The
organic layer was dried (Na2SO4) and concentrated. The
residue (923 mg) was purified by flash chromatography on
silica gel (eluant hexane/EtOAc, 2:1) to give methyl 4-O-benzyl-
2,3-isopropylidene-R-L-rhamnopyranoside (657 mg, 93%) as a
pale yellow oil: [R]D -55.2° (c 0.22, CHCl3); 1H NMR (200 MHz,
CDCl3) δ 1.31 (d, J ) 6.2 Hz, 3H), 1.378 (s, 3H), 1.52 (s, 3H),
3.23 (dd, J ) 7.0 Hz, J ) 10.0 Hz, 1H, H-4); 3.35 (s, 3H), 3.64-
3.72 (m, 1H, H-5), 4.13-4.30 (m, 2H, H-2, H-3), 4.64 (A part
of an AB system, J ) 11.6 Hz, 1H), 4.86 (s, 1H, H-1), 4.92 (B
part of an AB system, J ) 11.8 Hz, 1H), 7.24-7.41 (m, 5H);
13C NMR (50 MHz, CDCl3) δ 17.75, 26.22, 27.91, 54.66, 64.33,
72.81, 76.96, 78.60, 80.99, 97.99 (C-1), 109.10, 127.56, 127.90,
128.21, 138.36. Anal. Calcd for C17H24O5: C, 66.21; H, 7.84.
Found: C, 66.32; H, 7.79. A solution of 657 mg (2.1 mmol) of
methyl 4-O-benzyl-2,3-isopropylidene-R-L-rhamnopyranoside
in MeOH (5 mL) and H2O (500 µL) was treated with HCl
(3.7%) until pH ∼3 and stirred for 96 h at rt. Then the reaction
mixture was diluted with EtOAc (10 mL) and washed with
saturated Na2CO3 (2 × 5 mL), and the organic layer was dried
(Na2SO4). After concentration, the residue (503 mg, 89%)
obtained as white solid 4 was used without any other purifica-
J ) 1.8 Hz, J ) 4.0 Hz, 1H, H-2, minor diast), 5.14 (dd, J 1,2
)
1.4 Hz, J 2,3 ) 3.6 Hz, 1H, H-2, major diast), 7.18-8.16 (m,
13H); 13C NMR (50 MHz, CDCl3) δ 17.65, 17.92, 54.73, 54.81,
66.71, 70.03, 74.85, 81.28, 66.93, 70.43, 75.00, 81.53, 73.40,
74.20, 127.61, 127.76, 127.83, 128.18, 128.42, 128.54, 128.67,
130.69, 131.02, 131.40, 132.11, 132.37, 138.52, 143.16, 143.47,
166.43, 167.29. Anal. Calcd for C28H26O7: C, 70.87; H, 5.52.
Found: C, 70.97; H, 5.59. 8-10: 1H NMR (200 MHz, CDCl3)
δ 1.21-1.35 (m, 9H), 2.59 (at, 1H, J 3,4 ) J 4,5 ) 9.2 Hz, H-4),
3.01 (at, 1H, J 3,4 ) J 4,5 ) 9.6 Hz, H-4), 3.23, 3.26, 3.30 (s, 9H,
OCH3), 3.57-3.80 (m, 4H, H-4, 3 H-5), 3.89-4.06 (m, 3H, H-3),
4.29-4.89 (m, 9H, H-1, OCH2Ph), 5.02-5.27 (m, 3H, H-2),
7.15-8.15 (m, 39H, Harom).
Meth yl 4-O-p-Meth oxyben zyl-r-L-r h a m n op yr a n osid e
(11). To a solution of 323 mg (1.5 mmol) of 7 in DMF (4 mL)
was added 400 µL (3.0 mmol) of p-methoxybenzyl bromide. The
solution was cooled to 0 °C, and 111 mg (3.7 mmol) of NaH
(80%) and a catalytic amount of tetrabutyl amonium iodide
were added. The suspension was stirred at 0 °C for 30 min
and at rt until starting material was consumed (TLC, 6 h).
The reaction was diluted with CH2Cl2 (10 mL), washed with
saturated NH4Cl (3 × 10 mL), and dried (Na2SO4). The organic
layer was concentrated and the crude product (525 mg)
purified by flash chromatography on silica gel (eluant hexane/
EtOAc, 7:1) to give methyl 2,3-O-isopropylidene-4-O-p-methoxy-
benzyl-R-L-rhamnopyranoside (375 mg, 75%) as yellow oil: 1H
NMR (200 MHz, CDCl3) δ 1.27 (d, J ) 6.6 Hz, 3H), 1.37 (s,
3H), 1.52 (s, 3H), 3.19 (dd, J ) 7.0 Hz, J ) 9.8 Hz, 1H, H-4),
3.34 (s, 3H), 3.60-3.68 (m, 1H, H-5); 3.78 (s, 3H), 4.27-4.10
(m, 2H, H-2, H-3), 4.55 (A part of an AB system, J ) 11.0 Hz,
1H), 4.83 (B part of an AB system, J ) 10.8 Hz), 4.84 (s, 1H,
H-1), 6.87 (AA′ part of an AA′MM′ system, J ) 8.8 Hz, 2H),
7.28 (MM′ part of an AA′MM′ system, J ) 8.4 Hz, 2H). Methyl
2,3-O-isopropylidene-4-O-p-methoxybenzyl-R-L-rhamnopyrano-
side (360 mg, 1.1 mmol) in MeOH (4 mL), was treated with
HCl (3.7%) until pH ∼3 and with H2O (300 µL). The solution
was stirred at rt for 100 h and processed as reported for 4.
The crude product (271 mg) was purified by flash chroma-
tography on silica gel (eluant hexane/EtOAc, 1:3) to give 11
(200 mg, 64%) as white glassy solid: [R]D -58.7° (c 0.18,
CHCl3); 1H NMR (200 MHz, CDCl3) δ 1.34 (d, J ) 6.2 Hz, 3H),
2.26 (bs, 1H, OH), 2.37 (bs, 1H, OH), 3.26-3.35 (m, 1H, H-4);
3.34 (s, 3H), 3.64-3.72 (m, 1H, H-5), 3.80 (s, 3H), 3.82-3.93
(m, 2H, H-2, H-3), 4.65 (s, 2H), 4.67 (s, 1H, H-1), 6.89 (AA′
part of an AA′MM′ system, J ) 8.8 Hz, 2H) 7.28 (MM′ part of
an AA′MM′ system, J ) 9.2 Hz, 2H); 13C NMR (50 MHz,
CDCl3) δ 17.88,54.69, 55.19, 66.99, 70.97, 71.39, 74.52, 81.13,