The Journal of Organic Chemistry
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purified by flash silica gel column chromatography (AcOEt:hexane =
1:8 to 1:4) to yield diol 14j (180 mg, 67%) as a white solid;
[α]2D4 +12.9 (c 0.60, CHCl3); 1H NMR (600 MHz, CDCl3) δ 4.96 (d,
J = 11.1 Hz, 1H), 4.34 (dd, J = 5.6, 5.6 Hz, 1H), 3.80 (dd, J = 10.5, 5.6
Hz, 1H), 3.53 (dd, J = 10.5, 7.2 Hz, 1H), 3.49 (ddd, J = 11.1, 9.8, 2.2
Hz, 1H), 2.12−2.04 (m, 1H), 2.01−1.94 (m, 1H), 1.87 (dd, J = 14.1,
9.8 Hz, 1H), 1.82−1.73 (m, 2H), 1.68−1.60 (m, 1H), 1.60−1.52 (m,
2H), 1.35−1.14 (m, 3H), 1.28 (d, J = 14.1 Hz, 1H), 1.09−1.02 (m,
1H), 0.93 (s, 9H), 0.88 (s, 3H), 0.13 (s, 3H), 0.12 (s, 3H); 13C NMR
(150 MHz, CDCl3) δ 74.6, 72.9, 64.4, 53.0, 50.7, 45.0, 42.9, 36.1, 34.7,
32.8, 31.3, 29.2, 25.8, 24.7, 18.0, −4.7, −4.9; IR (neat, cm−1): 3408,
3298, 991; MS m/z 283 [M − tBu]+, 191 (100%); HRMS (EI) calcd.
for C15H27O3Si: 283.1730 [M − tBu]+, found: 283.1733.
(ddd, J = 12.0, 6.3, 3.9 Hz, 1H), 3.77 (ddd, J = 12.0, 7.0, 5.3 Hz, 1H),
3.58 (s, 3H), 3.55 (td, J = 9.0, 2.4 Hz, 1H), 3.45 (t, J = 9.0 Hz, 1H),
3.39 (t, J = 7.3 Hz, 1H), 3.34 (ddd, J = 9.0, 5.3, 3.9 Hz, 1H), 2.24 (d,
J = 2.4 Hz, 1H), 2.01 (dd, J = 7.0, 6.3 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 138.5, 138.3, 128.6, 128.4, 128.1, 128.0, 127.9, 127.7, 105.0,
83.8, 82.0, 75.2, 74.8, 74.6, 70.4, 62.7, 57.3; IR (neat, cm−1): 3420,
1061, 737, 698; MS m/z 283 [M − Bn]+, 91 (100%); HRMS (EI)
calcd. for C14H19O6:283.1182 [M − Bn]+, found: 283.1184.
Methyl (Methyl 2,3-Di-O-benzyl-β-D-glucopyranoside)urinate
(16m′).46 Colorless oil (42.3 mg, 94%); [α]2D9 −14.5 (c 2.05,
1
CHCl3); H NMR (400 MHz, CDCl3) δ 7.38−7.25 (m, 10H), 4.90
(d, J = 11.2 Hz, 1H), 4.89 (d, J = 11.2 Hz, 1H), 4.80 (d, J = 11.2 Hz,
1H), 4.71 (d, J = 11.2 Hz, 1H), 4.37 (d, J = 8.3 Hz, 1H), 3.87−3.81
(m, 2H), 3.83 (s, 3H), 3.59 (s, 3H), 3.52 (dd, J = 8.3, 8.3 Hz, 1H),
3.44 (dd, J = 8.3, 8.3 Hz, 1H), 2.80 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 169.7, 138.4, 138.3, 128.4, 128.3, 128.0, 127.9, 127.8, 127.7,
105.0, 83.0, 81.1, 75.3, 74.8, 74.2, 71.7, 57.4, 52.7; IR (neat, cm−1):
3490, 1749, 1069, 738, 698; HRMS (ESI) calcd. for C22H26O7Na:
425.1571 [M + Na]+, found: 425.1581.
(1R,3aR,4S,6S,7R,7aR)-1-((tert-Butyldimethylsilyl)oxy)-4-hydroxy-
6-methyloctahydro-3a,6-ethanoindene-7-carbaldehyde (15j). Pale
1
yellow oil (25.2 mg, 84%); [α]2D5 +60.7 (c 1.10, CHCl3); H NMR
(400 MHz, CDCl3) δ 9.87 (d, J = 2.4 Hz, 1H), 4.88 (d, J = 11.6 Hz,
1H), 4.16 (t, J = 5.8 Hz, 1H), 3.60−3.47 (m, 1H), 2.50 (d, J = 9.7 Hz,
1H), 2.27−2.07 (m, 2H), 2.07−1.86 (m, 2H), 1.86−1.74 (m, 1H),
1.64−1.48 (m, 2H), 1.48−1.22 (m, 3H), 1.22−1.10 (m, 1H), 1.10 (s,
3H), 0.92 (s, 9H), 0.07 (s, 3H), 0.05 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 204.6, 73.2, 72.5, 54.5, 50.2, 46.6, 44.3, 36.1, 34.6, 34.0, 31.2,
29.9, 25.7, 24.7, 18.0, −4.9, −5.1; IR (neat, cm−1): 3410, 1718, 1255;
MS m/z 281 [M − tBu]+, 263 (100%); HRMS (EI) calcd. for
C15H25O3Si: 281.1573 [M − tBu]+, found: 281.1576.
Methyl 2-O-n-Butyl-α-D-ribofuranoside (14n). To a solution of
methyl 3,5-di-O-benzyl-α-D-ribofuranoside47 (1.59 g, 4.62 mmol) in
DMF (12 mL), NaH (60% dispersion in mineral oil, 462 mg,
11.6 mmol) was added at 0 °C. After the reaction mixture was stirred
for 10 min at 0 °C, n-butyl bromide (1.09 mL, 10.2 mmol) was added
and the reaction mixture was stirred for 30 min at room temperature.
It was then quenched with water at 0 °C. The solution was extracted
with Et2O (twice), and the organic layers were washed with brine,
dried over Na2SO4, and concentrated under reduced pressure. The
residue was purified by flash silica gel column chromatography
(AcOEt:hexane = 1:4) to yield the corresponding ether (1.76 g, 95%)
(1R,3aR,4S,6S,7R,7aR)-1-((tert-Butyldimethylsilyl)oxy)-4-hydroxy-
6-methyloctahydro-3a,6-ethanoindene-7-carboxylic Acid (16j).
White solid (29.2 mg, 92%); [α]2D1 +16.5 (c 0.57, CHCl3); H NMR
1
(400 MHz, CDCl3) δ 4.96 (d, J = 11.2 Hz, 1H), 4.18 (dd, J = 5.2, 5.2
Hz, 1H), 3.61−3.51 (m, 1H), 2.58 (d, J = 10.2 Hz, 1H), 2.19 (dd, J =
9.8, 5.4 Hz, 1H), 2.15−1.87 (m, 3H), 1.87−1.73 (m, 1H), 1.65−1.52
(m, 2H), 1.52−1.40 (m, 1H), 1.40−1.22 (m, 2H), 1.12−1.01 (m, 1H),
0.96 (s, 3H), 0.93 (s, 9H), 0.11 (s, 3H), 0.10 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 179.7, 73.2, 72.6, 50.6, 49.4, 47.4, 44.2, 35.8, 34.1,
33.9, 30.9, 28.6, 25.7, 24.7, 18.0, −4.9, −5.3; IR (neat, cm−1): 3284,
1718, 1259, 1178; MS m/z 353 [M − H]+, 205 (100%); HRMS (EI)
calcd. for C19H33O4Si: 353.2148 [M − H]+, found: 353.2144.
as a pale yellow oil; [α]D25 +103 (c 0.280, CHCl3); H NMR (400
1
MHz, CDCl3) δ 7.40−7.21 (m, 10H), 4.97 (d, J = 4.4 Hz, 1H), 4.70
(d, J = 12.7 Hz, 1H), 4.59 (d, J = 12.7 Hz, 1H), 4.52 (d, J = 12.2 Hz,
1H), 4.46 (d, J = 12.2 Hz, 1H), 4.23 (ddd, J = 4.4, 3.9, 2.9 Hz, 1H),
3.84 (dd, J = 6.8, 2.9 Hz, 1H), 3.72 (dd, J = 6.8, 4.4 Hz, 1H), 3.58−
3.42 (m, 2H), 3.46 (s, 3H), 3.44 (dd, J = 10.3, 3.9 Hz, 1H), 3.38 (dd,
J = 10.3, 4.4 Hz, 1H), 1.73−1.58 (m, 2H), 1.48−1.31 (m, 2H), 0.93 (t,
J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 138.4, 138.0, 128.4,
128.21, 128.19, 127.7, 127.5, 102.4, 82.1, 79.5, 75.0, 73.5, 72.3, 70.8,
70.2, 55.4, 31.8, 19.2, 13.9; IR (neat, cm−1): 1109, 1028, 736, 698;
MS m/z 400 [M]+, 219 (100%); HRMS (EI) calcd. for
C24H32O5:400.2250 [M]+, found: 400.2250.
To a solution of 20% Pd(OH)2/C (wetted with 50% water, 170 mg)
in MeOH (5 mL) and AcOEt (35 mL), ether (1.70 g, 4.24 mmol)
was added. After the reaction flask was purged with H2 three times,
the reaction mixture was stirred at room temperature under a H2
atmosphere for 50 min. The catalyst was removed by filtration through
Celite. The filtrate was concentrated under reduced pressure. The
residue was purified by flash silica gel column chromatography
(AcOEt:hexane = 1:1) to yield diol 14n (730 mg, 78%) as a colorless
oil; [α]2D8 +88.8 (c 1.04, CHCl3); 1H NMR (400 MHz, CDCl3) δ 4.98
(d, J = 3.9 Hz, 1H), 4.21−4.14 (m, 1H), 4.09 (dd, J = 6.3, 1.9 Hz, 1H),
3.81 (dd, J = 11.7, 2.9 Hz, 1H), 3.78 (dd, J = 6.3, 4.4 Hz, 1H), 3.70 (dd,
J = 11.7, 2.9 Hz, 1H), 3.64 (dt, J = 9.2, 6.8 Hz, 1H), 3.57 (dt, J = 9.2,
6.8 Hz, 1H), 3.45 (s, 3H), 1.65 (q, J = 6.8 Hz, 1H), 1.63 (q, J = 6.8 Hz,
1H), 1.40 (sext, J = 7.3 Hz, 2H), 0.93 (t, J = 7.3 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 102.6, 86.4, 79.3, 70.7, 69.6, 62.9, 55.1, 31.7, 19.1,
13.8; IR (neat, cm−1): 3375, 1033; HRMS (ESI) calcd. for
C10H20O5Na: 243.1203 [M + Na]+, found: 243.1209.
1-Hydroxymethyl-7,7-dimethylbicyclo[2.2.1]heptan-2-ol (14k).32
1
White solid (524 mg, 74%); mp 159−160 °C (CHCl3-hexane); H
NMR (400 MHz, CDCl3) δ 4.00 (dd, J = 8.1 Hz, 3.7 Hz, 1H), 3.93 (d,
J = 11.1 Hz, 1H), 3.75 (d, J = 11.1 Hz, 1H), 2.76 (br s, 1H), 2.35 (br s,
1H), 1.88−1.65 (m, 4H), 1.56−1.43 (m, 1H), 1.19 (s, 3H), 1.17−1.00
(m, 2H), 0.90 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 78.6, 63.3,
52.9, 46.5, 46.0, 40.4, 30.0, 26.9, 21.0, 20.6; IR (neat, cm−1): 3343,
1067; MS m/z 152 [M − H2O]+, 108 (100%); HRMS (EI) calcd. for
C10H16O: 152.1201 [M − H2O]+, found: 152.1203.
Isopropyl 2,3-Dideoxy-α-D-glucopyranoside (14l). White solid
(780 mg, 56%); mp 66−67 °C (Et2O-hexane); [α]2D2 +159.7 (c 0.56,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 4.90 (d, J = 1.9 Hz, 1H), 3.89
(sept, J = 6.3 Hz, 1H), 3.85−3.74 (m, 2H), 3.68−3.56 (m, 2H), 2.65
(br s, 1H), 2.49 (br s, 1H), 1.91−1.79 (m, 2H), 1.87−1.67 (m, 2H),
1.21 (d, J = 6.3 Hz, 3H), 1.14 (d, J = 6.3 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 93.7, 72.8, 68.0, 67.3, 63.1, 29.7, 27.1, 23.3, 21.3;
IR (neat, cm−1): 3284, 1124; HRMS (ESI) calcd. for C9H18O4Na:
213.1097 [M + Na]+, found: 213.1105.
Methyl (Isopropyl 2,3-dideoxy-α-D-glucopyranoside)urinate
(16l′). Colorless oil (51.2 mg, 95%); [α]2D9 +95.9 (c 2.56, CHCl3);
1H NMR (400 MHz, CDCl3) δ 5.01 (t, J = 2.4 Hz, 1H), 4.19 (d, J =
9.2 Hz, 1H), 3.95 (sept, J = 6.3 H, 1H), 3.83 (s, 3H), 3.84−3.74 (m,
1H), 3.15 (s, 1H), 1.98−1.81 (m, 2H), 1.81−1.72 (m, 2H), 1.23 (d,
J = 6.3 Hz, 3H), 1.15 (d, J = 6.3 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 172.3, 94.3, 72.2, 68.7, 67.4, 52.4, 28.9, 25.8, 23.2, 21.3; IR
(neat, cm−1): 3476, 1750, 1126; MS m/z 175 [M − iPr]+, 129 (100%);
HRMS (EI) calcd. for C7H11O5:175.0607 [M − iPr]+, found:
175.0607.
Methyl (Methyl 2-O-n-Butyl-α-D-ribofuranoside)urinate (16n′).
Colorless oil (38.8 mg, 83%); [α]2D8 +83.9 (c 1.13, CHCl3); H NMR
1
(400 MHz, CDCl3) δ 5.11 (d, J = 4.4 Hz, 1H), 4.65 (d, J = 2.0 Hz,
1H), 4.29 (ddd, J = 8.8, 5.9, 2.0 Hz, 1H), 3.86 (dd, J = 5.9, 4.4 Hz,
1H), 3.79 (s, 3H), 3.63 (dt, J = 9.3, 6.8 Hz, 1H), 3.56 (dt, J = 9.3, 6.8
Hz, 1H), 3.48 (s, 3H), 3.21 (d, J = 8.8 Hz, 1H), 1.65 (q, J = 6.8 Hz,
1H), 1.63 (q, J = 6.8 Hz, 1H), 1.39 (sext, J = 7.3 Hz, 2H), 0.93 (t, J =
7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 170.7, 102.6, 83.7, 78.2,
71.8, 70.6, 55.5, 52.4, 31.6, 19.0, 13.7; IR (neat, cm−1): 3528, 1753,
1055; MS m/z 247 [M − H]+, 159 (100%); HRMS (EI) calcd. for
C11H19O6:247.1182 [M − H]+, found: 247.1179.
Methyl 2,3-Di-O-benzyl-β-D-glucopyranoside (14m).33 White
solid (603 mg, 92%); [α]D24 +20.3 (c 0.20, CH3CN); mp 118−120
1
°C (CHCl3-hexane); H NMR (400 MHz, CDCl3) δ 7.40−7.26 (m,
10H), 4.97 (d, J = 11.2 Hz, 1H), 4.93 (d, J = 11.2 Hz, 1H), 4.71 (d, J =
11.2 Hz, 1H), 4.67 (d, J = 11.2 Hz, 1H), 4.37 (d, J = 7.3 Hz, 1H), 3.89
J
dx.doi.org/10.1021/jo502426p | J. Org. Chem. XXXX, XXX, XXX−XXX