Synthesis of glyco-Fused Bicyclic Compounds
(1 m in THF, 1.17 mmol, 1.17 mL) was added to a solution of 9
(200 mg, 0.47 mmol) in anhydrous THF (3 mL) at –78 °C and the
reaction was stirred at –78 °C for 2 h. The reaction mixture was
warmed to 0 °C, a solution of NH4Cl (15 mL) was slowly added,
and the mixture was diluted with EtOAc (10 mL). The aqueous
phase was back-extracted with EtOAc (3ϫ 5 mL) and the organic
fractions were combined and dried with anhydrous Na2SO4. The
residue was purified by flash chromatography (petroleum ether/
EtOAc, 9:1) to give 10 (0.200 g, 94% yield) as a mixture of dia-
stereomers (62:38) as a pale-yellow oil. [α]2D5 = +24.0 (c = 0.5,
CHCl3). NMR characterization of the major isomer partially
CH=CH2, 2.38 (dd, J = 13.8, 7.6 Hz, 1 H, CHH-CH=CH2) ppm.
dried with Na2SO4 and concentrated under reduced pressure. The
residue was purified by flash chromatography (petroleum ether/
EtOAc, 8.5:1.5) to give 13 (1.67 g, 80%) as a yellow oil. [α]D25
=
+62.5 (c = 0.8, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.43–
7.23 (m, 10 H, Ar-H), 6.90–6.85 (m, 2 H, Ar-H), 5.35 (br. s, 1 H,
CHH=), 4.96 (s, 1 H, CHH=), 4.85 (d, J = 12.2 Hz, 1 H, CH2Ph),
4.80 (d, J = 11.3 Hz, 1 H, CH2Ph), 4.72 (d, J = 11.3 Hz, 1 H,
CH2Ph), 4.71–4.63 (m, 2 H, 1-H, CH2Ph), 4.55 (d, J = 11.7 Hz, 1
H, CH2Ph), 4.51 (d, J = 11.7 Hz, 1 H, CH2Ph), 4.35–4.27 (m, 2 H,
5-H, 3-H), 3.80 (s, 3 H, OMe), 3.76 (dd, J = 10.0, 4.9 Hz, 1 H, 6-
H), 3.65 (dd, J = 10.0, 5.9 Hz, 1 H, 6-H), 3.48 (dd, J = 9.6, 3.6 Hz,
1 H, 2-H), 3.43 (s, 3 H, OMe) ppm. 13C NMR (101 MHz, CDCl3):
13C NMR (101 MHz, CDCl3): δ = 138.8, 138.1, 138.0, 131.6, 128.4, δ = 159.2, 142.6, 138.5, 138.4, 130.0, 129.4, 128.4, 128.1, 127.8,
128.4, 128.2, 127.9, 127.5, 127.1, 119.9, 115.5, 98.3, 82.2, 78.9, 77.6,
76.1, 73.3, 72.1, 71.3, 55.5, 52.9, 34.0 ppm. HRMS: calcd. for [M
+ H]+ 455.2434; found 455.2424.
127.7, 127.6, 127.6, 113.8, 107.8, 98.8, 81.5, 79.2, 73.9, 73.6, 73.2,
69.2, 67.7, 55.4, 55.3 ppm. HRMS: calcd. for [M + H]+ 491.2434;
found 491.2424.
Compound 11: To a solution of 10 (77 mg, 0.17 mmol) in anhydrous
Methyl 2,3-Di-O-benzyl-4-deoxy-4-C-(hydroxymethylene)-6-O-(p-
CH2Cl2 (10 mL), Hoveyda–Grubbs 2nd generation catalyst (5% methoxybenzyl)-α-
D-galactopyranoside (15):
A
solution of
weight), was added. The reaction mixture was stirred at 40 °C for
90 min, then the crude product was concentrated and purified by
flash chromatography (petroleum ether/EtOAc, 6:4) to give 10
(70 mg, 97%) as a pale-brown oil. H NMR (400 MHz, CDCl3): δ
(major isomer) = 7.41–7.21 (m, 10 H, Ar-H), 5.71–5.63 (m, 1 H,
BH3·Me2S (7.3 mmol, 0.7 mL) was added dropwise to a solution
of 13 (2.9 g, 5.86 mmol) in anhydrous THF (54 mL) at room tem-
perature, under an argon atmosphere and stirred for 90 min. The
reaction mixture was cooled to 0 °C, aqueous NaOH 3 m (2.9 mL)
then aqueous H2O2 (30%, 2.9 mL) were added dropwise. After
1
6-H), 5.63–5.54 (m, 1 H, 5-H), 5.01 (d, J = 11.5 Hz, 1 H, CH2Ph), 12 h, the reaction mixture was diluted with H2O (200 mL) and ex-
4.82–4.75 (m, 2 H, 1-H, CH2Ph), 4.66 (d, J = 12.0 Hz, 1 H,
CH2Ph), 4.60 (d, J = 11.5 Hz, 1 H, CH2Ph), 4.46–4.40 (m, 1 H, 7-
H), 4.03 (dd, J = 10.0, 3.6 Hz, 1 H, 2-H), 3.76 (d, J = 10.0 Hz, 1
H, 3-H), 3.64 (d, J = 8.1 Hz, 1 H, 7-Ha), 3.44 (s, 3 H, OMe), 3.42
(s, 3 H, OMe), 2.91 (dd, J = 19.3, 4.5 Hz, 1 H, 4-Ha), 2.10–2.03
(br., 1 H, OH), 1.88 (br. d, J = 19.3 Hz, 1 H, 4-Hb) ppm. 13C NMR
tracted with EtOAc (3ϫ 70 mL), dried with Na2SO4, filtered, and
concentrated under vacuum. The resulting residue was purified by
flash chromatography (petroleum ether/EtOAc, 7.5:2.5) to give 15
(1.82 g, 49%) as a pale-brown oil. [α]2D5 = +33.3 (c = 1.5, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 7.38–7.22 (m, 12 H, Ar-H), 6.87
(d, J = 8.6 Hz, 2 H, Ar-H), 4.82 (d, J = 12.1 Hz, 1 H, CH2Ph),
(101 MHz, CDCl3): δ = 139.1, 138.5, 129.2, 128.6, 128.6, 128.3, 4.75 (d, J = 11.5 Hz, 1 H, CH2Ph), 4.70 (d, J = 11.5 Hz, 1 H,
128.1, 127.8, 124.1, 98.9, 83.3, 78.1, 76.4, 75.9, 73.6, 68.9, 55.5,
54.0, 29.2 ppm. HRMS: calcd. for [M + H]+ 427.2121; found
427.2113.
CH2Ph), 4.66 (d, J = 12.1 Hz, 1 H, CH2Ph), 4.64 (d, J = 3.9 Hz, 1
H, 1-H), 4.52 (d, J = 11.5 Hz, 1 H, CH2Ph), 4.48 (d, J = 11.5 Hz,
1 H, CH2Ph), 4.09–4.01 (m, 2 H, 5-H, 3-H), 3.94 (dd, J = 11.5,
5.5 Hz, 1 H, 6-H), 3.83–3.75 (m, 4 H, ArOMe, 6-H), 3.68 (dd, J =
10.2, 3.9 Hz, 1 H, 2-H), 3.61–3.54 (m, 2 H, CH2OH), 3.37 (s, 3 H,
OMe), 2.37–2.30 (m, 1 H, 4-H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 159.4, 138.3, 138.3, 129.5, 129.4, 128.4, 128.4, 128.0,
127.8, 127.7, 113.9, 98.7, 78.5, 76.7, 73.4, 73.1, 70.2, 67.8, 57.8,
55.2, 55.2, 43.7 ppm. HRMS: calcd. for [M + H]+ 509.2539; found
509.2530.
Compound 1: Compound 11 (693 mg, 1.62 mmol) and activated
MnO2 (988 mg, 11.37 mmol) were slurried in EtOAc (20 mL), and
the mixture was heated to reflux for 4 h. After consumption of the
starting material, the reaction mixture was hot-filtered though Ce-
lite and the residual black solid was washed copiously with EtOAc
(40 mL). The filtrate was concentrated in vacuo, to give 1 (656 mg,
95%yield) as pale-brown oil. [α]2D5 = +66.7 (c = 0.6, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 7.45–7.24 (m, 10 H, Ar-H), 6.71–
6.66 (m, 1 H, 5-H), 6.06 (dd, J = 10.1, 3.1 Hz, 1 H, 6-H), 5.04 (d,
J = 11.2 Hz, 1 H, CH2Ph), 4.84 (d, J = 3.4 Hz, 1 H, 1-H), 4.79 (d,
Compound 14 (Minor Byproduct): [α]2D5 = +8.3 (c = 1.2, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 7.46–7.17 (m, 12 H, Ar-H), 6.87 (d,
J = 8.6 Hz, 2 H, Ar-H), 4.94 (d, J = 11.8 Hz, 1 H, CH2Ph), 4.81
J = 11.7 Hz, 1 H, CH2Ph), 4.65 (d, J = 11.2 Hz, 1 H, CH2Ph), 4.62 (d, J = 11.9 Hz, 1 H, CH2Ph), 4.78 (d, J = 11.8 Hz, 1 H, CH2Ph),
(d, J = 11.7 Hz, 1 H, CH2Ph), 4.35 (s, 1 H, 7-Ha), 4.05 (dd, J =
10.0, 3.4 Hz, 1 H, 2-H), 3.90 (d, J = 10.0 Hz, 1 H, 3-H), 3.42 (s, 3
H, OMe), 3.38 (s, 3 H, OMe), 3.16 (dd, J = 19.6, 5.9 Hz, 1 H, 4-
4.62 (d, J = 11.9 Hz, 1 H, CH2Ph), 4.59 (d, J = 3.8 Hz, 1 H, 1-H),
4.51 (d, J = 11.7 Hz, 1 H, CH2Ph), 4.45 (d, J = 11.7 Hz, 1 H,
CH2Ph), 3.88 (br. t, J = 6.1 Hz, 1 H, 5-H), 3.82–3.78 (m, 4 H, 3-
H), 2.20–2.11 (m, 1 H, 4-H) ppm. 13C NMR (101 MHz, CDCl3): δ H, ArOMe), 3.68 (dd, J = 9.8, 6.1 Hz, 1 H, 6-H), 3.55 (dd, J = 9.8,
= 193.8, 142.2, 138.7, 138.2, 129.7, 128.7, 128.7, 128.4, 128.2, 128.0,
6.1 Hz, 1 H, 6-H), 3.46–3.36 (m, 4 H, 2-H, OMe), 1.18 (s, 3 H,
99.2, 82.2, 80.5, 77.5, 76.3, 76.3, 73.8, 56.3, 54.4, 30.3 ppm. HRMS: CH3) ppm. 13C NMR (101 MHz, CDCl3): δ = 159.2, 139.2, 138.3,
calcd. for [M + H]+ 425.1964; found 425.1954.
129.8, 129.3, 128.4, 128.4, 128.0, 127.8, 127.8, 127.6, 113.8, 98.0,
83.5, 78.5, 75.7, 74.3, 73.4, 73.2, 70.7, 68.6, 55.3, 55.1, 15.8 ppm.
Methyl
oxybenzyl-α-
2,3-Di-O-benzyl-4-deoxy-4-C-(methylene)-6-O-p-meth-
-xylo-hexopyranoside (13): To a suspension of meth-
D
Methyl
2,3-Di-O-benzyl-4-deoxy-4-C-(formyl)-6-O-(p-methoxy-
yltriphenylphosphonium bromide (10.6 g, 29.84 mmol) in anhy-
drous THF (50 mL) was added nBuLi (1.6 m in hexane, 17.31 mL)
at –78 °C with stirring under an argon atmosphere. After warming
to 0 °C for 30 min, the solution was re-cooled to –78 °C and treated
with a solution of ketone 5 (2.1 g, 4.26 mmol) in anhydrous THF
(90 mL). The mixture was stirred for 2 h and warmed to room tem-
perature, then poured in a saturated solution of NH4Cl (100 mL)
and extracted with Et2O (3ϫ 30 mL). The organic extracts were
benzyl)-α-D-galactopyranoside (16): To a solution of (COCl)2
(7.86 mmol, 0.7 mL) in anhydrous CH2Cl2 (16 mL) at –78 °C under
an argon atmosphere, solution of anhydrous DMSO
a
(15.76 mmol, 1.1 mL) in anhydrous CH2Cl2 (6 mL) was added
dropwise, and the resulting solution was stirred for 30 min. To the
reaction flask, a solution of 15 (1 g, 1.97 mmol) in anhydrous
CH2Cl2 (10 mL) was added dropwise at –78 °C. This final reaction
mixture was stirred for 1 h at –78 °C, then anhydrous Et3N
Eur. J. Org. Chem. 2014, 2549–2556
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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