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M. J. Comin et al. / Tetrahedron 60 (2004) 11851–11860
solution of a mixture of compounds 13 and 14 (42 mg) in
pyridine (1.0 mL) was added acetic anhydride (0.5 mL).
The reaction mixture was stirred at room temperature
overnight. Then, an aqueous 5% solution of hydrochloric
acid was added and the mixture was stirred for an additional
hour. The reaction mixture was partitioned between water
(2.0 mL) and ethyl acetate (5.0 mL). The organic phase was
washed with 5% HCl (2 mL) and brine (2!5 mL), dried
(MgSO4), and the solvent was evaporated. The residue was
purified by column chromatography (silica gel) eluting with
hexane–EtOAc (9:1) to afford 48 mg (94%) of an 1.2:1 ratio
of a mixture of acetates 15 and 16 as a colorless oil.
Compound 15: Rf 0.53 (hexane–EtOAc, 4:1); 1H NMR
(200 MHz, CDCl3) d 7.36 (m, 5H), 5.97 (dd, JZ7.7, 4.4 Hz,
1H), 4.63 (mAB, 2H), 3.86 (dd, JZ11.0, 7.7 Hz, 1H), 3.75
(dd, JZ11.0, 4.4 Hz, 1H), 3.31 (s, 3H), 2.13 (s, 3H); 13C
NMR (50 MHz, CDCl3) d 137.5, 128.5, 128.3, 126.7, 96.4,
74.6, 69.9, 55.3, 21.2. Compound 16: Rf 0.45 (hexane–
(m, 2H), 5.83, 5.80 (s, 1H), 4.65, 4.53 (p, JZ6.5 Hz, 1H),
4.25, 4.20 (m, 2H), 4.04 (m, 2H), 4.04, 3.96 (m, 2H), 3.36,
3.35 (s, 3H).
3.1.9. 1-Methoxymethoxy-3-(4-phenoxy-phenoxy)pro-
pan-2-yl Acetate (18). To a solution of compound 17
(56 mg, 0.18 mmol) in pyridine (1 mL) was added acetic
anhydride (0.5 mL) as depicted for compounds 15 and 16.
After the usual workup, the product was purified by column
chromatography (silica gel) eluting with hexane–EtOAc
(19:1) to afford 62 mg (97% yield) of pure compound 18 as
a colorless oil: Rf 0.75 (hexane–EtOAc, 1:1); 1H NMR
(500 MHz, CDCl3) d 7.29 (t, JZ7.9 Hz, 2H), 7.04 (t, JZ
7.6 Hz, 1H), 6.96 (d, JZ8.9 Hz, 2H), 6.94 (d, JZ8.7 Hz,
2H), 6.89 (d, JZ9.1 Hz, 2H), 5.32 (p, JZ5.0 Hz, 1H), 4.65
(mAB, 2H), 4.15 (dd, JZ10.2, 5.0 Hz, 1H), 4.12 (dd, JZ
10.2, 5.2 Hz, 1H), 3.82 (mAB, 2H), 3.36 (s, 3H), 2.12 (s,
3H); 13C NMR (125 MHz, CDCl3) d 170.4, 158.3, 154.7,
150.7, 129.6, 122.6, 120.7, 117.7, 115.8, 96.6, 71.0, 66.8,
65.8, 55.3, 21.0; MS (m/z, relative intensity) 346 (MC, 5),
186 (9), 161 (54), 131 (38), 71 (32), 45 (100). Anal. calcd
for C19H22O6: C 65.88, H 6.40. Found: C 66.17, H 6.62.
1
EtOAc, 4:1); H NMR (200 MHz, CDCl3) d 7.36 (m, 5H),
4.88 (dd, JZ6.5, 5.1 Hz, 1H), 4.61 (mAB, 2H), 4.26 (mAB,
2H), 3.39 (s, 3H), 2.09 (s, 3H); 13C NMR (50 MHz, CDCl3)
d 137.8, 128.6, 128.4, 127.1, 94.3, 75.6, 67.7, 55.4, 20.9.
3.1.7. 1-Methoxymethoxy-3-(4-phenoxy-phenoxy)pro-
pan-2-ol (17). A solution of compound 6 (230 mg,
0.88 mmol) in anhydrous methylene chloride (20 mL) was
treated as depicted for the preparation of compound 13
(Method A). The crude product was purified by column
chromatography (silica gel) eluting with a mixture of
hexane–EtOAc (4:1) to afford 240 mg (90% yield) of pure
compound 17 as a colorless oil: Rf 0.48 (hexane–EtOAc,
1:1); 1H NMR (500 MHz, CDCl3) d 7.29 (m, 2H), 6.98 (m,
7H), 4.70 (mAB, 2H), 4.17 (sxt, JZ5.0 Hz, 1H), 4.02 (d, JZ
5.5 Hz, 2H), 3.79 (dd, JZ10.5, 4.1 Hz, 1H), 3.72 (dd, JZ
10.5, 5.9 Hz, 1H), 3.40 (s, 3H), 2.80 (d, JZ4.8 Hz, 1H); 13C
NMR (50 MHz, CDCl3) d 158.2, 154.7, 150.4, 129.5, 122.4,
120.6, 117.6, 115.5, 96.7, 69.4, 69.3, 69.1, 55.3; MS (m/z,
relative intensity) 304 (MC, 13), 186 (48), 45 (100). Anal.
calcd for C17H20O5: C 67.09, H 6.62. Found: C 67.00, H 6.70.
3.1.10. N-(2,3-Dihydroxy-propyl)-N-(4-phenoxyphenyl)-
formamide (19); 3-[methyl-(4-phenoxy-phenyl)-amino]-
propane-1,2-diol (20). A solution of compound 7 (80 mg,
0.31 mmol) in methylene chloride (10 mL) was treated as
described for the preparation of 13 (Method A). The product
was purified by column chromatography (silica gel) eluting
with hexane–EtOAc (4:1) to afford 16 mg (20% yield) of
compound 20 as a colorless oil. In an independent
experiment, compound 19 was isolated as a white solid in
90% yield when DIBAL was not added to the reaction
mixture. Compound 19: 1H NMR (500 MHz, CDCl3) d 8.35
(s, 1H), 7.37 (m, 2H), 7.17 (m, 3H), 7.03 (d, JZHz, 2H),
3.93 (dd, JZ15.9, 8.2 Hz, 1H), 3.87 (m, 2H), 3.66 (m, 1H),
3.59 (dd, JZ11.6, 2.3 Hz, 1H); 13C NMR (125 MHz,
CDCl3) d 164.0, 157.0, 156.4, 135.9, 130.0, 126.4, 124.0,
119.42, 119.37, 70.1, 63.6, 49.2. Compound 20: Rf 0.25
1
(hexane–EtOAc, 2:3); H NMR (200 MHz, CDCl3) d 7.28
A solution of diol 6 (230 mg, 0.88 mmol) in anhydrous
methylene chloride (20 mL) was treated as depicted for
compound 13 (method B). The product was purified by
column chromatography (silica gel) employing hexane–
EtOAc (4:1) as eluent to give 180 mg (67% yield) of pure 17
as a colorless oil.
(m, 2H), 6.96 (m, 5H), 6.82 (m, 2H), 4.02 (ddt, JZ8.0, 5.0,
3.4 Hz, 1H), 3.80 (dd, JZ11.4, 3.3 Hz, 1H), 3.58 (dd, JZ
11.4, 5.1 Hz, 1H), 3.39 (dd, JZ14.3, 8.1 Hz, 1H), 3.25 (dd,
JZ14.7, 5.1 Hz, 1H), 2.94 (s, 3H), 2.09 (broad s, 2H); 13C
NMR (50 MHz, CDCl3) d 158.7, 147.1, 142.6, 129.5, 122.2,
120.8, 117.4, 115.1, 69.4, 64.3, 56.9, 39.9; MS (m/z, relative
intensity) 273 (MC, 9), 212 (100), 197 (17).
3.1.8. 2-Methoxy-4-(4-phenoxyphenoxymethyl)-[1,3]-
dioxolane (17a). A solution of compound 6 (25 mg,
0.10 mmol) in anhydrous methylene chloride (5 mL) was
treated with trimethyl orthoformate (21 mL, 0.20 mmol) and
CAN (5 mg) under argon atmosphere. The mixture was
stirred at room temperature for 2 h. The reaction was
worked up by addition of an aqueous saturated solution of
sodium bicarbonate (5 mL). The mixture was extracted with
methylene chloride (3!5 mL). The combined organic
layers were washed with water (2!5 mL), dried
(MgSO4), and the solvent was evaporated. The residue
was purified by preparative TLC eluting with hexane–
EtOAc (3:2) to afford 29 mg (95% yield) of 17a as an
equimolecular diastereomeric mixture as colorless oils: Rf
0.69, 0.66 (hexane–EtOAc, 1:1); 1H NMR (500 MHz,
CDCl3) d 7.30 (m, 2H), 7.05 (m, 1H), 6.97 (m, 4H), 6.89
3.1.11. Methyl 5-benzyloxy-b-D-ribofuranoside (22).
Protected D-ribose derivative 21 (900 mg, 3.06 mmol) was
treated with 60% acetic acid (5 mL). The reaction mixture
was stirred at 50 8C for 40 h. The solvent was evaporated
and the product was purified by column chromatography
(silica gel) employing hexane–EtOAc (7:3) as eluent to
afford 450 mg (63% yield) of pure compound 22 as a
yellowish oil: Rf 0.15 (hexane–EtOAc, 3:2); 1H NMR
(500 MHz, CDCl3) d 7.34 (m, 5H, aromatic protons), 4.83
(s, 1H, H-1), 4.59 (mAB, 2H, OCH2Ph), 4.19 (t, JZ5.7 Hz,
1H, H-3), 4.09 (q, JZ5.7 Hz, 1H, H-4), 4.00 (d, JZ4.8 Hz,
1H, H-2), 3.63 (dd, JZ10.0, 5.9 Hz, 1H, H-5a), 3.60 (dd,
JZ10.0, 5.5 Hz, 1H, H-5b), 3.33 (s, 3H, OCH3); 103C NMR
(125 MHz, CDCl3) d 137.9 (C-10), 128.4 (C-3 ), 127.8