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P. R. Krishna et al. / Tetrahedron 63 (2007) 9871–9880
solution of 16 (0.35 g, 1.4 mmol) in benzene (3 mL) at reflux
(ethoxycarbonylmethylene)triphenylphosphorane (0.73 g,
2.1 mmol) was added and the mixture allowed to reflux for
1 h. The workup and purification as described for compound
7 afforded 18 (0.31 g, 70% only E isomer) as a yellow syrup.
Rf (40% EtOAc/hexane) 0.52; [a]D +9.3 (c 0.7, CHCl3); 1H
NMR (300 MHz, CDCl3): d 7.27 (br s, 5H, Ar–H), 6.94–6.85
(m, 1H, –CH]CHCOOEt), 5.98 (t, J 15.8 Hz, 1H, –CH]
CHCOOEt), 4.69–4.54 (m, 1H, –CHCH]CHCOOEt),
4.54 (s, 2H, –OCH2Ph), 4.23–4.05 (m, 3H, –COOCH2CH3
and –CHO–), 3.93–3.83 (m, 1H, –CHOMe), 3.55–3.40 (m,
2H, –CH2OBn), 3.30 (s, 3H, –OCH3), 2.41–2.07 (m, 1H,
–CH2), 1.85–1.65 (m, 1H, –CH2), 1.29 (t, J 7.2 Hz, 3H,
–COOCH2CH3); 13C NMR (50 MHz, CDCl3): d 15.0, 31.2,
56.0, 60.1, 71.2, 72.1, 82.1, 83.0, 89.1, 127.4, 127.9, 128.8,
131.1, 135.1, 145.2, 163.8; IR (neat): 2960, 1660, 1450,
1190, 1010 cmÀ1; FABMS (m/z, %): 343 (M++Na, 2), 321
(M++H, 13), 215 (27), 138 (62), 73 (100). Anal. Calcd for
C18H24O5; C 67.48, H 7.55%; found C 67.38, H 7.50%.
4-[5-benzyloxymethyl-4-methoxy-(2R,4R,5S)-2H,3H,4H-
2-furanyl]-1H-3-pyrrolecarboxylate (20a and 20b). To
a stirred solution of TosMIC (0.080 g, 0.41 mmol) in dry
THF (2 mL) at À78 ꢀC was added n-BuLi (1.6 M solution
in n-hexane, 0.25 mL, 1.2 mmol) and the mixture stirred
for 15 min. To this 18 (0.110 g, 0.34 mmol) dissolved in
dry THF (2 mL) was added and the mixture stirred for
30 min. After completion of the reaction, the mixture was
quenched with satd NH4Cl (1 mL), extracted with EtOAc
(2Â5 mL), and the combined organic layers were washed
with water (1Â5 mL), brine (1Â5 mL), dried (Na2SO4),
and concentrated under reduced pressure. The crude product
was purified by column chromatography (Silica gel 60–120,
1:5 EtOAc:hexane), first eluted was 20a (0.046 g, 37%) as
a light yellow syrup. Rf (30% EtOAc/hexane) 0.38; [a]D
1
À48.3 (c 1.6, CHCl3); H NMR (300 MHz, CDCl3): d 8.4
(s, 1H, –NH–), 7.27 (br s, 5H, Ar–H), 7.21 (s, 1H, pyrrole-
H), 6.64 (s, 1H, pyrrole-H), 5.42 (dd, J 9.4, 5.2 Hz, 1H,
–CHpyrrole), 4.54 (s, 2H, –CH2Ph), 4.22 (m, 2H,
–COOCH2CH3), 4.09–4.05 (m, 1H, –CHCH2OBn), 3.84–
3.79 (m, 1H, –CHOCH3), 3.62–3.51 (m, 2H, –CH2OBn),
3.32 (s, 3H, –OCH3), 2.47 (ddd, J 8.2, 5.6, 1.8 Hz, 1H,
–CH2–), 1.78–1.69 (m, 1H, –CH2–), 1.32 (t, J 7.1 Hz, 3H,
–COOCH2CH3); 13C NMR (75 MHz, CDCl3): d 15.0,
29.9, 39.5, 56.8, 59.5, 60.0, 71.2, 73.3, 83.1, 83.6, 113.6,
116.6, 125.2, 126.9, 127.6, 128.6, 138.3, 164.8; IR (neat):
3260, 2920, 1500, 1450, 1120 cmÀ1; FABMS (m/z, %):
360 (M++H, 9), 327 (14), 207 (3), 147 (19), 91 (59), 69
(74), 55 (100). Anal. Calcd for C20H25NO5: C 66.83, H
7.01, N 3.90%; found C 66.74, H 7.11, N 3.85%.
4.1.17. 4-Methoxy-2-(1,3-oxazol-5-yl)-(2S,4R,5S)-
2H,3H,4H-5-furanylmethoxy-(phenyl)methane and
4-methoxy-2-(1,3-oxazol-5-yl)-(2R,4R,5S)-2H,3H,4H-5-
furanylmethoxy (phenyl)methane (19a and 19b). To
a stirred solution of aldehyde 17 (0.15 g, 0.6 mmol) in meth-
anol (2 mL) were added TosMIC (0.14 g, 0.72 mmol) and
potassium carbonate (0.248 g, 1.8 mmol) and the mixture
allowed to reflux for 1 h. The reaction mixture was concen-
trated under reduced pressure, the residue dissolved in water
(10 mL) and extracted into EtOAc (2Â10 mL). The com-
bined organic layers were washed with water (1Â10 mL),
brine (1Â10 mL), dried (Na2SO4), and concentrated under
reduced pressure. The crude product was purified by column
chromatography (60–120 Silica gel, 1:5 EtOAc:hexane) the
first eluted was 19a (0.048 g, 28%) as a thick yellow syrup.
Rf (50% EtOAc/hexane) 0.39; [a]D À0.5 (c 0.8, CHCl3); 1H
NMR (300 MHz, CDCl3): d 7.78 (s, 1H, oxazole-H), 7.28 (br
s, 5H, Ar–H), 6.96 (s, 1H, oxazole-H), 5.08 (dd, J 9.8,
6.0 Hz, 1H, –CHoxazole), 4.53 (s, 2H, –CH2Ph), 4.10 (m,
1H, –CHCH2OBn), 3.95–3.89 (m, 1H, –CHOCH3), 3.57
(dd, J 10.5, 5.2 Hz, 1H, –CH2OBn), 3.46 (dd, J 10.5,
5.2 Hz, 1H, –CH2OBn), 3.33 (s, 3H, –OCH3), 2.21–2.16
(m, 2H, –CH2); 13C NMR (50 MHz, CDCl3): d 36.3, 56.7,
70.8, 71.3, 73.5, 83.0, 83.7, 124.0, 127.5, 128.3, 129.6,
130.1, 138.1, 151.0; LCMS: 307 (M+NH4)+. Anal. Calcd
for C16H19NO4; C 66.42, H 6.62, N 4.84%; found C 66.40,
H 6.59, N 4.80%.
The second eluted was 20b (0.042 g, 34%) as a colorless
syrup. Rf (30% EtOAc/hexane) 0.37; [a]D +17.1 (c 0.35,
CHCl3); H NMR (300 MHz, CDCl3): d 8.90 (br s, 1H,
1
–NH–), 7.27 (br s, 5H, Ar–H), 7.21 (s, 1H, pyrrole-H),
6.69 (s, 1H, pyrrole-H), 5.47 (t, J 7.3 Hz, 1H, –CHpyrrole),
4.60 (s, 2H, –CH2Ph), 4.25–4.18 (m, 3H, –CHCH2OBn and
–COOCH2CH3), 3.96–3.90 (m, 1H, –CHOCH3), 3.56 (d, J
5.2 Hz, 2H, –CH2OBn), 3.26 (s, 3H, –OCH3), 2.81–2.72
(m, 1H, –CH2), 1.85–1.76 (m, 1H, –CH2), 1.31 (t, J
7.1 Hz, 3H, –COOCH2CH3); 13C NMR (75 MHz, CDCl3):
d 15.0, 29.8, 39.5, 56.6, 57.2, 59.5, 60.1, 71.1, 74.2, 83.0,
83.6, 113.5, 116.6, 125.1, 126.9, 127.5, 128.6, 138.4,
164.9; IR (neat): 3260, 2920, 1500, 1450, 1120 cmÀ1
;
FABMS (m/z, %): 360 (M++H, 5), 327 (2), 147 (21),
91(59), 69 (72), 55 (100). Anal. Calcd for C20H25NO5: C
66.83, H 7.01, N 3.90%; found C 66.80, H 7.10, N 3.79%.
The second eluted was 19b (0.043 g, 25%) as a yellow syrup.
Rf (50%EtOAc/hexane)0.38; [a]D À8.5(c 10.35, CHCl3); 1H
NMR (300 MHz, CDCl3): d 7.78 (s, 1H, Oxazole-H), 7.27
(br s, 5H, Ar–H), 7.01 (s, 1H, Oxazole-H), 5.16 (t, J 7.5 Hz,
1H, –CHOxazole), 4.56 (d, J 2.9 Hz, 2H, –OCH2Ph), 4.12–
4.08 (m, 1H, –CHCH2OBn), 4.03–3.97 (m, 1H, –CHOCH3),
3.56 (d, J 4.5 Hz, 2H, –CH2OBn), 3.32 (s, 3H, –OCH3), 2.56–
2.47 (m, 1H, –CH2), 2.20–2.15 (m, 1H, –CH2); 13C NMR
(50 MHz, CDCl3): d 36.3, 56.7, 70.8, 71.3, 73.5, 83.0, 83.7,
124.0, 127.5, 128.3, 129.6, 130.1, 138.1, 151.0; LCMS: 312
(M++Na). Anal. Calcd for C16H19NO4; C 66.42, H 6.62, N
4.84%; found C 66.29, H 6.65, N 4.83%.
4.1.19. (4S)-4-[(1R)-1-(Benzyloxy)-3-butenyl]-2,2-di-
methyl-1,3-dioxolane (21). To a stirred solution of 1
(2.5 g, 14.5 mmol) in dry DMF (8 mL) at 0 ꢀC was added
sodium hydride (0.68 g, 29.04 mmol, 60% dispersion in
mineral oil) and stirred for 20 min. Benzyl bromide
(2.47 g, 14.5 mmol) was added and the reaction stirred for
6 h. The reaction mixture was quenched with satd NH4Cl
(20 mL) at 0 ꢀC and stirred for 10 min. The organic com-
pound was extracted into EtOAc (2Â100 mL). The organic
layer was washed with water (1Â50 mL), brine
(2Â50 mL), dried (Na2SO4), and concentrated under re-
duced pressure. The crude product was purified by column
chromatography (60–120 Silica gel, 1:50 EtOAc:hexane)
to obtain 21 (2.48 g, 94%) as a colorless liquid. Rf (10%
4.1.18. Ethyl 4-[5-benzyloxymethyl-4-methoxy-(2S,4R,5S)-
2H,3H,4H-2-furanyl]-1H-3-pyrrolecarboxylate and ethyl
1
EtOAc/hexane) 0.41; [a]D +8.1 (c 1.25, CHCl3); H NMR