A. Neogi et al. / Tetrahedron 61 (2005) 9368–9374
9371
and Ph3P (2.09 g, 8 mmol) in dry benzene (50 mL) was
stirred and cooled to 0 8C, while I2 (1.52 g, 6 mmol) was
added in small portions over a period of 1 h. After
completion of addition, the reaction mixture was stirred at
rt for 3 h. The solid mass was extracted with diethyl ether
(6!25 mL). The combined organic layer was washed with
saturated aq Na2S2O3 (3!50 mL), water and dried
(Na2SO4) and concentrated under reduced pressure to afford
an oily material. The oil on column chromatography over
silica gel furnished the iodo derivatives 4a–c.
(CDCl3, 75 MHz): d 26.2 (CH3), 26.8 (CH3), 56.1 (2!
OCH3), 60.2 (CH2), 71.6 (CH2), 80.9 (CH), 81.5 (CH), 81.7
(CH), 105.6 (CH), 111.9 (C), 112.7 (CH), 113.4 (C), 115.2
(CH), 128.3 (C), 148.4 (C), 149.2 (C); ESIMS, m/z: 551, 553
(MCCNa for Br79, Br81).
4.4. General procedure for the synthesis of compounds
5a–c
Each of the iodides 4a–c (1 mmol) in dry THF (20 mL) was
added dropwise under inert atmosphere to a stirred solution
of KOBut (0.17 g, 1.5 mmol) in dry THF (20 mL) cooled to
0 8C. After completion of addition, the reaction mixture was
stirred at 0 8C for 1.5 h. The reaction was quenched with
saturated aq NH4Cl (30 mL) and the aq layer was extracted
with ethyl acetate (6!25 mL), the combined organic layer
was washed with water, dried (Na2SO4) and evaporated
under reduced pressure to provide a liquid. The liquid was
purified by flash chromatography on silica gel using PS:EA
as eluent to afford exo-methylene sugar derivatives 5a–c.
4.3.1. (3aR,5S,6R,6aR)-6-(2-Bromo-benzyloxy)-5-iodo-
methyl-2,2-dimethyl-tetrahydro-furo[2,3-d][1,3]dioxole
(4a). Yellow liquid; yield 60% (eluent PS/EA 24:1);
[Found: C, 38.29; H, 3.80. C15H18BrIO4 requires C,
38.40; H, 3.87]; [a]D25K52.6 (c 2.12, CHCl3); nmax (liquid
film) 2984, 2930, 1569, 1445, 1377, 1216, 1163, 1079,
1
1023 cmK1; H NMR (CDCl3, 300 MHz): d 1.33 (s, 3H,
CH3), 1.52 (s, 3H, CH3), 3.29–3.40 (m, 2H, CH2I), 4.16 (d,
1H, JZ3.0 Hz, H-6), 4.47–4.53, (m, 1H, H-5), 4.61 (d, 1H,
JZ12.1 Hz, Ha of ArCH2), 4.71 (d, 1H, JZ3.6 Hz, H-6a),
4.80 (d, 1H, JZ12.1 Hz, Hb of ArCH2), 5.98 (d, 1H, JZ
3.7 Hz, H-3a), 7.18 (td, 1H, JZ7.8, 1.6 Hz, ArH), 7.32 (td,
1H, JZ7.5, 1.1 Hz, ArH), 7.46 (dd, 1H, JZ7.6, 1.3 Hz,
ArH), 7.55 (dd, 1H, JZ8.1, 0.9 Hz, ArH); 13C NMR
(CDCl3, 75 MHz): d 26.2 (CH3), 26.8 (CH3), 71.3 (CH2),
71.6 (CH2), 80.9 (CH), 81.7 (2!CH), 105.6 (CH), 111.9
(C), 122.8 (C), 127.4 (CH), 129.3 (CH), 129.4 (CH), 132.5
(CH), 136.4 (C); ESIMS, m/z: 491, 493 (MCCNa for Br79,
Br81).
4.4.1.
(3aR,6R,6aR)-6-(2-Bromo-benzyloxy)-2,2-
dimethyl-5-methylene-tetrahydro-furo[2,3-d][1,3]diox-
ole (5a). Colorless liquid; yield 69% (eluent PS/EA 49:1);
[Found: C, 52.60; H, 5.00. C15H17BrO4 requires C, 52.80;
H, 5.02]; [a]2D5K19.0 (c 2.62, CHCl3); nmax (liquid film) 2989,
1
2937, 1662, 1569, 1440, 1378, 1224, 1109, 1004 cmK1; H
NMR (CDCl3, 300 MHz): d 1.39 (s, 3H, CH3), 1.47 (s, 3H,
CH3), 4.32 (s-like, 2H, overlapped by H-6 signal, Ha of
]CH2), 4.58 (d, 1H, JZ12.3 Hz, Ha of ArCH2), 4.63 (d, 1H,
JZ3.2 Hz, H-6a), 4.67 (d, 1H, JZ1.4 Hz, Hb ]CH2), 4.71 (d,
1H, JZ12.3 Hz, Hb ofArCH2), 6.10(d, 1H, JZ3.2 Hz, H-3a),
7.16 (t, 1H, JZ7.7 Hz, ArH), 7.30 (t, 1H, JZ6.7 Hz, ArH),
7.42 (d, 1H, JZ7.2 Hz, ArH), 7.54 (d, 1H, JZ7.9 Hz, ArH);
13C NMR (CDCl3, 75 MHz): 27.1 (CH3), 27.9 (CH3), 69.9
(CH2), 81.2(CH), 83.0(CH), 88.9(]CH2), 106.7(CH), 113.7
(C), 122.9 (C), 127.3 (CH), 129.2 (CH), 129.3 (CH), 132.6
(CH), 136.6 (C), 158.4 (C); ESIMS, m/z: 363, 365 (MCCNa
for Br79, Br81).
4.3.2. (3aR,5S,6R,6aR)-6-(2-Bromo-5-methoxy-benzy-
loxy)-5-iodomethyl-2,2-dimethyl-tetrahydro-furo[2,3-d]
[1,3]dioxole (4b). Yellow liquid; yield 66% (eluent PS/EA
24:1); [Found: C, 38.29; H, 4.00. C16H20BrIO5 requires C,
38.50; H, 4.04]; [a]D25K54.4 (c 1.20, CHCl3); nmax (liquid
film) 2984, 2933, 1577, 1474, 1377, 1296, 1238, 1164,
1
1079, 1020 cmK1; H NMR (CDCl3, 300 MHz): d 1.33 (s,
3H, CH3), 1.52 (s, 3H, CH3), 3.29–3.40 (m, 2H, CH2I), 3.80,
(br s, 3H, OCH3), 4.16 (d, 1H, JZ3.0 Hz, H-6), 4.47–4.52
(m, 1H, H-5), 4.56 (d, 1H, JZ12.3 Hz, Ha of ArCH2), 4.71
(d, 1H, JZ3.7 Hz, H-6a), 4.76 (d, 1H, JZ12.3 Hz, Hb of
ArCH2), 5.98 (d, 1H, JZ3.7 Hz, H-3a), 6.73 (dd, 1H, JZ
8.7, 3.0 Hz, ArH), 7.03 (d, 1H, JZ3.0 Hz, ArH), 7.42 (d,
1H, JZ8.7 Hz, ArH); 13C NMR (CDCl3, 75 MHz): d 26.1
(CH3), 26.7 (CH3), 55.3 (OCH3), 60.2 (CH2), 71.5 (CH2),
80.9 (CH), 81.6 (CH), 81.8 (CH), 105.6 (CH), 111.8 (C),
112.7 (C), 114.7 (CH), 115.0 (CH), 133.0 (CH), 137.4 (C),
158.9 (C); ESIMS, m/z: 521, 523 (MCCNa for Br79, Br81).
4.4.2. (3aR,6R,6aR)-6-(2-Bromo-5-methoxy-benzyloxy)-
2,2-dimethyl-5-methylene-tetrahydro-furo[2,3-d][1,3]
dioxole (5b). Colorless liquid; yield 70% (eluent PS/EA
49:1); [Found: C, 51.56; H, 5.00. C16H19BrO5 requires C,
51.77; H, 5.16]; [a]D25K32.0 (c 1.00, CHCl3); nmax (liquid
film) 2989, 2938, 1665, 1590, 1576, 1472, 1378, 1235,
1
1110, 1004 cmK1; H NMR (CDCl3, 300 MHz): d 1.39 (s,
3H, CH3), 1.47 (s, 3H, CH3), 3.79 (s, 3H, OCH3), 4.32
(s-like, 2H, overlapped by H-6 signal, Ha of ]CH2), 4.54
(d, 1H, JZ12.7 Hz, Ha of ArCH2), 4.63–4.68 (m, 3H, Hb of
]CH2 overlapped by Hb of ArCH2 and H-6a signal), 6.10
(d, 1H, JZ3.2 Hz, H-3a), 6.71 (dd, 1H, JZ8.7, 3.0 Hz,
ArH), 6.98 (d, 1H, JZ3.0 Hz, ArH), 7.41 (d, 1H, JZ8.7 Hz,
ArH); 13C NMR (CDCl3, 75 MHz): 27.6 (CH3), 28.3 (CH3),
55.8 (OCH3), 70.3 (CH2), 81.7 (CH), 83.5 (CH), 89.4
(]CH2), 107.2 (CH), 113.4 (C), 114.2 (C), 115.2 (CH),
115.4 (CH), 133.6 (CH), 138.0 (C), 158.9 (C), 159.5 (C);
ESIMS, m/z: 393, 395 (MCCNa for Br79, Br81).
4.3.3. (3aR,5S,6R,6aR)-6-(2-Bromo-4,5-dimethoxy-ben-
zyloxy)-5-iodomethyl-2,2-dimethyl-tetrahydro-furo[2,3-
d][1,3]dioxole (4c). Yellow liquid; yield 68% (eluent PS/
EA16:1); [Found: C, 38.38; H, 4.00. C17H22BrIO6 requires
C, 38.59; H, 4.19]; [a]2D5K31.8 (c 2.30, CHCl3); nmax (liquid
film) 2981, 2933, 1601, 1507, 1459, 1379, 1262, 1214,
1
1163, 1076, 1024 cmK1; H NMR (CDCl3, 300 MHz): d
1.36 (s, 3H, CH3), 1.52 (s, 3H, CH3), 3.31–3.35 (m, 2H,
CH2I), 3.87, (s, 3H, OCH3), 3.89 (s, 3H, OCH3), 4.13 (d, 1H,
JZ2.9 Hz, H-6), 4.49–4.52 (m, 1H, H-5), 4.53 (d, 1H, JZ
11.6 Hz, Ha of ArCH2), 4.71 (d, 1H, JZ3.6 Hz, H-6a), 4.77
(d, 1H, JZ11.5 Hz, Hb of ArCH2), 5.97 (d, 1H, JZ3.6 Hz,
H-3a), 6.99 (s, 1H, ArH), 7.02 (s, 1H, ArH); 13C NMR
4.4.3. (3aR,6R,6aR)-6-(2-Bromo-4,5-dimethoxy-benzy-
loxy)-2,2-dimethyl-5-methylene-tetrahydro-furo[2,3-d]
[1,3]dioxole (5c). Colorless liquid; yield 72% (eluent PS/
EA 32:1); [Found: C, 50.67; H, 5.00. C17H21BrO6 requires