Total Synthesis of Furano Lignans
J . Org. Chem., Vol. 67, No. 10, 2002 3247
P r ep a r a tion of 1-(3,4-Dim eth oxyp h en yl)-1-(-3-(3,4-m e-
t h y le n e d io x y p h e n y l)-2-p r o p e n y lo x y )-2,3-e p o x y p r o -
p a n e (4g). Compound 4g was prepared from 3b and 6a by
the same procedure as described for 4a : yield 84%; IR (neat)
2999, 2935, 2837, 1606, 1593, 1514, 1504, 1463, 1444, 1352,
1251, 1234 cm-1; 1H NMR δ 2.59-2.81 (m, 2H), 3.16-3.19 (m,
1/2H), 3.21-3.25 (m, 1/2H), 3.81-4.34 (m, 3H), 3.88, 3.89 (2s, 2
× OCH3), 5.93 (s, 2H), 6.04-6.17 (m, 1H), 6.46 (dd, J ) 15.8,
9.7 Hz, 1H), 6.72-6.93 (m, 6H, ArH); 13C NMR δ 44.3, 45.0,
54.3, 55.2, 55.8, 69.3, 69.4, 79.5, 82.1, 100.9, 105.6, 108.1, 109.8,
110.1, 110.9, 119.5, 119.8, 121.0, 123.8, 130.6, 131.0, 132.3,
147.2, 147.9, 148.9, 149.0. Anal. Calcd for C21H22O6: C, 68.09;
H, 5.99. Found: C, 68.02; H, 6.00.
Typ ica l P r oced u r e for Ra d ica l Cycliza tion of th e
Ep oxy Eth er s 4a -g: Syn th esis of Dih yd r osesa m in (1a ).
A solution of Cp2TiCl2 (73 mg, 0.292 mmol) in dry THF (5 mL)
was stirred with activated zinc dust (58 mg, 0.89 mmol) for 1
h under argon (activated zinc dust was prepared by washing
20 g of commercially available zinc dust with 60 mL of 4 N
HCl, thorough washing with water and finally with dry
acetone, and then drying in vacuo). The resulting green
solution was then added dropwise to a stirred solution of the
epoxide 4a (45 mg, 0.127 mmol) in dry THF (4 mL) at room
temperature under argon during 30 min. The reaction mixture
was stirred for an additional 1 h and decomposed with 10%
H2SO4 (5 mL). After removal of most of the tetrahydrofuran
under reduced pressure, the resulting residue was extracted
with diethyl ether (4 × 25 mL). The combined ether extract
was washed successively with saturated NaHCO3 (2 × 10 mL)
and brine (1 × 10 mL) and dried (Na2SO4). Solvent was
removed under reduced pressure, and the brown gummy
residue obtained was purified by column chromatography over
silica gel (40% ethyl acetate-light petroleum) to furnish a
colorless viscous liquid (41 mg, 90%) as a mixture of two
isomers in a ratio of 5:1. The major isomer was separated by
preparative TLC to afford 1a (29 mg, 64%): IR (neat) 3020,
2927, 2889, 1556, 1539, 1519, 1504, 1488, 1442, 1421, 1215
cm-1; 1H NMR δ 1.61 (br s, OH), 2.32-2.37 (m, 1H), 2.53 (dd,
J ) 13.2, 10.3 Hz, 1H), 2.63-2.76 (m, 1H), 2.87 (dd, J ) 13.2,
5.1 Hz, 1H), 3.69-3.78 (m, 2H), 3.89 (dd, J ) 10.6, 6.9 Hz,
1H), 4.04 (dd, J ) 8.4, 6.4 Hz, 1H), 4.79 (d, J ) 6.4 Hz, 1H),
5.93 (s, OCH2O), 5.94 (s, OCH2O), 6.62-6.83 (m, 6H, ArH);
13C NMR δ 33.3, 42.3, 52.6, 60.9, 72.9, 82.9, 100.8, 100.9, 106.3,
108.1, 108.3, 108.9, 119.0, 121.4, 134.2, 137.1, 145.9, 146.9,
147.8, 147.8.
OCH3), 4.04 (dd, J ) 8.4, 6.6 Hz, 1H), 4.78 (d, J ) 6.3 Hz,
1H), 5.13 (s, OCH2Ph), 5.94 (s, OCH2O), 6.65-6.84 (m, 6H,
ArH), 7.29-7.45 (m, 5H, ArH); 13C NMR δ 33.1, 42.2, 52.7,
56.0, 60.8, 71.1, 72.9, 82.7, 100.9, 106.2, 108.0, 112.4, 114.2,
119.0, 120.4, 127.2, 127.7, 128.4, 133.5, 136.1, 137.0, 146.6,
146.8, 147.8, 149.6. Anal. Calcd for C27H28O6: C, 72.30; H, 6.29.
Found: C,72.08; H, 6.25.
Syn th esis of Acu m in a tin Meth yl Eth er (1e). Compound
1e was prepared from 4e by the same procedure as described
for 1a : yield 63%; IR (neat) 3018, 2937, 1591, 1516, 1489, 1466,
1443, 1215 cm-1 1H NMR δ 1.56 (br s, OH), 2.33-2.42 (m,
;
1H), 2.56 (dd, J ) 13.2, 10.6 Hz, 1H), 2.68-2.78 (m, 1H), 2.92
(dd, J ) 13.2, 5.0 Hz, 1H), 3.72-3.95 (m, 3H), 3.86, 3.87(2s, 2
× OCH3), 4.05 (dd, J ) 8.5, 6.5 Hz, 1H), 4.79 (d, J ) 6.5 Hz,
1H), 5.94 (s, OCH2O), 6.68-6.88 (m, 6H, ArH); 13C NMR δ 33.1,
42.3, 52.7, 55.9, 60.9, 72.9, 82.8, 100.9, 106.3, 108.0, 111.3,
111.9, 119.1, 120.4, 132.9, 137.0, 146.9, 147.5, 147.8, 149.0.
P r ep a r a tion of La r icir esin ol Meth yl Ben zyl Eth er (1f).
Compound 1f was prepared from 4f by the same procedure as
described for 1a : yield 60%; IR (neat) 3016, 2933, 2850, 1732,
1606, 1593, 1514, 1463, 1454, 1417, 1261, 1217 cm-1; 1H NMR
δ 2.37-2.46 (m, 1H), 2.55 (dd, J ) 13.2, 10.5 Hz, 1H), 2.68-
2.81 (m, 1H), 2.91 (dd, J ) 13.5, 5.1 Hz, 1H), 3.71-3.81 (m,
2H), 3.81-3.97 (m, 1H), 3.87, 3.88, 3.90 (3s, 3 × OCH3), 4.06
(dd, J ) 8.4, 6.3 Hz, 1H), 4.81 (d, J ) 6.3 Hz, 1H), 5.12 (s, 2 ×
OCH2Ph), 6.65-6.88 (m, 6H, ArH), 7.29-7.45 (m, 5H, ArH);
13C NMR δ 33.2, 42.2, 52.5, 55.8, 55.9, 56.0, 60.9, 71.1, 72.9,
82.7, 108.9, 110.9, 112.5, 114.2, 118.0, 120.4, 127.2, 127.7,
128.5, 133.6, 135.4, 137.2, 146.6, 148.4, 149.0, 149.6. Anal.
Calcd for C28H32O6: C, 72.39; H, 6.94. Found: C, 72.27; H,
6.87.
Syn th esis of Sa n sh od iol Meth yl Eth er (1g). Compound
1g was prepared from 4g by the same procedure as described
for 1a : yield 62%; IR (neat) 3018, 1556, 1539, 1517, 1506, 1488,
1247, 1215 cm-1; 1H NMR δ 2.36-2.45 (m, 1H), 2.55 (dd, J )
13.5, 10.5 Hz, 1H), 2.66-2.76 (m, 1H), 2.89 (dd, J ) 13.2, 5.1
Hz, 1H), 3.71-3.80 (m, 2H), 3.84-3.97 (m, 1H), 3.87, 3.88 (2s,
2 × OCH3), 4.07 (dd, J ) 8.4, 6.6 Hz, 1H), 4.82 (d, J ) 6.6 Hz,
1H), 5.93 (s, OCH2O), 6.64-6.90 (m, 6H, ArH); 13C NMR δ 33.3,
42.3, 52.4, 55.9, 61.0, 72.8, 82.8, 100.8, 108.2, 108.9, 108.9,
111.0, 118.0, 121.4, 134.1, 135.4, 147.7, 147.7, 148.4, 149.1.
Syn th esis of La r icir esin ol (1h ). Compound 1c (30 mg,
0.05 mmol) was subjected to hydrogenolysis in ethyl acetate
(5 mL) with 10% Pd-C (15 mg) at room temperature for 1.5
h. The catalyst was filtered off, and the filtrate was concen-
trated under reduced pressure to furnish 1h (19 mg, 95%) as
a colorless oil: IR (neat) 3018, 1608, 1514, 1465, 1431, 1267,
Syn th esis of La r icir esin ol Dim eth yl Eth er (1b). Com-
pound 1b was prepared from 4b by the same procedure as
described for 1a : yield 63%; IR (neat) 3440, 3016, 2937, 2910,
2837, 1712, 1593, 1514, 1465, 1419, 1261,1217 cm-1; 1H NMR
δ 2.38-2.47 (m, 1H), 2.57 (dd, J ) 13.3, 10.5 Hz, 1H), 2.69-
2.79 (m, 1H), 2.93 (dd, J ) 13.3, 5.0 Hz, 1H), 3.73-3.82 (m,
2H), 3.86-3.96 (m, 1H), 3.86, 3.87, 3.88 (4s, 4 × OCH3), 4.06
(dd, J ) 8.5, 6.6 Hz, 1H), 4.81 (d, J ) 6.5 Hz, 1H), 6.71-6.88
(m, 6H, ArH); 13C NMR δ 33.7, 42.8, 52.9, 56.3, 61.4, 73.3, 83.1,
109.4, 111.4, 111.8, 112.4, 118.4, 120.9, 133.3, 135.8, 147.9,
148.8, 149.4, 149.5.
1
1209 cm-1; H NMR δ 2.36-2.45 (m, 1H), 2.55 (dd, J ) 13.2,
10.5 Hz, 1H), 2.67-2.79 (m, 1H), 2.92 (dd, J ) 13.8, 4.8 Hz,
1H), 3.72-3.80 (m, 2H), 3.87-3.94 (m, 1H), 3.87, 3.89 (2s, 2 ×
OCH3), 4.05 (dd, J ) 8.4, 6.6 Hz, 1H), 4.78 (d, J ) 6.6 Hz,
1H), 5.51, 5.59 (2s, 2 × PhOH), 6.68-6.89 (m, 6H, ArH); 13C
NMR δ 33.3, 42.4, 52.6, 55.9, 55.9, 60.9, 72.9, 82.8, 108.3, 111.2,
114.1, 114.4, 118.7, 121.2, 132.2, 134.8, 144.0, 145.0, 146.5,
146.6.
Syn th esis of Acu m in a tin (1i). Compound 1i was prepared
from 1d by the procedure as described for 1h : yield 95%; IR
P r ep a r a tion of La r icir esin ol Diben zyl Eth er (1c).
Compound 1c was prepared from 4c by the same procedure
as described for 1a : yield 61%; IR (neat) 3018, 2935, 1649,
(neat) 3018, 1514, 1488, 1215, 1039 cm-1 1H NMR δ 2.33-
;
1
1539, 1512, 1456, 1259, 1215 cm-1; H NMR δ 2.36-2.45 (m,
2.42 (m, 1H), 2.54 (dd, J ) 13.2, 10.5 Hz, 1H), 2.66-2.79 (m,
1H), 2.90 (dd, J ) 13.5, 5.1 Hz, 1H), 3.72-3.80 (m, 2H), 3.83-
3.97 (m, 1H), 3.87 (s, OCH3), 4.04 (dd, J ) 8.4, 6.3 Hz, 1H),
4.78 (d, J ) 6.3 Hz, 1H), 5.50 (s, PhOH), 5.94 (s, OCH2O),
6.65-6.91 (m, 6H, ArH); 13C NMR δ 33.2, 42.4, 52.7, 55.9, 60.9,
72.9, 82.8, 100.9, 106.3, 108.0, 111.1, 114.3, 119.0, 121.2, 132.2,
137.0, 143.9, 146.5, 146.8, 147.8.
1H), 2.55 (dd, J ) 13.2, 10.5 Hz, 1H), 2.67-2.79 (m, 1H), 2.90
(dd, J ) 13.5, 5.1 Hz, 1H), 3.71-3.81 (m, 2H), 3.86-3.95 (m,
1H), 3.87, 3.89 (2s, 2 × OCH3), 4.05 (dd, J ) 8.7, 6.6 Hz, 1H),
4.79 (d, J ) 6.5 Hz, 1H), 5.12, 5.14 (2s, 2 × OCH2Ph), 6.65-
6.90 (m, 6H, ArH), 7.29-7.45 (m, 10H, ArH); 13C NMR δ 33.2,
42.2, 52.4, 56.0, 60.9, 71.1, 71.1, 72.9, 82.7, 109.5, 112.5, 113.9,
114.2, 117.9, 120.4, 127.2, 127.7, 128.5, 133.6, 136.0, 137.2,
146.6, 149.7. Anal. Calcd for C34H36O6: C, 75.53; H, 6.71.
Found: C, 75.16; H, 6.80.
Syn t h esis of La r icir esin ol Mon om et h yl E t h er (1j).
Compound 1j was prepared from 1f by the procedure as
described for 1h : yield 95%; IR (neat) 3018, 2922, 2850, 1704,
1
P r ep a r a tion of Acu m in a tin Ben zyl Eth er (1d ). Com-
pound 1d was prepared from 4d by the same procedure as
described for 1a : yield 60%; IR (neat) 3018, 2933, 1733, 1510,
1488, 1444, 1215 cm-1; 1H NMR δ 2.33-2.42 (m, 1H), 2.54 (dd,
J ) 13.2, 10.5 Hz, 1H), 2.69-2.77 (m, 1H), 2.90 (dd, J ) 13.2,
4.8 Hz, 1H), 3.71-3.79 (m, 2H), 3.79-3.96 (m, 1H), 3.88 (s,
1685, 1652, 1514, 1461, 1419, 1263, cm-1; H NMR δ 2.37-
2.47 (m, 1H), 2.55 (dd, J ) 13.0, 10.8 Hz, 1H), 2.68-2.77 (m,
1H), 2.92 (dd, J ) 13.5, 5.1 Hz, 1H), 3.73-3.79 (m, 2H), 3.82-
3.96 (m, 1H), 3.87, 3.87, 3.88(3s, 3 × OCH3), 4.06 (dd, J ) 8.4,
6.6 Hz, 1H), 4.81 (d, J ) 6.6 Hz, 1H), 5.48 (s, PhOH), 6.65-
6.94 (m, 6H, ArH); 13C NMR δ 33.4, 42.5, 52.6, 55.5, 55.9, 61.1,