Stereoselective Synthesis of Lignans of Three Structural Types
gel chromatography with 1:2 pentane/EtOAc to yield title com-
pound 1 as a white solid (150 mg, 54%), m.p. (pentane/EtOAc)
114–115 °C. [α]D = +47.6 (c = 1, CHCl3); ref.[18] +44 (c = 1,
CHCl3). 1H NMR (400 MHz, CDCl3): δ = 3.09 (ddd, 2 H, m,
CHCH), 3.82 (s, 6 H, 2ϫ OMe), 3.87 (s, 12 H, 4ϫ OMe), 3.94
(dd, J = 3.5, 9.2 Hz, 2 H, OCHH), 4.31 (dd, J = 6.8, 9.1 Hz, 2 H,
OCHH), 4.75 (d, J = 4.1 Hz, 2 H, ArCH), 6.56 (s, 4 H, HAr) ppm.
13C NMR (101 MHz, CDCl3): δ = 54.2 (CHCH), 56.0 (m-OMe),
60.8 (p-OMe), 72.0 (CH2O), 85.8 (ArCH), 102.5 (CHAr), 136.7
(CAr), 137.5 (CAr), 153.3 (CAr) ppm. MS (ES): m/z [M + H]+469.09.
HRMS: calcd. for C24H30O8Na [M + H]+ 469.1838; found
469.1838. C24H30O8 (446.50): calcd. C 64.56, H 6.77; found C
64.55, H 6.82. HPLC (CHIRALPAK® IB Column, 60:40 heptane/
EtOH; 1.0 mL/min), tR(major enantiomer) = 8.38 min, tR(minor
enantiomer) = 13.52 min, 83% ee.
(CAr), 150.5 (CAr), 150.8 (CAr), 151.0 (CAr), 198.6 (C=O) ppm.
MS (ES): m/z [M + H]+ 445.14. HRMS: calcd. for C24H29O8 [M +
H]+ 445.1862; found 445.1860.
((3RS,4RS)-4-{(RS)-[(SR)-tert-Butylsulfinyl](3,4,5-trimethoxyphen-
yl)methyl}tetrahydrofuran-3-yl)(3,4,5-trimethoxyphenyl)methanone
[(؎)-17]: To a stirred solution of aldol (؎)-4 (335 mg, 0.47 mmol)
in acetonitrile (3 mL) trifluoroacetic acid (55 mg, 36 μL,
0.48 mmol) was added dropwise. The reaction mixture was stirred
at room temperature for 3 h and the reaction mixture was poured
onto water, quenched with NaHCO3 (2 mL) and extracted with
CH2Cl2 (3ϫ 5 mL). The combined organic extracts were dried with
magnesium sulfate and concentrated in vacuo to yield a mixture
(2:1) of cyclised compounds with the above compound as the major
product. The crude mixture was purified by using column
chromatography on silica (1:1, pentane/ethyl acetate) to yield title
compound (؎)-17 (132 mg, 0.24 mmol, 52%), m.p. (toluene/cyclo-
hexane) 158–161 °C. 1H NMR (300 MHz, CDCl3): δ = 1.12 [s, 9
H, C(CH3)3], 3.47 (obscured, 1 H, CH), 3.51 (s, 3 H, OMe), 3.73
(s, 6 H, OMe), 3.83 (s, 6 H, OMe), 3.85 (s, 3 H, OMe), 3.95 (m, 3
H, obscured, CH2O,CH), 4.11 (bdd, 2 H,CH2O), 4.39 (d, 1 H,
CHSO), 6.34 (s, 2 H, HAr), 6.78 (s, 2 H, HAr) ppm. 13C NMR
(125 MHz, CDCl3): δ = ppm 23.80 [C(CH3)3], 29.90 [C(CH3)3]
43.79, 49.36, 56.21 (CH3), 56.31 (2ϫ CH3), 56.56 (CH3), 60.58 (2ϫ
CH3), 103.94 (2ϫ CHAr), 107.64 (2ϫ CHAr), 116.57 (CAr) 131.60
(2ϫ CAr), 139.01 (CAr), 153.41 (2ϫ CAr), 153.71 (2ϫ CAr), 191.22
When this reaction was carried out with racemic starting material
rac-[(2S,3R,4R,5S)-2,5-bis(3,4,5-trimethoxyphenyl)tetrahydro-
furan-3,4-diyl]dimethanol (2a) was also isolated as a white solid in
1
10% yield. H NMR (400 MHz, CDCl3): δ = 2.28–2.38 (m, 2 H,
CH, CH), 3.28–3.41 (br. s, 2 H, OH), 3.64–3.72 (m, 2 H, CH2OH),
3.84–3.88 (m, 20 H, 6ϫ OMe, CH2OH), 4.79 (d, J = 8.8 Hz, 2 H,
CHO,CHO), 6.61 (s, 4 H, HAr) ppm. 13C NMR (101 MHz, CDCl3):
δ = 56.2 (m-OCH3), 56.8 (CH, CH), 60.8 (p-OCH3), 62.9 (CH2),
83.4 (CH,CH), 103.1 (CHAr), 137.2 (CAr), 137.6 (CAr), 153.3
(CAr) ppm. MS (ES): m/z [M + H]+ 487.14. HRMS: calcd. for
C24H32O9Na [M + H]+ 487.1944; found 487.1941.
(C=O) ppm. IR (KBr) ν = 2950, 2840, 1587, 1506, 1464, 1410,
˜
1148 cm–1. C28H38O9S (550.66): calcd. C 61.07, H 6.96; found C
60.96, H 6.72.
When this reaction was carried out with racemic starting material
rac-[(2S,3R,4R,5R)-2,5-bis(3,4,5-trimethoxyphenyl)tetrahydro-
furan-3,4-diyl]dimethanol (2b) was also isolated as a white solid in
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra for compounds 1, 2a, 2b, 3, 4, 6, 8
1
15% yield. H NMR (400 MHz, CDCl3): δ = 2.24–2.34 (m, 1 H,
and 9. X-ray crystal structures for compounds 2b and 17.
CH), 2.57–2.67 (m, 1 H, CH), 3.15–3.22 (br. t, 1 H, CH2OH), 3.41
(dd, J = 4.7, 10.7 Hz, 1 H, CH2OH), 3.67 (dd, J = 8.5, 10.5 Hz, 1
H, CH2OH), 3.83 (s, 4 H, OMe, obscured CH2OH), 3.85 (s, 9 H,
OMe), 3.88 (s, 6 H, OMe), 4.55 (d, J = 9.1 Hz, 1 H, CHO), 5.13
(d, J = 8.4 Hz, 1 H, CHO), 6.62 (s, 2 H, HAr), 6.73 (s, 2 H,
HAr) ppm. 13C NMR (101 MHz, CDCl3): δ = 50.7 (CH), 54.8
(CH), 56.0 (OCH3), 56.1 (OCH3), 60.85 (OCH3), 60.89 (OCH3),
63.1 (CH2), 63.5 (CH2), 81.4 (CH), 82.6 (CH), 103.4 (CHAr), 103.6
(CHAr), 134.4 (CAr), 135.9 (CAr), 137.8 (CAr), 153.1 (CAr), 153.3
(CAr) ppm. MS (ES): m/z [M + H]+ 487.14. HRMS: calcd. for
C24H32O9Na [M + H]+ 487.1944; found 487.1943.
Acknowledgments
The authors thank the University College Dublin for financial sup-
port, Dr Helge Müller-Bunz for carrying out the X-ray structure
determinations, and Dr Yannick Ortin for assistance with NMR
experiments.
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6,7-dihydro-6,12-methanodibenzo[a,d][8]annulen-5(12H)-one (O,O-
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(3ϫ 5 mL). The organic extracts were dried with magnesium sulf-
ate and concentrated in vacuo to yield the crude title compound.
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= 17.2, 7.1 Hz, 1 H, CH2), 3.58 (dd, J = 10.2, 9.8 Hz, 1 H,
CH2OH), 3.68 (ddd, J = 10.2, 6.2, 2.7 Hz, 1 H, CH2OH), 3.79 (s,
3 H, OMe), 3.80 (s, 3 H, OMe), 3.82 (s, 3 H, OMe), 3.84 (s, 3 H,
OMe), 3.94 (s, 3 H, OMe), 4.03 (s, 3 H, OMe), 4.52 (br. s, 1 H,
CH), 6.84 (s, 1 H, HAr), 7.29 (s, 1 H, HAr) ppm. 13C NMR
(126 MHz, CDCl3): δ = 27.2 (CH2), 32.8 (CH), 41.5 (CH), 42.3
(CH), 54.9 (CH3), 59.2 (CH3), 59.6 (CH3), 59.8 (CH3), 60.3 (CH3),
62.9 (CH2OH), 104.6 (CHAr), 106.4 (CHAr), 117.8 (CAr), 125.2
(CAr), 132.9 (CAr), 135.1 (CAr), 139.7 (CAr), 146.6 (CAr), 148.9
Eur. J. Org. Chem. 2014, 5549–5556
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