Y. R. Lee, L. Xia / Tetrahedron Letters 49 (2008) 3283–3287
3287
O
O
H
H
6a
6b
OH
OH
OH
H
EDDA/TEA
xylene
reflux, 24 h
EDDA/TEA
xylene
reflux, 24 h
H
H
H
HO
O
O
26
4
3
72%
73%
Scheme 3.
11. (a) Lee, Y. R.; Kim, J. H. Synlett 2007, 2232; (b) Lee, Y. R.; Lee, W.
K.; Noh, S. K.; Lyoo, W. S. Synthesis 2006, 853; (c) Lee, Y. R.; Kim,
D. H. Synthesis 2006, 603.
12. (a) Wang, X.; Lee, Y. R. Tetrahedron Lett. 2007, 48, 6275; (b) Wang,
X.; Lee, Y. R. Synthesis 2007, 3044; (c) Lee, Y. R.; Xia, L. Synthesis
2007, 3240.
(S)-(ꢀ)-citronellal (6b) for 24 h afforded the unnatural
product 4 in 73% yield. The specific rotation value of com-
pound 3 was [a]D ꢀ85.4 (c 0.30, CHCl3), whereas that of
compound 4 was [a]D +86.9 (c 0.10, CHCl3).22 The spectro-
scopic data of compounds 3 and 4 were in agreement with
the reported data.19
In conclusion, a new and efficient synthetic route for
biologically interesting cannabinoids was developed start-
ing from commercially available resorcinols and optically
pure citronellals utilizing the hetero Diels–Alder reaction
as the key step. This synthetic route provided the biologi-
cally interesting natural (ꢀ)-hexahydrocannabinol (3) and
its unnatural (+)-hexahydrocannabinol (4).
13. Spectral data for compound 7: 1H NMR (CDCl3, 300 MHz) d 11.35
(1H, s), 7.70–7.50 (2H, m), 6.43 (1H, d, J = 16.6 Hz), 6.07 (1H, dd,
J = 16.6, 7.8 Hz), 5.10 (1H, t, J = 7.1 Hz), 3.89 (3H, s), 2.40–2.31 (1H,
m), 2.06–1.99 (2H, m), 1.62 (3H, s), 1.58 (3H, s), 1.45–1.37 (2H, m),
1.10 (3H, d, J = 6.7 Hz); IR (neat) 3406, 2955, 1667, 1618, 1499, 1439,
1341, 1273, 1204, 1150, 984, 791 cmꢀ1
.
14. Spectral data for compound 8: 1H NMR (CDCl3, 300 MHz) d 11.56
(1H, s), 7.59 (1H, d, J = 8.9 Hz), 6.29 (1H, d, J = 8.9 Hz), 3.86 (3H,
s), 3.18 (1H, br d, J = 12.8 Hz), 2.52–2.44 (1H, m), 1.86–1.80 (2H, m),
1.67–1.52 (3H, m), 1.46–1.40 (1H, m), 1.37 (3H, s), 1.14–1.10 (1H, m),
1.05 (3H, s), 0.93 (3H, d, J = 6.6 Hz); 13C NMR (CDCl3, 75 MHz) d
171.2, 162.5, 160.2, 128.6, 112.9, 109.6, 104.3, 78.3, 51.8, 48.8, 38.2,
35.4, 35.2, 32.7, 27.9, 27.5, 22.5, 19.1; IR (neat) 2949, 1663, 1622,
1582, 1489, 1439, 1339, 1260, 1209, 1138, 1086, 1069, 1003, 914,
Acknowledgments
This study was supported by Grant No. RTI04-01-04
from the Regional Technology Innovation Program of
the Ministry of Commerce, Industry, and Energy
(MOCIE).
883 cmꢀ1
.
15. Talley, J. J. J. Org. Chem. 1985, 50, 1695.
1
16. Spectral data for compound 22: H NMR (CDCl3, 300 MHz) d 8.36–
8.32 (1H, m), 7.82–7.79 (1H, m), 7.51–7.46 (2H, m), 7.43–7.39 (2H,
m), 2.66–2.54 (2H, m), 1.94–1.90 (2H, m), 1.78–1.66 (1H, m), 1.61
(3H, s), 1.58–1.49 (1H, m), 1.29–1.11 (2H, m), 1.08 (3H, d, J = 6.6 Hz)
1.00–0.96 (1H, m); 13C NMR (CDCl3, 75 MHz) d 147.8, 133.0, 127.2,
125.5, 124.8, 124.1, 122.0, 121.9, 118.7, 118.4, 77.6, 47.1, 39.7, 35.9,
34.8, 32.6, 28.0, 27.6, 22.6, 20.1; IR (neat) 3055, 2922, 1572, 1507,
References and notes
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1458, 1385, 1265, 1209, 1144, 1096, 1020, 939, 909, 847, 745 cmꢀ1
.
17. Spectral data for compound 24: 1H NMR (CDCl3, 300 MHz) d 7.93
(1H, d, J = 8.4 Hz), 7.83 (1H, d, J = 8.0 Hz), 7.67 (1H, d, J = 8.9 Hz),
7.53 (1H, dt, J = 8.4, 1.4 Hz), 7.38 (1H, dt, J = 8.0, 1.1 Hz), 7.14 (1H,
d, J = 8.9 Hz), 2.95–2.80 (1H, m), 2.07–1.95 (2H, m), 1.75–1.67 (1H,
m), 1.55 (3H, s), 1.44–1.20 (3H, m), 1.16 (3H, s), 1.05 (3H, d, J = 6.5
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36.7, 36.0, 33.3, 28.4, 27.6, 22.6, 18.4; IR (neat) 3059, 2926, 1620,
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