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References and notes
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M. Agric. Biol. Chem. 1976, 40, 303–315; (e) Behr, D.; Wahlberg, I.; Nishida, T.;
Enzell, C. R. Acta Chem. Scand. 1978, 32, 391–394; (f) D’Abrosca, B.; DellaGreca,
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2. (a) Fujimori, T.; Kasuga, R.; Noguchi, M.; Kaneko, H. Agric. Biol. Chem. 1974, 38,
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Phytochemistry 1998, 48, 631–636.
5. For the syntheses of racemic 1, see; (a) Takazawa, O.; Tamura, H.; Kogami, K.;
Hayashi, K. Bull. Chem. Soc. Jpn. 1982, 55, 1907–1911; (b) Hong, H.; Hui, D.; Shi-
Gang, Y. Chem. World 2011, 5, 299–302; For the syntheses of racemic 2, see; (a)
Loeber, D. E.; Russell, S. W.; Toube, T. P.; Weedon, C. L. J. Chem. Soc. (C) 1971,
404–408; (b) 5a.; 5a. For the syntheses of optically active 2, see; (a) Mori, K.
Tetrahedron Lett. 1973, 28, 2635–2638; (b) Mayer, H.; Rüttimann, A. Helv. Chim.
Acta 1980, 63, 1456–1462; (c) Yamano, Y.; Tobe, C.; Ito, M. J. Chem. Soc., Perkin
Trans. 1 1998, 2569–2582; (d) Khachik, F.; Chang, A. N. Synthesis 2011, 509–
516.
Scheme 5. Synthesis of 1, 3 and 4. Reagents and conditions: (a) HF-pyridine, THF/
pyridine = 4/1, 40 °C, 3 h, 87%; (b) TPAP, NMO, CH2Cl2, 0 °C, 1 h, 85%; (c) TFA, CH2Cl2,
rt, 1 h, 74%; (d) DDQ, CH2Cl2/phosphate buffer (pH 7.0) = 10/1, 0 °C, 1.5 h, quant.; (e)
MnO2, CH2Cl2, 40 °C, 24 h, 87%; (f) HFꢁpyridine, THF/pyridine = 4/1, 40 °C, 4 h, 77%;
(g)HF pyridine, THF/pyridine=4/1, 40 °C, 5 h, quant.
PMB ether was cleaved with trifluoroacetic acid producing 3-oxo-
a
-ionol (1), {½a 2D9
ꢂ
+280 (c 0.70, CHCl3); lit.1e
[
a
]
+269 (c 1.29,
D
CHCl3)}, whose spectroscopic properties matched those reported
for the natural product. On the other hand, selective deprotection
of the PMB ether of 5 with DDQ provided the allyl alcohol 19,
which was desilylated to give 3,9-dihydroxy-4,7-megastigmadiene
6. Murakami, Y.; Yoshida, M.; Shishido, K. Tetrahedron Lett. 2009, 50, 1279–1281.
and references cited therein.
7. Trost, B. M.; Corte, J. R.; Gudiksen, M. S. Angew. Chem., Int. Ed. 1999, 38, 3662–
3664.
(3), {½a 3D1
ꢂ
+182 (c 0.62, CHCl3); lit.1e
[a] +197 (c 1.54, CHCl3)}.
8. Although syntheses of racemic 1 have been reported,5 there have been no
reports of an enantioselective synthesis.
D
Sequential oxidation and desilylation of 19 produced 3-hydroxy-
9. For reports on isolation, see; Ref. 1e,f There have been no reports on its
synthesis.
a
-ionone (4), {½a D31
ꢂ
+243 (c 0.44, dioxane); lit.10
½
a 2D5
+302 (c
ꢂ
1.00, dioxane)}. The spectral properties of the synthetic 3 and 4
were identical with those for the natural products21 (Scheme 5).
In summary, we have completed the first enantiocontrolled to-
10. For the reports on isolation, see; (a) Kikuchi, M.; Machida, K. Phytochemistry
1996, 41, 1333–1336; (b) Ref. 1f For the syntheses of optically active 4, see.; (c)
Mayer, H.; Rüttimann, A. Helv. Chim. Acta 1980, 63, 1451–1466; (d) Hanspeter,
P.; Pascal, S. Aust. J. Chem. 1995, 48, 145–151; For the racemic synthesis, see;
Lutz-Wahl, S.; Fischer, P.; Schmidt-Dannert, C.; Wohlleben, W.; Hauer, B.;
Schmid, R. D. Appl. Environ. Microbiol. 1998, 64, 3878–3881.
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2009, 15, 11490–11497.
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1265–1266.
13. Suffert, J.; Toussaint, D. J. Org. Chem. 1995, 60, 3550–3553.
14. (a) Nemoto, H. Tetrahedron Lett. 1994, 35, 7785–7788; (b) Sakamoto, K.;
Nemoto, H. J. Synth. Org. Chem., Jpn. 2007, 65, 626–628.
15. Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J. Am. Chem. Soc. 1991, 113,
4092–4096.
16. Noyori, R.; Tomino, I.; Nishizawa, M. J. Am. Chem. Soc. 1979, 101, 5843–5844.
17. Midland, M. M.; McDowell, D. C.; Hatch, R. L.; Tramontano, A. J. Am. Chem. Soc.
1980, 102, 867–869.
18. Brown, H. C.; Chandrasekharan, J.; Ramachandran, P. V. J. Am. Chem. Soc. 1988,
110, 1539–1546.
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1987, 109, 7925–7926.
tal synthesis of the ionone type bisnorsesquiterpene (+)-3-oxo-a-
ionol (1) with a longest linear sequence of 12 steps and an overall
yield of 8.5%. In addition, the first total synthesis of (+)-3,9-dihy-
droxy-4,7-megastigmadiene (3) and the synthesis of (+)-3-hydro-
xy-a-ionone (4) have been accomplished from an optically pure
common precursor 5, which was synthesized by employing an
intramolecular Heck reaction as the key step in a highly diastereo-
selective fashion. Since the synthetic route developed here is effi-
cient and adaptable, our synthetic studies may contribute not
only to the synthesis of other inone type natural products but also
to the assembly of a library of ionone type compounds for the
development of new types of environmentally benign agricultural
chemicals.
20. Attempted Heck reaction of the substrate 16 possessing the unprotected
secondary alcohol moiety resulted in the formation of the cyclized product in
55% yield as a 1:1 mixture of diastereoisomers.
Acknowledgment
This work was supported financially by a Grant-in-Aid for the
Program for Promotion of Basic and Applied Research for Innova-
tions in the Bio-oriented Industry (BRAIN).
21. The homogeneity of 3 and 4 was firmly established through spectroscopic
analyses, particularly by the 13C NMR.