Scheme 4 Plausible reaction mechanism.
a 1,3-diequatorial relationship. The intramolecular aldol-type
cyclization then occurs to give 2,5-cis-THF. On the other hand,
the transition state, TS-II, from 2,4-trans-1,3-dioxepin is relatively
unfavorable due to the 1,3-axial-equatorial disposition of the two
substituents. Therefore, stereomutation of the geometry of the
oxocarbenium ion from Z to E occurs to give a favorable chair-
like transition state. It is also known that the E configurations are
energetically more preferable than the Z configurations in mono-
substituted oxocarbenium ions.8 In addition, the more polar
solvent stabilizes the oxocarbenium ion, thus lowering the
oxocarbenium ion rotation barrier.9 Conformational control in
the transition state may also assist in the rotation process.
Scheme 5 Application to synthesis of the THF fragment of
(À)-amphidinolide K.
Science and Technology, the Japanese Government. The
financial support from the Hoansha Foundation and the
Uehara Memorial Foundation is also acknowledged.
Notes and references
1 For selected reviews, see: (a) T. L. B. Boivin, Tetrahedron, 1987,
43, 3309; (b) J. C. Harmange and B. Figadere,
Tetrahedron: Asymmetry, 1993, 4, 1711; (c) J. P. Wolfe and
M. B. Hay, Tetrahedron, 2007, 63, 261; (d) G. Jalce, X. Franck
and B. Figadere, Tetrahedron: Asymmetry, 2009, 20, 2537.
2 (a) H. Suzuki, H. Yashima, T. Hirose, M. Takahashi, Y. Morooka
and T. Ikawa, Tetrahedron Lett., 1980, 21, 4927; (b) H. Frauenrath,
J. Runsink and H. D. Scharf, Chem. Ber., 1982, 115, 2728;
(c) H. Frauenrath and J. Runsink, J. Org. Chem., 1987, 52, 2707;
(d) C. G. Nasveschuk, N. T. Jui and T. Rovis, Chem. Commun., 2006,
3119; (e) C. G. Nasveschuk and T. Rovis, J. Org. Chem., 2008, 73, 612.
3 (a) H. Fujioka, T. Okitsu, Y. Sawama, N. Murata, R. Li and Y. Kita,
J. Am. Chem. Soc., 2006, 128, 5930; (b) H. Fujioka, T. Okitsu,
T. Ohnaka, R. Li, O. Kubo, K. Okamoto, Y. Sawama and Y. Kita,
J. Org. Chem., 2007, 72, 7898; (c) H. Fujioka, T. Okitsu, T. Ohnaka,
Y. Sawama, O. Kubo, K. Okamoto and Y. Kita, Adv. Synth. Catal.,
2007, 349, 636.
4 TMSOTf was more effective than TESOTf in this case.
5 N. Dieltiens, C. V. Stevens, K. Masschelein, G. Hennebel and
S. Van der Jeught, Tetrahedron, 2008, 64, 4295. And see also ref. 2a.
6 Further reduction of the TfOH amount below 0.5 equiv. only
delayed the reaction rate without any improvement in selectivity.
7 DMSO gave as similar 2,5-cis selectivity as DMF, but longer
reaction time was needed.
For further application of this reaction, we synthesized a
fragment of (À)-amphidinolide K,10,11 which was isolated
from the Okinawan flatworm Amphiscolops sp12 containing a
2,5-cis-2,3,5-trisubstituted THF framework in its structure.
Synthesis of the (À)-amphidinolide K fragment began with
the mixed acetalization of 7 prepared by THF-protection
of the known (R)-1-(benzyloxy)but-3-en-2-ol.13 Desilylation
afforded the alcohol 8 in 86% yield over two steps. Benzoyl
protection followed by the RCM-isomerization sequential
protocol resulted in 1,3-dioxepin 10 (dr = 1 : 1) in 57%
yield over three steps. The key ring contraction gave the
(À)-amphidinolide K fragment 11 in 55% yield with over a
30 : 1 ratio of the 2,5-cis to trans isomers (Scheme 5).
In summary, we have developed a novel diastereoselective
ring contraction of 2,4-disubstituted 1,3-dioxepins for the
stereocontrolled construction of 2,5-cis-2,3,5-trisubstituted
THFs. In these reactions, the stereochemical outcome at the
2-position of the THFs does not depend on the stereo-
chemistry of the starting material and 2,5-cis-THF is always
preferred. The reactions are effective for the synthesis of a wide
range of 2,5-cis-2,3,5-trisubstituted THFs. The synthetic
application of this reaction was demonstrated in the synthesis
of the THF fragment of (À)-amphidinolide K. Studies related to
the construction of complex oxacycles are currently underway.
This work was financially supported by a Grant-in-Aid
for Scientific Research (B) and for Scientific Research for
Exploratory Research and Research Fellowships for Young
Scientists from the Japan Society for the Promotion of Science
(JSPS) and Special Coordination Funds for Promoting Science
and Technology of the Ministry of Education, Culture,
8 J. L. Broeker, R. W. Hoffmann and K. N. Houk, J. Am. Chem.
Soc., 1991, 113, 5006.
9 (a) D. Cremer, J. Gauss, R. F. Childs and C. Blackburn, J. Am.
Chem. Soc., 1985, 107, 2435. Recent report, see: (b) L. Liu and
P. E. Floreancig, Angew. Chem., Int. Ed., 2010, 49, 5894.
10 For the total synthesis of (+)-amphidinolide K, see:
D. R. Williams and K. G. Meyer, J. Am. Chem. Soc., 2001,
123, 765. For the total synthesis of (À)-amphidinolide K, see:
H. M. Ko, C. W. Lee, H. K. Kwon, H. S. Chung, S. Y. Choi,
Y. K. Chung and E. Lee, Angew. Chem., Int. Ed., 2009, 48, 2364.
11 For synthetic studies of (À)-amphidinolide K, see:
(a) D. R. Williams and K. G. Meyer, Org. Lett., 1999, 1, 1303;
(b) T. Andreou, A. M. Costa, L. Esteban, L. Gonzalez, G. Mas and
J. Vilarrasa, Org. Lett., 2005, 7, 4083; (c) H. Zhu, J. G. Wickenden,
N. E. Campbell, J. C. T. Leung, K. M. Johnson and
G. M. Sammis, Org. Lett., 2009, 11, 2019.
12 M. Ishibashi, M. Sato and J. Kobayashi, J. Org. Chem., 1993, 58, 6928.
13 A. K. Ghosh, S. Leshchenko and M. Noetzel, J. Org. Chem., 2004,
69, 7822.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 9197–9199 9199