ORGANIC
LETTERS
2011
Vol. 13, No. 14
3620–3623
Concise Entry to Both Enantiomers of
8-Oxabicyclo[3.2.1]oct-3-en-2-one Based
on Novel Oxidative Etherification: Formal
Synthesis of (þ)-Sundiversifolide
Muneo Kawasumi, Naoki Kanoh, and Yoshiharu Iwabuchi*
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences,
Tohoku University, Aobayama, Sendai 980-8578, Japan
Received May 12, 2011
ABSTRACT
Both enantiomers of 8-oxabicyclo[3.2.1]oct-3-en-2-one (6) have been synthesized from 4-hydroxycyclohept-2-enone (3) on the basis of a novel
oxidative cyclo-etherification using PhI(OH)OTs (Koser’s reagent). (ꢀ)-(1S,5R)-8-Oxabicyclo[3.2.1]oct-3-en-2-one [(ꢀ)-6, 95% ee] was
expeditiously transformed to (þ)-sundiversifolide (1).
The diastereoselective functionalization of a cycloheptane
derivative often poses challenges to synthetic chemists owing
to the inherent conformational uncertainties. To address this
issue, the structural motif of 8-oxabicyclo[3.2.1]octanes1 with
definite stereoelectronic basis has often served as a useful
platform for the manipulation of cycloheptane derivatives.2
Current methods of securing an 8-oxabicyclo[3.2.1]
octane skeleton rely predominantly on [4 þ 3]-3 or [5 þ 2]-
type4 cycloaddition reactions: Unfortunately, they typi-
cally require many steps in the elaboration of the sub-
strates, particularly in the case of enantioselective
synthesis. We envisioned that 8-oxabicyclo[3.2.1]oct-3-
en-2-one (6)5 would be accessible from 4-hydroxycyclo-
hept-2-enone (3) via an oxidative transformation.
In this paper, we disclose a concise entry to both enantio-
mers of 8-oxabicyclo[3.2.1]oct-3-en-2-one (6), featuring
PhI(OH)OTs6 (Koser’s reagent)-mediated, intramolecular
oxidative etherification7 of 4-hydroxycyclohept-2-enone
(3). We also demonstrate its use by converting (ꢀ)-6 to
(þ)-sundiversifolide (1), which was isolated from the
(1) For reviews, see: (a) Hartung, I. V.; Hoffmann, H. M. R. Angew.
Chem., Int. Ed. 2004, 43, 1934. (b) Harmata, M. Adv. Synth. Catal. 2006,
348, 2297.
(2) For reviews, see: (a) Battiste, M. A.; Pelphrey, P. M.; Wright,
D. L. Chem.;Eur. J. 2006, 12, 3438. (b) Harmata, M. Chem. Commun.
2010, 8886.
(3) For selected examples, see: (a) Orugunty, R. S.; Wright, D. L.;
Battiste, M. A.; Abboud, K. A. Org. Lett. 2002, 4, 1997. (b) Pelphrey,
P. M.; Abboud, K. A.; Wright, D. L. J. Org. Chem. 2004, 69, 6931. (c)
Chung, W. K.; Lam, S. K.; Lo, B.; Liu, L. L.; Wong, W.-T.; Chiu, P. J.
Am. Chem. Soc. 2009, 131, 4556.
(4) For selected examples, see: (a) Hendrickson, J. B.; Farina, J. S.
J. Org. Chem. 1980, 45, 3359. (b) Hendrickson, J. B.; Farina, J. S. J. Org.
Chem. 1980, 45, 3361. (c) Sammes, P. G.; Street, L, J. J. Chem. Soc.,
Chem Commun. 1982, 1056. (d) Wender, P. A.; Mascarenas, J. L.
Tetrahedron Lett. 1992, 33, 2115. (e) Padwa, A.; Weingarten, M. D.
Chem. Rev. 1996, 96, 223. (f) Ali, M. A.; Bhogal, N.; Findlay, J. B. C.;
Fishwick, C. W. G. J. Med. Chem. 2005, 48, 5655. (g) Snider, B. B.;
Grabowski, J. F. Tetrahedron Lett. 2005, 46, 823. (h) Snider, B. B.;
Grabowski, J. F. Tetrahedron 2006, 62, 5171. (i) Snider, B. B.; Wu, X. X.;
Nakamura, S.; Hashimoto, S. Org. Lett. 2007, 9, 873. (j) Garnier, E. C.;
Liebeskind, L. S. J. Am. Chem. Soc. 2008, 130, 7449. (k) Shimada, N.;
Hanari, T.; Kurosaki, Y.; Takeda, K.; Anada, M.; Nambu, H.; Shiro,
M.; Hashimoto, S. J. Org. Chem. 2010, 75, 6039.
(5) For a previous synthesis of 6, see: Fattori, D.; Henry, S.; Vogel, P.
Tetrahedron 1993, 49, 1649.
(6) (a) Moriarty, R. M.; Vaid, R. K.; Koser, G. F. Synlett 1990, 365.
(b) Koser, G. F. Aldrichim. Acta 2001, 34, 89. (c) Nabana, T.; Togo, H.
J. Org. Chem. 2002, 67, 4362. (d) Ueno, M.; Nabana, T.; Togo, H. J. Org.
Chem. 2003, 68, 6424. (e) Yamamoto, Y.; Togo, H. Synlett 2006, 798. (f)
Yamamoto, Y.; Kawano, Y.; Toy, P. H.; Togo, H. Tetrahedron 2007, 63,
4680. (g) Akiike, J.; Yamamoto, Y.; Togo, H. Synlett 2007, 2168.
(7) For similar oxidative etherification induced by hypervalent indine
compounds, see: (a) Fan, R.; Sun, Y.; Ye, Y. Org. Lett. 2009, 11, 5174.
(b) Ye, Y.; Wang, L.; Fan, R. J. Org. Chem. 2010, 75, 1760. (c) Uyanik,
M.; Okamoto, H.; Yasui, T.; Ishihara, K. Science 2010, 328, 1376.
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10.1021/ol201273b
Published on Web 06/09/2011
2011 American Chemical Society