ORGANIC
LETTERS
2002
Vol. 4, No. 25
4451-4453
CeCl3‚7H O−NaI Catalyzed
2
Hydrooxacyclization of Unsaturated
3-Hydroxy Esters
Emanuela Marotta, Elisabetta Foresti,† Tommaso Marcelli, Francesca Peri,
Paolo Righi, Noemi Scardovi, and Goffredo Rosini*
Dipartimento di Chimica Organica “A. Mangini” and Dipartimento di Chimica
“G. Ciamician”, Alma Mater Studiorum, UniVersita` di Bologna, Italy
Received September 25, 2002
ABSTRACT
Cerium(III) chloride heptahydrate and sodium iodide in boiling acetonitrile promote cyclization of 3-hydroxyalkenoic acids esters giving
5-substituted tetrahydrofuranacetic acid esters and 6-substituted tetrahydropyranacetic acid esters in fair to good yield and with complete
retention of the absolute configuration of the starting 3-hydroxy ester.
Cerium(III) chloride heptahydrate1 has emerged as a very
cheap, water-tolerant, and “friendly” reagent, able to promote
a variety of selective functional group transformations.2,3 It
was found that the presence of sodium iodide reinforces its
activity.4 Our attention was drawn to the dehydration of
â-hydroxy ketones and esters that selectively give the
corresponding (E)-R,â-unsaturated derivatives.5
Herein, we report the results that originated from the
attempts to apply this method to the dehydration of 3-
hydroxyalkenoic acid esters.6 When 3-hydroxy-3,6-dimethyl-
6-heptenoic acid ethyl ester was subjected to the reported
protocols1.5 equiv of CeCl3‚7H2O and 1.5 equiv of NaI in
boiling acetonitrilesno doubly unsaturated ester was formed,
instead (2,5,5-trimethyltetrahydrofuran-2-yl)acetic acid ethyl
ester was isolated in 91% yield (eq 1).
† Dipartimento di Chimica “G. Ciamician”.
(1) Imamoto, T. Lanthanides in Organic Synthesis; Academic Press: New
York, 1994.
(2) (a) Denmark, S. E.; Nicaise, O. Synlett 1993, 359. (b) Ballini, R.;
Marcantoni, E.; Perrella, S. J. Org. Chem. 1999, 64, 2954. (c) Alessandrini,
S.; Bartoli, G.; Bellucci, M. C.; Dalpozzo, R.; Malavolta, M.; Marcantoni,
E.; Sambri, L. J. Org. Chem. 1999, 64, 1986. (d) Liu, H.-J.; Shia, K.-S.;
Shang, X.; Zhu, B.-Y. Tetrahedron 1999, 55, 3803. (e) Di Deo, M.;
Marcantoni, E.; Torreggiani, E.; Bartoli, G.; Bellucci, M. C.; Bosco, M.;
Sambri, L. J. Org. Chem. 2000, 65, 2830.
Several different substrates and conditions were then
studied. From the results reported in Table 1, it is rather
interesting to note the following: (i) the use of only 10%
equiv of CeCl3‚7H2O-NaI gave better results in terms of
both yields and practicality; (ii) it is the more substituted
(3) Sabitha, G.; Babu, R.-S.; Rajkumar, M.; Srividia, R.; Yadav, J. S.
Org. Lett. 2001, 3, 1149.
(4) (a) Bartoli, G.; Bellucci, M. C.; Bosco, M.; Cappa, A.; Marcantoni,
E.; Sambri, L.; Torreggiani, E. J. Org. Chem. 1999, 64, 5696. (b) Bartoli,
G.; Bosco, M.; Marcantoni, E.; Nobili, F.; Sambri, L. J. Org. Chem. 1997,
62, 4183. (c) Bartoli, G.; Bosco, M.; Marcantoni, E.; Sambri, L.; Torreggiani,
L. Synlett 1998, 209. (d) Marcantoni, E.; Massaccesi, M.; Torreggiani, E.;
Bartoli, G.; Bosco, M.; Sambri, L. J. Org. Chem. 2001, 66, 4430. (e) Sabitha,
G.; Babu, R.-S.; Rajkumar, M.; Reddy, C. S.; Yadav, J. S. Tetrahedron
Lett. 2001, 42, 3955. (f) Reddy, L. R.; Reddy, A. M.; Bhanumathi, N.;
Rao, K. R. Synthesis 2001, 831.
(6) (a) Marotta, E.; Righi, P.; Rosini, G. Org. Lett. 2000, 2, 4145. (b)
Marotta, E.; Righi, P.; Rosini, G. Org. Proc. Res. DeV. 1999, 3, 206. (c)
Rosini, G.; Confalonieri, G.; Marotta, E.; Rama, F.; Righi, P. Organic
Syntheses; Wiley: New York, 1997; Collect. Vol. IX, p 275 and references
therein.
(5) Bartoli, G.; Bellucci, M. C.; Petrini, M.; Marcantoni, E.; Sambri, L.;
Torreggiani, E. Org. Lett. 2000, 2, 1791.
10.1021/ol026955z CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/16/2002