In tr a m olecu la r Rea ction of a P h en on iu m Ion . Novel La cton iza tion
of 4-Ar yl-5-tosyloxyp en ta n oa tes a n d 4-Ar yl-5-tosyloxyh exa n oa tes
Con com ita n t w ith a P h en yl Rea r r a n gem en t1
Shinji Nagumo,*,† Machiko Ono,‡ Yo-ichiro Kakimoto,† Tsuneo Furukawa,‡ Tomoaki Hisano,†
Megumi Mizukami,† Norio Kawahara,† and Hiroyuki Akita*,‡
Hokkaido College of Pharmacy, Katsuraoka 7-1, Otaru, Hokkaido 047-0264, J apan, and School of
Pharmaceutical Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, J apan
nagumo@hokuyakudai.ac.jp; akita@phar.toho-u.ac.jp
Received May 17, 2001
The novel lactonizations of methyl 4-aryl-5-tosyloxypentanoate 1 and 4-aryl-5-tosyloxyhexanoate
3 concomitant with a phenyl rearrangement are reported. The lactonizations were promoted by
silica gel or heating in various solvents. By examining the effects of substituents of the aromatic
ring on the reactivity, it was found that the reaction proceeded via a phenonium ion. This finding
was supported by the stereochemical results for the lactonization of optical active 1. Silica gel-
promoted lactonization of 1 gave only γ-lactone 2, whereas that of 3 afforded γ-lactone 4 and
δ-lactone 5. These lactonizations proved to be kinetically controlled. On the other hand, when 3c
was heated in CH3NO2 at 70 °C, the highly selective formation of 4c was observed. Further detailed
experiments confirmed that the thermal lactonization in CH3NO2 was thermodynamically controlled.
SCHEME 1
In tr od u ction
Symmetrical σ-bridged ethylenebenzenium (phenoni-
um) ions were proposed by Cram to explain the stereo-
chemical results in solvolyses of optically active threo-
and erythro-3-aryl-2-butyltosylates.2 Brown claimed that
these experimental findings could alternatively be ex-
plained by considering weakly π-bridged, rapidly equili-
brating open ions.3 This controversy became the most
important topic in modern physical organic chemistry,
and many reports on this subject have been published.4
On the basis of the results of these studies, Brown
concluded that a continuous spectrum of ions, from open
to completely bridged ions, exists depending upon the
solvent and substituent in the ions.5 Furthermore, NMR
spectral6 and theoretical7 studies have indicated that the
intermediate has a σ-bridged phenonium ion structure
rather than an equilibrating open ion structure. Despite
the impressive advances in phenonium ion chemistry due
to the contribution of results of many studies, the ion has
not been widely applied to synthetic chemistry. If a
phenonium ion has appropriately aligned intramolecular
nucleophilic functional groups, a novel type of ring
formation induced by the ion should proceed (Scheme 1).
Such a reaction should offer possibilities that are not
available in the case of an intermolecular reaction. For
* To whom correspondence should be addressed. For S.N.: phone
+81-(0)134-62-1842; fax +81-(0)134-62-5161. For H. A.: phone +81-
(0)474-72-1805; fax, +81-(0)474-72-1825.
† Hokkaido College of Pharmacy.
‡ Toho University.
(1) A part of this work was reported as a preliminary communica-
tion. (a) Nagumo, S.; Furukawa, T.; Ono, M.; Akita, H. Tetrahedron
Lett. 1997, 38, 2849. (b) Nagumo, S.; Hisano, T.; Kakimoto, Y.;
Kawahara, N.; Ono, M.; Furukawa, T.; Takeda, S.; Akita, H. Tetra-
hedron Lett. 1998, 39, 8109.
(2) (a) Cram, D. J . J . Am. Chem. Soc. 1949, 71, 3863. (b) Cram, D.
J .; Davis, R. J . Am. Chem. Soc. 1949, 71, 3871. (c) Cram, D. J . J . Am.
Chem. Soc. 1949, 71, 3875. (d) Cram, D. J . J . Am. Chem. Soc. 1964,
86, 3767.
(6) (a) Olah, G. A.; Head, N. J .; Rasul, G.; Prakash, G. K. S. J . Am.
Chem. Soc. 1995, 117, 875. (b) Manner, J . A. M.; Cook, J . A., J r.;
Ramsey, B. G. J . Org. Chem. 1974, 39, 1199. (c) Olah, G. A.; Porter,
R. D. J . Am. Chem. Soc. 1971, 93, 6877. (d) Olah, G. A.; Porter, R. D.
J . Am. Chem. Soc. 1970, 92, 7627. (e) Olah, G. A.; Comisarow, M. B.;
Namanworth, E.; Ramsey, B. J . Am. Chem. Soc. 1967, 89, 5259.
(7) (a) Sieber, S.; Schleyer, P. v. R. J . Am. Chem. Soc. 1993, 115,
6987. (b) Yamabe, S.; Tanaka, T. Nippon Kagaku Kaishi 1986, 1388.
(c) Loupy, A.; Ancian, B. Tetrahedron Lett. 1975, 951. (d) Hehre, W. J .
J . Am. Chem. Soc. 1972, 94, 5919.
(3) Brown, H. C.; Morgan, K. J .; Chloupek, F. J . J . Am. Chem. Soc.
1965, 87, 2137.
(4) For a review, see: (a) Lancelot, C. J .; Cram, D. J .; Schleyer, P.
v. R. In Carbonium Ions; Olah, G. A., Schleyer, P. v. R., Eds.; Wiley-
Interscience: New York, 1972; Vol. III, Chapter 27. (b) Vogel, P. In
Carbocation Chemistry; Elsevier: Amsterdam, 1985; Chapter 7.
(5) Brown, H. C.; Kim, C. J .; Lancelot, C. J .; Schleyer, P. v. R. J .
Am. Chem. Soc. 1970, 92, 5244.
10.1021/jo010500q CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/22/2002
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J . Org. Chem. 2002, 67, 6618-6622