ORGANIC
LETTERS
2004
Vol. 6, No. 15
2551-2554
Tin(IV) Chloride-Chiral Pyrogallol
Derivatives as New Lewis Acid-Assisted
Chiral Brønsted Acids for
Enantioselective Polyene Cyclization
,†
,‡
Keiko Kumazawa,† Kazuaki Ishihara,* and Hisashi Yamamoto*
Graduate School of Engineering, Nagoya UniVersity, Furo-cho, Chikusa,
Nagoya 464-8603, Japan, and Department of Chemistry, The UniVersity of Chicago,
5735 S. Ellis AVenue, Chicago, Illinois 60637
ishihara@cc.nagoya-u.ac.jp; yamamoto@uchicago.edu
Received May 12, 2004
ABSTRACT
New Lewis acid-assisted Brønsted acids (LBAs), tin(IV) chloride-2,6-dialkoxyphenols, serve as artificial cyclases for biomimetic polyene cyclization.
For example, the enantioselective cyclization of 4-(homogeranyl)toluene using tin(IV) chloride-2,6-di[(1′R,2′R)-trans-2′-(3′′,5′′-xylyl)cyclohexanoxy]-
phenol gave a trans-fused tricyclic compound with 85% ee.
We recently reported the first example of the enantio-
selective cyclization of polyprenyl alcohols and homo-
(polyprenyl)arenes induced by Lewis acid-assisted chiral
Brønsted acids (chiral LBAs).1,2 Optically pure 2-alkoxy-2′-
hydroxy-1,1′-binaphthyl 1 activated with SnCl4 is effective
for this enantioselective cyclization. The further refinement
of LBAs was required to establish LBA-induced biomimetic
polyene cyclization as a practical synthetic method. However,
we could not design any chiral Brønsted acids that were
superior to 1 by chemical modification of 1. For example,
the introduction of 3,3′-substituents on 1 unexpectedly
decreased not only the activity of the LBA but also the
enantioselectivity of the polyene cyclization. Thus, we
pursued the design of new chiral Brønsted acids, that did
not include a binaphthol skeleton, which were activated with
SnCl4. In this paper, we report a new design for Brønsted
acids that include a pyrogallol skeleton, achiral 2,6-dialkox-
yphenols 2, and optically pure 2,6-di[trans-2′-(3′′,5′′-xylyl)-
cyclohexanoxy]phenol (3c). SnCl4 preferentially chelates
pyrogallol derivatives compared with biphenol and binaph-
thol derivatives (Figure 1).
Our studies began with the diastereoselective cyclization
of 4-(homogeranyl)toluene (4) induced by achiral LBA
prepared in situ from a 1:1 molar mixture of a variety of
phenol derivatives and SnCl4. The reaction was conducted
in the presence of 20 mol % ArOH‚SnCl4 in dichloromethane
at -78 °C. The activity of the Brønsted acid was estimated
by the GC ratio of the crude products. In most cases, the
desired trans-fused AB-ring product 5 was obtained together
† Nagoya University.
‡ The University of Chicago.
(1) For a review, see: Ishibashi, H.; Ishihara, K.; Yamamoto, H. Chem.
Rec. 2002, 2, 177.
(2) (a) Ishihara, K.; Nakamura, S.; Yamamoto, H. J. Am. Chem. Soc.
1999, 121, 4906. (b) Nakamura, S.; Ishihara, K.; Yamamoto, H. J. Am.
Chem. Soc. 2000, 122, 8131. (c) Ishihara, K.; Ishibashi, H.; Yamamoto, H.
J. Am. Chem. Soc. 2001, 123, 1505. (d) Ishihara, K.; Ishibashi, H.;
Yamamoto, H. J. Am. Chem. Soc. 2002, 124, 3647.
10.1021/ol049126h CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/01/2004