A New Approach to Polycyclic Azonia
Cations by Ring-Closing Metathesis
‡
Ana Nu ´n ˜ ez, Ana M. Cuadro,* Julio Alvarez-Builla, and Juan J. Vaquero*
Departamento de Quı ´mica Orga ´ nica, UniVersidad de Alcala ´ ,
28871-Alcala ´ de Henares, Madrid, Spain
juanjose.Vaquero@uah.es
Received March 30, 2007
ABSTRACT
The ring-closing metathesis (RCM) reaction of N-vinyl-r-(2-styryl)azinium salts, using the Hoveyda-Grubbs catalyst, leads to different tricyclic
and tetracyclic azonia cations with moderate to good yields. This is the first time that a highly electron-deficient alkene such as an
N-vinylpyridinium has been involved in an RCM process.
Recently, we reported the first examples of a diene
1
and
enyne
2
ring-closing metathesis on azinium cations 1, a pro-
cess that gave dihydroquinolizinium cations 2. This strategy
proved to be very efficient for the synthesis of quinolizinium
derivatives and related systems
3,4
(Scheme 1). Indeed, it can
be envisaged as a unified approach to a range of azonia
cations,
5
including the 3 benzoquinolizinium and many of
the 18 possible dibenzo- and naphthoquinolizinium cations.
6
There are, however, a small number of dibenzo- and
naphthoquinoliziniums (4-6) for which this strategy, based
on the disconnection of the δ bond with respect to the
quaternary nitrogen, is not feasible because the presence of
two benzo fused rings precludes the appropriate bond
disconnection. For this class of cations, which includes the
dibenzo[a,g]quinolizinium cation 6 (the heterocyclic core of
cationic alkaloids such as coralyne,
7
berberine, and proto-
berberines
8
), we envisaged an alternative diene ring-closing
metathesis (RCM) process through the disconnection of a
bond (Scheme 2).
‡
Dedicated to Prof. Miguel Yus on the occasion of his 60th birthday.
(1) For recent reviews on diene RCM, see: (a) Deiters, A.; Martin, S.
F. Chem. ReV. 2004, 104, 2199-2238. (b) Poulsen, C. S.; Madsen, R.
Synthesis 2003,1-18. (c) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res.
2001, 34, 18-29.
(2) For reviews on enyne metathesis, see: (a) Fu ¨rstner, A.; Davies, P.
W. Chem. Commun. 2005, 2307-2320. (b) Hoveyda, A. H.; Hird, A. W.;
Kacprzynski, M. A. Chem. Commun. 2004, 1779-1785. (c) Diver, S. T.;
Giessert, A. J. Chem. ReV. 2004, 104, 1317-1382. (d) Mori, M. In
Handbook of Metathesis; Grubbs, R. H., Ed.; Wiley-VCH: Weinheim;
Germany, Vol. 2003; Vol. 2, 176-204. (e) Mori, M. Top. Organomet. Chem.
1998, 1, 133-154.
(3) Nun ˜ez, A.; Cuadro, A. M.; Alvarez-Builla, J.; Vaquero, J. J. Org.
Lett. 2004, 6, 4125-4127.
(4) Nun ˜ez, A.; Cuadro, A. M.; Alvarez-Builla, J.; Vaquero, J. J. Chem.
Commun. 2006, 2690-2692.
(5) Ihmels, H.; Faulhaber, K.; Vedaldi, D.; Dall’Acqua, F.; Viola, G.
Photochem. Photobiol. 2005, 81, 1107-1115.
(6) Arai, S.; Hida, M. AdV. Heterocycl. Chem. 1992, 55, 261-358.
(7) (a) Kwang-Yuen, K.-Y.; Zee-Cheng, Y.; Paul, K. D.; Cheng, C. C.
J. Med. Chem. 1974, 17, 347-351. (b) Robert, K.; Zee-Cheng, Y.; Cheng,
C. C. J. Med. Chem. 1976, 19, 882-886. (c) Wilson, W. D.; Gough, A.
N.; Doyle, J. J.; Davidson, M. W. J. Med. Chem. 1976, 19, 1261-1263.
(d) Lee, J. S.; Latimer, L. J. P.; Hampel, K. J. Biochemistry 1993, 32, 5591-
5597. (e) Wang, L.-K.; Rogers, B. D.; Hecht, S. M. Chem. Res. Toxicol.
1996, 9, 75-83.
Scheme 1. 3,4-Dihydroquinolizinium from δ Bond
Disconnection
ORGANIC
LETTERS
2007
Vol. 9, No. 16
2977-2980
10.1021/ol070773t CCC: $37.00 © 2007 American Chemical Society
Published on Web 07/11/2007