ORGANIC
LETTERS
2000
Vol. 2, No. 15
2323-2326
Asymmetric Total Synthesis of
(+)-Aphanamol I Based on the
Transition Metal Catalyzed [5 + 2]
Cycloaddition of Allenes and
Vinylcyclopropanes
Paul A. Wender* and Lei Zhang
Department of Chemistry, Stanford UniVersity, Stanford, California 94305-5080
Received May 19, 2000
ABSTRACT
A concise asymmetric total synthesis of (+)-aphanamol I is described, based on the transition metal catalyzed [5 + 2] allenyl−vinylcyclopropane
cycloaddition. The key cycloaddition precursor is convergently assembled from (R)-(+)-limonene and cyclopropane diester through a novel
decarboxylative dehydration reaction. The metal-catalyzed [5 + 2] cycloaddition of this precursor proceeds with complete chemo, endo/exo,
and diastereoselectivity in 93% yield, representing an effective general route to bicyclo[5.3.0]decane derivatives.
A significant program in our laboratory is directed at the
design and development of new metal-catalyzed [m + n]
cycloadditions that in the absence of catalyst would be
difficult or impossible to achieve. This effort has thus far
produced the first examples of metal-catalyzed intramolecular
[4 + 4] cycloadditions of bis-dienes and [4 + 2] cycload-
ditions of dienes and π-systems1 and two new processes
involving the metal-catalyzed [5 + 2] cycloadditions of
vinylcyclopropanes2 and [6 + 2] cycloadditions of vinylcy-
clobutanones.3 The further development of these reactions
Livinghouse, T. Tetrahedron 1994, 50, 6145-6154. O’Mahony, D. J. R.;
Belanger, D. B.; Livinghouse, T. Synlett 1998, 443-445. Gilbertson, S.
R.; Hoge, G. S. Tetrahedron Lett. 1998, 39, 2075-2078. Gilbertson, S. R.;
Hoge, G. S.; Genov, D. G.; J. Org. Chem. 1998, 63, 10077-10080.
(2) For intramolecular [5 + 2] cycloadditions with alkynes, see: Wender,
P. A.; Takahashi, H.; Witulski, B. J. Am. Chem. Soc. 1995, 117, 4720-
4721. For more recent reports, see: Wender, P. A.; Dyckman, A. J.; Husfeld,
C. O.; Kadereit, D.; Love, J. A.; Rieck, H. J. Am. Chem. Soc. 1999, 121,
10442-10443. Wender, P. A.; Dyckman, A. J. Org. Lett. 1999, 1, 2089-
2092. Trost, B. M.; Toste, F. D.; Shen, H. J. Am. Chem. Soc. 2000, 122,
2379-2380. For intermolecular [5 + 2] cycloadditions with alkynes, see:
Wender, P. A.; Rieck, H.; Fuji, M. J. Am. Chem. Soc. 1998, 120, 10976-
10977. Wender, P. A.; Dyckman, A. J.; Husfeld, C. O.; Scanio, M. J. C.
Org. Lett. 2000, 2, 1609-1611. For intramolecular [5 + 2] cycloadditions
with alkenes, see: Wender, P. A.; Husfeld, C. O.; Langkopf, E.; Love, J.
A. J. Am. Chem. Soc. 1998, 120, 1940-1941. Wender, P. A.; Husfeld, C.
O.; Langkopf, E.; Love, J. A.; Pleuss, N. Tetrahedron 1998, 54, 7203-
7220. For intramolecular [5 + 2] cycloadditions with allenes, see: Wender,
P. A.; Glorius, F.; Husfeld, C. O.; Langkopf, E.; Love, J. A. J. Am. Chem.
Soc. 1999, 121, 5348-5349. Wender, P. A.; Fuji, M.; Husfeld, C. O.; Love,
J. A. Org. Lett. 1999, 1, 137-139.
(1) For [4 + 4] cycloadditions, see: Wender, P. A.; Ihle, N. C. J. Am.
Chem. Soc. 1986, 108, 4678-4679. Wender P. A.; Ihle, N. C.; Correia, C.
R. D. J. Am. Chem. Soc. 1988, 110, 5904-5906. Wender, P. A.; Tebbe,
M. J. Synthesis 1991, 1089-1094. For more recent studies, see: Wender,
P. A.; Nuss, J. M.; Smith, D. B.; Suarez-Sobrino A, Vågberg, J.; Decosta,
D.; Bordner, J. J. Org. Chem. 1997, 62, 4908-4909. Sieburth, S. McN.;
Cunard, N. T. Tetrahedron 1996, 52, 6251-6282. Murakami, M.; Itami,
K.; Ito, Y. Synlett 1999, S1, 951-953. For [4 + 2] cycloadditions, see:
Wender, P. A.; Jenkins, T. E. J. Am. Chem. Soc. 1989, 111, 6432-6434.
Wender, P. A.; Jenkins, T. E.; Suzuki, S. J. Am. Chem. Soc. 1995, 117,
1843-1844. Wender, P. A.; Smith, T. E. J. Org. Chem. 1996, 61, 824-
825. Wender, P. A.; Smith, T. E. Tetrahedron 1998, 54, 1255-1275. For
more recent studies, see: Jolly, R. S.; Luedtke. G.; Sheehan, D.; Living-
house, T. J. Am. Chem. Soc. 1990, 112, 4965-4966. McKinstry, L.;
(3) Wender, P. A.; Correa, A. G.; Sato. Y.; Sun, R. J. Am. Chem. Soc.
In press.
10.1021/ol006085q CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/23/2000