COMMUNICATIONS
oxazolidin-2-ones with high enantiomeric excesses has al-
ready proved to be useful in generating a number of bio-
An Efficient One-Pot Enantio- and
Diastereoselective Synthesis of Heterocycles**
[
15a]
logically significant targets such as mannostatin A,
allosa-
mizoline,[15a]
[15b]
Barry M. Trost* and Michelle R. Machacek
and swainsonine.
Received: August 26, 2002 [Z50043]
Heterocycles comprise the core of many complex natural
products. The most common method for their formation is
based on intramolecular ring closure. However, in most
intramolecular closure strategies it is necessary to synthesize
and then isolate the open-chain precursor. On an industrial
scale the environmental and economic costs of the isolation
stepare considerable. In contrast, a more efficient strategy
[
1] For recent reviews, see: B. Clapham, T. S. Reger, K. D. Janda,
Tetrahedron 2001, 57, 4637 ± 4662; Y. R. de Miguel, E. Brule, R. G.
Margue, J. Chem. Soc. Perkin Trans. 1 2001, 3085 ± 3094; S. J.
Shuttleworth, S. M. Allin, R. D. Wilson, D. Nasturica, Synthesis
000, 1035 ± 1074; S. J. Shuttleworth, S. M. Allin, P. K. Sharma,
Synthesis 1997, 1217 ± 1239; K. Fodor, S. G. A. Kolmschot, R. A.
Sheldon, Enantiomer 1999, 4, 497 ± 511.
2
[1]
utilizes a domino alkylation±cyclization to form the ring
[
[
2] J. Tsuji, Palladium Reagents and Catalysts-innovations in Organic
Synthesis, Wiley, New York, 1995.
without isolation of the acyclic intermediate. For the develop-
ment of ideal syntheses, processes are sought that generate
multiple bonds in one pot.[
3] Y. Uozumi, H. Danjo, T. Hiyashi, Tetrahedron Lett. 1998, 39, 8303; Y.
Uozumi, H. Danjo, T. Hiyashi, J. Org. Chem. 1999, 64, 3884.
4] C. A. Parrish, S. L. Buchwald, J. Org. Chem. 2001, 66, 3820.
5] Heck reaction: P. W. Wang, M. A. Fox, J. Org. Chem. 1994, 59, 5358;
M. R. Buchmeiser, K. Wurst, J. Am. Chem. Soc. 1999, 121, 11101; J.
Schwarz, V. P. W. Bohm, M. G. Gardiner, M. Grosche, W. A. Herr-
mann, W. Hieringer, G. Raudashl-Sieber, Chem. Eur. J. 2000, 6, 1773;
Stille reaction: J. K. Stille, H. Su, D. H. Hill, P. Schneider, M. Tanaka,
D. L. Morrison, L. S. Hegedus, Organometallics 1991, 10, 1993; Suzuki
reaction: S.-B. Jang, Tetrahedron Lett. 1997, 38, 1793; I. Finger, C.
Le Drian, Tetrahedron Lett. 1998, 39, 4287; T. Y. Zhang, M. J. Allen,
Tetrahedron Lett. 1999, 40, 5813; ref. [4].
2]
[
[
We aimed to design a one-pot heterocyclization process
that was both efficient and permitted control of the stereo-
chemistry of our products. We therefore focused on the Pd-
catalyzed asymmetric allylic alkylation (AAA)[
3,4]
for the
critical stereochemical determining step. This was combined
[5]
with the Ru-catalyzed ene±yne coupling to create the proper
juxtaposition of functionality for the second step. Recently we
[6]
have shown that in the presence of [CpRu(CH CN) PF ],
3
3
6
[
6] K. Hallman, E. Macedo, K. Nordstrom, C. Moberg, Tetrahedron:
Asymmetry 1999, 10, 4037; K. Hallman, C. Moberg, Tetrahedron:
Asymmetry 2001, 12, 1475.
silyl-substituted alkynes form 1,4-dienes with complete regio-
and stereoselectivity. If the ene partner is a homoallylic
group, the resulting 1,4-diene will contain a newly formed
allylic groupas illustrated in Equation (1). This intermediate
[7]
[
7] Y. Uozumi, K. Shibatomi, J. Am. Chem. Soc. 2001, 123, 2919; see also:
H.-J. Park, J. W. Han, H. Seo, H. -Y, Jang, Y. K. Chung, J. Suh, J. Mol.
Catal. A 2001, 174, 151.
[
[
8] B. M. Trost, E. Kainan, J. Am. Chem. Soc. 1978, 100, 7779.
9] B. M. Trost, J. Zambrano, W. Reichter, Synlett 2001, 907.
Ru cat.
R3Si
XH
[
10] a) B. M. Trost, D. E. Patterson, J. Org. Chem. 1998, 63, 1339; b) B. M.
Trost, D. L. VanVranken, C. Bingel, J. Am. Chem. Soc. 1992, 114, 9327.
11] B. M. Trost, Chem. Pharm. Bull. 2002, 50, 1; B. M. Trost, C.-B. Lee in
Catalytic Asymmetric Synthesis, (Ed.: I. Ojima), Wiley-VCH, New
York, 2000, pp. 593 ± 650; B. M. Trost, Acc. Chem. Res. 1996, 29, 355.
12] A. J. Brouner, R. van der Linden, M. J. Liskamp, J. Org. Chem. 2000,
n
Y
n=0, 1
X=NR, O
[
R3Si
[
n
XH
Pd. cat.
R3Si
6
5, 1750; J. Skarzewski, A. Gupta, Tetrahedron: Asymmetry 1997, 8,
(1)
n
X
1
861.
[
[
13] J. M. Stewart, J. D. Young, Solid Phase Reptide Synthesis, 2nd ed.,
Pierce Chemical Co., Rockford, IL, 1984, p. 105 and 108.
14] For an overview of applications of solid supported reagents and
catalyst see: S. V. Ley, I. R. Baxendale, R. N. Bream, P. S. Jackson,
A. G. Leach, D. A. Longbottom, M. Nesi, J. S. Scott, R. I. Storer, S. J.
Taylor, J. Chem. Soc. Perkin Trans. 1 2000, 3815.
Y
may then without isolation be subjected to Pd-catalyzed
asymmetric allylic alkylation. An additional feature of this
strategy is that the resulting vinylsilanes offer a pathway for
further structural elaboration[ and permit differentiation of
the two resulting double bonds.
[
15] a) B. M. Trost, D. L. Vranken, J. Am. Chem. Soc. 1993, 115, 444;
b) B. M. Trost, D. E. Patterson, Chem. Eur. J. 1999, 5, 3279.
8]
[
*] Prof. B. M. Trost, M. R. Machacek
Department of Chemistry
Stanford University
Stanford, CA 94305-5080 (USA)
Fax : (þ 1)650-725-0002
E-mail: bmtrost@stanford.edu
[
**] We thank the National Science Foundation and the National Institutes
of Health, General Medical Science (GM-13598) for their generous
support of our programs. GMS has been supported in part by a
fellowshipfrom Bristol Myers Squibb Pharmaceutical Company. Mass
spectra were provided by the Mass Spectrometry Regional Center of
the University of California, San Francisco, supported by the NIH
Division of Research Resources.
Supporting information for this article is available on the WWW under
http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2002, 41, No. 24
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0044-8249/02/4124-4693 $ 20.00+.50/0
4693