ORGANIC
LETTERS
2002
Vol. 4, No. 14
2373-2376
Sulfinyl-Mediated Chirality Transfer in
Diastereoselective Claisen
Rearrangements
Roberto Ferna´ndez de la Pradilla,* Carlos Montero, and Mariola Tortosa
Instituto de Qu´ımica Orga´nica, CSIC, Juan de la CierVa, 3, 28006 Madrid, Spain
Received May 1, 2002
ABSTRACT
The highly selective Claisen rearrangements of substrates bearing a sulfinyl moiety at C-5 allow for creation of up to two asymmetric centers
and preserve a useful vinyl sulfoxide.
Enantiopure sulfoxides are becoming increasingly useful
chiral auxiliaries as a result of their ease of preparation,
remarkable synthetic versatility, and straightforward re-
moval.1 In recent years, we have been engaged in the
development of novel methodologies involving vinyl sul-
foxides,2 particularly focusing on strategies that allowed for
multiple sulfur-based chirality-transfer operations in acyclic
systems.3 Within this context, the Claisen rearrangement was
appealing since it is one of the most powerful methods for
stereoselective carbon-carbon bond formation.4 Furthermore,
the development of new enantioselective Claisen protocols
is a current problem in organic synthesis,5 with the use of
chiral sulfur atoms for that purpose scarcely documented.6
In this report we describe the first examples of diastereose-
lective Claisen rearrangements of readily available substrates
bearing a sulfinyl auxiliary at C-5 that take place with good
diastereoselectivities and preserve the synthetically useful
vinyl sulfoxide moiety.
We envisioned that readily available sulfinyl alcohols A7
(Scheme 1) could give rise to appropriate substrates B to
(5) (a) Kazmaier, U.; Maier, S.; Zumpe, F. L. Synlett 2000, 1523-1535.
(b) He, S.; Kozmin, S. A.; Rawal, V. J. Am. Chem. Soc. 2000, 122, 190-
191. (c) Yoon, T. P.; MacMillan, D. W. C. J. Am. Chem. Soc. 2001, 123,
2911-2912. (d) Enders, D.; Knopp, R.; Schiffers, R. Tetrahedron:
Asymmetry 1996, 7, 1847-1882. (e) Ito, H.; Taguchi, T. Chem. Soc. ReV.
1999, 28, 43-50.
(1) (a) Carren˜o, M. C. Chem. ReV. 1995, 95, 1717-1760. (b) Garc´ıa
Ruano, J. L.; Cid de la Plata, M. B. Top. Curr. Chem. 1999, 204, 1-126.
(c) Procter, D. J. J. Chem. Soc., Perkin Trans. 1 2001, 335-354.
(2) (a) Ferna´ndez de la Pradilla, R.; Montero, C.; Priego, J.; Mart´ınez-
Cruz, L. A. J. Org. Chem. 1998, 63, 9612-9613. (b) Ferna´ndez de la
Pradilla, R.; Me´ndez, P.; Priego, J.; Viso, A. J. Chem. Soc., Perkin Trans.
1 1999, 1247-1249.
(3) (a) Marino, J. P.; Viso, A.; Lee, J.-D.; Ferna´ndez de la Pradilla, R.;
Ferna´ndez, P.; Rubio, M. B. J. Org. Chem. 1997, 62, 645-653. (b)
Ferna´ndez de la Pradilla, R.; Montero, C.; Viso, A. Chem. Commun. 1998,
409-410. (c) Marino, J. P.; Anna, L. J.; Ferna´ndez de la Pradilla, R.;
Mart´ınez, M. V.; Montero, C.; Viso, A. J. Org. Chem. 2000, 65, 6462-
6473.
(4) (a) Claisen, B. Chem. Ber. 1912, 45, 3517. For reviews, see: (b)
Ziegler, F. Chem. ReV. 1988, 88, 1423-1452. (c) Wipf, P. In ComprehensiVe
Organic Synthesis; Trost, B. M., Fleming, I., Paquette, L. A., Eds.; Pergamon
Press: Oxford, U.K., 1991; Vol. 5, pp 827-874. (d) Frauenrath, H. In
Houben-Weyl; Helmchen, G., Hoffman, R., Mulzer, J., Schaumann, E., Eds.;
Thieme: Stuttgart-New York, 1995; pp 3301-3689.
(6) (a) Cookson, R. S.; Gopalan, R. J. Chem. Soc., Chem. Commun. 1978,
608. (b) Vate`le, J.-M. Tetrahedron Lett. 1983, 24, 1239-1242. (c) Posner,
G. H.; Crouch, D.; Kinter, C. M.; Carry, J.-C. J. Org. Chem. 1991, 56,
6981-6987. (d) Alayrac, C.; Fromont, C.; Metzner, P.; Anh, N. Angew.
Chem., Int. Ed. Engl. 1997, 36, 371-374. (e) Nowaczyk, S.; Alayrac, C.;
Reboul, V.; Metzner, P.; Averbuch-Pouchot, M.-T. J. Org. Chem. 2001,
66, 7841-7848.
(7) For convenience, most experiments were conducted with racemic
sulfoxides. Enantiopure (E)-sulfinyl alcohols were prepared (70-80%) from
vinyl sulfoxides (Craig, D.; Daniels, K.; McKenzie, A. R. Tetrahedron 1993,
49, 11263-11304) by treatment with LDA and an aldehyde. Racemic (Z)-
sulfinyl alcohols were prepared (52-60%) from the corresponding alkynyl
sulfides (Kabanyane, S. T.; MaGee, D. I. Can. J. Chem. 1992, 70, 2758-
2763) by Pd-catalyzed hydroestannylation (Magriotis, P. A.; Brown, J. T.;
Scott, M. E. Tetrahedron Lett. 1991, 32, 5047-5051), tin-lithium exchange,
condensation with an aldehyde, and diastereoselective oxidation with
mCPBA. For an enantioselective synthesis of (Z)-sulfenyl alcohols, see:
Berenguer, R.; Cavero, M.; Garc´ıa, J.; Mun˜oz, M. Tetrahedron Lett. 1998,
39, 2183-2186.
10.1021/ol0261130 CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/08/2002