ORGANIC
LETTERS
2002
Vol. 4, No. 20
3485-3488
Chemoselective Aldol Reaction of Silyl
Enolates Catalyzed by MgI2 Etherate
Wei-Dong Z. Li* and Xing-Xian Zhang
National Laboratory of Applied Organic Chemistry, Lanzhou UniVersity, Lanzhou,
Gansu 730000, P. R. China
Received July 23, 2002
ABSTRACT
Mukaiyama-type aldol coupling of typical silyl enolates 2−4 with aryl or vinyl aldehydes and acetals was realized in the presence of 1−5 mol
% of MgI2 etherate (1) in a mild, efficient, and highly chemoselective manner. Iodide counterion, weakly coordinating peripheral ethereal
ligands (Et2O) of Mg(II), and a noncoordinating reaction media (i.e. CH Cl2) are among the critical factors for the unique reactivity of this
2
catalytic system.
Magnesium(II) species are widely used as Lewis acid
catalysts in various functional transformations1 and C-C
bond-forming reactions2 due to the high electrophilicity of
the Mg2+ ion and its tendency to form a multi-coordinate
(up to 5 or 6) complex.3 Among them, magnesium halides
are most frequently used. Revelation of the intriguing
catalytic reactivity of magnesium halide-derived chiral Lewis
acids by Corey et al.4 has stimulated increased interest in
the asymmetric catalysis of the C-C bond formation reaction
by a Mg(II) complex.5 However, the use of Mg(II) Lewis
acids in aldol condensation has been rather limited so far.6
We report here the preliminary results on the unique catalytic
reactivity of MgI2 diethyl etherate (1) for the mild, efficient,
and chemoselective (Mukaiyama-type) aldol reaction of aryl
aldehydes and acetals with silyl enolates. To the best of our
knowledge, this is the first effective catalysis of Mukaiyama-
type aldol catalytic in magnesium halide.7 The Mukaiyama-
(1) For examples, see: (a) Ohnishi, Y.; Kagami, M.; Ohno, A. J. Am.
Chem. Soc. 1975, 97, 4766. (b) Meyers, A. I.; Oppenlaender, T. J. Am.
Chem. Soc. 1986, 108, 1989. (c) Bolm, C.; Beckmann, O.; Cosp, A.; Palazzi,
C. Synlett 2001, 1461. (d) Bouzide, A. Org. Lett. 2002, 4, 1347. (e)
Chowdhury, P. K. J. Chem. Res., Synop. 1990, 192 and 390. (f) Chowdhury,
P. K. J. Chem. Res., Synop. 1992, 68. (g) Yamaguchi, S.; Nedachi, M.;
Yokoyama, H.; Hirai, Y. Tetrahedron Lett. 1999, 40, 7363. (h) Jang, D.
O.; Joo, Y. H. Synth. Commun. 1998, 28, 871. (i) Martinez, A. G.; Barcina,
J. O.; del Veccio, G. H.; Hanack, M.; Subramanian, L. R. Tetrahedron
Lett. 1991, 32, 5931. (j) Murakata, M.; Tsutsui, H.; Taksuchi, N.; Hoshino,
O. Tetrahedron 1999, 55, 10295.
(4) (a) Corey, E. J.; Ishihara, K. Tetrahedron Lett. 1992, 33, 6807. (b)
Corey, E. J.; Wang, Z. Tetrahedron Lett. 1993, 34, 4001. See also: (c)
Corey, E. J.; Imai, N.; Zhang, H.-Y. J. Am. Chem. Soc. 1991, 113, 728.
(5) Cf: (a) Bromidge, S.; Wilson, P. C.; Whiting, A. Tetrahedron Lett.
1998, 39, 8905. (b) Gothelf, K. V.; Hazell, R. G.; Jorgensen, K. A. J. Org.
Chem. 1998, 63, 5483. (c) Desimoni, G.; Faita, G.; Mortoni, A.; Righetti,
P. P. Tetrahedron Lett. 1999, 40, 2001. (d) Ichiyanagi, T.; Shimizu, M.;
Fujisawa, T. J. Org. Chem. 1997, 62, 7937. (e) Sibi, M. P.; Asano, Y. J.
Am. Chem. Soc. 2001, 123, 9708.
(6) For a few examples, see: (a) Corey, E. J.; Li, W.; Reichard, G. A.
J. Am. Chem. Soc. 1998, 120, 2330. (b) Fujisawa, H.; Sasaki, Y.;
Mukaiyama, T. Chem. Lett. 2001, 190 and ref 7 therein. (c) Evans, D. A.;
Tedrow, J. S.; Shaw, J. T.; Downey, C. W. J. Am. Chem. Soc. 2002, 124,
392. (d) Evans, D. A.; Downey, C. W.; Shaw, J. T.; Tedrow, J. S. Org.
Lett. 2002, 4, 1127.
(2) For examples, see: (a) Sibi, M. P.; Porter, N. A. Acc. Chem. Res.
1999, 32, 163. (b) Yang, D.; Gu, S.; Yan, Y.-L.; Zhu, N.-Y.; Cheung, K.-
K. J. Am. Chem. Soc. 2001, 123, 8612. (c) Li, C.-J.; Zhang, W.-C. J. Am.
Chem. Soc. 1998, 120, 9102. (d) Rawat, D. S.; Zaleski, J. M. J. Am. Chem.
Soc. 2001, 123, 9675. (e) Alper, P. B.; Meyers, C.; Lerchner, A.; Siegel,
D. R.; Carreira, E. M. Angew. Chem., Int. Ed. 1999, 38, 3186. (f) Lautens,
M.; Han, W. J. Am. Chem. Soc. 2002, 124, 6312. (g) Bertozzi, F.;
Gustafsson, M.; Olsson, R. Org. Lett. 2002, 4, 3147-3150. (h) Yang, D.;
Gu, S.; Yan, Y.-L.; Zhao, H.-W.; Zhu, N.-Y. Angew. Chem., Int. Ed. 2002,
41, 3014. (i) Yang, D.; Gao, Q.; Lee, C.-S.; Cheung, K.-K. Org. Lett. 2002,
4, 3271-3274.
(3) (a) Tobe, M. L.; Burgess, J. Inorganic Reaction Mechanisms;
Addison-Wesley Longman: New York, 1999, Chapter 7. (b) Wehmschulte,
R. J.; Twamley, B.; Khan, M. A. Inorg. Chem. 2001, 40, 6004.
10.1021/ol026585e CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/05/2002