ORGANIC
LETTERS
1999
Vol. 1, No. 9
1383-1385
Highly Stereoselective Coupling
Reaction of Acrolein or Vinyl Ketone
with Aldehydes
Shigeki Uehira, Zhenfu Han, Hiroshi Shinokubo, and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
Received August 11, 1999
ABSTRACT
Treatment of acrolein with a TiCl4−n-Bu4NI mixed reagent in the presence of 2 equiv of aldehydes provided 4-hydroxy-1,3-dioxane derivatives
in good yields with high stereoselectivities. The use of vinyl ketones instead of acrolein afforded aldol-type adducts with high syn selectivities.
The conjugate addition reaction of various nucleophiles to
R,â-unsaturated compounds such as 1,2-enones has been
extensively explored, and it has been recognized as a
powerful route for enolate formation.1 Then, the sequential
reaction of the resulting enolate with electrophiles provides
organic chemists an extremely effective methodology for
construction of the carbon framework of organic molecules
(Scheme 1).2 With regard to acrolein, however, few examples
because of its high reactivity. Herein we wish to report that
a TiCl4-n-Bu4NI4 system mediates formation of an enolate
from acrolein and the subsequent trapping of the resulting
titanium enolate5 with aldehydes affords 3-hydroxy-aldehydes
and their derivatives with high stereoselectivities.
Treatment of tetrabutylammonium iodide with TiCl4 in
dichloromethane at 0 °C provided a dark-red solution. After
(1) (a) Organocopper Reagents; Taylor, R. J. K., Ed.; Oxford University
Press: New York, 1994. (b) Jung, M. E. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: New York,
1991; Vol. 4, Chapter 1.1, pp 1-67. (c) Lee, V. J. In ComprehensiVe
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: New
York, 1991; Vol. 4, Chapter 1.2 pp 69-137. (d) Lee, V. J. In ComprehensiVe
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: New
York, 1991; Vol. 4, Chapter 1.3, pp 139-168.
Scheme 1
(2) (a) Noyori, R.; Suzuki, M. Angew. Chem., Int. Ed. Engl. 1984, 23,
847-876. (d) Taylor, R. J. K. Synthesis 1985, 364-392. (c) Noyori, R.;
Suzuki, M. Chemtracts-Org. Chem. 1990, 3, 173-197. (d) Hulce, M.;
Chapdelaine, M. J. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 4, Chapter 1.6,
pp 237-268.
(3) Examples of conjugate addition to acrolein: (a) Alexakis, A.; Chuit,
C.; Commerc¸on-Bourgain, M.; Foulon, J. P.; Jarbi, N.; Mangeney, P.;
Normant, J. F. Pure Appl. Chem. 1984, 56, 91-98. (b) Park, Y. S.; Beak,
P. J. Org. Chem. 1997, 62, 1574-1575.
of conjugate addition to acrolein are described in the
literature.3 Moreover, trapping of the resulting enolate with
carbon electrophiles such as carbonyl compounds has been
quite limited. In most cases, 1,2-addition of nucleophiles to
acrolein is the predominant reaction. In addition, if 1,4-
addition to acrolein occurs, reaction of the resulting enolate
with acrolein could readily cause polymerization of acrolein
(4) (a) Taniguchi, M.; Hino, T.; Kishi, Y. Tetrahedron Lett. 1986, 39,
4767. (b) Yachi, K.; Maeda, K.; Shinokubo, H.; Oshima, K. Tetrahedron
Lett. 1997, 38, 5161.
(5) (a) Organotitanium and Organozirconium Reagents; Ferreri, C.,
Palumbo, G., Caputo, R., Eds.; Pergamon Press: Oxford, 1991; Vol. 1, pp
139-172. (b) Reetz, M. T. Organotitanium Reagents in Organic Synthesis;
Springer-Verlag: Berlin, 1986.
10.1021/ol990934w CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/30/1999