ORGANIC
LETTERS
2002
Vol. 4, No. 23
4097-4099
Pinacol Coupling Reaction of
â-Halo-r,â-unsaturated Aldehydes
Promoted by TiI4
Makoto Shimizu,* Hiroshi Goto, and Ryuuichirou Hayakawa
Department of Chemistry for Materials, Mie UniVersity, Tsu, Mie 514-8507, Japan
Received September 3, 2002
ABSTRACT
The pinacol reaction of â-halogenated r,â-unsaturated aldehydes was promoted by titanium tetraiodide to give coupling products in good
yields with high dl-selectivity. Subsequent reduction with H /Pd−C gave saturated vic-diols in good yields. Heck coupling reaction enabled the
2
displacement of halogens with vinyl groups without the loss of stereochemical integrities.
A number of 1,2-diols have been utilized as useful synthons
for the synthesis of biologically important compounds such
as HIV protease inhibitors and natural products,1 and several
approaches to their syntheses have been described. Among
them, the pinacol coupling reaction constitutes one of the
most straightforward methods.2 Recently, high diastereo-
selectivity, catalytic use of active species, and cross-coupling
have been attained in such reactions.3 Use of low-valent
metals such as titanium,4 zirconium,5 vanadium,6 samarium,7
and so on is, in principle, needed for promoting the pinacol
coupling, because, for a majority of cases, the reaction
proceeds via a single-electron-transfer mechanism.
We have been interested in the reaction using titanium
tetraiodide, which possesses good reducing ability for various
substrates, including ketones, imines, and sulfoxides,8 and
we have already reported that the pinacol coupling of
aromatic aldehydes is conducted under the influence of
titanium tetraiodide. However, the titanium tetraiodide could
not sufficiently promote the pinacol coupling reaction of
Oshiki, T.; Kiriyama, T.; Tsuchida, K.; Takai, K. Chem. Lett. 2000, 334-
335. (g) Tsuritani, T.; Ito, S.; Shinokubo, H.; Oshima, K. J. Org. Chem.
2000, 65, 5066-5068.; (h) Mukaiyama, T.; Yoshimura, N.; Igarashi, K.;
Kagayama, A. Tetrahedron 2001, 57, 2499-2506.
(5) Askham, F. R.; Carroll, K. M. J. Org. Chem. 1993, 58, 7328-7329.
(6) Freudenberger, J. H.; Konradi, A. W.; Pedersen, S. F. J. Am. Chem.
Soc. 1989, 111, 8014-8016. Raw, A. S.; Pedersen, S. F. J. Org. Chem.
1991, 56, 830-833. Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi,
F.; Giaroni, P. J. Org. Chem. 1992, 57, 782-784. Hirao, T.; Hatano, B.;
Imamoto, Y.; Ogawa, A. J. Org. Chem. 1999, 64, 7665-7667. Hirao, T.;
Takeuchi, H.; Ogawa, A.; Sakurai, H. Synlett 2000, 1658-1660 and
references therein.
(7) Namy, J. L.; Souppe, J.; Kagan, H. B. Tetrahedron Lett. 1983, 24,
765-766. Akane, N.; Hatano, T.; Kusui, H.; Nishiyama, Y.; Ishii, Y. J.
Org. Chem. 1994, 59, 7902-7907. Taniguchi, N.; Uemura, M. Tetrahedron
1998, 54, 12775-12788. Christensen, T. B.; Riber, D.; Daasbjerg, K.;
Skrydstrup, T. Chem. Commun. 1999, 2051-2052. Yanada, R.; Okaniwa,
M.; Kaieda, A.; Ibuka, T.; Takemoto, Y. J. Org. Chem. 2001, 66, 1283-
1286 and references therein.
(8) Hayakawa, R.; Shimizu, M. Org. Lett. 2000, 2, 4079-4081. Shimizu,
M.; Shibuya, K.; Hayakawa, R. Synlett 2000, 1437-1438. Hayakawa, R.;
Sahara, T.; Shimizu, M. Tetrahedron Lett. 2000, 41, 7939-7942. Hayakawa,
R.; Makino, H.; Shimizu, M. Chem. Lett. 2001, 756-757. Shimizu, M.;
Sahara, T.; Hayakawa, R. Chem. Lett. 2001, 792-793. Shimizu, M.;
Takeuchi, Y.; Sahara, T. Chem. Lett. 2001, 1196-1197.
(1) Kammermeier, B.; Beck, G.; Jacobi, D.; Jendralla, H. Angew. Chem.,
Int. Ed. Engl. 1994, 33, 685-687. McMurry, J. E.; Siemers, N. O.
Tetrahedron Lett. 1994, 35, 4505-4508. Kammermeier, B.; Beck, G.; Holla,
W.; Jacobi, D.; Napierski, B.; Jendralla, H. Chem. Eur. J. 1996, 2, 307-
315. Shiina, I.; Iwadare, H.; Sakoh, H.; Hasegawa, M.; Tani, Y.; Mukaiyama,
T. Chem. Lett. 1998, 1-2. Matsumoto, T.; Yamaguchi, H.; Tanabe, M.;
Yasui, Y.; Suzuki, K. Tetrahedron Lett. 2000, 41, 8393-8396.
(2) For general reviews, see: Robertson, G. M. In ComprehensiVe
Organic Synthesis; Trost B. M., Ed.; Pergamon: New York, 1991; Vol. 3,
pp 563-611. Wirth, T. Angew. Chem., Int. Ed. Engl. 1996, 35, 61-63.
Hirao, T. Synlett 1999, 175-181. Gansa¨uer, A.; Bluhm, H. Chem. ReV.
2000, 100, 2771-2788 and references therein.
(3) Fu¨rstner, A.; Hupperts, A. J. Am. Chem. Soc. 1995, 117, 4468-4475.
Hirao, T.; Hasegawa, T.; Muguruma, Y.; Ikeda, I. J. Org. Chem. 1996, 61,
366-367. Reetz, M. T.; Griebenow, N. Liebigs Ann. 1996, 335-348. Kang,
M.; Park, J.; Pederson, S. F. Synlett 1997, 41-43. Gansa¨uer, A. Synlett
1997, 363-364. Hirao, T.; Hatano, B.; Asahara, M.; Muguruma, Y.; Ogawa,
A. Tetrahedron Lett. 1998, 39, 5247-5348. Groth, U.; Jeske, M. Angew.
Chem., Int. Ed. Engl. 2000, 39, 574-576.
(4) (a) Mukaiyama, T.; Sato, T.; Hanna, J. Chem. Lett. 1973, 1041-
1044. (b) Handa, I.; Inanaga, I. Tetrahedron Lett. 1987, 28, 5717-5718.
(c) Clerici, A.; Clerici, L.; Porta, O. Tetrahedron Lett. 1996, 37, 3035-
3038. (d) Barden, M. C.; Schwartz, J. J. Am. Chem. Soc. 1996, 118, 5484-
5485. (e) Gansa¨uer, A.; Bauer, D. J. Org. Chem. 1998, 63, 2070-2071. (f)
10.1021/ol026842f CCC: $22.00 © 2002 American Chemical Society
Published on Web 10/25/2002