2390
K. Murakami et al. / Tetrahedron Letters 49 (2008) 2388–2390
2. Recent reviews: (a) Cozzi, P. G. Angew. Chem., Int. Ed. 2007, 46,
2568–2571; (b) Ocampo, R.; Dolbier, W. R., Jr. Tetrahedron 2004, 60,
9325–9374.
benzyl ethyl ketone (9) because of the acidic nature of the
benzylic protons. These two reactions starting from 1h
and 1i underscore the synthetic utility of the present
methodology.
3. Recent examples: (a) Iida, H.; Krische, M. J. Top. Curr. Chem. 2007,
279, 77–104; (b) Jang, H. Y.; Krische, M. J. Acc. Chem. Res. 2004, 37,
653–661; (c) Nishiyama, H.; Shiomi, T. Top. Curr. Chem. 2007, 279,
105–137; (d) Willis, M. C.; Woodward, R. L. J. Am. Chem. Soc. 2005,
127, 18012–18013; (e) Yoshida, K.; Ogasawara, M.; Hayashi, T. J.
Am. Chem. Soc. 2002, 124, 10984–10985; (f) Taylor, S. J.; Duffey, M.
O.; Morken, J. P. J. Am. Chem. Soc. 2000, 122, 4528–4529.
4. (a) Simpura, I.; Nevalainen, V. Angew. Chem., Int. Ed. 2000, 39,
3422–3425; (b) Xi, B.; Nevalainen, V. Tetrahedron Lett. 2006, 47,
2561–2564; (c) Xi, B.; Nevalainen, V. Tetrahedron Lett. 2006, 47,
7133–7135.
5. (a) Schneider, C.; Hansch, M. Chem. Commun. 2001, 1218–1219; (b)
Schneider, C.; Hansch, M. Synlett 2003, 837–840; (c) Schneider, C.;
Hansch, M.; Weide, T. Chem. Eur. J. 2005, 11, 3010–3021.
6. Organocatalytic sequential retro-aldol/aldol reactions: (a) Chandra-
sekhar, S.; Narsihmulu, C.; Reddy, N. R.; Sultana, S. S. Chem.
Commun. 2004, 2450–2451; (b) Chandrasekhar, S.; Reddy, N. R.;
Sultana, S. S.; Narsihmulu, C.; Reddy, K. V. Tetrahedron 2006, 62,
338–345.
In summary, we have devised a new method for the
preparation of rhodium enolates via retro-aldol reaction
and applied it to regioselective aldol reactions. The present
method is superior to the conventional deprotonation of
carbonyl compounds from the viewpoints of regioselectiv-
ity and functional group compatibility. Recently, reductive
generation of metal enolates has been attracting increasing
attention because of its mild conditions and high regiose-
lectivity.3 However, the reductive method would not allow
for using a,b-unsaturated carbonyl compounds as aldol
acceptors, which is in contrast to the result of entry 17
shown in Table 1. With improved stereoselectivity, the
present strategy would lead to significant progress in the
aldol reaction.
7. The exceptions are Refs. 4c and 5c, in which several enolates of
methyl ketones are described.
Acknowledgments
8. (a) Takada, Y.; Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K.
Org. Lett. 2006, 8, 2515–2517; (b) Jang, M.; Hayashi, S.; Hirano, K.;
Yorimitsu, H.; Oshima, K. Tetrahedron Lett. 2007, 48, 4003–4005; (c)
Sumida, Y.; Takada, Y.; Hayashi, S.; Hirano, K.; Yorimitsu, H.;
Oshima, K. Chem. Asian J. 2008, 3, 119–125.
This work was supported by Grants-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology, Government of Japan. H.O.
acknowledges JSPS for financial support.
9. b-Hydroxy ketones
1 were readily available according to the
procedures described as Supplementary data.
10. Experimental procedure: [RhCl(cod)]2 (2.5 mg, 0.005 mmol) and
Supplementary data
cesium carbonate (13 mg, 0.04 mmol) were placed in
a 20-mL
reaction flask under argon. 1-Hydroxy-2-methyl-1,1-diphenyl-3-buta-
none (1a, 51 mg, 0.20 mmol) in 1,4-dioxane (2.0 mL) was added to the
flask. Then, N,N,N0,N0-tetramethylethylenediamine (6 lL, 0.04 mmol)
and benzaldehyde (2a, 30 lL, 0.30 mmol) were added to the flask. The
mixture was stirred at 20 °C for 3 h. A saturated ammonium chloride
solution (2 mL) was added, and the organic compounds were
extracted with ethyl acetate (10 mL ꢀ 3). The combined organic part
was dried over anhydrous sodium sulfate and concentrated in vacuo.
Chromatographic purification on silica gel by using hexane/ethyl
acetate = 5:1 as an eluent afforded 3a (36 mg, 0.20 mmol) in quan-
titative yield (syn/anti = 53/47).
Supplementary data (procedure for the preparation of 1
and characterization data for new compounds) associated
with this article can be found, in the online version, at
References and notes
1. (a) Mahrwald, R. Chem. Rev. 1999, 99, 1095–1120; (b) Mahrwald, R.
Modern Aldol Reaction; Wiley-VCH: Weinheim, 2004; (c) Trost, B.
M.; Fleming, I.; Semmelhack, M. F. In Comprehensive Organic
Synthesis; Pergamon Press: New York, 1991; Vol. 2, Chapter 1.4–1.9;
(d) Mukaiyama, T. Org. React. 1982, 28, 203–331.
11. Nishiyama, H.; Shimada, T.; Itoh, H.; Sugiyama, H.; Motoyama, Y.
Chem. Commun. 1997, 1863–1864.