Organocatalytic Asymmetric Hydroxylation of β-Keto Esters: Metal-Free Synthesis of Optically Active anti-Diols Maria Rosaria Acocella, Olga Garcı´a Manchen˜o, Marco Bella, and Karl Anker Jørgensen* Danish National Research Foundation, Center for Catalysis, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark
[email protected] Received August 4, 2004
Abstract: The organocatalytic R-hydroxylation of β-keto esters using cinchona-alkaloid derivatives as the catalyst and peroxides as the terminal oxidant has been investigated and is shown to proceed in high yields and with good enantioselectivity. The scope of the reaction is demonstrated for various substrates, and furthermore, the preparation of optically active anti-diols is presented.
The direct catalytic enantioselective functionalization of carbon-hydrogen bonds to carbon-heteroatom bonds is an important synthetic transformation.1 Recently, several examples of catalytic formation of new stereocenters containing C-N, C-O, and C-X (X ) F, Cl, Br) bonds have been presented. The formation of C-N bonds can involve chiral Lewis-acid-catalyzed amination of R-keto esters2a and β-keto esters2b and organocatalyic amination of aldehydes3a-c and ketones.3d R-Oxidation of aldehydes4a-c and ketones4d,e has been achieved using mainly L-proline as the catalyst and nitrosobenzene or singlet oxygen4f as the oxygen donors, while oxaziridines are used for the R-hydroxylation of β-keto esters catalyzed by chiral Lewis-acids.5 The enantioselective halogenation of aldehydes6 and ketones7 can be catalyzed by chiral amines using different chloro donors, while a Lewis-acidic chiral titanium complex acts as catalyst for the fluorina* To whom correspondence should be addressed. Fax: 45 8619 6199. Tel: 45 8942 3910. (1) See, e.g.: (a) Genet, J. P.; Greck, C.; Lavergne, D. In Modern Amination Methods; Ricci, A., Ed.; Wiley-VCH: Weinheim, 2000; Chapter 3. (b) Ramon, D. J.; Yus, M. Curr. Org. Chem. 2004, 8, 149. (2) (a) Juhl, K.; Jørgensen, K. A. J. Am. Chem. Soc. 2002, 124, 2420. (b) Marigo, M.; Juhl, K.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2003, 42, 1367. (3) (a) Bøgevig, A.; Juhl, K.; Kumaragurubaran, N.; Zhuang, W.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2002, 41, 1790. (b) List, B. J. Am. Chem. Soc. 2002, 124, 5656. (c) Kumaragurubaran, N.; Juhl, K.; Zhuang, W.; Bøgevig, A.; Jørgensen, K. A. J. Am. Chem. Soc. 2002, 124, 6254. (d) Vogt, H.; Vanderheiden, S.; Brase, S. Chem. Commun. 2003, 19, 2448. (4) See, e.g.: (a) Zhong, G. Angew. Chem., Int. Ed. 2003, 42, 4247. (b) Brown, S. P.; Brochu, M. P.; Sinz, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2003, 125, 10808. (c) Hayashi, Y.; Yamaguchi, J.; Hibino, K.; Shoji, M. Tetrahedron Lett. 2003, 44, 8293. (d) Bøgevig, A.; Sunde´en, H.; Co´rdova, A. Angew. Chem., Int. Ed. 2004, 43, 1109. (e) Hayashi, Y.; Yamaguchi, J.; Sumiya, T.; Shoji, M. Angew. Chem., Int. Ed. 2004, 43, 1112. (f) Cordova, A.; Sunden, H.; Engquist, M.; Ibrahem, I.; Casas, J. J. Am. Chem. Soc. 2004, 126, 8914. (5) Toullec, P. Y.; Bonaccorsi, C.; Mezzetti, A.; Togni, A. Proc. Nat. Acad. Sci. U.S.A. 2004, 101, 5810. (6) (a) Bochu, M. P.; Brown, S. P.; MacMillan, D. C. W. J. Am. Chem. Soc. 2004, 126, 4108. (b) Halland, N.; Braunton, A.; Marigo, M.; Bachmann, S.; Jørgensen, K. A. J. Am. Chem. Soc. 2004, 126, 4790. (7) Marigo, M.; Bachmann, S.; Halland, N.; Braunton, A.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2004, 43, 5507.
tion of β-keto esters using SelectFluor.8 This complex also catalyzes the chlorination of β-keto esters,9a while chiral copper complexes are effective catalysts for the enantioselective chlorination and bromination with NCS and NBS.9b The enantioselective organocatalytic R-hydroxylation of β-keto esters10 has according to our knowledge been reported only for the single substrate 5-chloro-1-oxoindan-2-carboxylic acid methyl ester in order to produce an intermediate for the preparation of the insecticide indoxacarb by the Dupont group.11,12 This transformation was achieved by means of tert-butyl hydroperoxide as the terminal oxidant and cinchona-derived chiral amines, such as chinconine as the catalyst. Recently, we have demonstrated that cinchona-alkaloid derivatives can catalyzed new types of enantioselective addition reactions,13 and we envisioned that these organocatalysts could be applied for the enantioselective hydroxylation of β-keto esters in more general terms. In this paper, we further investigate the organocatalytic enantioselective hydroxylation of β-keto esters, showing that it proceeds for various β-keto esters. Furthermore, we will demonstrate that the R-hydroxy-β-keto esters prepared are starting materials for the formation of, e.g., optically active anti-R,β-diols, compounds of importance as precursors of pharmaceutical as well as natural products. The synthesis of optically active diols is routinely performed by the Sharpless dihydroxylation;14 however, this reaction gives syn-diols, and the present procedure thus compliments this method. The enantioselective R-hydroxylation of β-keto esters is based on the formation of a chiral nucleophile in a catalytic amount, prepared by reaction of the β-keto ester with the cinchona-alkaloid derivative, which then reacts (8) (a) Hintermann, L.; Togni, A. Angew. Chem., Int. Ed. 2000, 39, 4359. (b) Piana, S.; Devillers, I.; Togni, A.; Rothlisberger, U. Angew. Chem., Int. Ed. 2002, 41, 971. (9) (a) Ibrahim, A.; Kleinbeck, F.; Togni, A. Helv. Chim. Acta 2004, 78, 605. (b) Marigo, M.; Kumaragurubaran, N.; Jørgensen, K. A. Chem. Eur. J. 2004, 10, 2133. (10) For a recent review see: Christoffers, J.; Baro, A.; Werner, T. Adv. Synth. Catal. 2004, 346, 143. (11) For an overview of the enantioselective hydroxylation of 5-chloro-1-oxo-indan-2-carboxylic acid methyl ester used for the formation of the insecticide indoxacarb with tert-butyl hydroperoxide/ cinchona alkaloids see: (a) McCann, S. F.; Annis, G. D.; Shapiro, R.; Piotrowski, D. W.; Lahm, G. P.; Long, J. K.; Lee, K. C.; Hughes, M. M.; Myers, B. J.; Griswold, S. M.; Reeves, B. M.; March, R. W.; Sharpe, P. L.; Lowder, P.; Barnette, W. E.; Wing, K. D. Pest. Manag. Sci. 2001, 57, 153; see also: (b) Shapiro, R.; Annis, G. D.; Blaisdell, C. T.; Dumas, D. J.; Fuchs, J.; Grisweld, S. M.; Highly, G. W.; Hollinsed, W. C.; Mrowca, J. J.; Sternberg, J. A.; Woltkowski, P. ACS Symp. Ser. 2000, 800 (Synthesis and Chemistry of Agrochemicals VI), 178. (c) Taylor, E. G.; Birch, L. US Patent WO 03/040083, PTC/US02/35615, 2003. (12) For use of chiral phase-transfer catalysis and molecular oxygen under basic conditions for hydroxylation of aromatic cyclic ketones, see: (a) Masui, M.; Ando, A.; Shioiri, T. Tetrahedron Lett. 1988, 29, 2835. (b) Christoffers, J.; Werner, T.; Unger, S.; Frey, W. Eur. J. Org. Chem. 2003, 424. (13) For the use of this approach for catalytic enantioselective addition of β-dicarbonyl compounds to alkynones, see: (a) Bella, M.; Jørgensen K. A. J. Am. Chem. Soc. 2004, 126, 5672. Amination of R-cyano esters: (b) Saaby, S.; Bella, M.; Jørgensen, K. A. J. Am. Chem. Soc. 2004, 126, 8120. See also: (c) Li, H.; Wang, Y.; Deng, L. J. Am. Chem. Soc. 2004, 126, 9906. (14) (a) Jacobsen, E. N.; Marko´, I.; Mungall, W. S.; Schro¨der, G.; Sharpless, K. B. J. Am. Chem. Soc. 1988, 110, 1968. (b) Wang, L.; Sharpless, K. B. J. Am. Chem. Soc. 1992, 114, 7568.
10.1021/jo048655w CCC: $27.50 © 2004 American Chemical Society
Published on Web 10/21/2004
J. Org. Chem. 2004, 69, 8165-8167
8165
with the electrophilic peroxide in an enantioselective manner. A screening was performed for the R-hydroxylation of 5-chloro-1-oxoindan-2-carboxylic acid methyl ester 1a with various cinchona-alkaloid derivatives and organic peroxides under different reaction conditions (eq 1), and some results are presented in Table 1.
TABLE 2. Enantioselective Hydroxylation of β-Keto Esters 1a-f with Cumyl Hydroperoxide Catalyzed by HDQ in CH2Br2 at Room Temperature entry
1, R
yielda (%)
eeb (%)
1 2 3 4 5 6
4-ClC6H4, Me, 1a C6H4, Me, 1b C6H4, Et, 1c C6H4, t-Bu, 1d C6H4, Bn, 1e -, Bn, 1f
2a, 88 2b, 95 2c, 83 2d,
