ORGANIC
LETTERS
2012
Vol. 14, No. 17
4522–4524
pH-Independent Transfer Hydrogenation
in Water: Catalytic, Enantioselective
Reduction of β‑Keto Esters
Martin A. Ariger and Erick M. Carreira*
€
Laboratorium fu€r Organische Chemie, ETH Zu€rich, Honggerberg, Switzerland
Received July 10, 2012
ABSTRACT
A pH-independent asymmetric transfer hydrogenation of β-keto esters in water with formic acid/sodium formate is described. The reaction is
conducted open to air and gives access to β-hydroxy esters in excellent yields and selectivities.
In recent decades, the development of methods for
catalytic asymmetric synthesis has gained increasing im-
portance in chemistry. Within this area, asymmetric trans-
fer hydrogenation (ATH) plays an important role in
accessing small building blocks with procedures that are
significant, as it provided new opportunities for asym-
metric catalysis. A few years later Ogo documented Ir(III)
diamine complexes, which are able to reduce simple ke-
tones and aldehydes in water, a reaction which was noted
to be pH-dependent.3
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a simple vis-a-vis preparation of starting materials and
We recently described Ir(III) catalyzed ATH reactions
of nitroalkenes and cyano- and nitro-substituted aceto-
phenonesemployingmonosulfonylated diaminesaswellas
diamine ligands.4 Herein, we report the pH-independent
iridium-catalyzed ATH of β-keto esters5 in water with
formic acid as a reductant. Although the enantiomeric
excess observed when the reaction is conducted under very
experimental implementation. Additionally, ATH consti-
tutes an attractive alternative to the use of protocols
prescribing molecular hydrogen.1
The pioneering studies ofNoyori disclosing the ability of
Ru(II) complexes bearing monosulfonylated diamine
complexes to catalyze hydrogen transfer reactions2 were
(3) (a) Ogo, S.; Makihara, N.; Watanabe, Y. Organometallics 1999,
18, 5470. (b) Ogo, S.; Makihara, N.; Kaneko, Y.; Watanabe, Y.
Organometallics 2001, 20, 4903. (c) Abura, T.; Ogo, S.; Watanabe, Y.;
Fukuzumi, S. J. Am. Chem. Soc. 2003, 125, 4149. (d) Ogo, S.; Uehara,
K.; Abura, T.; Fukuzumi, S. J. Am. Chem. Soc. 2004, 126, 3020. For a
recent review on Ir-catalyzed ATH, see:(e) Saidi, O.; Williams, M. J.
Topics in Organometallic Chemistry, Vol. 34; Andersson, P. G., Ed.;
Springer, Heidelberg, 2011; p 77.
(1) For recent reviews on ATH, see: (a) Ikariya, T.; Murata, K.;
Noyori, R. Org. Biomol. Chem. 2006, 4, 393. (b) Gladiali, S.; Alberico, E.
Chem. Soc. Rev. 2006, 35, 226. (c) Samec, J. S. M.; Backvall, J.-E.;
Andersson, G. G.; Brandt, P. Chem. Soc. Rev. 2006, 35, 237. (d)
Everaere, K.; Mortreux, A.; Carpentier, J.-F. Adv. Synth. Catal. 2003,
345, 67. (e) Blaser, H.-U.; Malan, C.; Pugin, B.; Spindler, F.; Steiner, H.;
Studer, M. Adv. Synth. Catal. 2003, 345, 103. (f) Wang, C.; Wu, X.; Xiao,
J. Chem.;Asian J. 2008, 3, 1750.
€
(4) (a) Soltani, O.; Ariger, M. A.; Carreira, E. M. Org. Lett. 2009, 11,
(2) (a) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R.
J. Am. Chem. Soc. 1995, 117, 2675. (b) Hashiguchi, S.; Fujii, A.;
Takehara, J.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1995, 117,
7562. (c) Hashiguchi, S.; Fujii, A.; Takehara, J.; Ikariya, T.; Noyori, R.
J. Am. Chem. Soc. 1995, 117, 9532. (d) Fujii, A.; Hashiguchi, S.;
Uematsu, N.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1996, 118,
2521. (e) Uematsu, N.; Fujii, A.; Hashiguchi, S.; Ikariya, T.; Noyori, R.
J. Am. Chem. Soc. 1996, 118, 4916. (f) Hashiguchi, S.; Fujii, A.; Haack,
K. J.; Matsumura, K.; Ikariya, T.; Noyori, R. Angew. Chem., Int. Ed.
1997, 36, 288. (g) Yamakawa, M.; Ito, H.; Noyori, R. J. Am. Chem. Soc.
2000, 122, 1466. (h) Haack, K. J.; Hashiguchi, S.; Fujii, A.; Ikariya, T.;
Noyori, R. Angew. Chem., Int. Ed. 1997, 36, 285.
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4196. (b) Soltani, O.; Ariger, M. A.; Vazquez-Villa, H.; Carreira, E. M.
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Org. Lett. 2010, 12, 2893. (c) Vazquez-Villa, H.; Reber, S.; Ariger, M. A.;
Carreira, E. M. Angew. Chem., Int. Ed. 2011, 50, 8979.
(5) (a) Everaere, K.; Carpentier, J.-F.; Mortreux, A.; Bullieard, M.
Tetrahedron: Asymmetry 1998, 9, 2971. (b) Everaere, K.; Carpentier, J.-
F.; Mortreux, A.; Bullieard, M. Tetrahedron: Asymmetry 1999, 10, 4663.
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(c) Sterk, D.; Massoud, S. S.; Mohar, B. Tetrahedron: Asymmetry 2002,
13, 2605. (d) Li, Y.; Li, Z.; Li, F.; Wang, Q.; Tao, F. Org. Biomol. Chem.
2005, 3, 2513. (e) Huang, X.; Ying, J. Y. Chem. Commun. 2007, 1825. (f)
Wu, X.; Li, X.; Zanotti-Gerosa, A.; Pettman, A.; Liu, J.; Mills, A. J.;
Xiao, J. Chem.;Eur. J. 2008, 14, 2209.
r
10.1021/ol301903c
Published on Web 08/17/2012
2012 American Chemical Society