A R T I C L E S
Handa et al.
Scheme 1. Catalytic Enantio- and Diastereoselective Nitro-Mannich
Reaction
Cu/Sm catalyst for the syn-selective catalytic asymmetric nitro-
Mannich reaction, the mechanistic studies of the Cu/Sm catalyst,
reoptimization toward the second generation Cu/Sm catalyst,
and its application to catalytic asymmetric synthesis of
pharmaceuticals.
Results and Discussion
A. Development of the First-Generation Cu/Sm Schiff Base
Catalyst and Its Application to the Syn-Selective Asymmetric
Nitro-Mannich Reaction. The nitro-Mannich (aza-Henry) reac-
tion10 provides synthetically versatile ꢀ-nitroamines (Scheme
1) that can be converted to 1,2-diamines, R-aminocarbonyl
compounds, and others.11 Over the past decade, tremendous
effort has been devoted to the development of catalytic
enantioselective variants.12-17 Since our reports using hetero-
bimetallic metal-binolate complexes,12 diastereo- and enanti-
Figure 1. (a) Concept for bimetallic bifunctional catalysts, (b) a hetero-
bimetallic La/Li/BINOL catalyst, and (c) dinucleating Schiff bases 1-H4
and a heterobimetallic transition metal(M)/rare earth metal (RE)/Schiff base
1 complex.
(10) For a review of catalytic asymmetric nitro-Mannich reactions, see:
(a) Westermann, B. Angew. Chem., Int. Ed. 2003, 42, 151. (b)
Marque´s-Lo´pez, E.; Merino, P.; Tejero, T.; Herrera, R. P. Eur. J. Org.
Chem. 2009, 2401.
with an ErCl3-pybox system.7 However, the combination of
transition metal/rare earth metal as chiral heterobimetallic Schiff
base catalysts has not been investigated.
(11) (a) For the utility of the nitro group in organic synthesis, see: The
Nitro Group in Organic Synthesis; Ono, N., Ed.; Wiley-VCH: New
York, 2002. (b) Ballini, R.; Petrini, M. Tetrahedron 2004, 60, 1017.
(c) Czekelius, C.; Carreira, E. M. Angew. Chem., Int. Ed. 2005, 44,
612.
In this context, we launched a new investigation of transition
metal/rare earth metal/Schiff base catalysts to expand the
diversity of heterobimetallic rare earth metal asymmetric
catalysts and communicated the utility of a dinucleating Schiff
base 1a (Figure 1c) in 2007.8,9 The dinucleating Schiff base 1a
was suitable for incorporating both a transition metal and a rare
earth metal. A Cu/Sm/Schiff base 1a complex (M ) Cu, RE )
Sm) promoted the syn-selective catalytic asymmetric nitro-
Mannich reaction. In the present paper, we report the complete
details of the heterobimetallic Cu/Sm/Schiff base 1a catalysis.
Here, we describe the design of transition metal/rare earth metal
heterobimetallic catalysts, the development of the first-generation
(12) Yamada, K.-I.; Harwood, S. J.; Gro¨ger, H.; Shibasaki, M. Angew.
Chem., Int. Ed. 1999, 38, 3504.
(13) For selected examples of enantioselective nitro-Mannich reactions with
nitromethane, see: (a) Okino, T.; Nakamura, S.; Furukawa, T.;
Takemoto, Y. Org. Lett. 2004, 6, 625. (b) Fini, F.; Sgarzani, V.;
Pettersen, D.; Herrera, R. P.; Bernardi, L.; Ricci, A. Angew. Chem.,
Int. Ed. 2005, 44, 7975. (c) Bernardi, L.; Fini, F.; Herrera, R. P.; Ricci,
A.; Sgarzani, V. Tetrahedron 2006, 62, 375. (d) Palomo, C.; Oiarbide,
M.; Halder, R.; Laso, A.; Lo´pez, R. Angew. Chem., Int. Ed. 2006, 45,
117. (e) Gao, F.; Zhu, J.; Tang, Y.; Deng, M.; Qian, C. Chirality 2006,
18, 741. (f) Zhou, H.; Peng, D.; Qin, B.; Hou, Z.; Liu, X.; Feng, X.
J. Org. Chem. 2007, 72, 10302. (g) Chang, Y.-W.; Yang, J.-J.; Dang,
J.-N.; Xue, Y.-X. Synlett 2007, 2283. (h) Wang, C.; Zhou, Z.; Tang,
C. Org. Lett. 2008, 10, 1707. (i) Tan, C.; Liu, X.; Wang, L.; Wang,
J.; Feng, X. Org. Lett. 2008, 10, 5305. (j) Zhang, G.; Yashima, E.;
Woggon, W.-D. AdV. Synth. Catal. 2009, 351, 1255. In refs 13a and
13h, nitroethane is also utilized in one example, giving anti-adducts.
(14) Anti-selective reactions with metal catalysts: (a) Yamada, K.-I.; Moll,
G.; Shibasaki, M. Synlett 2001, 980. (b) Nishiwaki, N.; Knudsen, K. R.;
Gothelf, K. V.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2001, 40,
2992. (c) Knudsen, K. R.; Risgaard, T.; Nishiwaki, N.; Gothelf, K. V.;
Jørgensen, K. A. J. Am. Chem. Soc. 2001, 123, 5843. (d) Lee, A.;
Kim, W.; Lee, J.; Hyeon, T.; Kim, B. M. Tetrahedron: Asymmetry
2004, 15, 2595. (e) Anderson, J. C.; Howell, G. P.; Lawrence, R. M.;
Wilson, C. S. J. Org. Chem. 2005, 70, 5665. (f) Trost, B. M.; Lupton,
D. W. Org. Lett. 2007, 9, 2023.
(6) (a) Annamalai, V.; DiMauro, E. F.; Carroll, P. J.; Kozlowski, M. C.
J. Org. Chem. 2003, 68, 1973, and references therein. (b) Yang, M.;
Zhu, C.; Yuan, F.; Huang, Y.; Pan, Y. Org. Lett. 2005, 7, 1927. (c)
Li, W.; Thakur, S. S.; Chen, S.-W,; Shin, C.-K.; Kawthekar, R. B.;
Kim, G.-J. Tetrahedron Lett. 2006, 47, 3453. For related homobime-
tallic Schiff base catalysts, see: (d) Hirahata, W.; Thomas, R. M.;
Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2008, 130, 17658.
(e) Mazet, C.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2008, 47, 1762.
(f) Wu, B.; Gallucci, J. C.; Parquette, J. R.; RajanBabu, T. V. Angew.
Chem., Int. Ed. 2009, 48, 1126.
(7) Sammis, G. M.; Danjo, H.; Jacobsen, E. N. J. Am. Chem. Soc. 2004,
126, 9928.
(8) For the preliminary communication of this article, see: Handa, S.;
Gnanadesikan, V.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc.
2007, 129, 4900.
(15) Anti-selective reactions with thioureas: (a) Yoon, T. P.; Jacobsen, E. N.
Angew. Chem., Int. Ed. 2005, 44, 466. (b) Xu, X.; Furukawa, T.;
Okino, T.; Miyabe, H.; Takemoto, Y. Chem.sEur. J. 2006, 12, 466.
(c) Bode, C. M.; Ting, A.; Schaus, S. E. Tetrahedron 2006, 62, 11499.
(d) Robak, M. T.; Trincado, M.; Ellman, J. A. J. Am. Chem. Soc.
2007, 129, 15110. (e) Wang, C.-J.; Dong, X.-Q.; Zhang, Z.-H.; Xue,
Z.-Y.; Teng, H.-L. J. Am. Chem. Soc. 2008, 130, 8606. (f) Rampalakos,
C.; Wulff, W. D. AdV. Synth. Catal. 2008, 350, 1785. (g) Takada, K.;
Nagasawa, K. AdV. Synth. Catal. 2009, 351, 345.
(9) For the utility of 1a as Pd/La-1a cat., see: (a) Handa, S.; Nagawa, K.;
Sohtome, Y.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed.
2008, 47, 3230. (b) Sohtome, Y.; Kato, Y.; Handa, S.; Aoyama, N.;
Nagawa, K.; Matsunaga, S.; Shibasaki, M. Org. Lett. 2008, 10, 2231.
For related works, see also: (c) Mihara, H.; Xu, Y.; Shepherd, N. E.;
Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc. 2009, 131, 8384.
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4926 J. AM. CHEM. SOC. VOL. 132, NO. 13, 2010