S. Y. Kang, Y. S. Park
SHORT COMMUNICATION
[3]
a) C. M. Binder, A. Bautista, M. Zaidlewicz, M. P. Krzemin´ski,
A. Oliver, B. Singaram, J. Org. Chem. 2009, 74, 2337–2343; b)
D. Scarpi, E. G. Occhiato, A. Guarna, Tetrahedron: Asymmetry
2009, 20, 340–350; c) C. Anaya de Parrodi, E. Juaristi, Synlett
2006, 2699–2715; d) N. García-Delgado, M. Fontes, M. A. Per-
icàs, A. Riera, X. Verdaguer, Tetrahedron: Asymmetry 2004, 15,
2085–2090; e) J. Shannon, D. Bernier, D. Rawson, S. Wood-
ward, Chem. Commun. 2007, 3945–3947; f) N. García-Delgado,
K. S. Reddy, L. Solà, A. Riera, M. A. Pericàs, X. Verdaguer, J.
Org. Chem. 2005, 70, 7426–7428; g) T. Tanaka, Y. Yasuda, M.
Hayashi, J. Org. Chem. 2006, 71, 7091–7093; h) M. W. Paixão,
A. L. Braga, D. S. Lüdtke, J. Braz. Chem. Soc. 2008, 19, 813–
830; i) F. Schmidt, R. T. Stemmler, J. Rudolph, C. Bolm, Chem.
Soc. Rev. 2006, 35, 454–470; j) R. Noyori, M. Kitamura, An-
gew. Chem. 1991, 103, 34; Angew. Chem. Int. Ed. Engl. 1991,
30, 49–69.
a) Y. S. Sokeirik, A. Hoshina, M. Omote, K. Sato, A. Tarui, I.
Kumadaki, A. Ando, Chem. Asian J. 2008, 3, 1850–1856; b)
M. Hatano, T. Miyamoto, K. Ishihara, J. Org. Chem. 2006, 71,
6474–6484; c) W.-S. Huang, Q.-S. Hu, L. Pu, J. Org. Chem.
1999, 64, 7940–7956; d) B. Schmidt, D. Seebach, Angew. Chem.
1991, 103, 100; Angew. Chem. Int. Ed. Engl. 1991, 30, 99–101.
a) J.-C. Kizirian, Chem. Rev. 2008, 108, 140–205; b) J. Gonza-
lez-Sabin, V. Gotor, F. A. Rebolledo, Tetrahedron: Asymmetry
2006, 17, 449–454; c) M. L. Richmond, C. T. Seto, J. Org.
Chem. 2003, 68, 7505–7508; d) M. I. Burguete, J. Escorihuela,
S. V. Luis, A. Lledós, G. Ujaque, Tetrahedron 2008, 64, 9717–
9724; e) M. Asami, H. Watanabe, K. Honda, S. Inoue, Tetrahe-
dron: Asymmetry 1998, 9, 4165–4173.
Conclusions
We have developed a new class of dipeptide catalysts for
the enantioselective addition of dimethylzinc to aromatic
aldehydes. Three subunits within aa-l-Pro dipeptide were
varied to increase the enantioselectivity and the optimiza-
tion led us to identify l-Asp-l-Pro dipeptides 21–25 as ef-
fective catalysts for the addition. The simple modular struc-
ture in combination with the ready availability of l-amino
acids renders the dipeptide catalysts highly attractive. This
work paves the way for the synthesis and evaluation of
larger libraries of dipeptide catalysts for reactions involving
alkylzinc, as well as other organometallic reagents. Further
studies on the improvement of enantioselectivity and on the
structure of the zinc–dipeptide complex are now in progress.
[4]
[5]
Experimental Section
General Procedure: Dimethylzinc (2 m in toluene, 4.0 equiv.) was
added to a solution of the dipeptide catalyst (0.1 or 0.05 equiv.)
and aldehyde (1.0 equiv.) in toluene at 0 °C. The homogeneous
solution was stirred at room temperature for 48 h. The reaction was
quenched by the addition of 1 m HCl, and the solution was ex-
tracted with CHCl3. The combined organic extracts were dried with
anhydrous MgSO4, filtered, and concentrated in vacuo. Chromato-
graphic separation on silica gel (hexane/EtOAc) afforded the en-
antioenriched ethanols in 95–93% yield, and the enantioselectivity
of the products was measured by HPLC with chiral columns by
using racemic material as a standard.
[6]
For reviews on the enantioselective addition of dialkylzinc to
aldehydes by using α-amino amide based catalysts, see: a) B. D.
Dangel, R. Polt, Org. Lett. 2000, 2, 3003–3006; b) M. I. Burg-
uete, M. Collado, J. Escorihuela, S. V. Luis, Angew. Chem.
2007, 119, 9160; Angew. Chem. Int. Ed. 2007, 46, 9002–9005;
c) C. M. Spout, C. T. Seto, J. Org. Chem. 2003, 68, 7788–7794.
Supporting Information (see footnote on the first page of this arti-
cle): Detailed experimental procedures and characterization data
[7] a) P. G. Cozzi, P. Kotrusz, J. Am. Chem. Soc. 2006, 128, 4940–
4941; b) Y. S. Sokeirik, H. Mori, M. Omote, K. Sato, A. Tarui,
I. Kumadaki, A. Ando, Org. Lett. 2007, 9, 1927–1929; c) M.-
C. Wang, Q.-J. Zhang, G.-W. Li, Z.-K. Liu, Tetrahedron: Asym-
metry 2009, 20, 288–292; d) N. García-Delgado, M. Fontes,
M. A. Pericàs, A. Riera, X. Verdaguer, Tetrahedron: Asym-
metry 2004, 20, 2085–2090.
[8] a) J.-y. Chang, E.-k. Shin, H. J. Kim, Y. Kim, Y. S. Park, Tetra-
hedron 2005, 61, 2743–2750; b) J. Nam, J.-Y. Chang, E.-k. Shin,
H. J. Kim, Y. Kim, S. Jang, Y. S. Park, Tetrahedron 2004, 60,
6311–6318; c) J. Nam, J.-y. Chang, K.-S. Hahm, Y. S. Park,
Tetrahedron Lett. 2003, 44, 7727–7730; d) E.-k. Shin, J.-y.
Chang, H. J. Kim, Y. Kim, Y. S. Park, Bull. Korean Chem. Soc.
2006, 27, 447–449.
including copies of the H NMR and 13C NMR spectra.
1
Acknowledgments
This work was supported by a grant from the Korea Research
Foundation (2009–0089650) and the Seoul R&BD Program
(WR090671).
[1] a) J. Long, L. Xu, H. Du, K. Li, Y. Shi, Org. Lett. 2009, 11,
5226–5229; b) P. Fu, M. L. Snapper, A. H. Hoveyda, J. Am.
Chem. Soc. 2008, 130, 5530–5541; c) C. M. Spout, M. L. Rich-
mond, C. T. Seto, J. Org. Chem. 2005, 70, 7408–7417; d) N. S.
Josephsohn, K. W. Kuntz, M. L. Snapper, A. H. Hoveyda, J.
Am. Chem. Soc. 2001, 123, 11594–11599.
[2] a) L. Pu, H.-B. Yu, Chem. Rev. 2001, 101, 757–824; b) K. Soai,
S. Niwa, Chem. Rev. 1992, 92, 833–856; c) M. Hatano, T. Miya-
moto, K. Ishihara, Curr. Org. Chem. 2007, 11, 127–157.
[9] Catalysts 11–25 shown in Tables 2 and 3 were prepared by the
coupling of N-Boc-aa-OH and l-Pro-OMe and following N,N-
dibenzylation with the corresponding benzyl bromide. See the
Supporting Information for details.
Received: January 18, 2012
Published Online: Februars 21, 2012
1706
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1703–1706