3846
M. Limbach / Tetrahedron Letters 47 (2006) 3843–3847
AA
(20 mol%),
O
O
O
OH
O
DMSO,
20 ºC, time
H
NO2
NO2
NO2
3
( )- or ( )-4
5
R
S
Scheme 2. b3-Homoamino acids in the intermolecular aldol reaction of acetone with p-nitrobenzaldehyde.
Table 2. Catalyst screening in the intermolecular aldol-reaction of acetone with p-nitrobenzaldehyde
Amino acid (AA)
Time (d)
Yield 4a (%)
eeb (%)
Ratio 4/5c
H-Pro-OH
H-(R)-Pro-OH
H-Val-OH
H-Ala-OH, H-Phe-OH, H-b3hAla-OH, H-b3hIle-OH,
H-b3hPhe-OH, H-b3hTrp-OH, H-b3hHis(Trt)-OH
3
3
3
65 (hom.)
48 (hom.)
50 (hom.)
<5 (hom.)
54 (R)
76 (S)
72 (R)d
n.d.e
6.23:1
1.03:1
1.19:1
—
22
3
58 (hom.)
48 (R)
3.34:1
O
MeHN
OH
a Isolated yield after flash column chromatography.
b Determined by HPLC on a Chiralcel OJ (0.46 · 25 cm). Flow 1 mL/min, k = 254 nm, hexane/iPrOH = 9:1. tR (R) = 28.2 min, tR (S) = 31.5 min.
c Determined from the crude 1H NMR spectrum.
d In the presence of 1 mol % water.
e Not determined.
K. A. Chem. Commun. 2002, 620–621; (f) Tang, Z.; Jiang,
F.; Yu, L.-T.; Cui, X.; Gong, L.-Z.; Mi, A.-Q.; Jiang,
Y.-Z.; Wu, Y.-D. J. Am. Chem. Soc. 2003, 125, 5262–5263;
(g) Mase, N.; Tanaka, F.; Barbas, C. F., III. Angew.
Chem., Int. Ed. 2004, 43, 2420–2423; (h) Torii, H.;
Nakadai, M.; Ishihara, K.; Saito, S.; Yamaoto, H. Angew.
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Sultana, S. S. Chem. Commun. 2004, 2450–2451; (l)
Allemann, C.; Gordillo, R.; Clemente, F. R.; Cheong, P.
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Acknowledgements
M.L. gratefully acknowledges fellowships from the
German Merit Foundation (Studienstiftung des Deuts-
chen Volkes) during undergraduate (2000–2002) and
graduate studies (2002–2004). Novartis Pharma AG,
CH-Basel, is thanked for financial support. M.L. is
grateful to Professor D. Seebach, ETH Zurich, for
¨
fruitful discussions and proofreading of the manuscript
and Professor E. M. Carreira for sharing HPLC
facilities.
Supplementary data
Experimental procedures, characterization data and
chromatographic analyses of enantiomerically enriched
products. This material is available free of charge via
mentary data associated with this article can be found,
´
3. (a) Bassan, A.; Zou, W.; Reyes, E.; Himo, F.; Cordova, A.
´
Angew. Chem., Int. Ed. 2005, 44, 7028–7032; (b) Cordova,
´
A.; Ibrahem, I.; Casas, J.; Sunden, H.; Engqvist, M.;
´
Reyes, E. Chem. Eur. J. 2005, 11, 4772–4784; (c) Cordova,
A.; Zou, W.; Ibrahem, I.; Reyes, E.; Engqvist, M.; Liao,
W.-W. Chem. Commun. 2005, 3586–3588.
4. Shigehisa, H.; Mizutani, T.; Tosaki, S.-Y.; Ohshima, T.;
Shibasaki, M. Tetrahedron 2005, 61, 5057–5065; For the
use of H-Phe-OH in the asymmetric intramolecular aldol
References and notes
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