992
S. B. Tsogoeva et al. / Tetrahedron: Asymmetry 17 (2006) 989–992
11.4 Hz, 1H), 3.09–3.23 (m, 2H), 3.49–3.55 (m, 1H), 3.82 (t,
J = 7.8 Hz, 1H), 4.00 (quin, J = 5.4 Hz, 1H), 4.14 (t,
J = 8.1 Hz, 1H), 4.36 (quin, J = 5.4 Hz, 1H). ESI-MS (po-
sitive ion): m/z = 343.1 [M+H]+, 684.9 [2M+H]+. HRMS
(ESI): calcd for C15H26N4O5 [M+H]+ 343.19760; found
343.19760.
References
1. Review: Jarvo, E. R.; Miller, S. J. Tetrahedron 2002, 58,
2481–2495.
2. Review: Groeger, H; Wilken, J.; Berkessel, A. In Simple
Amino Acids and Short-chain Peptides as Efficient Metal-free
Catalysts in Asymmetric Synthesis. Schmalz, H.-G., Wirth, T.,
Eds.; Organic Synthesis Highlights V; WILEY-VCH: Wein-
heim, 2003; pp 178–186.
4.3. Tetrapeptide 2
3. Review: Tsogoeva, S. B. Lett. Org. Chem. 2005, 2, 208–213.
4. Copeland, G. T.; Jarvo, E. R.; Miller, S. J. J. Org. Chem.
1998, 63, 6784–6785.
5. Sculimbrene, B. R.; Morgan, A. J.; Miller, S. J. Chem.
Commun. 2003, 1781–1785.
6. Jarvo, E. R.; Copeland, G. T.; Papaioannou, N.; Bonitate-
bus, P. J., Jr.; Miller, S. J. J. Am. Chem. Soc. 1999, 121,
11638–11643.
1H NMR (300 MHz, CD3OD) d 1.42 (s, 9H, C(CH3)3),
1.99–2.13 (m, 4H), 2.27–2.35 (m, 4H), 2.85–2.93 (m, 2H),
3.16–3.21 (m, 4H), 3.57–3.61 (m, 2H), 3.88–4.05 (m, 4H),
4.17–4.44 (m, 4H). ESI-MS (positive ion): m/z = 567.7
[M+H]+. HRMS (ESI): calcd for C25H42N8O7 [M+H]+
567.32492; found 567.32477.
7. Horstmann, T. E.; Guerin, D. J.; Miller, S. J. Angew. Chem.
2000, 112, 3781–3784; Angew. Chem., Int. Ed. 2000, 39, 3635–
3638.
8. Guerin, D. J.; Miller, S. J. J. Am. Chem. Soc. 2002, 124, 2134–
2136.
9. Tsogoeva, S. B.; Jagtap, S. B. Synlett 2004, 2624–2626.
10. Tsogoeva, S. B.; Jagtap, S. B.; Ardemasova, Z. A.; Kalikhe-
vich, V. N. Eur. J. Org. Chem. 2004, 4014–4019.
11. Tanaka, K.; Mori, A.; Inoue, S. J. Org. Chem. 1990, 55, 181–
185.
12. Iyer, M. S.; Gigstad, K. M.; Namdev, N. D.; Lipton, M.
J. Am. Chem. Soc. 1996, 118, 4910–4911.
13. Sigman, M. S.; Vachal, P.; Jacobsen, E. N. Angew. Chem.
2000, 112, 1336–1338; Angew. Chem., Int. Ed. 2000, 39, 1279–
1281.
14. Vachal, P.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124,
10012–10014.
15. Sculimbrene, B. R.; Miller, S. J. J. Am. Chem. Soc. 2001, 123,
10125–10126.
4.4. General procedure for the Michael reaction
4.4.1. (R)-(+)-3-(2-Nitropropane-2-yl) cyclohexanone 5. 2-
Nitropropane (0.63 mmol) was added to a stirred solution
of 2-cyclohexen-1-one (0.5 mmol), trans-2,5-dimethylpiper-
azine (0.5 mmol), and peptide catalyst (2 mol %) in pre-
dried solvent (CHCl3, 4 mL), and the reaction mixture stir-
red at room temperature for 5 days. The reaction mixture
was worked up as described in the literature.24 The residues
were purified by chromatography on SiO2-column (hexane/
ethyl acetate) to afford the desired product 5. The enantio-
meric excess of the product was measured by 13C NMR of
corresponding ketal with (2R,3R)-2,3-butane diol.24 1H
NMR (300 MHz, CDCl3) d 2.48–2.34 (m, 3H), 2.31–2.21
(m, 1H), 2.19–2.08 (m, 2H), 1.85–1.76 (m, 1H), 1.71–1.53
(m, 1H), 1.58 (s, 3H), 1.57 (s, 3H), 1.48–1.34 (m, 1H).
13C NMR (150.8 MHz, CDCl3) d 208.9 (C@O), 90.6
(Cquat.), 46.5 (CH), 42.6 (CH2), 40.7 (CH2), 25.9 (CH2),
24.3 (CH2), 23.3 (CH3), 22.5 (CH3). ESI-MS (positive
ion): m/z 208.1 [M+Na]+.
16. Imbriglio, J. E.; Vasbinder, M. M.; Miller, S. J. Org. Lett.
2003, 5, 3741–3743.
17. (a) 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; (b) Tang, Z.; Jiang, F.; Cui, X.; Gong, L.-Z.; Mi,
A.-Q.; Jiang, Y.-Z.; Wu, Y.-D. PNAS 2004, 101, 5755–5760;
(c) Tang, Z.; Yang, Z.-H.; Cun, L.-F.; Gong, L.-Z.; Mi,
A.-Q.; Jiang, Y.-Z. Org. Lett. 2004, 6, 2285–2287.
18. Martin, H. J.; List, B. Synlett 2003, 1901–1902.
19. Kofoed, J.; Nielsen, J.; Reymond, J.-L. Bioorg. Med. Chem.
Lett. 2003, 13, 2445–2447.
4.5. General procedure for the aldol reaction
4.5.1. (4R)-(4-Nitrophenyl)-4-hydroxy-2-butanone 12. Pep-
tide catalyst (5–15 mol %) was added to a dry acetone/
DMSO (or DMF) (1:4) mixture and stirred for 20 min.
4-Nitrobenzaldehyde (0.05 M) was added and the result-
ing mixture stirred at room temperature under nitro-
gen. After completion of the reaction, the mixture was
worked up as described in the literature.28 1H NMR
(300 MHz, CDCl3) d 2.20 (s, 3H), 2.84 (m, 2H), 3.58 (br
s, 1H), 5.24 (m, 1H), 7.53 (d, 2H), 8.20 (d, 2H). HPLC
(Daicel Chiralpak AS): n-hexane/2-propanol = 75:25, flow
rate 1 mL/min, k = 254 nm: tR (major) = 18.84 min, tR
(minor) = 26.58 min.
}
´
´
20. Szo¨llosi, G.; London, G.; Balaspiri, L.; Somlai, C.; Bartok,
M. Chirality 2003, 15, S90–S96.
21. Shi, L.-X.; Sun, Q.; Ge, Z.-M.; Zhu, Y.-Q.; Cheng, T.-M.; Li,
R.-T. Synlett 2004, 2215–2217.
22. Tsogoeva, S. B.; Wei, S.-W. Tetrahedron: Asymmetry 2005,
16, 1947–1951.
´
´
23. Zou, W.; Ibrahem, I.; Dziedzic, P.; Sunden, H.; Cordova, E.
A. Chem. Commun. 2005, 4946–4948.
24. Hanessian, S.; Pham, V. Org. Lett. 2000, 2, 2975–2978.
25. Hanessian, S.; Govindan, S.; Warrier, J. S. Chirality 2005, 17,
540–543.
26. Andrey, O.; Alexakis, A.; Tomassini, A.; Bernardinelli, G.
Adv. Synth. Catal. 2004, 346, 1147–1168.
Acknowledgment
27. For iminium and enamine catalysis, see: List, B. Chem.
Commun. 2006, 819–824.
28. Sakthivel, K.; Notz, W.; Bui, T.; Barbas, C. F., III. J. Am.
Chem. Soc. 2001, 123, 5260–5267.
The authors gratefully acknowledge the Deutsche Fors-
chungsgemeinschaft and Fonds der Chemischen Industrie
for generous financial support.