1H), 7.95 (br s, 1H), 8.64 (d, J = 4.5 Hz, 1H); 13C NMR (100 MHz,
d6-DMSO, 80 ◦C) d 11.30, 24.57, 24.84, 26.21, 27.69, 36.45, 40.28,
55.12, 55.74, 56.52, 59.25, 102.96, 119.96, 120.43, 127.56, 130.57,
143.72, 145.59, 146.86, 156.54, 181.77; HRMS (FAB) calcd for
[C41H52N6O2S+H]+: 693.3951 (100.0%); found: 693.3951 (100.0%);
IR (powder) 3307, 2935, 2870, 1622, 1508, 1454, 1363, 1226, 1080,
1030, 853, 827, 716 cm-1.
10029, MEST) and Cooperative R&D Program (B551179-
10-03-00, Korea Research Council Industrial Science and
Technology).
Notes and references
1 (a) A. Berkessel, H. Gro¨ger, Asymmetric Organocatalysis (eds), Wiley-
VCH, Weinheim, 2005, pp. 1–8; (b) P. I. Dalko, Enantioselective
Organocatalysis (ed), Wiley-VCH, Weinheim, 2007, pp. 1–17; (c) C.
E. Song, In Cinchona Alkaloids in Synthesis and Catalysis, WILEY-
VCH, Weinheim, 2009, pp. 105–355; (d) B. List and Chem, Rev., 2007,
107, 5413–5883 (special issue on organocatalysis); (e) K. N. Houk and
B. List, Acc. Chem. Res., 2004, 37, 487–631 (special issue on asymmetric
organocatalysis); (f) B. List and J. W. Yang, Science, 2006, 313, 1584–
1586; (g) D. W. C. MacMillan, Nature, 2008, 455, 304–308.
2 (a) J.-A. Ma and D. Cahard, Angew. Chem., Int. Ed., 2004, 43, 4566–
4583; (b) C. Allemann, R. Gordillo, F. R. Clemente, P. H.-Y. Cheong
and K. N. Houk, Acc. Chem. Res., 2004, 37, 558–569.
3 For Reviews (a) Y. Takemoto, Org. Biomol. Chem., 2005, 3, 4299–4306;
(b) M. S. Taylor and E. N. Jacobsen, Angew. Chem., Int. Ed., 2006,
45, 1520–1543; (c) T. Marcelli, J. H. van Maarseveen and H. Hiemstra,
Angew. Chem., Int. Ed., 2006, 45, 7496–7504; (d) S. J. Connon, Chem.–
Eur. J., 2006, 12, 5418–5427; (e) S. J. Connon, Chem. Commun., 2008,
2499–2510.
4 (a) H. B. Jang, H. S. Rho, J. S. Oh, E. H. Nam, S. E. Park, H. Y. Bae
and C. E. Song, Org. Biomol. Chem., 2010, 8, 3918–3922; (b) S. H. Oh,
H. S. Rho, J. W. Lee, J. E. Lee, S. H. Youk, J. Chin and C. E. Song,
Angew. Chem., Int. Ed., 2008, 47, 7872–7875; (c) H. S. Rho, S. H. Oh,
J. W. Lee, J. Y. Lee, J. Chin and C. E. Song, Chem. Commun., 2008,
1208–1210.
5 (a) T. Okino, Y. Hoashi, T. Furukawa, X. Xu and Y. Takemoto, J.
Am. Chem. Soc., 2005, 127, 119–125; (b) A. Berkessel, S. Mukherjee, F.
Cleeman, Mu¨ller and J. Lex, Chem. Commun., 2005, 1898–1900; (c) A.
Berkessel, F. Cleeman, S. Mukherjee, T. N. Mu¨ller and J. Lex, Angew.
Chem., Int. Ed., 2005, 44, 807–811.
Bis-QN-TU (Id). mp 170 ◦C, aD: -145.4 (c = 0.1 in CHCl3). 1H
◦
NMR (400 MHz, d6-DMSO, 80 C) d 0.78–0.85 (m, 1H), 1.13–
1.23 (m, 1H), 1.44–1.55 (m, 3H), 2.15–2.25 (m, 1H), 2.59–2.68 (m,
1H), 2.90–3.18 (m, 4H), 3.92 (s, 3H), 4.87–4.97 (m, 2H), 5.64 (d,
J = 10.5 Hz, 1H), 5.69–5.81 (m, 1H), 7.31 (d, J = 4.5 Hz, 1H), 7.37
(dd, J = 2.6 and 9.2 Hz, 1H), 7.81 (d, J = 2.6 Hz, 1H), 7.93 (d, J =
9.2 Hz, 1H), 7.94 (br s, 1H), 8.65 (d, J = 4.5 Hz, 1H); 13C NMR
(100 MHz, d6-DMSO, 80 ◦C) d 24.98, 26.62, 26.90, 38.46, 40.22,
54.86, 55.14, 55.72, 59.28, 102.95, 113.45, 119.98, 120.48, 127.53,
130.58, 141.37, 143.73, 145.41, 146.86, 156.58, 181.80; HRMS
(FAB) calcd for [C41H48N6O2S+H]+: 689.3638 (100.0%); found:
689.3638 (100.0%); IR (powder) 3255, 2938, 2870, 1623, 1510,
1468, 1350, 1231, 1031, 915, 847, 676 cm-1.
General procedure for DKR of racemic azlactones
To a stirred solution of azlactone 1 (0.5 mmol) and catalyst
(0.05 mmol) in CH2Cl2 (1 mL), allyl alcohol (1 mmol) was added
at room temperature. The resulting mixture was vigorously stirred
at room temperature until the reaction was complete by TLC.
The mixture was extracted with ethyl acetate (3 ¥ 5 mL). The
combined organics were dried (Na2SO4) and concentrated under
reduced pressure. The residue was purified by chromatography on
a silica gel column with EtOAc–hexanes (1 : 6) to afford the desired
ester 2.
6 (a) G. Ta´rka´nyi, P. Kira´ly, S. Varga, B. Vakulya and T. Soo´s, Chem.–
Eur. J., 2008, 14, 6078–6086; (b) P. Kira´ly, T. Soo´s, S. Varga, B. Vakulya
and G. Ta´rka´nyi, Magn. Reson. Chem., 2010, 48, 13–19.
7 We have recently reported an another type of self-association free chiral
bis-squaramide catalysts J. W. Lee, T. H. Ryu, J. S. Oh, H. Y. Bae, H. B.
Jang and C. E. Song, Chem. Commun., 2009, 7224–7226.
8 Bis-cinchonine thiourea catalyst Bis-CN-TU was reported first by
Dixon and coworkers. However, this catalyst exhibited very poor
enantioselectivity (17% ee) in the malonate Michael addition to b-
nitrostyrene J. Ye, D. J. Dixon and P. S. Hynes, Chem. Commun., 2005,
4481–4483.
9 For reviews, (a) K. Faber, Chem.–Eur. J., 2001, 7, 5004–5010; (b) H.
Pellissier, Tetrahedron, 2003, 59, 8291–8327; (c) N. J. Turner, Curr. Opin.
Chem. Biol., 2004, 8, 114–119.
10 For urea or thiourea catalyzed DKR of racemic azlactones, (a) A.
Berkessel, F. Cleemann, S. Mukherjee, T. N. Mu¨ller and J. Lex, Angew.
Chem., Int. Ed., 2005, 44, 807–811; (b) A. Berkessel, S. Mukherjee, F.
Cleemann, T. N. Mu¨ller and J. Lex, Chem. Commun., 2005, 1898–1900;
(c) A. Peschiulli, C. Quigley, S. Tallon, Y. K. Gun’ko and S. J. Connon,
J. Org. Chem., 2008, 73, 6409–6412.
11 The racemic azlactones were prepared from the corresponding amino
acids according to the literature procedure J. Liang, J. C. Ruble and G.
C. Fu, J. Org. Chem., 1998, 63, 3154–3155.
12 (R)-2a was obtained at a slightly lower level of ee using a hydrocincho-
nine (HCN), cinchonine (CN)-, hydroquinidine (HQD)- or quinidine
(QD)-derived analogue. Bis-HCN-TU (64% ee), Bis-CN-TU (69% ee),
Bis-HQD-TU (67% ee) or Bis-QD-TU (69% ee).
13 (a) D. F. Nogales, J.-S. Ma and D. A. Lightner, Tetrahedron, 1993, 49,
2361–2372; (b) C. Ikeda, N. Nagahara, E. Motegi, N. Yoshioka and H.
Inoue, Chem. Commun., 1999, 1759–1760.
One-pot procedure for the DKR reactions starting from the
racemic N-acylated a-amino acids
The N-acylated a-amino acids 3 (0.5 mmol) was added to a
stirred solution of DCC (108.3 mg, 0.53 mmol) in CH2Cl2 (1
mL) at rt. After the complete conversion (ca. 2 h) of the N-
acylated a-amino acids 3 to the corresponding azlactones 1, the
catalyst (Ia, 0.05 mmol) and alcohol (1 mmol) were added to the
reaction mixture. The reaction mixture was stirred at -20 ◦C and
the reaction progress was monitored by TLC. After completion
of the reaction, 2 M HCl (10 mL) was added to the reaction
mixture. The heterogenous reaction mixture was then filtered
to remove the dicyclohexylurea. The filtrate was extracted with
CH2Cl2 (2 ¥ 10 mL). The combined organic extract was dried
over anhydrous MgSO4 and concentrated. The obtained crude
product was purified by column chromatography on silica gel
(EtOAc : hexane = 1 : 4) to give the N-acylated a-amino ester 2.
1H and 13C NMR spectra for the obtained products 2a–j were in
agreement with previously reports (see ESI).†
14 CCDC 836783 contains the supplementary crystallographic
data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif or by contacting The
Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge
CB2 1EZ, UK; fax: (+44)-1223-336-033.
15 C. E. Humphrey, M. Furegati, K. Laumen, L. L. Veccjia, T. Leutert, J.
C. Mu¨ller-Hartwieg and M. Vo¨gtle, Org. Process Res. Dev., 2007, 11,
1069–1075.
Acknowledgements
This work was supported by grants from the Basic Science
Research Program (NRF-20090085824, MEST), Priority Re-
search Centers Program (NRF-2011-0031392, MEST), SRC
Program (2011-0001334, MEST), WCU Program (R31-2008-
This journal is
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