Alfredo Ricci et al.
COMMUNICATIONS
J=6.3, 15.6 Hz), 3.10 (dd, 1H, J=6.1, 15.6 Hz), 4.70 (m,
1H), 5.56 (d, 1H, J=7.6 Hz), 6.96–7.20 (m, 9H), 7.24–7.38
(m, 3H), 7.47–7.54 (m, 2H); 13C NMR (100 MHz, CDCl3):
d=21.7, 49.7, 55.2, 126.7, 127.0, 127.3, 128.1, 128.8, 129.4,
129.7, 129.9, 134.5, 137.4, 139.1, 143.5, 195.7; Chiral HPLC
[4] a) Enantioselective Synthesis of b-Amino Acids, (Eds.:
E. Juaristi, V. A. Soloshonok), Wiley, New York, 2005;
2 volumes; b) R. P. Cheng, S. H. Gellaman, W. F. De-
Grado, Chem. Rev. 2001, 101, 3219–3232; for reviews
on the catalytic asymmetric Mannich reaction, see:
c) A. Córdova, Acc. Chem. Res. 2004, 37, 102–112;
d) S. Kobayashi, H. Ishitani, Chem. Rev. 1999, 99,
1069–1094.
[5] For reviews, see: a) H. Wynberg, Top. Stereochem.
1986, 16, 87–129; b) K. Kacprzak, J. Gawronski, Syn-
thesis 2001, 961–998; c) S.-K. Tian, Y. Chen, J. Hang,
L. Tang, P. McDaid, L. Deng, Acc. Chem. Res. 2004, 37,
621–631.
[6] Y. Iwabuchi, M. Nakatani, N. Hatakeyama, S. Hata-
keyama, J. Am. Chem. Soc. 1999, 121, 10219–10220.
[7] Use of imines with other protecting groups was found
to give unsatisfactory results.
[8] The ee was found to be constant during the progress of
the reaction.
[9] The desired N-Ts b-amino acids could be obtained by a
facile hydrolysis, following a literature procedure: C.
Fehr, N. Chaptal-Gradoz, J. Galindo, Chem. Eur. J.
2002, 8, 853–858. For example, treatment of 4a with
LiOH and H2O2 in H2O/EtOH gave the corresponding
N-Ts b-amino acid in 82% yield {[a]2D5: À17.0 (c 1.3,
MeOH)}; [lit. 92% ee of the (S)-isomer; [a]2D5: À33.1 (c
1.0, CHCl3), S. A. Sergeyev, M. Hesse, Helv. Chim.
Acta 2002, 85, 161–167].
[10] The moderate yields observed in some cases can be as-
cribed to the low reaction rate observed for these reac-
tions. It seems unlikely that competing formation of ca.
10–30% S-phenyl thioacetate (see note [13]) might in-
fluence the yields of the addition products since the
malonic acid half thioesters are used in 200 mol%.
[11] No reaction could be observed between substrate 2a
and imine 3a in the absence of catalyst.
analysis
(Chiralpak
OD,
90:10
n-hexane:i-PrOH,
0.75 mLminÀ1, l=254 nm) indicated 48% ee, tR (minor)=
32.5 min, tR (major)=37.7 min; [a]2D0: 13.7 (c 1.1, EtOAc);
HR-MS: m/z=411.0960, calcd. for C22H21NO3S2: 411.0963.
Acknowledgements
We acknowledge financial support by the “Consorzio CINM-
PIS”, Stereoselezione in Sintesi Organica Metodologie ed
Applicazioni 2005” and by the EC-RTN (HPRN-CT-2001–
00172). D. P. is grateful for the fellowship received by the
Bengt Lundqvist Foundation, Sweden. The financial support
of the Merck-ADP grant is also gratefully recognized.
References
[1] a) Modern Aldol Reactions, (Ed.: R. Mahrwald),
Wiley-VCH, Weinheim, 2004, Vol. 2; b) M. J. Yost, G.
Zhou, D. M. Coltart, Org. Lett. 2006, 8, 1503–1506;
c) S. Saito, S. Kobayashi, J. Am. Chem. Soc. 2006, 128,
8704–8705; d) D. A. Evans, C. W. Downey, J. T. Shaw,
J. S. Tedrow, J. Am. Chem. Soc. 2002, 4, 1127–1130;
e) D. A. Evans, J. S. Tedrow, J. T. Shaw, C. W. Downey,
J. Am. Chem. Soc. 2002, 124, 392–393; f) D. A. Evans,
C. W. Downey, J. L. Hubbs, J. Am. Chem. Soc. 2003,
125, 8706–8707; g) S. Harada, S. Handa, S. Matsunaga,
M. Shibasaki, Angew. Chem. Int. Ed. 2005, 44, 4365–
4368.
[12] Using S-phenyl thioacetate as substrate resulted in no
[2] As a result most of the developed procedures providing
a-functionalized carboxylates rely on the use of pre-
formed silyl ketene acetals or acid chlorides. Alterna-
tively, the ester enolate can benefit by a second anion-
stabilising group (e.g., malonates) present in the prod-
uct.
[3] a) G. Lalic, A. D. Aloise, M. D. Shair, J. Am. Chem.
Soc. 2003, 125, 2852–2853; b) S. Orlandi, M. Benaglia,
F. Cozzi, Tetrahedron Lett. 2004, 45, 1747–1749; c) D.
Magdziak, G. Lalic, H. M. Lee, K. C. Fortner, A. D.
Aloise, M. D. Shair, J. Am. Chem. Soc. 2005, 127,
7284–7285; d) K. C. Fortner, M. D. Shair, J. Am.
Chem. Soc. 2007, 129, 1032–1033.
reaction with imine 2a in the presence of 1.
[13] The enolate can also be quenched by the protonated
catalyst forming a thioacetate. In fact, this thioacetate
is usually formed in 10–30% indicating a competitive
reaction between the thioacetate enolate with the
imine or the protonated catalyst. Increasing the
amount of imine to 300 mol%, resulted in minor for-
mation of thioacetate.
[14] F. Chemla, V. Hebbe, J-F. Normant, Synthesis 2000,
75–77.
[15] a) Y. Kobuke, J. Yoshida, Tetrahedron Lett. 1978, 19,
367–370; b) N. Sakai, N. Sordꢁ, S. Matile, Molecules
2001, 6, 845–851.
1040
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1037 – 1040