H. Zhou et al. / Tetrahedron Letters 42 (2001) 1107–1110
1109
Table 2. The enantioselective reduction of prochiral ketones and diketones with BH3·Me2S catalyzed by diaminoalcohols of
squaric acid 5 and 6
Entry
Ligand (equiv.)
Ketone
[h]2D0 (c, MeOH)
meso/R,R+S,S
Ee%
Config.
1
2
3
4
5
6
7
8
9
(1%R)-5 (0.025)
(1%R)-5 (0.05)
(1%R)-5 (0.05)
(1%R)-5 (0.1)
(1%R)-6 (0.05)
(1%R)-5 0.05)
(1%R)-5 (0.1)
(1%R)-5 (0.15)
(1%R)-6 (0.1)
(1%R)-5 (0.1)
PhCOCH2Br
PhCOCH2Br
PhCOMe
PhCOCH2Br
84
91
80
82
R
R
S
R
PhCOCH2Br
35
S
PhCO(CH2)4COPh
PhCO(CH2)4COPh
PhCO(CH2)4COPh
PhCO(CH2)4COPh
PhCO(CH2)3COPh
−13.44 (1.5)
−13.87 (1.5)
−13.57 (1.5)
+7.87 (1.5)
−20.21 (1.0)
4/96
3/97
3/97
18/82
5/95
95a
99a
97a
61a
89b
(S,S)
(S,S)
(S,S)
(R,R)
(S,S)
10
see footnotes a–c of Table 1.
a The ee% and meso% of chiral diols were determined by HPLC with Chiralpak AS column.
b The ee% and meso% of chiral diols were determined by HPLC with Whelk-01 column.
reduction of 1,6-diphenyl-1,6-hexanedione with 10
mol% of ligand 5; while for ligand 6, only moderate ee
values were obtained. This is probably due to the
remote flexible phenyl group which may obstruct the
substrate ketones from getting in close proximity to the
catalytic center or the enantioselective transfer of the
hydride. Obviously more in-depth study is needed to
elucidate this interesting phenomenon and to apply
these novel chiral ligands to the other catalytic asym-
metric reactions.
3. (a) Sibi, M. P.; Cook, G. R.; Liu, P. Tetrahedron Lett.
1999, 40, 2477; (b) Yang, G. S.; Hu, J. B.; Zhao, G.;
Tang, M. H. Tetrahedron: Asymmetry 1999, 10, 4307; (c)
Inoue, T.; Sato, D.; Komure, K.; Itsuno, S. Tetrahedron
Lett. 1999, 40, 5379.
4. (a) Wesa, R. Oxocarbons; Academic Press: New York,
1980; (b) Schmidt, A. H. Synthesis 1980, 961; (c) Pro-
hens, R.; Toma`s, S.; Morey, J.; Deya`, P. M.; Ballester,
P.; Costa, A. Tetrahedron Lett. 1998, 39, 1063; (d)
Yuan, D. Q.; Chen, Y. Z.; Li, J. C.; Zhao, H. M. You
Ji Hua Xue (Chin. J. Org. Chem.) 1992, 312.
In summary, two series of new chiral ligands, aminoal-
cohols and C2-symmetric diaminoalcohols of squaric
acid were prepared by convenient synthetic routes and
were applied successfully to the enantioselective reduc-
tion of prochiral ketones and diketones, giving chiral
alcohols and diols in good to excellent ee’s. This paper
discloses, for the first time, that chiral derivatives of
squaric acid can be successfully used in asymmetric
catalytic reactions. These results will open a new way
for the design and synthesis of novel chiral ligands
derived from squaric acid for asymmetric reactions and
also open new applications for chiral derivatives of
squaric acid.
5. Tietze, L. F.; Arlt, M.; Beller, M.; Glu¨senkamp, K.;
Ja¨hde, E.; Rajewsky, M. F. Chem. Ber. 1991, 124, 1215.
6. Sample procedure, synthesis of 3-ethoxyl-4-[(2%S)-2%-
(diphenylhydroxymethyl)pyrrolidino]-3-cyclobutene-1,2-
dione 1a: To a solution of squaric acid diethyl ester (1.1
mmol) and triethylamine (1.0 mmol) in dry ethanol (10
mL) was added slowly a solution of (S)-(−)-2-(diphenyl-
hydroxymethyl)pyrrolidine (1.0 mmol) in ethanol (10
mL) at room temperature. The reaction was monitored
by TLC and after completion of the reaction (ꢀ24 h),
the solvent was removed under reduced pressure. Fur-
ther purification was achieved by chromatography
(petroleum ether (60–90°C): ethyl acetate, 1:1). Data for
1a: Colorless flake. 65% yield; mp 107–109°C; [h]2D0=
−-175.3 (c 0.8, CH2Cl2). IR (KBr): 3403, 3032, 2966,
2885, 1799, 1707, 1608, 1585 cm−1. lH (200 MHz,
CDCl3): 1.33 (t, J=7.2 Hz, 3H, -CH3), 2.04 (m, 2H,
-CH2-), 2.76–3.33 (m, 5H, -CH2-, -CH-), 4.69 (q, J=7.2
Hz, 2H, -CH2O-), 5.18 (s, 1H, -OH), 7.24–7.54 (m, 10H,
2-ArH) ppm. MS(m/z): 378 (M++1, 30), 360, 195 (100).
Anal. Calcd for C23H23NO4: C 73.18, H 6.15, N 3.71;
found: C 73.01, H 6.11, N 3.66.
Acknowledgements
This work was supported by the Hong Kong Polytech-
nic University.
7. Zhou, H. B.; Yuan, Y.; Chan, A. S. C.; Yang, T. K.;
Xie, R. G. Acta Cryst. C. 2000, 56, e57 and unpublished
results.
8. (a) Corey, E. J.; Bakshi, R. K.; Shibate, S. J. Am.
Chem. Soc. 1987, 109, 5551; (b) Martens, J.; Dauelsberg,
Ch.; Behnen, W.; Wallbaum, S. Tetrahedron: Asymmetry
1992, 3, 347; (c) Jones, G. B.; Heaton, S. B.; Chapman,
B. J.; Guzel, M. Tetrahedron: Asymmetry 1997, 8, 3625;
(d) Yang, T. K.; Lee, D. S. Tetrahedron: Asymmetry
1999, 10, 405.
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