Table 2 Asymmetric hydrogenation of enamide ester 7a
Footnotes and References
* E-mail: sj11@liverpool.ac.uk
Enantiomeric
† Experimental procedure for the asymmetric hydrogenation of compound
7a. A mixture of complex 6 (8 mg, 0.01 mmol) and a-acetamidocinnamic
acid 7a (205 mg, 1 mmol) was cooled (2 °C) under a nitrogen atmosphere.
Dry, degassed MeOH (5 ml) was added to the mixture, which was stirred
vigorously. The flask was evacuated, filled with hydrogen and stirred for 10
min. A 0.5 ml aliquot was removed from the reaction vessel and treated with
Me3SiCHN2 (2.0 m solution in hexane) in order to convert the acid to the
methyl ester. The solvent was evaporated and the residue was treated with
diethyl ether; filtration and evaporation gave a crude residue (21 mg). The
enantiomeric excess of the product 8a was determined to be 92.5% by chiral
gas chromatography, using a Chirasil-Val-III column.
Volume of
solvent/ml
excess of
product (%)
T/°C
25
12
2
25
25
2
15
15
15
10
5
81
83.5
87.5
88
91.5
92.5
5
1 Review: R. Noyori, Asymmetric Catalysts in Organic Systhesis, Wiley,
New York, 1994, ch. 2; recent publications: G. Zhu, P. Cao, Q. Jiang and
X. Zhang, J. Am. Chem. Soc., 1997, 119, 1799; R. Selke, M. Ohff and
A. Riepe, Tetrahedron, 1996, 52, 15079; M. J. Burk, Y. M. Wang and
J. R. Lee, J. Am. Chem. Soc., 1996, 118, 5142; H.-J. Kreuzfeld,
U. Schmidt, C. Do¨bler and H. W. Krause, Tetrahedron: Asymmetry,
1996, 7, 1011; C. Dobler, H.-J. Kreuzfeld, M. Michalik and
H. W. Krause, Tetrahedron: Asymmetry, 1996, 7, 117; J. Albrechy and
U. Nagel, Angew. Chem., Int. Ed. Engl., 1996, 35, 407.
2 K. Tanaka, O. Kakinoki and F. Toda, Tetrahedron: Asymmetry, 1992, 3,
517.
3 Z. Grudzinski and S. M. Roberts, J. Chem. Soc., Perkin Trans. 1, 1975,
1767.
4 For enzymatic resolution of related bromohydrins, see I. C. Cotterill,
A. G. Sutherland, S. M. Roberts, R. Grobbauer, J. Spreitz and K. Faber,
J. Chem. Soc., Perkin Trans. 1, 1991, 1365; I. C. Cotterill and
S. M. Roberts, J. Chem. Soc., Perkin Trans. 1, 1992, 2585.
5 R. F. Newton, J. Paton, D. P. Reynolds, S. Young and S. M. Roberts,
J. Chem. Soc., Chem. Commun., 1979, 908; J. Davies, S. M. Roberts,
D. P. Reynolds and R. F. Newton, J. Chem. Soc., Perkin Trans. 1, 1981,
1317; See also G. Fantin, M. Fogagnolo, A. Medici, P. Pedrini,
E. Marotta, M. Monti and R. Righi, Tetrahedron: Asymmetry, 1996, 7,
277.
given the subtlety of the chirality of the bicyclo[3.2.0]heptane
framework, the observed level of enantioselectivity is surpris-
ingly high. The reaction rates were perfectly satisfactory (the
reaction was completed in 2–10 min) using 1 mmol substrate
and 0.01 mmol catalyst in MeOH (15 ml) under an atmosphere
of hydrogen. Using similar conditions, itaconic acid was
reduced to (2S)-methylsuccinate in quantitative yield and 80.5%
ee.
The reaction conditions for the asymmetric reduction of
substrate 7a were investigated further. Lowering the temper-
ature of the reaction and increasing the concentration of the
reactants both proved to be beneficial, with a satisfactory 92.5%
ee for product 8a being obtained at low temperature and high
concentration (Table 2).† The concentration effect may be
explained by the effect on the rate of delivery of hydrogen to the
catalyst, which will be slower in the reactions using small
amounts of solvent. Thus, in the more concentrated solution the
catalyst may experience a lower ‘effective’ hydrogen concen-
tration.6
We thank the BBSRC for a Fellowship (to U. V.) and a CASE
award (to M. J. G.), Chiroscience, and EPSRC and the
University of Exeter for studentships (to J. M. and G. W.) and
Donna Blackmond for enlightening discussions.
6 Y. Sun, R. N. Landau,J. Wang, C. LeBlond and D. G. Blackmond, J. Am.
Chem. Soc., 1996, 118, 1348.
Received in Cambridge, UK, 13th June 1997; 7/04136E
1714
Chem. Commun., 1997