COMMUNICATIONS
In summary, we have clearly demonstrated that two kinds
of reducing systems (NaBH /Me SiCl or NaBH /BF ´ OEt )
1990, 1859; d) C. Caze, N. EI Moualij, P. Hodge, C. J. Lock, J. Ma, J.
Chem. Soc. Perkin Trans. 1 1995, 345; e) C. Caze, N. EI Moualij, P.
Hodge, C. J. Lock, Polym. 1995, 36, 621; f) M. Felder, G. Giffels, C.
Wandrey, Tetrahedron: Asymmetry 1997, 8, 1975; g) W.-S. Huang, Q.-
S. Hu, L. Pu, J. Org. Chem. 1999, 64, 7940.
4
3
4
3
2
in combination with the new, chiral, polymer-supported N-
sulfonamide 1 are effective in the reduction of prochiral
ketones. The best ee values are obtained when the reduction is
carried out in refluxing THF. The chiral polymer can be
recovered easily and reused. The two reducing systems
described should offer advantages over other reducing
systems and thus find new applications.
[5] K. Adjidjonou, C. Caze, Eur. Polym. J. 1995, 31, 749.
[
6] a) P. Lecavalier, E. Bald, Y. Jiang, J. M. J. Fr e chet, P. Hodge, React.
Polym. 1985, 4, 315; b) J. M. J. Fr e chet, E. Bald, P. Lecavalier, J. Org.
Chem. 1986, 51, 3462; c) D. Seebach, R. E. Marti, T. Hintermann,
Helv. Chim. Acta 1996, 79, 1710.
[7] A. Giannis, K. Sandhoff, Angew. Chem. 1989, 101, 220; Angew. Chem.
Int. Ed. Engl. 1989, 28, 218.
[
8] S. S. Sengupta, D. V. Sahu, S. K. Chatterjee, Ind. J. Chem. 1994, 33B,
85.
Experimental Section
2
[
9] D. W. Emerson, R. R. Emerson, S. C. Joshi, E. M. Sorensen, J. E.
All reactions were carried out under nitrogen. THF was dried over sodium
and freshly distilled before use. (S)-Diphenylprolinol was prepared
according to a literature procedure.[ Cross-linked polystyrene resin
Turek, J. Org. Chem. 1979, 44, 4634.
[
[
[
10] J. M. Brunel, M. Maffei, G. Buono, Tetrahedron: Asymmetry 1993, 4,
255.
11] Y. Okamoto, Z.-K. Cao, R. Aburatani, K. Hatada, Bull. Chem. Soc.
Jpn. 1987, 60, 3999.
12] D. J. Mathre, T. K. Jones, L. C. Xavier, T. J. Blacklock, R. A. Reamre,
J. J. Mohan, E. T. Jones, K. Hoogsteen, M. W. Baum, E. J. Grabowski,
J. Org. Chem. 1991, 56, 751.
12]
2
(
2%, 200 ± 400 mesh) was obtained from Merck Company. The purity of all
the reagents were checked by NMR spectroscopy.
Preparation of 1: Polymeric sulfonyl chloride (0.214 g, 1 mmol) was added
to a solution of (S)-diphenylprolinol (1.016 g, 4 mmol) in CH
2 2
Cl (30 mL)
and Et N (0.104 g, 1 mmol) at room temperature. The resulting mixture was
3
stirred for four days. The polymer was then filtered off and washed
successively with methanol, water, methanol/water (1:1), and methanol.
After drying in vacuo at 508C for 5 h, the desired polymer (0.451 g) was
obtained in approximately 96% yield.
General procedure for the asymmetric reduction of prochiral ketones using 1
and NaBH
suspension of NaBH
was heated at reflux and stirred for 1 h. Polymer-supported catalyst 1
98 mg, 0.25 mmol) was added, and the reaction mixture was heated at
reflux for a further 0.5 h. A solution of acetophenone (120 mg, 1 mmol) in
4
/Me
3
SiCl: Me
3
SiCl (0.132 mg, 1.2 mmol) was added to a
4
(45 mg, 1.2 mmol) in THF (10 mL). The suspension
An Asymmetric Enzyme-Catalyzed Retro-
Claisen Reaction for the Desymmetrization of
Cyclic b-Diketones**
(
�
1
THF (10 mL) was added at a rate of 3 mLh with a syringe pump. After
the addition was complete, the mixture was treated with water and filtered.
The polymer-supported catalyst was washed several times with EtOAc and
water. The resulting aqueous solution was extracted with EtOAc (3 Â
Gideon Grogan,* Jürgen Graf, Aileen Jones,
Simon Parsons, Nicholas J. Turner,* and
Sabine L. Flitsch*
4
10 mL) and dried with MgSO . The solution was evaporated and purified
by silica-gel chromatography to give the pure product (120 mg, 0.98 mmol,
0
9
8%). [a]2
D
52.6 (c 2.23, CHCl
3
). The optical yield was determined to
The desymmetrization of prochiral compounds is of in-
creasing importance in asymmetric synthesis because, in
principle, quantitative yields with absolute optical purity
may be obtained.[ Enzyme-catalyzed approaches to desym-
metrization have, for the most part, involved the application
of carbon ± heteroatom hydrolases such as lipases and ester-
ases.[ Reactions involving C�C bond cleavage are much
be 95.7% by using chiralcel OJ column chromatography.
General procedure for the asymmetric reduction of prochiral ketones using
polymer-supported catalyst 1 and NaBH
.8 mmol) was added to a suspension of NaBH
10 mL). The suspension was heated at reflux for 0.5 h. Polymer-supported
4
/BF
3
2 3 2
´ OEt : BF ´ OEt (0.254 mg,
1]
1
4
(46 mg, 1.2 mmol) in THF
(
catalyst 1 (59 mg, 0.15 mmol) was added, and the reaction mixture was
heated at reflux for a further 0.5 h. A solution of acetophenone (120 mg,
2]
�
1
1
mmol) in THF (10 mL) was then added at a rate of 3 mLh with a
rarer, although the group of Taschner was successful in
applying an enzyme-catalyzed Baeyer± Villiger reaction to
syringe pump. After the addition was complete, the mixture was treated
with water and filtered. The polymer-supported catalyst was washed
several times with EtOAc and water. The resulting aqueous solution was
[3]
the desymmetrization of a variety of prochiral ketones. The
extracted with EtOAc (3 Â 10 mL) and dried with MgSO
4
. The solution was
desymmetrization of prochiral b-diketones by a retro-Claisen
reaction has been reported using chiral bases, although
diastereomeric and enantiomeric excesses were generally
evaporated and purified by silica-gel chromatography to give the pure
2
0
product (120 mg, 0.98 mmol, 98%). [a]
D
52.4 (c 1.01, CHCl
3
). The
optical yield was determined to be 95.1% by using chiralcel OJ column
chromatography.
[*] Dr. G. Grogan,[ Prof. N. J. Turner, Prof. S. L. Flitsch, J. Graf,
]
Received: September 6, 2000 [Z15769]
A. Jones, Dr. S. Parsons
Edinburgh Centre for Protein Technology
Department of Chemistry, University of Edinburgh
The Kingꢁs Buildings, West Mains Road, Edinburgh EH9 3JJ (UK)
Fax : (44)131-650-4737
[
[
1] Reviews: a) V. K. Singh, Synthesis 1992, 605; b) E. J. Corey, C. J.
Helal, Angew. Chem. 1998, 110, 2092; Angew. Chem. Int. Ed. 1998, 37,
1
986.
2] a) W. Trentmann, T. Mehler, J. Martens, Tetrahedron: Asymmetry
997, 8, 2033; b) P. S. Mukund, R. C. Gregory, L. Pingrong, Tetrahe-
1
dron Lett. 1999, 40, 2477.
[
] Current address: York Structural Biology Laboratory
Department of Chemistry, University of York
Heslington, York YO10 5DD (UK)
[
3] a) S. J. Shuttleworth, S. M. Allin, P. K. Sharma, Synthesis 1997, 1217;
b) R. ter Halle, E. Schulz, M. Spagnol, M. Lemaire, Synlett 2000, 680.
4] a) S. Itsuno, K. Ito, A. Hirao, S. Nakahama, J. Chem. Soc. Perkin Trans.
[
1
1984, 2887; b) S. Itsuno, M. Nakano, K. Ito, A. Hirao, M. Owa, N.
[**] This work was supported by the BBSRC (grants to N.J.T. and S.L.F.)
and the European Commission (grant to J.G.). We also thank Mr. J.
Millar and Dr. D. Uhrin for assistance with NMR spectroscopy.
Kanda, S. Nakahama, J. Chem. Soc. Perkin Trans. 1 1985, 2615; c) S.
Itsuno, Y. Sakuri, K. Shimizu, K. Ito, J. Chem. Soc. Perkin Trans. 1
Angew. Chem. Int. Ed. 2001, 40, No. 6
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