Hydrogenation of ethyl acetoacetate catalyzed by hydrosoluble BINAP derivatives

Article abstract of DOI:10.1016/S0040-4039(00)02035-9

A new Ru hydrosoluble BINAP derivative has been synthesized. This water-soluble catalyst was revealed to be enantioselective up to 94% and recyclable (at least three times) for the asymmetric hydrogenation of ethyl acetoacetate in a biphasic system.

Full text of DOI:10.1016/S0040-4039(00)02035-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 663–664
Hydrogenation of ethyl acetoacetate catalyzed by hydrosoluble
BINAP derivatives
Thierry Lamouille,a Christine Saluzzo,a Rob ter Halle,a Frede´ric Le Guyaderb and Marc Lemairea,*
aLaboratoire de Catalyse et Synthe`se Organique, UMR 5622, UCBL, CPE, 43 Bd du 11 novembre 1918,
69622 Villeurbanne Cedex, France
bRhodia, CR de Lyon, 85 av. des Fre`res Perret, 69192 Saint Fons Cedex, France
Received 9 October 2000; accepted 9 November 2000
Abstract—A new Ru hydrosoluble BINAP derivative has been synthesized. This water-soluble catalyst was revealed to be
enantioselective up to 94% and recyclable (at least three times) for the asymmetric hydrogenation of ethyl acetoacetate in a
biphasic system. © 2001 Elsevier Science Ltd. All rights reserved.
During the last 20 years, the synthesis of several chelat-
ing water-soluble organometallic complexes for asym-
metric catalytic hydrogenation in aqueous/organic
two-phase systems has been reported.1 Among them,
chiral phosphines were employed. Their water-solubi-
lization is mainly due to either the introduction of a
sodium sulfonate2–4 or a quaternary ammonium5 func-
tion into their backbone, or their grafting onto a water-
soluble polymer such as polyacrylic acid sodium salt6 or
PEG.7,8 The advantage of such a system towards homo-
geneous catalysis is easy catalyst separation, affording
both economic and environmental benefits.9–11
synthesis of asymmetric water-soluble diphosphines
derived from diam-BINAP and their use in hydrogena-
tion of prochiral ketones.
First, we synthesized a water-soluble PEG derivative of
diam-BINAP (number of PEG units: 110–113, M=
5000 g mol−1) according to the Veronese et al.13 proce-
dure. Unfortunately,
a
mixture of mono- and
disubstituted PEGdiam-BINAP derivatives (mono/di
ratio 70/30) were formed, as shown by MALDI-TOF14
Table 1. Ruthenium catalyzed reduction of ethyl acetoace-
tate with complex 2
Recently, we have reported the synthesis of a BINAP
derivative bearing two amine functions: the 6,6%-
dimethylamino-BINAP (diam-BINAP).12 We have
shown that these amino groups could be used in order
to introduce new functionalities. Thus, we have per-
formed the heterogeneization of BINAP by polycon-
densation of diam-BINAP with diisocyanates.12 In this
paper, we describe some preliminary results on the
Run Reuse
Substrate/catalyst Conversiona (%)
Eea (%)
1
1000
1000
1000
1000
100
97
100
100
94
91
94
83
2
3
4
1st
2nd
3rd
a Conversion and enantioselectivity were determined on a lipodex A
(25 m×0.25 mm) column.
Scheme 1. (i) 2 equiv. aq. HBr, CH2Cl2, rt, Ar, 1 h, 96%; (ii) [Ru-(2-methylallyl)2(COD)], Me2CO, Ar, rt, aq. HBr.
Keywords: asymmetric reactions; biphasic catalysis; hydrogenation; keto ester.
* Corresponding author. Tel.: 33-(0)4-72-43-14-07; fax: 33-(0)4-72-43-14-08; e-mail: marc.lemaire@univ-lyon1.fr
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02035-9

664
T. Lamouille et al. / Tetrahedron Letters 42 (2001) 663–664
Scheme 2.
analysis. Their corresponding ruthenium complexes
were synthesized from the [RuCl2(benzene)]2 precursor
according to the Noyori et al.15 procedure. The reduc-
tion of ethyl acetoacetate by this ruthenium complex
mixture affords, after careful extraction of the water-
soluble product with pentane, 100% of conversion and
75% ee and, after recycling, only 20% of conversion and
56% ee.
mL of aqueous HBr (0.05 mmol). The reaction was
allowed to stir for 0.5 h and the solvent was then
removed.
Typical reduction procedure of ethyl acetoacetate: Under
Ar, to the preceding catalyst 2 dissolved in H2O (1 mL),
the water-insoluble ethyl acetoacetate (2.2 mL) was
added (substrate/catalyst: 1000). This biphasic mixture
was allowed to stir and stand overnight in a stainless
steel hydrogenation vessel at 50°C under 40 bar H2.
The resulting water-soluble reduced product was
extracted twice with pentane (10 mL). The aqueous
phase containing the catalyst was reused as previously
described.
Then, we chose to synthesize the bromhydrate form of
diam-BINAP (Scheme 1). The formation of ammonium
salt 1 was easily performed with aqueous hydrobromic
acid in CH2Cl2 solution with a 96% yield. The corre-
sponding ruthenium complex was prepared from the
[Ru(h3-2-methylallyl)2(h2-COD)] precursor according
to the Geneˆt et al.16 procedure.
References
Table 1 summarizes the results of the hydrogenation of
ethyl acetoacetate using the water-soluble ruthenium
complex 2 (Scheme 2). Catalyst 2 led to good enantiose-
lectivity (run 1). The recycling of the catalyst 2 is also
performed by careful extraction of the water-soluble
product with pentane. From the first to the third recy-
cling (runs 2–4), catalyst 2 showed no loss of activity
but a slight decrease of enantioselectivity from 91 to
83% ee was observed.
1. Joo, F.; Katho, A. In Aqueous-phase Organometallic
Catalysis, Concepts and Applications; Cornils, B.; Her-
rmann, W. A., Eds.; John Wiley: New York, 1998; pp.
340–372.
2. Wan, K.; Davis, M. Tetrahedron: Asymmetry 1993, 4,
2461–2468.
3. Benhamza, R.; Amrani, Y.; Sinou, D. J. Organomet.
Chem. 1985, 288, C37–C39.
4. Alario, F.; Amrani, Y.; Colleuille, Y.; Dang, T. P.; Jenck,
J.; Morel, D.; Sinou, D. Chem. Commun. 1986, 202–203.
5. Nagel, U.; Kingel, E. Chem. Ber. 1986, 119, 1731–1733.
6. Malmstrom, T.; Andersson, C. J. Mol. Catal. A: Chem.
1999, 139, 259–270.
7. Amrani, Y.; Sinou, D. J. Mol. Catal. 1984, 24, 231–233.
8. Sinou, D.; Amrani, Y. J. Mol. Catal. 1986, 36, 319–327.
9. Cornils, B.; Kuntz, E. G. J. Organomet. Chem. 1995, 502,
177–186.
We have demonstrated that little modification of diam-
BINAP provides a water-soluble BINAP analog, such
as the ammonium derivative, suitable for asymmetric
biphasic catalytic hydrogenation of ethyl acetoacetate.
The use of such a ligand is interesting because high
conversions and attractive enantioselectivities were
obtained. In addition, it allows easy separation of the
catalyst from the reaction product by extraction. The
reuse of ruthenium complex 2 is effective without any
loss of either conversion or enantioselectivity.
10. Herrmann, W. A.; Kohlpaintner, C. W. Angew. Chem.,
Int. Ed. Engl. 1993, 32, 1524–1544.
11. Papadogianakis, G.; Sheldon, R. A. New. J. Chem. 1996,
20, 175–185.
Other substrates have to be tested in order to screen the
scope and limitations of these new catalytic systems.
12. ter Halle, R.; Collason, B.; Schulz, E.; Spagnol, M.;
Lemaire, M. Tetrahedron Lett. 2000, 41, 643–646.
13. Veronese, F. M.; Caliceti, P.; Pastorino, A.; Schiavon, O.;
Sartore, L.; Banci, L.; Monsu Scolaro, L. J. Control.
Release 1989, 10, 145–154.
14. MALDI-TOF (matrix-assisted laser desorption ionization
time-of-flight): Barbacci, D. C.; Edmondson, R. D.; Rus-
sell, D. H. Int. J. Mass Spectrom. Ion Process. 1987,
165/166, 221–235 and references cited therein.
15. Kitamura, M.; Tokunaga, M.; Ohkuma, T.; Noyori, R.
Tetrahedron Lett. 1991, 32, 4163–4166.
Experimental
Synthesis of 1: Under Ar, at 25°C, 8.4 mL of an
aqueous HBr solution (0.05 mmol) was added to a
stirred solution of (R)-diam-BINAP (17 mg, 0.025
mmol) in CH2Cl2 (1 mL). The reaction was allowed to
stir for 1 h and the solvent was then removed to give 2
(96% yield). IR: 3500–2200; 2962; 2924; 1437; 1261; 803
cm−1.
16. Geneˆt, J. P.; Pinel, C.; Ratovelomanana-Vidal, V.; Mal-
lart, S.; Pfister, X.; Cano de Andrade, M.; Laffitte, J. A.
Tetrahedron: Asymmetry 1994, 5, 665–674.
Catalyst 2: Under Ar, at 25°C, to a stirred solution of
Ru[(2-methylallyl)2(COD)] (7.5 mg, 0.024 mmol) and 1
(16 mg, 0.024 mmol) in acetone (1 mL) was added 8.4
.
.