'Diam-BINAP'; a highly efficient monomer for the synthesis of heterogeneous enantioselective catalysts

Article abstract of DOI:10.1016/S0040-4039(99)02129-2

The synthesis of a monomeric analogue of BINAP, diam-BINAP, is described. The polyaddition of this monomer with 2,6-diisocyanato toluene gave the corresponding oligomer, poly-NAP, with a polymerization degree of 8. The ruthenium complex of this polymer proved to be a very efficient heterogeneous catalyst for the hydrogenation of β-ketoesters (99% ee, 0.1 mol% of catalyst). Furthermore the catalyst could be easily reused four times by simple filtration without loss of activity or enantioselectivity. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(99)02129-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 643–646
‘Diam-BINAP’; a highly efficient monomer for the synthesis of
heterogeneous enantioselective catalysts
a
a
a
b
Rob ter Halle, Benoist Colasson, Emmanuelle Schulz, Michel Spagnol and
a,∗
Marc Lemaire
a
Laboratoire de Catalyse et Synthèse Organique, IRC, UCBL, CPE, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne Cedex,
France
b
Rhône Poulenc, CRIT-Carrières, 85, av. des Frères-Perret, BP 62, 69192 Saint-Fons Cedex, France
Received 27 August 1999; accepted 10 November 1999
Abstract
The synthesis of a monomeric analogue of BINAP, diam-BINAP, is described. The polyaddition of this monomer
with 2,6-diisocyanato toluene gave the corresponding oligomer, poly-NAP, with a polymerization degree of 8. The
ruthenium complex of this polymer proved to be a very efficient heterogeneous catalyst for the hydrogenation of
β-ketoesters (99% ee, 0.1 mol% of catalyst). Furthermore the catalyst could be easily reused four times by simple
filtration without loss of activity or enantioselectivity. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: asymmetric reactions; hydrogenation; polymer support; ruthenium.
Although asymmetric catalysis is without doubt one of the most promising methods for the synthesis
1
of chiral compounds, industrial applications are surprisingly still underdevelopped. The main reasons
for this are not the qualitative aspects of the transformations where high ees and conversions are routinely
obtained for a wide variety of reactions but the rather high costs of the ligand and/or metal.
These drawbacks could be avoided if the catalyst is separated and reused after reaction. An evident way
of achieving this is the use of heterogeneous catalysis, allowing easy work-up procedures and possible
recycling. Among many different strategies, supporting an already existing homogeneous catalyst seems
the most straightforward and with this approach, it can be hoped that the advantages of homogeneous
and heterogeneous catalysis can be combined.
We decided to attempt the heterogenization of probably one of the most successful known ligands,
2
3
BINAP. In contrast to a recently published method, we choose not to attach the ligand to an already
existing polymer, but to polymerize the ligand to form a macromolecule with backbone chirality that
can maintain the required C symmetric character of BINAP in order to achieve high ees. Since we
2
have obtained good results in heterogenization of chiral ligands by polycondensation of diamines with
4
diisocyanates, we decided to synthesize a BINAP symmetrically functionalized with two amine moieties
(diam-BINAP) which allows easy polymerization (see Scheme 1).
∗
Corresponding author. Fax: 33 (0) 4 72 43 14 08; e-mail: marc.lemaire@univ-lyon1.fr (M. Lemaire)
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02129-2
tetl 16057

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Scheme 1. Synthesis of (S)-diam-BINAP and polymerization to (S)-poly-NAP
5
0
6
Enantiopure (S)-BINOL 1 was brominated at position 6,6 by the procedure described by Cram et al.
7
Triflation of compound 2 according to Hayashi, gave 3 in 92% yield. This molecule could be directly
converted by action of CuCN in N-methyl pyrolidone at 180°C into its dicyano-derivative 4.8 The key
step was the introduction of the two diphenylphosphino moieties to give diphosphine 5 without modifying
the two cyano groups at the other side of the molecule. This transformation was performed in 47% yield
by the recently developed procedure of Cai et al.10
,9
The two dicyano groups were subsequently reduced with LiAlH to give the (S)-diam-BINAP 6 in
4
quantitative yield ([α] =−101.3 (c=0.3, DMF)). No oxidation of the phosphines was observed during
D
the last two steps.
Finally we polymerized this monomer with 2,6-tolylene diisocyanate. This reaction in CH Cl yielded
2
2
a white precipitate in 95% yield whose structure was confirmed to be polymer 7 ((S)-poly-NAP) with
1
a degree of polymerization of 8 as was determined by end-group analysis by H NMR and elemental
analysis.
Poly-NAP is insoluble in organic solvents such as dichloromethane, toluene and methanol, but
soluble in polar non-protic solvents like dimethylformamide and dimethylsulfoxide. The fact that it has
the polyurea functionality in the backbone is important for obtaining the right solubility/swellability
properties in methanol, which is used as solvent for the hydrogenations.
In order to evaluate the optical purity of (S)-diam-BINAP and the scope and limitation of the

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45
catalytic properties of poly-NAP, the corresponding ruthenium complexes were prepared by reaction
of [RuCl (benzene)] or [(COD)Ru(bis-methallyl) ] according to the general procedures described by
2
2
2
1
1,12
13
Noyori et al.
and Genêt et al. The complexes were tested for the catalytic hydrogenation of various
β-keto esters (Table 1).
Table 1
Ruthenium catalyzed reduction of different β-keto-esters with BINAP, diam-BINAP and poly-NAP as
ligands
Through heterogenization of BINAP by polymerization a negligible loss of enantioselectivity was
observed (entries 1 and 2). The almost perfect enantioselection observed for diam-BINAP (entry 3)
proves that no racemization has occured during the synthesis. With ethylacetoacetate as substrate the
same promising results were obtained (entries 4 and 5). At last with methyl 3-oxo-6-octenoate as
substrate (entries 6 and 7) the selectivity lowered, but this can be explained by the higher pressure we
used in our catalytic test compared to literature conditions.13
The most important advantage of heterogeneous catalysis over its homogeneous counterpart is the
possibility of reusing the catalyst after reaction by simple filtration (Table 2).
Table 2
Reuse of the poly-NAP–Ru catalyst
The catalyst could be reused four times without loss of neither selectivity nor activity (entries 1–4)
with catalyst loading as low as 0.1 mol%.

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46
We have thus polymerized BINAP functionalized with methylamine groups (diam-BINAP) to give a
polymer with backbone chirality in which the complexing moieties are in a C symmetric environment.
2
This polymer is capable of hydrogenating heterogeneously different β-keto esters with high enantioselec-
tivities and activity. It was also shown that this catalyst can be reused at least four times without loss of
activity or enantioselectivity. The success of our catalyst can be explained by the balance between the
heterogeneous and homogeneous character. The fact that the polymer has a polymerization degree of 8
leads to a solubility/swellability which allows the high selectivity and activity of the catalyst.
Other substrates have to be tested in order to screen the scope and limitations of this new catalytic
system. The choice of the diisocyanate and the polymerization conditions can have large effects on the
selectivity and activity of this type of catalysts and are currently being examined.
Experimental: All experiments were performed under an argon atmosphere and all solvents were
degassed by argon bubbling followed by three freeze/thaw cycles in vacuo, under argon.
Catalysts: Catalysts have been prepared according to literature procedures,1
1–13
by doubling the
reaction times.
Hydrogenation: To the above obtained catalyst was added 2 mL of MeOH and the calculated amount of
β-keto-ester. This suspension was put in a stainless steel hydrogenation vessel. After purging three times
with argon and three times with hydrogen, the pressure was raised to 40 bar and the reaction mixture
was stirred at 50°C overnight. The liquid part of the reaction mixture was analysed by GC (lipodex A
column) after centrifugation of the suspension to determine both conversion and ee.
Reuse: To the solid which was obtained after centrifugation was added the same amounts of MeOH
and methylacetoacetate and the hydrogenation was performed as previously described.
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