Recyclable diguanidinium-BINAP and PEG-BINAP supported catalysts: Syntheses and use in Rh(I) and Ru(II) asymmetric hydrogenation reactions

Article abstract of DOI:10.1016/S0040-4039(01)00476-2

The syntheses of new recyclable cationic BINAP type ligand diguanidinium 1 and PEG-bound BINAP ligand 2 are described. The use of ethylene glycol instead of water increased the enantioselectivity in the ruthenium-promoted hydrogenation reaction of functionalized ketones. These catalysts are highly active (catalyst/substrate ratio up to 1:10 000, up to 99% e.e.). The rhodium-mediated hydrogenation of acetamidoacrylic acid was also examined using 1 and 3 as chiral auxiliaries.

Full text of DOI:10.1016/S0040-4039(01)00476-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3423–3426
Recyclable diguanidinium-BINAP and PEG-BINAP supported
catalysts: syntheses and use in Rh(I) and Ru(II) asymmetric
hydrogenation reactions
Patricio Guerreiro,a Virginie Ratovelomanana-Vidal,a Jean-Pierre Geneˆta,* and Philippe Dellisb
aLaboratoire de Synthe`se Se´lective Organique et Produits Naturels, UMR 7573, Ecole Nationale Supe´rieure de Chimie de Paris,
11 rue P. et M. Curie, 75231 Paris Cedex 05, France
bSynkem S.A., 47 rue de Longvic 21301 Chenove Cedex, France
Received 21 March 2001; accepted 22 March 2001
Abstract—The syntheses of new recyclable cationic BINAP type ligand diguanidinium 1 and PEG-bound BINAP ligand 2 are
described. The use of ethylene glycol instead of water increased the enantioselectivity in the ruthenium-promoted hydrogenation
reaction of functionalized ketones. These catalysts are highly active (catalyst/substrate ratio up to 1:10 000, up to 99% e.e.). The
rhodium-mediated hydrogenation of acetamidoacrylic acid was also examined using 1 and 3 as chiral auxiliaries. © 2001 Elsevier
Science Ltd. All rights reserved.
The development of water-soluble organometallic cataly-
sis has expanded significantly.1 One key challenge in
the development of homogeneous catalysis2 has always
been the separation of product from the catalyst, the
recycling and recovery of the expensive chiral catalyst.
Since the early development of homogeneous biphasic
catalysts,3 increasing interest has been focused on asym-
metric hydrogenation using water-soluble catalysts4–7
including Rh8 and Ru-based complexes.9 Several suc-
cessful approaches using the anionic phosphines TPPTS
(e.g. triphenylphosphine trisulfonate) for the prepara-
tion of in situ water soluble palladium catalysts10 and
their use in a large number of CꢀC bond coupling
reactions11 have been demonstrated by our group.
Some applications in the field of palladium-catalyzed
cross coupling reactions using achiral cationic phosphi-
+
Cl
NBoc
NH2
BocHN
N
H2N
N
H
N-Tf
H2N
H2N
H
PPh2
PPh2
PPh2
PPh2
HCl 3N
MeOH
Boc-HN NH-Boc
CH2Cl2,
PPh2
PPh2
H
N
H
N
quant
35%
BocHN
H2N
+
NBoc
NH2
Cl
(R)-Diam-BINAP
1 (R)-Digm-BINAP
O
O
n
O
n
O
3
O
0.9 eq.
O
OH
3
O
O
N
H
DCC, DMAP,CH2Cl2
quant
PPh2
PPh2
H2N
2 PEG-(R)-Am-BINAP
Scheme 1.
Keywords: asymmetric hydrogenation; polymer-supported catalyst; ruthenium; rhodium.
* Corresponding author. Fax: +33 1 44 07 10 62; e-mail: genet@ext.jussieu.fr
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00476-2

3424
P. Guerreiro et al. / Tetrahedron Letters 42 (2001) 3423–3426
R
Br-
Ph2
P
P
Acetone
in situ Ru-catalyst =
+ P*P + HBr
Ru
RuBr2
r.t., 30 min
Ph2
R'
Br-
+NH2
R = R' H2N
N
H
Ru-1 : (R)-Digm-BinapRuBr2
+
Ru-2 : PEG-(R)-Am-BinapRuBr2
Ru-3 : (R)-Diamo-BinapRuBr2
R = MeO(CH2CH2O)n-CO(CH2)3CONH- R'=NH3
+
R = R' = NH3
Scheme 2.
nes bearing quaternary ammonium12 and more recently
guanidinium13 have been reported. Another approach for
the separation of the product from the catalyst involves
polymer supported catalysts.14 Recently, a linear homo-
polymer polyethyleneglycol monomethylether (MeO-
PEG) was attached first to an alkaloid15 then to a
pyrimidine and pyridazine ligand16 and used for asym-
metric dihydroxylation of olefins both in good yields and
enantioselectivities. The use of highly efficient soluble
chiral polyester-supported BINAP ligands obtained by
polycondensation of 5,5%-diamino-BINAP was reported
for the ruthenium-promoted asymmetric hydrogenation
of 2-(6%-methoxy-2-naphtyl)acrylic acid.17 In our continu-
ous interest for the transition-metal catalyzed enantio-
selective hydrogenation reactions18 and water-soluble
catalysts10,11 and due to the outstanding performances of
various Rh and Ru-BINAP complexes,19 we report here
both the synthesis of recyclable BINAP-type ligands
functionalized with guanidinium functions (Digm-
BINAP 1), and PEG-bound BINAP-type (PEG-Am-
BINAP 2) ligands and their use in ruthenium and
rhodium-mediated hydrogenation. During this work,
Diam-BINAP was simultaneously synthesized by
Lemaire20 and our group21 using the same sequence. This
group reported its use for the synthesis of heterogeneous
enantioselective catalysts.20 These reports prompted us to
present our own results in this area (Scheme 1).
As a preliminary evaluation of the best experimental
conditions, the hydrogenation was carried out using the
standard methyl acetoacetate 4 as the substrate (Scheme
3) and (R)-Diamo-BINAPRuBr2 Ru-3 as the catalyst
under 20 bar of hydrogen as shown in Table 1. In all
cases, complete conversion was obtained. The homoge-
neous catalytic system based on (R)-Diamo-BINAPRu-
Br2 Ru-3 gave moderate e.e. when hydrogenation reac-
tion was conducted in water, both at room temperature
and 50°C (60 and 62% e.e., respectively, entries 1 and 2).
By changing water to methanol, the e.e. increased to 80%
(entry 3). The Ru-3 catalyst containing Diamo-BINAP
displayed the best catalytic activity at room temperature
using ethylene glycol as the solvent affording (R)-3-
hydroxybutyrate 7 in 96% e.e. (entry 4). Comparable
catalytic activity was observed in ethylene glycol using
(R)-Digm-BINAPRuBr2 Ru-1 (96% e.e., entry 5).
In the hydrogenation reaction of representative b-
ketoesters such as isobutyrylacetate 5 and ethyl benzoyl-
acetate 6, promoted by the Diamo-BINAPRuBr2 Ru-3
and Digm-BINAPRuBr2 Ru-1 complexes, both the activ-
ity and e.e. were excellent, the b-hydroxyesters 8 and 9
being synthesized in 98 and 99% e.e., respectively (entries
6–8). On the other hand, PEG-(R)-Am-BINAPRuBr2
Ru-3 catalyst also promoted highly enantioselective
hydrogenation of methyl acetoacetate 4 at 50°C in
MeOH (99% e.e., entry 9). The advantage of MeO-PEG
modification was that the hydrogenation was performed
The guanidinium phosphine (R)-Digm-BINAP 1 was
prepared in a two step sequence (35% yield) by reaction
of (R)-Diam-BINAP with 2.5 equiv. of N,N%-di-Boc-N%%-
triflylguanidine22 and triethylamine in CH2Cl2 at 50°C
for 24 h followed by addition of a solution of 3N HCl
in methanol. The commercially available poly(ethyleneg-
lycol) methylether (MeO-PEG, Mn 5000) was acylated
using glutaric anhydride in the presence of 4-N,N%-
dimethylaminopyridine (DMAP) to provide the corre-
sponding carboxylic acid. The (R)-Diam-BINAP reacted
with 0.9 equiv. of the acid in CH2Cl2 at rt in the presence
of dicyclohexylcarbodiimide and DMAP to afford quan-
titatively the monosubstituted PEG-(R)-Am-BINAP 2.
Only one of the amine functions of (R)-Diam-BINAP
reacted with the solid support as shown by MALDI-TOF
mass spectrometry.23 The Ru(II)-catalysts containing the
chiral auxiliaries 1, 2 and (R)-Diamo-BINAPRuBr2 Ru-3
catalyst were prepared from [Ru(COD)(2-methylallyl)2]
and the corresponding ligand by addition of a methanolic
solution of HBr in acetone using our in situ procedure18a
(Scheme 2).
in the homogeneous phase. 3-Hydroxybutyrate
7
was easily separated from the supported catalyst
by simple addition of ether, which allowed the preci-
pitation of the enlarged catalyst. Thus, the poly-
mer bound catalyst could be recycled four times, under
20 bar at 50°C, by adding 2 equiv. of a methanolic
solution of bromhydric acid for each run (Table 2). The
H2
OH O
O
O
20 bar, 24 h
R
OR'
R
OR'
1% mol in situ Ru-catalyst
100% conv.
4 R=R'=CH3
5 R=i-Pr, R'=C2H5
6 R=C6H5, R'=CH3
7
8
9
Scheme 3.

P. Guerreiro et al. / Tetrahedron Letters 42 (2001) 3423–3426
Table 1. Ruthenium-catalyzed hydrogenation of b-ketoesters 4–6
3425
Entry
Catalyst
Substratea
Solvent
T (°C)
e.e. (%)b (R)
1
2
3
4
5
6
7
8
9
(R)-Diamo-BINAPRuBr2
(R)-Diamo-BINAPRuBr2
(R)-Diamo-BINAPRuBr2
(R)-Diamo-BINAPRuBr2
(R)-Digm-BINAPRuBr2
(R)-Diamo-BINAPRuBr2
(R)-Digm-BINAPRuBr2
(R)-Diamo-BINAPRuBr2
PEG-(R)-Am-BINAPRuBr2
4
4
4
4
4
5
5
6
4
H2O
Rt
50
50
Rt
Rt
Rt
Rt
Rt
50
60
62
80
96
96
99
99
98
98
H2Oc
MeOH
Ethylene glycol
Ethylene glycol
Ethylene glycol
Ethylene glycol
Ethylene glycol
MeOH
a Conversion rates were determined by 1H NMR on the crude mixture.
b The enantiomeric excesses were determined by chiral GC on a Lipodex-A column.
c The corresponding acid was obtained.
Table 2. Recycling of PEG-(R)-Am-BINAPRuBr2 Ru-3 and (R)-Digm-BINAPRuBr2 Ru-1 in the reduction of 4
Runa
Catalyst
S/C
Solvent
Conv. (%)b
e.e. (%)c
1
2
3
4
1
2
3
Ru-3
Ru-3
Ru-3
Ru-3
Ru-1
Ru-1
Ru-1
100
100
100
MeOH
MeOH
MeOH
MeOH
Ethylene glycol
Ethylene glycol
Ethylene glycol
100
100
100
100
100
100
60
98
98
96
95
97
93
87
100
1000
1000
500
a Reaction time: 24 h.
b Conversion rates were determined by 1H NMR on the crude mixture.
c The enantiomeric excesses were determined by chiral GC on a Lipodex-A column.
(R)-Digm-BINAPRuBr2 Ru-1 was recycled three times
under 100 bar and 50°C (Table 2).
ligands 1 and 3 was examined (Scheme 4). The
rhodium catalysts such as Rh-1 and Rh-3 were pre-
pared by stirring [Rh(COD)2]+OTf− and the chiral
ligands in THF at room temperature for 30 min. We
found that the hydrogenation of the standard sub-
strate acetamidoacrylic acid 10 performed in ethylene
glycol under 2 bar of hydrogen at 50°C using
Rh-1 and Rh-3 as the catalyst occurred quantitatively
with excellent enantiofacial discrimination leading to
the (S)-N-acetylalanine 11 (94 and 95% e.e., respec-
tively).
All hydrogenations in Table 1 have been preliminarily
carried out on a 1 mmol scale and extended to prepar-
ative amounts (3.6 g) of methyl acetoacetate 4 in the
case of PEG-(R)-Am-BINAPRuBr2 Ru-2 catalyst.
Interestingly, this supported catalyst was efficient using
a catalyst:substrate ratio up to 1:10 000 under 100 bar
of hydrogen at 50°C.24 Finally, the reactivity of
some cationic rhodium complexes containing the
H2
COOH
COOH
NHAc
Rh-1 or Rh-3
NHAc
2 bar, 50°C
ethylene glycol
10
11
NH
H3N
N
H
H3N
OTf
Ph2
Ph2
P
P
Cl
OTf
OTf
Rh
Rh
P
P
H
N
Ph2
Ph2
H3N
H3N
OTf
NH
Cl
Rh-1
Rh-3
Scheme 4.

3426
P. Guerreiro et al. / Tetrahedron Letters 42 (2001) 3423–3426
In summary, we have described the first chiral recy-
clable guanidinium-BINAP. Our preliminary experi-
ments demonstrate the significant potential of the
guanidinium-BINAP and PEG-Am-BINAP ligands
both in the homogeneous ruthenium (e.e. up to 99%)
and rhodium-mediated (e.e. up to 95%) hydrogenation
reactions. After completion of this manuscript, hydro-
genation of ethyl acetoacetate using the bromhydrate of
DiamBINAP was reported.25
15. (a) Han, H.; Janda, K. D. J. Am. Chem. Soc. 1996, 118,
7632–7633; (b) Han, H.; Janda, K. D. Tetrahedron Lett.
1997, 38, 1527–1530; (c) Han, H.; Janda, K. D. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1731–1733.
16. Bolm, C.; Gerlach, A. Angew. Chem., Int. Ed. Engl. 1997,
36, 741–743.
17. (a) Fan, Q. H.; Ren, C. Y.; Yeung, C. H.; Hu, W. H.;
Chan, A. S. C. J. Am. Chem. Soc. 1999, 121, 7407–7408;
(b) Fan, Q. H.; Deng, G. J.; Chen, X. M.; Xie, W.-C.;
Jiang, D. Z.; Liu, D. S.; Chan, A. S. C. J. Mol. Catal.
2000, 159, 37–43.
18. (a) Genet, J.-P.; Pinel, C.; Ratovelomanana-Vidal, V.;
Mallart, S.; Pfister, X.; Can˜o de Andrade, M. C.; Laffitte,
J. A. Tetrahedron: Asymmetry 1994, 5, 665–674; (b)
Genet, J. P. Reductions in Organic Synthesis; A.C.S.
Symposium Series 641, 1996; pp. 31–51; (c) Ratovelo-
manana-Vidal, V.; Genet, J. P. J. Organomet. Chem.
1998, 567, 163–171; (d) Ratovelomanana-Vidal, V.;
Genet, J. P. Can. J. Chem. 2000, 78, 846–851; (e) Rauten-
strauch, V.; Grazi, P.; Vanhessche, K. P. M.; Lenoir, J.
Y.; Genet, J. P.; Woles, J. A.; Bergens, S. H. Angew.
Chem., Int. Ed. 2000, 39, 1992–1995.
19. (a) Noyori, R. Asymmetric Catalysis in Organic Synthe-
sis; John Wiley: New York, 1994; (b) Ohkuma, T.;
Kitamura, M.; Noyori, R. In Catalytic Asymmetric Syn-
thesis; Ojima, I., Ed.; 2000; pp. 1–110.
20. (a) Lemaire, M.; ter Halle, R.; Samson, E.; Colasson, B.;
Spagnol, M. French patent 99 02510; (b) ter Halle, R.;
Colasson, B.; Schulz, E.; Spagnol, M.; Lemaire, M. Tet-
rahedron Lett. 2000, 41, 643–646.
References
1. (a) Herrmann, W. A.; Kohlpaintner, C. W. Angew.
Chem., Int. Ed. Engl. 1993, 32, 1524–1544; (b) Aqueous-
Phase Organometallic Catalysis; Cornils, B.; Herrmann,
W. A., Eds.; 1998; (c) Grieco, P. A. Organic Synthesis in
Water; Blackie Academic & Professional, 1998.
2. (a) Kagan, H. B. In Comprehensive Organometallic
Chemistry; Wilkinson, G.; Stone, F. G. A.; Abel, E. W.,
Eds.; Pergamon Press: Oxford, 1982; Vol. 8, pp. 463–498;
(b) Asymmetric Synthesis; Morrison, J. D.; Ed.; Aca-
demic Press: New York, 1985; Vol. 5.
3. (a) Sinou, D. Bull. Soc. Chim. Fr. 1987, 480–486; (b)
Sinou, D. Metal catalysis in water. Topics Current Chem-
istry 1999, 206, 41–60; (c) Nagel, U; Kinzel, E. Chem.
Ber. 1986, 119, 1731–1733; (d) Sinou, D. In Transition
Metals for Organic Synthesis; Beller, M.; Bolm, Eds.;
Wiley VCH, 1998; Vol. 2, pp. 398–411.
4. Schmid, R.; Broger, E. A.; Cereghetti, M.; Crameri, Y.;
Foricher, J.; Lalonde, M.; Mu¨ller, R. K.; Scalone, M.;
Schoettel, G.; Zutter, U. Pure Appl. Chem. 1996, 68,
131–138.
5. Holz, J.; Heller, D.; Stu¨rmer, R.; Bo¨rrner, A. Tetrahedron
Lett. 1999, 40, 7059–7062.
21. (a) Guerreiro, P. PhD Thesis, Universite´ P. et M. Curie,
2000; (b) Guerreiro, P.; Genet, J. P.; Dellis P. French
patent 99 15217.
22. Feichtinger, K.; Zapf, C.; Sings, H. L.; Goodman, M. J.
Org. Chem. 1998, 63, 3804–3805.
6. Li, W.; Zhang, Z.; Xiao, D.; Zhang, X. J. Org. Chem.
23. MALDI-TOF (matrix-assisted laser desorption ionization
time-of-flight) on Voyager Elite PerSeptive Bio System.
24. General procedure for asymmetric hydrogenation: PEG-
(R)-Am-BINAP (20 mg, 0.033 mmol) and (COD)Ru(h3-
(CH2)2CCH3)2 (1 mg, 0.031 mmol) were placed in a 50
mL flask, and 2 mL of anhydrous dichloromethane was
added dropwise. A methanolic solution of HBr (40 mL,
0.18 M) was added dropwise to the suspension. The
reaction mixture was stirred at room temperature for
about 30 min and a resulting orange suspension was
observed. The solvent was removed under vacuum. The
yellow solid residue was used in situ as a catalyst for the
hydrogenation reaction of methyl acetoacetate (3.6 g, 31
mmol) in methanol (2 mL). The reaction vessel were
placed in a 500 mL stainless steel autoclave, which was
pressurized at 100 bar of hydrogen pressure and 50°C for
48 h. The methanol was concentrated and the ligand was
precipitated using 15 mL of anhydrous ether. After filtra-
2000, 65, 3489–3496.
7. Sollewinjn Gelpke, A. E.; Kooijman, H.; Spek, A. L.;
Hiemstra, H. Chem. Eur. J. 1999, 5, 2472–2482.
8. Wan, K. T.; Davis, M. E. J. Chem. Soc., Chem. Commun.
1993, 1262–1264.
9. Wan, K.; Davis, M. E. Tetrahedron: Asymmetry 1993, 4,
2461–2468.
10. Amatore, C.; Blart, E.; Genet, J. P.; Jutand, A.; Savignac,
M.; Lemaire-Audoire, S. J. Org. Chem. 1995, 60, 6829–
6839.
11. (a) Genet, J. P.; Savignac, M. J. Organomet. Chem. 1999,
576, 305–317; (b) Genet, J. P.; Savignac, M. In Perspec-
tives in Organopalladium Chemistry; Tsuji, J., Ed.; 1999;
pp. 305–317; (c) Transition Metal Catalyzed Reactions;
Murahashi, S. I.; Davies, S., Eds.; Blackwell Science,
1999; pp. 55–79.
12. Smith, R. T.; Ungar, R. K.; Sanderson, L. J.; Baird, M.
C. Organometallics 1983, 2, 1138–1144.
13. (a) Dibowski, H.; Schmidtchen, F. P. Tetrahedron 1995,
51, 2325–2330; (b) Hessler, A.; Stelzer, O. J. Org. Chem.
1997, 62, 2362–2369; (c) Dibowski, H.; Schmidtchen, F.
P. Tetrahedron Lett. 1998, 39, 525–528.
14. Pittman, C. U. In Comprehensive Organometallic Chem-
istry; Stone, G. A.; Wilkinson, G.; Abel, E. W., Eds.;
Pergamon Press: Oxford, 1982; Vol. 8, pp. 553–611.
tion, the mixture was dissolved in
2
mL of
dichloromethane and precipitated once again using 15
mL of anhydrous ether. 3-Hydroxybutyrate was then
separated from the chiral catalyst and obtained in total
conversion and with 99% e.e.
25. Lamouille, T.; Saluzzo, C.; ter Halle, R.; Le Guyader, F.;
Lemaire, M. Tetrahedron Lett. 2001, 42, 663–664.
.
.