Mesoporous silica anchored Ru catalysts for highly enantioselective hydrogenation of β-ketoesters

Article abstract of DOI:10.1039/b406697a

Recyclable and reusable mesoporous silica anchored Ru catalysts based on 4,4′-substituted BINAPs were synthesized and used for the hydrogenation of β-alkyl β-ketoesters with up to 98.6% e.e. and β-aryl β-ketoesters with up to 95.2% e.e.

Full text of DOI:10.1039/b406697a

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Mesoporous silica anchored Ru catalysts for highly enantioselective
hydrogenation of b-ketoesters{
Banu Kesanli and Wenbin Lin*
Department of Chemistry, CB#3290, University of North Carolina, Chapel Hill, NC 27599, USA.
E-mail: wlin@unc.edu
Received (in Columbia, MO, USA) 3rd May 2004, Accepted 1st July 2004
First published as an Advance Article on the web 25th August 2004
Recyclable and reusable mesoporous silica anchored Ru
Table 2 (entries 1–4), b-alkyl b-ketoesters were hydrogenated with
complete conversions and e.e. values in the 96.3 to 98.6% range in
the presence of 1 mol% of 1. These b-alkyl b-ketoesters were
hydrogenated over solid catalyst 2 (2 mol%) with similar e.e. values
to 1 and complete conversions.10 The e.e. values exhibited by 1 and
2 are comparable to those of the parent Ru(BINAP) homogeneous
catalyst11 and are 4–5% higher than those of zirconium
phosphonate-derived heterogeneous catalysts.3a The level of e.e.’s
exhibited by 1 and 2 is also comparable to the best polymer-
anchored Ru catalysts for the hydrogenation of b-alkyl
b-ketoesters.12
catalysts based on 4,4’-substituted BINAPs were synthesized
and used for the hydrogenation of b-alkyl b-ketoesters with
up to 98.6% e.e. and b-aryl b-ketoesters with up to 95.2% e.e.
New routes are being explored to achieve the economical synthesis
of optically pure feedstocks through asymmetric catalysis.1
Heterogenization of well-established soluble transition metal-
based asymmetric catalysts on inorganic oxide or polymer supports
allows easy separation and hence recycling and reuse of expensive
asymmetric catalysts.2 Appropriate covalent attachment of soluble
transition metal-based asymmetric catalysts onto the supports can
also prevent the leaching of toxic metals into the organic products
which can present a formidable challenge if the organic products
are to be used as pharmaceutical ingredients. We have recently
developed a molecular building block approach toward the
heterogenization of homogeneous asymmetric catalysts in zirco-
nium phosphonate hybrid solids.3 Herein we wish to report the
immobilization of Ru complexes of 4,4’-substituted BINAPs on
well-ordered mesoporous silica SBA-15, and the applications of
these heterogeneous asymmetric catalysts in highly enantioselective
hydrogenation of b-ketoesters.
The hydrogenation of b-aryl b-ketoesters was carried out in the
presence of 2 mol% of solid catalyst 1 or 4 mol% of solid catalyst 2.
E.e. values in the range of 81.7–95.2% were obtained for 1, while
e.e. values in the range of 71.9–93.5% were obtained for 2 (Table 2,
Since their discovery in the early 1990’s, well-ordered mesopor-
ous materials have been examined for a number of applications.4
Immobilization of homogeneous asymmetric catalysts on the inner
walls of such mesoporous solids offers several advantages
(including higher surface areas and larger open channels) over
other less defined supports such as organic polymers. Mesoporous
siliceous materials such as MCM-41 and SBA-15 have indeed been
used as supports for the immobilization of several asymmetric
catalysts.5 We have chosen SBA-15 as the supports for this work
because of their ease of synthesis and very large pore sizes (so that
diffusion of substrates and products would be more facile).6
Scheme 1
Table 1 Surface area, pore volume, and pore size of SBA-15, 1, and 2
Lithiation
of
4,4’-bis(cyclopentanol)-2,2’-bis(diphenylpho-
SBA-15
1
2
sphino)-1,1’-binaphthyl and 4-(cyclopentanol)-2,2’-bis(diphenyl-
phosphino)-1,1’-binaphthyl7 followed by treatment with
3-iodopropyltrimethoxysilane afforded the modified BINAPs L1
and L2 (Scheme 1). Ligands L1 and L2 have been characterized by
1H{31P} and 31P{1H} NMR spectroscopy. RuL1(DMF)2Cl2 and
RuL2(DMF)2Cl2 were synthesized by heating [RuCl2(p-cymene)]2
and L1 and L2 in DMF at 100 uC, respectively. A suspension of
SBA-15 and RuL1(DMF)2Cl2 or RuL2(DMF)2Cl2 in toluene was
refluxed overnight to give the heterogenized precatalysts 1 and 2.{8
The Ru precatalyst loadings were determined by direct current
plasma (DCP) analysis of the Ru content in the modified SBA-15.9
The pristine SBA-15 has a BJH surface area of 724 m2/g and a BJH
BJH surface area (m2/g)
BJH pore volume (mL/g)
˚
BJH pore size (A)
724
1.98
113
487
1.38
96
529
1.52
101
˚
average pore size of 113 A. Upon the immobilization of the Ru
complexes, the solid catalysts 1 and 2 exhibited expected diminished
surface areas and pore sizes (Table 1). 2 has slightly larger surface
area, pore volume, and pore size than 1, consistent with the
presence of the bulky 1-cyclopentanol group in 1.
Catalytic asymmetric hydrogenation of both b-alkyl and b-aryl
b-ketoesters was carried out under a hydrogen pressure of 1400 psi
in the presence of 1 or 2 in methanol at r.t. for 20 h.§ As shown in
{ Electronic supplementary information (ESI) available: experimental
section. See http://www.rsc.org/suppdata/cc/b4/b406697a/
Fig. 1 N2 adsorption isotherms for SBA-15, 1, and 2 at 77 K.
2 2 8 4
C h e m . C o m m u n . , 2 0 0 4 , 2 2 8 4 – 2 2 8 5
T h i s j o u r n a l i s ß T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

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Table 2 Catalytic asymmetric hydrogenation of b-ketoesters by 1 and
Table 3 Recycling and reuse of 1 for the hydrogenation of methyl
acetoacetatea
213
Run
1
2
3
4
5
e.e. (%)
Conversion (%)
98.6
w 99
98.4
w 99
96.2
w 99
89.2
91
82.1
83
a All the reactions were carried out with 1 mol% catalyst in MeOH
under 1400 psi of H2 for 20 h.
Entry
R1
R2
1a
2b
1
2
Me
Me
Me
Me
2’-CF3-Ph
2’-Cl-Ph
3’-CF3-Ph
4’-OMe-Ph
Ph
4’-CF3-Ph
4’-F-Ph
4’-Cl-Ph
Me
iPr
98.6
98.4
97.3
96.3
95.2
94.2
92.7
91.5
91.0
87.4
86.3
81.7
97.6
98.6
97.1
96.3
93.5
90.0
90.4
82.3
79.9
71.9
81.4
81.4
Notes and references
3
tBu
Me
Me
Me
Me
Et
{ Preparation of solid catalysts. A mixture of [Ru(p-cymene)Cl2]2 (15.3 mg,
0.025 mmol) and L1 (50 mg, 0.052 mmol) in anhydrous DMF (4 mL) was
heated at 100 uC under Ar for 30 min and then cooled to 25 uC. All the
volatile components were removed under vacuum to give a dark red solid.
This solid was refluxed with 335 mg of SBA-15, that had been dried under
vacuum at 135 uC for 3 h, in 10 mL of toluene overnight. The mixture was
cooled to r.t. and centrifuged for 30 min, the supernatant was removed.
The solid was washed with dry toluene and dried under vacuum. 400 mg of
solid catalyst 1 was obtained after this treatment.
§ A typical procedure for asymmetric hydrogenation of b-ketoester. 19.2 mg
of solid catalyst 1 (2.5 mmol) was weighed into a Teflon-capped vial inside
a drybox, and to this vial was added ethyl benzoylacetoacetate (24 mL,
0.125 mmol) and anhydrous methanol (0.5 mL) under Ar. The vial was
quickly transferred inside a stainless steel autoclave, and sealed. After
purgingwithhydrogenfor6 times, final H2 pressure was adjusted to1400 psi;
20 h later, H2 pressure was released and water (10 mL) was added. The
hydrogenated product was extracted with diethyl ether and passed through a
mini silica-gel column before chiral GC, HPLC and SFC analyses.
4c
5
6
7
8
9
10
11
12
Et
Me
Me
Me
a 1 mol% catalyst loading for entries 1–4 and 2 mol% catalyst load-
ing for entries 5–12. b 2 mol% catalyst loading for entries 1–4 and
4 mol% catalyst loading for entries 5–12. c R3 ~ Me.
entries 5–12). These e.e. values are much higher than those afforded
by the homogeneous Ru(BINAP)(DMF)2Cl2 catalyst, but a few
percent lower than those afforded by the parent Ru[4,4’-(1-
cyclopentanol)2BINAP](DMF)2Cl2 catalyst reported by us
recently.7 Consistent with our earlier discovery of the 4,4’-
substituent effects of BINAP in the hydrogenation of b-aryl
b-ketoesters,7 2 gave lower e.e.’s than 1 for all the substrates tested
because of the lack of a bulky substituent in the 4’-position of the
modified BINAP L2.
We have attempted to recycle and reuse 1 in the hydrogenation
of methyl acetoacetate. As shown in Table 3, 1 was successfully
used for 5 consecutive runs of asymmetric hydrogenation of methyl
acetoacetate. Complete conversions were obtained for the first
three runs, and the conversion started to drop in the fourth and
fifth run. The e.e. value also deteriorated as the conversion
dropped. We believe that the loss of activity and the deterioration
of enantioselectivity are probably a result of the air-sensitivity of
the catalytically active Ru-hydride species (but not the leaching of
Ru-containing complexes). Control experiments showed that the
supernatant did not catalyze the hydrogenation of methyl
acetoacetate. Consistent with this, DCP spectroscopy showed
that less than 0.12% of Ru-containing complexes had leached into
the organic phase during each run of asymmetric hydrogenation.
In summary, we have designed recyclable and reusable
heterogeneous asymmetric catalysts via covalent anchoring to the
inner walls of mesoporous SBA-15. These immobilized catalysts
have been used for the hydrogenation of b-ketoesters with up to
98.6% e.e.
1 (a) R. Noyori, Angew. Chem., Int. Ed., 2002, 41, 2008; (b) W. S. Knowles,
Adv. Synth. Catal., 2003, 345, 3; (c) H.-U. Blaser, Adv. Synth. Catal.,
2002, 344, 17.
2 (a) Q. H. Fan, Y.-M. Li and A. S. C. Chan, Chem. Rev., 2002, 102, 3385;
(b) P. McMorn and G. J. Hutchings, Chem. Soc. Rev., 2004, 33, 108.
3 (a) A.Hu,H.L.NgoandW.Lin,Angew.Chem.,Int.Ed.,2003,42,6000;
(b) A. Hu, H. L. Ngo and W. Lin, J. Am. Chem. Soc., 2003, 125, 11490.
4 C. T. Kresge, M. E. Leonowicz, W. J. Roth, J. C. Vartuli and J. S. Beck,
Nature, 1992, 359, 710.
5 (a) S. J. Bae, S.-W. Kim, T. Hyeon and B. M. Kim, Chem. Commun.,
2000, 31; (b) A. Corma, H. Garcia, A. Moussaif, M. J. Sabater, R. Zniber
and A. Redouane, Chem. Commun., 2002, 1058; (c) S. Xiang, Y. Zhang,
Q. Xin and C. Li, Angew. Chem., Int. Ed., 2002, 41, 821; (d) M. D. Jones,
R. Raja, J. M. Thomas, B. F. G. Johnson, D. W. Lewis, J. Rouzaud and
K. D. M. Harris, Angew. Chem., Int. Ed., 2003, 42, 4326.
6 (a) D. Zhao, J. Feng, Q. Huo, N. Melosh, G. H. Frederickson,
B. F. Chmelka and G. D. Stucky, Science, 1998, 279, 548; (b) P. Yang,
D. Zhao, D. I. Margolese, B. F. Chmelka, G. D. Stucky and D. Galen,
Nature, 1998, 396, 152.
7 A. Hu, H. L. Ngo and W. Lin, Angew. Chem., Int. Ed., 2004, 43, 2501.
8 H. Gao and R. J. Angelici, Organometallics, 1998, 17, 3063.
9 Typical loadings are 0.0125 mmol of 1 and 0.0112 mmol of 2 per gram of
SBA-15, respectively.
10 Although b-alkyl b-ketoesters can be hydrogenated with complete
conversions in the presence of 1% of 2, much inferior e.e. values (10–15%
lower) were obtained.
11 R. Noyori, T. Ohkuma, M. Kitamura and H. Takaya, J. Am. Chem.
Soc., 1987, 109, 5856.
12 R. Halle, B. Colasson, E. Schulz, M. Spagnol and M. Lemaire,
Tetrahedron Lett., 2000, 41, 643.
We acknowledge financial support from NSF (CHE-0208930).
We thank Dr A. Hu for his generous help. W.L. is an Alfred
P. Sloan Fellow, an Arnold and Mabel Beckman Young
Investigator, a Cottrell Scholar of Research Corp, and a Camille
Dreyfus Teacher-Scholar.
13 All the reactions were judged to have w 99% conversions based on
integrations of NMR peaks. E.e.% values were determined by GC using
a Superco c-Dex 225 column or by HPLC using a Chiralpak AD column
and by SFC using a Chiralpak AS column.
C h e m . C o m m u n . , 2 0 0 4 , 2 2 8 4 – 2 2 8 5
2 2 8 5