Chiral, Porous, Hybrid Solids for Highly Enantioselective Heterogeneous Asymmetric Hydrogenation of β-Keto Esters

Article abstract of DOI:10.1002/anie.200351264

Catalytic building blocks: Chiral porous zirconium phosphonates containing Rubinap moieties are synthesized by a molecular building-block approach, and characterized by a variety of techniques. These hybrid solids are used for enantioselective heterogeneous asymmetric hydrogenation of β-keto esters with ee values of up to 95% (see picture). Ready tunability of such a molecular building-block approach promises to lead to useful heterogeneous asymmetric catalysts.

Full text of DOI:10.1002/anie.200351264

Communications
Supported Catalysts
Chiral, Porous, Hybrid Solids for Highly
Enantioselective Heterogeneous Asymmetric
Hydrogenation of b-Keto Esters**
Aiguo Hu, Helen L. Ngo, and Wenbin Lin*
The chemistry of hybrid solids constructed from organic
linkers and metal nodes has received much recent attention,
owing to the propensity of incorporating and fine-tuning
[*] Prof. W. Lin, Dr. A. Hu, H. L. Ngo
Department of Chemistry, CB 3290
University of North Carolina
Chapel Hill, NC 27599 (USA)
Fax: (+1)919-962-2388
E-mail: wlin@unc.edu
[**] We acknowledge financial support from NSF (CHE-0208930). 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.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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DOI: 10.1002/anie.200351264
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Angewandte
Chemie
desired properties by judicious choice of the building blocks.[1]
The use of biphenyl-derived bridging ligands has, for example,
led to novel microporous pillared zirconium phosphonates[2]
as well as ordered mesoporous organosilica hybrid solids.[3]
We believe that the incorporation of axially chiral rigid
organic linkers into such hybrid materials can lead to porous
solids exploitable for heterogeneous asymmetric catalysis and
chiral separations.[4] We have recently synthesized single-
crystalline, chiral porous lanthanide bisphosphonates for
potential chiral separations.[4a,b] Herein we report novel
chiral porous zirconium phosphonates for the highly enantio-
selective asymmetric hydrogenation of b-
keto esters.
involves nickel-catalyzed phosphonation of 2,2’-bis(triflato)-
1,1’-binaphthyl bis(diethylphosphonate). All the intermedi-
ates and L1-H4 were characterized by 1H, 13C{1H}, and 31P{1H}
NMR spectroscopy and mass spectrometry. L2-H4 was syn-
thesized according to a literature procedure.[9]
[Ru(L1-H4)(dmf)2Cl2] and [Ru(L2-H4)(dmf)2Cl2] inter-
mediates were synthesized by treating L1-H4 and L2-H4 with
0.46 equivalents of [{Ru(benzene)Cl2}2] in DMF at 1008C.[10]
Chiral porous zirconium phosphonates with approximate
formulae [Zr{Ru(L1)(dmf)2Cl2}]·2MeOH (Zr-Ru-L1) and
[Zr{Ru(L2)(dmf)2Cl2}]·2MeOH (Zr-Ru-L2) were synthesized
Catalytic asymmetric hydrogenation
is one of the most efficient strategies for
the synthesis of optically active mole-
cules.[5] The ruthenium and rhodium
complexes of 2,2’-bis(diphenylphos-
phanyl)-1,1’-binaphthyl (binap) are par-
ticularly useful for the reduction of a
wide range of substrates including keto
esters, alkenes, and ketones with high
enantioselectivity.[5a,6] Both high costs of
Ru–binap and Rh–binap precatalysts and
the necessity to remove trace amounts of
metals from the organic products have,
however, hindered their applications in
many industrial processes. Heterogeniza-
tion of these homogeneous asymmetric
catalysts presents an interesting solution
to both recycling and reusing expensive
catalysts and preventing the leaching of
metals. To date, several approaches have
been used to heterogenize homogeneous
asymmetric catalysts including attach-
ment to porous inorganic-oxide and
insoluble organic-polymer supports,
incorporation into soluble organic mac-
romolecules and membranes, and immo-
bilization through biphasic systems.[7]
We envision that metal phosphonates
containing pendant chiral chelating
bisphosphanes can be designed using
rigid bisphosphonic acid ligands, 2,2’-bis-
(diphenylphosphanyl)-1,1’-binaphthyl-6,6’-
bis(phosphonic acid), L1-H4, and 2,2’-
bis(diphenylphosphanyl)-1,1’-binaphth-
yl-4,4’-bis(phosphonic acid), L2-H4. Such
hybrid materials will combine the robust
framework structure of metal phospho-
nates[8] and enantioselectivity of metal
complexes of the pendant chiral bisphos-
phanes,[5] and may find applications in
heterogeneous asymmetric catalysis.
Enantiopure L1-H4 was synthesized in
three steps starting from previously
reported 2,2’-dihydroxy-1,1’-binaphthyl-
6,6’-bis(diethylphosphonate)[4b] in 47%
Figure 1. Preparation of L1-H4, Zr-Ru-L1, and Zr-Ru-L2. dppe=1,2-bis(diphenylphosphanyl)ethene,
overall yield (Figure 1). The key step DABCO=1,4-diazabicyclo[2.2.2]octane, Tf=Trifluoromethanesulfonyl.
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by refluxing Zr(OtBu)4 and 1 equivalent of [Ru(L1-
H4)(dmf)2Cl2] and [Ru(L2-H4)(dmf)2Cl2] in methanol. These
chiral porous zirconium phosphonates have been character-
ized with a variety of techniques including thermogravimetric
analysis (TGA), nitrogen adsorption isotherms, X-ray dif-
fraction (XRD), SEM, IR spectroscopy, and microanalysis.
While the compositions of Zr-Ru-L1 and Zr-Ru-L2 were
established by TGA and microanalysis results, the IR spectra
supported the formation of zirconium phosphonate bonds as
À1
À
the P O stretches at 950–1150 cm are at lower wave
numbers than those of [Ru(L1-H4)(dmf)2Cl2] and [Ru(L2-
H4)(dmf)2Cl2]. The IR spectra also exhibit intense and broad
O H stretching vibrations at around 3400 cmÀ1, consistent
À
Figure 3. SEM image of the Zr-Ru-L1 solid precatalyst. The scale bar
indicates 1 mm.
with the presence of MeOH solvates.[11] Nitrogen-adsorption
measurements indicate that both Zr-Ru-L1 and Zr-Ru-L2 are
highly porous with rather wide pore size distributions
(Figure 2). Zr-Ru-L1 exhibits a total BET surface area of
homogeneous binap-Ru catalyst. This level of enantioselec-
tivity is only slightly lower than that of their best homoge-
neous counterparts.[5,6,12] Zr-Ru-L1 gave a turnover frequency
(TOF) of 364 hÀ1 with a 0.1% solid loading, in comparison
with a TOF of 810 hÀ1 for the homogeneous binap-Ru catalyst
under identical conditions.[13] Similar to the binap-Ru cata-
lyst,[6a] Zr-Ru-L1 catalyzes the hydrogenation of b-aryl-
substituted b-keto esters with modest ee value.[14]
In contrast, Zr-Ru-L2 catalyzes the hydrogenation of b-
keto esters with only modest ee values. Supernatants of Zr-
Ru-L1 and Zr-Ru-L2 in MeOH did not catalyze the hydro-
genation of b-keto esters, which unambiguously demonstrates
Table 1: Heterogeneous asymmetric hydrogenation of b-keto esters.[a]
Substrate
Catalyst
loading
[%]
T
H2
pressure ee
[psi][b]
Zr-Ru-L1
Zr-Ru-L2
ee
(yield [%]) (yield [%])
94.0 (100)
Figure 2. N2 adsorption isotherms for Zr-Ru-L1 and Zr-Ru-L2 at 77 K.
The inset shows BET plot for Zr-Ru-L1 in the mesoporous region.
1
608C 700
1
0.1
RT
1400
95.0 (100) 73.1 (90)
93.3 (100)
475 m2 gÀ1 with a microporous surface area of 161 m2 gÀ1 and a
pore volume of 1.02 cm3 gÀ1 (by BJH method). Zr-Ru-L2
exhibits a total BET surface area of 387 m2 gÀ1 with a
microporous surface area of 154 m2 gÀ1 and a pore volume
of 0.53 cm3 gÀ1 (by BJH method). SEM images show that both
solids are composed of sub-micrometer particles (Figure 3),
while powder X-ray diffraction (PXRD) indicate that both
solids are amorphous.
Although the amorphous nature of the present chiral
porous zirconium phosphonates has prevented us from
elucidating their exact structures, we have successfully
utilized the binap-Ru moieties on the surfaces for heteroge-
neous asymmetric catalysis. As Table 1 shows, both Zr-Ru-L1
and Zr-Ru-L2 are highly active catalysts for asymmetric
hydrogenation of b-keto esters. Zr-Ru-L1 catalyzes the
hydrogenation of a wide range of b-alkyl-substituted b-keto
esters with complete conversions and ee values ranging from
91.7 to 95.0% with the same enantio-enrichment as the parent
608C 700
1
1
RT
RT
1400
1400
92.0 (100) 65.0 (90)
91.7 (100) 68.1 (85)
1
1
1
RT
RT
RT
1400
1400
1400
69.6 (100) 15.7 (50)
93.1 (100) 64.0 (100)
93.3 (100) 78.8 (70)
[a] All the reactions were carried out in 20 h, and the ee values (%) were
determined by GC on a Supelco g-Dex 225 column. The absolute
configurations of the products are identical to those obtained by the
Ru-(R)-binap catalyst. The conversions were determined by the integra-
1
tions of H NMR spectra. [b] 1 psi=6.89476 kPa.
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Res. 2001, 34, 319; d) M. J. Zaworotko, B. Moulton, Chem. Rev.
heterogeneous nature of the present asymmetric catalytic
systems. We have further confirmed the heterogeneous nature
of the present systems using direct current plasma (DCP)
spectroscopy. DCP results indicated that less than 0.01% of
the ruthenium has leached into the organic solution for each
round of hydrogenation.
We have also successfully reused the Zr-Ru-L1 system for
asymmetric hydrogenation of methyl acetoacetate without
significant deterioration of enantioselectivity. The Zr-Ru-L1
system was used for five cycles of hydrogenation with
complete conversions and ee values of 93.5, 94.2, 94.0, 92.4,
and 88.5%, respectively.
In summary, we have synthesized novel chiral porous
zirconium phosphonates. These ruthenium-containing chiral
porous solids have been used for heterogeneous asymmetric
hydrogenation of b-keto esters with ee values of up to 95%
and can be readily recycled and reused. Ready tunability of
such a molecular building-block approach will allow the
optimization of the catalytic performance of these hybrid
materials and lead to practically useful heterogeneous
asymmetric catalysts.
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Experimental Section
Zr-Ru-L1: L1-H4 was synthesized in three steps from 2,2’-dihydroxy-
1,1’-binaphthyl-6,6’-bis(diethylphosphonate) and treated with
[{Ru(benzene)Cl2}2] (0.46 equivalents) in DMF at 1008C under
argon for 40 min and then cooled to 408C. All the volatile
components were removed under vacuum, and the dark-red solid
was directly used for the synthesis of Zr-Ru-L1 solid precatalyst. This
solid was first dissolved in anhydrous degassed methanol, and heated
overnight under reflux with Zr(OtBu)4 (1 equivalent). After centri-
fugation and rinsing with anhydrous methanol three times, the residue
was dried under vacuum to give a dark-brown solid in 96% yield. This
dark-brown solid is not soluble in common organic solvents including
methanol. Elemental analysis (%) calcd for C52H52Cl2N2O10P4RuZr,
[Zr{Ru(L1)(dmf)2Cl2}]·2MeOH: C 49.9, H 4.19, N 2.24, Cl 5.66, P
9.90, Ru 8.07, Zr 7.29; found: C 50.6, H 3.87, N 2.54, Cl 4.98, P 9.32,
Ru 7.87, Zr 7.70.
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[10] A slight excess of ligand is used to ensure that no ligand-free Ru
centers are present in the solid catalyst.
[11] There may also be residual protons on the bisphosphonic acids
À
that contribute to the O H stretching vibrations.
[12] Both [Ru(L1-H4)(dmf)2Cl2] and [Ru(L2-H4)(dmf)2Cl2] gave
98.3% ee for homogeneous hydrogenation of methyl acetoace-
tate in MeOH.
[13] This level of TOF value is comparable to those reported in the
literature for the Ru-bisphosphane catalysts. See: H.-U. Blaser,
C. Malan, B. Pugin, F. Spindler, H. Steiner, M. Studer, Adv.
Synth. Catal. 2003, 345, 103.
[14] The homogeneous Ru-binap catalyst gave an ee value of 80.3%
for hydrogenation of ethyl benzoylacetate.
General procedure for catalysis: Methyl acetoacetate (55 mL,
0.5 mmol) and anhydrous methanol (1 mL) were added to solid
precatalyst (6.0 mg, 5 mmole) in a test tube under argon. The test tube
was quickly transferred into a stainless steel autoclave, and sealed.
After purging with H2 six times, the final H2 pressure was adjusted to
1400 psi or 700 psi (9652.664 and 4826.332 kPa). H2 pressure was
released 20 h later, and methanol was removed in vacuo. The
hydrogenated product was extracted with diethyl ether and passed
through a mini silica-gel column. The conversions were assessed
based on the integration of peaks in the 1H NMR spectra of the
products and starting materials, while the ee values were determined
using chiral GC.
Received: February 24, 2003
Revised: June 10, 2003 [Z51264]
Keywords: asymmetric catalysis · hybrid materials ·
.
hydrogenation · ruthenium · supported catalysts · zirconium
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