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F. Glorius et al.
DOI: 10.1002/anie.200504212
Catalysis
Keywords:
asymmetric catalysis coordination
compounds heterogeneous
catalysis metalorganic
frameworks supported
catalysts
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Limited natural resources and an increasing demand for enantiomerically pure compounds render catalysis and especially heterogeneous asymmetric catalysis a key technology. The field has rapidly
advanced from the initial use of chiral biopolymers, such as silk, as a
support for metal catalysts to the modern research areas. Mesoporous
supports, noncovalent immobilization, metalorganic catalysts, chiral
modifiers: many areas are rapidly evolving. This Review shows that
these catalysts have more to them than facile separation or recycling.
Better activities and selectivities can be obtained than with the
homogeneous catalyst and novel, efficient reaction mechanisms can be
employed. Especially fascinating is the outlook for highly ordered
metalorganic catalysts that might allow a rational design, synthesis,
and the unequivocal structural characterization to give tailor-made
catalysts.
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2. Immobilization of Chiral
Homogeneous Catalysts
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6. Diastereoselective
Heterogeneous Catalysis
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7. Conclusion
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1. Introduction
Catalysis of organic reactions is key for an efficient
synthesis and, thus, represents one of the most economically
important technologies.[1] The growing demand for enantiopure compounds in the life sciences has stimulated an
increased interest in asymmetric catalysis.[2] Although homogeneous catalysts are often expensive and their separation
and recycling troublesome, the field of asymmetric catalysis
has been dominated for a long time by homogeneous catalysis
because of the excellent selectivities and activities obtained.
In more recent years, significant developments in the area of
solid-phase chemistry has resulted in enormous progress
being made in interdisciplinary research on stereoselective
heterogeneous catalysis.[3] The potential advantages of heterogeneous catalysis, such as easy separation, efficient recycling, minimization of metal traces in the product, and an
improved handling and process control, that finally result in
overall lower costs are well known. Furthermore, in some
cases heterogeneous catalysts are even more selective than
their homogeneous counterparts. Ideally, the advantages of
homogeneous and heterogeneous catalysis, such as high
activity and selectivity on one hand and separation and
recycling on the other, should be combined.[4] However, the
different areas of asymmetric heterogeneous catalysis have
reached widely different levels of maturity. Whereas the
immobilization of homogeneous catalysts on solid supports
represents an established field that is on the verge of being
applied in industry, the young field of metalorganic catalysts
is in a rapidly growing development phase.
It is the goal of this Review to give an overview of
asymmetric heterogeneous catalysis from the point of view of
an organic chemistpresenting the state of the art and
discussing their potential and limitations. Heterogeneous
asymmetric catalysis has been subdivided into three major
categories: 1) application of immobilized homogeneous catalysts (Sections 2 and 3), 2) catalysis on surfaces that are chiral
themselves or modified with chiral modifiers (Sections 4 and
5), and 3) diastereoselective reactions of chiral substrates
promoted by achiral catalysts (Section 6).
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Disadvantages
metalorganic systems
relatively easy immobilization technique
synthesis of modified ligands necessary
no support necessary
structure of the network is hard to predict
high density of active catalyst centers
crystalline catalyst (still rare), structure can be determined by X-ray structural
analysis
+ high levels of porosity
+ often no leaching
+
+
+
+
chiral modifier
+ synthetically rather facile
+ inexpensive
+ unique mechanisms that have no counterpart in homogeneous catalysis
macromolecular catalysts
+ simple synthesis of catalyst, suited for scale-up (polypeptides)
only a few successful systems known
+ unique mode of action
relatively low turnover frequencies (TOFs)
challenging analysis of mechanisms
substrate limitations
+ known mechnism
+ robust and reliable
+ often rationally designed
diastereoselective catalysis
cost of the chiral auxiliary
demanding substrate synthesis
additional steps for the attachment and cleavage of the auxiliary
necessary
*
*
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Frank Glorius studied chemistry at the Universit*t Hannover, Stanford University (Prof.
Paul A. Wender), the Max-Planck-Institut f3r
Kohlenforschung and Universit*t Basel (Prof.
Andreas Pfaltz), and Harvard University
(Prof. David A. Evans). In 2001 he began
his independent research career at the MaxPlanck-Institut f3r Kohlenforschung in Germany (Prof. Alois F3rstner). Since 2004 he
has been a Professor for Organic Chemistry
at the Philipps-Universit*t Marburg. His
research focuses on the development of new
concepts for catalysis and their implementation in organic synthesis.
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The success of the solid-phase peptide synthesis developed by Merrifield in the 1960s has resulted in the covalent
attachment of chiral ligands onto a functionalized polymer
becoming a popular approach. In addition to only slightly
cross-linked Merrifield resins (poly(styrenedivinylbenzene)polymers),[13] other resins such as JandaJEL (polystyrene
polymers containing a tetrahydrofuran-derived crosslinker),[14]
TentaGel
(polystyrene-poly(ethyleneglycolOC2H4-NHCOC2H5),[15] and other PS-PEG (polystyrenepolyethyleneglycol) resins[16] have been employed successfully for anchoring metalligand complexes.
Han and co-workers developed ligand 2, a variation of the
chiral Trost ligand 1, in which the cyclohexyldiamine moiety
was replaced by a pyrrolidinediamine unit so as to allow facile
anchoring onto the support and minimal disturbance to the
catalytic site (Scheme 1).[17] It was shown that the use of
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These ligands were screened successfully in the rutheniumcatalyzed asymmetric transfer hydrogenation of acetophenone.[21]
2.1.3. Covalent Immobilization on an Inorganic Support
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morpholine-N-oxide (NMO) as cooxidant three times without loss of selectivity in the asymmetric dihydroxylation of amethylstyrene. The significant deactivation observed when
using K3[Fe(CN)6] or molecular oxygen as the cooxidant was
explained by a competitive exchange of the OsO42 ions for
ferrocyanide or phosphate ions.[46] Catalysts prepared by the
immobilization of OsO42 on quaternary ammonium groups
supported on a polymer such as chloromethylated styrenedivinylbenzene copolymers (Merrifield resin, resin-OsO4 ;
Scheme 12 b) or silica gel (SiO2-OsO4 ; Scheme 12 c) did not
show any undesired leaching of osmium in the presence of
K3[Fe(CN)6] (Table 2). A higher activity was observed with
Entry
Olefin
Yield [%]
ee [%]
Catalyst
Cooxidant
LDH-OsO4
NMO
96
99
2
3
4
resin-OsO4
LDH-OsO4
resin-OsO4
K3[Fe(CN)6]
NMO
K3[Fe(CN)6]
95
97
92
99
97
98
resin-OsO4
K3[Fe(CN)6]
85
82
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The immobilized cationic [{(R,R)-Meduphos}Rh(cod)]OTf complex was prepared by simple mixing the
complex with MCM-41 in CH2Cl2. Presumably, it is bound
through the hydrogen bonding of the triflate counterion to the
support.[36a] In the asymmetric hydrogenation of olefins in
hexane, the heterogeneous catalyst gave superior selectivities
than the homogeneous system that performed in methanol
(Scheme 20). Remarkably, this impregnated, heterogeneous
catalyst could be recycled and reused up to four times without
loss of activity and selectivity.
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Scheme 20. Asymmetric hydrogenation with impregnated [{(R,R)Meduphos}Rh(cod)]OTf; results obtained with the homogeneous catalyst are given in brackets (in hexane/methanol). Tf = triflate.
In a different approach Augustine et al. used phosphotungstic acid (PTA) as the linker between the support and the
chiral metalligand complex.[70] The immobilization is based
on the interaction of both the metalligand complex as well as
the support with an oxygen atom or a hydroxy group of the
PTA. Therefore, a synthetic modification of the ligand
structure is not necessary for the immobilization. In the Rhcatalyzed asymmetric hydrogenation of methyl 2-acetamidoacrylate (17) similarly high selectivities were obtained
using [Rh(Meduphos)]-PTA-alumina as under homogeneous
conditions (up to 95 % ee after three cycles, Scheme 21 b).
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Entry Catalyst
(mol %)
Yield of 23
ee (S)(Conversion) [%] 23 [%]
1
2
3
4
5
6
7
CH2Cl
CH2Br
(CH2)2OH
Ph
(CH2)2OH
(CH2)2OH
Ph
41 (5152)
94[b]
36 (40)
(50)
(34)
(3639)
32
9295[a]
96[a]
94[a]
96
93
94
96
> 99[a]
59[a]
90
48
5461
98
CH2Cl
43
98
99
21 a (0.25)
21 a (0.5)
21 a (0.4)
21 b (0.3)
21 b (0.4)
21 b (0.5)[c]
[Co(24)]PF6
(0.5)
[Co(25)]PF6
(0.5)
ee (R)22 [%]
[a] Result over 5 cycles. [b] Dynamic kinetic resolution of epibromohydrin. [c] Applied as a stationary phase in a continuous flow reactor.
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Entry Catalyst
1
2
3
4
85
67
81
78
[VO(salen)], homogeneous
SWNT-[VO(salen)]
activated carbon-[VO(salen)]
silica gel-[VO(salen)]
3.5
3.1
3.75
2.7
89
66
48
85
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Scheme 34. Effect of the zeolite on the ee value (results obtained with
the corresponding homogeneous catalystis are given in brackets).
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2.4. Conclusion
For a long time, the immobilization of homogeneous
chiral catalysts had been accompanied by a loss in activity and
selelectivity. Today, by choosing a suitable support, especially
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Figure 3. View along the c-axis of 49. Clearly visible are the large chiral
channels, with the accessible surface highlighted. (Reproduced from
Ref. [105].)
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Scheme 39. Chiral metalorganic polymers for the enantioselective ene reaction or oxidation of sulfides (CMHP:
cumene hydroperoxide).
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4. Chiral Modifiers
Scheme 44. Titanium(IV)-catalyzed ZnEt2 addition to aromatic aldehydes (ee values obtained with the corresponding homogeneous
conditions are given in brackets).
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Scheme 45. Enantioselective hydrogenation of aromatic ketones (results of the corresponding homogeneous catalyst are given in brackets).
Scheme 47. Suitable substrates for ketone hydrogenation with platinum/cinchona alkaloids.
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Scheme 49. Influence of the structure of the modifier on the enantioselectivity in the hydrogenation of ethyl pyruvate.[129, 130]
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Figure 5. Adsorption model of the interaction between the platinumadsorbed chinchonidine and methyl pyruvate on the basis of DFT
calculations. (Reproduced from Ref. [138].)
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4.4. Conclusion
The examples shown above illustrate clearly that the
cooperation between an achiral heterogeneous catalyst and a
chiral modifier has enormous potential for asymmetric
catalysis. It can be expected that the field of chiral modifiers
(organocatalysts!) will benefit from the rapidly developing
field of organocatalysis.[151] New mechanistic insights into the
existing systems will hopefully lead to the rational design of
these catalyst systems in the future.
(S)-leucine (92; Scheme 54) can be prepared on a multi-kilogram scale, and are
commercially available.[155a, 156]
JuliV and Colonna initially reported a
highly enantioselective epoxidation of
chalcone with polyamino acid catalysts,
the best results being obtained with poly(S)-alanine (91) with a degree of polymerization of n = 30 (Scheme 55).[157]
Since the reaction takes place in a threephase system (water, organic solvent,
insoluble catalyst), vigorous stirring is
important for the proper mixing of the
reactants.
The development of a biphasic system by Robert and coworkers was a great improvement for the practical application
of the JuliVColonna epoxidation.[158] The use of a solid urea/
hydrogen peroxide complex as the oxidant allows for waterfree reaction conditions and results in a significant enhancement in the reaction rate of up to a hundred times relative to
the original three-phase system (Scheme 56).
Scheme 53. Enantioselective hydrocyanation of aromatic aldehydes
with cyclic dipeptides as catalysts.
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Scheme 57. Schematic presentation of: a) steric and b) electronic influences on the facial selectivity.
Angew. Chem. Int. Ed. 2006, 45, 4732 4762
Functional groups such as amines or alcohols can influence the diastereoselectivity through an attractive interaction
with the surface of the catalyst (see Scheme 57 b).[169] Hydrogen transfer occurs from the site of the interacting OH group,
and therefore the cyclopentanol derivative 95 is hydrogenated
with good diastereoselectivity to product 96 (Scheme 59). As
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glycinamide provides the substituted Z-enamide 99. Hydrogen bonding results in a rigid conformation of 99, with the
phenyl substituent on the auxiliary shielding the top face of
the molecule, which results in stereoselectivities of up to 200:1
being obtained in the hydrogenation over PtO2
(Scheme 61).[174a] Pretreatment of the catalyst with acetic
hydrogenation of the corresponding aromatic or heteroaromatic compounds. However, so far, only a few highly selective
examples have been reported.[176]
Our research group obtained good results in the asymmetric hydrogenation of pyridines.[177] 2-Oxazolidinone-substituted pyridines that can be readily prepared from 2halogen-substituted pyridines by copper catalysis, are the
substrates of choice. Remarkably, the hydrogenation of 2oxazolidinone-5-methylpyridine (104) provided (S)-3-methylpiperidine (105) in high enantiomeric excess (Scheme 63).
Scheme 61. Synthesis of b-aminoacids with (S)-phenylglycinamide (97)
as an auxiliary.
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7. Conclusion
fied in the formation of 108 with four newly formed sterocenters in the ring.[177]
Benzene derivatives can also be hydrogenated heterogeneously with diastereoselectivities of up to 96 %. However,
the spectrum of substrates is very limited, and 2-methylbenzoic acid derivatives have almost always been used
(Scheme 65).[166, 178] The substrates have to adopt highly
preferred conformations (minimization of the dipole
moment) or have rigid cyclic structures to obtain high
selectivities, such as in tricycle 114.[178e,f] However, the hydrogenation of aromatic substrates remains a challenging problem. The implementation of new strategies such as the
innovative utilization of readily accessible chiral auxiliaries
might advance this field to the next level of sophistication.[179]
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[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
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[80]
[81]
[82]
[83]
[84]
[85]
[86]
[87]
[88]
[89]
[90]
[91]
[92]
[93]
[94]
[95]
[96]
[97]
[98]
[99]
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[156]
[157]
[158]
[159]
[160]
[161]
[162]
[163]
[164]
[165]
[166]
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[167]
[168]
[169]
[170]
[171]
[172]
[173]
[174]
[175]
[176]
[177]
[178]
[179]
[180]
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