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Exploiting nanospace for asymmetric catalysis: Confinement of immobilized, single-site chiral catalysts enhances enantioselectivity

Exploiting nanospace for asymmetric catalysis: Confinement of immobilized, single-site chiral catalysts enhances enantioselectivity
Exploiting nanospace for asymmetric catalysis: Confinement of immobilized, single-site chiral catalysts enhances enantioselectivity
In the mid-1990s, it became possible to prepare high-area silicas having pore diameters controllably adjustable in the range ca. 20?200 Å. Moreover, the inner walls of these nanoporous solids could be functionalized to yield single-site, chiral, catalytically active organometallic centers, the precise structures of which could be determined using in situ X-ray absorption and FTIR and multinuclear magic angle spinning (MAS) NMR spectroscopy. This approach opened up the prospect of performing heterogeneous enantioselective conversions in a novel manner, under the spatial restrictions imposed by the nanocavities within which the reactions occur. In particular, it suggested an alternative method for preparing pharmaceutically and agrochemically useful asymmetric products by capitalizing on the notion, initially tentatively perceived, that spatial confinement of prochiral reactants (and transition states formed at the chiral active center) would provide an altogether new method of boosting the enantioselectivity of the anchored chiral catalyst. Initially, we anchored chiral single-site heterogeneous catalysts to nanopores covalently via a ligand attached to Pd(II) or Rh(I) centers. Later, we employed a more convenient and cheaper electrostatic method, relying in part on strong hydrogen bonding. This Account provides many examples of these processes, encompassing hydrogenations, oxidations, and aminations. Of particular note is the facile synthesis from methyl benzoylformate of methyl mandelate, which is a precursor in the synthesis of pemoline, a stimulant of the central nervous system; our procedure offers several viable methods for reducing ketocarboxylic acids. In addition to relying on earlier (synchrotron-based) in situ techniques for characterizing catalysts, we have constructed experimental procedures involving robotically controlled catalytic reactors that allow the kinetics of conversion and enantioselectivity to be monitored continually, and we have access to sophisticated, high-sensitivity chiral chromatographic facilities and automated high-throughput combinatorial test rigs so as to optimize the reaction conditions (e.g., H2 pressure, temperature, time on-stream, pH, and choice of ligand and central metal ion) for high enantioselectivity. This Account reports our discoveries of selective hydrogenations and aminations of synthetic, pharmaceutical, and biological significance, and the findings of other researchers who have achieved similar success in oxidations, dehydrations, cyclopropanations, and hydroformylations. Although the practical advantages and broad general principles governing the enhancement of enantioselectivity through spatial confinement are clear, we require a deeper theoretical understanding of the details pertaining to the phenomenology involved, particularly through molecular dynamics simulations. Ample scope exists for the general exploitation of nanospace in asymmetric hydrogenations with transition metal complexes and for its deployment for the formation of C?N, C?C, C?O, C?S, and other bonds.
heterogeneous catalysts, catalysts, epoxidation, design, silica surfaces, complexes, one-step, mesoporous materials, chemistry, molecular-sieves, organometallic
0001-4842
708-720
Thomas, J.M.
98879775-7bc8-4aeb-89c1-da6c60c856c2
Raja, R.
74faf442-38a6-4ac1-84f9-b3c039cb392b
Thomas, J.M.
98879775-7bc8-4aeb-89c1-da6c60c856c2
Raja, R.
74faf442-38a6-4ac1-84f9-b3c039cb392b

Thomas, J.M. and Raja, R. (2008) Exploiting nanospace for asymmetric catalysis: Confinement of immobilized, single-site chiral catalysts enhances enantioselectivity. Accounts of Chemical Research, 41 (6), 708-720. (doi:10.1021/ar700217y).

Record type: Article

Abstract

In the mid-1990s, it became possible to prepare high-area silicas having pore diameters controllably adjustable in the range ca. 20?200 Å. Moreover, the inner walls of these nanoporous solids could be functionalized to yield single-site, chiral, catalytically active organometallic centers, the precise structures of which could be determined using in situ X-ray absorption and FTIR and multinuclear magic angle spinning (MAS) NMR spectroscopy. This approach opened up the prospect of performing heterogeneous enantioselective conversions in a novel manner, under the spatial restrictions imposed by the nanocavities within which the reactions occur. In particular, it suggested an alternative method for preparing pharmaceutically and agrochemically useful asymmetric products by capitalizing on the notion, initially tentatively perceived, that spatial confinement of prochiral reactants (and transition states formed at the chiral active center) would provide an altogether new method of boosting the enantioselectivity of the anchored chiral catalyst. Initially, we anchored chiral single-site heterogeneous catalysts to nanopores covalently via a ligand attached to Pd(II) or Rh(I) centers. Later, we employed a more convenient and cheaper electrostatic method, relying in part on strong hydrogen bonding. This Account provides many examples of these processes, encompassing hydrogenations, oxidations, and aminations. Of particular note is the facile synthesis from methyl benzoylformate of methyl mandelate, which is a precursor in the synthesis of pemoline, a stimulant of the central nervous system; our procedure offers several viable methods for reducing ketocarboxylic acids. In addition to relying on earlier (synchrotron-based) in situ techniques for characterizing catalysts, we have constructed experimental procedures involving robotically controlled catalytic reactors that allow the kinetics of conversion and enantioselectivity to be monitored continually, and we have access to sophisticated, high-sensitivity chiral chromatographic facilities and automated high-throughput combinatorial test rigs so as to optimize the reaction conditions (e.g., H2 pressure, temperature, time on-stream, pH, and choice of ligand and central metal ion) for high enantioselectivity. This Account reports our discoveries of selective hydrogenations and aminations of synthetic, pharmaceutical, and biological significance, and the findings of other researchers who have achieved similar success in oxidations, dehydrations, cyclopropanations, and hydroformylations. Although the practical advantages and broad general principles governing the enhancement of enantioselectivity through spatial confinement are clear, we require a deeper theoretical understanding of the details pertaining to the phenomenology involved, particularly through molecular dynamics simulations. Ample scope exists for the general exploitation of nanospace in asymmetric hydrogenations with transition metal complexes and for its deployment for the formation of C?N, C?C, C?O, C?S, and other bonds.

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More information

Published date: 2008
Keywords: heterogeneous catalysts, catalysts, epoxidation, design, silica surfaces, complexes, one-step, mesoporous materials, chemistry, molecular-sieves, organometallic

Identifiers

Local EPrints ID: 54509
URI: http://eprints.soton.ac.uk/id/eprint/54509
ISSN: 0001-4842
PURE UUID: c6ebca9a-8c10-4ed4-b054-90e9381016bd
ORCID for R. Raja: ORCID iD orcid.org/0000-0002-4161-7053

Catalogue record

Date deposited: 01 Aug 2008
Last modified: 26 Nov 2019 01:44

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