Composite Polymer/Oxide Hollow Fibers As Scalable Continuous Reactors for Heterogeneous Catalysis in Flow Chemistry

Composite Polymer/Oxide Hollow Fibers as Scalable Continuous Reactors for Heterogeneous Catalysis in Flow Chemistry   Eric G. Moschetta,¹ Solymar Negretti,² Kathryn M. Chepiga,² Nicholas A. Brunelli,^1,2 Ying Labreche,¹ Yan Feng,¹ Fateme Rezaei,¹ Ryan P. Lively,¹ William J. Koros,¹ Huw M. L. Davies,² and Christopher W. Jones^{1*   1}School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive NW, Atlanta, GA 30332   ²Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322   ^*cjones@chbe.gatch.edu               Flow chemistry in organic synthesis is emerging as a viable platform for large-scale production in the fine chemical and pharmaceutical industries.^[1] Presently, there are numerous flow reactors from μL to L in volume available commercially worldwide.^[2] When compared to batch reactors, these flow reactors are capable of handling reactions at higher pressures and temperatures, have superior heat and mass transfer properties, and provide safer facilitation of toxic and explosive reagents.^[3,4] An issue currently facing these flow reactors, especially microreactors, is the challenge associated with handling solids such as heterogeneous catalysts in the flow channels.^[3–5] Solid particles may clog the flow channels and induce excessive pressure drop, reducing the overall productivity of the flow reactor.^[2] Another challenge in flow chemistry is designing reactors that accommodate expensive supported organometallic catalysts for low temperature liquid-phase reactions, such as C–H functionalizations.^[6] While homogeneous C–H functionalization catalysts are extremely active and enantioselective, retaining these levels of activity and selectivity remains challenging once the catalysts are tethered to a heterogeneous support.             To address these challenges in flow chemistry, we sought inspiration from advances in gas separation technology. Hollow fiber membranes are most commonly used to separate the components of a gas stream with the membrane providing selective flow from bore to shell or vice versa. Recently, composite polymer/oxide hollow fibers have found large-scale use in gas adsorption processes, for example involving CO₂ capture from flue gas ^[7,8] In hollow fiber sorbent systems, the flue gas flows over the outside of the sorbent-containing fibers while cooling water flows through the bores to mitigate the heat of adsorption, with no mass transfer from shell to bore or vice versa.^[7,8] These composite fibers are easy and inexpensive to synthesize, and can be tuned to allow flow (or no flow) through the fiber walls, making them attractive as alternative platforms for performing heterogeneously catalyzed reactions in organic synthesis on a large scale.  This work discusses the use and versatility of hybrid polymer/oxide fibers as flow reactors in organic synthesis.^[9] In the initial work, the reactants flow through the bore and contact the catalyst via radial flow due to a dead-end configuration, which provides short reactant-catalyst contact times. Three different inorganic catalysts are incorporated into the walls of the fibers: ZSM-5 (a Brønsted acid catalyst), aminopropyl-functionalized silica (a basic organocatalyst), and a silica-supported analogue of Rh₂(S-DOSP)₄ (an organometallic C–H functionalization catalyst). These fibers are used to catalyze three different reactions in flow: an acid-catalyzed acetal deprotection, a base-catalyzed C–C bond forming reaction, and dirhodium(II)-catalyzed cyclopropanations and C–H functionalizations. The yields and enantioselectivities of the flow reactions are compared to similar batch reactions to assess the viability of the hollow fibers as scalable flow reactors in organic synthesis.   References

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[9]      E. G. Moschetta, S. Negretti, K. M. Chepiga, N. A. Brunelli, Y. Labreche, Y. Feng, F. Rezaei, R. P. Lively, W. J. Koros, H. M. L. Davies, C. W. Jones, Accepted to Angew. Chem. Int. Ed. 2015.