Title: A generalized kinetic model for compartmentalization of organometallic catalysis
Compartmentalization is an attractive approach to enhance catalytic activity by retaining reactive intermediates and mitigating deactivating pathways. Such a concept has been well explored in biochemical and more recently, organometallic catalysis to ensure high reaction turnovers with minimal side reactions. However, the scarcity of theoretical frameworks towards confined organometallic chemistry impedes broader utility for the implementation of compartmentalization. Herein, we report a general kinetic model and offer design guidance for a compartmentalized organometallic catalytic cycle. In comparison to a non-compartmentalized catalysis, compartmentalization is quantitatively shown to prevent the unwanted intermediate deactivation, boost the corresponding reaction efficiency ( γ ), and subsequently increase catalytic turnover frequency (TOF). The key parameter in the model is the volumetric diffusive conductance ( F V ) that describes catalysts' diffusion propensity across a compartment's boundary. Optimal values of F V for a specific organometallic chemistry are needed to achieve maximal values of γ and TOF. As illustrated in specific reaction examples, our model suggests that a tailored compartment design, including the use of nanomaterials, is needed to suit a specific organometallic catalytic cycle. This work provides justification and design principles for further exploration into compartmentalizing organometallics to enhance catalytic performance. The conclusions from this work are generally applicable to other catalytic systems that need proper design guidance in confinement and compartmentalization. more »« less
Natinsky, Benjamin S.; Jolly, Brandon J.; Dumas, David M.; Liu, Chong(
, Chemical Science)
null
(Ed.)
Compartmentalization is a viable approach for ensuring the turnover of a solution cascade reaction with ephemeral intermediates, which may otherwise deactivate in the bulk solution. In biochemistry or enzyme-relevant cascade reactions, extensive models have been constructed to quantitatively analyze the efficacy of compartmentalization. Nonetheless, the application of compartmentalization and its quantitative analysis in non-biochemical reactions is seldom performed, leaving much uncertainty about whether compartmentalization remains effective for non-biochemical reactions, such as organometallic, cascade reactions. Here, we report our exemplary efficacy analysis of compartmentalization in our previously reported cascade reaction for ambient CH 4 -to-CH 3 OH conversion, mediated by an O 2 -deactivated Rh II metalloradical with O 2 as the terminal oxidant in a Si nanowire array electrode. We experimentally identified and quantified the key reaction intermediates, including the Rh II metalloradical and reactive oxygen species (ROS) from O 2 . Based on such findings, we experimentally determined that the nanowire array enables about 81% of the generated ephemeral intermediate Rh II metalloradical in air, to be utilized towards CH 3 OH formation, which is 0% in a homogeneous solution. Such an experimentally determined value was satisfactorily consistent with the results from our semi-quantitative kinetic model. The consistency suggests that the reported CH 4 -to-CH 3 OH conversion surprisingly possesses minimal unforeseen side reactions, and is favorably efficient as a compartmentalized cascade reaction. Our quantitative evaluation of the reaction efficacy offers design insights and caveats into application of nanomaterials to achieve spatially controlled organometallic cascade reactions.
De Jesus Silva, Jordan; Ferreira, Marco A.; Fedorov, Alexey; Sigman, Matthew S.; Copéret, Christophe(
, Chemical Science)
A combination of high-throughput experimentation (HTE), surface organometallic chemistry (SOMC) and statistical data analysis provided the platform to analyze in situ silica-grafted Mo imido alkylidene catalysts based on a library of 35 phenols. Overall, these tools allowed for the identification of σ-donor electronic effects and dispersive interactions and as key drivers in a prototypical metathesis reaction, homodimerization of 1-nonene. Univariate and multivariate correlation analysis confirmed the categorization of the catalytic data into two groups, depending on the presence of aryl groups in ortho position of the phenol ligand. The initial activity (TOF in ) was predominantly correlated to the σ-donor ability of the aryloxy ligands, while the overall catalytic performance (TON 1 h ) was mainly dependent on attractive dispersive interactions with the used phenol ligands featuring aryl ortho substituents and, in sharp contrast, repulsive dispersive interactions with phenol free of aryl ortho substituents. This work outlines a fast and efficient workflow of gaining molecular-level insight into supported metathesis catalysts and highlights σ-donor ability and noncovalent interactions as crucial properties for designing active d 0 supported metathesis catalysts.
Xin, Tiansi; Geeson, Michael B.; Zhu, Hui; Qu, Zheng-Wang; Grimme, Stefan; Cummins, Christopher C.(
, Chemical Science)
Herein is reported the structural characterization and scalable preparation of the elusive iron–phosphido complex FpP( t Bu)(F) (2-F, Fp = (Fe(η 5 -C 5 H 5 )(CO) 2 )) and its precursor FpP( t Bu)(Cl) (2-Cl) in 51% and 71% yields, respectively. These phosphide complexes are proposed to be relevant to an organoiron catalytic cycle for phosphinidene transfer to electron-deficient alkenes. Examination of their properties led to the discovery of a more efficient catalytic system involving the simple, commercially available organoiron catalyst Fp 2 . This improved catalysis also enabled the preparation of new phosphiranes with high yields ( t BuPCH 2 CHR; R = CO 2 Me, 41%; R = CN, 83%; R = 4-biphenyl, 73%; R = SO 2 Ph, 71%; R = POPh 2 , 70%; R = 4-pyridyl, 82%; R = 2-pyridyl, 67%; R = PPh 3 + , 64%) and good diastereoselectivity, demonstrating the feasibility of the phosphinidene group-transfer strategy in synthetic chemistry. Experimental and theoretical studies suggest that the original catalysis involves 2-X as the nucleophile, while for the new Fp 2 -catalyzed reaction they implicate a diiron–phosphido complex Fp 2 (P t Bu), 4, as the nucleophile which attacks the electron-deficient olefin in the key first P–C bond-forming step. In both systems, the initial nucleophilic attack may be accompanied by favorable five-membered ring formation involving a carbonyl ligand, a (reversible) pathway competitive with formation of the three-membered ring found in the phosphirane product. A novel radical mechanism is suggested for the new Fp 2 -catalyzed system.
Lim, Samuel; Jung, Gi Ahn; Glover, Dominic J.; Clark, Douglas S.(
, Small)
Abstract
Precisely organized enzyme complexes are often found in nature to support complex metabolic reactions in a highly efficient and specific manner. Scaffolding enzymes on artificial materials has thus gained attention as a promising biomimetic strategy to design biocatalytic systems with enhanced productivity. Herein, a versatile scaffolding platform that can immobilize enzymes on customizable nanofibers is reported. An ultrastable self‐assembling filamentous protein, the gamma‐prefoldin (γ‐PFD), is genetically engineered to display an array of peptide tags, which can specifically and stably bind enzymes containing the counterpart domain through simple in vitro mixing. Successful immobilization of proteins along the filamentous template in tunable density is first verified using fluorescent proteins. Then, two different model enzymes, glucose oxidase and horseradish peroxidase, are used to demonstrate that scaffold attachment could enhance the intrinsic catalytic activity of the immobilized enzymes. Considering the previously reported ability of γ‐PFD to bind and stabilize a broad range of proteins, the filament's interaction with the bound enzymes may have created a favorable microenvironment for catalysis. It is envisioned that the strategy described here may provide a generally applicable methodology for the scaffolded assembly of multienzymatic complexes for use in biocatalysis.
Metal-mediated cross-coupling reactions offer organic chemists a wide array of stereo- and chemically-selective reactions with broad applications in fine chemical and pharmaceutical synthesis.1 Current batch-based synthesis methods are beginning to be replaced with flow chemistry strategies to take advantage of the improved consistency and process control methods offered by continuous flow systems.2,3 Most cross-coupling chemistries still encounter several issues in flow using homogeneous catalysis, including expensive catalyst recovery and air sensitivity due to the chemical nature of the catalyst ligands.1 To mitigate some of these issues, a ligand-free heterogeneous catalysis reaction was developed using palladium (Pd) loaded into a polymeric network of a silicone elastomer, poly(hydromethylsiloxane) (PHMS), that is not air sensitive and can be used with mild reaction solvents (ethanol and water).4
In this work we present a novel method of producing soft catalytic microparticles using a multiphase flow-focusing microreactor and demonstrate their application for continuous Suzuki-Miyaura cross-coupling reactions. The catalytic microparticles are produced in a coaxial glass capillary-based 3D flow-focusing microreactor. The microreactor consists of two precursors, a cross-linking catalyst in toluene and a mixture of the PHMS polymer and a divinyl cross-linker. The dispersed phase containing the polymer, cross-linker, and cross-linking catalyst is continuously mixed and then formed into microdroplets by the continuous phase of water and surfactant (sodium dodecyl sulfate) introduced in a counter-flow configuration. Elastomeric microdroplets with a diameter ranging between 50 to 300 micron are produced at 25 to 250 Hz with a size polydispersity less than 3% in single stream production. The physicochemical properties of the elastomeric microparticles such as particle swelling/softness can be tuned using the ratio of cross-linker to polymer as well as the ratio of polymer mixture to solvent during the particle formation. Swelling in toluene can be tuned up to 400% of the initial particle volume by reducing the concentration of cross-linker in the mixture and increasing the ratio of polymer to solvent during production.5
After the particles are produced and collected, they are transferred into toluene containing palladium acetate, allowing the particles to incorporate the palladium into the polymer network and then reduce the palladium to Pd0 with the Si-H functionality present on the PHMS backbones. After the reduction, the Pd-loaded particles can be washed and dried for storage or switched into an ethanol/water solution for loading into a micro-packed bed reactor (µ-PBR) for continuous organic synthesis. The in-situ reduction of Pd within the PHMS microparticles was confirmed using energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS) and focused ion beam-SEM, and TEM techniques.
In the next step, we used the developed µ-PBR to conduct continuous organic synthesis of 4-phenyltoluene by Suzuki-Miyaura cross-coupling of 4-iodotoluene and phenylboronic acid using potassium carbonate as the base. Catalyst leaching was determined to only occur at sub ppm concentrations even at high solvent flow rates after 24 h of continuous run using inductively coupled plasma mass spectrometry (ICP-MS).
The developed µ-PBR using the elastomeric microparticles is an important initial step towards the development of highly-efficient and green continuous manufacturing technologies in the pharma industry. In addition, the developed elastomeric microparticle synthesis technique can be utilized for the development of a library of other chemically cross-linkable polymer/cross-linker pairs for applications in organic synthesis, targeted drug delivery, cell encapsulation, or biomedical imaging.
References
1. Ruiz-Castillo P, Buchwald SL. Applications of Palladium-Catalyzed C-N Cross-Coupling Reactions. Chem Rev. 2016;116(19):12564-12649.
2. Adamo A, Beingessner RL, Behnam M, et al. On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system. Science. 2016;352(6281):61 LP-67.
3. Jensen KF. Flow Chemistry — Microreaction Technology Comes of Age. 2017;63(3).
4. Stibingerova I, Voltrova S, Kocova S, Lindale M, Srogl J. Modular Approach to Heterogenous Catalysis. Manipulation of Cross-Coupling Catalyst Activity. Org Lett. 2016;18(2):312-315.
5. Bennett JA, Kristof AJ, Vasudevan V, Genzer J, Srogl J, Abolhasani M. Microfluidic synthesis of elastomeric microparticles: A case study in catalysis of palladium-mediated cross-coupling. AIChE J. 2018;0(0):1-10.
Jolly, Brandon J., Co, Nathalie H., Davis, Ashton R., Diaconescu, Paula L., and Liu, Chong. A generalized kinetic model for compartmentalization of organometallic catalysis. Retrieved from https://par.nsf.gov/biblio/10378048. Chemical Science 13.4 Web. doi:10.1039/D1SC04983F.
Jolly, Brandon J., Co, Nathalie H., Davis, Ashton R., Diaconescu, Paula L., & Liu, Chong. A generalized kinetic model for compartmentalization of organometallic catalysis. Chemical Science, 13 (4). Retrieved from https://par.nsf.gov/biblio/10378048. https://doi.org/10.1039/D1SC04983F
Jolly, Brandon J., Co, Nathalie H., Davis, Ashton R., Diaconescu, Paula L., and Liu, Chong.
"A generalized kinetic model for compartmentalization of organometallic catalysis". Chemical Science 13 (4). Country unknown/Code not available. https://doi.org/10.1039/D1SC04983F.https://par.nsf.gov/biblio/10378048.
@article{osti_10378048,
place = {Country unknown/Code not available},
title = {A generalized kinetic model for compartmentalization of organometallic catalysis},
url = {https://par.nsf.gov/biblio/10378048},
DOI = {10.1039/D1SC04983F},
abstractNote = {Compartmentalization is an attractive approach to enhance catalytic activity by retaining reactive intermediates and mitigating deactivating pathways. Such a concept has been well explored in biochemical and more recently, organometallic catalysis to ensure high reaction turnovers with minimal side reactions. However, the scarcity of theoretical frameworks towards confined organometallic chemistry impedes broader utility for the implementation of compartmentalization. Herein, we report a general kinetic model and offer design guidance for a compartmentalized organometallic catalytic cycle. In comparison to a non-compartmentalized catalysis, compartmentalization is quantitatively shown to prevent the unwanted intermediate deactivation, boost the corresponding reaction efficiency ( γ ), and subsequently increase catalytic turnover frequency (TOF). The key parameter in the model is the volumetric diffusive conductance ( F V ) that describes catalysts' diffusion propensity across a compartment's boundary. Optimal values of F V for a specific organometallic chemistry are needed to achieve maximal values of γ and TOF. As illustrated in specific reaction examples, our model suggests that a tailored compartment design, including the use of nanomaterials, is needed to suit a specific organometallic catalytic cycle. This work provides justification and design principles for further exploration into compartmentalizing organometallics to enhance catalytic performance. The conclusions from this work are generally applicable to other catalytic systems that need proper design guidance in confinement and compartmentalization.},
journal = {Chemical Science},
volume = {13},
number = {4},
author = {Jolly, Brandon J. and Co, Nathalie H. and Davis, Ashton R. and Diaconescu, Paula L. and Liu, Chong},
}
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