Divergent Compound Library Synthesis by Cascaded, Heterogeneous Catalysis - NCCR MSE

Divergent Compound Library Synthesis by Cascaded, Heterogeneous Catalysis

Our research focuses on the deployment of multiple immobilized molecular catalysts on a flow microreactor platform to convert elementary starting materials over telescoped reactions into chemically and structurally complex products. The interactions of different agents in multiple compartments on a solid-state platform result in a molecular factory.

A combination of multiple catalyst permutations and applied reaction conditions enables screening of diverse parameter spaces for the conversion of suitable starting materials. This approach aims at not only synthesizing one catalysis product from one starting material, but multiple products from the same starting material and whole compound libraries. This bio-inspired approach resembles the biosynthetic processes that are taking place in a biological cell, in which multiple metabolites are often produced from a single molecule.

Our research comprises the design and synthesis of complementary catalysts, linkers and starting materials for heterogeneous catalysis with molecular catalyst monolayers, as well as the immobilization of these catalysts in flow microreactors and conducting synthetic operation on these platforms. This project is in close collaboration with the Mayor group and IBM Research - Zurich in Rüschlikon. The silicon-based flow microreactors are being fabricated by microfabrication techniques, are scalable in the number of compartments, and allow various reaction control features such as nanoscale electrode arrays, catalyst-supporting surfaces, externally controllable micro-heaters and nanophotonic sensing sites to be implemented and to be used as reaction feedback controls.

Publications

T. A. Schmidt, C. Sparr “Catalyst-Controlled Stereoselective Barton–Kellogg Olefination“ Angew. Chem. Int. Ed. 2021. [DOI]
D. Scherrer, D. Vogel, U. Drechsler, A. Olziersky, C. SparrM. MayorE. Lörtscher “Monitoring Solid-phase Reactions in Self-assembled Monolayers by Surface-enhanced Raman Spectroscopy“ Angew. Chem. Int. Ed. 2021. [DOI]
D. Moser, A. Castrogiovanni, D. Lotter, R. M. Witzig, V. C. Fäseke, F. C. Raps, C. Sparr “Catalytic Cascade Reactions Inspired by Polyketide Biosynthesis“ Chimia 2020. [DOI]
F. C. Raps, V. C. Fäseke, D. Häussinger, C. Sparr “Catalyst-Controlled Transannular Polyketide Cyclization Cascades: Selective Folding of Macrocyclic Polyketides“ Angew. Chem. Int. Ed. 2020. [DOI]
A. Castrogiovanni, D. Lotter, F. R. Bissegger, C. Sparr “JoyaPhos: An Atropisomeric Teraryl Monophosphine Ligand“ Chem. Eur. J. 2020. [DOI]
B. Zilate, C. Fischer, C. Sparr “Design and application of aminoacridinium organophotoredox catalysts“ Chem. Commun. 2020. [DOI]
V. C. Fäseke, F. C. Raps, C. Sparr “Polyketide Cyclizations for the Synthesis of Polyaromatics“ Angew. Chem. Int. Ed. 2019. [DOI]
C. Fischer, C. Kerzig, B. Zilate, O. WengerC. Sparr “Modulation of Acridinium Organophotoredox Catalysts Guided by Photophysical Studies“ ACS Catal. 2019. [DOI]
A. Castrogiovanni, P. Herr, X. Guo, C. Larsen, C. SparrO. Wenger “Shortcuts for Electron-Transfer through the Secondary Structure of Helical Oligo-1,2-naphthylenes“ Chem. Eur. J. 2019. [DOI]
R. M. Witzig, C. Sparr “Synthesis of Enantioenriched Tetra-ortho-3,3′-substituted Biaryls by Small-Molecule-Catalyzed Noncanonical Polyketide Cyclizations“ Synlett 2019. [DOI]
R. M. Witzig, V. C. Fäseke, D. Häussinger, C. Sparr “Atroposelective synthesis of tetra-ortho-substituted biaryls by catalyst-controlled non-canonical polyketide cyclizations“ Nat. Catal. 2019. [DOI]
D. Kaldre, F. Gallou, C. Sparr, M. Parmentier “Interface-rich Aqueous Systems for Sustainable Chemical Synthesis“ Chimia 2019, 73:714-19. [DOI]
M. Jakobi, F. Gallou, C. Sparr, M. Parmentier “A General Protocol for Robust Sonogashira Reactions in Micellar Medium“ Helv. Chim. Acta 2019. [DOI]
C. Fischer, C. Sparr “Synthesis of 1,5-bifunctional organolithium reagents by a double directed ortho-metalation: Direct transformation of esters into 1,8-dimethoxy-acridinium salts“ Tetrahedron 2018, 74:5486-5493. [DOI]
M. Grogg, D. Hilvert, M. Ebert, A. K. Beck, D. Seebach, F. Kurth, P. DittrichC. Sparr, S. Wittlin, M. Rottmann, P. Mäser “Cell Penetration, Herbicidal Activity, and in-vivo-Toxicity of Oligo-Arginine Derivatives and of Novel Guanidinium-Rich Compounds Derived from the Biopolymer Cyanophycin“ Helv. Chim. Acta 2018. [DOI]
C. Fischer, C. Sparr “Configurationally Stable Atropisomeric Acridinium Fluorophores“ Synlett 2018. [DOI]
A. Link, C. Sparr “Remote Central‐to‐Axial Chirality Conversion: Direct Atroposelective Ester to Biaryl Transformation“ Angew. Chem. Int. Ed. 2018. [DOI]
D. Lotter, A. Castrogiovanni, M. Neuburger, C. Sparr “Catalyst-Controlled Stereodivergent Synthesis of Atropisomeric Multiaxis Systems“ ACS Cent. Sci. 2018. [DOI]
A. Link, C. Sparr “Stereoselective arene formation“ Chem. Soc. Rev. 2018. [DOI]
B. Zilate, A. Castrogiovanni, C. Sparr “Catalyst-Controlled Stereoselective Synthesis of Atropisomers“ ACS Catalysis 2018. [DOI]
C. Fischer, C. Sparr “Direkte Umwandlung von Estern in Heterocyclische Fluorophore“ Angew. Chem. Int. Ed. 2017. [DOI]