Stahl Research Group
UW-Madison Department of Chemistry

Research

  1. Catalytic Oxidation with Molecular Oxygen
  2. Catalytic Radical C–H Oxidation and Cross-Coupling
  3. Catalytic Methods for Biomass Conversion and Valorization
  4. Electrocatalysis and Electrochemical Organic Synthesis
  5. Electrocatalysts and Electrochemical Energy Storage and Conversion

Catalytic Oxidations with Molecular Oxygen

Heterogeneous Catalytic Aerobic Oxidation

  • Developing new heterogeneous catalysts for organic chemical synthesis
  • Synthesizing and characterizing M-N-C, single-atom catalysts for chemical synthesis applications
  • Characterizing the mechanism of liquid-phase heterogeneous aerobic oxidation catalysts

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Key References

Review Articles:

Bates, J. S.; Johnson, M. R.; Khamespanah, F.; Root, T. W.; Stahl, S. S. Heterogeneous M-N-C Catalysts for Aerobic Oxidation Reactions: Lessons from Oxygen Reduction Electrocatalysts. Chem. Rev. 2022, Accepted Article. DOI: 10.1021/acs.chemrev.2c00424

Representative Publications:

Iosub, A. V.; Stahl, S. S. Catalytic Aerobic Dehydrogenation of Nitrogen Heterocycles Using Heterogeneous Cobalt Oxide Supported on Nitrogen-Doped Carbon. Org. Lett. 2015, 17, 4404-4407. DOI:10.1021/acs.orglett.5b01790

Mannel, D. S.; Ahmed, M. S.; Root, T. W.; Stahl, S. S. Discovery of Multicomponent Heterogeneous Catalysts via Admixture Screening: PdBiTe Catalysts for Aerobic Oxidative Esterification of Primary Alcohols. J. Am. Chem. Soc. 2017, 139, 1690-1698. DOI:10.1021/jacs.6b12722

Ahmed, M. S.; Mannel, D. S.; Root, T. W.; Stahl, S. S. Aerobic Oxidation of Diverse Primary Alcohols to Carboxylic Acids with a Heterogeneous Pd-Bi-Te/C (PBT/C) Catalyst. Org. Process Res. Dev. 2017, 21, 1388-1393. DOI:10.1021/acs.oprd.7b00223

Mannel, D. S.; King, J.; Preger, Y.; Ahmed, M. S.; Root, T. W.; Stahl, S. S. Mechanistic Insights into Aerobic Oxidative Methyl Esterification of Primary Alcohols with Heterogeneous PdBiTe Catalysts. ACS Catal. 2018, 8, 1038-1047. DOI:10.1021/acscatal.7b02886

Bates, J. S.; Biswas, S.; Suh, S.-E.; Johnson, M. R.; Mondal, B.; Root, T. W.; Stahl, S. S. Chemical and Electrochemical O2 Reduction on Earth-Abundant M-N-C Catalysts and Implications for Mediated Electrolysis. J. Am. Chem. Soc. 2022, 144, 922-927. DOI: 10.1021/jacs.1c11126.

Organic (Co)Catalysts for Aerobic Oxidation

  • Developing Cu/aminoxyl catalysts for selective aerobic alcohol oxidation
  • Establishing mechanisms of redox cooperativity between redox-active organic co-catalysts (aminoxyls, quinones) with transition metals (Cu, Co)
  • Developing biomimetic quinones as catalysts for selective aerobic oxidation and oxidative coupling of amines

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Key References

Review Articles:

Ryland, B. L.; Stahl, S. S. Practical Aerobic Oxidations of Alcohols and Amines with Homogeneous Copper/TEMPO and Related Catalyst Systems. Angew. Chem. Int. Ed. 2014, 53, 8824-8838. DOI:10.1002/anie.201403110

Representative Publications:

Hoover, J. M.; Stahl, S. S. Highly Practical Copper(I)/TEMPO Catalyst System for Chemoselective Aerobic Oxidation of Primary Alcohols. J. Am. Chem. Soc. 2011, 133, 16901-16910. DOI:10.1021/ja206230h

Steves, J. E.; Stahl, S. S. Copper(I)/ABNO-Catalyzed Aerobic Alcohol Oxidation: Alleviating Steric and Electronic Constraints of Cu/TEMPO Catalyst Systems. J. Am. Chem. Soc. 2013, 135, 15742-15745. DOI:10.1021/ja409241h

Hoover, J. M.; Ryland, B. L.; Stahl, S. S. Mechanism of Copper(I)/TEMPO-Catalyzed Aerobic Alcohol Oxidation. J. Am. Chem. Soc. 2013, 135, 2357-2367. DOI:10.1021/ja3117203

Ryland, B. L.; McCann, S. D.; Brunold, T. C.; Stahl, S. S. Mechanism of Alcohol Oxidation Mediated by Copper(II) and Nitroxyl Radicals. J. Am. Chem. Soc. 2014, 136, 12166–12173. DOI:10.1021/ja5070137

Piszel, P. E.; Vasilopoulos, A.; Stahl, S. S. Oxidative Amide Coupling from Functionally Diverse Alcohols and Amines using Aerobic Copper/Nitroxyl Catalysis. Angew. Chem. Int. Ed. 2019, 131, 12211-12215. DOI: 10.1002/anie.20190613

Nutting, J. E.; Mao, K.; Stahl, S. S. Iron(III) Nitrate/TEMPO-Catalyzed Aerobic Alcohol Oxidation: Distinguishing between Serial versus Integrated Redox Cooperativity. J. Am. Chem. Soc. 2021, 143, 10565-10570. DOI: 10.1021/jacs.1c05224

Copper Catalyzed Aerobic Oxidation

  • How do catalysts that undergo one-electron redox chemistry mediate two-electron oxidation reactions with a four-electron oxidant (O2)?
  • Establishing principles to distinguish between single-electron-transfer (SET) and organometallic oxidation pathways, including the demonstration of organocopper(III) intermediates
  • Developing and characterizing oxidative N–N coupling reactions

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Key References

Review Articles:

Wendlandt, A. E.; Suess, A. M.; Stahl, S. S. Copper-Catalyzed Aerobic Oxidative C-H Functionalizations: Trends and Mechanistic Insights. Angew. Chem. Int. Ed. 2011, 50, 11062-11087.  DOI:10.1002/anie.201103945

McCann, S. D.; Stahl, S. S. Copper-Catalyzed Aerobic Oxidations of Organic Molecules: Pathways for Two-Electron Oxidation with a Four-Electron Oxidant and a One-Electron Redox-Active Catalyst. Acc. Chem. Res. 2015, 48, 1756–1766. DOI:10.1021/acs.accounts.5b00060

Representative Publications:

McCann, S. D.; Lumb, J.-P.; Arndtsen, B. A.; Stahl, S. S. Second-Order Biomimicry: In Situ Oxidative Self-Processing Converts Copper(I)/Diamine Precursor into a Highly Active Aerobic Oxidation Catalyst. ACS Cent. Sci. 2017, 3, 314-321. DOI:10.1021/acscentsci.7b00022

Ryan, M. C.; Martinelli, J. R.; Stahl, S. S. Cu-Catalyzed Aerobic Oxidative N–N Coupling of Carbazoles and Diarylamines Including Selective Cross-Coupling. J. Am. Chem. Soc. 2018, 140, 9074-9077. DOI:10.1021/jacs.8b05245

Wang, F.; Gerken, J. B.; Bates, D. M.; Kim, Y. J.; Stahl, S. S. Electrochemical Strategy for Hydrazine Synthesis: Development and Overpotential Analysis of Methods for Oxidative N–N Coupling of an Ammonia Surrogate. J. Am. Chem. Soc. 2020, 142, 12349–12356. DOI: 10.1021/jacs.0c04626

Liu, W.; Twilton, J.; Wei, B.; Lee, M.; Hopkins, M. N.; Bacsa, J.; Stahl, S. S.; Davies, H. M. L. Copper-Catalyzed Oxidation of Hydrazones to Diazo Compounds Using Oxygen as the Terminal Oxidant. ACS Catal. 2021, 11, 2676-2683. DOI: 10.1021/acscatal.1c00264

Palladium Catalyzed Aerobic Oxidation

  • Developing catalytic aerobic oxidation methods, including reactions of alcohols, alkenes, and aliphatic and aromatic C–H bonds
  • Mechanistic understanding of catalytic mechanisms, elucidating the basis for ligand-promoted catalytic turnover with O2 as the oxidant
  • Characterizing fundamental Pd-O2 reactivity, including structural characterization of Pd-peroxo and hydroperoxo complexes

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Key References

Review Articles:

Campbell, A. N.; Stahl, S. S. Overcoming the “Oxidant Problem”: Strategies to Use O2 as the Oxidant in Organometallic C-H Oxidation Reactions Catalyzed by Pd (and Cu). Acc. Chem. Res. 2012, 45, 851-863. DOI:10.1021/ar2002045

Wang, D.; Weinstein, A. B.; White, P. B.; Stahl, S. S. Ligand-Promoted Palladium-Catalyzed Aerobic Oxidation Reactions. Chem. Rev. 2018, 118, 2636-2679. DOI:10.1021/acs.chemrev.7b00334

Representative Publications:

Izawa, Y.; Pun, D.; Stahl, S. S. Palladium-Catalyzed Aerobic Dehydrogenation of Substituted Cyclohexanones to Phenols. Science 2011, 333, 209-213. DOI:10.1126/science.1204183

Jaworski, J. N.; Kozack, C. V.; Tereniak, S. J.; Knapp, S. M. M.; Landis, C. R.; Miller, J. T.; Stahl, S. S. Operando Spectroscopic and Kinetic Characterization of Aerobic Allylic C–H Acetoxylation Catalyzed by Pd(OAc)2/4,5-Diazafluoren-9-one. J. Am. Chem. Soc. 2019, 141, 10462-10474. DOI:10.1021/jacs.9b04699

Bruns, D. L.; Musaev, D. G.; Stahl, S. S. Can Donor Ligands Make Pd(OAc)2 a Stronger Oxidant? Access to Elusive Palladium(II) Reduction Potentials and Effects of Ancillary Ligands via Palladium(II)/Hydroquinone Redox Equilibria. J. Am. Chem. Soc. 2020, 142, 19678–19688. DOI: 10.1021/jacs.0c09464

Salazar, C. A.; Flesch, K. N.; Haines, B. E.; Zhou, P. S.; Musaev, D. G.; Stahl, S. S. Tailored Quinones Support High-Turnover Pd Catalysts for Oxidative C–H Arylation with O2. Science 2020, 370, 1454–1460. DOI: 10.1126/science.abd1085

Catalytic Radical C‒H Oxidation and Cross-Coupling

  • Developing new methods for chemo-, regio-, and stereoselective functionalization of C(sp3)‒H bonds
  • Utilizing radical-relay strategies to achieve benzylic C(sp3)‒H functionalization and cross-coupling
  • Controlling the selectivity of radical and non-radical C‒H oxidation methods for medicinal chemistry

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Key References

Review Articles:

Golden, D. L.; Suh, S.-E.; Stahl, S. S. Radical C(sp3)–H Functionalization and Cross-Coupling Reactions. Nat. Rev. Chem. 2022, 6, 405-427. DOI: 10.1038/s41570-022-00388-4

Representative Publications:

Zhang, W.; Wang, F.; McCann, S. C.; Wang, D.; Chen, P.; Stahl, S. S.; Liu, G. Enantioselective Cyanation of Benzylic C-H Bonds via Copper-Catalyzed Radical Relay. Science 2016, 353, 1014-10158. DOI:10.1126/science.aaf7783

Vasilopoulos, A.; Zultanski, S. L.; Stahl, S. S. Feedstocks to Pharmacophores: Cu-Catalyzed Oxidative Arylation of Inexpensive Alkylarenes Enabling Direct Access to Diarylalkanes. J. Am. Chem. Soc. 2017, 139, 7705-7708. DOI:10.1021/jacs.7b03387

Hu, H.; Chen, S. J.; Mandal, M.; Pratik, S. M.; Buss, J. A.; Krska, S. W.; Cramer, C. J.; Stahl, S. S. Copper-Catalyzed Benzylic C-H Coupling with Alcohols via Radical Relay Enabled by Redox Buffering. Nat. Catal. 2020, 3, 358-367. DOI:10.1038/s41929-020-0425-1

Suh, S.-E.; Chen, S.-J.; Mandal, M.; Guzei, I. A.; Cramer, C. J.; Stahl, S. S. Site-Selective Copper-Catalyzed Azidation of Benzylic C–H Bonds. J. Am. Chem. Soc. 2020, 142, 11388–11393. DOI: 10.1021/jacs.0c05362

Chen, S.-J.; Golden, D. L.; Krska, S. W.; Stahl, S. S. Copper-Catalyzed Cross-Coupling of Benzylic C–H Bonds and Azoles with Controlled N-Site Selectivity. J. Am. Chem. Soc. 2021, 143, 14438-14444. DOI: 10.1021/jacs.1c07117

Suh, S.-E.; Nkulu, L. E.; Lin, S.; Krska, S. W.; Stahl, S. S. Benzylic C–H Isocyanation/Amine Coupling Sequence Enabling High-Throughput Synthesis of Pharmaceutically Relevant Ureas. Chem. Sci. 2021, 12, 10380-10387. DOI: 10.1039/D1SC02049H

Vasilopoulos, A.; Krska, S. W.; Stahl, S. S. C(sp3)–H Methylation Enabled by Peroxide Photosensitization and Ni-Mediated Radical Coupling. Science 2021, 372, 398-403. DOI: 10.1126/science.abh2623

 

Catalytic Methods for Biomass Conversion and Valorization

  • Using a two-step oxidation/depolymerization sequence for conversion of lignin into aromatic monomers
  • Demonstrating selective aerobic and electrochemical oxidation methods for oxidative deconstruction of lignin and illustrating how this reactivity contributes to acid-promoted cleavage of the lignin polymer
  • Developing oxidative catalytic fractionation methods for direct convertion of biomass into high-quality sugar and aromatic streams

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Key References

Review Articles:

Cui, Y.; Goes, S. L.; Stahl, S. S. Sequential Oxidation-Depolymerization Strategies for Lignin Conversion to Low Molecular Weight Aromatic Chemicals. Adv. Inorg. Chem. 2021, 77, 99-136. DOI: 10.1016/bs.adioch.2021.02.003

Representative Publications:

Rahimi, A.; Azarpira, A.; Kim, H.; Ralph, J.; Stahl, S. S. Chemoselective Metal-Free Aerobic Alcohol Oxidation in Lignin. J. Am. Chem. Soc. 2013, 135, 6415–6418. DOI:10.1021/ja401793n

Rahimi, A.; Ulbrich, A.; Coon, J. J.; Stahl S. S. Formic-acid-induced depolymerization of oxidized lignin to aromatics. Nature 2014, 515, 249–252. DOI:10.1038/nature13867

Rafiee, M.; Alherech, M.; Karlen, S. D.; Stahl, S. S. Electrochemical Aminoxyl-Mediated Oxidation of Primary Alcohols in Lignin to Carboxylic Acids: Polymer Modification and Depolymerization. J. Am. Chem. Soc. 2019, 141, 15266-15276. DOI:10.1021/jacs.9b07243

Luo, H.; Weeda, E. P.; Alherech, M.; Anson, C. W.; Karlen, S. D.; Cui, Y.; Foster, C. E.; Stahl, S. S. Oxidative Catalytic Fractionation of Lignocellulosic Biomass under Non-alkaline Conditions. J. Am. Chem. Soc. 2021, 143, 15462-15470. DOI: 10.1021/jacs.1c08635

Alherech, M.; Omolabake, S.; Holland, C. M.; Klinger, G. E.; Hegg, E. L.; Stahl, S. S. From Lignin to Valuable Aromatic Chemicals: Lignin Depolymerization and Monomer Separation via Centrifugal Partition Chromatography. ACS Cent. Sci. 2021, 7, 1831-1837. DOI: 10.1021/acscentsci.1c00729

Electrocatalysis and Electrochemical Organic Synthesis

  • Using electron-proton-transfer mediators to lower overpotential in electrochemical oxidations and to expand their scope and utility for pharmaceutical synthesis
  • Developing HAT and hydride-transfer mediators to enable electrochemical C‒H functionalization
  • Utilizing scalable flow processes for suitable electrochemical synthesis

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Key References

Review Articles:

Nutting, J. E.; Rafiee, M.; Stahl, S. S. Tetramethylpiperidine N-Oxyl (TEMPO), Phthalimide N-Oxyl (PINO), and Related N-Oxyl Species: Electrochemical Properties and Their Use in Electrocatalytic Reactions. Chem. Rev. 2018, 118, 4834-4885. DOI:10.1021/acs.chemrev.7b00763

Wang, F.; Stahl, S. S. Electrochemical Oxidation of Organic Molecules at Lower Overpotential: Accessing Broader Functional Group Compatibility with Electron-Proton Transfer Mediators. Acc. Chem. Res. 2020, 53, 561-574. DOI: 10.1021/acs.accounts.9b00544

Nutting, J. E.; Gerken, J. B.; Stamoulis, A. G.; Bruns, D. L.; Stahl, S. S. “How Should I Think about Voltage? What is Overpotential?”: Establishing an Organic Chemistry Intuition for Electrochemistry. J. Org. Chem. 2021, 86, 15875-15885. DOI: 10.1021/acs.joc.1c01520

Representative Publications:

Badalyan, A.; Stahl, S. S. Cooperative electrocatalytic alcohol oxidation with electron-proton-transfer mediators. Nature 2016, 535, 406–410. DOI:10.1038/nature18008

Wang, F.; Rafiee, M.; Stahl, S. S. Electrochemical Functional-Group-Tolerant Shono-Type Oxidation of Cyclic Carbamates Enabled by Aminoxyl Mediators. Angew. Chem. Int. Ed. 2018, 57, 6686-6690. DOI:10.1002/anie.201803539

Rafiee, M.; Wang, F.; Hruszkewycz, D. P.; Stahl, S. S. N-Hydroxyphthalimide-Mediated Electrochemical Iodination of Methylarenes and Comparison to Electron-Transfer-Initiated C–H Functionalization. J. Am. Chem. Soc. 2018, 140, 22-25. DOI:10.1021/jacs.7b09744

Lennox, A. J. J.; Goes, S. L.; Webster, M. P.; Koolman, H. F.; Djuric, S. W.; Stahl, S. S. Electrochemical Aminoxyl-Mediated α-Cyanation of Secondary Piperidines for Pharmaceutical Building Block Diversification. J. Am. Chem. Soc. 2018, 140, 11227-11231. DOI:10.1021/jacs.8b08145

Wang, F.; Stahl, S. S. Merging Photochemistry with Electrochemistry: Functional Group Tolerant Electrochemical Amination of sp³ C–H Bonds. Angew. Chem. Int. Ed. 2019, 58, 6385-6390. DOI:10.1002/anie.201813960

Zhong, X.; Hoque, M. A.; Graaf, M. D.; Harper, K. C.; Wang, F.; Genders, J. D.; Stahl, S. S. Scalable Flow Electrochemical Alcohol Oxidation: Maintaining High Stereochemical Fidelity in the Synthesis of Levetiracetam. Org. Process Res. Dev. 2021, 25, 2601-2607. DOI: 10.1021/acs.oprd.1c00036

Hoque, M. A.; Twilton, J.; Zhu, J.; Graaf, M. D.; Harper, K. C.; Tuca, E.; DiLabio, G. A.; Stahl, S. S. Electrochemical PINOylation of Methylarenes: Improving the Scope and Utility of Benzylic Oxidation through Mediated Electrolysis. J. Am. Chem. Soc. 2022, 144, 15295-15302. DOI: 10.1021/jacs.2c05974

Electrocatalysts and Electrochemical Energy Storage and Conversion

  • Developing stable organic electron-proton transfer mediators for use in energy storage and conversion application
  • Investigating molecular catalysts for low-overpotential O2 reduction to H2O2 and water
  • Developing and characterizing heterogeneous catalysts for energy conversion applications

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Key References

Review Articles:

Anson, C. W.; Stahl, S. S. Mediated Fuel Cells: Soluble Redox Mediators and Their Applications to Electrochemical Reduction of O2 and Oxidation of H2, Alcohols, Biomass, and Complex Fuels. Chem. Rev. 2020, 120, 3749-3786. doi: 10.1021/acs.chemrev.9b00717

Speelman, A. L.; Gerken, J. B.; Heins, S. P.; Wiedner, E. S.; Stahl, S. S.; Appel, A. M. Determining Overpotentials for the Oxidation of Alcohols by Molecular Electrocatalysts in Non-Aqueous Solvents. Energy Environ. Sci. 2022, Advance Article. DOI: 10.1039/D2EE01458K

Representative Publications:

Gerken, J. B.; Stahl, S. S. High-Potential Electrocatalytic O2 Reduction with Nitroxyl/NOx Mediators: Implications for Fuel Cells and Aerobic Oxidation Catalysis. ACS Cent. Sci. 2015, 1, 234-243. DOI:10.1021/acscentsci.5b00163

Preger, Y.; Gerken, J. B.; Biswas, S.; Anson, C. W.; Johnson, M. R.; Root, T. W.; Stahl, S. S. Quinone-Mediated Electrochemical O2 Reduction Accessing High Power Density with an Off-Electrode Co-N/C Catalyst. Joule 2018, 2, 2722-2731. DOI:10.1016/joule.2018.09.010

Wang, Y.-H.; Schneider, P. E.; Goldsmith, Z. K.; Mondal, B.; Hammes-Schiffer, S.; Stahl, S. S. Brønsted Acid Scaling Relationships Enable Control Over Product Selectivity from O2 Reduction with a Mononuclear Cobalt Porphyrin Catalyst. ACS Cent. Sci. 2019, 5, 1024-1034. DOI:10.1021/acscentsci.9b00194

Wang, Y.-H.; Mondal, B.; Stahl, S. S. Molecular Cobalt Catalysts for O2 Reduction to H2O2: Benchmarking Performance via Rate–Overpotential Correlations. ACS Catal. 2020, 10, 12031-12039. DOI: 10.1021/acscatal.0c02197

Wang, F.; Li, W.; Wang, R.; Guo, T.; Sheng, H.; Fu, H.-C.; Stahl, S. S.; Jin, S. Modular Electrochemical Synthesis Using a Redox Reservoir Paired with Independent Half- Reactions. Joule 2021, 5, 149-165. DOI: 10.1016/j.joule.2020.11.011