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Catalytic Oxidations with Molecular Oxygen

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 ReactionsChem. Rev. 2018118, 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 PhenolsScience 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-oneJ. Am. Chem. Soc. 2019141, 10462-10474. DOI:10.1021/jacs.9b04699

Salazar, C. A.; Gair, J. J.; Flesch, K. N.; Guzei, I. A.; Lewis, J. C.; Stahl, S. S. Catalytic Behavior of Mono-N-Protected Amino Acid Ligands in Ligand-Accelerated C-H Activation by Palladium(II)Angew. Chem. Int. Ed. 202059, 10873-10877. doi: 10.1002/anie.202002484

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 EquilibriaJ. Am. Chem. Soc2020142, 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 O2Science 2020, 370, 1454–1460. DOI: 10.1126/science.abd1085.

 

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

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 CatalystACS 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-CouplingJ. Am. Chem. Soc. 2018, 140, 9074-9077. DOI:10.1021/jacs.8b05245

Ryan, M. C.; Whitmire, L. D.; McCann, S. D.; Stahl, S. S. Copper/TEMPO Redox Redux: Analysis of PCET Oxidation of TEMPOH by Copper(II) and the Reaction of TEMPO with Copper(I)Inorg. Chem. 201958, 10194-10200. DOI: 10.1021/acs.inorgchem.9b01326

Ryan, M. C.; Kim, Y.-J.; Gerken, J. B.; Wang, F.; Aristov, M. M.; Martinelli, J. R.; Stahl, S. S. Mechanistic Insights into Copper-Catalyzed Aerobic Oxidative Coupling of N–N BondsChem. Sci202011, 1170-1175. DOI: 10.1039/C9SC04305E

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 SurrogateJ. Am. Chem. Soc. 2020142, 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 OxidantACS Catal. 202111, 2676-2683. DOI: 10.1021/acscatal.1c00264

 

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

Representative Publications:

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

 Zultanski, S. L.; Zhao, J.; Stahl, S. S. Practical Synthesis of Amides via Copper/ABNO-Catalyzed Aerobic Oxidative Coupling of Alcohols and AminesJ. Am. Chem. Soc. 2016, 138, 6416–6419. DOI:10.1021/jacs.6b03931

Piszel, P. E.; Vasilopoulos, A.; Stahl, S. S. Oxidative Amide Coupling from Functionally Diverse Alcohols and Amines using Aerobic Copper/Nitroxyl CatalysisAngew. Chem. Int. Ed. 2019131, 12211-12215. DOI: 10.1002/anie.20190613

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

Representative Publications:

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 AlcoholsJ. 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) CatalystOrg. Process Res. Dev. 2017, 21, 1388-1393. DOI:10.1021/acs.oprd.7b00223

 

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

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 BondsJ. Am. Chem. Soc. 2020, 142, 11388–11393. DOI: 10.1021/jacs.0c05362

Vasilopoulos, A.; Golden, D. L.; Buss, J. A.; Stahl, S. S. Copper-Catalyzed C–H Fluorination/Functionalization Sequence Enabling Benzylic C–H Cross Coupling with Diverse Nucleophiles. Org. Lett. 2020, 22, 5753-5757. DOI: 10.1021/acs.orglett.0c02238

Buss, J. A.; Vasilopoulos, A.; Golden, D. L.; Stahl, S. S. Copper-Catalyzed Functionalization of Benzylic C–H Bonds with N-Fluorobenzenesulfonimide: Switch from C–N to C–F Bond Formation Promoted by a Redox Buffer and Brønsted Base. Org. Lett. 2020, 22, 5749-5752. DOI: 10.1021/acs.orglett.0c02239

 

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

Representative Publications:

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

Das, A.; Rahimi, A.; Ulbrich, A.; Alherech, M.; Motagamwala, A. H.; Bhalla, A.; da Costa Sousa, L.; Balan, V.; Dumesic, J. A.; Hegg, E. L.; Dale, B. E.; Ralph, J.; Coon, J. J.; Stahl, S. S. Lignin Conversion to Low-Molecular-Weight Aromatics via an Aerobic Oxidation-Hydrolysis Sequence: Comparison of Different Lignin SourcesACS Sustainable Chem. Eng. 2018, 6, 3367-3374. DOI:10.1021/acssuschemeng.7b03541

Perez, J. M.; Kontur, W. S.; Alherech, M.; Coplien, J.; Karlen, S. D.; Stahl, S. S.; Donohue, T. J.; Noguera, D. R. Funneling aromatic products of chemically depolymerized lignin into 2-pyrone-4-6-dicarboxylic acid with Novosphingobium aromaticivorans. Green Chem. 2019, 21, 1340-1350. DOI: 10.1039/C8GC03504K

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. 2019141, 15266-15276. DOI:10.1021/jacs.9b07243

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 ReactionsChem. Rev. 2018118, 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 MediatorsAcc. Chem. Res. 202053, 561-574. DOI: 10.1021/acs.accounts.9b00544

Representative Publications:

Wang, F.; Rafiee, M.; Stahl, S. S. Electrochemical Functional-Group-Tolerant Shono-Type Oxidation of Cyclic Carbamates Enabled by Aminoxyl MediatorsAngew. Chem. Int. Ed. 201857, 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 FunctionalizationJ. Am. Chem. Soc. 2018140, 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 DiversificationJ. Am. Chem. Soc. 2018140, 11227-11231. DOI:10.1021/jacs.8b08145

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 SurrogateJ. Am. Chem. Soc. 2020142, 12349–12356. DOI: 10.1021/jacs.0c04626

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

Representative Publications:

Anson, C. W.; Ghosh, S.; Hammes-Schiffer, S.; Stahl, S. S. Co(salophen)-Catalyzed Aerobic Oxidation of p-Hydroquinone: Mechanism and Implications for Aerobic Oxidation Catalysis. J. Am. Chem. Soc. 2017138, 4186-4193. DOI:10.1021/jacs.6b00254

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

Gerken, J. B.; Stamoulis, A.; Suh, S.- E.; Fischer, N. D.; Kim, Y. J.; Guzei, I. A.; Stahl, S. S. Efficient Electrochemical Synthesis of Robust, Densely Functionalized Water Soluble Quinones. Chem. Commun. 2020, 56, 1199-1202. DOI:10.1039/C9CC08878D

Gerken, J. B.; Anson, C. W.; Preger, Y.; Symons, P. G.; Genders, J. D.; Qiu, Y.; Li, W.; Root, T. W.; Stahl, S. S. Comparison of Quinone‐Based Catholytes for Aqueous Redox Flow Batteries and Demonstration of Long‐Term Stability with Tetrasubstituted QuinonesAdv. Energy Mater. 202010, 2000340. doi: 10.1002/aenm.202000340