Research

(1) Metal-Mediated Gif-type Oxygenation Chemistry. In earlier work, we have been engaged in deciphering complicated mechanistic enigmas surrounding the workings of iron- and copper-mediated Gif-type oxygenation chemistry.1,2 These systems were introduced by Prof. Derek Barton and comprised of rather simple Fe(III) or Cu(II) precursor catalysts in pyridine/acetic acid, mediating oxygenation of alkanes (mostly to ketones) in the presence of O2/reducing agent, hydrogen peroxide or tert-butyl hydroperoxide. The t-BuOOH-based systems were soon proved to generate t-BuO• radicals (Minisci’s work), which is not surprising if one considers that even bona fide P450 systems (which operate via Fe=O oxidants) release t-BuO• radicals in the presence of t-BuOOH as a sacrificial oxidant. Our work centered on systems supported by O2/reducing agent or H2O2, which proved to be very complex and controversial in their mode of operation. In addition, the underlying inorganic chemistry was completely unknown in terms of metal-centered species generated in solution and engaged in catalysis. The original suggestion of Derek Barton that Gif chemistry operates via metal-oxo species was not particularly convincing to us. Nevertheless, there was interest at the time about the potential involvement of metal-peroxo or -hydroperoxo species in ketonization of alkanes and epoxidation o alkenes. Our painstaking work called for the generation of several Gif-like systems, for comparative purposes, and showed conclusively (via a battery of catalytic and mechanistic probes) that oxygen- and carbon-centered radical pathways are operative in all cases. The oxygen-centered radicals are largely hydroxyl radicals as well as substrate derived alkoxyl radicals. The latter are more selective in their mode of action and can affect the product profile, giving the erroneous impression that a metal-centered oxidant may be involved. Moreover, we showed that even if Fe(III) pre-catalysts are used, the catalytic cycles operate within the Fe(II)/H2O2 manifold for the most productive H2O2-supported systems. A number of metal-peroxo species was also isolated and fully characterized in this work, but their reactivity vis-à-vis alkanes and alkenes is negligible. This work highlighted the importance of obtaining a pristine and detailed experimental record in attempting to formulate mechanistic scenarios. Many controversies surrounding Gif chemistry were resolved by amassing complete sets of experimental data from catalytic and mechanistic studies (minor products can be of major significance). As the contribution of radical chemistry in synthesis increased exponentially in subsequent years, a handful of reagents generated from this work have found applications in organic synthesis and are still discussed in the chemical literature.3,4 

(2) Metal-Mediated Construction of C–N Bonds via Nitrene-Transfer Chemistry.  

More recently, at Missouri S&T, we have developed a family of divalent base metal (Mn, Fe, Co, Ni) and monovalent coinage metal (Cu, Ag) reagents, supported by tripodal trisamido/imido-amine and bipodal bisamido/imido-amine ligands (Figure 1). The weak ligand field and the ability to decorate the equatorial amido/imido residues by a wide range of aryl, acyl, alkyl and guanidinyl arms has given rise to a plethora of anionic, neutral and cationic catalysts employed in nitrene (and chloro) transfer to C–H and C=C bonds of hydrocarbons.5-9  

  1. Stavropoulos, P.; Çelenligil-Çetin, R.; Tapper, A. The Gif Paradox. Acc. Chem. Res. 2001, 34, 745–752.   DOI: 10.1021/ar000100%2B 
  1. Kiani, S.; Tapper, A.; Staples, R. J.; Stavropoulos, P. Functional Aspects of Gif-type Oxidation of Hydrocarbons Mediated by Iron Picolinate H2O2-Dependent Systems: Evidence for the Generation of Carbon- and Oxygen-Centered Radicals. J. Am. Chem. Soc. 2000, 122, 7503–7517. DOI: 10.1021/ja000063h  
  1. Stavropoulos, P.; Çelenligil-Çetin, R.; Kiani, S.; Tapper, A.; Pinnapareddy, D.; Paraskevopoulou, P. Iron, bis(pyridine)bis(2-pyridinecarboxylato-N1,O2), in Encyclopaedia of Reagents for Organic Synthesis; Fuchs, P. (Ed.); Wiley: New York, 2006; pp 414–415. (invited peer-reviewed research article) 
  1. Stavropoulos, P.; Çelenligil-Çetin, R.; Kiani, S.; Tapper, A.; Pinnapareddy, D.; Paraskevopoulou, P. Gif Reactions, in Handbook of C–H Transformations. Applications in Organic Synthesis; Dyker, G. (Ed.); Wiley-VCH: Weinheim, 2005; pp 497-507. (invited peer-reviewed research article) 
  1. Sahoo, S. K.; Harfmann, B.; Ai, L.; Wang, Q.; Mohapatra, S.; Choudhury, A.; Stavropoulos, P. Cationic Divalent Metal Sites (M = Mn, Fe, Co) Operating as Both Nitrene-Transfer Agents and Lewis Acids toward Mediating the Synthesis of Three- and Five-Membered N-Heterocycles. Inorg. Chem. 2023, 62, 10743-10761. DOI: 10.1021/acs.inorgchem.3c01209 
  1. Kalra, A.; Bagchi, V.; Paraskevopoulou, P.; Das, P.; Ai, L.; Sanakis, Y.; Raptopoulos, G.; Mohapatra, S.; Choudhury, A.; Sun, Z.; Cundari, T. R.; Stavropoulos, P. Is the Electrophilicity of the Metal Nitrene the Sole Predictor of Metal-Mediated Nitrene Transfer to Olefins? Secondary Contributing Factors as Revealed by a Library of High-Spin Co(II) Reagents. Organometallics 2021, 40, 1974-1996. DOI: 10.1021/acs.organomet.1c00267   
  1. Bagchi, V.; Kalra, A.; Das, P.; Paraskevopoulou, P.; Gorla, S.; Ai, L.; Wang, Q.; Mohapatra, S.; Choudhury, A.; Sun, Z.; Cundari, T. R.; Stavropoulos, P. Comparative Nitrene-Transfer Chemistry to Olefinic Substrates Mediated by a Library of Anionic Mn(II) Triphenylamido-Amine Reagents and M(II) Congeners (M = Fe, Co, Ni) Favoring Aromatic over Aliphatic Alkenes. ACS Catal. 2018, 8, 9183-9206. DOI: 10.1021/acscatal.8b01941  
  1. Bagchi, V.; Paraskevopoulou, P.; Das, P.; Chi, L.; Wang, Q.; Choudhury, A.; Mathieson, J. S.; Cronin, L.; Pardue, D. B.; Cundari, T. R.; Mitrikas, G.; Sanakis, Y.; Stavropoulos, P. A Versatile Tripodal Cu(I) Reagent for C–N Bond Construction via Nitrene-Transfer Chemistry: Catalytic Perspectives and Mechanistic Insights on C–H Aminations/Amidinations and Olefin Aziridinations. J. Am. Chem. Soc. 2014, 136, 11362-11381. DOI: 10.1021/ja503869j 
  1. Bagchi, V.; Raptopoulos, G.; Das, P.; Christodoulou, S.; Wang, Q.; Ai, L.; Choudhury, A.; Pitsikalis, M.; Paraskevopoulou, P.; Stavropoulos, P. Synthesis and Characterization of a Family of Co(II) Triphenylamido-Amine Complexes and Catalytic Activity in Radical Polymerization of Olefins. Polyhedron 2013, 52, 78-90 (A. Werner issue). DOI: 10.1016/j.poly.2012.11.020   
  1. Sahoo, S. K.; Harfmann, B.; Bhatia, H.; Singh, H.; Balijapelly, S.; Choudhury, A.; Stavropoulos, P. “A Comparative Study of Cationic Copper(I) reagents Supported by Bipodal Tetramethylguanidinyl-Containing Ligands as Nitrene-Transfer Catalysts” ACS Omega 2024, 9, 15697-15708. DOI: 10.1021/acsomega.4c00909  
  1. Sharma, M.; Fritz, R. M.; Adebanjo, J. O.; Lu, Z.; Cundari, T. R.; Omary, M. A.; Choudhury, A.; Stavropoulos, P. “Nitrene-Transfer Chemistry to C–H and C=C Bonds Mediated by Triangular Coinage Metal Platforms Supported by Triply Bridging Pnictogen Elements Sb(III) and Bi(III)” Organometallics 2024, 43, 634-652. DOI: 10.1021/acs.organomet.3c00493 
  1. Sharma, M.; Fritz, R. M.; Bhatia, H.; Adebanjo, J. O.; Lu, Z.; Omary, M. A.; Cundari, T. R.; Choudhury, A.; Stavropoulos, P. “C–H Amination Chemistry Mediated by Trinuclear Cu(I) Sites Supported by a Ligand Scaffold Featuring an Arene Platform and Tetramethylguanidinyl Residues” Dalton Trans. 2024, accepted manuscript DT-ART-06-2024-001670.R1 
  1. Stavropoulos, P. Metal-Catalyzed and Metal-Free Intermolecular Amination of Light Alkanes and Benzenes. Comm. Inorg. Chem. 2016, 1-57. DOI: 10.1080/02603594.2016.1183487   
  1. Singh, K.; Long, J. R.; Stavropoulos, P. Ligand-Unsupported Metal-Metal (M = Cu, Ag) Interactions Between Closed-Shell d10 Trinuclear Systems. J. Am. Chem. Soc. 1997, 119, 2942–2943. DOI: 10.1021/ja963664a  
  1. Wang, Y.; Zhao, H.; Yang, C.; Fang, L.; Zheng, L.; Lv, H.; Stavropoulos, P.; Ai, L.; Zhang, J. “Chiral Recognition of Chiral (Hetero)Cyclic Derivatives Probed by Tetraaza Macrocyclic Chiral Solvating Agents via 1H NMR Spectroscopy” Anal. Chem. 2024, 96, 5188-5194. DOI: 10.1021/acs.analchem.3c05395