More Like this

1. Redox‐Active Reagents for Photocatalytic Generation of the OCF ₃ Radical and (Hetero)Aryl C−H Trifluoromethoxylation

   https://doi.org/10.1002/anie.201808495  

   Zheng, Weijia; Lee, Johnny W.; Morales‐Rivera, Cristian A.; Liu, Peng; Ngai, Ming‐Yu (September 2018, Angewandte Chemie International Edition)

   Abstract The trifluoromethoxy (OCF₃) radical is of great importance in organic chemistry. Yet, the catalytic and selective generation of this radical at room temperature and pressure remains a longstanding challenge. Herein, the design and development of a redox‐active cationic reagent (1) that enables the formation of the OCF₃radical in a controllable, selective, and catalytic fashion under visible‐light photocatalytic conditions is reported. More importantly, the reagent allows catalytic, intermolecular C−H trifluoromethoxylation of a broad array of (hetero)arenes and biorelevant compounds. Experimental and computational studies suggest single electron transfer (SET) from excited photoredox catalysts to1resulting in exclusive liberation of the OCF₃radical. Addition of this radical to (hetero)arenes gives trifluoromethoxylated cyclohexadienyl radicals that are oxidized and deprotonated to afford the products of trifluoromethoxylation. 

   more » « less
2. δ C–H (hetero)arylation via Cu-catalyzed radical relay

   https://doi.org/10.1039/c8sc04366c  

   Zhang, Zuxiao; Stateman, Leah M.; Nagib, David A. (January 2019, Chemical Science)

   null (Ed.)

   A Cu-catalyzed strategy has been developed that harnesses a radical relay mechanism to intercept a distal C-centered radical for C–C bond formation. This approach enables selective δ C–H (hetero)arylation of sulfonamides via intramolecular hydrogen atom transfer (HAT) by an N-centered radical. The radical relay is both initiated and terminated by a Cu catalyst, which enables incorporation of arenes and heteroarenes by cross-coupling with boronic acids. The broad scope and utility of this catalytic method for δ C–H arylation is shown, along with mechanistic probes for selectivity of the HAT mechanism. A catalytic, asymmetric variant is also presented, as well as a method for accessing 1,1-diaryl-pyrrolidines via iterative δ C–H functionalizations. 

   more » « less
3. The Role of Electron Transfer in Copper‐Mediated C(sp ² )−H Trifluoromethylation

   https://doi.org/10.1002/anie.202420677  

   Ball, Margaret_A P; Myers, Preston J; Ritch, Grayson D; Bower, Jamey K; Moore, Curtis E; Szymczak, Nathaniel K; Zhang, Shiyu (February 2025, Angewandte Chemie International Edition)

   Abstract We report copper(II) and copper(III) trifluoromethyl complexes supported by a pyridinedicarboxamide ligand (L) as a platform for investigating the role of electron transfer in C(sp²)−H trifluoromethylation. While the copper(II) trifluoromethyl complex is unreactive towards (hetero)arenes, the formal copper(III) trifluoromethyl complex performs C(sp²)−H trifluoromethylation of a wide range of (hetero)arenes. Mechanistic studies using the copper(III) trifluoromethyl complex suggest that the mechanism of arene trifluoromethylation is substrate‐dependent. When the thermodynamic driving force for electron transfer is high, the reaction proceeds through a previously unidentified single electron transfer (SET) mechanism, where an initial electron transfer occurs between the substrate and oxidant prior to CF₃group transfer. Otherwise, a CF₃radical release/electrophilic aromatic substitution (S_EAr) mechanism is followed. These studies provide valuable insights into the role of strong oxidants and potential mechanistic dichotomy in Cu‐mediated C(sp²)−H trifluoromethylation. 

   more » « less
4. Intermolecular C–H silylations of arenes and heteroarenes with mono-, bis-, and tris(trimethylsiloxy)hydrosilanes: control of silane redistribution under operationally diverse approaches

   https://doi.org/10.1039/D4SC03394A  

   Swann, Noah; Tang, Kiki; Nam, Jihyeon; Lee, Jooyeon; Domin, Marek; Shaw, Thomas E; Kozimor, Stosh A; Som, Salina; Lee, Kangsang L (July 2024, Chemical Science)

   Operationally diverse C–H silylations of (hetero) arenes with a broad silane scope are reported. The control of silane redistribution improves overall catalytic efficiency, affording the various arylsiloxysilanes useful for polysiloxane materials. 

   more » « less
5. A general strategy for C(sp3)–H functionalization with nucleophiles using methyl radical as a hydrogen atom abstractor

   https://doi.org/10.1038/s41467-021-27165-z  

   Leibler, Isabelle Nathalie-Marie; Tekle-Smith, Makeda A.; Doyle, Abigail G. (November 2021, Nature Communications)

   Abstract Photoredox catalysis has provided many approaches to C(sp³)–H functionalization that enable selective oxidation and C(sp³)–C bond formation via the intermediacy of a carbon-centered radical. While highly enabling, functionalization of the carbon-centered radical is largely mediated by electrophilic reagents. Notably, nucleophilic reagents represent an abundant and practical reagent class, motivating the interest in developing a general C(sp³)–H functionalization strategy with nucleophiles. Here we describe a strategy that transforms C(sp³)–H bonds into carbocations via sequential hydrogen atom transfer (HAT) and oxidative radical-polar crossover. The resulting carbocation is functionalized by a variety of nucleophiles—including halides, water, alcohols, thiols, an electron-rich arene, and an azide—to effect diverse bond formations. Mechanistic studies indicate that HAT is mediated by methyl radical—a previously unexplored HAT agent with differing polarity to many of those used in photoredox catalysis—enabling new site-selectivity for late-stage C(sp³)–H functionalization. 

   more » « less