Persistent Radicals Derived from N-Heterocyclic Carbenes for Material Applications.

Persistent radicals are potential building blocks of novel materials in many fields. Recently, highly stable persistent radicals are considered to be within reach, thanks to several radical stabilization strategies such as spin delocalization and steric protection. N-Heterocyclic carbene (NHC)-derived substituents can be attached to a radical center for these purposes, as illustrated by numerous NHC-stabilized radicals reported in the last two decades.This Account describes our recent work on developing NHC-derived persistent radicals, as well as their prospective applications. Considering that NHCs not only stabilize radicals but also reversibly interact with gas molecules, in 2015 our group reported NHC-nitric oxide (NHC-NO) radicals produced by reversibly trapping nitric oxide (NO) radical gas in NHCs. The resultant compounds were loaded into biocompatible poly(ethylene glycol)-block-poly(caprolactone) (PEG-b-PCL) micelles and injected into tumor-bearing mice. Then, NO release was triggered by high-intensity focused ultrasound irradiation of the tumor tissue. Furthermore, the NHC-NO radicals could also serve as a platform to generate other organic radicals such as oxime ether or iminyl radicals. Apart from medicine-related applications, radicals stabilized by NHCs can be used as energy storage materials. In this context, the triazenyl radical containing two NHC units reported by our laboratory could be a cathode active material in batteries, as an organic alternative to LiCoO2. The subsequently prepared unsymmetrical triazenyl radical derivatives were applied as anolytes in nonaqueous all-organic redox flow batteries. In addition, a ferrocene-based redox flow battery anolyte was obtained by introducing NHC-derived substituents that effectively stabilize the ferrocenate derivatives previously reported only at low temperatures. The batteries containing NHC-supported radicals exhibited high energy efficiency and insignificant radical decomposition over multiple cycles. Finally, toward developing air-persistent organic radicals for flexible devices and MRI contrasting agents, we also highlight our recent air- and physiologically stable organic radicals derived from NHCs. Coordination of tris(pentafluorophenyl)borane to the NHC-NO radical produced a new radical cation that is stable in an organic solvent under air for several months. The readily accessible 1,2-dicarbonyl radical cations generated by the reaction of NHCs with oxalyl chloride are remarkably persistent even in an aqueous solution for several months. They are also highly stable even under physiological conditions, making them particularly attractive potential candidates for organic MRI contrast agents. We hope that this Account will serve as a guide for the future development of stable NHC-derived organic radicals and draw the attention of the synthetic community to their potential applications in material science.

Cobalt-Catalyzed Formation of Grignard Reagents via C-O or C-S Bond Activation.

C(aryl)-OMe bond functionalization catalyzed by cobalt(II) chloride in combination with a nacnac-type ligand and magnesium as a reductant is reported. Borylation and benzoylation of aryl methoxides are demonstrated, and C(aryl)-SMe bond borylation can be achieved under similar conditions. This is the first example of achieving these transformations using cobalt catalysis. Mechanistic studies suggest that a Grignard reagent is generated as an intermediate in a rare example of a magnesiation via a C-O bond activation reaction. Indeed, an organomagnesium species could be directly observed by electrospray ionization mass spectroscopic analysis. Kinetic experiments indicate that a heterogeneous cobalt catalyst performs the C-O bond activation.

Grignard reagent formation via C-F bond activation: a centenary perspective.

Examples of Grignard reagents obtained by C-F bond activation with magnesium have kept appearing in the literature over the last century. Due to the high bond dissociation energy of the C-F bond, a lot of effort has been invested in the preparation of highly active forms of magnesium for this purpose. Originally, magnesium activation was achieved by the application of additives, notably iodine. Later work focused on the generation of highly active magnesium powder by reduction of magnesium salts with alkali metals ("Rieke magnesium"). Modern approaches to the problem involve the application of Mg(I)-Mg(I) dimers and C-F bond activation performed by a transition metal catalyst followed by transmetallation with a magnesium salt. The purpose of this article is to provide an overview of fluoro-Grignard reagent preparation approaches reported to date.

Generation of N-H Imines from α-Azidocarboxylic Acids through Ru-Catalyzed Decarboxylation.

A new method for the synthesis of N-H imines from α-azidocarboxylic acids was developed, which proceeds through decarboxylative C-C bond cleavage catalyzed by a commercial diruthenium complex ([CpRu(CO)2]2) under visible light irradiation at room temperature within several minutes. The reactive products undergo condensation, which forms cyclic trimers (2,4,6-trialkylhexahydro-1,3,5-triazines) or linear N,N'-bis(arylmethylidene)arylmethanediamines in quantitative yields. Alternatively, the N-H imines can be trapped with benzylamine and 2-(aminomethyl)aniline, providing stable N-benylimines and tetrahydroquinazolines, respectively. Subsequent oxidation of tetrahydroquinazolines produced quinazolines.

Programmable Synthesis of Silver Wheels.

The synthesis of sandwich-shaped multinuclear silver complexes with planar penta- and tetranuclear wheel-shaped silver units and a central anion, [Agn(2-HPB)2(A-)](OTf-)n-1, nAgA, n = 4 or 5 and A- = OH- or F- or Cl-, is reported, along with complete spectroscopic and structural characterization. An NMR mechanistic study reveals that silver complexes were formed in the following order: 2Ag → 3AgH2O → 5AgOH → 4AgOH. The central hydroxides in 4AgOH and 5AgOH exhibit exotic physical properties due to the confined environment inside the complex. The size of these silver wheels can be tuned by changing the central anion or extracting/adding one silver atom. This study provides the facile way to synthesize discrete wheel-shaped multinuclear silver complexes and provides valuable insights into the dynamics of the self-assembly process.

Direct Trifluoromethylation of Alcohols Using a Hypervalent Iodosulfoximine Reagent.

The direct trifluoromethylation of a variety of aliphatic alcohols using a hypervalent iodosulfoximine reagent afforded the corresponding ethers in moderate to good yields (14-72 %). Primary, secondary, and even tertiary alcohols, including examples derived from natural products, underwent this transformation in the presence of catalytic amounts of zinc bis(triflimide). Typical reaction conditions involved a neat mixture of 6.0 equivalents of the alcohol with 1.0 equivalent of the reagent, with the majority of reactions complete within 2 h with 2.5 mol % of the Lewis acid catalyst. Furthermore, experimental evidence was provided that the C-O bond-forming process occurred via the coordination of the alcohol to the iodine atom and subsequent reductive elimination.

Understanding 125Te NMR chemical shifts in disymmetric organo-telluride compounds from natural chemical shift analysis.

Organotellurium compounds of general formula X-Te-R display a broad range of chemical shifts that are very sensitive to the X and R substituents. In order to link the 125Te chemical shift of a series of perfluoroalkyl aryl tellurides to their electronic structure, the chemical shielding tensors of the 125Te nuclei were calculated by density functional theory (DFT) and further analyzed by a decomposition into contributions of natural localized molecular orbitals (NLMOs). The analysis indicated that the variation in 125Te chemical shifts in molecules 1-13 is mainly due to the magnetic coupling of the tellurium p-character lone pair with antibonding orbitals perpendicular to it {σ*(Te-X) and σ*(Te-C(Ar))} upon action of an external magnetic field. The strength of the coupling is affected by electronic properties of the X-substituents, polarization of the antibonding orbitals and presence of secondary interactions perturbing the energy of these orbitals. The lower in energy and the more polarized towards tellurium the antibonding orbitals are, the stronger is the coupling and the more deshielded the tellurium nucleus.

Pentafluoro(aryl)-λ6 -tellanes and Tetrafluoro(aryl)(trifluoromethyl)-λ6 -tellanes: From SF5 to the TeF5 and TeF4 CF3 Groups.

The TeF5 group is significantly underexplored as a highly fluorinated substituent on an organic framework, despite it being a larger congener of the acclaimed SF5 group. In fact, only one aryl-TeF5 compound (phenyl-TeF5 ) has been reported to date, synthesized using XeF2 . Our recently developed mild TCICA/KF approach to oxidative fluorination provides an affordable and scalable alternative to XeF2 . Using this method, we report a scope of extensively characterized aryl-TeF5 compounds, along with the first SC-XRD data on this compound class. The methodology was also extended to the synthesis and structural study of heretofore unknown aryl-TeF4 CF3 compounds. Additionally, preliminary reactivity studies unveiled some inconsistencies with previous literature regarding phenyl-TeF5 . Although our studies conclude that the arene-based TeF5 (and TeF4 CF3 ) group is not quite as robust as the SF5 group, we find that the TeF5 group is more stable than previously thought, thus opening a door to explore new applications of this motif.

Radical Trifluoromethoxylation of Arenes Triggered by a Visible-Light-Mediated N-O Bond Redox Fragmentation.

A simple trifluoromethoxylation method enables non-directed functionalization of C-H bonds on a range of substrates, providing access to aryl trifluoromethyl ethers. This light-driven process is distinctly different from conventional procedures and occurs through an OCF3 radical mechanism mediated by a photoredox catalyst, which triggers an N-O bond fragmentation. The pyridinium-based trifluoromethoxylation reagent is bench-stable and provides access to synthetic diversity in lead compounds in an operationally simple manner.

Expanding the Scope of Hypervalent Iodine Reagents for Perfluoroalkylation: From Trifluoromethyl to Functionalized Perfluoroethyl.

A series of new hypervalent iodine reagents based on the 1,3-dihydro-3,3-dimethyl-1,2-benziodoxole and 1,2-benziodoxol-3-(1H)-one scaffolds, which contain a functionalized tetrafluoroethyl group, have been prepared, characterized, and used in synthetic applications. Their corresponding electrophilic fluoroalkylation reactions with various sulfur, oxygen, phosphorus, and carbon-centered nucleophiles afford products that feature a tetrafluoroethylene unit, which connects two functional moieties. A related λ(3) -iodane that contains a fluorophore was shown to react with a cysteine derivative under mild conditions to give a thiol-tagged product that is stable in the presence of excess thiol. Therefore, these new reagents show a significant potential for applications in chemical biology as tools for fast, irreversible, and selective thiol bioconjugation.

One-pot synthesis of hypervalent iodine reagents for electrophilic trifluoromethylation.

Simplified syntheses suited for large scale preparations of the two hypervalent iodine reagents 1 and 2 for electrophilic trifluoromethylation are reported. In both cases, the stoichiometric oxidants sodium metaperiodate and tert-butyl hypochlorite have been replaced by trichloroisocyanuric acid. Reagent 1 is accessible in a one-pot procedure from 2-iodobenzoic acid in 72% yield. Reagent 2 was prepared via fluoroiodane 11 in a considerably shorter reaction time and with no need of an accurate temperature control.