Visible-Light-Mediated Vicinal Dihalogenation of Unsaturated C-C Bonds Using Dual-Functional Group Transfer Reagents.

The growing demand for chemical production continues to drive the development of sustainable and efficient methods for introducing molecular complexity. In this context, the exploration of unconventional functional group transfer reagents (FGTRs) has led to significant advancements in practical and atom-efficient synthetic protocols. Aiming to advance the field of valuable organic synthesis, herein we report the successful development of carbon-based, bench-stable, modular, and inexpensive reagents implemented in dual halogen transfer to unsaturated hydrocarbons via photocatalytic activation of reagents based on a radical-polar crossover mechanism.

Facile Access to Terminal Nitroalkanes via Anti-Markovnikov Hydronitration and Hydronitroalkylation of Alkenes Using Photoredox Catalysis.

The evolution of catalysis and functional group transfer reagents play a significant role in the development of anti-Markovnikov alkene hydrofunctionalization reactions, facilitating the access to value-added molecules. We herein report the first rational design of a modular intermolecular anti-Markovnikov hydronitration of alkenes, enabling the direct synthesis of terminal nitroalkanes under visible light-mediated photoredox catalysis. By employing the redox-active organic nitrating reagent N-nitrosuccinimide, the produced nitryl radicals, in the presence of an olefin and a hydrogen atom transfer (HAT) mediator, lead to an anti-Markovnikov addition with complete regioselectivity.

Divergent functionalization of alkenes enabled by photoredox activation of CDFA and α-halo carboxylic acids.

Herein we present our studies on the solvent-controlled difunctionalization of alkenes utilizing chlorodifluoroacetic acid (CDFA) and α-halo carboxylic acids for the synthesis of γ-lactones, γ-lactams and α,α-difluoroesters. Mechanistic insights revealed that photocatalytic reductive mesolytic cleavage of the C-X bond delivers elusive α-carboxyl alkyl radicals. In the presence of an olefin molecule, this species acts as a unique bifunctional intermediate allowing for stipulated formation of C-O, C-N and C-H bonds on Giese-type adducts single electron transfer (SET) or hydrogen atom transfer (HAT) events.

Overcoming Challenges in O-Nitration: Selective Alcohol Nitration Deploying N,6-Dinitrosaccharin and Lewis Acid Catalysis.

Nitrate esters hold pivotal roles in pharmaceuticals, energetic materials, and atmospheric processes, motivating the development of efficient synthesis routes. Here, we present a novel catalytic method for the synthesis of nitrates via the direct O-nitration of alcohols, addressing limitations of current traditional methods. Leveraging bench-stable and recoverable N,6-dinitrosaccharin reagent, our catalytic strategy employs magnesium triflate to achieve mild and selective O-nitration of alcohols, offering broad substrate scope and unprecedentedly large functional group tolerance (e.

Mechanochemistry Drives Alkene Difunctionalization via Radical Ligand Transfer and Electron Catalysis.

A general and modular protocol is reported for olefin difunctionalization through mechanochemistry, facilitated by cooperative radical ligand transfer (RLT) and electron catalysis. Utilizing mechanochemical force and catalytic amounts of 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO), ferric nitrate can leverage nitryl radicals, transfer nitrooxy-functional group via RLT, and mediate an electron catalysis cycle under room temperature. A diverse range of activated and unactivated alkenes exhibited chemo- and regioselective 1,2-nitronitrooxylation under solvent-free or solvent-less conditions, showcasing excellent functional group tolerance.

Simplifying Nitration Chemistry with Bench-stable Organic Nitrating Reagents.

Nitro compounds play a crucial role in academia and industries, serving as building blocks for the synthesis of drugs, agrochemicals, and materials. Nitration, a fundamental process in organic synthesis, has undergone significant evolution since the 19th century. While electrophilic nitration dominates historically, recent decades have seen a focus on new reagents and their reactivity modes for achieving mild and robust synthesis of nitro compounds.

Review and Theoretical Analysis of Fluorinated Radicals in Direct C-H Functionalization of (Hetero)arenes.

We highlight key contributions in the field of direct radical C- H (hetero)aromatic functionalization involving fluorinated radicals. A compilation of Functional Group Transfer Reagents and their diverse activation mechanisms leading to the release of radicals are discussed. The substrate scope for each radical is analyzed and classified into three categories according to the electronic properties of the substrates.

Catalytic ipso-Nitration of Organosilanes Enabled by Electrophilic N-Nitrosaccharin Reagent.

Nitroaromatic compounds represent one of the essential classes of molecules that are widely used as feedstock for the synthesis of intermediates, the preparation of nitro-derived pharmaceuticals, agrochemicals, and materials on both laboratory and industrial scales. We herein disclose the efficient, mild, and catalytic ipso-nitration of organotrimethylsilanes, enabled by an electrophilic N-nitrosaccharin reagent and allows chemoselective nitration under mild reaction conditions, while exhibiting remarkable substrate generality and functional group compatibility. Additionally, the reaction conditions proved to be orthogonal to other common functionalities, allowing programming of molecular complexity via successive transformations or late-stage nitration.

Electron-Driven Nitration of Unsaturated Hydrocarbons.

Herein, we introduce an electrochemically assisted generation of nitryl radicals from ferric nitrate under mild reaction conditions using a simple setup with inexpensive graphite and stainless-steel electrodes. The mechanism of the reaction is supported by detailed spectroscopic and experimental studies. Powered by electricity and driven by electrons, the synthetic diversity of this reaction has been demonstrated through the development of highly efficient nitration protocols of various unsaturated hydrocarbons.

Photoredox Activation of Anhydrides for the Solvent-Controlled Switchable Synthesis of gem-Difluoro Compounds.

The incorporation of the gem-difluoromethylene (CF ) group into organic frameworks is highly sought due to the influence of this unit on the physicochemical and pharmacological properties of molecules. Herein we report an operationally simple, mild, and switchable protocol to access various gem-difluoro compounds that employs chlorodifloroacetic anhydride (CDFAA) as a low-cost and versatile fluoroalkylating reagent. Detailed mechanistic studies revealed that electron-transfer photocatalysis triggers mesolytic cleavage of a C-Cl bond generating a gem-difluoroalkyl radical.

Radical Trifluoroacetylation of Alkenes Triggered by a Visible-Light-Promoted C-O Bond Fragmentation of Trifluoroacetic Anhydride.

We report a mild and operationally simple trifluoroacylation strategy of olefines, that utilizes trifluoroacetic anhydride as a low-cost and readily available reagent. This light-mediated process is fundamentally different from conventional methodologies and occurs through a trifluoroacyl radical mechanism promoted by a photocatalyst, which triggers a C-O bond fragmentation. Mechanistic studies (kinetic isotope effects, spectroelectrochemistry, optical spectroscopy, theoretical investigations) highlight the evidence of a fleeting CF CO radical under photoredox conditions.

Synthesis, Characterization, and Reactivity of a Hypervalent-Iodine-Based Nitrooxylating Reagent.

Herein, the synthesis and characterization of a hypervalent-iodine-based reagent that enables a direct and selective nitrooxylation of enolizable C-H bonds to access a broad array of organic nitrate esters is reported. This compound is bench stable, easy-to-handle, and delivers the nitrooxy (-ONO ) group under mild reaction conditions. Activation of the reagent by Brønsted and Lewis acids was demonstrated in the synthesis of nitrooxylated β-keto esters, 1,3-diketones, and malonates, while its activity under photoredox catalysis was shown in the synthesis of nitrooxylated oxindoles.

-Nitroheterocycles: Bench-Stable Organic Reagents for Catalytic -Nitration of Aryl- and Heteroarylboronic Acids.

Photocatalytic and metal-free protocols to access various aromatic and heteroaromatic nitro compounds through -nitration of readily available boronic acid derivatives were developed using non-metal-based, bench-stable, and recyclable nitrating reagents. These methods are operationally simple, mild, regioselective, and possess excellent functional group compatibility, delivering desired products in up to 99% yield.

Facile access to nitroarenes and nitroheteroarenes using N-nitrosaccharin.

Nitroaromatics and nitroheteroaromatics serve as key building blocks and intermediates in synthesis, and form the core scaffold of a vast number of materials, dyes, explosives, agrochemicals and pharmaceuticals. However, their synthesis relies on harsh methodologies involving excess mineral acids, which present a number of critical drawbacks in terms of functional group compatibility and environmental impact. Modern, alternative strategies still suffer from significant limitations in terms of practicality, and a general protocol amenable to the direct C-H functionalization of a broad range of aromatics has remained elusive.

Synthetic Diversity from a Versatile and Radical Nitrating Reagent.

We leverage the slow liberation of nitrogen dioxide from a newly discovered, inexpensive succinimide-derived reagent to allow for the C-H diversification of alkenes and alkynes. Beyond furnishing a library of aryl β-nitroalkenes, this reagent provides unparalleled access to β-nitrohydrins and β-nitroethers. Detailed mechanistic studies strongly suggest that a mesolytic N-N bond fragmentation liberates a nitryl radical.

Taming Radical Intermediates for the Construction of Enantioenriched Trifluoromethylated Quaternary Carbon Centers.

Demonstrated herein is the construction of trifluoromethylated quaternary carbon centers by an asymmetric radical transformation. Enantioenriched trifluoromethylated oxindoles were accessed using a hypervalent iodine-based trifluoromethyl transfer reagent in combination with a magnesium Lewis acid catalyst and PyBOX-type ligands to achieve up to 99 % ee and excellent chemical yields. Mechanistic studies were performed by experimental and computational methods and suggest a single-electron transfer induced S 2-type mechanism.

Mapping Perfluoroalkyl Effects in Togni-Type Reagents by Thermolysis.

We present the thermolysis of cyclic hypervalent iodine(III) perfluoroalkyl transfer reagents carried out in standard GC-MS instrumentation. Through heating, these structures undergo fragmentation to afford perfluoroalkyl radicals F C and each reagent can be characterized by means of a threshold temperature, T (n). This parameter T (n) not only reflects the stability of the F C -I bond, but potentially also carries information regarding fundamental properties of the linear perfluoroalkyl chains.

Magnesium-Catalyzed Electrophilic Trifluoromethylation: Facile Access to All-Carbon Quaternary Centers in Oxindoles.

The first example of a magnesium-catalyzed direct trifluoromethylation of 3-substituted oxindoles using an electrophilic hypervalent iodine reagent is reported. The reaction proceeds under unprecedented mild conditions leading to the formation of an all-carbon quaternary center in oxindoles in high chemical yield and demonstrates excellent functional group tolerance. In addition to trifluoromethyl, other perfluoroalkyl groups can be introduced with similar level of efficacy.

Lewis Acid Catalyzed Synthesis of α-Trifluoromethyl Esters and Lactones by Electrophilic Trifluoromethylation.

An electrophilic trifluoromethylation of ketene silyl acetals (KSAs) by hypervalent iodine reagents 1 and 2 has been developed. The reaction proceeds under very mild conditions in the presence of a catalytic amount of trimethylsilyl bis(trifluoromethanesulfonyl)imide (up to 2.5 mol %) as a Lewis acid providing a direct access to a variety of secondary, tertiary, and quaternary α-trifluoromethyl esters and lactones in high yield (up to 98%).

Palladium-N-heterocyclic carbene (NHC)-catalyzed asymmetric synthesis of indolines through regiodivergent C(sp3)-H activation: scope and DFT study.

Two bulky, chiral, monodentate N-heterocyclic carbene ligands were applied to palladium-catalyzed asymmetric C-H arylation to incorporate C(sp(3))-H bond activation. Racemic mixtures of the carbamate starting materials underwent regiodivergent reactions to afford different trans-2,3-substituted indolines. Although this CAr-Calkyl coupling requires high temperatures (140-160 °C), chiral induction is high.

Copper-mediated ortho-nitration of (hetero)arenecarboxylates.

Various (hetero)arenecarboxylic acids were converted to the corresponding Daugulis amides and nitrated selectively in the ortho-position in the presence of [CuNO3(PPh3)2] and AgNO2 at 50 °C. A microwave-assisted saponification allows regenerating the carboxylate group within minutes, which may then be removed tracelessly by protodecarboxylation, or substituted by aryl- or alkoxy-groups via decarboxylative cross-coupling.

Synthesis of 3,3-Disubstituted Oxindoles by Palladium-Catalyzed Asymmetric Intramolecular α-Arylation of Amides: Reaction Development and Mechanistic Studies.

Palladium complexes incorporating chiral N-heterocyclic carbene (NHC) ligands catalyze the asymmetric intramolecular α-arylation of amides producing 3,3-disubstituted oxindoles. Comprehensive DFT studies have been performed to gain insight into the mechanism of this transformation. Oxidative addition is shown to be rate-determining and reductive elimination to be enantioselectivity-determining.

Aza-oxindole synthesis via base promoted Truce-Smiles rearrangement.

A novel efficient NaOtBu-mediated protocol for the synthesis of 3,3-disubstituted aza-oxindoles proceeds via a Truce-Smiles rearrangement-cyclisation pathway.

Palladium-NHC catalyzed enantioselective synthesis of fused indolines via inert C(sp(3))-H activation.

New sterically hindered chiral N-heterocyclic carbene (NHC) ligands were used in palladium catalysis to bring about a highly enantioselective C(sp(3))-H activation on the methylene site of a cycloalkane moiety. The intramolecular coupling reaction of a prochiral N-aryl-N-cycloalkyl methyl carbamate required high temperatures (140-160 °C) and afforded highly enantioenriched trans-2,3-fused indolines.