Introduction to Radical Intermediates

The electrophilic amidyl radical intermediates can participate in 5-exo or 6-exo cyclization with alkenes and alkynes to afford C-centered radicals, which can then undergo various transformations such as H atom abstraction, single-electron transfer oxidation to a carbocation, cyclization, or aromatic substitution, leading to a diverse range of N-heterocyclic products.

Mechanistic experiments indicate that a silylcopper intermediate activates alkyl halides by single electron transfer to form alkyl radical intermediates, and that carbon-halogen bond cleavage is not involved in the rate-determining step.

Visible-light photoredox catalysis in combination with hydrogen atom transfer (HAT) catalysis is used to access the necessary α-amino radical intermediates for C–C bond formation.

Mechanistic and computational studies support the intermedicacy of a primary isodiazene which exhibits an unexpected divergence from previously studied secondary isodiazenes, leading to cage-escaping, free radical species that engage in a chain, hydrogen-atom transfer process involving aliphatic and diazenyl radical intermediates.

The synergetic effect mechanism was studied by detecting the variation of free radical intermediates.

The AMGMs not only served as a substrate with good conductivity and a large specific surface area for loading abundant primary antibodies but also acted as an effective co-reaction accelerator; the co-reaction accelerator could interact with a co-reactant rather than the luminophore to boost the generation of free radical intermediates, thereby producing abundant excited states of luminophores to amplify the ECL signal response.

The per-/polyfluoroaryl group acts as an electron acceptor in single electron transfer events to generate radical intermediates through cleavage of the C−S bond of mercaptans and utilize them in nickel-catalyzed reductive cross-coupling reactions.

, cleavage of the endoperoxide bond at the infected cell that generates radical intermediates and the subsequent chemical rearrangements plays a key role in the antimalarial activities.

Under copper-catalyzed conditions, a wide variety of alkyl xanthate esters, readily synthesized from alcohol feedstocks, were activated by catalytically generated aryl radicals and were converted to the alkyl-difluoromethane products via alkyl radical intermediates.

Through this, variants of 1-tetralone and 1-benzosuberone bearing a substituent at the benzylic position were selectively obtained through the regioselective ring closure of alkyl radical intermediates depending on the substitution pattern of the alkene moiety.

However, their electronic structures favor single-electron transfers that generate highly reactive radical intermediates (3).

Despite significant advances in this area, the catalytic asymmetric version still remains a challenging task mainly due to the difficulty in the stereocontrol of the highly reactive radical intermediates.

This review summarizes the recent advances in NHC-catalyzed reactions involving radical intermediates.

The development of new synthetic methods involving radical intermediates to control the absolute configuration of newly formed stereocenters has seen unprecedented growth in the past few decades.

Low-temperature spectroscopy and analysis of kinetic isotope effects for C-H amination indicate halogen-dependent photoreactivity: Photolysis of N -chloroamides proceeds via initial cleavage of the Mn-N bond to generate Mn(II) and amidyl radical intermediates; in contrast, photolysis of N -iodoamides proceeds via N-I cleavage to generate a Mn(IV) nitrenoid ( i.

[] Recently, powerful copperbased redox catalysis has been explored for the activation and synthetic utility of the N-F bond by Zhu[a] and Nagib, who explored the use of preformed N-F bonds to initiate positionselective C-H functionalization reactions from amidyl radical intermediates (Scheme 1).

This feature article summarises the recent progress in the visible light photoredox organic reactions, including decarboxylative addition reactions, alkylation, allylation, alkenylation, alkynylation, arylation, heteroarylation and cascade annulation of N-(acyloxy)phthalimide derivatives through the formation of carbon-carbon bonds, decarboxylative borylation, amination, oxygenation, sulfuration, selenylation, fluorination and iodination of N-(acyloxy)phthalimide derivatives through the formation of carbon-heteroatom bonds, and additions to arenes and alkenes, hydrogen atom transfer and the cleavage of α-carbon-carbon bonds via the iminyl radical intermediates for oxime derivatives.

Utilizing this protocol, a sequence of structurally diversiform 2-halomethyl pyrrolines are efficiently synthesized and a mechanism involving iminyl radical intermediates, which were initiated by Cu(I) species, was proposed.

This tutorial describes recent advances in trifluoromethylation of carbon-centered radical intermediates.

This review summarizes advances in photoredox-mediated Giese reactions since 2013, with a focus on the breadth of methods that provide access to crucial carbon-centered radical intermediates that can engage in radical conjugate addition processes.

Owing to the persistent radical effect (PRE) demonstrated by copper, organic radical intermediates generated by the visible light–induced photocatalytic cycles are efficiently trapped at the metal center and get stabilized.

A review of metal-catalysed carbonylation reactions involving single-electron transfer mechanisms and organic radical intermediates is presented, emphasizing new avenues to carbonyl compounds that are enabled by this approach.

The reactions are shown to proceed via cobalt(III)-carbene radical intermediates, which are in-volved in intramolecular hydrogen transfer (HAT) from the allylic position to the carbene radical, followed by a near barrierless radical rebound step in the coordination sphere of cobalt.

: Square-planar cobalt(II)-systems have emerged as powerful carbene transfer catalysts for the synthesis of a variety of (hetero)cyclic compounds via redox non-innocent Co(III)-carbene radical intermediates.

Recent research has brought to light a number of examples where the presence of certain functional groups opens up reaction pathways for key radical intermediates, including alkyl radicals, alkoxy radicals, and peroxy radicals, that are substantially different from traditional oxidation mechanisms.

A series of controlled experiments, including divided-cell electrolysis that compartmentalized the anodic and cathodic events, allowed us to identify the key radical intermediates and the pathway to their electrocatalytic formation.

Visible-light photoredox catalysis in combination with hydrogen atom transfer (HAT) catalysis is used to access the necessary α-amino radical intermediates for C–C bond formation.

This report describes the site-selective α-functionalization of primary amine derivatives through the generation of α-amino radical intermediates.

These reactions proceed via proton-coupled electron-transfer activation of alcohol O-H bonds followed by subsequent C-C β-scission of the resulting alkoxy radical intermediates.

A Minisci-type C–H alkylation reaction of N-heteroarenes with aliphatic alcohols via β-scission of alkoxy radical intermediates under photoredox-catalyzed conditions was developed.

Here, we examined whether such non-enzymatic DNA repair can be effected by the common cellular antioxidant glutathione, investigating both permanent DNA damage products and the guanine radical intermediates that form them, using the flash quench technique to carry out the 1-electron oxidation of guanine.

Using poly(dGdC)2 or poly(dAdT)2 DNA, we uncovered the dependence of DNA protection by Dps to the formation of guanine radical intermediates.

And the TM/PRF molecule tends to stabilize different radical intermediates at the TM site.

Hydrogen abstraction at the CH3 or OH site of CH3OH leads to different radical intermediates.

By employing a copper complex as a photocatalyst with blue LED irradiation, NHPI esters underwent one-electron reduction and heteroaryl methenamine derivatives underwent one-electron oxidation in one photo-redox catalytic cycle to form radical intermediates, respectively, followed by the recombination of these two radicals to form new C–C bonds.

Their propensity to form radical intermediates from alkyl electrophiles has greatly expanded the scope of traditional cross-coupling reactions.

Boryl radicals have emerged as powerful radical intermediates in organic synthesis.

Advanced oxidation treatment processes used in various applications to treat contaminated soil, water, and groundwater involve powerful radical intermediates, including hydroxyl radicals (•OH).

Reactions proceed through trifluoromethyl ketyl radical and allyl radical intermediates which undergo challenging cross radical-radical coupling.

Mechanistic studies indicated that allyl radical intermediates were involved in this process.

, paracetamol and anesthetics, to cytotoxic end products, (iii) its unique ability to effectively reduce dioxygen to radical species causing liver injury, (iv) its capability to reduce compounds, often generating radical intermediates of direct toxic or indirect immunotoxic properties and (v) its contribution to the development of alcoholic liver disease, steatosis and NASH.

Electrochemistry has recently emerged as a sustainable approach for efficiently generating radical intermediates utilizing eco-friendly electric energy.

To the best of our knowledge, this is the first report on CO₂ hydrosilylation catalyzed by transition-metal radical intermediates.

To the best of our knowledge, this is the first report on CO2 hydrosilylation catalyzed by transition-metal radical intermediates.

Mechanism studies show that the thiol groups on the surface of ZIS-100 play an important role in the formation of Cα radical intermediates.

The mechanism studies confirm that the Cα-H in PP-ol and lignin is firstly dehydrogenated to form Cα radical intermediates, and then the photogenerated electrons break the adjacent Cβ-O bond.

By taking advantage of radical clock reactions, the diradical intermediates generated from MSC would rearrange to new diradicals with much longer separation and weaker interactions between two radical centers.

The power and limitations of the EPR spin trapping and spin scavenging techniques in the detection and identification of nonpersistent radical intermediates generated in the photocatalytic particulate systems in water or organic solvents are also discussed in detail.

These results confirmed the formation of DPA•• diradical intermediates formed by injection of two electrons from the bottom electrode.

It is also shown that the induction period observed experimentally can be represented by either slow initiation/reinitiation of primary radicals or by assuming that radical intermediates formed by addition of primary radicals to the RAFT agent have increased stability; however, the associated rate constants for these reactions had to be adjusted from literature values.

Special emphasis is put on various new transformations involving the generation of radical intermediates via thermal, photochemical, and electrochemical means.

Mechanistic investigation including control experiments, transient fluorescence, UV-vis spectra, and DFT calculations suggests that the formation of active biradical intermediates via intramolecular single electron transfer (SET) is key stage in the catalytic cycle.