Direct Amination of Benzene with Ammonia by Flow Plasma Chemistry.

Amine derivatives, including aniline and allylic amines, can be formed in a single-step process from benzene and an ammonia plasma in a microreactor. Different process parameters such as temperature, residence time, and plasma power were evaluated to improve the reaction yield and its selectivity toward aminated products and avoid hydrogenated or oligomerized products. In parallel, simulation studies of the process have been carried out to propose a global mechanism and gain a better understanding of the influence of the different process parameters. The exploration of diverse related alkenes showed that the double bonds, conjugation, and aromatization influenced the amination mechanism. Benzene was the best reactant for amination based on the lifetime of radical intermediates. Under optimized conditions, benzene was aminated in the absence of catalyst with a yield of 3.8 % and a selectivity of 49 % in various amino compounds.

Regime Switch in the Dual-Catalyzed Coupling of Alkyl Silicates with Aryl Bromides.

Metallaphotoredox catalyzed cross-coupling of an arylbromide (Ar-Br) with an alkyl bis(catecholato)silicate (R-Si⊖ ) has been analyzed in depth using a continuum of analytical techniques (EPR, fluorine NMR, electrochemistry, photophysics) and modeling (micro-kinetics and DFT calculations). These studies converged on the impact of four control parameters consisting in the initial concentrations of the iridium photocatalyst ([Ir]0 ), nickel precatalyst ([Ni]0 ) and silicate ([R-Si⊖ ]0 ) as well as light intensity I0 for an efficient reaction between Ar-Br and R-Si⊖ . More precisely, two regimes were found to be possibly at play. The first one relies on an equimolar consumption of Ar-Br with R-Si⊖ smoothly leading to Ar-R, with no side-product from R-Si⊖ and a second one in which R-Si⊖ is simultaneously coupled to Ar-Br and degraded to R-H. This integrative approach could serve as a case study for the investigation of other metallaphotoredox catalysis manifolds of synthetic significance.

Reactant-induced photoactivation of in situ generated organogold intermediates leading to alkynylated indoles via Csp2-Csp cross-coupling.

Photosensitization of organogold intermediates is an emerging field in catalysis. In this context, an access to 2,3-disubstituted indoles from o-alkynyl aniline and iodoalkyne derivatives via a gold-catalyzed sequence under visible-light irradiation and in the absence of an exogenous photocatalyst was uncovered. A wide scope of the process is observed. Of note, 2-iodo-ynamides can be used as electrophiles in this cross-coupling reaction. The resulting N-alkynyl indoles lend themselves to post-functionalization affording valuable scaffolds, notably benzo[a]carbazoles. Mechanistic studies converge on the fact that a potassium sulfonyl amide generates emissive aggregates in the reaction medium. Static quenching of these aggregates by a vinylgold(I) intermediate yields to an excited state of the latter, which can react with an electrophile via oxidative addition and reductive elimination to forge the key C-C bond. This reactant-induced photoactivation of an organogold intermediate opens rich perspectives in the field of cross-coupling reactions.

Mesoporous Graphitic Carbon Nitride as a Heterogeneous Organic Photocatalyst in the Dual Catalytic Arylation of Alkyl Bis(catecholato)silicates.

Mesoporous graphitic carbon nitride (mpg-CN) is introduced as a heterogeneous photocatalyst to perform dual photoredox- and nickel-catalyzed cross-coupling reactions between alkyl bis(catecholato)silicates as radical precursors and aryl or alkenyl bromides. The synergy between this recyclable photocatalyst and the broadly applied homogeneous nickel complex [Ni(dtbbpy)Br2] gives access to C(sp2)-C(sp3) cross-coupling products in a sustainable fashion. The recycled mpg-CN photocatalyst was analyzed by time-resolved emission spectroscopy and EPR spectroscopy.

Organometallic catalysis under visible light activation: benefits and preliminary rationales.

Organometallic catalysis under visible light activation is an emerging field. Activation by photosensitization or by direct light absorption of organometallic complexes can facilitate or trigger elementary steps in a catalytic cycle such as pre-catalyst reduction, oxidative addition, transmetalation and reductive elimination, as well as the ability of generating radical intermediates, widening the structural diversity offered by classical couplings. This perspective aims to highlight key examples of these light-induced or enhanced processes, with an emphasis on the underlying mechanisms involved.

Boron, silicon, nitrogen and sulfur-based contemporary precursors for the generation of alkyl radicals by single electron transfer and their synthetic utilization.

Recent developments in the use of boron, silicon, nitrogen and sulfur derivatives in single-electron transfer reactions for the generation of alkyl radicals are described. Photoredox catalyzed, electrochemistry promoted or thermally-induced oxidative and reductive processes are discussed highlighting their synthetic scope and discussing their mechanistic pathways.

Phenyl Silicates with Substituted Catecholate Ligands: Synthesis, Structural Studies and Reactivity.

While the generation of aryl radicals by photoredox catalysis under reductive conditions is well documented, it has remained challenging under an oxidative pathway. Because of the easy photo-oxidation of alkyl bis-catecholato silicates, a general study of phenyl silicates bearing substituted catecholate ligands has been achieved. The newly synthesized phenyl silicates have been fully characterized, and their reactivity has been explored. It was found that, thanks to the substitution of the catecholate moiety, notably with the 4-cyanocatecholato ligand, the phenyl radical could be generated and trapped. Computational studies provided a rationale for these findings.

A Parisian Vision of the Chemistry of Hypercoordinated Silicon Derivatives.

Less than ten years of acquaintance with hypercoordinated silicon derivatives in our lab is described in this account. Martin's spirosilane derivatives open new opportunities as ligands and as agents for the activation of small molecules and bis-catecholato silicates have proven to be exquisite radical precursors in photoredox conditions for broad synthetic applications.

Iron and cobalt catalysis: new perspectives in synthetic radical chemistry.

This review deals with some key synthetic developments based on the use of iron or cobalt complexes to promote radical reactivity which have been devised over the last decades. We have more particularly focused on reactions for which the impact of this chemistry has yielded greener alternatives to existing processes and also on new transformations, notably hydrogen atom transfer (HAT) triggered processes, which can be promoted through the use of metallic complexes. Preliminary synthetic developments based on the use of photoactive iron and cobalt complexes are also covered.

Photosensitized oxidative addition to gold(I) enables alkynylative cyclization of o-alkylnylphenols with iodoalkynes.

The well-established oxidative addition-reductive elimination pathway is the most followed one in transition metal-catalysed cross-coupling reactions. While readily occurring with a series of transition metals, gold(I) complexes have shown some reluctance to undergo oxidative addition unless special sets of ligands on gold(I), reagents or reaction conditions are used. Here we show that under visible-light irradiation, an iridium photocatalyst triggers-via triplet sensitization-the oxidative addition of an alkynyl iodide onto a vinylgold(I) intermediate to deliver C(sp)2-C(sp) coupling products after reductive elimination. Mechanistic and modelling studies support that an energy-transfer event takes place, rather than a redox pathway. This particular mode of activation in gold homogenous catalysis was applied in several dual catalytic processes. Alkynylbenzofuran derivatives were obtained from o-alkynylphenols and iodoalkynes in the presence of catalytic gold(I) and iridium(III) complexes under blue light-emitting diode irradiation.

Carbonylation of Alkyl Radicals Derived from Organosilicates through Visible-Light Photoredox Catalysis.

Primary, secondary, and tertiary alkyl radicals formed by the photocatalyzed oxidation of organosilicates underwent efficient carbonylation with carbon monoxide (CO) to give a variety of unsymmetrical ketones. This study introduces the possibility of radical carbonylation under a photooxidative regime.

On the Influence of the Protonation States of Active Site Residues on AChE Reactivation: A QM/MM Approach.

Acetylcholinesterase (AChE), an enzyme of the serine hydrolase superfamily, is a mediator of signal transmission at cholinergic synapses by catalyzing acetylcholine cleavage into acetate and choline. This enzyme is vulnerable to covalent inhibition by organophosphate compounds (like VX). Covalent inhibition of AChE does not revert spontaneously. Known reactivator compounds have limited action in restoring catalytic activity. QM/MM simulations of VX-inhibited AChE reactivation by pralidoxime (2-PAM), a classical reactivator, were performed. These afforded a broad view of the effect of protonation states of active-site residues, and provide evidence for the role of Glu202, which needs to be protonated for reactivation to occur. In situ deprotonation of 2-PAM for both protonation states of Glu202 showed that His447 is able to deprotonate 2-PAM with the assistance of Glu202. Because the active site of serine hydrolases is highly conserved, this work provides new insights on the interplay between the catalytic triad residues and this glutamate, newly identified as protonatable.

Photoredox Catalysis for the Generation of Carbon Centered Radicals.

Radical chemistry has witnessed over the last decades important advances that have positioned it as a methodology of choice in synthetic chemistry. A number of great attributes such as specific reactivities, the knowledge of the kinetics of most elementary processes, the functional group tolerance, and the possibility to operate cascade sequences are clearly responsible for this craze. Nevertheless, at the end of the last century, radical chemistry appeared plagued by several hurdles to overcome such as the use of environmentally problematic mediators or the impossibility of scale up. While the concept of photocatalysis was firmly established in the coordination chemistry community, its diffusion in organic synthetic chemistry remained sporadic for decades until the end of the 2000s with the breakthrough merging of organocatalysis and photocatalysis by the MacMillan group and contemporary reports by the groups of Yoon and Stephenson. Since then, photoredox catalysis has enjoyed particularly active and intense developments. It is now the topic of a still increasing number of publications featuring various applications from asymmetric synthesis, total synthesis of natural products, and polymerization to process (flow) chemistry. In this Account, we survey our own efforts in this domain, focusing on the elaboration of new photocatalytic pathways that could lead to the efficient generation of C-centered functionalized alkyl and aryl radicals. Both reductive and oxidative manifolds are accessible through photoredox catalysis, which has guided us along these lines in our projects. Thus, we studied the photocatalytic reduction of onium salts such as sulfoniums and iodoniums for the production of the elusive aryl radical intermediates. Progressing to more relevant chemistry for synthesis, we examined the cleavage of C-O and the C-Br bonds for the generation of alkyl C-centered radicals. Activated epoxides could serve as valuable substrates of a photocatalyzed variant of the Nugent-RajanBabu-Gansäuer homolytic cleavage of epoxides. Using imidazole based carbamates, we could also devise the first photocatalyzed Barton-McCombie deoxygenation reaction. Finally, bromophenylacetate can be reduced using the [Au2(µ-dppm)2]Cl2 photocatalyst under UVA or visible-light. This was used for the initiation of the controlled atom transfer radical polymerization of methacrylates and acrylates in solution or laminate. Our next endeavors concerned the photocatalyzed oxidation of stabilized carbanions such as enolates of 1,3-dicarbonyl substrates, trifluoroborates, and more extensively bis-catecholato silicates. Because of their low oxidation potentials, the later have proved to be exquisite sources of radical entities, which can be engaged in diverse intermolecular reactions such as vinylation, alkynylation, and conjugate additions. The bis-catecholato silicates were also shown to behave as excellent partners of dual photoredox-nickel catalysis leading in an expeditious manner to libraries of cross coupling products.

Organic photoredox catalysis for the oxidation of silicates: applications in radical synthesis and dual catalysis.

Metal free photooxidation of alkyl bis(catecholato)silicates with the organic dye 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyano-benzene (4CzIPN) allows the smooth formation of alkyl radicals. The latter can be efficiently engaged either with radical acceptors to provide homolytic addition products or in photoredox/nickel dual catalysis reactions to obtain cross-coupling products.

Dual Photoredox/Gold Catalysis Arylative Cyclization of o-Alkynylphenols with Aryldiazonium Salts: A Flexible Synthesis of Benzofurans.

A new method for the arylative cyclization of o-alkynylphenols with aryldiazonium salts via dual photoredox/gold catalysis is described. The reaction proceeds smoothly at room temperature in the absence of base and/or additives and offers an efficient approach to benzofuran derivatives. The scope of the transformation is wide, and the limitations are discussed. The reaction is proposed to proceed through a photoredox-promoted generation of a vinylgold(III) intermediate that undergoes reductive elimination to provide the heterocyclic coupling adduct.

Chiral Phosphate in Rhodium-Catalyzed Asymmetric [2+2+2] Cycloaddition: Ligand, Counterion, or Both?

Investigations based on NMR spectroscopy, mass spectrometry, and DFT calculations shed light on the metallic species generated in the rhodium-catalyzed asymmetric [2+2+2] cycloaddition reaction between diynes and isocyanates with the chiral phosphate TRIP. The catalytic mixture comprising [{Rh(cod)Cl}2 ], 1,4-diphenylphosphinobutane (dppb), and Ag(S)-TRIP actually gives rise to two species, both having an effect on the stereoselectivity. One is a rhodium(I) complex in which TRIP is a weakly coordinating counterion, whereas the other is a bimetallic Rh/Ag complex in which TRIP is a strongly coordinating X-type ligand.

Tin-free Alternatives to the Barton-McCombie Deoxygenation of Alcohols to Alkanes Involving Reductive Electron Transfer.

Echoing the recent celebration of the fortieth anniversary of the Barton-McCombie reaction, this review aims to explore another facet of radical processes for deoxygenation of alcohols by considering SET (single electron transfer) reduction of carboxylic ester, thiocarbonate and thiocarbamate derivatives. Various protocols have been developed relying on the use of organic and organometallic SET reagents, electrochemical conditions, photoinduced electron transfer processes and visible-light photoredox catalysis. Applications to the synthesis of molecules of interest provide a glimpse into the scope of these different approaches.

Double-Stereodifferentiation in Rhodium-Catalyzed [2 + 2 + 2] Cycloaddition: Chiral Ligand/Chiral Counterion Matched Pair.

The first enantioselective metal-catalyzed [2 + 2 + 2] cycloaddition involving a double asymmetric induction has been devised. It relies on the use of an in situ generated chiral cationic rhodium(I) catalyst with a matched chiral ligand/chiral counterion pair. Careful optimization of the catalytic system, as well as of the reaction conditions, led to atroposelective [2 + 2 + 2] pyridone cycloadducts with high ee's up to 96%. This strategy outperformed those previously described involving a chiral ligand only or a chiral counterion only.

Silicates as Latent Alkyl Radical Precursors: Visible-Light Photocatalytic Oxidation of Hypervalent Bis-Catecholato Silicon Compounds.

This works introduces hypervalent bis-catecholato silicon compounds as versatile sources of alkyl radicals upon visible-light photocatalysis. Using Ir[(dF(CF3)ppy)2(bpy)](PF6) (dF(CF3)ppy = 2-(2,4-difluorophenyl)-5-trifluoromethylpyridine, bpy = bipyridine) as catalytic photooxidant, a series of alkyl radicals, including highly reactive primary ones can be generated and engaged in various intermolecular homolytic reactions. Based on cyclic voltammetry, Stern-Volmer studies, and supported by calculations, a mechanism involving a single-electron transfer from the silicate to the photoactivated iridium complex has been proposed. This oxidative photocatalyzed process can be efficiently merged with nickel-catalyzed Csp2-Csp3 cross-coupling reactions.