In recent decades, the traceless nature of visible photons has been exploited for the development of efficient synthetic strategies for the photoconversion of colourless compounds, namely, photocatalysis, chromophore activation, and the formation of an electron donor/acceptor (EDA) complex. However, the use of photoreactive coloured organic compounds is the optimal strategy to boost visible photons as ideal reagents in synthetic protocols. In view of such premises, the present review aims to provide its readership with a collection of recent photochemical strategies facilitated via direct light absorption by coloured molecules. The protocols have been classified and presented according to the nature of the intermediate/excited state achieved during the transformation.
In contemporary drug discovery, enhancing the sp3-hybridized character of molecular structures is paramount, necessitating innovative synthetic methods. Herein, we introduce a deoxygenative cross-electrophile coupling technique that pairs easily accessible carboxylic acid-derived redox-active esters with aldehyde sulfonyl hydrazones, employing Eosin Y as an organophotocatalyst under visible light irradiation. This approach serves as a versatile, metal-free C(sp3)-C(sp3) cross-coupling platform. We demonstrate its synthetic value as a safer, broadly applicable C1 homologation of carboxylic acids, offering an alternative to the traditional Arndt-Eistert reaction. Additionally, our method provides direct access to cyclic and acyclic ß-arylethylamines using diverse aldehyde-derived sulfonyl hydrazones. Notably, the methodology proves to be compatible with the late-stage functionalization of peptides on solid-phase, streamlining the modification of intricate peptides without the need for exhaustive de-novo synthesis.
Activated by visible light, arylazo sulfones can serve as multifaceted reactants and are employed in diazenylation, sulfonylation, and arylation reactions under (photo)catalyst-free conditions. Such versatile reactivity enabled us to develop an operationally simple, regioselective, and tunable difunctionalization of styrenes with arylazo sulfones to produce α-sulfonyl arylhydrazones and 1,2-alkoxyarylated products in moderate to excellent yields. Furthermore, such difunctionalized products have been exploited as key building blocks for the synthesis of various heterocycles.
Single-atom catalysis is a field of paramount importance in contemporary science due to its exceptional ability to combine the domains of homogeneous and heterogeneous catalysis. Iron and manganese metalloenzymes are known to be effective in CâH oxidation reactions in nature, inspiring scientists to mimic their active sites in artificial catalytic systems. Herein, a simple and versatile cation exchange method is successfully employed to stabilize low-cost iron and manganese single-atoms in poly(heptazine imides) (PHI). The resulting materials are employed as photocatalysts for toluene oxidation, demonstrating remarkable selectivity toward benzaldehyde. The protocol is then extended to the selective oxidation of different substrates, including (substituted) alkylaromatics, benzyl alcohols, and sulfides. Detailed mechanistic investigations revealed that iron- and manganese-containing photocatalysts work through a similar mechanism via the formation of high-valent MâO species. Operando X-ray absorption spectroscopy (XAS) is employed to confirm the formation of high-valent iron- and manganese-oxo species, typically found in metalloenzymes involved in highly selective CâH oxidations.
Arylazo sulfonates (Ar-N=N-SO3 Na) have been found to undergo photografting on gold surface through both Au-Nsp2 - and Au-Csp2 - bond formation. The functionalized materials have been fully characterized by infrared reflection absorption spectroscopy (IRRAS), Raman, XPS, DFT calculations and UV-Vis absorption spectroscopy. These methods permit to evidence aromatic substituents (IRRAS), the Au-N=N signature (Raman and XPS spectroscopy), and the bond dissociation energy values of the two linkages (DFT calculation). The grafting proceeds through two competitive paths, namely a stepwise reaction involving an aryl radical (for the formation of the Au-Ar bonds) and a concerted reaction on the surface of gold (for Au-N=N-Ar bond formation). The occurrence of an aryl radical upon irradiation has been fully evidenced by EPR spectroscopy. Finally, E/Z photoisomerisation of the N=N bonds present on prepared few layer films has been observed by means of UV-Vis absorption spectroscopy.
A set of arylazo sulfones, known to undergo N-S bond cleavage upon light exposure, has been synthesized, and their activity in the dark and upon irradiation towards DNA has been investigated. Their interaction with calf-thymus DNA has been examined, and the significant affinity observed (most probably due to DNA intercalation) was analyzed by means of molecular docking "in silico" calculations that pointed out polar contacts, mainly via the sulfonyl moiety. Incubation with plasmid pBluescript KS II revealed DNA cleavage that has been studied over time and concentration. UV-A irradiation considerably improved DNA damage for most of the compounds, whereas under visible light the effect was slightly lower. Moving to in vitro experiments, irradiation was found to slightly enhance the death of the cells in the majority of the compounds. Naphthylazosulfone 1 showed photo-disruptive effect under UV-A irradiation (IC50 ~13 µΜ) followed by derivatives 14 and 17 (IC50 ~100 µΜ). Those compounds were irradiated in the presence of two non-cancer cell lines and were found equally toxic only upon irradiation and not in the dark. The temporal and spatial control of light, therefore, might provide a chance for these novel scaffolds to be useful for the development of phototoxic pharmaceuticals.
Melanoma , Sulfones , Humans , Sulfones/pharmacology , Molecular Docking Simulation , DNA/chemistry , Ultraviolet Rays , DNA Cleavage
A versatile, inexpensive and sustainable protocol for the preparation of valuable bis-indolyl methanes via visible light-mediated, metal-free Friedel-Crafts arylation has been developed. The procedure, that exploits the peculiar behavior of arylazo sulfones as non-ionic photoacid generators (PAGs), was applied to the conversion of a variety of aliphatic and aromatic aldehydes into diarylmethanes in good to highly satisfactory yields, employing a low-catalyst loading (0.5 mol%) and irradiation at 456 nm.
The protection of a carbonyl is a standard procedure to mask the reactivity of this group towards nucleophiles and reductants. The present work pointed out the potentialities of arylazo sulfones as non-ionic photoacid generators (PAGs) to promote the efficient conversion of aldehydes and ketones into acetals, ketals, and 1,3-oxazolidines upon visible-light irradiation. This approach employed mild conditions and exhibited an easy scalability and a broad scope (80 examples included).
The selective visible-light-driven generation of a weak acid (sulfinic acid, in nitrogen-purged solutions) or a strong acid (sulfonic acid, in oxygen-purged solutions) by using shelf-stable arylazo sulfones was developed. These sulfones were then used for the green, smooth, and efficient photochemical catalytic protection of several (substituted) alcohols (and phenols) as tetrahydropyranyl ethers or acetals.
There is an urgent need to develop uncharged radical precursors to be activated under mild photocatalyzed conditions. 2-Substituted-1,3-oxazolidines (E ox < 1.3 V vs SCE, smoothly prepared from the corresponding aldehydes) have been herein employed for the successful release of tertiary, α-oxy, and α-amido radicals under photo-organo redox catalysis. The reaction relies on the unprecedented C-C cleavage occurring from the radical cation of these heterocyclic derivatives. Such a protocol is applied to the visible-light-driven conjugate radical addition onto Michael acceptors and vinyl (hetero)arenes under mild metal-free conditions.
The valorization of alkenoic acids possibly deriving from biomass (fumaric and citraconic acids) was carried out through conversion in important building blocks, such as γ-keto acids and succinic acid derivatives. The functionalization was carried out by addition onto the C=C double bond of radicals generated under photocatalyzed conditions from suitable hydrogen donors (mainly aldehydes) and by adopting a decatungstate salt as the photocatalyst. Syntheses were performed under batch (in a glass vessel) and flow (by using 3D-printed reactors) conditions. The design of the latter reactors allowed for an improved yield and productivity.
Aldehydes , Hydrogen , Aldehydes/chemistry , Biomass , Printing, Three-Dimensional
The preparation of symmetrical (hetero)biaryls via arylazo sulfones has been successfully carried out upon visible light irradiation in the presence of PPh3AuCl as the catalyst. The present protocol led to the efficient synthesis of a wide range of target compounds in an organic-aqueous solvent under photocatalyst-free conditions.
With the aim of generating new, thermally inaccessible diradicals, potentially able to induce a double-strand DNA cleavage, the photochemistry of a set of chloroaryl-substituted carboxylic acids in polar media was investigated. The photoheterolytic cleavage of the Ar-Cl bond occurred in each case to form the corresponding triplet phenyl cations. Under basic conditions, the photorelease of the chloride anion was accompanied by an intramolecular electron-transfer from the carboxylate group to the aromatic radical cationic site to give a diradical species. This latter intermediate could then undergo CO2 loss in a structure-dependent fashion, according to the stability of the resulting diradical, or abstract a hydrogen atom from the medium. In aqueous environment at physiological pH (pH=7.3), both a phenyl cation and a diradical chemistry was observed. The mechanistic scenario and the role of the various intermediates (aryl cations and diradicals) involved in the process was supported by computational analysis.
Carboxylic Acids , Water , Cations/chemistry , DNA , Photochemistry
Direct photocatalyzed hydrogen atom transfer (d-HAT) can be considered a method of choice for the elaboration of aliphatic C-H bonds. In this manifold, a photocatalyst (PCHAT) exploits the energy of a photon to trigger the homolytic cleavage of such bonds in organic compounds. Selective C-H bond elaboration may be achieved by a judicious choice of the hydrogen abstractor (key parameters are the electronic character and the molecular structure), as well as reaction additives. Different are the classes of PCsHAT available, including aromatic ketones, xanthene dyes (Eosin Y), polyoxometalates, uranyl salts, a metal-oxo porphyrin and a tris(amino)cyclopropenium radical dication. The processes (mainly C-C bond formation) are in most cases carried out under mild conditions with the help of visible light. The aim of this review is to offer a comprehensive survey of the synthetic applications of photocatalyzed d-HAT.
Hydrogen , Porphyrins , Hydrogen/chemistry , Ketones , Molecular Structure , Porphyrins/chemistry
Selenium-containing organic molecules have recently found a plethora of applications, ranging from organic synthesis to pharmacology and material sciences. In view of these concepts, the development of mild, efficient, and general protocols for the formation of C-Se bonds is desirable, and light induced approaches are appealing ways. The aim of this Review is to provide the reader with the most recent examples of light promoted selenylation processes.
The photochemistry of aryl chlorides having a X-SiMe3 group (X = O, NR, S, SiMe2) tethered to the aromatic ring has been investigated in detail, with the aim to generate valuable Ï,π-heterodiradicals. Two competitive pathways arising from the excited triplet state of the aromatics have been observed, namely heterolysis of the aryl-chlorine bond and homolysis of the X-silicon bond. The former path is found in chlorinated phenols and anilines, whereas the latter is exclusive in the case of silylated thiophenols and aryl silanes. A combined experimental/computational approach was pursued to explain such a photochemical behavior.Graphical abstract.
Chlorides , Chlorides/chemistry , Photochemistry
The photochemical behaviour of selected aryl sulfonates and phosphates (ArOX) in polar and nonpolar media has been investigated by laser flash photolysis (LFP) experiments. Two main pathways have been identified, namely the photohomolysis of the ArO-X bond or the photoheterolysis of the Ar-OX bond depending on the nature of the leaving group (OX) and on the nature of the substituents on the aromatic ring. In nonpolar solvents the esters are quite photostable due to an efficient triplet deactivation. In polar solvents, the homolytic fragmentation of the ArO-S bond from the exited singlets was found in aryl sulfonates bearing moderately electron-donating groups as well as electron-withdrawing groups. In electron-rich aryl phosphates and sulfonates photoheterolysis of the Ar-OP/Ar-OS bond took place as the exclusive pathway.
A visible-light-driven protocol for the synthesis of aryl trifluoromethyl thioethers under photocatalyst- and metal-free conditions has been pursued. The procedure exploits the peculiar properties of arylazo sulfones (having electron-rich or electron-poor substituents on the (hetero)aromatic ring) as photochemical precursors of aryl radicals and S-trifluoromethyl arylsulfonothioates as easy-to-handle trifluoromethylthiolating agents.
The synthesis of α-arylketones and α-arylazo esters has been achieved in mixed organic-aqueous media under photocatalyst- and metal-free conditions via visible light activation of arylazo sulfones in the presence of enol silyl ethers and ketene silyl acetals, respectively. The process took place efficiently and exhibits an excellent tolerance for a broad variety of functional groups.
