Photogenerated α,<i>n</i>‑Didehydrotoluenes from Chlorophenylacetic Acids at Physiological pH

Aromatic diradicals are recognized as promising intermediates for DNA cleavage, but their formation has thus far been limited to the Bergman and Myers–Saito cycloaromatizations. We report here the phototriggered generation of all isomers of the potential DNA-cleaving α,<i>n</i>-didehydrotoluene diradicals at physiological pH, accomplished by the irradiation of chlorophenylacetic acids under mild conditions. The desired diradicals were formed upon photolysis of the chosen aromatic in aqueous phosphate buffer solution (pH = 7.3), with the consecutive elimination of biologically compatible chloride ion and carbon dioxide. Theoretical simulations reveal that the efficient decarboxylation of the primarily generated phenyl cations involves a previously not known diradical structure

From Phenyl Chlorides to α,<i>n</i>‑Didehydrotoluenes via Phenyl Cations. A CPCM–CASMP2 Investigation

Calculations with the complete active space self-consistent field (CASSCF) method were carried out for rationalizing the photochemical generation of the three isomeric didehydrotoluenes (DHTs) from the corresponding (<i>n</i>-chlorobenzyl)­trimethylsilanes. Moreover, the original CASSCF energies were corrected through the introduction of the dynamic electron correlation term (at the MP2 level) and of an appropriate solvent model (CPCM). The work demonstrated the viability of intersystem crossing (conical intersection located) leading to the lowest lying triplet state of the silanes that fragments to give the corresponding triplet phenyl cations. The <i>para</i>- and <i>ortho</i>-isomers desilylate directly from such states of radical/radical cation character and yield the corresponding DHTs in their triplet state. Different from the other isomers, the <i>meta</i>-cation has a radical/radical cation structure in both spin states and thus two potential accesses to the different spin states of the corresponding DHT

Methoxy-Substituted α,<i>n</i>‑Didehydrotoluenes. Photochemical Generation and Polar vs Diradical Reactivity

The photoreactivity of differently substituted (chloromethoxybenzyl)­trimethylsilanes in alcohols and alcohol/water mixtures has been investigated by means of a combined computational and experimental approach. Subsequent elimination of the chloride anion and the trimethylsilyl cation gives the corresponding methoxy-substituted α,<i>n</i>-didehydrotoluenes (α,<i>n</i>-MeO-DHTs). The rate of desilylation is evaluated through the competition with arylation via phenyl cation (ca. 10⁸ s^–1). α,2-MeO- and α,4-MeO-DHTs show a purely radical behavior (H abstraction from the solvent, methanol), while α,3-MeO-DHT shows mainly a ionic chemistry, as when the parent α,3-DHT is thermally generated. This is likely due to triplet–singlet surfaces crossing occurring during desilylation

Homoconjugation and Tautomeric Isomerism in Triptycene-Fused Pyridylbenzimidazoles

The facile, metal-free synthesis and characterization of three new series of triptycene-fused pyridylbenzimidazoles are reported; such compounds possess an imidazole moiety fused within the benzene rings of the trypticene and a pyridine ring installed at position 2 of the imidazole rings. The position of the nitrogen atom of the pyridyl moiety linked to position 2 of the fused benzimidazole scaffold is systematically changed from the ortho to para position. The number of substituted blades bearing the pyridyl-substituted fused benzimidazole scaffolds has been increased from one to three. Such a library of compounds allowed us to evaluate the enhancement of two main effects: tautomeric isomerism and homoconjugation. The characteristic dynamic equilibrium between different isomers induced by prototropic tautomerization was examined by 1H nuclear magnetic resonance spectroscopy. By comparison of the photophysical properties of the new compounds with those of classical planar pyridylbenzimidazoles, the presence of the homoconjugation effect between the different triptycene blades was demonstrated. Fine details of the electronic structure of the new derivatives were unraveled by a computational analysis. The novel compounds can be employed for the construction of intriguing self-assembled supramolecular architectures

Smooth Photocatalyzed Benzylation of Electrophilic Olefins via Decarboxylation of Arylacetic Acids

Arylacetic acids were used as sources of benzyl radicals under tetrabutylammonium decatungstate photocatalyzed conditions for the benzylation of electron-poor olefins. The reaction proceeds smoothly in a mixed aqueous medium (MeCN/H₂O 2/1) in the presence of NaHCO₃, NaClO₄, and an electron transfer agent (biphenyl). The reaction tolerates a wide variety of functional groups on the aromatic ring (whether electron donating or electron withdrawing) and can be extended to heteroaromatic analogues. The olefins have the double role of radical trap and electron acceptor. The present approach can also be extended to arylpropionic acids (including the nonsteroidal anti-inflammatory drugs ibuprofen and flurbiprofen), as well as mandelic acid derivatives

Sugar-Assisted Photogeneration of Didehydrotoluenes from Chlorobenzylphosphonic Acids

Irradiation of the three isomeric chlorobenzylphophonic acids in aqueous buffer led to a pH-dependent photochemistry. Under acidic conditions (pH = 2.5), photocleavage of the Ar–Cl bond occurred and a phenyl cation chemistry resulted. Under basic conditions (pH = 11), a photoinduced release of the chloride anion followed by the detachment of the metaphosphate anion gave α,<i>n</i>-didehydrotoluene diradicals (α,<i>n</i>-DHTs), potential DNA cleaving intermediates. At a physiological pH (pH = 7.2), both a cationic and a diradical reactivity took place depending on the phosphonic acid used. It is noteworthy that the complexation exerted by a monosaccharide (glucose or methylglucopyranoside) present in solution induced an exclusive formation of α,<i>n</i>-DHTs. The mechanistic scenario of the different photoreactivities occurring when changing the pH of the solution and the role of the various intermediates (phenyl cations, diradicals, etc.) in the process was studied by computational analysis

Homoconjugation and Tautomeric Isomerism in Triptycene-Fused Pyridylbenzimidazoles

The facile, metal-free synthesis and characterization of three new series of triptycene-fused pyridylbenzimidazoles are reported; such compounds possess an imidazole moiety fused within the benzene rings of the trypticene and a pyridine ring installed at position 2 of the imidazole rings. The position of the nitrogen atom of the pyridyl moiety linked to position 2 of the fused benzimidazole scaffold is systematically changed from the ortho to para position. The number of substituted blades bearing the pyridyl-substituted fused benzimidazole scaffolds has been increased from one to three. Such a library of compounds allowed us to evaluate the enhancement of two main effects: tautomeric isomerism and homoconjugation. The characteristic dynamic equilibrium between different isomers induced by prototropic tautomerization was examined by 1H nuclear magnetic resonance spectroscopy. By comparison of the photophysical properties of the new compounds with those of classical planar pyridylbenzimidazoles, the presence of the homoconjugation effect between the different triptycene blades was demonstrated. Fine details of the electronic structure of the new derivatives were unraveled by a computational analysis. The novel compounds can be employed for the construction of intriguing self-assembled supramolecular architectures

Decatungstate As Photoredox Catalyst: Benzylation of Electron-Poor Olefins

Excited tetrabutylammonium decatungstate (TBADT), known to activate a variety of compounds via hydrogen atom transfer (HAT), has now been applied as a photoredox catalyst for the effective oxidative cleavage of benzyl silanes and radical benzylation of reducible olefins occurring in isolated yields from poor to excellent

Unraveling the Key Features of the Reactive State of Decatungstate Anion in Hydrogen Atom Transfer (HAT) Photocatalysis

The decatungstate anion [W₁₀O₃₂]^4– is a widely used photocatalyst for promoting hydrogen atom transfer (HAT) reactions. The mechanism implicated in the activation of organic substrates, however, still needs to be clarified and has been claimed to involve an unknown relaxed excited state of triplet multiplicity, tagged <b>wO</b>. A subpicosecond investigation allowed us to follow early events leading to the chemically reactive species. A hot singlet excited state (S₁^HOT) has been individuated through pump–probe experiments, yielding S₁ by ultrafast decay (<1 ps). The reactive species <b>wO</b> arises from S₁ in competition with decay to S₀ (efficiency ca. 0.5) and has been detected spectroscopically by flash photolysis experiments, with peculiar absorption bands in the near-UV (370 nm) and visible (600–800 nm) regions. TD-DFT calculations demonstrated that excitation to S₁ occurs through a ligand to metal charge transfer (LMCT) transition, involving a displacement of electron density from dicoordinated (bridging) oxygen to tungsten atoms. Population of <b>wO</b> ensues and involves a reorganization of the singly occupied orbital centered on oxygen (not tungsten) atoms. As a result, monocoordinated O centers acquire a partial radical character that well explains the known chemistry, essentially hydrogen atom transfer (HAT), and highlights the similarity with nπ* carbonyl triplets. This rationalization may help in devising other photocatalysts able to promote HAT processes from unactivated precursors

Singlet vs Triplet Reactivity of Photogenerated α,<i>n</i>‑Didehydrotoluenes

The reactivity of α,<i>n</i>-didehydrotoluenes (DHTs) in protic media (organic/aqueous mixtures) was explored by means of a combined computational and experimental approach. These intermediates were generated via a photoinduced double elimination process occurring in (chlorobenzyl)­trimethylsilanes and led to the formation of a varied products distribution, depending on the isomer tested. Irradiation of ortho- and para-derivatives resulted, respectively, in the formation of triplet α,2- and α,4-DHTs, whose diradical reactivity led to both radical and polar products. On the other hand, irradiation of the meta-precursor led to the singlet α,3-DHT isomer. The latter showed a marked preference for the formation of polar products and this was rationalized, as supported by computational evidence, via the involvement of a zwitterionic species arising through interaction of the nucleophilic solvent with the benzylic position of the DHT