Sugar-Assisted Photogeneration of Didehydrotoluenes from Chlorobenzylphosphonic Acids

Abstract

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,n-didehydrotoluene diradicals (α,n-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,n-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.

Diradicals Photogeneration from Chloroaryl‐Substituted Carboxylic Acids

“…Moreover, the stability of phenyl cations strongly increased when enhancing the proticity of the medium [30] . The presence of a modest amount of glucose (0.05 M, a good hydrogen donor) slightly increased the amount of photodechlorinated 2 , but did not affect carbon dioxide loss (Table 1), as previously demonstrated in related cases [9] …”

“…The irradiation in this aqueous‐alcoholic solution gave a complex mixture, with an overall predominance of carboxylate/chlorine‐free products, being 5 the compound formed with the highest yield (entry 8). Irradiation of 1 a in neat PBS gave roughly an equimolar amount of chlorine‐free and carboxylate/chlorine‐free derivatives ( 4 and 7 as the major products, respectively, entry 9) that was slightly affected by the presence of 0.05 M glucose (entry 10) [9] . Shifting the irradiation wavelength to 310 nm led to the same products (entry 11), while the addition of t butyl acrylate (2 equiv.)…”

“…In fact, our group found that the very same intermediates can be formed, even in aqueous phosphate buffer solution (PBS, pH=7.3), by a one‐photon double‐elimination reaction starting from an aromatic derivative. Notably, this approach could be extended to the photogeneration of all α, n ‐DHT ( n =2–4) isomers (Scheme 1a) [8,9] . This process is based on the photoheterolytic elimination (via a C(sp 2 )‐X bond cleavage) of a nucleofugal group (usually, the chloride anion) from the aromatic ring followed by the detachment of a stable electrofugal group (EG, such as the trimethylsilyl cation, [8a–c] carbon dioxide [8d] or a metaphosphate anion [9] ) from the benzylic position of the resulting phenyl cation.…”

“…Notably, this approach could be extended to the photogeneration of all α, n ‐DHT ( n =2–4) isomers (Scheme 1a) [8,9] . This process is based on the photoheterolytic elimination (via a C(sp 2 )‐X bond cleavage) of a nucleofugal group (usually, the chloride anion) from the aromatic ring followed by the detachment of a stable electrofugal group (EG, such as the trimethylsilyl cation, [8a–c] carbon dioxide [8d] or a metaphosphate anion [9] ) from the benzylic position of the resulting phenyl cation. Intriguingly, a different reaction course has been identified, depending on the actual electrofugal group.…”

Aryl–Cl vs heteroatom–Si bond cleavage on the route to the photochemical generation of σ,π-heterodiradicals

“…The reaction is effective when starting from both the parent [36][37][38][39] and methoxy substituted [40] (chlorobenzyl) trimethylsilane isomers (LG = Cl, EG = Me 3 Si). Electrofugal groups able to ameliorate the water solubility of α,n-DHT precursors have been likewise designed and efficiently tested in chlorophenylacetic acids (EG = COOH) [41] and chlorobenzylphosphonic acids (EG = P(O)(OH) 2 )) [42]. An alternative generation of α,n-DHTs involves the photolysis of (trimethylsilylmethyl)aryl sulfonates and phosphates (LG = OSO 2 R, OP(O)(OEt) 2 ) [43].…”