Evidence of Two Key Intermediates Contributing to the Selectivity of P450‐Biomimetic Oxidation of Sulfides to Sulfoxides and Sulfones

Abstract

A mild process for the selective oxidation of sulfides is in great demand. Therefore, probing the mechanism underlying the biological oxidation of sulfides under ambient conditions may provide valuable insights for the development of such a reaction. Based on porphyrin models of P450 enzymes, evidence of two key intermediates, Int0 and Int1, in this reaction is provided. Spectroscopic studies indicated the formation of a hydroperoxide-iron(III) species (Int0) upon addition of H(2)O(2). This intermediate proved to be highly selective for sulfoxide production. By contrast, a defined porphyrin oxoiron(IV) cation radical (Int1) directly reacted with sulfoxides, leading selectively to the corresponding sulfones. Interestingly, the available sulfoxides reversibly act as a new axial ligand for Int0 forming a more active species Int0(SO). The amount of Int0 increased in the presence of alkyl, aryl, or aromatic sulfides, while Int1 formed in the absence of these sulfides. Thus, sulfoxides and sulfones would selectively form under conditions that favor the corresponding intermediates, which elucidate the biological oxidation pathway.

Unique Thia‐Baeyer–Villiger‐Type Oxidation of Dibenzothiophene Sulfoxides Derivatives

“…Alternatively, DBTO is flexible and ready to develop many reactions. Thus, our initial interest was on the selective oxidation of DBT to DBTO . In this regard, the mimetic oxidation system using H 2 O 2 or t BuOOH in the presence of porphyrin iron(III) was established.…”

“…Int0 so complex importance in diverting the reaction pathway and leading to the thia ‐Baeyer–Villiger product was emphasized by the designed experiment. UV/Vis spectroscopic detection indicated the formation of Int0 so complex established by our previous research, according to the typical signal at 412 nm of o ‐TCPPFeCl shifting to 392 nm upon irradiation (Figure , left), and PBS was generated. Addition of 0.1 equiv.…”

“…A plausible mechanism is proposed according to the present results (Scheme ). DBT is selectively oxidized to DBTO by t BuOOH in the presence of porphyrin iron(III), which acts as the axial ligand of porphyrin iron(III) to form complex Int0 so based the previous research . Irradiation of Int0 so leads to photo‐induced electron transfer from sulfur atom to anti‐π orbital of S=O, and further delocalized to conjugated tetrapyrrole ring through axial bond to form intermedaite A .…”

“…Thus, our initial interest waso nt he selective oxidation of DBT to DBTO. [9] In this regard, the mimetic oxidation system using H 2 O 2 or tBuOOH in the presence of porphyrin iron(III) was established. At nearn atural conditions, the results found DBT uniquelyc onverted to DBTO.F urther mechanistic study revealed that al ow-valent hydroperoxy porphyrin iron(III) (Int0 so)c omplex wasi nvolved, which provedt ob ehighly selectivef or sulfoxide production.…”

Bacterial Synthesis of Unusual Sulfonamide and Sulfone Antibiotics by Flavoenzyme‐Mediated Sulfur Dioxide Capture

“…[11] However,t hese biosynthetic schemes are not credible for the formation of aromatic sulfonamides or diarylsulfones.…”