Late‐Stage Phenylation From [ ¹³ C ₆ ] and [ ² H ₅ ]Benzene: A Versatile Tool for Stable Isotope Labeled MS Standards

We explored aryl thianthrenation as a tool for directly incorporating multiple isotopes into molecular scaffolds starting from full isotopically labeled benzene. Stable isotope‐labeled (SIL) molecules are indispensable tools for investigating chemical and biological mechanisms and quantifying metabolites. However, the late‐stage incorporation of isotopically labeled benzene remains challenging and under‐investigated. This challenge stems from the direct functionalization of non‐substituted benzene, which remains a difficult task. The approach described in this work is based on sulfonium salts used as a source of [ 13 C 6 ] and [ 2 H 5 ]benzene under palladium catalysis conditions. This approach demonstrates its efficiency in C─C and C─S bond formation with different substrates. Additionally, this methodology was employed for the synthesis of poly‐substituted [ 13 C 6 ]benzene derivatives.