Platform for Multiple Isotope Labeling via Carbon–Sulfur Bond Exchange

Abstract

In this work, we explore a nickel-catalyzed reversible carbon−sulfur (C−S) bond activation strategy to achieve selective sulfur isotope exchange. Isotopes are at the foundation of applications in life science, such as nuclear imaging, and are essential tools for the determination of pharmacokinetic and dynamic profiles of new pharmaceuticals. However, the insertion of an isotope into an organic molecule remains challenging, and current technologies are element-specific. Despite the ubiquitous presence of sulfur in many biologically active molecules, sulfur isotope labeling is an underexplored field, and sulfur isotope exchange has been overlooked. This approach enables us to move beyond standardized element-specific procedures and was applied to multiple isotopes, including deuterium, carbon-13, sulfur-34, and radioactive carbon-14. These results provide a unique platform for multiple isotope labeling and are compatible with a wide range of substrates, including pharmaceuticals. In addition, this technology proved its potential as an isotopic encryption device for organic molecules.

A Bioinspired C–O/C–X σ-Bond Metathesis

“…1b). [15][16][17][18][19][20] Other strategies often require C-X bonds to be the same type, [21][22][23] which limits its application due to the availability of certain reaction partners. Furthermore, ring-closing σbond metathesis reactions were only reported for two C-O bonds (Fig.…”

Heterogeneously catalyzed thioether metathesis by a supported Au–Pd alloy nanoparticle design based on Pd ensemble control

“…Thus, thiols and lithium bis(trimethylsilyl)amide are required for their reaction systems: indirect C–S/C–S cross-metathesis via C–S/S–H metathesis between diaryl thioethers and thiols ( Scheme 1b ). 5 Quite recently, Audisio et al reported Ni-catalyzed direct C–S/C–S cross-metathesis of various thioethers for isotope labelling without using thiols and bases; 6 however, C–S bond metathesis of diaryl thioethers was not demonstrated. On the other hand, recently, we achieved the first example of direct C–S bond metathesis of diaryl thioethers using only Pd acetate and tricyclohexylphosphine (PCy 3 ) as catalyst precursors.…”

Combining Umpolung and Carbon Isotope Exchange Strategies for Accessing Isotopically Labeled α-Keto Acids

“…Traditional early stage methods for introducing diverse isotopes often prove time-consuming and resource-intensive, encompassing multiple synthesis steps, harsh conditions, and expensive materials, presenting a significant challenge. However, recent advancements in late-stage approaches, − particularly isotope exchange reactions involving hydrogen, − carbon, − fluorine, nitrogen, − and sulfur, now allow for the direct labeling of the desired compound in a single step, effectively addressing challenges inherent in traditional methodologies.…”