Ton Stephanie J, Ravn Anne K, Hoffmann Daniel Vrønning, Day Craig S, Kingston Lee, Elmore Charles S, Skrydstrup Troels
Carbon Dioxide Activation Center (CADIAC), The Interdisciplinary Nanoscience Center (iNANO) and Department of Chemistry, Aarhus University, Gustav Wieds Vej 14, Aarhus 8000, Denmark.
Isotope Chemistry, Early Chemical Development, Pharmaceutical Sciences, R&D, AstraZeneca Pharmaceuticals, Gothenburg 43183, Sweden.
JACS Au. 2023 Feb 13;3(3):756-761. doi: 10.1021/jacsau.2c00708. eCollection 2023 Mar 27.
Herein, we report a strategy for the formation of isotopically labeled carboxylic esters from boronic esters/acids using a readily accessible palladium carboxylate complex as an organometallic source of isotopically labeled functional groups. The reaction allows access to either unlabeled or full C- or C-isotopically labeled carboxylic esters, and the method is characterized by its operational simplicity, mild conditions, and general substrate scope. Our protocol is further extended to a carbon isotope replacement strategy, involving an initial decarbonylative borylation procedure. Such an approach allows access to isotopically labeled compounds directly from the unlabeled pharmaceutical, which can have implications for drug discovery programs.
在此，我们报道了一种利用易于获得的羧酸钯配合物作为同位素标记官能团的有机金属源，从硼酸酯/硼酸形成同位素标记羧酸酯的策略。该反应能够得到未标记的、完全碳-13或碳-14同位素标记的羧酸酯，且该方法具有操作简单、条件温和以及底物范围广泛的特点。我们的方案进一步扩展到碳同位素取代策略，包括初始的脱羰硼化步骤。这种方法能够直接从未标记的药物获得同位素标记的化合物，这可能对药物发现计划具有重要意义。
