²¹¹At and ¹²⁵I‐Labeling of (Hetero)Aryliodonium Ylides: Astatine Wins Again

Abstract

Despite the growing interest in radioiodine and ²¹¹ At-labeled radiopharmaceuticals, the search for radiolabeling reactions has been somewhat neglected, resulting in a limited number of available radiosynthetic strategies. Herein we report a comparative study of nucleophilic ¹²⁵ I and ²¹¹ At-labeling of aryliodonium ylides. Whereas radioiodination efficiency was low, ²¹¹ At-labeling performed efficiently on a broad scope of precursors. The most activated aryliodonium ylides led rapidly to quantitative reactions at room temperature in acetonitrile. For deactivated precursors, heating up to 90 °C in glyme and addition of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) as radical scavenger appeared essential to avoid precursor degradation and to achieve high radiochemical yields and molar activity. The approach was applied successfully to the preparation of 4-[²¹¹ At]astatophenylalanine (4-APA), an amino acid derivative increasingly studied as radiotherapeutic drug for cancers. This validated aryliodonium ylides as a valuable tool for nucleophilic ²¹¹ At-labeling and will complement the short but now growing list of available astatination reactions.