Spirocyclic Iodonium Ylides for Fluorine‐18 Radiolabeling of Non‐Activated Arenes: From Concept to Clinical Research

Abstract

Positron emission tomography (PET) is a powerful imaging tool for drug discovery, clinical diagnosis, and monitoring of disease progression. Fluorine‐18 is the most common radionuclide used for PET, but advances in radiotracer development have been limited by the historical lack of methodologies and precursors amenable to radiolabeling with fluorine‐18. Radiolabeling of electron‐rich (hetero)aromatic rings remains a long‐standing challenge in the production of PET radiopharmaceuticals. In this personal account, we discuss the history of spirocyclic iodonium ylide precursors, from inception to applications in clinical research, for the incorporation of fluorine‐18 into complex non‐activated (hetero)aromatic rings.

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

“…Iodonium ylides are a subset of hypervalent iodine (HVI) reagents that were first reported in 1957 by Neiland [ 1 ]. These have since been investigated under a variety of thermal, photochemical, radical and transition metal-catalyzed conditions [ 2 ], and they have been successfully employed in numerous reactions such as metallocarbene chemistry [ 3 – 8 ], cycloadditions [ 9 – 14 ], and radiofluorinations [ 15 – 18 ]. As with most HVI reagents, reactions of iodonium ylides are often described using terminologies (e.g., ylide transfer, coupling or reductive elimination) more commonly associated with transition metal-mediated chemistry; however, halogen- or σ-hole bonding has recently emerged as a credible explanation for the diverse reactivity that iodonium ylides undergo.…”