Efficient Pathway for the Preparation of Aryl(isoquinoline)iodonium(III) Salts and Synthesis of Radiofluorinated Isoquinolines

Abstract

AbstractIodonium compounds play a pivotal role in 18F‐fluorination of radiopharmaceuticals containing non‐activated arenes. However, preparation of these species is limited to oxidation conditions or exchange with organometallics that are prepared from aryl halides. Herein we describe a novel “one‐pot” process to assemble aryl(isoquinoline)iodonium salts in 40–94 % yields from mesoionic carbene silver complex and Aryl‐I‐Py2(OTf)2. The method is general, practical, and compatible with well‐functionalized molecules as well as useful for the preparation of a wide range of 18F‐labeled isoquinolines resulting in up to 92 % radiochemical conversion. As proof of concept, a fluorinated isoquinoline alkaloid, 18F‐aspergillitine is prepared in 10 % isolated radiochemical yield from the corresponding phenyl(aspergillitine)iodonium salt.