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

Article abstract of DOI:10.1002/anie.201606381

Iodonium compounds play a pivotal role in¹⁸F-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 of¹⁸F-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.