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

Abstract

Iodonium compounds play a pivotal role in (18) F-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 (18) F-labeled isoquinolines resulting in up to 92 % radiochemical conversion. As proof of concept, a fluorinated isoquinoline alkaloid, (18) F-aspergillitine is prepared in 10 % isolated radiochemical yield from the corresponding phenyl(aspergillitine)iodonium salt.