Late-stage [¹⁸F]fluorination: new solutions to old problems

Abstract

The last 2–3 years have seen numerous relationships develop between organometallic chemists, fluorine chemists and PET Centers around the world. These collaborations have led to the development of many new strategies for the late-stage introduction of fluorine-18 into complex bioactive molecules. In this perspective we highlight recent developments and key milestones since 2011.

Diaryliodonium Salts in Organic Syntheses: A Useful Compound Class for Novel Arylation Strategies

“…In 2011, Ackermann's group reported the C3-arylation of indoles 47 (43) and pyrroles in the absence of metal catalyst and additives using diaryliodonium salts in dimethylformamide at high temperature ( Scheme 20). N-protected and free indole derivatives were also suitable substrates for the transformation, and easily converted to the desired products (44).…”

“…This topic was reviewed earlier by Zhdankin, 42 and others. 43,44 Similarly arylation of iodide is also possible. 45 …”

Catalytic Nucleophilic Fluorination of Secondary and Tertiary Propargylic Electrophiles with a Copper–N‐Heterocyclic Carbene Complex

“…Compounds containing CÀFb onds are of vital importance to the pharmaceutical [1] and agrochemical industries, [2] positron-emission tomography, [3] and materials science.…”

“…Our protocol involves the use of aC u(NHC) complex as the catalyst and is suitable for the preparation of secondary and tertiary propargylic fluorides without the formation of isomeric fluoroallenes. Preliminary mechanistic investigations suggest that fluorination proceeds via copper acetylides and that cationic species are involved.Compounds containing CÀFb onds are of vital importance to the pharmaceutical [1] and agrochemical industries, [2] positron-emission tomography, [3] and materials science.[4] Catalytic fluorination has been the focus of many investigations, [5] in which either electrophilic or nucleophilic fluorine sources have been used.[6] Despite these significant advances,catalytic nucleophilic fluorination remains ac hallenge,p articularly at C(sp 3 )c enters. [7] Theh igh charge density of unsolvated fluoride anions imparts high nucleophilicity but also strong basicity, [8] thus enabling elimination pathways to alkenes.…”

“…Compounds containing CÀFb onds are of vital importance to the pharmaceutical [1] and agrochemical industries, [2] positron-emission tomography, [3] and materials science. [4] Catalytic fluorination has been the focus of many investigations, [5] in which either electrophilic or nucleophilic fluorine sources have been used.…”