Site-selective ¹⁸F fluorination of unactivated C–H bonds mediated by a manganese porphyrin

Abstract

A direct aliphatic C–H 18F labeling method using [18F]fluoride ion at inaccessible and unreactive sites is reported.

Site‐Selective, Late‐Stage C−H 18F‐Fluorination on Unprotected Peptides for Positron Emission Tomography Imaging

“…To the best of our knowledge the only direct C À H 18 Ffluorination of an unprotected peptide was carried out on ac yclic RGD peptide using [ 18 F]AcOF,a nd the extreme reactivity of this reagent resulted in am ixture of fluorinated products. [19] Here we show that ar ange of unprotected and unaltered peptides can be directly labelled with 18 Fu sing an inexpensive photocatalyst and apparatus under mild aqueous reaction conditions (Figure 1, inset).…”

“…[8,17] Thus,anideal scenario would involve the direct and selective 18 F-fluorination of as ingle CÀHb ond in an ative peptide under rapid, mild, and aqueous conditions. While important contributions towards the selective 18 F-and 19 F-fluorination of CÀHbonds in peptides have been made, [18] amine and carboxylic acid protecting groups are mandatory. To the best of our knowledge the only direct C À H 18 Ffluorination of an unprotected peptide was carried out on ac yclic RGD peptide using [ 18 F]AcOF,a nd the extreme reactivity of this reagent resulted in am ixture of fluorinated products.…”

Site‐Specific Deoxyfluorination of Small Peptides with [18F]Fluoride

“…[14] Direct CÀHfluorination of peptides has been shown by the Britton group,however,through the use of [ 18 F]fluorine gas,w hich is more difficult to make and handle than [ 18 F]fluoride. [14] Direct CÀHfluorination of peptides has been shown by the Britton group,however,through the use of [ 18 F]fluorine gas,w hich is more difficult to make and handle than [ 18 F]fluoride.…”

Chemistry for Positron Emission Tomography: Recent Advances in 11C‐, 18F‐, 13N‐, and 15O‐Labeling Reactions

“…18 Aliphatic nucleophilic 18 F-fluorination is usually performed in basic conditions at high temperature;h owever, these conditions may not be compatible with highly functionalized molecules and result in the formation of undesired side products.T ransition-metal-mediated aliphatic 18 F-fluorination may,t hus,p rovide an alternative approach to generate alkyl- 18 Fb onds under mild conditions.I n2 011, Gouverneur, Brown, and co-workers reported the Pd-catalyzed fluorination of highly active allyl p-nitrobenzoates with TBAF at room temperature. [107] Theu se of the more reactive Mn-porphyrin complex Mn(TPFPP)OTs was essential to enable efficient transformation. In the same year, Nguyen and co-workers developed an Ir-catalyzed allylic fluorination of trichloroacetimidates.…”