A General Protocol for Cu-Mediated Fluoro-deamination: Sandmeyer Fluorination of Diverse Aromatic Substrates

Abstract

A Cu(I)-mediated fluoro-deamination method for nucleophilic radiofluorination was devised. The method affords fluorinated aromatic products directly from anilines under both no-carrier added and stoichiometric conditions. Isolated radiochemical yields range from 11% to 81% with high radiochemical purities and a molar activity of 58 MBq/nmol. The reaction conditions were implemented successfully in an automated process for production of ( S )-4[ 18 F]fluorogluthetimide on a radiosynthesis module.

Room-Temperature Copper-Mediated Radiocyanation of Aryldiazonium Salts and Aryl Iodides via Aryl Radical Intermediates

“…Sandmeyer-type reactions involve electron transfer from Cu­(I) complexes to aryl diazonium salts to generate reactive aryl radical intermediates. , The aryl radicals are then captured by the resultant Cu­(II) species in the presence of a nucleophile to afford functionalized arene products (Scheme , bottom). ,− These transformations are known to proceed under mild conditions and with fast reaction rates and a broad substrate scope. While Sandmeyer-type cyanation is well-precedented in the literature, analogous radiocyanation reactions have not been reported to date.…”

Direct synthesis of haloaromatics from nitroarenes via a sequential one-pot Mo-catalyzed reduction/Sandmeyer reaction

“…20 In this field, the Balz–Schiemann reaction 21 is one of the most conventional methods for synthesizing aryl fluorides. 22 This reaction based on the decomposition of aryl diazonium salts under heating in the presence of a fluoride source was demonstrated to be more challenging due to the lower reactivity of the fluoride.…”

Mild, Organo-Catalysed Borono-Deamination as a Key to Late-Stage Pharmaceutical Precursors and 18F-Labelled Radiotracers

“…Without optimization, and with a modified literature procedure ( Figure 2 ) (Detailed procedures are available in the Supplementary Material ) ( Mossine et al, 2020 ), we were able to radiofluorinate compounds [ 18 F] 25- [ 18 F] 28 , which were obtained in radiochemical yields of less than 20%. To optimize radiolabeling conditions ( Table 3 ), we chose conditions from recent publication ( Peréz-García et al, 2021 ) as a starting point for a small study using compound 2 as the substrate. After testing different stoichiometries of copper(I) and copper (II) triflates, one equivalent of tetrakis pyridine copper (II)triflate relative to starting material more than doubled radiochemical conversion (RCC) from 26.2 to 56.2%.…”

“…After testing different stoichiometries of copper(I) and copper (II) triflates, one equivalent of tetrakis pyridine copper (II)triflate relative to starting material more than doubled radiochemical conversion (RCC) from 26.2 to 56.2%. Preference for copper (II) indicates a B-Cu-transmetalation followed by reductive elimination upon nucleophilic attack by fluoride ion as the key mechanism, rather than a redox mechanism which would be more likely for Cu(I) ( Peréz-García et al, 2021 ). N,N-dimethylacetamide was identified as the optimal solvent to bring the RCC to 99% and isolated radiochemical yields (RCY) up to 41% at the end of the process.…”

“…In our efforts to synthesize precursors for the radiosynthesis of the PolyADP-ribose polymerase (PARP) inhibitor [ 18 F]Rucaparib, we devised a deamination strategy to obtain a labelling precursor ( Riss et al, 2012a ; Alluri and Riss, 2018 ; Peréz-García et al, 2021 ). Methods for C-N borylation based on thermal degradation or metal mediated mechanisms with diazonium intermediates have been introduced to exploit the ample variety of accessible nitrogen compounds and their utility as intermediates in synthesis ( Fang et al, 2004 ; Bej et al, 2012 ; Kundu et al, 2012 ; Qiu et al, 2013 ; Chen et al, 2020 ; Shegavi et al, 2020 ; Wang and Shi, 2020 ).…”