Copper(II)-Mediated [¹¹C]Cyanation of Arylboronic Acids and Arylstannanes

Abstract

A copper-mediated method for the transformation of diverse arylboron compounds and arylstannanes to aryl-[C]-nitriles is reported. This method is operationally simple, uses commercially available reagents, and is compatible with a wide variety of substituted aryl- and heteroaryl substrates. This method is applied to the automated synthesis of high specific activity [C]perampanel in 10% nondecay-corrected radiochemical yield (RCY).

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

“…This method was compatible with a broad range of substrates. For example, [ 11 C]perampanel was prepared in 10 % RCY and with 70 GBq μmol −1 molar activity by using an automated radiosynthesis module (Scheme 10 B) …”

“…[68] Arylboron compounds and arylstannanes can also be used as precursors in the Cu-mediated cyanation. [70] [69] In 2018, Scott, Sanford, and co-workers further extended labeling precursors to other arylboron compounds and arylstannanes by using Cu II (OTf) 2 .T his method was compatible with ab road range of substrates.F or example, [ 11 C]perampanel was prepared in 10 %R CY and with 70 GBq mmol À1 molar activity by using an automated radiosynthesis module (Scheme 10 B2).…”

Chemie der Positronenemissionstomographie: Aktuelle Fortschritte bei 11C‐, 18F‐, 13N‐ und 15O‐Markierungsreaktionen

“…Diese Methode war mit einem breiten Spektrum von Substraten kompatibel. Zum Beispiel wurde [ 11 C]Perampanel unter Verwendung eines automatisierten Radiosynthesemoduls mit 10 % RCY und 70 GBq μmol −1 molarer Aktivität hergestellt (Schema 10 B) …”

[11C]HCN Radiochemistry: Recent Progress and Future Perspectives

“…30,[15] In recent years, one of the most elegant development on Pd-mediated [ 11 C]cyanoarene formation is the instantaneous room temperature 11 C-cyanation using biaryl phosphine Pd(0) complexes, [66] the direct labeling of unprotected peptides with [ 11 C]cyano group was achieved through Pd-mediated sequential cross-coupling reactions [67] and the Pd-mediated arylboron [ 11 C] cyanation. [68] In regarding recent progress of Cu-mediated aromatic 11 C-cyanation, either Cu(I) or Cu(II) could be used for the aromatic 11 C-cyanation of arylboronic acids [6,69] and arylstannanes 30 in a dual solvent system (a polar aprotic solvent (DMF or DMA) and H 2 O). The proposed reaction mechanism showed Cu(I) and Cu(II) both effective in mediating the 11 C-cyanation of arylboronic acids.…”

“…Essential to the reaction, Cs 2 CO 3 was a better base than NaOH in promoting the model reaction while K 2 CO 3 and Et 3 N were both ineffective. Furthermore, the presence of water didn't affect the RCY, in turn, it provided convenience for using the aqueous base solution trapped with [ 11 C]HCN directly without the drying step that traditionally performed for the 11 In 2018, researchers from the University of Michigan reported a successful development of 11 C-cyanation chemistry from the extension of their Cu(II)-mediated 18 F-fluorination method, [69] ]aryl/heteroaryl nitriles were synthesized using this operation-friendly method, which also illustrated the wide functional group tolerance. Finally, the practical applicability of this method was demonstrated by successfully producing 11 C-labeled perampanel (FDA-approved drug for epilepsy), Figure 34.…”