Reaction of ¹¹C‐benzoyl chlorides with metalloid reagents: ¹¹C‐labeling of benzyl alcohols, benzaldehydes, and phenyl ketones from [¹¹C]CO

Abstract

In this article, we describe the carbon-11 ( C, t = 20.4 minutes) labeling of benzyl alcohols, benzaldehydes, and ketones using an efficient 2-step synthesis in which C-carbon monoxide is used in an initial palladium-mediated reaction to produce C-benzoyl chloride as a key intermediate. In the second step, the obtained C-benzoyl chloride is further treated with a metalloid reagent to furnish the final C-labeled product. Benzyl alcohols were obtained in moderated to high non-isolated radiochemical yields (RCY, 35%-90%) with lithium aluminum hydride or lithium aluminum deuteride as metalloid reagent. Changing the metalloid reagent to either tributyltin hydride or sodium borohydride, allowed for the reliable syntheses of C-benzaldehydes in RCYs ranging from 58% to 95%. Finally, sodium tetraphenylborate were utilized to obtain C-phenyl ketones in high RCYs (77%-95%). The developed method provides a new and efficient route to 3 different classes of compounds starting from aryl iodides or aryl bromides.

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

“…[ 11 C]CO is an established building block for the synthesis of 11 C-carbonyl-labeled carboxylic acids,e sters,a mides, ketones,and aldehydes by transition-metal-mediated carbonylation reactions. [42,43] In addition, aP d-mediated transmetalation of boronate precursors could allow 11 C-carbonylation with [ 11 C]CO (Scheme 5A2). [12,[37][38][39] Fore xample,[ 11 C]eprosartan was synthesized in 54 %R CY by using the corresponding aryl iodide and [ 11 C]CO in the presence of Pd(PPh 3 ) 4 and Bu 4 NOH.…”

“…Similarly, aryl(mesityl)iodonium salts could replace aryl halides in the reaction with [ 11 C]CO to generate 11 C‐labeled carboxylic acids . Aryl halides could also be converted into 11 C‐labeled arylformyl chlorides in situ in the presence of Bu 4 NCl, then transformed into 11 C‐labeled amides, esters, acids, aldehydes, alcohols, and ketones . In addition, a Pd‐mediated transmetalation of boronate precursors could allow 11 C‐carbonylation with [ 11 C]CO (Scheme 5 A).…”

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

“…Auf ähnlichem Wege konnten Aryl(mesityl)iodoniumsalze die Arylhalogenide ersetzen, damit bei der Reaktion mit [ 11 C]CO die 11 C‐markierten Carbonsäuren erzeugt werden konnten . Die Arylhalogenide konnten in Gegenwart von Bu 4 NCl auch in situ in 11 C‐markierte Arylformylchloride umgewandelt und dann in 11 C‐markierte Amide, Ester, Säuren, Aldehyde, Alkohole und Ketone überführt werden . Außerdem konnte mit Boronat‐Vorstufen über eine Pd‐vermittelte Transmetallierung eine 11 C‐Carbonylierung mit [ 11 C]CO realisiert werden (Schema 5 A).…”

[11C]Carbon monoxide: advances in production and application to PET radiotracer development over the past 15 years

“…This methodology has been successfully extended to the synthesis of [ 11 C]benzyl alcohols, [ 11 C]benzaldehydes, and [ 11 C]phenyl ketones (Fig. 12, b) (Roslin et al 2018) and is an attractive alternative to a former method for accessing [ 11 C]aryl acid chlorides based on the 11 C-carboxylation of Grignard reagents (Pike et al 1982; Krasikova et al 2009).

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