Recent progress in [¹¹C]carbon dioxide ([¹¹C]CO₂) and [¹¹C]carbon monoxide ([¹¹C]CO) chemistry

Abstract

[ 11 C]Carbon dioxide ([ 11 C]CO 2 ) and [ 11 C]carbon monoxide ([ 11 C]CO) are 2 attractive precursors for labelling the carbonyl position (C═O) in a vast range of functionalised molecules (eg, ureas, amides, and carboxylic acids). The development of radiosynthetic methods to produce functionalised 11 C‐labelled compounds is required to enhance the radiotracers available for positron emission tomography, molecular, and medical imaging applications. Following a brief summary of secondary 11 C‐precursor production and uses, the review focuses on recent progress with direct 11 C‐carboxylation routes with [ 11 C]CO 2 and 11 C‐carbonylation with [ 11 C]CO. Novel approaches to generate [ 11 C]CO using CO‐releasing molecules (CO‐RMs), such as silacarboxylic acids and disilanes, applied to radiochemistry are described and compared with standard [ 11 C]CO production methods. These innovative [ 11 C]CO synthesis strategies represent efficient and reliable [ 11 C]CO production processes, enabling the widespread use of [ 11 C]CO chemistry within the wider radiochemistry community.

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

“…Thes hort half-life of 11 Cr equires ah ighly efficient transformation, which usually occurs on the ultimate or penultimate step to maximize the use of rapidly decaying radioactivity.C omplementary to previous reviews on 11 C, [5,[9][10][11][12][13][14] we highlight some recent developments and breakthroughs in 11 Cc hemistry,w ith an emphasis on commonly used synthons and novel building blocks (Scheme 1). Thes hort half-life of 11 Cr equires ah ighly efficient transformation, which usually occurs on the ultimate or penultimate step to maximize the use of rapidly decaying radioactivity.C omplementary to previous reviews on 11 C, [5,[9][10][11][12][13][14] we highlight some recent developments and breakthroughs in 11 Cc hemistry,w ith an emphasis on commonly used synthons and novel building blocks (Scheme 1).…”

“…Most noteworthy is that these [ 11 C]CO 2 fixation reactions are simple,carried out in one pot, generally require no heating or cooling,a nd are easily automated. [10][11][12][13][14] Pd-mediated cross-coupling reactions between aryl/benzylic/methyl halides and [ 11 C]CO can provide 11 C-labeled carboxylic acids or esters in the presence of hydroxides or alcohols,r espectively (Scheme 5A1). [9,12] Rather than 11 C-carbonylation, Billard and co-workers developed as imple method to achieve 11 C-methylation of amines with [ 11 C]CO 2 under reducing conditions.…”

“…[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. 11 C-Labeled amides could also be obtained from appropriate primary or secondary amines in Pd-mediated crosscoupling reactions between aryl halides and [ 11 C]CO. [10][11][12][13][14] Several representative radiotracers are shown in Scheme 5B1. [41] 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,a nd ketones.…”

“…[40] Similarly,a ryl-(mesityl)iodonium salts could replace aryl halides in the reaction with [ 11 C]CO to generate 11 C-labeled carboxylic acids. Since [ 11 C]CO has limited solubility in organic solvents, efficient trapping of radioactive gas in the reaction system is challenging.S everal novel strategies were developed to address this problem, [11,14] including the use of ahigh-pressure reactor, ac ontinuous-flow microreactor,g as-liquid segmented microfluidics,u se of ap alladium dimer catalyst or NHC ligand, trapping [ 11 C]CO by aPdcatalyst, NHC ligand, borane,o rc opper(I) complex, ax enon gas carrier,a nd improved methods to produce [ 11 C]CO. [46][47][48] Among these methods,arecent example by Skrydstrup,A ntoni, and coworkers highlighted the use of [ 11 C]CO in as imple lowpressure vessel with preactivated aryl-Pd species as stoichiometric reagents to produce highly functionalized radioligands in high RCYs (Scheme 5B2). [42,43] In addition, aP d-mediated transmetalation of boronate precursors could allow 11 C-carbonylation with [ 11 C]CO (Scheme 5A2).…”

New trends and applications in carboxylation for isotope chemistry

“…They used this methodology to produce 11 C‐labeled oxytocin receptor radioligand 9 (Scheme ). Compehensive reviews of 11 C carboxylations have recently been published by Gee and Vasdev …”