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

Abstract

[¹¹ C]Carbon dioxide ([¹¹ C]CO₂ ) 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]CO₂ 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.

Keywords: 11C-carbonylation; 11C-carboxylation; 11C-labelling; CO-releasing molecules; PET; [11C]CO; [11C]CO2; carbon-11.

Scheme 1

Primary and secondary ¹¹C‐precursors

Scheme 2

Production of ¹¹C‐methylating reagents

Scheme 3

¹¹C‐methylation reactions: (A) nucleophilic substitution on thiols, amine, and alcohols; (B) Stille cross‐coupling with organostannanes; (C) Suzuki cross‐coupling with boron compounds

Scheme 4

Production of [¹¹C]HCN and its use in ¹¹C‐cyanation reactions

Scheme 5

Production of [¹¹C]COCl₂ and subsequent synthesis of [¹¹C]ureas, [¹¹C]carbamates, and [¹¹C]amides

Scheme 6

(A) and (B) [¹¹C]CO₂ fixation using Grignard regents; (C) [¹¹C]CO₂ incorporation into organolithium reagents

Scheme 7

[¹¹C]CO₂ incorporation into benzyl boronic esters

Scheme 8

Direct fixation of [¹¹C]CO₂ yielding [¹¹C]carbamates

Scheme 9

Synthesis of [¹¹C]ureas or [¹¹C]carbamates from [¹¹C]isocyanates

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(A) and (B) Synthesis of asymmetrical and symmetrical [¹¹C]ureas via Mitsunobu reaction. (C) Synthesis of [¹¹C]amides via Mitsunobu reaction

Scheme 11

[¹¹C]CO₂ trapping loop combined with a reaction loop for the Mitsunobu reaction yielding N,N′‐[¹¹C]dibenzylurea presented by Downey et al

Scheme 12

Reduction of [¹¹C]CO₂ to [¹¹C]CO on a metal surface

Scheme 13

Potential ¹¹C‐labelled compounds using [¹¹C]CO

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¹¹C‐Carbonylation reaction mechanism leading [¹¹C]amides and [¹¹C]esters

Scheme 15

Copper scorpionate‐[¹¹C]CO complex and in situ ¹¹C‐carbonylation reaction

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Borocarbonates complexes as CO‐RMs

Scheme 17

COware 2‐chamber system92; COgen92 (first chamber) for ex situ carbonylation reactions (second chamber)

Scheme 18

(A) and (B) Thermolysis of silacarboxylic acids and silacarboxylate esters; (C) base‐catalysed CO elimination of silacarboxylic acids

Scheme 19

1,2‐Brook rearrangement of silacarboxylate derivatives

Scheme 20

(A) Copper complexes coordinate with diboron and boronsilane reagents; (B) coordination with CO₂ and release of CO upon thermal decomposition

Scheme 21

(A) Cu(OAc)₂/DPPBz complex. (B) KOAc catalysing the CO₂ to CO transformation via (MePh₂Si)₂

Scheme 22

[¹¹C]CO₂ to [¹¹C]CO conversion via [¹¹C]silacarboxylates

Scheme 23

Produced ¹¹C‐tracers with the [¹¹C]CO synthesis process via [¹¹C]3 and [¹¹C]4

Scheme 24

[¹¹C]CO₂ to [¹¹C]CO via fluoride‐activated disilanes. (A) Model ¹¹C‐carbonylation reaction; (B) tested ¹¹C‐carbonylation reaction