Palladium‐Mediated [¹¹C]Carbonylation at Atmospheric Pressure: A General Method Using Xantphos as Supporting Ligand

Abstract

The palladium‐catalyzed [11C]carbonylation of aryl halides and triflates was achieved at atmospheric pressure by employing xantphos as the supporting ligand. Aryl halides were converted into their corresponding [11C]amides in good to excellent yields. The conditions were also successfully employed in the radiolabeling of an [11C]ester, a [11C]carboxylic acid, an [11C]aldehyde, and a [11C]ketone.

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

“…This method is one of three primary methods to access 11 C-labeled amides,inaddition to [ 11 C]CO 2 (by acylation and aminolysis) and [ 11 C]CN (by controlled hydrolysis) methods. [51] Furthermore, Suzuki-type reactions were also capable of providing 11 Ccarbonyl-labeled ketones (Scheme 6B). [49] Thes ame authors also applied this strategy in the N-11 C-acetylation of peptides with [ 11 C]CO and bisphosphine-ligated Pd complexes (Scheme 5B3).…”

Synthesis of ([11C]carbonyl)raclopride and a comparison with ([11C]methyl)raclopride in a monkey PET study

“…The trapping and incorporation of 11 CO was carried out at ambient pressure following a protocol published previously [26]. [ 11 C]Carbonyl labelled raclopride (3) was obtained in a reproducible radiochemical yield (RCY) of 50±5% (calculated from the total radioactivity transferred into the reaction vial) and 95% radiochemical purity (RCP) using the present conditions.…”

Efficient Synthesis of 11C‐Acrylesters, 11C‐Acrylamides and Their Application in Michael Addition Reactions for PET Tracer Development

“…To investigate the radiosynthesis of other functionalized 11 Cacrylesters and to be able to obtain 11 C-acrylamides, the focus shifted to Pd-catalyzed carbonylation reactions with [ 11 C]CO. To be able to perform these reactions, first, the reduction of [ 11 C]CO 2 to [ 11 C]CO was performed according to the procedures described by Eriksson et al and Van der Wildt et al [11,22] Here, [ 11 C]CO 2 was reduced to [ 11 C]CO by passing it online through (20) 14.3 ± 2.1 (N = 2) 7 [d] vinyl iodide (10) [(cinnamyl)PdCl] 2 (7) AsPh 3 (56) 75.1 ± 1.2 (N = 2) 8 [c] [(cinnamyl)PdCl] 2 (7) xantphos (7) 9.0 ± 6.2 (N = 2) 9 [d] 73.0 ± 5.0 (N = 10)…”

“…The first approach to develop 11 C-acrylesters made use of Grignard reactions between different vinylmagnesium halides and [ 11 C]CO 2 , followed by quenching with a nucleophile to obtain the Michael acceptor acrylic acid 1 [8] or methyl acrylate 2 for further synthesis. [9,10] Another advantage, when applying the second methodology is the low isotopic dilution when making use of [ 11 C]CO compared to [ 11 C]CO 2 , which in general yields higher A M . Furthermore, the application of these reagents was limited to 1,2-additions.…”

“…Carbon-11 labeled acrylic acid and its methyl esters, 1 and 2, have been reported before, however, only in low molar activity (molar activity A M : measured radioactivity per mol of compound [GBq μmol -1 ] readjusted from specific activity). [10,11] Moreover, nowadays also alternative procedures have been published to obtain [ 11 C]CO from [ 11 C]CO 2 using simplified and straightforward methodologies. The second approach implemented here is a Pdmediated carbonylation reaction with [ 11 C]CO to obtain acrylester 3 and acrylamide 4.…”