Pd‐mediated rapid cross‐couplings using [¹¹C]methyl iodide: groundbreaking labeling methods in ¹¹C radiochemistry

Abstract

Prof. Bengt Långström is a pioneer in the field of chemistry-driven positron emission tomography (PET) imaging. He has developed a variety of excellent radiolabeling methodologies using the methods of organic chemistry, with the aim of widening the potential of PET in the study of life. Among his groundbreaking achievements in (11) C radiochemistry, there is the discovery of the Pd-mediated rapid cross-coupling reaction using [(11) C]methyl iodide. It was first reported by his Uppsala group in 1994-1995 and was further investigated by his and other groups with a view of enhancing its generality and practicability. This reaction is currently considered one of the basic methods for (11) C-labeling of low-weight organic compounds. This paper presents a short summary of the background and the development of Pd-mediated rapid cross-couplings of [(11) C]methyl iodide, with a focus not only on organostannanes, but also on organoboranes, organozincs, and terminal acetylene compounds. All these reactions have proven to be dependable (11) C-labeling methodologies that use chemically reliable carbon-carbon bond formation reactions.

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

“…Carbon-11 ( 11 C) is an unstable positron-emitting isotope of carbon with a half-life of 20.4 minutes. It is generally produced using a cyclotron by the proton bombardment of 14 N according to the following nuclear reaction: 14 N(p, α) 11 C. The 2 major primary 11 C-precursors used in radiosynthesis are [ 11 C]CO 2 and [ 11 C]CH 4 . These are produced in the gas target when the proton bombardment of 14 N occurs in the presence of traces of oxygen (0.5%-1%) or hydrogen (5%-10%), respectively.…”

“…It is generally produced using a cyclotron by the proton bombardment of 14 N according to the following nuclear reaction: 14 N(p, α) 11 C. The 2 major primary 11 C-precursors used in radiosynthesis are [ 11 C]CO 2 and [ 11 C]CH 4 . These are produced in the gas target when the proton bombardment of 14 N occurs in the presence of traces of oxygen (0.5%-1%) or hydrogen (5%-10%), respectively. 1 One of the main challenges in 11 C-chemistry is the development of rapid, versatile, and reliable methods to integrate these primary One of the most widespread 11 C-incorporation methodology uses [ 11 C]methyl iodide ([ 11 C]CH 3 I) as a 11 C-methylation reagent.…”

“…Due to its simplicity, 11 C-methylation is widely used for research and clinical production of functionalised 11 C-tracers as extensively reviewed in the literature. 2,4,5,[10][11][12][13][14][15][16][17][18] The recent development of "loop" chemistry has enabled technical and yield improvements in 11 C-methylation reactions. 2 "Loop" 11 C-methylation involves depositing a solution of the reagents in a thin film on the inside of an HPLC loop.…”

Radiosynthesis of 1‐iodo‐2‐[11C]methylpropane and 2‐methyl‐1‐[11C]propanol and its application for alkylation reactions and C―C bond formation

“…So far, N ‐alkylation and O ‐alkylation reactions and [ 11 C]carbon‐carbon bond formation based on alkylation of the α‐C‐atom of amino acetates have been performed by using these alternative synthons. Interestingly, no palladium catalysed couplings like Stille reaction or Suzuki reaction have been reported to date, although these reactions are frequently applied for the radiolabeling reagent [ 11 C]methyl iodide . We were interested in the synthesis of 1‐iodo‐2‐[ 11 C]methylpropane as 2‐methylpropane as an important functional group in medicinal chemistry and drug development, eg, for cyclooxygenase‐2 (COX‐2) inhibitors (Figure ) .…”

“…Interestingly, no palladium catalysed couplings like Stille reaction or Suzuki reaction have been reported to date, although these reactions are frequently applied for the radiolabeling reagent [ 11 C]methyl iodide. 14,15 We were interested in the synthesis of 1-iodo-2-[ 11 C] methylpropane as 2-methylpropane as an important functional group in medicinal chemistry and drug development, eg, for cyclooxygenase-2 (COX-2) inhibitors ( Figure 1). 16 Radiosynthesis of 1-iodo-2-[ 11 C] methylpropane has been reported by Långström et al with a decay corrected radiochemical yield of 20% and a radiochemical purity of 65% for 1-iodo-2-[ 11 C] methylpropane.…”