Related Experiment Video
Updated: Jan 6, 2026
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Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
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One-Pot Base-Free Suzuki-Miyaura [11C]Methylation: Kinetic and Mechanistic Insights
Oscar Moreno1,2, Imad Azzeggarh1, Jason P Holland3
1Department of Radiology and Nuclear Medicine, Amsterdam UMC, De Boelelaan 1117, Amsterdam, Netherlands.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|November 29, 2025
Summary
This study explores base-free Suzuki-Miyaura cross-coupling for carbon-11 radiotracer synthesis. We elucidated mechanistic insights enabling efficient [11C]methylation under these conditions.
Area of Science:
- Organic Chemistry
- Radiochemistry
- Catalysis
Background:
- Suzuki-Miyaura cross-coupling is vital for synthesizing carbon-11 labeled PET radiotracers.
- Traditional methods require a base, which can complicate radiochemical synthesis.
Purpose of the Study:
- Investigate base-free Suzuki-Miyaura conditions for one-pot [11C]methylation.
- Elucidate the mechanism enabling base-free cross-coupling with [11C]CH3I.
Main Methods:
- Optimization of one-pot, base-free methylation using [11C]CH3I.
- Substrate scope evaluation.
- Kinetic studies with [14C]CH3I, kinetic isotope effect (KIE) measurements, and DFT calculations.
Main Results:
- Successful one-pot [11C]methylation achieved under base-free conditions in moderate yields.
- Reaction outcome influenced by electronic properties of boron substrates, suggesting alternative transmetallation.
- Oxidative addition identified as the rate-determining step via a heterolytic pathway.
Conclusions:
- Mechanistic understanding of base-free Suzuki-Miyaura cross-coupling with [11C]CH3I.
- Provides insights into Pd-mediated [11C]C-C bond formation under radiochemical constraints.
- Expands knowledge of base-free cross-coupling reactions.
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