Year: 2025
Type: article
Abstract: ABSTRACT The Suzuki–Miyaura cross‐coupling reaction is one of the most powerful approaches for forming carbon–carbon bonds in the synthesis of carbon‐11–labeled positron emission tomography (PET) radiotracers. Typically, Suzuki cross‐coupling is performed in the presence of a base to activate the boron reagent and sustain the catalytic cycle. Here, we investigate the capacity of the Suzuki reaction to proceed under one‐pot base‐free conditions for [ 11 C]methylation reactions and elucidate the mechanistic features that enable this transformation. Conditions were optimized to successfully achieve one‐pot methylation of a model substrate using [ 11 C]CH 3 I in the absence of base in moderate yields. Systematic substrate studies reveal that the reaction is partly governed by the electronic properties of the boron substrate, suggesting an alternative transmetallation pathway in this case. Kinetic studies using [ 14 C]CH 3 I, together with kinetic isotope effect (KIE) measurements and density functional theory (DFT) calculations, reveal that oxidative addition remains the rate‐determining step through a heterolytic pathway, consistent with the formation of a cationic Pd(II) intermediate that can undergo transmetallation in the absence of base. Together, these results provide new mechanistic insights into Pd‐mediated [ 11 C]C–C bond formation under the unique stoichiometric constraints of radiochemical conditions, expanding the understanding of base‐free cross‐coupling reactions with [ 11 C]CH 3 I.
Source: Chemistry - A European Journal
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,640
OpenAlex ID: W4416816563