Abstract: The photocatalytic generation and trapping of alkyl radicals is a powerful synthetic tool in organic chemistry, but it remains underexplored in biological settings. Here, we present two photoredox systems that leverage green- or red-light irradiation for the activation and subsequent Giese coupling of redox-active alkyl phthalimide esters. Besides utilizing mild low-energy light sources, these reactions operate with biocompatible BnNAH or NADH as electron donor. Notably, they display compatibility with air, water and biologically relevant conditions, including cell-culture media or even cell lysates. This work marks a significant step towards integrating synthetic alkyl-radical chemistry into biological settings.

External link: https://pubs.rsc.org/en/content/articlelanding/2025/ob/d5ob00476d

Abstract: Pd-catalyzed annulations of ACPs with different C=N partners in both inter- and intramolecular ways are described. The methods provide access to pyrrolidines and pyrrolidine-fused polycyclic systems, featuring β-exo-methylene moieties. Preliminary enantioselective variant has been shown by using a chiral phosphoramidite ligand and DFT studies shed light on the reaction mechanism

External link: https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/ceur.202500005

Abstract: Carbonyl-tethered alkylidenecyclopropanes can react with aryl isocyanates in presence of Pd(0)-phosphoramidite catalysts to give seven-membered heterobicyclic products in a formal [3+2+2] cycloaddition process. The reaction involves the formation of a palladium π-allyl complex intermediate (A), which behaves as a formal 1,5-dipole, and can be trapped by externally added isocyanates. This report also includes preliminary assays of asymmetric variants, as well as DFT computational studies that shed some light on the nature of the catalytic cycle.

Abstract: Optically active 2-aminobiaryls are valuable chiral frameworks with broad applications in catalysis, synthetic chemistry, and materials science. Here, we present a simple and practical methodology for their asymmetric synthesis via enantioselective palladium catalyzed C−H arylations or alkenylations of racemic precursors. The methodology utilizes a kinetic resolution strategy, producing two highly valuable enantioenriched axially chiral molecules: the C−C coupling product and the unreacted starting material. Notably, we have established reaction conditions that enable the in situ regeneration of the active Pd(II) catalyst using atmospheric air as the sole oxidant. Finally, we showcase the synthetic utility of this approach by preparing several derivatives relevant to the field of asymmetric catalysis.

External link: https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202425512

We are really pleased to announce here that our research article at ChemCatChem, entitled "Photocatalytic Arylations with Diazonium Salts in Aqueous and Biorelevant Media" and authored by X. Fernández, J. Miguel, J. L. Mascareñas and M. Tomás-Gamasa has been accepted and it's already on-line.

Abstract: Performing designed, abiotic chemical transformations in live environments represents a powerful approach to interrogate and manipulate biology, and to uncover new types of biomedical tools. Despite significant advances in the area, the list of bioorthogonal reactions so far available is still very short, and mainly restricted to the use of strained reactants, or metal-promoted processes. En route to further expanding the repertoire of biocompatible reactions, we demonstrate here that aryldiazonium salts, well-established as radical precursors, can react with unsaturated systems in biologically relevant media under photocatalytic conditions, to give either addition or cycloaddition products, depending on the reactants.

External link: https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cctc.202401778