Toward Pd-Free Pharma: Iron Catalysis in Cross-Coupling Reactions for Medicinal Chemistry

Objetivo

IRONMED aims to unlock a new, iron-based cross-coupling platform for the synthesis of complex small-molecule pharmaceuticals and to demonstrate its commercial potential. Modern drug manufacture relies almost exclusively on palladium-catalysed cross-couplings to construct biaryl and alkyl–aryl motifs that pervade antivirals, oncology drugs and CNS agents. This creates structural dependence on a scarce, expensive and geopolitically sensitive metal, and drives significant costs for catalyst, purification and compliance with strict metal-residue limits, with negative implications for affordability and supply resilience. Building on the PI’s recent advances, IRONMED will exploit a family of well-defined, ligand-controlled iron complexes that have already been shown to perform demanding transformations under mild conditions and to construct representative biaryl and alkyl–aryl bonds with high yields and a well-understood mechanism. The project will translate this chemistry from advanced academic results (TRL 2–3) to a pharma-relevant technology (TRL 4) by (i) adapting and validating iron-catalysed cross-couplings on selected drug-like building blocks and fragments of real or representative active ingredients, (ii) benchmarking them directly against state-of-the-art palladium processes in terms of yield, robustness, metal residues, purification needs and indicative cost of goods, and (iii) co-developing with industrial stakeholders a small set of standardised protocols, decision guidelines and business models (reagent, process/IP or service-based). By integrating technical data with techno-economic and market analyses, IRONMED will identify the most promising application niches and define clear go/no-go paths towards scale-up and follow-on funding. IRONMED will deliver a credible alternative catalytic platform that reduces dependence on palladium, improves process sustainability and opens new options for cost-effective access to advanced medicines.

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