Effective Alkyl‐Alkyl Cross‐Coupling with an Iron‐Xantphos Catalyst: Mechanistic and Structural Insights

While iron-catalyzed C(sp²)-C(sp³) cross-couplings have been widely studied and developed in the last decade, alkyl-alkyl cross-coupling systems with iron remain underdeveloped despite the importance of C(sp³)-C(sp³) bonds in organic synthesis. A major challenge to the development of these reactions is the current lack of fundamental insight into ligand effects and organoiron intermediates that enable effective alkyl-alkyl couplings. The current study addresses this longstanding limitation using a combination of ⁵⁷Fe Mössbauer spectroscopy, SC-XRD (single-crystal X-ray diffraction) and reactivity studies of alkyl-alkyl coupling with iron-Xantphos to define the in situ formed iron-Xantphos intermediates in catalysis. Combined with detailed reactivity studies, the nature of the key mechanistic pathways in catalysis and ligands effects to achieve effective alkyl-alkyl cross-coupling over competing β-H elimination pathways are probed. Overall, these foundational studies provide a platform for future bespoke ligand and pre-catalyst design for alkyl-alkyl cross-coupling methods development with sustainable iron catalysis.