Mechanochemical ligand-controlled regiodivergent hydroarylation of alkenes via iron-catalyzed C-H activation.

Abstract

The iron-catalyzed hydroarylation of alkenes with indoles is a sustainable, effective synthetic transformation towards the construction of functionalized indoles - crucial motifs for various bioactive molecules and drug candidates. However, such transformations have proven challenging for unactivated alkenes, and the requirement for (super)stoichiometric amounts of reactive Grignard reagents has limited broader applications. Herein, we address these major challenges by integrating iron/N-heterocyclic carbene-catalyzed C-H activation with mechanochemistry techniques. This approach enables mechanochemical iron-catalyzed anti-Markovnikov hydroarylations of unactivated alkenes using a bis(N-heterocyclic carbene) ligand, as well as regiodivergent hydroarylation of aryl alkenes by varying the N-heterocyclic carbene ligand. To this end, magnesium metal serves as a convenient reductant to form catalytically active iron(0) species by mechanochemistry, thereby improving the sustainability and functional group compatibility. Experimental and computational studies elucidate the possible catalytic mode of action, and a data science analysis captured the key features of the N-heterocyclic carbene ligands in controlling regiodivergent selectivity.