DFT Insights intoTitanocene-Catalyzed Hydroborationof Pyridines: Importance of Redox-Neutral and Redox-Active Ti(IV)/Ti(II)and Ti(IV)/Ti(III) Pathways

Abstract Catalytic dearomative hydroboration of N-heteroarenes affords dihydropyridines, key motifs in natural products and pharmaceuticals. Commercially available, Cp2TiCl2 is an efficient catalyst for various organic transformations, yet the role of its oxidation state in the hydroboration of N-heteroarenes remains poorly understood. DFT calculations reveal that the uncatalyzed process proceeds through a prohibitively high activation barrier, while the Cp2TiCl2 (A) alone is ineffective in reducing this barrier, as the generation of the corresponding metal–hydride species is a prerequisite for catalytic activity. Reduction of A by Mg generates a Cp2Ti(II) (B), which subsequently forms a metallacyclic intermediate with HBPin and pyridine, preactivating the C–N bond and lowering the barrier relative to Cp2TiCl2. In the presence of H2, species B undergoes oxidative addition to form Cp2Ti(IV)H2 (C), which catalyzes hydroboration with a substantially lower activation barrier than A. Furthermore, Ti(III)-mediated hydroboration, initiated by the reduction of A with AllylMgBr and PhSiH3, generates an in situ Cp2Ti(III)H (D) as the key active species in a Ti(IV)/Ti(III) redox cycle, offering a distinct radical pathway. The observed reactivity trend Cp2Ti(III)H> Cp2Ti(IV)H2 > Cp2Ti(II) > Cp2Ti(IV)Cl2 underscores the oxidation-state flexibility in governing catalytic efficiency of titanocenes for selective dearomative functionalization of N-heterocycles.