Rh(III)-Catalyzed [4+3] Annulation: Temperature Dependent Ste-reodivergent Synthesis of Point-Planar Chiral Ferrocene Fused Azepines

Planar chiral ferrocenes are extensively researched molecules in the fields of asymmetric catalysis, materials science, and medicinal chemistry. Yet, achieving complete control over planar and point chirality simultaneously in a single step remains challenging. Herein, we disclose the first temperature-dependent stereodivergent [4+3] annulation of ferrocene-p-tosylamides via C-H activation with allenes by Rh-catalyst. At room temperature, Rh-catalyzed [4+3] annulation selectively offered one diastereomer (>20:1 dr), whereas at 60 ᵒC, another diastereomer was obtained exclusively with >20:1 dr. Further, [4+3] annulation reaction in the presence of a chiral RhCpX catalyst yielded chiral thermodynamic controlled ferrocenyl azepines up to 84% yield and 96:4 er and chiral kinetically controlled ferrocenyl azepines upto 55% and 97:3 er. The control experiments, isotopic labelling study, and DFT calculations suggested that the reaction proceeds via a σ-bonded rhodacycle avoiding steric repulsion between the phenyl ring of allene and Cp of Rh-catalyst. Which upon reductive elimination offered a kinetically controlled diastereomer at room temperature. Under heating (60 ᵒC) conditions, kinetically controlled diastereomer undergo C-N bond ring opening to afford completely thermodynamically controlled diastereomer and this conversion has also been observed experimentally on isolated kinetically controlled diastereomer.