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

Planar chiral ferrocenes are extensively investigated structures in asymmetric catalysis, materials science, and medicinal chemistry. Although the synthetic approaches for six-membered fused planar chiral ferrocenes are well-established, the construction of a seven-membered fused ring via [4+3] annulation has remained unexplored and seems to be challenging. Herein, an efficient rhodium-catalyzed temperature-dependent stereodivergent [4+3] annulation reaction has been developed for the synthesis of novel seven-membered ferrocenylazepines via C-H activation of substituted ferrocene-p-tosylamides with allenes. At room temperature, Rh-catalyzed [4+3] annulation selectively offered one diastereomer (>20:1 dr), whereas, at 60 ºC, another diastereomer was obtained exclusively (>20:1 dr). Further, [4+3] annulation reaction in the presence of chiral RhCpX catalyst (2 mol %) yielded chiral ferrocenyl azepines in 56% yield and up to 90:10 er. Mechanistic investigations by control experiments, iso-topic labelling study, and DFT computation suggested that the reaction proceeds via a formation of a σ-bonded rhodacycle, having low energy due to less steric repulsion between the phenyl ring of allene and Cp*(pentamethyl cyclopentadienyl), which upon reductive elimination offered kinetically controlled diastereomer. Under heating (60 ºC) conditions and in the presence of a base, kinetically controlled diastereomer could undergo CH-allylic isomerization to afford completely thermodynamic controlled diastereomer, which has also been observed experimentally.