Cp*Rh(III)-Catalyzed Enantioselective C(sp3)–H Amidation of Azine-Linked Cyclobutanes

Abstract

The highly enantioselective desymmetrizing C(sp3)–H amidation of azine-linked cyclobutanes with dioxazolones, to afford enantioenriched cis-configured amido-cyclobutane scaffolds is described. The reaction is catalyzed by an electron-deficient Cp*Rh(III) complex in combination with a newly designed axially chiral carboxylic acid (CCA) that was found to be key in obtaining high levels of enantiocontrol. Computational studies using DFT uncovered the reaction pathway and revealed the presence of multiple non-covalent interactions including inter- and intramolecular n–π* interactions and CH−π interactions which contributed to the high enantioselectivity. The methodology was found to be broad in scope with respect to the dioxazolone and could be further extended to larger cycloalkyl derivatives as well as bis-amidated cyclobutane derivatives.