C-H Activation and Sequential Addition to Dienes and Imines: Synthesis of Amines with β-Quaternary Centers and...

A Rh(III)-catalyzed sequential C-H bond addition to dienes and in situ formed aldimines was developed, allowing for the preparation of otherwise challenging to access amines with quaternary centers at the β-position. A broad range of dienes were effective inputs and installed a variety of aryl and alkyl substituents at the quaternary carbon site. Aryl and alkyl sulfonamide and carbamate nitrogen substituents were incorporated by using different formaldimine precursors. Moreover, the in situ formed N-Cbz aldimine from ethyl glyoxylate provided β,β-disubstituted α-amino esters with high diastereoselectivity. Two rhodacycle intermediates along the catalytic cycle were isolated and characterized by X-ray structural analysis, and the equilibria between the rhodacycle species in the presence of different reactants were determined. Deuterium labeling studies provided additional information to explain the uncommon 1,3-addition selectivity to the conjugated diene. Density functional theory calculations were consistent with the equilibria determined between the rhodacycle intermediates in the presence of different reactants and provided further insight on the transition state structures and energies for key steps in the catalytic cycle.