C–H Activation\nand Sequential Addition to Dienes\nand Imines: Synthesis of Amines with β‑Quaternary Centers\nand Mechanistic Studies on the Complex Interplay Between the Catalyst\nand Three Reactants

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