Iridium(III)-Catalyzed Intermolecular C(sp3)-H Amidation for the Synthesis of Chiral 1,2-Diamines

Abstract

Chiral 1,2-diamines are privileged scaffolds among bioactive natural products, active pharmaceutical ingredients, ligands for transition-metal-based asymmetric catalysis and organocatalysts. Despite this interest, the construction of chiral 1,2-diamine motifs still remains a challenge. To address this, an iridium(III)-catalyzed intermolecular C(sp3)-H amidation reaction was developed. This method relies on the design of a new, cheap and cleavable exo-protecting/directing group derived from camphorsulfonic acid, which is directly installed from easily accessible precursors, and furnishes scalemic free 1,2-diamines upon cleavage of both nitrogen substituents. It was found applicable to both α-secondary and α-tertiary-1,2-diamines, for which a two-step protocol involving intermolecular olefin hydroamination and C(sp3)-H amidation was developed. Kinetic and computational studies provided insights into the observed reactivity difference between pairs of diastereoisomeric substrates.