Iridium(III)-Catalyzed Intermolecular C(sp(3))-H Amidation for the Synthesis of Chiral 1,2-Diamines

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 a-secondary and a-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.

Automated summary

Chiral 1,2-diamines are important structures in bioactive natural products, active pharmaceutical ingredients, ligands for asymmetric catalysis, and organocatalysts. However, constructing chiral 1,2-diamine motifs is still challenging. To address this, researchers developed an iridium(III)-catalyzed intermolecular C(sp3)-H amidation reaction using a new and cleavable exo-protecting/directing group. This method allows for the synthesis of scalemic free 1,2-diamines from easily accessible precursors.