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.