Asymmetric Iron‐Catalyzed Vicinal C(sp ³ )─H Diamination of Carboxylic Acids

Abstract

ABSTRACT The direct construction of chiral 1,2‐diamines through the stereoselective functionalization of two vicinal C(sp 3 )─H bonds remains a significant synthetic challenge. We report an iron‐catalyzed, carboxylate‐directed asymmetric vicinal α,β‐C(sp 3 ) ─H diamination of readily available carboxylic acids that furnishes chiral α,β‐diamino acids in a single pot with high regio‐, diastereo‐, and enantioselectivity (up to >20:1 dr and >99% ee). Using a chiral tetradentate N4‐ligated Fe(II) catalyst and BocNHOMs as the aminating reagent, a broad range of aromatic and aliphatic substrates undergo two sequential, nitrene‐mediated C─H aminations under mild conditions. Mechanistic studies indicate stepwise amination via iron−nitrenoid species, where the initial site of hydrogen‐atom transfer (β for aromatic substrates, α for aliphatic ones) dictates the order of functionalization. The method tolerates diverse functional groups and operates enantioconvergently for selected racemic substrates. This sustainable iron‐catalyzed strategy enables direct conversion of abundant carboxylic acids into versatile chiral α,β‐diamino building blocks amenable to peptide synthesis and heterocycle formation.