Selective Chiral Diamine-bisoxazoline Iron(II) Catalysts for Pyrrolidine Formation via Intramolecular C(sp ³ )–H Amination of Aliphatic Azides

High Resolution Image Download MS PowerPoint Slide The utilization of iron-catalyzed intramolecular C(sp 3 )–H amination starting from organic aliphatic azides, which are easily available precursors, represents a particularly promising route to synthesize sought-after N -heterocyclic motifs. While significant advances in achiral iron catalysis have been made by the field in recent years, we introduce here a new, highly reactive chiral diamine-bisoxazoline iron(II) system for asymmetric C–H amination with primary azides. The presence of two distinctly different chiral components, i.e., an atropisomeric binaphthyl-diamine backbone and two stereochemically identical oxazoline units, leads to the formation of four stereoisomers, which revealed distinctly different reactivity for the two sets of diastereomers available. Kinetic experiments and detailed computation studies point to a stepwise radical mechanism after the initial rate-limiting azide activation via a 1,5-HAT process at the quintet spin surface. Ligand modification (substitution at the oxazoline ring) significantly enhanced the reactivity, chemoselectivity, and enantioselectivity, thus enabling the synthesis of pyrrolidines in high yield with good stereocontrol under mild, additive-free conditions and with N 2 as the sole byproduct.