Cobalt‐Porphyrin‐Catalysed Intramolecular Ring‐Closing C−H Amination of Aliphatic Azides: A Nitrene‐Radical Approach to Saturated Heterocycles

Cobalt‐porphyrin‐catalysed intramolecular ring‐closing C−H bond amination enables direct synthesis of various N‐heterocycles from aliphatic azides. Pyrrolidines, oxazolidines, imidazolidines, isoindolines and tetrahydroisoquinoline can be obtained in good to excellent yields in a single reaction step with an air‐ and moisture‐stable catalyst. Kinetic studies of the reaction in combination with DFT calculations reveal a metallo‐radical‐type mechanism involving rate‐limiting azide activation to form the key cobalt(III)‐nitrene radical intermediate. A subsequent low barrier intramolecular hydrogen‐atom transfer from a benzylic C−H bond to the nitrene‐radical intermediate followed by a radical rebound step leads to formation of the desired N‐heterocyclic ring products. Kinetic isotope competition experiments are in agreement with a radical‐type C−H bond‐activation step (intramolecular KIE=7), which occurs after the rate‐limiting azide activation step. The use of di‐ tert ‐butyldicarbonate (Boc 2 O) significantly enhances the reaction rate by preventing competitive binding of the formed amine product. Under these conditions, the reaction shows clean first‐order kinetics in both the [catalyst] and the [azide substrate], and is zero‐order in [Boc 2 O]. Modest enantioselectivities (29–46 % ee in the temperature range of 100–80 °C) could be achieved in the ring closure of (4‐azidobutyl)benzene using a new chiral cobalt‐porphyrin catalyst equipped with four (1 S )‐(−)‐camphanic‐ester groups.