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Cobalt‐Porphyrin‐Catalysed Intramolecular Ring‐Closing C−H Amination of Aliphatic Azides: A Nitrene‐Radical Approach to Saturated Heterocycles
Author(s) -
Kuijpers Petrus F.,
Tiekink Martijn J.,
Breukelaar Willem B.,
Broere Daniël L. J.,
van Leest Nicolaas P.,
van der Vlugt Jarl Ivar,
Reek Joost N. H.,
de Bruin Bas
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201700358
Subject(s) - chemistry , nitrene , intramolecular force , azide , photochemistry , amination , catalysis , porphyrin , medicinal chemistry , polymer chemistry , organic chemistry
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.