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 (Boc2O) 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 [Boc2O]. 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 (1S)-(-)-camphanic-ester groups.
Van 't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam (UvA), Science Park 904, 1098 XH, Amsterdam, The Netherlands.
Petrus F
PF
Kuijpers
Van 't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam (UvA), Science Park 904, 1098 XH, Amsterdam, The Netherlands.
Martijn J
MJ
Tiekink
Van 't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam (UvA), Science Park 904, 1098 XH, Amsterdam, The Netherlands.
Willem B
WB
Breukelaar
Van 't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam (UvA), Science Park 904, 1098 XH, Amsterdam, The Netherlands.
Daniël L J
http://orcid.org/0000-0002-6641-4092
DLJ
Broere
Van 't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam (UvA), Science Park 904, 1098 XH, Amsterdam, The Netherlands.
Nicolaas P
NP
van Leest
Van 't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam (UvA), Science Park 904, 1098 XH, Amsterdam, The Netherlands.
Jarl Ivar
http://orcid.org/0000-0003-0665-9239
JI
van der Vlugt
Van 't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam (UvA), Science Park 904, 1098 XH, Amsterdam, The Netherlands.
Joost N H
http://orcid.org/0000-0001-5024-508X
JNH
Reek
Van 't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam (UvA), Science Park 904, 1098 XH, Amsterdam, The Netherlands.
Bas
http://orcid.org/0000-0002-3482-7669
B
de Bruin
C−H activation; cobalt porphyrin; nitrogen heterocycles; radical reactions; ring-closing reactions