10.1002/anie.201704260
Angewandte Chemie International Edition
COMMUNICATION
corresponding indoline 26 in good isolated yield, but with
significant erosion in enantiopurity (Scheme 1). Amination of C-
H-bonds adjacent to cyclopropyl groups were investigated
subsequently (Scheme 1). In the absence of any catalyst the
reaction leads to a complex mixture of products 48 – 51.[14]
Employing a Rh-catalyst under otherwise identical conditions led
to the formation of the C-H-amination products 48 and 49 plus
amine 50. Product 50 indicative of a radical reaction pathway
was not observed. Upon addition of TBA[Fe] products 48 and 49
were formed as main products together with amine in minor
quantities. Only traces of product 50 were observed. Apart from
arylazides, we became interested in transferring the protocol
also to aminations using alkylazides. Complementary to Betley´s
original report treatment of tertiary azide 52 with catalytic
amounts of TBA[Fe] gave access to the corresponding
pyrrolidine 53 in an excellent yield of 77 % instead of 11 %[10c]
using his catalyst. On the contrary, less substituted secondary
and primary azides did not give any product using TBA[Fe], but
reacted cleanly using Betley´s catalyst.[10c] These results indicate
the two catalytic systems to operate under different mechanistic
manifolds.
accessible in one step from inexpensive Fe(CO)5 on a multigram
scale which makes this process particularly attractive from a
synthetic point of view. Mechanistic investigations indicate the
reaction to proceed via
spectroscopic studies
a
stepwise mechanism. In-depth
accompanied by high-level
quantumchemical calculations are currently performed in order
to validate the experimental results.
Acknowledgements
Financial support by the Landesgraduiertenstiftung Baden-
Württemberg (Ph.D.-fellowship for
I.A.)
is
gratefully
acknowledged. We are grateful to M.Sc. Fabian Rami for
calculating the ECD-spectra of compound (S)-25 and to Prof. Dr.
Albert Jeltsch for measuring the ECD-spectra of compound (S)-
25.
Keywords: iron • C-H activation • C(sp3)-H-amination • indoline
• tetrahydroquinoline • catalysis
Within recent years we were able to show through a
combination of experiment, spectroscopy and quantumchemical
calculations that Bu4N[Fe(CO)3(NO)]-catalyzed transformation
do not follow radical reaction pathways but are rather
characterized by a ligand-based two-electron transfer event.[12e-h]
Moreover, most recently we were able to show that the ferrate
can act as a proton transfer catalyst.[12l] Based on these result
and the fact that the radical clock experiment indicates radicals
to be most likely not involved in TBA[Fe]-catalyzed C(sp3)-
aminations we propose a mechanism in which the C-H-bond is
activated in a stepwise manner. Although the KIE for the Fe-
catalyzed process is of comparable size as for Driver´s Rh-
based system (6.7)[6b] we think that the increase in C-H-acidity
leads to a preferred formation of six-membered rings, a reaction
that is not reported for any of the established intramolecular C-
H-amination systems, is best explained by a complementary
proton-transfer as C-H-bond activating step (Figure 3).
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Figure 3. Mechanistic hypothesis for Fe-catalyzed C(sp3)-H-bond amination.
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Herein we report that the nucleophilic Fe-complex
Bu4N[Fe(CO)3(NO)] catalyzes the intramolecular amination of
C(sp3)-H-bonds in azidoarylalkanes to the corresponding
indoline or tetrahydroquinoline derivatives. The catalyst is
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