Communication
Chemistry—A European Journal
doi.org/10.1002/chem.202005508
&
Amination
Air Stable Iridium Catalysts for Direct Reductive Amination of
[a]
[a]
[b]
[a, b]
formation, and a necessity to add ammonia hampered its
Abstract: Half-sandwich iridium complexes bearing biden-
tate urea-phosphorus ligands were found to catalyze the
direct reductive amination of aromatic and aliphatic ke-
tones under mild conditions at 0.5 mol% loading with
high selectivity towards primary amines. One of the com-
plexes was found to be active in both the Leuckart–Wal-
lach (NH CO H) type reaction as well as in the hydrogena-
[
3c]
broad application. Significant breakthrough was achieved by
[
3d–h]
utilizing iridium half-sandwich complexes.
The performance
of those catalysts bearing L-X type ligands was similar and
demonstrated a high substrate to catalyst molar ratio (1000–
2
0000) but demanded air-free conditions. The reactions take
place in methanol and require addition of superstoichiomeric
amounts of acetic acid or formic acid—triethylamine azeotrope
in order to work at low catalyst loading. While the catalyst li-
gands can be extensively tuned to adjust steric or electronic
effects, chiral variants have not been reported.
4
2
tive (H /NH AcO) reductive amination. The protocol with
2
4
ammonium formate does not require an inert atmosphere,
dry solvents, as well as additives and in contrast to previ-
ous reports takes place in hexafluoroisopropanol (HFIP) in-
stead of methanol. Applying NH CO D or D resulted in a
Besides the LW reaction, ketones can be converted into pri-
mary amines by reductive amination utilizing a combination of
4
2
2
high degree of deuterium incorporation into the primary
[
4]
dihydrogen and ammonia or its equivalent (e.g., NH AcO).
4
amine a-position.
Several protocols presented heterogeneous catalysts which op-
erated at elevated temperatures (1208C) in a high-pressure
[
4a–c]
vessel setup.
While the reaction can be practical in industri-
Primary amines are key intermediates in fine and bulk chemical
al applications, adapting this protocol for lab use can be labo-
rious. The same holds true for a molecular Co-catalyst reported
for hydrogenative DRA of aldehydes and ketones utilizing a tri-
[
1]
production, in this regard, access to them from ketones in a
single step is a desired but yet challenging chemical transfor-
mation. The classical uncatalyzed Leuckart–Wallach (LW) reac-
tion utilizes ammonium formate both as a nitrogen source and
as a reducing agent but requires high temperature (150–
[
4d]
phosphine ligand. A significant breakthrough was achieved
by employing a chiral diphosphine Ru-catalyst, which allowed
access to highly enantioenriched primary amines using molec-
[
2]
[4e]
1
858C). Additionally, the hydrolysis of the formed N-formyl
ular hydrogen and ammonium acetate.
side product to the corresponding primary amine decreases
the yield significantly.
Herein, we present a simple Ir-based catalyst that is active in
both types of reductive amination under mild conditions
(508C) for a variety of substrates. The complex can be pre-
pared in two simple steps, which makes it convenient for labo-
ratory applications in primary amine synthesis and deuterium
labeling.
In the last two decades, the original reaction conditions
have been improved via application of transition metal cataly-
[3a]
sis. One of the first reports on the catalytic LW-type direct re-
ductive amination (DRA) utilized [Cp*RhCl ] complex, which
2
2
accelerated the conversion of a limited number of ketones and
Due to the straightforward assembly and high tunability, var-
ious P,N-chelating ligands have found utility in many catalytic
a-keto acids into the corresponding primary amines and
[
3b]
[5]
amino acids. Soon after, a protocol of highly enantioselective
Ru-catalyzed DRA of aryl ketones was published, yet the limit-
ed scope of substrates, high degree of formamide side product
hydrogenation reactions. Preparation of L1 and L2 was
achieved by treatment of N,N’-dimethylurea with the corre-
sponding chlorophosphine or phosphorochloridate in the pres-
ence of a base (Figure 1). The carbamide moiety was used to
[
6]
[
a] I. Polishchuk, Dr. J. Sklyaruk, Prof. Dr. M. Rueping
Institute of Organic Chemistry, RWTH Aachen University
Landoltweg 1, Aachen (Germany)
build the rigid frame of the five-membered iridacycles. After
the reaction of [Cp*IrCl ] with the corresponding ligands in
2
2
the presence of triethylamine, the complexes Ir-L1 and Ir-L2
were isolated in good yields. The characterization was achiev-
ed via NMR and IR spectroscopies, as well as single-crystal XRD
analysis. Comparison of the n(CO) positions indicates that L1 is
more electron donating than L2. The molecular structures of
Ir-L1 and Ir-L2 show a very similar distorted three-legged
piano stool coordination geometry at the iridium center
E-mail: magnus.rueping@kaust.edu.sa
[
b] Dr. Y. Lebedev, Prof. Dr. M. Rueping
KAUST Catalysis Center, King Abdullah University of Science and
Technology, Thuwal (Saudi Arabia)
E-mail: yury.lebedev@kaust.edu.sa
Supporting information and the ORCID identification number(s) for the
(
Figure 1). Both complexes are bench-stable solids that can be
This manuscript is part of a special collection on Chemistry in Saudi
Arabia.
stored for at least several months under an ambient atmosphere.
Chem. Eur. J. 2021, 27, 5919 – 5922
5919
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