Ruthenium Catalyzed Direct Asymmetric Reductive Amination of Simple Aliphatic Ketones Using Ammonium Iodide and Hydrogen

Article abstract of DOI:10.1002/ejoc.202000750

The direct conversion of ketones into chiral primary amines is a key transformation in chemistry. Here, we present a ruthenium catalyzed asymmetric reductive amination (ARA) of purely aliphatic ketones with good yields and moderate enantioselectivity: up to 99 percent yield and 74 percent ee. The strategy involves [Ru(PPh₃)₃H(CO)Cl] in combination with the ligand (S,S)-f-binaphane as the catalyst, NH₄I as the amine source and H₂ as the reductant. This is a straightforward and user-friendly process to access industrially relevant chiral aliphatic primary amines. Although the enantioselectivity with this approach is only moderate, to the extent of our knowledge, the maximum ee of 74 percent achieved with this system is the highest reported till now apart from enzyme catalysis for the direct transformation of ketones into chiral aliphatic primary amines.

Full text of DOI:10.1002/ejoc.202000750

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: Ruthenium Catalyzed Direct Asymmetric Reductive Amination of
Simple Aliphatic Ketones using Ammonium Iodide and Hydrogen
Authors: Tamal Ghosh, Martin Ernst, A. Stephen K. Hashmi, and
Thomas Schaub
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000750
Link to VoR: https://doi.org/10.1002/ejoc.202000750
01/2020

10.1002/ejoc.202000750
European Journal of Organic Chemistry
COMMUNICATION
Ruthenium Catalyzed Direct Asymmetric Reductive Amination of
Simple Aliphatic Ketones using Ammonium Iodide and Hydrogen
Tamal Ghosh,[a] Martin Ernst,[b] A. Stephen K. Hashmi,[a,c] and Thomas Schaub*[a,b]
[a]
Dr. T. Ghosh, Prof. Dr. A. S. K. Hashmi, Dr. T. Schaub*
Catalysis Research Laboratory (CaRLa)
Im Neuenheimer Feld 584, 69120 Heidelberg, Germany, www.carla-hd.de
E-mail: thomas.schaub@basf.com
[b]
[c]
Dr. M. Ernst, Dr. T. Schaub
Organic Synthesis
BASF SE, Carl-Bosch-Str. 38, 67056 Ludwigshafen, Germany, www.basf.com
Prof. Dr. A. S. K. Hashmi
Organisch-Chemisches Institut
Heidelberg University
Im Neuenheimer Feld 270, 69120 Heidelberg, Germany, www.hashmi.de
Supporting information for this article is given via a link at the end of the document.
Abstract: The direct conversion of ketones into chiral primary
amines is a key transformation in chemistry. Here, we present a
ruthenium catalysed asymmetric reductive amination (ARA) of purely
aliphatic ketones with good yields and moderate enantioselectivity:
up to 99% yield and 74% ee. The strategy involves
[Ru(PPh3)3H(CO)Cl] in combination with the ligand (S,S)-f-
binaphane as the catalyst, NH4I as the amine source and H2 as the
reductant. This is a straightforward and user-friendly process to
access industrially relevant chiral aliphatic primary amines. Although
the enantioselectivity with this approach is only moderate, to the
extent of our knowledge, the maximum ee of 74% achieved with this
system is the highest reported till now apart from enzyme catalysis
for the direct transformation of ketones into chiral aliphatic primary
amines.
Shortly afterwards, Xumu Zhang et. al. reported a similar
approach to asymmetric reductive amination by using
stoichiometric amounts of ammonium salt and hydrogen.6 These
two methods were very effective for aryl-alkyl ketones, but when
applied to alkyl-alkyl ketones, the enantioselectivity achieved
was less than 20%. In 2014, Guijarro et. al. reported microwave-
assisted asymmetric transfer hydrogenation of N-(tert-
butylsulfinyl)imines to obtain primary amines as the HCl salts in
good yield and enantiomeric excess (ee). In contrast, they had
to prepare and isolate the N-(tert-butylsulfinyl)imines from the
corresponding ketones using the Ellman-reagent7a before the
asymmetric transfer hydrogenation followed by desulfinylation to
obtain the amine.’This adds up two more steps to obtain the
amines from the ketone.7b Similarly, in 2003, Kadyrov et. al.
reported one example of an aliphatic ketone (2-octanone) in an
asymmetric version of the Leuckart-Wallach-reaction with very
low conversion and 24% ee with the undesired formation of
formylated amine as intermediate, ultimately requiring an
additional hydrolysis step.8 On the other hand, in the past years,
several biocatalytic approaches have been reported involving
kinetic resolution, deracemization of racemic amines, alcohol
amination and transamination using enzymes to obtain chiral
aliphatic primary amines.9 Despite all those advances, a simple
and dedicated method for the direct one-step synthesis of solely
aliphatic chiral primary amines from prochiral ketones without
enzymatic processes, has not been reported yet.
Optically active amines are ubiquitous in pharmaceuticals,
agrochemicals and widely used in organic synthesis.1 Among all
the amines, chiral primary amines are extremely valued as they
are very important building blocks for active ingredients in
medicine, biology and materials.2 In many cases, the
pharmacological activities of these amines depend on the
absolute configuration of the stereocenter.3 Therefore, practical
synthesis of chiral primary amines by imine hydrogenation,
enamine
hydrogenation,
reductive
amination,
oxime
hydrogenation, alcohol amination has gained remarkable
attention in the past few decades.4 However, most of the existing
processes to obtain unprotected chiral primary amines involve
multistep procedures with protected imine intermediates (in situ
formed or isolated), followed by asymmetric hydrogenation and
then deprotection leading to the unprotected amines (Scheme
1a). In this respect, in 2018, we have reported an atom-efficient
approach to obtain optically pure aryl-alkyl amines from the
corresponding prochiral ketones using ammonia and hydrogen.5
1
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000750
European Journal of Organic Chemistry
COMMUNICATION
Scheme 1. Comparison of transition metal catalyzed ARA to access pure
aliphatic chiral primary amines
was observed, but with an enhanced ee of 63% (Table 1, entry
1). Using MeOH as the reaction solvent at 80 °C, the conversion
was increased to 88% but the ee was decreased to 55% (Table
1, entry 2). Then our immediate thought was to use a (1:1)
mixture of toluene and MeOH, which to our delight, gave rise to
84% of 1a with 68% ee (Table 1, entry 3). Using NH4OAc
instead of NH4I or commercially available [Ru(OAc)2(S)-
Segphos] as the catalyst did not improve the result (Table 1,
entries 4-5). A series of other Ru-catalysts as well as 21 other
chiral phosphine ligands were tested which is summarized in the
Supporting Information (Table S1). Among all the other ligands,
only (4S,5S)-(+)-DIOP and (S,S)-BDPP resulted in a promising
ee of 52% and 61% respectively (Table 1, entries 6-7).
Comparing entries 8-9 with entry 3 in Table 1, it is evident that
2.5 equiv. of NH4I is optimal for the reaction condition. Addition
of ammonia or iodine diminished the enantioselectivity (Table 1,
entries 10-11). To facilitate the stability of the imine we added
different acids, which did not have a positive effect on the
enantioselectivity (Table 1, entries 12-14). Although a 1:1
mixture of toluene and MeOH was optimal for our system, we
have tested different other solvents and solvent-mixtures, which
is summarized in the Supporting Information (Table S2). A
mixture of toluene/EtOH (1:1) provided an ee similar to that in
toluene/MeOH but with a lower reaction rate (Table 1, entry 15).
Toluene/iPrOH (1:1) was the best choice of solvent (73% ee at
80 °C), but only 40% conversion to 1a was observed (Table 1,
entry 16). By increasing the reaction temperature to 100 °C, we
achieved a good conversion of 81% but the ee was reduced to
65% (Table 1, entry 17). After having established the optimal
reaction conditions, we intended to scale up our reaction from
0.2 mmol scale in a HEL CAT-7 autoclave to 1 mmol scale in a
Premex autoclave (see the Supporting Information, Fig. S2 for
details on this autoclave). The amine (1a) was isolated in a free,
unprotected form in 78% yield with 74% ee (Table 1, entry 18). It
is worth mentioning that while transferring the optimal reaction
conditions from HEL CAT-7 autoclave to a Premex autoclave,
the reaction time was extended to 36h to achieve a better
conversion, and as a matter of fact, the ee was improved by 4-
7% for all the substrates.
Herein, we report an update on our ongoing investigation of ARA
of purely aliphatic ketones using [Ru(PPh3)3H(CO)Cl] in
combination with the ligand (S,S)-f-binaphane as the catalyst,
ammonium iodide and hydrogen with good yield and moderate
enantioselectivity (Scheme 1b). In our previous findings in 2018,
we have reported an ee of 14% for the asymmetric amination of
2-heptanone,5 which in our present work increased to 32%. In
this work, we could achieve an ee of up to 74% for chiral
aliphatic primary amines. This, to the best of our knowledge, is
by far the highest reported ee for an aliphatic amine obtained
directly from a ketone without using biocatalysis.
Considering the limitations in the enantioselectivity of ARA of
alkyl-alkyl ketones, we started our investigation by employing
cyclohexyl methyl ketone (1) under the optimized reaction
conditions from our previous report5 on the ARA using NH3 (4
bar) and H2 (40 bar), with 1 mol% [Ru(PPh3)3H(CO)Cl], 1.1
mol% (S,S)-f-binaphane, 2 mol% NaPF6 and 10 mol% NH4I in
toluene at 120 °C for 16h. We achieved 74% of the amine with
45% ee (see the Supporting Information, Scheme S1). To
improve the enantioselectivity, we started optimizing the reaction
conditions using cyclohexyl methyl ketone (1) as the model
substrate and the results are summarized in Table 1. The yields
were determined by GC/FID with n-dodecane as the internal
standard, after 24h reaction in a HEL CAT-7 autoclave (see the
Supporting Information, Fig. S1 for details on this autoclave)).
We began our exploration with 1 mol% [Ru(PPh3)3H(CO)Cl], 1.5
mol% (S,S)-f-binaphane and 2.5 equiv. of ammonium iodide in
toluene at 100 °C, as the reaction was too slow at 80 °C in
toluene. A low conversion of 15% to 1-cyclohexylethylamine (1a)
2
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000750
European Journal of Organic Chemistry
COMMUNICATION
Table 1. Optimization of reaction conditions (a)
Yield of
1a
ee
er
Entry
Catalyst
Ligand
Solvent
Toluene
Additives (equiv.)
(%)(c)
[R/S](d)
(%)(b)
1(e)
2
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
[Ru(OAc)2(S)-Segphos]
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
[Ru(PPh3)3H(CO)Cl]
(S,S)-f-binaphane
(S,S)-f-binaphane
(S,S)-f-binaphane
(S,S)-f-binaphane
-
NH4I (2.5)
NH4I (2.5)
15
88
84
40
86
70
32
52
74
82
50
80
56
75
62
40
81
78(g)
63
82/18
77/23
84/16
81/19
35/65
76/24
20/80
84/16
84/16
69/31
76/24
84/16
83/17
83/17
84/16
87/13
83/17
87/13
MeOH
55
68
62
31
52
61
69
68
37
51
68
65
66
67
73
65
74
3
Toluene/MeOH (1:1)
Toluene/MeOH (1:1)
Toluene/MeOH (1:1)
Toluene/MeOH (1:1)
Toluene/MeOH (1:1)
Toluene/MeOH (1:1)
Toluene/MeOH (1:1)
Toluene/MeOH (1:1)
Toluene/MeOH (1:1)
Toluene/MeOH (1:1)
Toluene/MeOH (1:1)
Toluene/MeOH (1:1)
Toluene/EtOH (1:1)
Toluene/iPrOH (1:1)
Toluene/iPrOH (1:1)
Toluene/MeOH (1:1)
NH4I (2.5)
4
NH4OAc (2.5)
NH4I (2.5)
5
6
(4S,5S)-(+)-DIOP
(S,S)-BDPP
NH4I (2.5)
7
NH4I (2.5)
8
(S,S)-f-binaphane
(S,S)-f-binaphane
(S,S)-f-binaphane
(S,S)-f-binaphane
(S,S)-f-binaphane
(S,S)-f-binaphane
(S,S)-f-binaphane
(S,S)-f-binaphane
(S,S)-f-binaphane
(S,S)-f-binaphane
(S,S)-f-binaphane
NH4I (1.0)
9
NH4I (2.0)
10
11
12
13
14
15
16
17(e)
18(f)
NH3(4 bar); NH4I (2.5)
I2 (1.0); NH4I (2.5)
AcOH (1.0); NH4I (2.5)
Zn(OTf)2 (1.0); NH4I (2.5)
Ti(OiPr)4 (1.0); NH4I (2.5)
NH4I (2.5)
NH4I (2.5)
NH4I (2.5)
NH4I (2.5)
(a)Optimization of reaction conditions: in HEL CAT-7 autoclave; cyclohexyl methyl ketone (0.2 mmol), catalyst (1 mol%), ligand (1.5 mol%), additives
(equiv.), H2 (30 bar), (1:1) toluene/MeOH (2 mL), 80 °C, 24 h. (b)GC/FID determined yield with n-dodecane as internal standard. (c)The ee values were
3a
(f)
determined by chiral HPLC after benzoylation. (d)Enantiomeric ratio (er) of [R] and [S] enantiomers of 1a. (e)Reactions were performed at 100 °C;
wer
e
reaction was performed in a Premex autoclave; cyclohexyl methyl ketone (1.0 mmol), [Ru(PPh3)3H(CO)Cl] (1 mol%), (S,S)-f-binaphane (1.5 mol%),
NH4I (2.5 equiv.), H2 (30 bar), (1:1) toluene/MeOH (10 mL), 80 °C, 36 h. (g) Isolated yield of 1a.
obta
ined in 70% yield, 66% ee and 54% yield, 65% ee respectively.
Our primary goal was to isolate the aliphatic amines in an
unprotected form, but because of the volatility of amines
(especially for compound 3a) we obtained lower yields. So, we
carried out separate reactions to isolate several of the amines as
their corresponding HCl salts to show that the amines can also
be isolated in excellent yields as the hydrochloride, when
needed. For example, 1a, 2a and 3a were isolated in 94%, 99%
and 98% respectively as their corresponding HCl salts. In
addition to that, in the process of isolating the amines as their
HCl salt, 40% of the used NH4I in the reaction (2.5 equiv.) was
precipitated and could be reused in further reactions, reducing
the waste to a minimum amount. We believe that for most of the
To demonstrate the utility of our method, we started to screen
different alkyl-alkyl ketones under the optimized reaction
conditions in a Premex autoclave under 30 bars of H2 at 80 °C
for 36h (Table 2). A wide range of simple aliphatic amines were
obtained with moderate enantioselectivity and good to excellent
yield. The enantioselectivity of the reactions was determined
after benzoylation of the products using chiral HPLC. As
mentioned before, the model substrate (1) was reductively
aminated in 78% isolated yield and 74% ee. The absolute
configuration of the product (1a) was determined by comparing
with commercially available enantiomers of 1a. Similarly, 2a and
3
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000750
European Journal of Organic Chemistry
COMMUNICATION
Table 2. Substrate Scope (a)
of the ketone, the reaction was strongly impeded, and the
conversion was only 15% (15a) and 7% (16a) even at 100 °C.
We have also considered whether the hydrogenation of oximes,
obtained from the corresponding ketones, would increase the
enantioselectivity. However, with the oximes 1b and 8b derived
from ketones 1 and 8 respectively, we could only achieve a
similar yield or enantioselectivity compared to the current result
(see the Supporting Information, Table S3). Moreover, we had
to increase the reaction temperature to 100-120 °C as the
oximes were less reactive compared to the ketones. With the
optimized reaction conditions, we have also tested
acetophenone (17), to compare the results with our previous
system5 of ARA using NH3 and H2. In this case, the reaction
yield was lower than our previous system, providing 65% of the
corresponding amine (17a) but with an increased ee of 93%
(see the Supporting Information, Scheme S2).
In summary, we report an update on our ongoing research
activities for the ARA of aliphatic ketones using a simple method
and a versatile range of substrates. Using a 1:1 mixture of
toluene/MeOH as the reaction solvent and NH4I as the ammonia
source was the key to improve the yield as well as the
enantioselectivity. As for the aryl-alkly-ketones, the Ru-(S,S)-f-
binaphane catalysts provided the highest ee compared to all the
other tested systems Although the enantioselectivity is only
moderate, we believe that these are the highest reported ee
values for aliphatic amines directly obtained from corresponding
ketones apart from biocatalysis. Although the reaction doesn’t
work well for α-tertiary ketones, for secondary ones it works well
with moderate ee values of 55-74% and for linear n-alkyl
ketones, the ee is in the range of 21-33%. We believe that to
further improve the ee of this system, we need to find and
design new catalysts, as it seems that the available
catalyst/ligand systems are not able to deliver higher ee than the
ones reported here. Overall, ARA of aliphatic ketones remains
challenging but attractive.
(a)Reaction conditions: in
a Premex autoclave; ketones 1-16 (1.0 mmol),
[Ru(PPh3)3H(CO)Cl] (1 mol%), (S,S)-f-binaphane (1.5 mol%), NH4I (2.5 equiv.),
H2 (30 bar), (1:1) toluene/MeOH (10 mL), 80 °C, 36 h. (b)In the parentheses:
isolated yield of the amine as HCl salt from an independent reaction. (c)GC/FID
determined yield with n-decane as internal standard. (c)The ee values were
determined by chiral HPLC after benzoylation. (d)Reaction was carried out for
48h. (e)Reactions were performed at 100 °C.
other amines it would be possible to achieve better yields when
isolated as HCl salts. Amines 4a, 5a, 7a and 8a were too volatile
to be isolated as free amines on our scale; so, GC/FID
determined yields are reported using n-decane as the internal
standard. When the α-position of the ketone is a secondary
carbon atom, 55-74% ee was obtained. On the other hand,
when the steric bulk due to the secondary carbon atom shifts to
β-, γ- or δ- position (5a-7a) from the carbonyl carbon, or when it
is a linear n-alkyl chain (8a-12a), the enantioselectivity dropped
significantly, varying from 21-33% ee. Keeping a secondary
carbon atom on one side, when R2 is changed from Me- to an
Et-group, the reaction rate was reduced (13a and 14a), but the
enantioselectivity was maintained at 64% and 59% ee
respectively. In the case of 13a, due to low conversion and high
volatility, we have isolated the product as its HCl salt in 21%
yield, and the reaction time was extended to 48h. But
unfortunately, in case of a tertiary carbon atom at the α-position
Acknowledgements
CaRLa (Catalysis Research Laboratory) is co-financed by the
Ruprechts-Karls-University Heidelberg (Heidelberg University)
and BASF SE
Keywords: Asymmetric reductive amination (ARA), chiral,
aliphatic, primary amines, enantioselectivity.
[1] a) M. Breuer, K. Ditrich, T. Habicher, B. Hauer, M. Kesseler,
R. Sturmer, T. Zelinski, Angew. Chem., Int. Ed. 2004, 43,
788−824; b) T. C. Nugent, M. El-Shazly, Adv. Synth. Catal. 2010,
352, 753−819; c) D. Ferraris, Tetrahedron 2007, 63, 9581−9597;
4
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000750
European Journal of Organic Chemistry
COMMUNICATION
d) F. van Rantwijk, R. A. Sheldon, Tetrahedron 2004, 60,
501−519.
i) S. Yoon, M. D. Patil, S. Sarak, H. Jeon, G. -H. Kim, T. P.
Khobragade, S. Sung, H. Yun, ChemCatChem 2019, 11, 1898–
1902.
[2] a) H. Y. Aboul-Enein, I. W. Wainer, The Impact of
Stereochemistry on Drug Development and Use, Wiley, New
York, 1997; b) E. J. Ariëns, W. Soudijn, P. B. M. W. M.
Timmermans, Stereochemistry and Biological Activity of Drugs,
Blackwell, Oxford, 1983; c) S. A. Lawrence, Amines: Synthesis,
Properties and Applications, Cambridge University Press,
Cambridge, UK, 2004; d) S. D. Roughley, A. M. Jordan, J. Med.
Chem. 2011, 54, 3451−3479; e) V. Froidevaux, C. Negrell, S.
Caillol, J. -P. Pascault, B. Boutevin, Chem. rev. 2016, 116,
14181−14224.
[3] a) S. H. Snyder, K. M. Tayler, Science 1970, 168, 1487–
1489; b) G. T. Hajos, S. Garattin, J. Pharm. Pharmacol. 1973,
25, 418–419.
[4] a) S. Gomez, J. A. Peters, T. Maschmeyer, Adv. Synth. Catal.
2002, 344, 1037−1057; b) T. C. Nugent, M. El-Shazly, Adv.
Synth. Catal. 2010, 352, 753−819; c) J. H. Xie, S. F. Zhu, Q. L.
Zhou, Chem. Rev. 2011, 111, 1713−1760; d) W. Tang, J. Xiao,
Synthesis 2014, 46, 1297−1302; e) C. Wang, J. Xiao, Top. Curr.
Chem. 2013, 343, 261−282; f) J. H. Xie, S. F. Zhu, Q. L. Zhou,
Chem. Soc. Rev. 2012, 41, 4126−4139; g) H. Huang, X. Liu, L.
Zhou, M. Chang, X. Zhang, Angew. Chem., Int. Ed. 2016, 55,
5309−5312; h) D. Steinhuebel, Y. Sun, K. Matsumura, N. Sayo,
T. Saito, J. Am. Chem. Soc. 2009, 131, 11316−11317; i) H.
Huang, Y. Zhao, Y. Yang, L. Zhou, M. Chang, Org. Lett. 2017,
19, 1942−1945; j) D. C. Iffland, T.-F. Yen, J. Am. Chem. Soc.,
1954, 76, 4180-4181; k) T. Imamoto, Rhodium(I)-Catalyzed
Asymmetric
Hydrogenation.,
2019,
1–
37, doi:10.1002/9783527811908.ch1; l) W. Baumann, A.
Spannenberg, J. Pfeffer, T. Haas, A. Koeckritz, A. Martin, J.
Deutsch, Chem. Eur. J. 2013, 19, 17702−17706; m) K.
Murugesan, Z. Wei, V. G. Chandrashekhar, H. Jiao, M. Beller, R.
V. Jagadeesh, Chem. Sci. 2020, doi: 10.1039/D0SC01084G; n)
K. Murugesan, V. G. Chandrashekhar, T. Senthamarai, R. V.
Jagadeesh, M. Beller, Nature Protocols 2020, 15, 1313-1337.
[5] J. Gallardo-Donaire, M. Hermsen, J. Wysocki, M. Ernst, F.
Rominger, O. Trapp, A. S. K. Hashmi, A. Schäfer, P. Comba, T.
Schaub, J. Am. Chem. Soc. 2018, 140, 355−361.
[6] X. Tan, S. Gao, W. Zeng, S. Xin, Q. Yin, X. Zhang, J. Am.
Chem. Soc. 2018, 140, 2024−2027.
[7] a) M. T. Robak, M. A. Herbage, J. A. Ellman, Chem. Rev.
2010, 110, 3600–3740; b) Ó. Pablo, D. Guijarro, M. Yus, Eur. J.
Org. Chem. 2014, 7034–7038; c) D. Guijarro, O. Pablo, M. Yus,
J. Org. Chem. 2010, 75, 5265–5270.
[8] R. Kadyrov, T. H. Riermeier, Angew. Chem. Int. Ed. 2003, 42,
5472–5474.
[9] a) D. Koszelewski, D. Clay, D. Rozzell, W. Kroutil, Eur. J. Org.
Chem. 2009, 2289–2292; b) H. Ismail, R. M. Lau, L. M. van
Langen, F. van Rantwijk, V. K. Svedas, R. A. Sheldon, Green
Chem. 2008, 10, 415–418; c) L. El Blidi, M. Nechab, N.
Vanthuyne, S. Gastaldi, M. P. Bertrand, G. Gil, J. Org. Chem.
2009, 74, 2901–2903; d) L. El Blidi, N. Vanthuyne, D. Siri, S.
Gastaldi, M. P. Bertrand, G. Gil, Org. Biomol. Chem. 2010, 8,
4165–4168; e) S. Schätzle, F. Steffen-Munsberg, A. Thontowi,
M. Höhne, K. Robins, U. T. Bornscheuera, Adv. Synth. Catal.
2011, 353, 2439–2445; f) H. Leisch, S. Grosse, H. Iwaki, Y.
Hasegawa, P. C. K. Lau, Can. J. Chem. 2012, 90, 39–45; g) F.
G. Mutti, T. Knaus, N. S. Scrutton, M. Breuer, N. J. Turner,
Science 2015, 349, 1525–1529; h) T. Knaus, L. Cariati, M. F.
Masman, F. G. Mutti, Org. Biomol. Chem. 2017, 15, 8313–8325;
5
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000750
European Journal of Organic Chemistry
COMMUNICATION
Entry for the Table of Contents
On the direct asymmetric reductive amination of aliphatic ketones to primary amines: By using Ru-Binaphane as catalyst and NH4I as
the amine source, it is possible to aminate prochiral aliphatic ketones with moderate ee´s up to 74%.
Key topic: Asymmetric Amination
Institute and/or researcher Twitter usernames: @LaboratoryCaRLa
6
This article is protected by copyright. All rights reserved.