Mild N-Alkylation of Amines with Alcohols Catalyzed by the Acetate Ru(OAc)2(CO)(DiPPF) Complex

Article abstract of DOI:10.1002/chem.201702996

The acetate complex Ru(OAc)₂(DiPPF) (2) obtained from Ru(OAc)₂(PPh₃)₂ (1) and 1,1′-bis(diisopropylphosphino)ferrocene (DiPPF) reacts cleanly with formaldehyde affording Ru(OAc)₂(CO)(DiPPF) (3) in high yield. The monocarbonyl complex 3 (0.4-2 mol %) efficiently catalyzes the N-alkylation of primary and secondary alkyl and aromatic amines using primary alcohols ROH (R=Et, nPr, nBu, PhCH₂) under mild reaction conditions (30–100 °C) with an alcohol/amine molar ratio of 10-100. Formation of the monohydride RuH(OAc)(CO)(DiPPF) (4) has been observed by reaction of 3 with iPrOH in the presence of NEt₃ at RT through an equilibrium reaction.

Full text of DOI:10.1002/chem.201702996

A Journal of
Accepted Article
Title: Mild N-Alkylation of Amines with Alcohols Catalyzed by the
Acetate Ru(OAc)2(CO)(DiPPF) Complex
Authors: Walter Baratta, Rosario Figliolia, Salvatore Baldino, Hans
Günter Nedden, and Antonio Zanotti-Gerosa
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: Chem. Eur. J. 10.1002/chem.201702996
Link to VoR: http://dx.doi.org/10.1002/chem.201702996
Supported by

Chemistry - A European Journal
10.1002/chem.201702996
Accepted
Communication
Chem. Eur. J.
Mild
N-Alkylation of Amines with Alcohols Catalyzed by the Acetate
Ru(OAc)
2
(CO)(D PPF) Complex
i
[
a]
[a]
[b]
[b]
Rosario Figliolia, Salvatore Baldino, Hans Günter Nedden, Antonio Zanotti-Gerosa, and
Walter Baratta*[a]
Abstract: The acetate complex Ru(OAc)
bis(diisopropylphosphino)ferrocene (DiPPF) reacts cleanly with formaldehyde affording
Ru(OAc) (CO)(DiPPF) (3) in high yield. The monocarbonyl complex 3 (0.4-2 mol %) efficiently
catalyzes the N-alkylation of primary and secondary alkyl and aromatic amines using primary alcohols
ROH (R = Et, nPr, nBu, PhCH ) under mild reaction conditions (30 - 100 °C) with an alcohol / amine
molar ratio of 10-100. Formation of the monohydride RuH(OAc)(CO)(DiPPF) (4) has been observed by
reaction of 3 with iPrOH in the presence of NEt at RT through an equilibrium reaction.
2
(DiPPF) (2) obtained from Ru(OAc)
2
(PPh
3
)
2
(1) and 1,1'-
2
2
3
Keywords: N-alkylation • amines • alcohols • borrowing hydrogen • ruthenium
The selective formation of C-N bonds is a reaction of high relevance for the synthesis of amine and
[1]
heterocycle compounds for fine and pharma chemicals. As a matter of fact, the preparation of several
drug molecules involves N-substitution transformations, which are usually performed by reaction of
amines with alkylating agents or via reductive amination. In this context, the catalytic N-alkylation of
amines using environmentally friendly alcohols as alkylating reagents and affording water as only
byproduct, is an attractive atom-economic way for the C-N bond formation, widely studied in academia
and of great interest for industrial applications.[2] It is generally accepted that this reaction may occur
through a catalytic borrowing hydrogen approach, in which primary alcohols are dehydrogenated to
carbonyl compounds which react with amines, affording imines that are hydrogenated to N-alkylated
amines (Scheme 1).
1
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201702996
Scheme 1. N-alkylation of amines with alcohols via borrowing hydrogen
Main group metal hydroxides and alkoxides were found to catalyze the N-alkylation of amines with
[
3]
[2]
alcohols under harsh conditions, resulting in low yield and selectivity. In the last decades, Ir, Ru and
[
4]
more recently Mn and Fe and have attracted a great deal of attention for N-alkylation via borrowing
hydrogen. Examples of ruthenium catalysts generated in situ entails the use of the precursors
O,[5] Ru
(CO)12,[6] [RuCl
(p-cymene)]
[7]
[Ru(COD)Cl
]
2 n
[8]
RuHCl(CO)(PPh
)
,[9] and
RuCl
RuH
3
·nH
2
3
2
2
3
3
[10]
2
(CO)(PPh
3
)
3
in combination with phosphanes, phosphates and nitrogen ligands. Conversely,
,[11] RuH
(PPh
)
4
,[12] RuCl(η -C
5
H
5 5
)(PPh
)
,[13] [RuCl(p-
well-defined catalysts are RuCl
2
(PPh
3
)
3
2
3
3
2
cymene)(PN)]X,[14] RuHCl(CO)(PNY) (Y = N, P),[15] RuCl(CNN)(dppb)[16] and Ru pincer NNN
complexes.[17] N-alkylation is generally performed at high temperature (typically 120 or 180 °C), primary
alcohols are generally more reactive than secondary and long reaction times are required. Therefore, the
development of selective catalysts which can work at low temperature is of crucial importance for the
application of this relevant sustainable transformation. Monocarbonyl Ru complexes, namely the Dobson
[18]
[19]
catalyst Ru(OCOCF
active catalysts for alcohol dehydrogenation, which is the first step of the catalytic N-alkylation.
Recently, the in situ generated complex Ru(OCOCF (CO)(PPh / (R)-BINAP has been found active
3
)
2
(CO)(PPh
3
)
2
and [Ru(μ-OCOC
2
F
4
OCO)(CO)(PP)]
2
(PP = diphosphane), are
3
)
2
)
3 2
in the asymmetric C-C coupling between olefin and primary alcohols. [20] It is worth pointing out that the
coordination properties of carboxylate ligands, which display moderate stability with relatively high
lability, are particularly attracting for catalytic reactions, but no examples of carboxylate Ru complexes
have been reported in the N-alkylation reaction.
We describe here the straightforward preparation of the acetate complexes Ru(OAc)
2
(CO) (DiPPF)
n
(
n = 0, 1), bearing the bulky ferrocene diphosphane DiPPF.[21] The monocarbonyl acetate complex has
2
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201702996
been found highly active in the alkylation of primary and secondary amines with primary alcohols under
mild reaction conditions. Evidence has been provided for the formation of the monohydride species
RuH(OAc)(CO)(DiPPF) in the alcohol / amine media.
The ruthenium diphosphane compound Ru(OAc)
2
(DiPPF) (2) was easily prepared by treatment of the
acetate precursor Ru(OAc)
2
(PPh
3
)
2
(1) with one equivalent of DiPPF in cyclohexane at reflux (4 h, 87 %
yield) (Scheme 2).
Scheme 2. Synthesis of Ru(OAc)
2
(DiPPF) (2) and Ru(OAc) (CO)(DiPPF) (3).
2
1
13
1
The H and C{ H} NMR spectra of 2 at RT show two signals for the ferrocene CH moieties, consistent
with a rapid displacement of the Ru-O acetate bond trans to the P atom. Complex 2 reacts cleanly with
formaldehyde (5 equiv) in toluene at reflux within 2 h, affording the monocarbonyl acetate complex 3 in
7
8 % yield. Alternatively, complex 3 can also be prepared by reaction of 2 with paraformaldehyde in
3
1
1
toluene. At RT the P{ H} NMR spectrum of 3 in CD
2
Cl
2
shows a broad singlet at δ = 61.7 ppm (Δν
½
1
=
110 Hz), while the H NMR spectrum exhibits four C-H signals for the ferrocene C
5
H
4
moiety and a
-
singlet at δ = 1.92 ppm for the two acetate ligands, indicating an exchange of the OAc groups on the
3
1
1
NMR time scale at RT. Upon cooling at -75 °C both the P and H NMR spectra become more complex,
possibly due to the formation of conformers with the bulky isopropyl ferrocene ligand and the different
coordination mode of the two acetates (see Supporting Information). The CO stretching of 3 is at
-1
relatively low wavelength (1939 cm ), in agreement with the presence of the electron-reach diphosphane.
The carboxylates complexes 1-3 (0.4-2 mol %) were found active in the N-ethylation of N-
methylcyclohexylamine (a) using commercially grade ethanol under mild reaction conditions (Scheme
3
). With the diacetate derivative 1, the tertiary amine NMeEtCy is formed in 25 % at 78 °C (20 h), with
a EtOH/NHMeCy = 100 (entry 1, Table 1).
3
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201702996
Scheme 3. N-alkylation of amines with alcohols catalyzed by ruthenium acetate complexes
Table 1. N-ethylatacion of methylcyclohexylamine (a) with EtOH catalyzed by ruthenium acetate
complexes (1 mol %).
Entry Complex
Ligand or
additive
EtOH/
NHMeCy [°C]
T
Time Conv[a] Byproducts[a]
[h]
[%]
[%]
(equiv)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
2
2
100
10
10
100
10
10
10
100
10
10
10
78
65
65
78
78
78
78
78
65
65
30
30
78
30
15
15
16
29
25
25
6
24
6
40
40
22
25
80
96
6
0
51
1
97
92
98
68
97
0
3
1
< 1
0
5
5
< 1
1
< 1
1
< 1
-
TFA (15)
Ru(OAc)
Ru(OAc)
Ru(OAc)
Ru(OAc)
3
3
3
3
3
2
2
2
2
(DPPF)
(CO)(PPh
(CO)(PPh
(CO)(PPh
3
3
3
)
2
)
2
)
2
DiPPF (1.5)
DPPF (1.5)
0
1
2
3
TFA (10)
TFA (10)
[
[
b]
b]
10
10
no catalyst
[
a] The conversion was determined by GC analysis. [b] Catalyst loading 2 mol%.
By employment of 2 bearing DiPPF 80 % conversion was achieved in 15 h at 65 °C with a lower
EtOH/NHMeCy = 10 (entry 2). Interestingly, an increase of rate is observed by addition of CF COOH
TFA) (15 equiv, with respect to Ru) to 2, affording 96 % of the ethylated amine (entry 3). The use of
3
(
the corresponding DPPF[2121] complex Ru(OAc)
(DPPF) leads to poor conversion (6 %) (entry 4). The
2
monocarbonyl derivative Ru(OAc)
2
(CO)(PPh
3
)
2
gives no conversion under these catalytic conditions
4
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201702996
(entry 5). Addition of DiPPF (1.5 equiv) to the latter derivative affords 51 % of NMeEtCy at 78 °C in 25
h, whereas with DPPF poor conversion is achieved (1 %), indicating that the more basic DiPPF leads to
a more active catalytic species, with respect to DPPF (entries 6, 7). Employment of the isolated
monocarbonyl DiPPF complex 3 results in 97 % conversion in 6 h at 78 °C, whereas at 65 °C 92 % of
product is achieved in 24 h, with EtOH/NHMeCy = 100 and 10 respectively (entries 8, 9). The higher
catalytic activity of 3 with respect to the in situ generated catalyst Ru(OAc)
ascribed to the incomplete diphosphane substitution. Similar to 2, addition of TFA (10 equiv) to 3 at 65
C results in an acceleration effect, affording 98 % of product in 6 h (entry 10). Interestingly, by
2
(CO)(PPh
3
)
2
/ DiPPF can be
°
performing the reaction at 30 °C with 3 (2 mol %), 67 % of NMeEtCy is attained in 40 h (entry 11),
whereas addition of TFA, resulted in 97 % of product (entry 12), indicating that quantitative N-alkylation
can be achieved at low temperature. Control experiments carried out with 1.5-50 equiv of TFA with
respect to 3, show that the faster conversion of a into NMeEtCy has been observed with 3-10 equiv of
-1
acid (TOF up to 200 h at 50 % conv. at 65 °C, see Figure S-31 of SI), suggesting that the N-alkylation
occurs in a suitable pH window. An increase of rate by addition of acids has previously been reported
/ xantophos system,[1010] and for Ru(OCOCF
)
2
(CO)(PPh
)
2
[18]
in the alcohol
for the RuH
2
(CO)(PPh
3
)
3
3
3
dehydrogenation. By carrying out the reaction without Ru catalysts no N-ethylation is observed after 22
h (entry 13). In addition, no formation of ethyl acetate was observed during the N-ethylation of a with 3,
suggesting that the in situ generated acetaldehyde undergoes a faster attack of the amine with respect to
ethanol.
Complex 3 (0.4-1 mol %) shows catalytic activity for the N-alkylation of primary and secondary
amines with primary alcohols (Scheme 3). Cyclohexylamine (b) reacts with EtOH affording
quantitatively the tertiary amine NEt
detected by GC analysis.
2
Cy in 21 h at 78 °C (entry 1, Table 2), via the NHEtCy intermediate
Table 2. N-alkylation of amines with alcohols catalyzed by 3 (1 mol %).
Alcohol/
Amine
Time
[h]
Conv.[a] Byproducts[a]
Entry
Amine
Alcohol
T [°C]
[%]
[%]
1
2
3
4
5
6
7
b
c
d
e
f
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
MeOH
100
100
10
10
10
78
78
65
65
65
65
65
21
24
24
5
5
6.5
24
96[b]
3
1
2
-
1
-
15
70[
b]
100
99
100
10
g
a
10
10
1
5
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201702996
8
9
a
a
a
a
a
b
MeOH
nPrOH
nBuOH
10
10
10
5
10
2
100
65
65
100
65
100
78
24
27
30
48
36
30
15
16
68
60
87
0
1
1
7
1
0
1
2
3
4
1
1
1
1
PhCH
iPrOH
2
OH
1
1
10[
-
d]
1,4-butanediol
EtOH
87
100
[
c]
e
10
[
[
a]
b]
1
The conversion was determined by GC analysis and assessed by H NMR spectroscopy.
Dialkylated product. Catalyst loading 0.4 mol%. Monoalkylated product.
[c]
[d]
The bulky amine NHiPr
gives NEt Ph (70 %) at 65 °C after 24 h (entry 3). Conversely, the drug precursors N-benzylpiperazine
e), N-phenylpiperazine (f) and morpholine (g) were quantitatively ethylated at 65 °C to the
2
(c) leads to NEtiPr
2
in poor conversion (15 %) (entry 2), whereas aniline (d)
2
(
corresponding amines in 5 h (entries 4, 5) and 6.5 h (entry 6), indicating that more basic and less sterically
hindered amines undergo faster alkylation with 3. Experiments carried out with a and using different
primary alcohols show that while with MeOH poor conversion is attained at 65 and 100 °C (10 and 16
%
, entries 7 and 8), nPrOH and nBuOH afforded the corresponding amines NMeRCy (R = Pr, Bu) in 68
and 60 % yield in 27 and 30 h (entries 9 and 10). With benzyl alcohol NMe(CH Ph)Cy is formed in 87
yield at 100 °C after 48 h (entry 11), whereas the use of the secondary alcohol iPrOH gave no
2
%
conversion at 65 °C (entry 12). The use of the 1,4-butanediol in molar ratio 2/1 with respect to the primary
amine b afforded the cyclic tertiary amine N-cyclohexylpyrrolidine in 87 % yield at 100 °C after 30 h,
the reaction efficiently occurs at low alcohol / amine ratio (entry 13, Eq 1).
Although the dehydrogenation step is thermodynamically favored for secondary alcohol compared to
primary ones,[22] it is likely that the higher reactivity of the primary ones is due to easier formation or
hydrogenation of the corresponding aldimines with respect to ketimines. To show the practical potential
of catalyst 3, the amine 1-benzyl-4-ethylpiperazine (1.87 g, 81 %) was obtained from e (1.98 g) and
ethanol (5.7 mL) using 30 mg of 3 (0.4 mol %) at 78 °C in 15 h (entry 14, see SI).
In the catalytic N-akylation reaction the formation of a Ru hydride species is expected during the
alcohol dehydrogenation (Scheme 1).[23] Complex 3 is soluble in alcohols (EtOH, iPrOH) affording a
6
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201702996
3
1
broad P NMR singlet rather similar to that observed for 3 in CD
weakly coordinating NEt
RuH(OAc)(CO)(DiPPF) (4), which equilibrates with the dicarboxylate 3 (4 / 3 = 1 / 9 molar ratio) (Eq
).
2
Cl
2
. Interestingly, addition to 3 of the
3
amine (20 equiv) at RT in 2-propanol leads quickly to the monohydride
2
3
1
1
The P{ H} NMR spectrum of 4 shows two doublets at δ = 80.0 and 24.6 ppm (external CDCl lock)
3
2
with a small J(P,P) of about 7.7 Hz, the high field resonance being attributed to the P trans to the H,
2
displaying a J(H,P) of 135 Hz (see SI). Complex 4 also forms by reacting 3 with dihydrogen (4 atm) in
1
[
D
8
]toluene through an equilibrium reaction, affording in the H NMR spectrum a doublet of doublets at
2
δ = -5.98 ppm for the Ru-H with J(H,P) of 31.3 and 133 Hz for the cis and trans P atoms, respectively,
likewise the RuH(CNN)(dppb) system.[24] It is worth pointing out that, while the dinuclear hydride
complex [Ru(µ-H)(CO)(BINAP)]
2
(O
2
CC
2
F
4
CO ) has been described as resting state in the alcohol
2
dehydrogenation,[19] the mononuclear species RuHX(CO)(PP) (X = Cl, carboxylate) have been
postulated to play a key role in the catalytic cycles of alcohol dehydrogenation[1919] and C-C coupling
reactions.[25]
As regards the mechanism of the N-alkylation by 3, it is likely that the monohydride 4 is formed by
substitution of one acetate with the alkoxide, generated in the alcohol / amine media, followed by β-H-
elimination. The resulting aldehyde reacts with the amine, affording the imine (and water) which gives
insertion into the Ru-H bond. Protonation with alcohol leads to the alkylated amine and formation of the
Ru-alkoxide which closes the cycle.
In summary, we have shown that the easily accessible carboxylate Ru(OAc) (CO)(DiPPF) (3),
2
containing the bulky DiPPF diphosphane, displays high activity in the N-alkylation of amines with
primary alcohols under mild reaction conditions. This system is one of the most active catalysts reported
to date, allowing unprecedented mild N-alkylation at temperature as low as 30 °C and without the use of
additional base or solvents. A monohydride species forms promptly at RT in alcohol in the presence of
NEt
3
via an equilibrium reaction. Studies are ongoing to rationalize the acceleration effect of CF
3
COOH
7
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201702996
and give new insights on the mechanism of the N-alkylation reaction, as well as to extend this protocol
for other C-X coupling reactions, including the use of chiral diphosphanes in asymmetric catalysis.
Acknowledgments
We thank Dr. P. Martinuzzi (Università di Udine) for NMR assistance and Mr. P. Polese for carrying out
the elemental analyses.
[
a] Dr. R. Figliolia, Dr. S. Baldino, Prof. W. Baratta
Dipartimento DI4A, Università di Udine
Via Cotonificio 108, 33100 Udine, Italy
Fax: +39-0432-558803
E-mail: walter.baratta@uniud.it
[
b] Dr. A. Zanotti-Gerosa, Dr. H. G. Nedden
Johnson Matthey Fine Chemicals Division
2
8 Cambridge Science Park, Milton Road
Cambridge, CB4 0FP, United Kingdom
References and notes
[
1] a) S. A. Lawrence, Amines: Synthesis, Properties and Applications, Cambridge University Press
004; b) J. S. Carey, D. Laffan, C. Thomson, M. T. Williams, Org. Biomol. Chem. 2006, 4, 2337.
2
[
2] a) X. Ma, C. Su, Q. Xu, Top. Curr. Chem. (Z) 2016, 374, 27; b) Q. Yang, Q. Wang, Z. Yu, Chem.
Soc. Rev. 2015, 44, 2305; c) J. Leonard, A. J. Blacker, S. P. Marsden, M. F. Jones, K. R.
Mulholland, R. Newton, Org. Process Res. Dev. 2015, 19, 1400; d) C. Gunanathan, D. Milstein,
Science 2013, 341, 249; e) G. E. Dobereiner, R. H. Crabtree, Chem. Rev. 2010, 110, 681; f) G.
Guillena, D. J. Ramón, M. Yus, Chem. Rev. 2010, 110, 1611.
[3] a) J. U. Nef, Liebigs Ann. Chem. 1901, 318, 137; b) W. A. Lazier, H. Adkins, J. Am. Chem. Soc.
1
924, 46, 741; c) Y. Sprinzak, J. Am. Chem. Soc. 1956, 78, 3207.
[4] a) S. Elangovan, J. Neumann, J.-B. Sortais, K. Junge, C. Darcel, M. Beller, Nat. Commun. 2016,
7
, 12641; b) M. Mastalir, M. Glatz, N. Gorgas, B. Stçger, E. Pittenauer, G. Allmaier, L. F. Veiros,
8
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201702996
K. Kirchner, Chem. Eur. J. 2016, 22, 12316; c) T. Yan, B. L. Feringa, K. Barta, Nat. Commun.
014, 5, 5602.
2
[
[
[
5] a) K.-T. Huh, Y. Tsuji, M. Kobayashi, F. Okuda, Y. Watanabe, Chem. Lett. 1988, 449; b) G. Bitsi,
E. Schleiffer, F. Antoni, G. J. Jenner, Organomet. Chem. 1989, 373, 343.
6] a) A. Tillack, D. Hollman, D. Michalik, M. Beller, Tetrahedron Lett. 2006, 47, 8881; b) D.
Hollman, A. Tillack, D. Michalik, R. Jackstell, M. Beller, Chem. Asian J. 2007, 2, 403.
7] a) A. S. Stalsmeden, J. L. Belmonte Vazquez, K. van Weerdenburg, R. Rae, P.-O. Norrby, N. Kann,
ACS Sustainable Chem. Eng. 2016, 4, 5730; b) A. B. Enyong, B. Moasser, J. Org. Chem. 2014, 79,
7
553; c) M. H. S. A. Hamid, C. L. Allen, G. W. Lamb, A. C. Maxwell, H. C. Maytum, A. J. A.
Watson, J. M. J. Williams, J. Am. Chem. Soc. 2009, 131, 1766; d) M. H. S. A. Hamid, J. M. J.
Williams, Tetrahedron Lett. 2007, 48, 8263; e) M. H. S. A Hamid, J. M. J. Williams, Chem.
Commun. 2007, 725.
[
8] V. R. Jumde, L. Gonsalvi, A. Guerriero, M. Peruzzini, M. Tadde, Eur. J. Org. Chem. 2015, 1829.
9] N. Nakagawa, E. J. Derrah, M. Schelwies, F. Rominger, O. Trapp, T. Schaub, Dalton Trans. 2016,
[
4
5, 6856.
10] A. J. Blacker, M. M. Farah, M. I. Hall, S. P. Marsden, O. Saidi, J. M. J. Williams, Org. Lett. 2009,
1, 2039.
[
1
[
11] a) Y. Watanabe, Y. Tsuji, Y. Ohsugi, Tetrahedron Lett. 1981, 22, 2667; b) Y. Watanabe, Y. Tsuji,
H. Ige, Y. Ohsugi, T. J. Ohta, Org. Chem. 1984, 49, 3359; c) A. Arcelli, B.-T. Khai, G. Porzi, J.
Organomet. Chem. 1982, 235, 93; d) S. Ganguly, F. L. Joslin, D. M. Roundhill, Inorg. Chem. 1989,
2
8, 4562; e) J. A. J. Marsella, Org. Chem. 1987, 52, 467.
[12] a) S.-I. Murahashi, K. Kondo, T. Hakata, Tetrahedron Lett. 1982, 23, 229; b) C. S. Cho, J. H. Kim,
T.-J. Kim, S. C. Shim, Tetrahedron 2001, 57, 3321.
[
13] A. Del Zotto, W. Baratta, M. Sandri, G. Verardo, P. Rigo, Eur. J. Inorg. Chem. 2004, 524.
14] a) J. J. A. Celaje, X. Zhang, F. Zhang, L. Kam, J. R. Herron, T. J. Williams, ACS Catal. 2017, 7,
[
1
136; b) K. O. Marichev, J. M. Takacs JACS Catal. 2016, 6, 2205.
[15] a) E. Balaraman, D. Srimani, Y. Diskin-Posner, D. Milstein, Catal. Lett. 2015, 145, 139; b) B.
Gnanaprakasam, E. Balaraman, Y. Ben-David, D. Milstein, Angew. Chem. Int. Ed. 2011, 50,
1
2240; c) B. Gnanaprakasam, D. Milstein, Angew. Chem. Int. Ed. 2008, 47, 8661.
[16] S. Agrawal, M. Lenormand, B. Martin-Matute, Org. Lett. 2012, 14, 1456.
[17] F.-L. Yang, Y.-H. Wang, Y.-F. Ni, X. Gao, B. Song, X. Zhu, X.-Q. Hao, Eur. J. Org. Chem. 2017,
3
341.
9
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201702996
[18] a) A. Dobson, S. D. Robinson, Inorg. Chem. 1977, 16, 137; b) C. J. Creswell, A. Dobson, D. S.
Moore, S. D. Robinson, Inorg. Chem. 1979, 18, 2055.
[
19] J. van Buijtenen, J. Meuldijk, J. A. J. M. Vekemans, L. A. Hulshof, H. Koojiman, A. L. Spek,
Organometallics 2006, 25, 873.
[
[
[
[
20] K. D. Nguyen, D. Herkommer, M. J. Krische, J. Am. Chem. Soc. 2016, 138, 5238.
21] DiPPF = 1,1'-bis(diisopropylphosphino)ferrocene; DPPF = 1,1'-bis(diphenylphosphino)ferrocene.
22] H. Adkins, R. M. Elofson, A. G. Rossow, C. C. Robinson, J. Am. Chem. Soc. 1949, 71, 3622.
23] a) S. E. Clapham, A. Hadzovic, R. H. Morris, Coord. Chem. Rev. 2004, 248, 2201; b) P. Espinet,
A. C. Albéniz Fundamentals of Molecular Catalysis, Current Methods in Inorganic Chemistry,
Vol. 3 (Eds. H. Kurosawa, A. Yamamoto) Elsevier: Amsterdam, 2003, Chap. 6, p 328.
24] a) W. Baratta, G. Chelucci, S. Gladiali, K. Siega, M. Toniutti, M. Zanette, E. Zangrando, P. Rigo,
Angew. Chem. Int. Ed. 2005, 44, 6214; b) W. Baratta, S. Baldino, M. J. Calhorda, P. J. Costa, G.
Esposito, E. Herdtweck, S. Magnolia, C. Mealli, A. Messaoudi, S. A. Mason, L. F. Veiros, Chem.
Eur. J. 2014, 20, 13603.
[
[25] S. Oda, J. Franke, M. J. Krische, Chem. Sci. 2016, 7, 136.
1
0
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201702996
Graphical abstract
Mild N-Alkylation of Amines with Alcohols Catalyzed by the Acetate Ru(OAc)
2
(CO)(DiPPF)
Complex
Rosario Figliolia, Salvatore Baldino, Hans Günter Nedden, Antonio Zanotti-Gerosa, and Walter Baratta
The novel complex Ru(OAc)
2
(CO)(DiPPF) easily prepared by carbonylation of Ru(OAc) (DiPPF) with
2
H
2
CO efficiently catalyzes the alkylation of primary and secondary amines with alcohols under mild
reaction conditions. Addition of a suitable amount of TFA increases the rate of reaction. Evidence of the
formation of the monohydride RuH(OAc)(CO)(DiPPF) species is provided.
1
1
This article is protected by copyright. All rights reserved.