Catalyst Evolution in Ruthenium-Catalyzed Coupling of Amines and Alcohols

Article abstract of DOI:10.1021/acscatal.9b03679

We describe the mechanism, scope, and catalyst evolution for our ruthenium-based coupling of amines and alcohols, which proceeds from a [(η⁶-cymene)RuCl(PyCH₂P^tBu₂)]OTf (1) precatalyst. The method selectively produces secondary amines through a hydrogen borrowing mechanism and is successfully applied to several heterocyclic carbinol substrates. Under the reaction conditions, precatalyst 1 evolves through a series of catalytic intermediates: [(η⁶-cymene)RuH(PyCH₂P^tBu₂)]OTf (3), [Ru₃H₂Cl₂(CO)(PyCH₂P^tBu₂)₂{μ-(C₅H₃N)CH₂P^tBu₂}]OTf (4), and a diastereomeric pair of [Ru₂HCl(CO)₂(PyCH₂P^tBu₂)₂(μ-O₂CⁿPr)]X (trans-5, X = Cl; cis-6, X = OTf). The structures of 4 and 6 were established by single-crystal X-ray diffraction. A study of catalytic activity shows that 4 is a dormant (but alive) form of the catalyst, whereas 5 and 6 are the ultimate dead forms. Electrochemical studies show that 4 is redox active and undergoes electrochemically reversible one-electron oxidation at E_1/2 = 0.442 V (vs Fc⁺/Fc) in CH₂Cl₂ solution. We discuss the factors that govern the formation of 3-6 and the role of selective ruthenium carbonylation, which is essential for enabling generation of the active catalyst. We also connect these discoveries to the identification of conditions for amination of aliphatic alcohols, which eluded us until we understood the catalyst's complex speciation behavior.

Full text of DOI:10.1021/acscatal.9b03679

Subscriber access provided by UB der LMU Muenchen
Article
Catalyst Evolution in Ruthenium-Catalyzed Coupling of Amines and Alcohols
Valeriy Cherepakhin, and Travis J. Williams
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b03679 • Publication Date (Web): 31 Oct 2019
Downloaded from pubs.acs.org on November 4, 2019
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 14
ACS Catalysis
1
2
3
4
5
6
7
8
9
Catalyst Evolution in Ruthenium-Catalyzed Coupling of Amines and
Alcohols
Valeriy Cherepakhin and Travis J. Williams*
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Donald P. and Katherine B. Loker Hydrocarbon Institute and Department of Chemistry, University of Southern
California, Los Angeles, California, 90089-1661, United States.
ABSTRACT: We describe the mechanism, scope, and catalyst evolution for our ruthenium-based coupling of amines and
t
alcohols, which proceeds from a [(η6-cymene)RuCl(PyCH2PBu2 )]OTf (1) precatalyst. The method selectively produces
secondary amines through a hydrogen borrowing mechanism and is successfully applied to several heterocyclic carbinol
substrates. Under the reaction conditions, precatalyst 1 evolves through a series of catalytic intermediates: [(η6-
t
cymene)RuH(PyCH2PBu2 )]OTf (3), [Ru3H2Cl2(CO)(PyCH2PBut2)2{µ-(C5H3N)CH2PBut2}]OTf (4), and a diastereomeric pair of
[Ru2HCl(CO)2(PyCH2PBut2)2(µ-O2CPrn)]X (trans-5, X = Cl; cis-6, X = OTf). The structures of 4 and 6 were established by single-
crystal X-ray diffraction. A study of catalytic activity shows that 4 is a dormant (but alive) form of the catalyst, whereas 5 and
6 are the ultimate dead forms. Electrochemical studies show that 4 is redox-active and undergoes electrochemically-
reversible one-electron oxidation at E1/2 = 0.442 V (vs. Fc+/Fc) in CH2Cl2 solution. We discuss the factors that govern formation
of 3 – 6 and the role of selective ruthenium carbonylation, which is essential for enabling generation of the active catalyst. We
also connect these discoveries to the identification of conditions for amination of aliphatic alcohols, which eluded us until we
understood the catalyst’s complex speciation behavior.
KEYWORDS Alcohol, Amine, Hydrogen Borrowing, Ruthenium, Metal Hydride, Metal Cluster
the ways in which different ligands govern catalytic activity,
INTRODUCTION
turnover, and deactivation of a homogeneous catalyst: it’s
impossible to tell a story until you know the characters.
While such understanding ultimately can direct design of
new, more prolific catalytic systems, we see little detailed
work on this problem for these arene-ligated ruthenium-
based amination catalysts. Moreover, we have
characterized unexpected transformations of precatalytic
species including ligand derivatization and displacement,
ligation with substrate degradation products, cluster
formation, etc. with a number of ruthenium- and iridium-
based precursors that we expected to behave simply.27
Over the last decade many ruthenium-based catalytic
systems have been developed that enable alcohol-amine
coupling through hydrogen borrowing. This reaction is of
vital importance because of its relevance to the efficient
preparation of medicinal synthons. We divide the known
catalysts into three structural groups. First, some catalysts
are formed in situ from a metal precursor (such as
Ru3(CO)12,1–5 [RuCl2(η6-p-cymene)]2,6–13 [RuCl2(COD)]n,14
RuCl2(PPh3)3,7 [Cp*RuCl2]2,15 or RuCl3·xH2O16) and
a
phosphine. Second, some proceed from arene complexes,
e.g. [(η6-arene)RuClL2]X17–21 or [(η6-arene)RuCl2L]18,22 (L =
PR3, NHC, Py, SR2, SeR2; X = Cl, PF6, OTf). Third, there are
several excellent pincer complexes of PNN,23 PNO/PNS,24
PNP,25 and NNC26 types (Figure 1) that typically contain
RuH(CO) fragments and operate through a metal-ligand
cooperative mechanism that is enabled by deprotonation of
CH2PR2 group. About half of the reported methods proceed
from arene complexes (the second group), but very little is
known about the bonding and speciation of ruthenium in
these catalyst systems. Although some authors sketch
We recently reported
a
ruthenium complex [(η6-
cymene)RuCl(PyCH2PBut2)]OTf (1, Figure 1) that efficiently
catalyzes coupling of primary amines and benzylic alcohols
without the aid of a strong base.21 In this study we extend
the reaction scope to aliphatic alcohols and certain
heterocyclic carbinols. Our identification of these
conditions presaged a complicated story of why we had not
found them before. To answer this, we present a study on
the speciation and life cycle of the ruthenium complexes in
this reaction and show how the story reveals the way that
precatalyst 1 activates, reacts, deactivates, and dies.
intermediates
and
catalytic
cycles
for
their
systems,10,15,18,19,22,24 we find most these proposals not to be
supported by experiment, and we see that few address
precatalyst speciation and activation, which are almost
certainly not simple when an (arene)ruthenium complex is
introduced into a solution of amines and alkoxides.
OTf
N
Ru
H
N
Cl
N
Ru
PPh2
P
1
Cl
tBu
CO
tBu
Understanding composition, structure, and reactivity of
catalytic intermediates is crucial for systematic
comprehension and analysis of reaction mechanisms and
D. Milstein, 2015
T. Williams, 2017
Figure 1. Precatalysts for Alcohol-Amine Coupling.
ACS Paragon Plus Environment

ACS Catalysis
Page 2 of 14
activity among the tested complexes under the specified
conditions.
RESULTS AND DISCUSSION
Coupling of Aliphatic Amines and Alcohols
1
2
3
4
5
6
7
8
The scope of alcohol-amine coupling with precatalyst 1 can
be successfully extended to heterocyclic substrates, such as
pyridines, thiophenes, and indoles (Table 2). Acidic
substrates, such as phenols (entry 2), can be reacted since
the system does not need a strong base to activate the
catalyst.
We developed complex 1 as a catalyst for N-alkylation of
primary amines with benzylic alcohols, which left an
opportunity to optimize the system for aliphatic alcohols.
We found excellent results with catalyst loadings down to 1
mol% in our original study. While benzyl alcohols react
smoothly with this catalyst loading, providing secondary
amines with excellent yield and selectivity, aliphatic
alcohols, tended to overalkylate and proceed in low
efficiency, giving an undesirable yield and selectivity of
amine products. Here we demonstrate cutting the catalyst
load even further slows down the overalkylation by aliphatic
alcohol and enables selective, high yielding formation of
secondary amine products that we were not able to achieve
with our initial conditions.
Table 2. Expansion of Substrate Scope for Amine-Alcohol
Coupling.a
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Complex 1
R1
NH2
R2
OH
+
H2O
+
R1
N
R2
110 oC, Neat
H
Catalyst, %
Time, h
Yield, %
0.2
En
try
Alcohol
Amine
Product
NH2
OH
NH
1b
A
36
90
We demonstrate this finding by using 1-aminohexane and
1-butanol as representative substrates at 0.2 mol% Ru
loading (Table 1). In the absence of alcohol (entry 1) 1-
aminohexane undergoes slow homocoupling to give
dihexylamine and NH3. When 1-butanol is present, the
homocoupling route is halted and amine-alcohol coupling
becomes the major reaction pathway (entries 2 – 4). The
catalytic system exhibits high selectivity of amine
monoalkylation by providing 98% yield of N-
butylhexylamine (entry 2). Increasing the alcohol/amine
ratio above 1:1 does not significantly affect the product
distribution indicating slowness of the second alkylation
step. Thus, the catalytic system is highly selective for
secondary amine formation. Possible by-products, such as
amides, esters, carboxylates, and imines are not detected.
Imine formation is easily suppressed by conducting the
reaction in a closed reactor. Although the reaction is rapid
(full conversion is reached within 1 hour with 1.0 mol% Ru),
we find that the catalyst fails to give full conversion of 1-
aminohexane at loadings below 0.05 mol% (vide infra).
NH2
HO
0.4
42
70
NHBu
2
3
BuOH
NH2
B
HO
MeO
MeO
MeO
0.4
30
83
0.4
30
81
0.7
42
62
NHBu
BuOH
BuOH
C
MeO
D
4
N
NH2
N
S
NHBu
HexNH2
OH
E
5c
S
NHHex
0.2
20
74
NHBu
NH2
6b
N
H
N
F
BuOH
H
a
Reaction conditions: a mixture of amine (2.0 mmol),
alcohol (3.0 mmol), and complex 1 was stirred for required
period in a closed reactor at 110 oC. b Alcohol loading is 2.0
mmol. c Alcohol loading is 1.3 mmol.
Time-Course Study; Synthesis and Characterization of
Ruthenium Complexes
Table 1. Coupling of 1-Aminohexane with 1-Butanol.a
Discovery of improved catalyst performance at reduced
catalyst loadings presaged a very interesting story about
dimerization, cluster formation, or some combination of
multi-metallic pathways that could be involved in the
process, probably to the detriment of catalyst turnover.
Despite its potential complexity, we determined to uncover
this story.
N
NH2
H
N
1
(0.2 mol%)
110 oC, 36 h
OH
H
N
[BuOH]/
[HexNH2
Entr
y
HexNH2
, %b
Hex2NH
, %
HexNHBu
, %
HexNBu2
, %
]
We started looking into catalyst speciation with a time-
course study using a stoichiometric loading of precatalyst 1
with 1-butanol and 1-aminohexane as coupling partners.
These starting materials are particularly convenient for this
purpose, since they allow a reaction at high temperature
and are easily separated from reaction mixture. This
facilitates analysis and isolation of ruthenium
intermediates. In a typical experiment the molar ratio of
[1]:[HexNH2]:[BuOH] was 1 : 6.5 : 144. The reaction was
1
2
3
4
0
1
2
3
62
0
0
38
0
0
–
–
2
7
7
98
93
93
0
0
a Reaction conditions: a mixture of 1-aminohexane (100 mg,
9.88 x 10-4 mol), 1-butanol, and complex 1 (1.3 mg, 2.0
mol) was stirred in a closed reactor at 110 oC for 36 h. b The
yields were calculated from 1H NMR spectra.
We compared catalytic activity of complex 1 and the known
o
performed in a closed reactor at 110 C, then the organic
alcohol-amine
coupling
catalysts,
such
as
materials were removed under vacuum and the residue was
[(cymene)RuCl2]2–dppf,10,12,13 Shvo complex,28 Ru3(CO)12–
PPh3,1,2,4,5,29 CpRuCl(PPh3)2,30 and RuH2(CO)(PPh3)3 (Table
S1). Complexes 1 and CpRuCl(PPh3)2 enable conversion of
1-aminohexane at 100% and 15%, respectively, while
others show no catalytic activity ([BuOH]/[HexNH2] = 1.5,
1.0 mol% Ru, 110 oC, 1 h). Thus, 1 exhibits superior catalytic
analyzed by 1H and 31P NMR spectroscopy (Figure S22).
Initially, the reaction was terminated after three minutes.
According to 31P NMR, two major ruthenium species in ca. 1
: 1 ratio are present in the system at this point: complex 1
(31P  = 87.31 ppm) and a new ruthenium compound (3)
ACS Paragon Plus Environment

Page 3 of 14
ACS Catalysis
that gives a doublet at 31P  = 109.75 ppm (2JPH = 42.8 Hz).
The H NMR spectrum contains the corresponding doublet
ligand appears to derive from our starting alcohol, by
analogy to an iridium-based alcohol oxidation system that
we have recently characterized.27 While the ortho-
metalated pyridyl fragment is a common substructure in
ruthenium carbonyl clusters,35–37 typically derived from
Ru3(CO)12, complex 4 is a unique example of tandem
selective monocarbonylation, pyridine ortho-metalation,
1
1
2
3
4
5
6
7
8
at –8.65 ppm, which is characteristic of a metal hydride
ligand. Thus, complex 3 is a product of chloride replacement
by hydride to give [(η6-cymene)RuH(PyCH2PBut2)]OTf.
Fractional crystallization failed to separate 3 from 1,
therefore, we confirmed its identity by independent
synthesis from 1.
and cluster self-assembly all happening from
mononuclear precursor.
a
OTf
OTf
OTf
9
OTf
Ru
Ru
CO
AgOTf, CH2Cl2
- AgCl
P
N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N
OH
N
TfO
PBut2
Cl
P
P
NH2
N
Ru
Ru
Ru
tBu
tBu
N
Cl
tBu
2 (92%)
tBu
H
Cl
110 oC, 1 h
63%
P
Cl
H
1
Ru
tBu
4
tBu
N
P
1
OTf
OTf
O
Scheme 2. Synthesis of Intermediate 4.
Complex was characterized by multinuclear NMR
Ru
Ru
110 o
C
OH
+
N
N
TfO
H
4
+
P
P
spectroscopy in CD2Cl2 solution. In its 1H spectrum, 4
presents two hydride ligands with chemical shifts at –16.50
(ddd, 2JPH = 51.6, 27.3, 9.1 Hz) and –21.36 (dd, 2JPH = 20.0, 4.5
Hz) ppm. These hydrides do not correlate in a COSY
spectrum, meaning that their peak multiplicities originate
from 1H–31P coupling. We use this feature to justify location
and coordination mode of the hydrides. Based on coupling
pattern of the peaks at –16.50 and –21.36 ppm we attribute
them to µ3-H and µ-H ligands, respectively. This assignment
fulfils coordinative saturation of all ruthenium atoms in the
molecule. 31P NMR data are consistent with three
inequivalent PN ligands (31P δ = 128.34, 116.38, and 89.76
ppm).
HOTf
tBu
tBu
tBu
3 (50%)
tBu
2
Scheme 1. Synthesis of Intermediate 3.
Although converts
[RuCl2(η6-cymene)]2
to
[(η6-
cymene)RuH(PPh3)2]+ when treated with AgPF6 and PPh3 in
methanol at 25 oC,31 treatment of 1 with AgOTf in the
presence of alcohols gives high yield of the corresponding
triflate complex, [(η6-cymene)Ru(OTf)(PyCH2PBut2)]OTf
(2), rather than the hydride (Scheme 1). The 19F NMR
spectrum of 2 in CD2Cl2 solution contains two distinct peaks
at –78.66 and –78.82 ppm with equal intensities, belonging
to the coordinated and free triflate groups. Complex 2 reacts
reversibly with 2-propanol to give hydride 3 (Scheme 1). Its
o
formation is favored at 110 C in a closed reactor; rapid
removal of acetone under vacuum provided the product in
50% yield. At room temperature the equilibrium is
completely shifted to the right. We showed this by reacting
3 with HOTf in acetone-d6 to give rapid and selective
formation of 2 as identified by its 31P peak at 91.03 ppm. The
chemical shifts of the phosphine (31P δ = 109.75 ppm) and
hydride (1H δ = –8.65 ppm) ligands are identical for the
compound obtained in this reaction and for the compound
detected in the catalytic reaction after three minutes. Thus,
complex 3 is the first ruthenium intermediate in the
sequence of precatalyst speciation.
Figure 2. Molecular structures of the cations of 4 (left) and
6 (right) shown with 50% probability ellipsoids. Hydrogen
atoms and methyl groups are omitted for clarity.
As the reaction proceeds among complex 1, 1-aminohexane,
and 1-butanol, the color of the reaction solution changes
from orange-red to black-green within 30 minutes. If the
reaction is stopped after 1 hour, a black crystalline
compound, 4, is isolated with 63% yield (Scheme 2). The
structure of 4 was established by single-crystal X-ray
diffraction (Figure 2). The complex is a trinuclear cluster
formed by three Ru(II) atoms and arranged in an
asymmetrical triangular fashion. The observed Ru–Ru
distances (2.717, 2.897, and 2.907 Å) are near Ru–Ru
distances in Ru3(CO)12,32 Ru3Cl6(PCy3)3,33 and ruthenium
metal34 (2.854, 2.593, and 2.649 Å, respectively), indicating
significant intermetallic interaction within Ru3 core. We
omit these bonds from the structural diagram for clarity’s
sake only. Complex 4 features ortho-metalated bridging
pyridyl ligand coordinated to Ru–CO group. This carbonyl
Complex 1 is further derivatized when treated with an
excess of 1-aminohexane (> 10 equivalents, Scheme 3).
After 24 hours, two major complexes, 5 and 6, were
detected by their hydride peaks at 1H δ = –15.34 and –21.03
ppm, respectively. Complexes 5 and 6 are formed in ca. 1:1
ratio, and they persist even when 100 equivalents of 1-
aminohexane is used (Figure S24). Chromatographic
purification followed by crystallization afforded 6·CH2Cl2 in
18% yield. Although we failed to obtain a pure sample of 5
from this reaction mixture, it can be isolated as 5·½THF in
3% yield as a by-product in the synthesis of complex 4.
ACS Paragon Plus Environment

ACS Catalysis
Page 4 of 14
generation of trinuclear complex 4 from mononuclear
species 1 and 3 proceeds through the intermediacy of a
dinuclear species. To look for possible dinuclear
OTf
1
2
3
4
5
6
7
8
O
O
N
P
N
P
a
Cl
H
Ru
Ru
6
OTf
intermediate, we terminated the catalytic reaction
([1]:[HexNH2]:[BuOH] is 1 : 6.5 : 144) after 10 minutes. We
find a 31P NMR spectrum from this experiment that contains
peaks of 1, 3, and 4, in addition to three new signals at
106.19, 105.65, and 104.57 ppm (Figure 4B). We
chromatographically separated the new catalytic
intermediates and analyzed them by MALDI-MS. The major
components were identified as a dinuclear (785.22 Da) and
a trinuclear (1193.76 Da) complexes, which undergo
complete transformation to 4 within 30 min (Figures 4C and
S23). Unfortunately, we could not obtain sufficient data to
establish the structures and stabilities of the new species,
hereinafter referred to as complex 4 predecessors.
tBu
tBu
OH
CO
CO
O
tBu
tBu
Ru
NH2
N
Cl
P
110 oC, 24 h
Cl
tBu
tBu
tBu
O
tBu
P
N
P
Cl
H
1
Ru
Ru
5
N
tBu
CO
CO
tBu
9
Scheme 3. Synthesis of Intermediates 5 and 6.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The structure of dinuclear species 6 was established by
single-crystal X-ray diffraction (Figure 2). Surprisingly,
apart from CO ligands derived from the alcohol, the complex
contains a bridging butyrate anion, itself the product of 1-
butanol oxidation. NMR and MALDI-MS data on complexes
5 and 6 necessitate them to be diastereomers. Identical
composition of the cations in 5 and 6 was deduced from the
mass spectra showing molecular ion peaks at m/z 857.01
and 857.21 Da, respectively. While 6 has a reflection plane
and contains two chemically equivalent PN ligands, complex
5 has lower symmetry, generating two sets of peaks for two
different PN ligands in 1H NMR spectrum. Based on this, we
formulate 5 and 6 as trans- and cis-isomers due to the
arrangement of the PN ligands (Figure 3). Consequently,
their respective bridging hydride ligands have different
coupling patterns in 1H NMR spectra: a doublet of doublets
in 5 (2Jtrans-PH = 44.7 Hz and 2Jcis-PH = 12.5 Hz) and a triplet in
6 (2Jcis-PH = 10.2 Hz).
1
A
3
*
B
*
*
4
4
4
C
5
5
130
125
120
115
110
105
100
95
90
85
(ppm)
Figure 4. 31P{1H} NMR Spectra of Ruthenium Species
Formed after 3 min (A), 10 min (B), and 30 min (C). Species
of Unknown Structure are Marked with Asterisks.
tBu
tBu
O
O
O
O
P
N
N
N
Cl
H
Cl
H
Ru
Ru
Ru
Ru
P
N
P
P
tBu
tBu
tBu
CO
CO
CO
CO
tBu
tBu
group)
tBu
group)
3. None of complexes 3 – 6 is the catalyst resting state. After
preparing samples of 3 – 6 we wanted to know if any of
these could be the catalyst resting state in amine-alcohol
coupling. For this purpose, we compared catalytic activity of
1 and 3 – 6 in the reaction between 1-aminohexane and
alcohols (Table 3). As expected, pre-catalyst 1 gives full
conversion of 1-aminohexane, as one would anticipate if the
resting catalyst were added directly to the reaction. None of
the remaining complexes gives an analogous result: they all
either suffer from poor activity (complexes 3 and 4) or have
no activity at all (complexes 5 and 6). Full conversion of 1-
aminohexane is achieved when the mixture of complex 4
predecessors is used, indicating that one of the components
is (or can access) the catalyst resting state (entry 8). Thus,
we term complex 4 as a dormant form of the catalyst,
whereas inactivity of 5 and 6 makes them ultimate, dead
forms.
5 (
6 (
cis-, Cs
trans-, C1
1
Figure 3. Coupling Patterns of the Hydride Ligands in H
NMR Spectra of Diastereomers 5 and 6.
Mechanism of Precatalyst Evolution and Death
We conducted a series of additional experiments to
investigate reactivity of 3 – 6 and determine the factors that
govern their formation in the catalytic reaction. The results
of these studies can be formulated in the following 5 points.
Table 3. Catalytic Activity Comparison Test.a
NH2
[Ru] (1 mol%)
110 oC, 18 h
NHR
NR2
1. Complex 4 preferentially forms at high ruthenium loading.
Formation of 4 depends on the [HexNH2]/[Ru] ratio in the
reaction, and the complex is detected only when
[HexNH2]/[Ru] < 40 (e.g., Ru loading must be higher than
2.5 mol% for 4 to form). Under typical catalytic conditions,
the catalyst loading is below 1 mol%, so complex 4 is not
readily formed.
ROH
HexNH2,
%
HexNHR,
%
HexNR2,
Entry
[Ru]
R
b
%
1
2
3
4
5
1
1
3
4
4
PhCH2
Bu
PhCH2
PhCH2
Bu
0
0
6
55
32
> 99
52
73
28
68
0
48
0
0
0
2. Complex 4 forms from 1 and 3 through respectively
dinuclear and trinuclear intermediates. It appears that
ACS Paragon Plus Environment

Page 5 of 14
ACS Catalysis
6
7
8
5
6
Bu
Bu
Bu
100
100
0
0
0
85
0
0
15
where the amine is an HCl scavenger. The resulting butoxide
1
2
3
4
5
6
7
8
9
complex 1-OBu undergoes rapid -hydride elimination to
form butanal and hydride complex 3. We have not observed
1-OBu directly, but its intermediacy is required for the
formation of 3. Following transformations of 3 include p-
cymene dissociation, selective carbonylation of one of the
metals, and dimerization through ortho-metalation of a
pyridine fragment. We propose that the resulting dinuclear
species 7 of unknown structure could be the active catalyst,
and a predecessor of complex 4. At high ruthenium loading,
when catalytic reaction is complete, unreacted 1 can trap
the dinuclear active catalyst 7 to form trinuclear dormant 4.
The process is fast and selective due to high kinetic stability
of 4. Then, the system slowly reaches thermodynamic rest
through a reaction among 4, 1-(butylamino)hexane, water,
and 1-butanol to form the dead catalyst forms 5 and 6.
see text
a Reaction conditions: a mixture of 1-aminohexane (51 mg,
0.5 mmol), benzyl alcohol (81 mg, 0.75 mmol) and Ru
complex (5.00 x 10-6 mol of Ru atoms) was stirred in a
closed reactor at 110 oC for 18 h. The yields were
b
calculated from 1H NMR spectra.
4. Complex 4 forms when primary amine is consumed, and the
catalytic reaction is over. Whereas it is formed at 110 oC with
a good yield, complex 4 should be quite stable under the
catalytic conditions. Indeed, it does not react with H2, CO,
and/or CO2 in CH2Cl2 solution at 1 atm; no change is
observed upon its treatment with 1-butanol or 1-
aminohexane independently at 110 oC over 24 hours. When
4 is heated with both 1-butanol and 1-aminohexane,
however, it undergoes full conversion to a diversity of
species within 7 hours (Figure S24). Also, 1H NMR analysis
of organic materials formed in the catalytic reaction shows
absence of 1-aminohexane when complex 4 begins to form.
This correlation shows limited compatibility of 4 and the
primary amine and renders 4 a kinetically stable product of
post-catalytic transformations.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
HexNH2
BuOH
H
Ru
Ru
Ru
N
N
N
H
Cl
O
P
P
P
tBu
tBu
tBu
1-OBu
HexNH3Cl
CHO
tBu
tBu
tBu
3
1
5. Complex 4 reacts slowly with a secondary amine and water
to form the ultimate dead species 5 and 6. Why does the
catalyst die? Since complex 4 begins to form as soon as
alcohol-amine coupling is complete, the subsequent slow
transformations of dormant catalyst 4 to the terminal
(dead) forms 5 and 6 should be taking place in the medium
of 1-(butylamino)hexane, water, and 1-butanol. Indeed,
when complex 4 reacts directly with 1-(butylamino)hexane,
water, and 1-butanol (110 oC, 20 h), complexes 5 and 6 are
1
Ru
N
CO
Cl
P
N
N
PBu2
P
Ru
Ru
Cl
tBu
CO
L
P
X
N
tBu
PBu2
H
N
Cl
Ru
Ru
H
FAST
Ru
p-Cymene
p-Cymene
X
X
4
N
P
7
tBu
tBu
HexNHBu
O
O
O
O
BuOH, H2O
P
N
N
P
1
Cl
H
N
P
Cl
H
formed, as shown by a H NMR experiment (Figure S24).
+
Ru
CO
Ru
Ru
CO
Ru
CO
N
SLOW
P
This process does not affect product yields in alcohol-amine
coupling when precatalyst loading is higher than 50 ppm.
However, catalyst deactivation becomes a problem at lower
catalyst loading (below 50 ppm), where a smaller portion of
catalyst is available to be sacrificed to destructive
interaction with reaction by-products.
tBu
tBu
tBu
tBu
CO
tBu
tBu
5
6
Scheme 5. Precatalyst Activation and Death.
Discovery of the trinuclear ruthenium cluster 4 illustrates
the high complexity of the inorganic side of our catalytic
story. It is a well-known phenomenon that ruthenium,47,48
osmium,48 and iridium49,50 halide complexes can
consecutively dehydrogenate and decarbonylate primary
alcohols in the presence of a phosphine ligand, giving rise to
M–CO fragment. This is the reason for carbonyl ligand being
present in 4 – 6 and some other metal complexes, that are
catalytically competent in alcohol dehydrogenation.
Scheme 6 demonstrates generation of such complexes and
highlights their common fragment (PN)MH(CO) (M = RuII
In contrast to formation of complex 4, generation of 5 and 6
is independent of the system’s [HexNH2]/[Ru] ratio. The
bridging butyrate ligand in
5 and 6 emerges from
ruthenium-catalyzed acceptorless dehydrogenation of
butanol to butyrate, which is well known.38–46 Typically, the
reaction requires hydroxide as a source of oxygen (Scheme
4A), however, in our case combination of water and
secondary amine seems sufficient (Scheme 4B). We find
that 1-butanol oxidation happens stoichiometrically rather
than catalytically, since we did not detect free butyrate in
the reaction mixture.
and IrIII). This structural analogy appears to be
a
consequence of the thermodynamic stability of
(PN)MH(CO) fragments, this allows them to form and be
stable under catalytic reaction conditions (Scheme 6B and
6C).27 We believe that selective monocarbonylation in all
these cases is the crucial step in precatalyst evolution to the
active catalyst. We are presently working to test this
hypothesis.
O
[Ru]
heat
+
+
2H2
A.
R
OH
OH
R
O
[Ru]
heat
O
B.
+
+
H2O
R2NH
R2NH2
+ 2H2
R
OH
R
O
Scheme 4. Ruthenium-Catalyzed Alcohol Oxidation.
Considering these points, we propose below a unified
scheme for precatalyst activation, evolution, and death
(Scheme 5). The process begins with substitution of
chloride for butoxide in precatalyst 1, this requires
equimolar amounts of 1-butanol and 1-aminohexane,
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 14
1
2
3
4
5
6
7
8
N
Cl
Ru
CO
Precatalyst for
alcohol-amine
coupling
N
N
PPh2
H
Ph3P
Ph3P
PPh3
H
A.
B.
C.
N
Ru
CO
PPh2
Cl
(D. Milstein, 2015)
CO
P
N
PBut2
1-butanol
1-aminohexane
N
Ru
Ru
Ru
P
H
Cl
4
N
Deactivated
catalyst
(this work)
Cl
Cl
catalytic
alcohol-amine
coupling
H
Ru
tBu
tBu
N
P
1
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
tBu
tBu
H
N
P
N
1-butanol, KOH
P
N
PBut2
Catalyst
resting state
(T. Williams, 2018)
Ir
Ir
Ir
H
catalytic alcohol
oxidation
H
CO
Scheme 6. Formation of Structurally Related Catalytic
Figure 5. Cyclic voltammogram of 4 (1.0 mM) in CH2Cl2 with
0.1 M [Bu4N]PF6 at a scan rate of 50 mV/s.
Based on high positive potential of Ru32+/Ru3 couple, we
believe that we are not generating persistent
concentration of a paramagnetic metal species in our
catalytic reaction. In sum, we find that these observed
electrochemical potentials and magnetic moments,
although interesting in their own right, are inconsistent
with any species that we observed in the catalytic pathway.
Complexes.
+
Electrochemistry
a
Triruthenium clusters are known to exhibit rich redox
chemistry.51–54 Because we were concerned that single-
electron transformations of 4 could be causing important
events in our catalyst lifecycle that would be invisible by
NMR, we thought it prudent to determine whether 4 has
facile 1-electron redox transitions and whether these
transitions are reversible and/or their products are stable.
SUMMARY
+
Redox properties of 4 (Ru3 ) were investigated by cyclic
In conclusion, we have demonstrated the utility of complex
1 as a precatalyst for alcohol-amine coupling of aliphatic
and some heterocyclic carbinol substrates. Detailed
analysis of the catalytic reaction between 1-butanol and 1-
aminohexane unraveled the precatalyst evolution
sequence, that involves complexes 3 – 6. Complex 4 is a
kinetically stable dormant catalyst form, whereas
complexes 5 and 6 are the ultimate dead catalyst forms.
Selective formation of 4 is facilitated by a high ruthenium
loading (> 2.5 mol% Ru) and forms via trapping a dinuclear
active catalyst with unreacted precatalyst. Exhaustive
catalyst poisoning is caused by the reaction with secondary
amine, alcohol, and water to give 5 and 6. For the first time,
we reveal the inherence of MH(CO) fragment to alcohol
dehydrogenation catalysts, that is generated from an
alcohol during precatalyst activation.
voltammetry in 0.1 M CH2Cl2 solution of [Bu4N]PF6 at
ambient temperature. Overall, four redox events were
detected in the potential range of –2.0 to 1.7 V vs. Fc+/Fc.
Upon scanning cathodically, the first reduction occurs at
E1/2 = –0.784 V. This redox event is electrochemically
irreversible (ΔEp = 213 mV), and the back feature appears
only at scan rates higher than 400 mV/s. Applying more
negative potential causes the second reduction event at Ep =
–1.776 V (at 100 mV/s). The corresponding back feature is
not observed even at high scan rates. Thus, the products of
both reduction steps are unstable in the solution, making
these events chemically irreversible.
+
Applying
positive
potential,
Ru3
undergoes
2+
electrochemically reversible one electron oxidation to Ru3
at E1/2 = 0.442 V (ΔEp = 63 mV) (Figure 5). Variable scan rate
study showed that Ru32+/Ru3 couple obeys the
+
Randles−Sevcik equation and, therefore, Ru32+ and Ru3+ are
freely diffusing in the solution. The second oxidation event
occurs at Ep = 1.481 V (at 100 mV/s), it is irreversible
because of subsequent chemical transformation.
Electrochemical reversibility of the first oxidation step
indicates possibility for chemical oxidation of complex 4
using an oxidant with the formal potential higher than 0.442
V. For example, oxidation with AgOTf (EAg+/Ag = 0.65 V)55 in
CH2Cl2 solution followed by crystallization from THF gives
[Ru3](OTf)2·THF (8·THF) in 73% yield. Composition of the
product was established by elemental analysis. Effective
magnetic moment (µeff) of 8 was measured in CD2Cl2
solution by Evans method56,57 using a change of CH2Cl2
chemical shift and found to be 1.88 BM. This value
corresponds to one unpaired electron in Ru32+ and is slightly
higher than the spin-only value (1.73 BM) for S = ½ state.
EXPERIMENTAL SECTION
Materials and Methods. Complex 1 was synthesized
according to published procedure.21 CDCl3 and CD2Cl2 were
purchased from Cambridge Isotope Laboratories and were
dried and distilled over CaH2. All alcohols and amines were
purchased from commercial sources and were dried and
distilled over CaH2 as well. Tyramine was sublimed in
vacuum. Hexane, CH2Cl2, Et2O, and THF were dried using a
solvent purification system. HPLC grade hexane and ethyl
acetate (EDM Millipore) were used without purification for
chromatographic isolation of A – F on Teledyne CombiFlash
instrument with “RediSep Rf Gold Amine” columns. All
reactions were conducted under nitrogen either in a
Vacuum Atmospheres glovebox (0-5 ppm O2 for all
manipulations) or outside the glovebox in a closed reactor.
1H, 13C, 19F, and 31P NMR spectra were acquired on Varian
Mercury 400, VNMRS-500, and VNMRS-600 spectrometers
and processed using MestReNova 12.0.1. All chemical shifts
ACS Paragon Plus Environment

Page 7 of 14
ACS Catalysis
3-(2-(Hexylamino)ethyl)thiophene (E). Colorless oil
are reported in ppm and referenced to the residual 1H or 13
C
solvent peaks. Following abbreviations are used: (s) singlet,
(bs s) broad singlet, (d) doublet, (t) triplet, (dd) doublet of
doublets, etc. NMR spectra of all metal complexes were
taken in 8” J. Young tubes (Wilmad or Norell) with Teflon
valve plugs. GC-MS analyses were performed on Thermo
Scientific Focus DSQ II instrument. MALDI-MS spectra were
acquired on Bruker Autoflex Speed MALDI Mass
Spectrometer. Elemental analyses were conducted on Flash
2000 CHNS Elemental Analyzer. Infrared spectra were
recorded on Bruker OPUS FTIR spectrometer. Electronic
absorption spectra were acquired on Perkin-Elmer UV-Vis-
NIR spectrometer. Cyclic voltammetry experiments were
(0.17 g, 62%). 1H NMR (500 MHz, CDCl3): δ 7.30 – 7.24 (m,
1H, ArH), 7.03 – 6.94 (m, 2H, ArH), 2.92 – 2.80 (m, 4H, 2CH2),
2.61 (t, J = 7.3 Hz, 2H, CH2), 1.46 (p, J = 7.0 Hz, 2H, CH2), 1.37
– 1.22 (m, 6H, 3CH2), 1.04 (br s, 1H, NH), 0.88 (t, J = 6.6 Hz,
3H, CH3). 13C NMR (126 MHz, CDCl3): δ 140.62, 128.31,
125.65, 120.99, 50.55, 50.07, 31.91, 30.99, 30.24, 27.18,
22.75, 14.18. IR (PE film, cm-1): 1732, 1464, 1129, 774.
MALDI-MS: m/z calcd. for [C12H22NS]+ 212.15, found 212.51.
1
2
3
4
5
6
7
8
3-(2-(Butylamino)ethyl)indole (F). Yellow solid (0.32 g,
74%). 1H NMR (600 MHz, CDCl3): δ 8.66 (br s, 1H, NH), 7.60
(d, J = 7.9 Hz, 1H, ArH), 7.35 (d, J = 8.1 Hz, 1H, ArH), 7.16 (t,
J = 7.6 Hz, 1H, ArH), 7.08 (t, J = 7.5 Hz, 1H, ArH), 7.01 (s, 1H,
ArH), 3.90 (br s, 1H, NH), 3.09 (t, J = 7.2 Hz, 2H, CH2), 3.01 (t,
J = 7.2 Hz, 2H, CH2), 2.69 (t, J = 7.8 Hz, 2H, CH2), 1.54 (p, J =
7.6 Hz, 2H, CH2), 1.28 (h, J = 7.4 Hz, 2H, CH2), 0.86 (t, J = 7.4
Hz, 3H, CH3). 13C NMR (151 MHz, CDCl3): δ 136.55, 127.29,
122.59, 122.09, 119.39, 118.76, 112.48, 111.45, 49.21,
48.90, 30.67, 24.52, 20.41, 13.90. IR (KBr, cm-1): 3289, 2729,
1626, 1456, 1358, 1237, 1107, 748. MALDI-MS: m/z calcd.
for [C14H21N2]+ 217.17, found 217.52.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
carried out using
compartment cell under nitrogen.
a Pine potentiostat in a single
General Procedure for Coupling of Amines and
Alcohols. A mixture of primary amine (2.0 mmol), alcohol,
and complex 1 (see table 2) was stirred for required period
in a closed reactor at 110 oC. Then, all volatile components
were removed under vacuum, and the product was purified
by flash column chromatography (SiO2, hexane/ethyl
acetate gradient).
[Ru(OTf)(η6-C10H14)(PyCH2PBut2)]OTf (2). Complex
1
1-(Butylamino)hexane (A). Yellow oil (0.28 g, 90%). 1H
NMR (400 MHz, CDCl3): δ 2.58 (t, J = 7.3 Hz, 2H, CH2), 2.57
(t, J = 7.3 Hz, 2H, CH2), 1.52 – 1.40 (m, 4H, 2CH2), 1.38 – 1.21
(m, 8H, 4CH2), 1.04 (br s, 1H, NH), 0.94 – 0.84 (m, 6H, 2CH3).
13C NMR (101 MHz, CDCl3): δ 50.34, 49.98, 32.49, 31.95,
30.33, 27.25, 22.76, 20.68, 14.18, 14.16. IR (PE film, cm-1):
2927, 1467, 1131, 892. GC-MS: m/z calcd. for [C10H23N]+
157.18, found 157.15.
(100 mg, 1.54 x 10-4 mol) and AgOTf (39 mg, 1.54 x 10-4 mol)
were stirred in CH2Cl2 (4 mL) for 1 hour at 25 oC. Then, the
solution was filtered and treated with Et2O (10 mL) to
induce crystallization of the product. Orange flakes were
filtered, washed with Et2O, and dried in vacuum (108 mg,
92%). 1H NMR (500 MHz, CD2Cl2): δ 9.52 (d, J = 5.9 Hz, 1H,
Py), 7.93 (t, J = 7.9 Hz, 1H, Py), 7.60 – 7.45 (m, 2H, Py), 6.70
(d, J = 6.4 Hz, 1H, C6H4), 6.65 (d, J = 5.5 Hz, 1H, C6H4), 6.48 (d,
J = 6.4 Hz, 1H, C6H4), 5.84 (d, J = 5.9 Hz, 1H, C6H4), 3.47 (dd, J
= 16.9, 13.9 Hz, 1H, CH2), 3.13 (dd, J = 16.8, 7.9 Hz, 1H, CH2),
2.76 (hept, J = 7.0 Hz, 1H, Pri), 2.13 (s, 3H, CH3), 1.51 (d, J =
14.6 Hz, 9H, But), 1.34 (d, J = 6.8 Hz, 3H, Pri), 1.31 – 1.23 (m,
12H, Pri, But). 13C{1H} NMR (151 MHz, CD2Cl2): δ 164.3 (d, J
= 3.2 Hz), 158.5, 141.7, 125.5, 125.1 (d, J = 8.6 Hz), 106.3,
99.7, 93.7, 89.7, 87.6, 81.7, 38.9 (m), 32.2 (d, J = 21.1 Hz),
31.4, 30.2 (d, J = 2.6 Hz), 30.0 (d, J = 2.4 Hz), 23.9, 21.3, 18.6.
31P{1H} NMR (202 MHz, CD2Cl2): δ 90.65. 19F NMR (564 MHz,
CD2Cl2): δ –78.66 (s, 3F, RuOTf), –78.82 (s, 3F, TfO-). IR (KBr,
cm-1): 2978, 1613, 1479, 1330, 1274, 1234, 1204, 1163,
1033, 1003, 640, 518. MALDI-MS: m/z calcd for
[C25H38F3NO3PRuS]+ 622.13, found 622.28. Anal. calcd for
C26H38F6NO6PRuS2: C 40.52, H 4.97, N 1.82. Found: C 40.43,
H 5.21, N 1.80.
4-(2-(Butylamino)ethyl)phenol (B). Colorless crystals
1
(0.27 g, 70%). H NMR (500 MHz, CDCl3): δ 7.03 (d, J = 8.2
Hz, 2H, ArH), 6.71 (d, J = 8.2 Hz, 2H, ArH), 4.26 (br s, 2H, NH,
OH), 2.88 (t, J = 6.8 Hz, 2H, CH2), 2.75 (t, J = 6.8 Hz, 2H, CH2),
2.64 (t, J = 7.4 Hz, 2H, CH2), 1.47 (p, J = 7.5 Hz, 2H, CH2), 1.29
(h, J = 7.0 Hz, 2H, CH2), 0.88 (t, J = 7.3 Hz, 3H, CH3). 13C NMR
(126 MHz, CDCl3): δ 155.55, 130.46, 129.86, 115.93, 50.98,
49.48, 34.91, 31.78, 20.59, 14.06. IR (KBr, cm-1): 1618, 1598,
1520, 1465, 1379, 1255, 1109, 831. MALDI-MS: m/z calcd.
for [C12H20NO]+ 194.15, found 194.44.
N-(3,4-Dimethoxyphenethyl)butan-1-amine (C). Yellow
1
oil (0.39 g, 83%). H NMR (600 MHz, CDCl3): δ 6.82 – 6.78
(m, 1H, ArH), 6.76 – 6.72 (m, 2H, ArH), 3.86 (s, 3H, OMe),
3.85 (s, 3H, OMe), 2.85 (t, J = 7.1 Hz, 2H, CH2), 2.75 (t, J = 7.1
Hz, 2H, CH2), 2.61 (t, J = 7.4 Hz, 2H, CH2), 1.44 (p, J = 7.2 Hz,
2H, CH2), 1.31 (h, J = 7.7 Hz, 2H, CH2), 0.89 (t, J = 7.4 Hz, 3H,
CH3). 13C NMR (151 MHz, CDCl3): δ 149.02, 147.53, 132.91,
120.66, 112.12, 111.45, 56.05, 55.94, 51.53, 49.81, 36.15,
32.41, 20.63, 14.14. IR (PE film, cm-1): 1594, 1519, 1466,
1421, 1264, 1240, 1159, 1143, 1033, 809, 766. MALDI-MS:
m/z calcd. for [C14H24NO2]+ 238.18, found 238.64.
[RuH(η6-C10H14)(PyCH2PBut2)]OTf (3). Complex 2 (100
mg, 1.30 x 10-4 mol) and 2-propanol (4 mL) were heated in
a closed reactor at 110 oC for 1 hour. Then, the solvent was
o
removed in vacuum (oil bath, 60 C) to give a dark-yellow
oil. Upon its crystallization from CH2Cl2–Et2O two fractions
of crystals were obtained: orange unreacted complex 2 and
yellow product 3. The crystals were filtered, washed with
Et2O, and dried in vacuum (40 mg, 50%). 1H NMR (600 MHz,
CD2Cl2): δ 8.64 (d, J = 5.8 Hz, 1H, Py), 7.65 (t, J = 7.6 Hz, 1H,
Py), 7.38 (d, J = 7.8 Hz, 1H, Py), 7.11 (t, J = 6.7 Hz, 1H, Py),
5.91 (d, J = 6.1 Hz, 1H, C6H4), 5.81 (d, J = 6.0 Hz, 1H, C6H4),
5.61 (d, J = 6.2 Hz, 1H, C6H4), 4.81 (d, J = 6.0 Hz, 1H, C6H4),
3.38 (dd, J = 16.9, 10.3 Hz, 1H, CH2), 3.09 (dd, J = 16.9, 7.7 Hz,
1H, CH2), 2.71 (hept, J = 6.8 Hz, 1H, Pri), 2.34 (s, 3H, CH3),
1.34 (d, J = 7.0 Hz, 3H, Pri), 1.33 (d, J = 7.0 Hz, 3H, Pri), 1.29
(d, J = 14.0 Hz, 9H, But), 1.25 (d, J = 13.2 Hz, 9H, But), –8.65
2-(2-(Butylamino)ethyl)pyridine (D). Yellow oil (0.29 g,
1
81%). H NMR (600 MHz, CDCl3): δ 8.50 (d, J = 4.8 Hz, 1H,
ArH), 7.55 (td, J = 7.6, 1.8 Hz, 1H, ArH), 7.14 (d, J = 7.8 Hz,
1H, ArH), 7.08 (ddd, J = 7.5, 4.9, 0.9 Hz, 1H, ArH), 3.01 – 2.92
(m, 4H, 2CH2), 2.60 (t, J = 7.3 Hz, 2H, CH2), 1.43 (p, J = 7.3 Hz,
2H, CH2), 1.29 (h, J = 7.6 Hz, 3H, NH, CH2), 0.86 (t, J = 7.4 Hz,
3H, CH3). 13C NMR (151 MHz, CDCl3): δ 160.52, 149.48,
136.40, 123.36, 121.28, 49.72, 49.62, 38.75, 32.38, 20.59,
14.10. IR (PE film, cm-1): 1594, 1573, 1476, 1438, 1130, 751.
GC-MS: m/z calcd. for [C11H18N2]+ 178.15, found 178.10.
ACS Paragon Plus Environment

ACS Catalysis
Page 8 of 14
(d, 2JPH = 42.8 Hz, 1H, RuH). 13C{1H} NMR (151 MHz, CD2Cl2):
1H, CH2), 3.69 (dd, J = 16.7, 9.9 Hz, 1H, CH2), 2.09 (dt, J = 14.1,
1
2
3
4
5
6
7
8
δ 163.0 (d, J = 3.1 Hz), 157.6, 138.2, 124.0, 123.8 (d, J = 8.8
Hz), 117.8, 105.9, 95.4, 88.5, 87.9 (d, J = 6.5 Hz), 77.7, 38.2
(d, J = 10.7 Hz), 36.5 (d, J = 26.1 Hz), 35.7 (d, J = 24.8 Hz),
32.8, 30.3 (d, J = 3.1 Hz), 29.5 (d, J = 4.5 Hz), 24.7, 23.0, 19.7.
31P{1H} NMR (243 MHz, CD2Cl2): δ 109.75 (d, J = 11.8 Hz).
19F NMR (564 MHz, CD2Cl2): δ –78.84. IR (KBr, cm-1): 2976,
2023 (νRuH), 1477, 1281, 1265, 1154, 1034, 639. MALDI-MS:
m/z calcd for [C24H39NPRu]+ 474.19, found 474.30. Anal.
calcd for C25H39F3NO3PRuS: C 48.22, H 6.31, N 2.25. Found:
C 48.33, H 6.37, N 2.23.
7.0 Hz, 1H, CH2CO2), 2.00 (dt, J = 15.8, 7.8 Hz, 1H, CH2CO2),
1.44 (d, J = 14.0 Hz, 9H, But), 1.40 (d, J = 14.2 Hz, 9H, But),
1.38 (d, J = 14.0 Hz, 9H, But), 1.33 – 1.23 (m, 2H, CH2), 1.18
(d, J = 13.6 Hz, 9H, But), 0.61 (t, J = 7.3 Hz, 3H, CH3), –15.34
2
(dd, JPH = 44.7, 12.5 Hz, 1H, RuH). 13C{1H} NMR (151 MHz,
CD2Cl2): δ 204.01 (d, 2JCP = 12.9 Hz, CO), 203.69 (d, 2JCP = 15.0
Hz, CO), 186.34 (CO2), 165.95 (d, J = 3.7 Hz), 163.45 (d, J =
1.6 Hz), 158.30, 155.46, 139.55, 139.42, 125.55 (d, J = 8.4
Hz), 124.78 (d, J = 8.4 Hz), 123.95, 123.47, 40.23, 37.92 (d, J
= 22.4 Hz), 37.79 (d, J = 18.7 Hz), 37.62 (d, J = 14.1 Hz), 37.38
(d, J = 17.0 Hz), 36.45 (d, J = 20.9 Hz), 35.09 (d, J = 18.7 Hz),
30.07 (d, J = 2.6 Hz), 29.85 (d, J = 3.0 Hz), 29.50 (d, J = 2.7
Hz), 29.32 (d, J = 2.6 Hz), 19.31, 13.66. 31P{1H} NMR (243
MHz, CD2Cl2): δ 108.22, 93.26. IR (KBr, cm-1): 2975, 2911,
2878, 1967 (νCO), 1937 (νCO), 1558 (νCOO), 1478, 1432.
MALDI-MS: m/z calcd for [C34H56ClN2O4P2Ru2]+ 857.15,
found 857.01. Anal. calcd for C72H120Cl4N4O9P4Ru4: C 46.60,
H 6.52, N 3.02. Found: C 46.21, H 6.48, N 2.97.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
[Ru3H2Cl2(CO)(PyCH2PBut2)2{µ-(C5H3N)CH2PBut2}]OTf
(4). Complex 1 (2.00 g, 3.04 x 10-3 mol), 1-butanol (42 mL,
0.459 mol), and 1-aminohexane (1.54 g, 1.52 x 10-2 mol)
o
were stirred under N2 in a closed reactor at 110 C for 1
hour. The orange suspension turned dark-green. All volatile
components were removed from the hot solution under
vacuum. The evacuated reactor was transferred inside a
glovebox. The remains of organic materials were extracted
by trituration with hexane and then with Et2O to give dark-
green precipitate. It was filtered and washed with Et2O. The
material contains 4 and 5. The solid was recrystallized twice
from CH2Cl2–Et2O affording the product as black-green
crystals (808 mg, 63%). Crystals suitable for X-ray analysis
were obtained by slow evaporation of CH2Cl2–Et2O solution.
1H NMR (600 MHz, CD2Cl2): δ 8.64 (d, J = 5.4 Hz, 1H, Py), 8.30
(d, J = 5.7 Hz, 1H, Py), 7.71 (d, J = 7.8 Hz, 1H, Py), 7.62 (t, J =
7.5 Hz, 1H, Py), 7.29 (t, J = 7.4 Hz, 1H, Py), 7.24 (d, J = 7.5 Hz,
1H, Py), 6.90 (t, J = 6.5 Hz, 1H, Py), 6.80 – 6.70 (m, 3H, C5H3N,
Py), 6.11 (d, J = 7.7 Hz, 1H, C5H3N), 3.71 (dd, J = 16.7, 11.1
Hz, 1H, CH2), 3.60 (dd, J = 17.3, 11.7 Hz, 1H, CH2), 3.48 – 3.29
(m, 3H, CH2), 3.07 (dd, J = 16.6, 7.9 Hz, 1H, CH2), 1.73 (d, J =
14.4 Hz, 9H, But), 1.34 (d, J = 13.4 Hz, 9H, But), 1.23 (d, J =
12.7 Hz, 9H, But), 1.17 (d, J = 13.3 Hz, 9H, But), 0.96 (d, J =
13.5 Hz, 9H, But), 0.90 (d, J = 12.4 Hz, 9H, But), –16.50 (ddd,
2JPH = 51.6, 27.3, 9.1 Hz, 1H, RuH), –21.36 (dd, 2JPH = 20.0, 4.5
Hz, 1H, RuH). 13C{1H} NMR (151 MHz, CD2Cl2): δ 205.9 (d, J
= 12.1 Hz), 189.0, 168.2, 165.6, 164.1 (d, J = 5.4 Hz), 156.8,
154.6, 135.7, 133.8, 131.2, 130.1, 124.0 (d, J = 9.0 Hz), 122.3,
121.8 (d, J = 9.4 Hz), 121.6, 115.5 (d, J = 8.8 Hz), 38.3 (d, J =
18.4 Hz), 38.1 (d, J = 19.9 Hz), 37.2 (d, J = 11.0 Hz), 36.7 (d, J
= 22.0 Hz), 35.5 (d, J = 19.8 Hz), 34.7 (d, J = 14.5 Hz), 34.5 (d,
J = 11.3 Hz), 30.8, 30.7, 29.8, 29.1, 28.6, 28.5. 31P{1H} NMR
(243 MHz, CD2Cl2): δ 128.34, 116.38, 89.76. 19F NMR (564
MHz, CD2Cl2): δ –78.89. IR (KBr, cm-1): 2957, 2908, 2875,
1941 (νCO), 1273, 1035, 639. UV-Vis (CH2Cl2; λmax, nm (ε, M-
1 cm-1)): 293 (15772), 420 (16409), 586 (4362). MALDI-MS:
m/z calcd for [C43H73Cl2N3OP3Ru3]+ 1115.15, found 1114.71.
Anal. calcd for C44H73Cl2F3N3O4P3Ru3S: C 41.80, H 5.82, N
3.32. Found: C 41.60, H 5.88, N 3.25.
cis-[Ru2HCl(CO)2(PyCH2PBut2)2(µ-O2CPrn)]OTf
(6).
Complex 1 (200 mg, 3.04 x 10-4 mol), 1-butanol (4 mL, 0.044
mol), and 1-aminohexane (308 mg, 3.04 x 10-3 mol) were
stirred under N2 in a closed reactor at 110 oC for 24 hours.
The orange suspension turned brown. All volatile
components were removed from the hot solution under
vacuum to give a brown paste containing 5 and 6. The
following manipulations were performed inside a glovebox.
To enable crystallization of 6, organic and Ru-containing by-
products were separated by column chromatography on
“RediSep Rf reversed-phase C18” silica dried in an oven at
120 oC. The reaction mixture was dissolved in CH2Cl2,
filtered, and dry loaded on the sorbent. A column (d = 1.5
cm) was filled with the sorbent (10 mL) in Et2O and the dry
loaded mixture. Elution with Et2O gave a yellow band
containing mostly organic by-products. Then, elution with
Et2O–CH2Cl2 (9 : 1) gave another yellow band containing 5
and 6. The process was completed by washing the column
with CH2Cl2 that gave the final portion of 5 and 6. At this
point a green-colored band of 4 should remain on the
column. The Et2O–CH2Cl2 and CH2Cl2 solutions were
combined and after a few days the product crystallized as
6·CH2Cl2. The orange crystals were separated, washed with
Et2O, and dried in vacuum (30 mg, 18%). Crystals suitable
for X-ray analysis were obtained by slow evaporation of
CH2Cl2–Et2O solution. 1H NMR (600 MHz, CD2Cl2): δ 9.06 (d,
J = 5.8 Hz, 2H, Py), 7.93 (t, J = 8.0 Hz, 2H, Py), 7.73 (d, J = 7.9
Hz, 2H, Py), 7.33 (t, J = 6.7 Hz, 2H, Py), 3.83 (dd, J = 16.8, 10.9
Hz, 2H, CH2), 3.57 (dd, J = 16.9, 8.5 Hz, 2H, CH2), 2.16 (t, J =
7.5 Hz, 2H, CH2), 1.48 (d, J = 14.2 Hz, 18H, 2But), 1.39 (h, J =
7.4 Hz, 2H, CH2), 1.13 (d, J = 13.6 Hz, 18H, 2But), 0.79 (t, J =
7.4 Hz, 3H, CH3), –21.07 (t, 2JPH = 10.2 Hz, 1H, RuH). 13C{1H}
NMR (151 MHz, CD2Cl2): δ 202.8 (d, 2JCP = 17.3 Hz, CO), 186.6
(CO2), 163.3, 155.8, 139.4, 124.3 (d, J = 8.2 Hz), 124.2, 40.6,
38.1 (d, J = 14.6 Hz), 37.6 (d, J = 22.7 Hz), 37.3 (d, J = 22.2
Hz), 30.5 (d, J = 2.7 Hz), 29.4 (d, J = 2.6 Hz), 19.6, 13.8. 31P{1H}
NMR (243 MHz, CD2Cl2): δ 104.65 (d, J = 9.0 Hz). 19F NMR
(564 MHz, CD2Cl2): δ –78.94. IR (KBr, cm-1): 2974, 1975
(νCO), 1944, 1559 (νCOO), 1283, 1262, 1027, 633. MALDI-MS:
m/z calcd for [C34H56ClN2O4P2Ru2]+ 857.15, found 857.21.
trans-[Ru2HCl(CO)2(PyCH2PBut2)2(µ-O2CPrn)]Cl (5).
A
brown-yellow CH2Cl2–Et2O solution, obtained in the
synthesis of 4, was evaporated to dryness and treated with
THF. Concentration of the resulting solution afforded
yellow crystals of 5·½THF. They were filtered, washed with
THF, and dried in vacuum. Yellow crystalline powder (57
1
mg, 3%). H NMR (600 MHz, CD2Cl2): δ 9.01 (d, J = 5.4 Hz,
1H, Py), 8.98 (d, J = 5.4 Hz, 1H, Py), 7.96 – 7.88 (m, 2H, Py),
7.88 – 7.80 (m, 2H, Py), 7.29 (t, J = 6.3 Hz, 1H, Py), 7.16 (t, J
= 6.3 Hz, 1H, Py), 4.07 (dd, J = 16.7, 9.2 Hz, 1H, CH2), 3.93
(dd, J = 16.8, 10.2 Hz, 1H, CH2), 3.75 (dd, J = 16.6, 10.3 Hz,
[Ru3H2Cl2(CO)(PyCH2PBut2)2{(C5H3N)CH2PBut2}](OTf)2
(8). Complex 4 (20 mg, 1.58 x 10-5 mol) and AgOTf (5 mg,
ACS Paragon Plus Environment

Page 9 of 14
ACS Catalysis
1.94 x 10-5 mol) were stirred in CH2Cl2 (4 mL) for 1 hour at
25 C. Dark-green solution turned dark-blue, then it was
Chem. 2008, 2008 (28), 4745–4750.
(5)
(6)
Tillack, A.; Hollmann, D.; Michalik, D.; Beller, M. A Novel
Ruthenium-Catalyzed Amination of Primary and Secondary
Alcohols. Tetrahedron Lett. 2006, 47 (50), 8881–8885.
Broomfield, L. M.; Wu, Y.; Martin, E.; Shafir, A. Phosphino-
Amine (PN) Ligands for Rapid Catalyst Discovery in
Ruthenium-Catalyzed Hydrogen-Borrowing Alkylation of
Anilines: A Proof of Principle. Adv. Synth. Catal. 2015, 357
(16–17), 3538–3548.
Leonard, J.; Blacker, A. J.; Marsden, S. P.; Jones, M. F.;
Mulholland, K. R.; Newton, R. A Survey of the Borrowing
Hydrogen Approach to the Synthesis of Some
Pharmaceutically Relevant Intermediates. Org. Process Res.
Dev. 2015, 19 (10), 1400–1410.
Peishan, S.; Dang, T. T.; Seayad, A. M.; Ramalingam, B.
Reusable Supported Ruthenium Catalysts for the Alkylation
of Amines by Using Primary Alcohols. ChemCatChem 2014, 6
(3), 808–814.
Enyong, A. B.; Moasser, B. Ruthenium-Catalyzed N-Alkylation
of Amines with Alcohols under Mild Conditions Using the
Borrowing Hydrogen Methodology. J. Org. Chem. 2014, 79
(16), 7553–7563.
o
1
2
3
4
5
6
7
8
filtered. The solvent was removed in vacuum giving a blue
oil. It was dissolved in THF (2 mL) and shortly after the
product crystallized as 8·THF. It was filtered, washed with
THF, then with hexane, and dried in vacuum. Black
crystalline powder (16 mg, 73%). IR (KBr, cm-1): 2961, 1971
(νCO), 1820, 1479, 1436, 1277, 1157, 1034, 828, 639. UV-Vis
(CH2Cl2; λmax, nm (ε, M-1 cm-1)): 305 (14043), 357 (9165),
605 (4465), 730 (3629). MALDI-MS: m/z calcd for
[C43H73Cl2N3OP3Ru3]+ 1115.15, found 1114.72. Anal. calcd
for C49H81Cl2F6N3O8P3Ru3S2: C 39.62, H 5.50, N 2.83. Found:
C 39.99, H 5.54, N 2.77.
(7)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(8)
ASSOCIATED CONTENT
Supporting Information.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/**.
Experimental procedures, characterization, and X-ray data
(PDF)
(9)
(10)
Maxwell, A. C.; Watson, A. J. A.; Hamid, M. H. S. A.; Williams, J.
M. J.; Maytum, H. C.; Lamb, G. W.; Allen, C. L. Ruthenium-
Catalyzed N-Alkylation of Amines and Sulfonamides Using
Borrowing Hydrogen Methodology. J. Am. Chem. Soc. 2009,
131, 1766–1774.
Crystallographic data for 4 (CIF)
Crystallographic data for 6 (CIF)
(11)
Watson, A. J. A.; Maxwell, A. C.; Williams, J. M. J. Borrowing
Hydrogen Methodology for Amine Synthesis under Solvent-
Free Microwave Conditions. J. Org. Chem. 2011, 76 (7), 2328–
2331.
Hamid, M. H. S. A.; Williams, J. M. J. Ruthenium Catalysed N-
Alkylation of Amines with Alcohols. Chem. Commun. 2007, 43
(7), 725–727.
Hamid, M. H. S. A.; Williams, J. M. J. Ruthenium-Catalysed
Synthesis of Tertiary Amines from Alcohols. Tetrahedron Lett.
2007, 48 (47), 8263–8265.
AUTHOR INFORMATION
Corresponding Author
*E-mail for T.J.W.: travisw@usc.edu
(12)
(13)
(14)
ORCID
Valeriy Cherepakhin: 0000-0003-1966-9794
Travis J. Williams: 0000-0001-6299-3747
Jumde, V. R.; Gonsalvi, L.; Guerriero, A.; Peruzzini, M.; Taddei,
M.
A Ruthenium-Based Catalytic System for a Mild
Notes
Borrowing-Hydrogen Process. European J. Org. Chem. 2015,
2015 (8), 1829–1833.
Dang, T. T.; Ramalingam, B.; Seayad, A. M. Efficient
Ruthenium-Catalyzed N-Methylation of Amines Using
Methanol. ACS Catal. 2015, 5 (7), 4082–4088.
Monrad, R. N.; Madsen, R. Ruthenium-Catalysed Synthesis of
2- and 3-Substituted Quinolines from Anilines and 1,3-Diols.
Org. Biomol. Chem. 2011, 9 (2), 610–615.
Marichev, K. O.; Takacs, J. M. Ruthenium-Catalyzed Amination
of Secondary Alcohols Using Borrowing Hydrogen
Methodology. ACS Catal. 2016, 6 (4), 2205–2210.
Huynh, H. V.; Gnanaprakasam, B.; Ramalingam, B.; Shan, S. P.;
Seayad, A. M.; Dang, T. T.; Xiaoke, X. Benzimidazolin-2-Ylidene
N-Heterocyclic Carbene Complexes of Ruthenium as a Simple
Catalyst for the N-Alkylation of Amines Using Alcohols and
Diols. RSC Adv. 2014, 5 (6), 4434–4442.
Fernández, F. E.; Puerta, M. C.; Valerga, P. Ruthenium(II)
Picolyl-NHC Complexes: Synthesis, Characterization, and
Catalytic Activity in Amine N-Alkylation and Transfer
Hydrogenation Reactions. Organometallics 2012, 31 (19),
6868–6879.
While complex 1 is commercially available from TCI, the
authors receive no royalties from its sale and thus declare no
competing financial interest.
(15)
(16)
(17)
(18)
ACKNOWLEDGMENTS
This work is sponsored by the NSF (CHE-1856395), and the
Hydrocarbon Research Foundation. We thank the NSF (DBI-
0821671, CHE-0840366, CHE-1048807) and NIH (1 S10
RR25432) for sponsorship of research instrumentation. V.C.
acknowledges Sonosky fellowship support from the USC
Wrigley Institute for Environmental Studies. We thank Prof.
Ralf Haiges for help with X-ray crystallography. We are grateful
to the Smaranda Marinescu group for providing equipment for
electrochemical studies.
(19)
(20)
REFERENCES
(1)
(2)
(3)
(4)
Peña-López, M.; Neumann, H.; Beller, M. (Enantio)Selective
Hydrogen Autotransfer: Ruthenium-Catalyzed Synthesis of
Oxazolidin-2-Ones from Urea and Diols. Angew. Chemie - Int.
Ed. 2016, 55 (27), 7826–7830.
Zhang, M.; Imm, S.; Bähn, S.; Neumann, H.; Beller, M. Synthesis
of α-Amino Acid Amides: Ruthenium-Catalyzed Amination of
α-Hydroxy Amides. Angew. Chemie - Int. Ed. 2011, 50 (47),
11197–11201.
Bähn, S.; Imm, S.; Mevius, K.; Neubert, L.; Tillack, A.; Williams,
J. M. J.; Beller, M. Selective Ruthenium-Catalyzed N-Alkylation
of Indoles by Using Alcohols. Chem. - A Eur. J. 2010, 16, 3590–
3593.
Tillack, A.; Hollmann, D.; Mevius, K.; Michalik, D.; Bähn, S.;
Beller, M. Salt-Free Synthesis of Tertiary Amines by
Ruthenium-Catalyzed Amination of Alcohols. European J. Org.
Dubey, P.; Gupta, S.; Singh, A. K. Complexes of Pd(II), Η6-
C6H6Ru(II), and Η5-Cp*Rh(III) with Chalcogenated Schiff
Bases of Anthracene-9-Carbaldehyde and Base-Free Catalytic
Transfer Hydrogenation of Aldehydes/Ketones and
N -
Alkylation of Amines. Organometallics 2019, 38 (4), 944–961.
Celaje, J. J. A.; Zhang, X.; Zhang, F.; Kam, L.; Herron, J. R.;
Williams, T. J. A Base and Solvent-Free Ruthenium-Catalyzed
Alkylation of Amines. ACS Catal. 2017, 7 (2), 1136–1142.
Şahin, N.; Özdemir, N.; Gürbüz, N.; Özdemir, İ. Novel N-
Alkylbenzimidazole-Ruthenium (II) Complexes: Synthesis
and Catalytic Activity of N-Alkylating Reaction under Solvent-
Free Medium. Appl. Organomet. Chem. 2019, 33 (2), 1–13.
Balaraman, E.; Srimani, D.; Diskin-Posner, Y.; Milstein, D.
Direct Synthesis of Secondary Amines From Alcohols and
(21)
(22)
(23)
ACS Paragon Plus Environment

ACS Catalysis
Page 10 of 14
Ammonia Catalyzed by a Ruthenium Pincer Complex. Catal.
Letters 2015, 145 (1), 139–144.
Ramachandran, R.; Prakash,
Viswanathamurthi, P.; Malecki, J. G. Ruthenium(II) Carbonyl
Complexes Designed with Arsine and PNO/PNS Ligands as
Catalysts for N-Alkylation of Amines via Hydrogen
Autotransfer Process. J. Organomet. Chem. 2015, 791, 130–
140.
Oldenhuis, N. J.; Dong, V. M.; Guan, Z. From Racemic Alcohols
to Enantiopure Amines: Ru-Catalyzed Diastereoselective
Amination. J. Am. Chem. Soc. 2014, 136 (36), 12548–12551.
Agrawal, S.; Lenormand, M.; Martín-Matute, B. Selective
Alkylation of (Hetero)Aromatic Amines with Alcohols
Catalyzed by a Ruthenium Pincer Complex. Org. Lett. 2012, 14
(6), 1456–1459.
Cherepakhin, V.; Williams, T. J. Iridium Catalysts for
Acceptorless Dehydrogenation of Alcohols to Carboxylic
Acids: Scope and Mechanism. ACS Catal. 2018, 8 (5), 3754–
3763.
Oxidation of Alcohols to Carboxylic Acids in Water. Dalt.
Trans. 2015, 44 (39), 17409–17414.
1
2
3
4
5
6
7
8
(24)
G.;
Nirmala,
M.;
(41)
(42)
Li, Y.; Nielsen, M.; Li, B.; Dixneuf, P. H.; Junge, H.; Beller, M.
Ruthenium-Catalyzed Hydrogen Generation from Glycerol
and Selective Synthesis of Lactic Acid. Green Chem. 2015, 17
(1), 193–198.
Raffa, G.; Dumeignil, F.; Paul, S.; Capet, F.; Nguyen, D. H.;
Desset, S.; Gauvin, R. M.; Zhang, L.; Trivelli, X. Catalytic
Conversion of Alcohols into Carboxylic Acid Salts in Water:
Scope, Recycling, and Mechanistic Insights. ChemSusChem
2016, 9 (12), 1413–1423.
(25)
(26)
(43)
Santilli, C.; Makarov, I. S.; Fristrup, P.; Madsen, R.
Dehydrogenative Synthesis of Carboxylic Acids from Primary
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Alcohols and Hydroxide Catalyzed by
a Ruthenium N-
Heterocyclic Carbene Complex. J. Org. Chem. 2016, 81 (20),
9931–9938.
Sarbajna, A.; Dutta, I.; Daw, P.; Dinda, S.; Rahaman, S. M. W.;
Sarkar, A.; Bera, J. K. Catalytic Conversion of Alcohols to
Carboxylic Acid Salts and Hydrogen with Alkaline Water. ACS
Catal. 2017, 7 (4), 2786–2790.
(27)
(44)
(45)
(28)
(29)
Yan, T.; Feringa, B. L.; Barta, K. Direct N-Alkylation of
Unprotected Amino Acids with Alcohols. Sci. Adv. 2017, 3, 1–
8.
Dai, Z.; Luo, Q.; Meng, X.; Li, R.; Zhang, J.; Peng, T. Ru(II)
Complexes Bearing 2,6-Bis(Benzimidazole-2-Yl)Pyridine
Imm, S.; Neubert, L.; Neumann, H.; Beller, M. An Efficient and
General Synthesis of Primary Amines by Ruthenium-
Catalyzed Amination of Secondary Alcohols with Ammonia.
Angew. Chemie - Int. Ed. 2010, 49 (44), 8126–8129.
Del Zotto, A.; Baratta, W.; Sandri, M.; Verardo, G.; Rigo, P.
Cyclopentadienyl Ru(II) Complexes as Highly Efficient
Catalysts for the N-Methylation of Alkylamines by Methanol.
Eur. J. Inorg. Chem. 2004, 2004, 524–529.
Singh Sisodia, O.; Sahay, A. N.; Pandey, D. S.; Agarwala, U. C.;
Jha, N. K.; Sharma, P.; Toscano, A.; Cabrera, A. Synthesis and
Characterization of Some Arene Hydrido-Complexes [Ru(Η6-
Arene)(EPh3)2H]+ (Η6-Arene=benzene, p-Cymene or
Hexamethylbenzene; E=P, As or Sb). Crystal Structure of
[Ru(Η6-C6H6)(PPh3)2H] BF4. J. Organomet. Chem. 1998, 560
(1–2), 35–40.
Churchill, M. R.; Hollander, F. J.; Hutchinson, J. P. An Accurate
Redetermination of the Structure of Triruthenium
Dodecacarbonyl, Ru3(CO)12. Inorg. Chem. 1977, 16 (10),
2655–2659.
Solari, E.; Gauthier, S.; Scopelliti, R.; Severin, K. Multifaceted
Chemistry of [(Cymene)RuCl2]2 and PCy3. Organometallics
2009, 28 (15), 4519–4526.
Hall, E. O.; Crangle, J. An X-Ray Investigation of the Reported
High-Temperature Allotropy of Ruthenium. Acta Crystallogr.
1957, 10 (3), 240–241.
Liu, S.-H.; Han, Z.-J.; Meng, T.; Luo, X.; Yuan, J.; Wu, Q.-G.; Chen,
J.; Yu, G.-A. Novel Dinuclear and Trinuclear Ruthenium
Clusters Derived from 2-Aryl-Substituted Indenylphosphines
via C─H Bond Cleavage. Appl. Organomet. Chem. 2016, 31 (8),
e3670.
Cifuentes, M. P.; Humphrey, M. G.; Skelton, B. W.; White, A. H.
High-Nuclearity Ruthenium Carbonyl Cluster Chemistry. 2.
Reaction of [Ru2(μ-H)(μ-NC5H4)2(CO)4(NC5H5)2][Ru10(μ-
H)(Μ6-C)(CO)24] with Triphenylphosphine: Stepwise Apical
Ligands:
A
New Class of Catalysts for Efficient
Dehydrogenation of Primary Alcohols to Carboxylic Acids and
H2 in the Alcohol/CsOH System. J. Organomet. Chem. 2017,
830, 11–18.
Singh, A.; Singh, S. K.; Saini, A. K.; Mobin, S. M.; Mathur, P.
Facile Oxidation of Alcohols to Carboxylic Acids in Basic
Water Medium by Employing Ruthenium Picolinate Cluster as
an Efficient Catalyst. Appl. Organomet. Chem. 2018, 32 (12),
1–10.
Chatt, J.; Shaw, B. L.; Field, A. E. The Formation of Hydrido- and
Carbonyl Complexes of Ruthenium by Reaction of Certain of
Its Complexes with Alcohols. J. Chem. Soc. 1964, 3466–3475.
Vaska, L.; DiLuzio, J. W. Complex Carbonyl Hydrides of
Osmium and Ruthenium. J. Am. Chem. Soc. 1961, 83 (5), 1262–
1263.
Capitani, D.; Mura, P. Do Paramagnetic Platinum Metal
Hydrides Really Exist? A Reinvestigation of the Synthesis and
Magnetochemical Properties of Ir(H)x(Cl)2(P-i-Pr3)2 (1).
Inorganica Chim. Acta 1997, 258, 169–181.
(30)
(31)
(46)
(47)
(48)
(49)
(32)
(33)
(34)
(35)
(50)
(51)
(52)
Harris, P.; Madsen, R.; Olsen, E. P. K.; Singh, T.; Andersson, P.
G. Experimental and Theoretical Mechanistic Investigation of
the Iridium-Catalyzed Dehydrogenative Decarbonylation of
Primary Alcohols. J. Am. Chem. Soc. 2014, 137 (2), 834–842.
Nikolaou, S.; Toma, H. E. Synthesis, Spectroscopy and
Electrochemistry of a μ-Oxo-Triruthenium Cluster Containing
a
Bridged
Bis(2,2′-Bipyridyl)Ruthenium(II)
Moiety.
Polyhedron 2001, 20 (3–4), 253–259.
Dai, F. R.; Wu, Y. H.; Zhang, L. Y.; Li, B.; Shi, L. X.; Chen, Z. N.
Spectroscopic, Electrochemical, and DFT Studies of Oxo-
Centered Triruthenium Cluster Complexes with
a
(36)
Bis(Tridentate) Triazine Ligand. Eur. J. Inorg. Chem. 2011, 1
(14), 2306–2316.
Cabeza, J. A.; Del Río, I.; Pérez-Carreño, E.; Pruneda, V.
Reactivity of Cationic Triruthenium Carbonyl Clusters: From
Pyrimidinium Ligands to N-Heterocyclic Carbenes.
Organometallics 2011, 30 (5), 1148–1156.
Zhang, H. X.; Sasaki, Y.; Abe, M.; Zhang, Y.; Ye, S.; Osawa, M.
Preparation, Spectroscopy, and Electrochemistry of Cyano-
Bridged Bis(Oxo-Centered-Hexa(μ-Acetato)-Triruthenium)
Complexes. J. Organomet. Chem. 2015, 797, 29–36.
Connelly, N. G.; Geiger, W. E. Chemical Redox Agents for
Organometallic Chemistry. Chem. Rev. 1996, 96, 877–910.
Evans, D. F. The Determination of the Paramagnetic
Susceptibility of Substances in Solution by Nuclear Magnetic
Resonance. J. Chem. Soc. 1959, 2003–2005.
(53)
(54)
Substitution
on
a
“Giant
Tetrahedral”
Cluster.
Organometallics 1995, 14 (3), 1536–1538.
(37)
(38)
Ellis, D.; Farrugia, L. J. X-Ray Crystal Structures of Ru3(μ-H)(μ-
C,N-C5H4N)(CO)10-n(PiPr3)n, N=0,1: A A Case of the Hydride
Following the Phosphine? J. Clust. Sci. 2005, 7 (1), 71–83.
Balaraman, E.; Khaskin, E.; Leitus, G.; Milstein, D. Catalytic
Transformation of Alcohols to Carboxylic Acid Salts and H2
Using Water as the Oxygen Atom Source. Nat. Chem. 2013, 5
(2), 122–125.
Choi, J. H.; Heim, L. E.; Ahrens, M.; Prechtl, M. H. G. Selective
Conversion of Alcohols in Water to Carboxylic Acids by in Situ
Generated Ruthenium Trans Dihydrido Carbonyl PNP
Complexes. Dalt. Trans. 2014, 43 (46), 17248–17254.
Malineni, J.; Keul, H.; Möller, M. A Green and Sustainable
Phosphine-Free NHC-Ruthenium Catalyst for Selective
(55)
(56)
(39)
(40)
(57)
Deutsch, J. L.; Poling, S. M. The Determination of Paramagnetic
Susceptibility by NMR: A Physical Chemistry Experiment. J.
Chem. Educ. 1969, 46 (3), 167–168.
ACS Paragon Plus Environment

Page 11 of 14
ACS Catalysis
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
TOC/Abstract Graphic. For Table of Contents Only
11
ACS Paragon Plus Environment

ACS Catalysis
Page 12 of 14
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 2. Molecular structures of the cations of 4 (left) and 6 (right) shown with 50% probability ellipsoids.
Hydrogen atoms and methyl groups are omitted for clarity.
651x531mm (96 x 96 DPI)
ACS Paragon Plus Environment

Page 13 of 14
ACS Catalysis
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 2. Molecular structures of the cations of 4 (left) and 6 (right) shown with 50% probability ellipsoids.
Hydrogen atoms and methyl groups are omitted for clarity.
538x532mm (96 x 96 DPI)
ACS Paragon Plus Environment

ACS Catalysis
Page 14 of 14
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
63x35mm (120 x 120 DPI)
ACS Paragon Plus Environment