Hydrogenation of N-Heteroarenes Using Rhodium Precatalysts: Reductive Elimination Leads to Formation of Multimetallic Clusters

Article abstract of DOI:10.1021/jacs.9b09540

A rhodium-catalyzed method for the hydrogenation of N-heteroarenes is described. A diverse array of unsubstituted N-heteroarenes including pyridine, pyrrole, and pyrazine, traditionally challenging substrates for hydrogenation, were successfully hydrogenated using the organometallic precatalysts, [(η⁵-C₅Me₅)Rh(N-C)H] (N-C = 2-phenylpyridinyl (ppy) or benzo[h]quinolinyl (bq)). In addition, the hydrogenation of polyaromatic N-heteroarenes exhibited uncommon chemoselectivity. Studies into catalyst activation revealed that photochemical or thermal activation of [(η⁵-C₅Me₅)Rh(bq)H] induced C(sp²)-H reductive elimination and generated the bimetallic complex, [(η⁵-C₅Me₅)Rh(μ₂,η²-bq)Rh(η⁵-C₅Me₅)H]. In the presence of H₂, both of the [(η⁵-C₅Me₅)Rh(N-C)H] precursors and [(η⁵-C₅Me₅)Rh(μ₂,η²-bq)Rh(η⁵-C₅Me₅)H] converted to a pentametallic rhodium hydride cluster, [(η⁵-C₅Me₅)₄Rh₅H₇], the structure of which was established by NMR spectroscopy, X-ray diffraction, and neutron diffraction. Kinetic studies on pyridine hydrogenation were conducted with each of the isolated rhodium complexes to identify catalytically relevant species. The data are most consistent with hydrogenation catalysis prompted by an unobserved multimetallic cluster with formation of [(η⁵-C₅Me₅)₄Rh₅H₇] serving as a deactivation pathway.

Full text of DOI:10.1021/jacs.9b09540

Subscriber access provided by - Access paid by the | UCSF Library
Article
Hydrogenation of N-Heteroarenes Using Rhodium Precatalysts: Re-
ductive Elimination Leads to Formation of Multimetallic Clusters
Sangmin Kim, Florian Loose, Máté J. Bezdek, Xiaoping Wang, and Paul J. Chirik
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b09540 • Publication Date (Web): 07 Oct 2019
Downloaded from pubs.acs.org on October 7, 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 13
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Hydrogenation of N-Heteroarenes Using Rhodium Precatalysts:
Reductive Elimination Leads to Formation of Multimetallic Clusters
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
Sangmin Kim,† Florian Loose,† Máté J. Bezdek,† Xiaoping Wang‡ and Paul J. Chirik*,†
†Department of Chemistry, Frick Laboratory, Princeton University, Princeton, NJ 08544, USA
‡Neutron Scattering Division, Neutron Sciences Directorate, Oak Ridge National Laboratory, Oak Ridge, TN 37831,
USA
ABSTRACT:
A
rhodium-catalyzed
method
for
the
hydrogenation of N-heteroarenes is described. A diverse array
of unsubstituted N-heteroarenes including pyridine, pyrrole and
pyrazine, traditionally challenging substrates for hydrogenation,
were successfully hydrogenated using the organometallic
precatalysts, [(η5-C5Me5)Rh(N-C)H] (N-C = 2-phenylpyridinyl
(ppy) or benzo[h]quinolinyl (bq)). In addition, the hydrogenation
of polyaromatic N-heteroarenes exhibited uncommon
chemoselectivity. Studies into catalyst activation revealed that
photochemical or thermal activation of [(η5-C5Me5)Rh(bq)H]
induced C(sp2)–H reductive elimination and generated the bimetallic complex, [(η5-C5Me5)Rh(µ2,η2-bq)Rh(η5-C5Me5)H].
In the presence of H2 both of the [(η5-C5Me5)Rh(N-C)H] precursors and [(η5-C5Me5)Rh(µ2,η2-bq)Rh(η5-C5Me5)H]
converted to a pentametallic rhodium hydride cluster, [(η5-C5Me5)4Rh5H7], the structure of which was established by
NMR spectroscopy, X-ray and neutron diffraction. Kinetic studies on pyridine hydrogenation were conducted with each
of the isolated rhodium complexes to identify catalytically relevant species. The data are most consistent with
hydrogenation catalysis prompted by an unobserved multimetallic cluster with formation of [(η5-C5Me5)4Rh5H7] serving
as a deactivation pathway.
nitrogen atoms that promote deleterious side reactions.6-
INTRODUCTION
8
As a result, most hydrogenations of this type are
N-Heterocycles are one of the most important and
limited to polyaromatic N-heteroarenes such as
common substructures within pharmaceuticals with
approximately 59% of the recent FDA-approved small
molecule drugs containing such a ring.1 As interest in
drug discovery transitions from aromatic structure to
those with more three dimensionality, so will interest for
the synthesis of saturated N-heterocycles including
piperidines, pyrrolidines and related structures (Scheme
1, a).2 Current routes to these structures are less
developed than their aromatic counterparts and as such
the hydrogenation of N-heteroarenes has been of long
standing interest.3-5
quinoline and quinoxaline.9-19 General methods for the
hydrogenation of a broader subset of N-heteroarenes
including pyridine, pyrrole, pyrimidine, pyridazine, or
pyrazine have not been realized. In most successful
cases, base additives or alcohols are required and
conversions are low.20 Discovery of additive-free catalysts
with high turnovers and conversion would therefore be
of value in synthesis.
Scheme 1. (a) Preparation of three-dimensional
pharmacophores
by
hydrogenation
of
N-
heteroarenes. (b) Arene hydrogenation with [(5-
C5Me5)RhCl2]2 and catalytically active cluster. (c)
Reductive elimination as a strategy to generate [(5-
C5Me5)Rh] or [(5-C5Me5)RhH2] for nucleation toward
multimetallic cluster formation. (d) [(5-C5Me5)Rh(N-
C)H] precatalysts.
While advances have been made, including
asymmetric variants,3-5 this class of hydrogenation
remains a challenge in contemporary catalysis due to
poisoning by strongly coordinating nitrogen atoms or
from the presence of weak C-H bonds adjacent to
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 13
a. 3D-Pharmacores from 2D-pharmacores and challenging hydrogenation substrates
Unsubstituted N-heteroarenes:
A few examples using
a homogeneous precatalyst known
H
N
H
N
H
H
N
1
N
N
N
[M]
N
N
N
2
3
4
5
6
7
8
9
N
N
H
N
hydrogenation
2D-flat pharmacores
3D-pharmacores
H
N
N
N
 Readily accessible
 Limited diversity
 Not easily accessible
 Diversity and tunability
N
b. Arene hydrogenation using [(5-C5Me5)RhCl2]2 and catalytically active multimetallic cluster
Rh
Unanswered questions
cat. [(-C5Me5)RhCl2
]
2
Formation pathway?
Intermediates?
Rh
Rh
50 atm H2
Rh
NEt3, iPrOH
100 oC
Isolability?
[(-C5Me5)2.4Rh4Cl4Hc]
R
R
General reactivity?
Deactivation species?
 In operando EXAFS
 Kinetics
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
c. Strategy to generate a multimetallic cluster without additives
[(-C5Me5)RhHm
]
n
Reductive
elimination
H2
 Stability?
 Isolability?
 Structure?
 Reactivity?
Rh
L
Rh
L
-
H
Rh
H
H
X
X
H
[(-C5Me5)RhH2
]
[(-C5Me5)Rh]
precatalyst
No additive
needed
d. [(-C5Me5)Rh(N-C)H] precatalysts: [(-C5Me5)Rh(ppy)H] (1 ) and [(-C5Me5)Rh(bq)H] (2)
Rh
N
Rh
N
H
H
1, [(-C5Me5)Rh(ppy)H]
2, [(-C5Me5)Rh(bq)H]
Table 1. (a) Scope of N-heteroarene hydrogenation promoted by 1.a (b) Catalytic deuteration of pyridine.
ACS Paragon Plus Environment

Page 3 of 13
Journal of the American Chemical Society
a
N-Het
N
N-Het
[Rh]
1
N
H
N-heteroarene
Hydrogenated
2
product
3
4
5
method A(preactivation) : 5.0mmol substrate, 1 mol % 1, 4 atm H2, neat, 80 oC, 48 h
method B (in situ activation) : 5.0 mmol substrate, 1 mol % 1, 36 atm H2, neat, 100 oC, 48 h
method C (preactivation) : 1.0 mmol substrate, 5 mol % 1, 4 atm H2, THF, 80 oC, 48 h
H
N
N
6
H
N
H
N
H
N
N
N
N
A
B
B
B
7
8
9
pyridine
3a
81 %
2-picoline
3b
85 %
3-picoline
3c
77 %
4-picoline
3d
63 %
H
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
N
H
N
H
N
N
b
H
N
H
N
N
B
B
B
A, B
CF3
CF3
N
N
2,6-lutidine
3e
69 %
(d.r.>20:1)
3-trifluoromethyl
pyridine
3f
17 %
4-dimethyl
aminopyridine
3g
>99 %
pyrrole
3h
A: 53 %
B : 74 %
H
N
N
NH2
N
N
N
N
N
B
B
N
A, B
NH
N-N cleaved
product
NH2
or
N
NH
N
N
H
pyrazine
3i
87 %
pyrimidine
3j
55 %
pyridazine
3k
A: 75 %
3l
B: 78 %
N
N
NH
NH
N
NH
H
H
B
B
N
N
+
N
+
+
2-phenylpyridine
3m
32 %
3n
17 %
3o
39 %
2,2'-bipyridine
3p
27 %
3q
34 %
H
N
H
H
N
H
N
N
N
N
B
C
A
N
N
+
H
N
H
N
N
H
(S)-nicotine
3r
91 %
d.r. = 1.8 : 1
quinoline
3s
3t
quinoxaline
3u
92 %
5,6,7,8-THQ
1,2,3,4-THQ
14 %
58 %
H
N
N
N
N
N
N
N
C
C
+
+
N
N
H
acridine
3v
3w
1,2,3,4,5,6,7,8-OHA
50 %
phenazine
3x
3y
19 %
1,2,3,4-THA
54 %
35 %
b
H
N
1 mol % 1
4 atm D2
N
N
+
 Statistical distributions of D
neat, 80 o
48 h
C
Dn
Dn
D-incorporation in pyridine
D-incorporation in piperidine
35
30
25
20
15
10
5
32.7
30
25
20
15
10
5
31.1
H
26.2
N
N
22.7
19.7
Dn
Dn
16.6
12.8
13.5
9.5
4.6
3.9
2.7
2.4
1
0.5
0.1
0
0
0
1
2
3
4
5
0
1
2
3
4
5
6
7
8
9
# of deuterium incorporated
# of deuterium incorporated
aYields were determined by H NMR spectroscopy using mesitylene as an internal standard. 5 mol% 1, 1.0 mmol
substrate (4-dimethylaminopyridine) and 1.0 mL THF.
1
b
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Among various transition metals known to catalytically
hydrogenate unsaturated organic compounds, rhodium
is one of the most widely utilized in both homogeneous
and heterogeneous catalysis.21,22 It has recently been
demonstrated that well-defined organometallic rhodium
of selected arenes and heteroarenes.23-26 Subsequent
mechanistic studies on these catalytic mixtures have
indicated that the organometallic rhodium compounds
are converted into catalytically active multimetallic
clusters or nanoparticles (Scheme 1, b).27-31 While these
multimetallic clusters have been definitively established
as catalytically competent, rational generation and
precatalysts
such
as
[(η5-C5Me5)RhCl2]2
[(CAAC)Rh(COD)Cl] (CAAC = cyclic alkyl amino carbene,
COD = 1,5-cyclooctadiene) promote the hydrogenation
or
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 13
modification of such species for improved performance was observed between phenyl and pyridine rings of 2-
1
2
3
4
5
6
7
8
remains a challenge.
phenylpyridine (3m, 3n).
As part of our broader program exploring the
chemistry of [(η5-C5Me5)Rh(ppy)H]32,33 as a catalyst for
formation of N-H bonds by proton-coupled electron
transfer (PCET),34-36 the use of this complex as a
precatalyst for N-heteroarene hydrogenation was of
interest. Inspiration from studies on identification of [(η5-
C5Me5)2.4Rh4Cl4Hc] formed from [(η5-C5Me5)RhCl2]2 as an
active catalyst for arene hydrogenation27-29 suggested
that C(sp2)–H reductive elimination of 2-phenylpyridine
may provide a unique source of [(η5-C5Me5)Rh]n or [(η5-
C5Me5)RhH2]n compounds without the need for additives
(Scheme 1, c).
Unusual chemoselectivity was observed in the
hydrogenation of polyaromatic N-heteroarenes (3s-y).
Most known partial reduction reactions of quinoline and
acridine yield 1,2,3,4-tetrahydroquinoline and 1,10-
dihydroacridine, respectively. However, with 1 as the
precatalyst,
5,6,7,8-tetrahydroquinoline
(3s)
and
1,2,3,4,5,6,7,8-octahydroacridine (3w) were obtained as
the major products in 58 and 50% yields, respectively,
when THF was used as the solvent. Only one other
example of this selectivity has been reported using a
ruthenium hydride catalyst.37,38 Hydrogenation of
phenazine produced 1,2,3,4,6,7,8,9-octahydrophenazine
(3x) as the major product in 54% yield analogous to the
selectivity observed in acridine hydrogenation. Pyrazole
and imidazole were unreactive given the endergonic
nature of the hydrogenation at reaction temperature.39,40
No reaction was also observed with 1,3,5-triazine and
isoquinoline.
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
Here we describe studies on the reductive elimination
chemistry of [(η5-C5Me5)Rh(ppy)H] (1, ppy
phenylpyridinyl)
=
2-
and [(η5-C5Me5)Rh(bq)H] (2, bq =
benzoquinolinyl) (Scheme 1, d) and identification of
multimetallic rhodium hydrides en route to nanoparticle
formation. The resulting clusters proved active for the
reduction of a range of N-heteroarenes many of which
had not been previously hydrogenated and therefore
open a new avenue in synthesis.
The catalytic deuteration of pyridine was examined
using [(η5-C5Me5)Rh(ppy)H] as a precatalyst (Table 1, b).
With 1 mol% of 1 at 80 ºC for 48 hours, formation of
both deuterated piperidine and pyridine was observed
with a statistical distribution of deuterium in both
organic molecules. Analysis of the deuterated piperidine
product by quantitative 13C NMR spectroscopy revealed
RESULTS AND DISCUSSION
Our studies commenced with evaluation of [(η5-
C5Me5)Rh(N-C)H] precatalysts for the additive-free
hydrogenation of pyridine. Initial conditions employed
0.05 mmol of pyridine in THF-d8 solution with 4 atm of
H2 at 60 ºC with 0.16 mol% of 1 as the precatalyst.
Monitoring the reaction by 1H NMR spectroscopy
revealed 11% conversion to piperidine (3a) in 24 hours.
Performing the reaction on a preparative scale using
neat pyridine with 4 atm of H2 at 80 ºC produced
piperidine in 81% yield (Table 1, a). Because neat
conditions produced optimal reactivity, other liquid
substrates were evaluated under these conditions. In
each case, 1-5 mol% of 1 was used along with 4 or 36
atm of H2. Substituted pyridine derivatives including
challenging substrates such as 3-picoline were
successfully hydrogenated (3b-g). The electron-poor
pyridine, 3-trifluoromethylpyridine, produced the desired
piperidine (3f) in only 17% yield but it should be noted
that fluorinated piperidines are not easily accessed by
other methods.
complex
patterns,
consistent
with
irregular
stereochemistry and formation of various isotopomers
and isotopologues (Figure S14). These results
demonstrate that the N-heteroarene hydrogenation
reaction involves rapid H–D exchange prior to
deuteration and the insertion of the pyridine into the
metal-hydride(deuteride) bonds is reversible.
The synthesis and catalytic PCET reactivity of 1 and 2
with organic substrates have been thoroughly
investigated,32,33 while our group has explored the role of
1 as a PCET catalyst to promote N-H bond-formation
using H2 as the stoichiometric hydrogen source.34-36
Despite these studies and applications, little is known
about the thermal stability of these compounds and their
propensity to undergo reductive elimination. Recently, it
was reported that [(η5-C5Me5)Rh(bq)R] (R = 4-CF3Ph, Me)
undergoes reductive elimination by chemical oxidation
but not under thermal conditions41 but the reactivity of
the corresponding hydride, 2 was not addressed in that
study. Given the utility of 1 as a precatalyst with unique
reactivity for N-heteroarene hydrogenation and the likely
formation of clusters as the active species, the reductive
elimination chemistry and thermal stability of both 1 and
2 was systematically investigated.
Unsubstituted N-heteroarenes other than pyridine
were also successful hydrogenated including examples
that have not been hydrogenated previously (3h-j). With
pyridazine, two different products were obtained
depending on the conditions of the reaction (3k, 3l). The
rhodium-catalyzed
hydrogenation
of
substituted
pyridines was also investigated including the bioactive
molecule, (S)-nicotine (3m-r). Although high conversions
were generally obtained, relatively poor chemoselectivity
Monitoring the hydrogenation of pyridine with 1 in
THF-d8 by 1H NMR spectroscopy resulted in the
ACS Paragon Plus Environment

Page 5 of 13
Journal of the American Chemical Society
a
observation of new rhodium hydride signals over 24 h
(Figure S7, Supporting Information). Interestingly, these
1
2
3
4
5
6
7
8
H
Rh
Blue light
Rh
N
Rh
signals were also generated in THF-d8 in the absence of
pyridine, demonstrating that 1 is converted into different
rhodium hydride derivatives under H2. Notably, these
new compounds form in the absence of base or alcohols,
reagents typically required for multimetallic cluster
formation.
2
N
H
THF, rt
15 h
- (bq)-H
4, [(-C5Me5)Rh(2,2-bq)Rh(-C5Me5)H]
2
62 %
b
Independent syntheses were conducted to identify the
new rhodium hydride(s) formed under catalytic
conditions. Irradiation of a THF-d8 solution of 1 or 2 with
blue light at ambient temperature or heating to 70 ºC in
the absence of H2 resulted in formation of a new
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
Rh1-Rh2 : 2.7306(2)
1
bimetallic complex as judged by H NMR spectroscopy.
Isolation of the bimetallic product obtained from 1
proved challenging due to rapid isomerization (vide
infra) but the bimetallic product, [(η5-C5Me5)Rh(µ2,η2-
bq)Rh(η5-C5Me5)H] (4) obtained from 2 was isolated and
fully characterized by X-ray diffraction and NMR
spectroscopy (Scheme 2). The hydride was located in the
solid-state structure. Diamagnetic 4 contains two [(η5-
C5Me5)Rh] fragments with a Rh-Rh distance of 2.7306(2)
Å and is best described as an adduct of [(η5-C5Me5)RhH]
with [(η5-C5Me5)Rh(bq)]. The net loss of one
benzoquinoline ligand, observed by NMR spectroscopy,
supports C(sp2)–H reductive elimination followed by
dissociation of the N-heteroarene from the coordination
sphere of one rhodium. Analysis of the NMR data
The observed loss of one of the supporting ligands
upon photochemical or thermal activation of 1 or 2
prompted an additional deuterium labeling study. The
rhodium deuteride 1-d1 was prepared by the reaction of
[(η5-C5Me5)Rh(ppy)] and D2 in THF for 30 min at 23 ºC.
1
Monitoring a THF-d8 solution of the compound by H
NMR spectroscopy established rapid H-D exchange
between the rhodium-hydride (deuteride) site and the
aryl ligand, consistent with rapid C(sp2)–H(D) reductive
elimination, C–C bond rotation and oxidative addition
(Scheme 3). The thermal or photochemical activation is
therefore crucial for dissociation of ligand rather than for
promoting the C–H bond forming step.
following irradiation or thermolysis of
1 support
formation of a similar bimetallic complex along with free
phenylpyridine although the number of isomers and
byproducts detected complicated definitive assignment.
Scheme 2. (a) Synthesis of the bimetallic complex, 4.
(b) Solid state structure of 4 at 30% probability
ellipsoids. Hydrogen atoms, except the Rh-H omitted
for clarity.
Scheme 3. Observation of H/D exchange on the
ligand at room temperature under dark conditions.
The photochemical and thermal stabilities of both 1
and 2 were studied to explore the possibility of ligand
loss as a route to higher order rhodium hydride clusters.
Irradiation with blue light or heating a THF-d8 solution of
either rhodium hydride to 70 ºC under 4 atm of H2
resulted in a color change from yellow to dark brown
over the course of 30 minutes. Complete conversion was
observed after 24 hours and analysis of the product
1
mixture by H NMR spectroscopy established liberation
of free 2-phenylpyridine or benzo[h]quinoline along with
formation of new η5-C5Me5 and rhodium-hydride
resonances (Rh–H = -13.23, -14.14 and -22.73 ppm in
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 13
THF-d8). Recrystallization from pentane at -35 ºC yielded
4 atm of D2 gas to a benzene-d6 solution containing [(η5-
C5Me5)4Rh5H7] at ambient temperature resulted in rapid
exchange in all of the metal hydride positions.
1
2
3
4
5
6
7
8
brown crystals suitable for X-ray diffraction and neutron
scattering. The combined NMR spectroscopic and
crystallographic data support formation of a neutral
To assay whether the bimetallic complex, 4 was a
precursor to the pentametallic cluster, 5, a THF-d8
solution of the former was exposed to 4 atm of H2 and
the progress of the reaction monitored by 1H NMR
spectroscopy. Over the course of 18 hours at ambient
temperature, 5 was observed along with 2, free
benzo[h]quinoline and C5Me5H (Scheme 5, Figure S9).
The observation of 2 supports hydrogenolysis of 4 to
generate [(η5-C5Me5)RhH2] and [(η5-C5Me5)Rh(N-C)H].
The formation of 5 implies one of the intermediates after
hydrogenolysis, [(η5-C5Me5)RhH2], is related to its
formation.
pentametallic
rhodium–hydride
cluster,
[(η5-
C5Me5)4Rh5H7] (5) (Scheme 4). Unlike other transition
metal clusters containing η5-C5Me5 and hydride ligands,
the complex has a unique structure comprised of a
tetrahedral Rh4 core with the additional rhodium at the
apex.42-50 Three of the rhodium atoms in the core are
ligated by η5-C5Me5 rings while the other is ligand free
and capped by the unique [(η5-C5Me5)Rh]. The bond
distance of Rh4-Rh5 is significantly shorter than the
other Rh–Rh bonds. All seven hydrides were successfully
located by neutron diffraction (Scheme 4, b). Addition of
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
Scheme 4. (a) Synthesis of the pentametallic cluster, 5. (b) Solid state structure of 5 and expanded view of the
Rh core at 30% probability ellipsoids. Hydrogen atoms, except the Rh-H omitted for clarity.
a
b
Rh-Rh bond distances (10-10m, X-ray)
Rh1-Rh2 : 2.7098 (3)
3Ha + 3Hb +1Hc
Rh
Rh
 (70 oC) or Blue light
Rh1-Rh3 : 2.6975 (3)
H7
Rh
N
5
Rh1-Rh4 : 2.7199 (3)
4 atm H2
H
Rh2-Rh3 : 2.7204 (3)
THF
Rh
Rh
Rh2-Rh4 : 2.6810 (3)
- 5(N-C)H
- C5Me5H
Rh
Rh3-Rh4 : 2.7277 (3)
Rh4-Rh5 : 2.5475 (3)
1 or 2
5, [(-C5Me5)4Rh5H7
]
Rh4-Rh5 is significantly shorter
39 %
Three hydride signals in 1H NMR in THF-d8
T1(min) (500MHz)
1270 ms at -35 o
 (ppm)
3Ha 3Hb
1Hc
3Ha
3Ha : H5m, H6m and H7m
3Hb : H1m, H3m and H4m
1Hc : H2m
-13.23 (dd)
C
606 ms at -35 o
C
3Hb
1Hc
-14.14 (br m)
-22.73 (q)
722 ms at -10 o
C
-13 -14 -15 -16 -17 -18 -19 -20 -21 -22 -23
f1(ppm)
Scheme 5. Hydrogenolysis of 4 yielding 5 and the
starting monometallic precatalyst, 2.
C5Me5)Rh(I)] and [(η5-C5Me5)RhH2] by reductive
elimination from [(η5-C5Me5)Rh(N–C)H].
To identify the nature of the active species and gain
insight into the mechanism of additive-free N-
heteroarene hydrogenation, kinetic experiments using
each of the isolated rhodium complexes were conducted
(Figure 1). Pyridine was selected as a representative
substrate and the rate of each reaction was determined
by monitoring hydrogen uptake with 0.25 mol% of total
rhodium (3.1 µmol of Rh) and 530 psi of H2 at 78 ºC. The
plots of H2 uptake versus time are reported in the
Supporting Information.
Examination of the kinetic profile when 1 was used as
the precatalyst revealed a significant induction period
within the first three hours and completion of the
reaction after 28 h (Figure 1, a). Following the induction
period, an exponential decay of the pyridine
concentration was observed, signaling a first order
dependence on the substrate, which was confirmed by
the relationship between conversion vs. reaction rate
(Figure 1, b). The induction period followed by the first-
order kinetic behavior implies that the precatalyst is
converted to a new rhodium species, which can be either
a single metal center catalyst or a multimetallic cluster.
The maximum reaction rate during the reaction was 23.3
Based on the experimental observations, the most
plausible pathway for formation of the cluster likely
involves: (i) rapid, initial C(sp2)–H reductive elimination to
form [(η5-C5Me5)Rh(I)(κ1-N-C)]; (ii) dissociation of the
neutral ligand by thermal or photochemical activation to
yield transient [(η5-C5Me5)Rh]; (iii) interaction of [(η5-
C5Me5)Rh] and [(η5-C5Me5)Rh(N–C)H] to generate the
bimetallic intermediate, [(η5-C5Me5)Rh(µ2,η2-bq)Rh(η5-
C5Me5)H]; (iv) generation of [(η5-C5Me5)RhH2] and (v) the
final formation of the cluster 5 by the aggregation of
[(η5-C5Me5)RhH2] likely via [(η5-C5Me5)3Rh4H7] (Scheme
6). This pathway likely involves formation of [(η5-
ACS Paragon Plus Environment

Page 7 of 13
Journal of the American Chemical Society
psiH2 h-1. Performing the hydrogenation of pyridine in the
presence of Hg(0) produced no conversion, consistent
with a multimetallic cluster rather than a monometallic
compound.27-31
hydrogenation is therefore likely a result of 1 and the
1
2
3
4
5
6
7
8
bimetallic product being converted to the active species
during the course of hydrogenation and subsequent
interaction with substrate.
A filtration test was also conducted whereby the crude
reaction mixture following catalytic hydrogenation was
passed through Celite to remove observed black
particulates and the volatiles removed in vacuo and the
Using isolated bimetallic complex, 4 as the precatalyst,
a similar kinetic profile to 1 was obtained (Figure 1, d).
An induction period was observed in the first 3 hours
followed by exponential decay. Fitting the exponential
region produced the maximum reaction rate of 19.6 psiH2
h-1, similar to the value obtained with 1. Completion of
the hydrogenation was observed at 24 hours, slightly
faster than with 1. Again, first-order kinetics was
observed after the induction period based on the
relationship between conversion vs. reaction rate (Figure
1, e). In the proposed evolution of the rhodium
complexes shown in Scheme 6, the intermediate [(η5-
C5Me5)RhH2] can result either from [(η5-C5Me5)Rh] that
forms directly from reductive elimination of [(η5-
C5Me5)Rh(N–C)H] or from hydrogenolysis of 4. Because
of the similar kinetic behavior of 1 and 4, it is likely that
[(η5-C5Me5)RhH2] is related to formation of the active
species.
1
rhodium residue was analyzed by H NMR spectroscopy.
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
Both the bimetallic complex and 5 were observed (Figure
S10). With the recovered soluble rhodium residue, a
second cycle of pyridine hydrogenation was conducted
and the uptake of H2 monitored (Figure 1, c). A rapid
initial rate of 4.5 psiH2 h-1 was observed until 3 h and the
reaction rate was gradually increased up to 11.2 psiH2 h-1
over the course of time (Figure S19). A fast initial rate
was observed, suggesting that a homogeneous catalyst
is operative at early reaction times. This behavior was
also observed in rhodium-catalyzed arene hydrogenation
where a multimetallic cluster was proposed as the most
active species formed from the precatalyst.28 The
increasing reaction rate observed during pyridine
Scheme 6. Proposed pathway of the cluster formation from the precatalyst based on the experimental
observations.
Rh
H
Rh
[(-C5Me5)Rh(N-C)H]
Rh
H7
Rh
N
Rh
Rh
N
H
Rh
Rh
[(-C5Me5)Rh(N-C)H]
(i)
[(-C5Me5)Rh(2,2-N-C)
Rh(-C5Me5)H]
[(-C5Me5)4Rh5H7]
[(-C5Me5)RhH2]
(iii)
ox.
add.
red.
H2
elim.
- H2
(iv)
-[(-C5Me5)Rh(N-C)H]
H7
Rh
Rh
Rh
(v)
(ii)
Rh
Rh
N
heat or light
H2
aggregation
- C5Me5H
[(-C5Me5)Rh]
[(-C5Me5)RhH2]
- (N-C)H
[(-C5Me5)Rh(1-N-C)]
[(-C5Me5)3Rh4H7]
The kinetics of pyridine hydrogenation were evaluated
using 0.05 mol% (0.25 mol% total rhodium) pentanuclear
rhodium hydride cluster, [(η5-C5Me5)4Rh5H7] (Figure 1, f).
Sigmoidal behavior was observed with relatively flat
The insoluble rhodium black particulates were then
recovered following pyridine hydrogenation initiated by
5 and was assayed for additional activity (Figure 1, g).
The activity of this material was diminished from the
initial sample 5 with a constant reaction rate of 4.8-5.3
psiH2 h-1 for 30 h from the initial stage, best fit to the
curvature and
a
completion time of 49 hours,
significantly longer than the value obtained with 1. Best
fit of the plot yielded the maximum reaction rate of 8.5
psiH2 h-1 which is distinctly lower than other kinetic data
(Figure S23). A sigmoidal curve with an induction period
indicates that 5 is converted into another catalytically
active species. However, due to the significant difference
in reactivity, the catalytic species from 5 can be
eliminated at the most active catalyst during pyridine
hydrogenation. The THF-d8 1H NMR spectrum of the
soluble Rh residue after the reaction revealed remaining
5 (Figure S11).
linear decrease of zero-order kinetics,
a
feature
characteristic of heterogeneous catalysis, which implies
catalytically active Rh(0) nanoparticles were generated
from 5 (Figure S48). Although the reaction seems to be
slower compared to the maximum reaction rate of 5, it
could be a result of decreased metal surface of
nanoparticles by further agglomeration during recovery.
Therefore, it is believed that 5 is further converted into a
nanocluster which is catalytically active, but less reactive
than the unidentified most active species generated from
1
and
4.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 13
a. 0.25 mol% 1
1
2
3
4
H
0.25 mol% Rh atoms
530 psi H2
a
b. logarithmic form of a.
c. 2nd-run of soluble Rh from a.
d. 0.125 mol% 4
e. 0.05 mol% 5
f. 2nd-run of insoluble Rh from e.
with 0.25 mol% 1
N
N
100
80
60
40
20
0
550
500
450
400
350
300
neat, 78 o
time
C
5
fit
6
7
8
9
PH (psi)
2
[Rh]
conversion
H
Rh
H7
Rh
Rh
Rh
N
N
H
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
[Rh]
[Rh]
[Rh]
5
0
6
12
time (h)
18
24
30
1
4
[Rh] = (-C5Me5)Rh
PH (psi)
400
2
d
b
c
second run of soluble [Rh] from (a)
with 0.125 mol% 4
300
350
450
500
550
100
80
60
40
20
0
100
80
60
40
20
0
30
24
18
12
6
550
500
450
400
350
300
550
500
450
400
350
300
− d PH / dt = − k PH + b
2
2
k = 0.12 h-1
b = − 35 psi h-1
R2 = 0.98
−
0
100
80
60
40
20
0
0
6
12
time (h)
18
24
30
0
6
12
time (h)
18
24
30
conversion (%)
PH (psi)
400
2
e
f
g
with 0.05 mol% 5
second run of insoluble [Rh] from (e)
300
30
350
450
500
550
100
80
60
40
20
0
100
80
60
40
20
0
550
500
450
400
350
300
550
500
450
400
350
300
− d PH / dt = − k PH + b
2
2
k = 0.09 h-1
b = − 23 psi h-1
R2 = 0.91
24
18
12
6
−
0
100
80
60
40
20
0
0
10
20
time (h)
30
40
50
0
10
20
time (h)
30
40
50
conversion (%)
Figure 1. (a) Exponential decay of pyridine with a short induction period in pyridine hydrogenation using the
precatalyst 1. (b) First order kinetics of (a) after the induction period. (c) Kinetic profile using soluble Rh from (a). (d)
Kinetic profile of pyridine hydrogenation using the bimetallic complex 4. (e) First order kinetics of (d) after the induction
period. (f) Kinetic profile of the reaction using the pentanuclear cluster 5. (g) Kinetic profile of the second-run of (e).
Scheme 7. Evolution of the catalytically active species, catalyst deactivation and formation of nanoparticles
based on synthetic and kinetic experiments.
ACS Paragon Plus Environment

Page 9 of 13
Journal of the American Chemical Society
1
2
3
catalytically
active species
Rh
Rh(0) nanoparticle
N
H
[(-C5Me5)Rh]
 Zero-order kinetics
4
5
6
precatalyst
1, [(-C5Me5)Rh(ppy)H]
 Induction period
7
8
Rh
H7
9
Rh
H
unidentified
most active
multimetallic
Rh
10
11
12
13
14
15
16
17
18
19
Rh
Rh
Rh
N
[(-C5Me5)RhH2]
Rh
Rh cluster
Catalyst deactivation
and
 First-order kinetics
 Poisoned by Hg(0)
 Fast initial rate
 The number of
Rh atoms < 5
nanoparticle formation
Evolution of catalytically
most active species
5, [(-C5Me5)4Rh5H7 ]
deactivated species
of the most active cluster
 Sigmoidal curve
4,
[(-C5Me5)Rh(2,2-bq)
Rh(-C5Me5)H]
 Induction period
 Slower reaction rate
C5Me5)Rh(N-C)H] has been discovered. Challenging
substrates for hydrogenation, unsubstituted N-
heteroarenes such as pyridine, pyrrole, pyrazine and 3-
picoline, were reduced in high yields. Polyaromatics
afforded unusual chemoselectivity, for example, yielding
Analysis of all of the kinetic data and the various
activities of the isolable rhodium complexes toward
pyridine hydrogenation is summarized in Scheme 7.
Because of the induction periods detected with [(η5-
C5Me5)Rh(ppy)H] (1) and [(η5-C5Me5)Rh(µ2,η2-bq)Rh(η5-
C5Me5)H] (4), these compounds are the preferred
precatalysts for the formation of most active catalytic
species; likely a homogeneous multimetallic cluster.
Support for this assignment derives from: i) the observed
first-order behavior with respect to substrate, consistent
with a single metal compound or a multimetallic cluster
and not heterogeneous nanoparticle and ii) this catalyst
(or a precursor to it) was poisoned by Hg(0), excluding a
single metal compound. Because the cluster 5 was
generated from 1 and 4 and inactive for pyridine
hydrogenation, the most active species is likely formed
prior to [(η5-C5Me5)4Rh5H7] and thus has less than five
rhodium atoms. The most active catalytic species likely
retains η5-C5Me5 ligands given the molecular geometry
of 5. Such an organometallic cluster also may rationalize
the observed chemoselectivity in the hydrogenation of
polyaromatic substrates. The η5-C5Me5 ligands likely
create unique catalytically active sites that protect the
core of the cluster and promote hydrogenation at the
periphery. As such, the “outer” portions of polyaromatic
substrates are preferentially reduced as in the case of
5,6,7,8-tetrahydroquinoline. This hypothesis needs to be
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
5,6,7,8-tetrahydroquinoline
or
1,2,3,4,5,6,7,8-
octahydroacridine. To identify the catalytically active
species, the bimetallic and pentametallic rhodium
hydride complexes were separately synthesized from
precatalysts and fully characterized. Following kinetic
experiments using various rhodium complexes
elucidated the evolution of catalytically active
multimetallic cluster formed from [(η5-C5Me5)Rh(N-C)H]
or [(η5-C5Me5)Rh(µ2,η2-bq)Rh(η5-C5Me5)H]. This most
active species was deactivated by forming the
pentametallic cluster, but the pentametallic cluster was
further converted to nanoparticles which are catalytically
active, but less reactive than the most active
multimetallic cluster.
This result shows that reductive elimination of
precatalysts can lead to the formation of catalytically
active multimetallic species without additives such as
bases or alcohols. Our new strategic method for
multimetallic cluster formation will be able to give a new
chance for hydrogenation in medicinal and agrochemical
and petroleum chemistry.
ASSOCIATED CONTENT
Supporting Information
validated
with
additional
experimental
and
computational studies. Notably 5 can be further
transformed into Rh(0) nanoparticles which are also
catalytically active for pyridine hydrogenation as signaled
by the zero-order dependence on substrate. Importantly
the nanoparticles are less active than the rhodium
aggregate formed prior to formation of 5.
The Supporting Information is available free of charge on
the ACS Publications website at DOI: 10.1021/
AUTHOR INFORMATION
CONCLUSION
Corresponding Author
In summary, an additive-free hydrogenation of N-
heteroarene using a homogeneous precatalyst [(η5-
*pchirik@princeton.edu
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 10 of 13
Experiments and Computations. Inorg. Chem. 2014, 53, 6361-
6373.
(8) Crabtree, R. H. Deactivation in Homogeneous Transition
Metal Catalysis: Causes, Avoidance, and Cure. Chem. Rev. 2015,
115, 127-150.
(9) Dobereiner, G. E.; Nova, A.; Schley, N. D.; Hazari, N.; Miller,
S. J.; Eisenstein, O.; Crabtree, R. H. Iridium-Catalyzed
Hydrogenation of N-Heterocyclic Compounds under Mild
Conditions by an Outer-Sphere Pathway. J. Am. Chem. Soc.
2011, 133, 7547-7562.
(10) Sridharan, V.; Suryavanshi, P. A.; Menendez, J. C.
Advances in the Chemistry of Tetrahydroquinolines. Chem. Rev.
2011, 111, 7157-7259.
1
2
3
4
5
6
7
8
ORCID
Paul J. Chirik: 0000-0001-8473-2898
Sangmin Kim: 0000-0002-7289-0693
Florian W. Loose: 0000-0003-1643-4607
Máté J. Bezdek: 0000-0001-7860-2894
Xiaoping Wang: 0000-0001-7143-8112
Notes
9
The authors declare no competing financial interest
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
ACKNOWLEDGMENT
(11) Liu, Y.; Du, H. Metal-Free Borane-Catalyzed Highly
Stereoselective Hydrogenation of Pyridines. J. Am. Chem. Soc.
2013, 135, 12968-12971.
(12) Wu, J.; Barnard. J. H.; Zhang, Y.; Talwar, D.; Robertson, C.
M.; Xiao, J. Robust cyclometallated Ir(III) catalysts for the
homogeneous hydrogenation of N-heterocycles under mild
conditions. Chem. Comm. 2013, 49, 7052-7054.
(13) Mahdi, T.; Nathaniel del Castillo, J.; Stephan, D. W. Metal-
Free Hydrogenation of N-Based Heterocycles. Organometallics,
2013, 32, 1971-1978.
This research was supported by the U.S. Department of
Energy, Office of Science, Office of Basic Energy Sciences,
Catalysis Science program, under Award DE-SC0006498.
Single crystal neutron diffraction performed on TOPAZ used
resources at the Spallation Neutron Source, a DOE Office of
Science User Facility operated by the Oak Ridge National
Laboratory, under Contract No. DE-AC05-00OR22725 with
UT-Battelle, LLC. S.K. thanks Samsung Scholarship for
financial support. F.L. acknowledges financial support from a
DFG research fellowship (LO 2377/1-1). M.J.B. thanks the
Natural Sciences and Engineering Research Council of
Canada for a predoctoral fellowship (PSG-D) and Princeton
University for a Porter Ogden Jacobus Honorific Fellowship.
S.K. and P.J.C. acknowledge István Pelczer and Kenith
Conover at Princeton University for measurement of T1(min).
The authors acknowledge the use of Princeton's Imaging
and Analysis Center (IAC), which is partially supported by
the Princeton Center for Complex Materials (PCCM), a
National Science Foundation (NSF) Materials Research
Science and Engineering Center (MRSEC; DMR-1420541).
S.K. thanks Taeho Son and C. Rose Kennedy for plotting
kinetic data and Hongyu Zhong for the ORTEP.
(14) Chakraborty, S.; Brennessel, W. W.; Jones, W. D. A
Molecular Iron Catalyst for the Acceptorless Dehydrogenation
and Hydrogenation of N-Heterocycles. J. Am. Chem. Soc. 2014,
136, 8564-8567.
(15) Zhang, Z.; Du, H.
A
Highly cis-Selective and
Enantioselective Metal-Free Hydrogenation of 2,3-Disubstituted
Quinoxalines. Angew. Chem,. Int. Ed. 2015, 54, 623-626.
(16) Xu, R.; Chakraborty, S.; Yuan, H.; Jones, W. D.
Acceptorless, Reversible Dehydrogenation and Hydrogenation
of N-Heterocycles with a Cobalt Pincer Catalyst. ACS Catal.
2015, 5, 6350-6354.
(17) Zhang, Z.; Du, H. Enantioselective Metal-Free
Hydrogenations of Disubstituted Quinolines. Org. Lett. 2015, 17,
6266-6269.
(18) Ji, Y.-G.; Wei, K.; Liu, T.; Wu, L.; Zhang, W.-H. “Naked”
Iridium(IV) Oxide Nanoparticles as Expedient and Robust
Catalysts for Hydrogenation of Nitrogen Heterocycles:
Remarkable Vicinal Substitution Effect and Recyclability. Adv.
Synth. Catal. 2017, 359, 933-940.
(19) Adam, R.; Cabrero-Antonino, J. R.; Spannenberg, A.;
Junge, K.; Jackstell, R.; Beller, M. A General and Highly Selective
Cobalt-Catalyzed Hydrogenation of N-Heteroarenes under Mild
Reaction Conditions. Angew. Chem., Int. Ed. 2017, 56, 3216-
3220.
(20) Jardine, I.; McQuillin, F. J. Homogeneous Hydrogenation
of the -N=N-, -CH=N-, and -NO2 Groupings. Chem. Commun.
1970, 626.
(21) Zweifel, G. S.; Nantz, M. H. Ch5. Functional Group
Transformations: The Chemistry of Carbon-Carbon -Bonds and
Related Reactions, Modern Organic Synthesis, Wiley, 2006.
(22) Frediani, P.; Pistolesi, V.; Frediani, M.; Rosi, L. Catalytic
activity of dihydride ruthenium complexes in the hydrogenation
of nitrogen containing heterocycles. Inorg. Chim. Acta 2006,
359, 917-925.
REFERENCES
(1) Vitaku, E.; Smith, D. T.; Njardarson, J. T. Analysis of the
Structural Diversity, Substitution Patterns, and Frequency of
Nitrogen
Heterocycles
among
U.S.
FDA
Approved
Pharmaceuticals. J. Med. Chem. 2014, 57, 10257-10274.
(2) Lovering, F.; Bikker, J.; Humblet, C. Escape from Flatland:
Increasing Saturation as an Approach to Improving Clinical
Success. J. Med. Chem. 2009, 52, 6752-6756.
(3) Wang, D.-S.; Chen, Q.-A.; Lu, S.-M.; Zhou, Y.-G.
Asymmetric Hydrogenation of Heteroarenes and Arenes. Chem.
Rev. 2012, 112, 2557-2590.
(4) Balakrishna, B.; Núñez-Rico, J. L.; Vidal-Ferran, A. Substrate
Activation in the Catalytic Asymmetric Hydrogenation of N-
Heteroarenes. Eur. J. Org. Chem. 2015, 5293-5303.
(5) Chen, Z.-P.; Zhou, Y.-G. Asymmetric Hydrogenation of
Heteroarenes with Multiple Heteroatoms. Synthesis 2016, 48,
1769-1781.
(6) Glorius, F. Asymmetric hydrogenation of aromatic
compounds. Org. Biomol. Chem. 2005, 3, 4171-4175.
(7) Perrin, L.; Werkema, E. L.; Eisenstein, O.; Anderson, R. A.
Two [1,2,4-(Me3C)3C5H2]2CeH Molecules are Involved in
Hydrogenation of Pyridine to Piperidine as Shown by
(23) Russell, M. J.; White, C.; Maitlis, P. M. Stereoselective
Homogeneous Hydrogenation of Arenes to Cyclohexanes
Catalysed by [Rh(5-C5Me5)Cl2]2. J. Chem. Soc., Chem. Commun.
1977, 427-428.
ACS Paragon Plus Environment

Page 11 of 13
Journal of the American Chemical Society
(24)
Gill,
D.
S.;
White,
C.;
Maitlis,
P.
M.
(38) Borowski, A. F.; Vendier, L.; Sabo-Etienne, S.; Rozycka-
Sokolowska E.; Gaudyn, A. V. Catalyzed hydrogenation of
condensed three-ring arenes and their N-heteroaromatic
analogues by a bis(dihydrogen) ruthenium complex. Dalton
Trans. 2012, 41, 14117-14125.
(39) Clot, E.; Eisenstein, O.; Crabtree, R. H. Computational
structure-activity relationships in H2 storage: how placement of
N atoms affects release temperatures in organic liquid storage
materials. Chem. Commun. 2007, 2231-2233.
1
2
3
4
5
6
7
8
Pentamethylcyclopentadienyl-rhodium and -iridium complexes.
Part 16. Homogeneous hydrogenation catalysts. J. Chem. Soc.,
Dalton Trans. 1978, 617-626.
(25) Nairoukh, Z.; Wollenburg, M.; Schlepphorst, C.;
Bergander, K.; Glorius, F. The formation of all-cis-
(multi)fluorinated
piperidines
by
a
dearomatization-
hydrogenation process. Nat. Chem. 2019, 11, 264-270.
(26) Wiesenfeldt, M. P.; Nairoukh, Z.; Dalton, T.; Glorius, F.
Hydrogenation of Borylated Arenes. Angew. Chem., Int. Ed.
2019, 58, 6549-6553.
(40) Crabtree, R. H. Hydrogen storage in liquid organic
heterocycles. Energy Environ. Sci. 2008, 1, 134-138.
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
(27) Hagen, C. M.; Widegren, J. A.; Maitlis, P. M.; Finke, R. G. Is
It Homogeneous or Heterogeneous Catalysis? Compelling
Evidence for Both Types of Catalysts Derived from [Rh(5-
C5Me5)Cl2]2 as a Function of Temperature and Hydrogen
Pressure. J. Am. Chem. Soc. 2005, 127, 4423-4432.
(28) Bayram, E.; Linehan, J. C.; Fulton, J. L.; Roberts, J. A. S.;
Szymczak, N. K.; Smurthwaite, T. D.; Özkar, S.; Balasubramanian,
M.; Finke, R. G. Is It Homogeneous or Heterogeneous Catalysis
Derived from [RhCp*Cl2]2? In Operando XAFS, Kinetic, and
Crucial Kinetic Poisoning Evidence for Subnanometer Rh4
Cluster-Based Benzene Hydrogenation Catalysis. J. Am. Chem.
Soc. 2011, 133, 18889-18902.
(29) Bayram, E.; Linehan, J. C.; Fulton, J. L.; Szymczak, N. K.;
Finke, R. G. [RhCp*Cl2]2 Precatalyst System: Is it Single-Metal
Rh1Cp*-Based, Subnanometer Rh4 Cluster-Based, or Rh(0)n
Nanoparticle-Based Cyclohexene Hydrogenation Catalysis at
Room Temperature and Mild Pressures? ACS Catal. 2015, 5,
3876-3886.
(30) Tran, B. L.; Fulton, J. L.; Linehan, J. C.; Lercher, J. A.;
Bullock, R. M. Rh(CAAC)-Catalyzed Arene Hydrogenation:
Evidence for Nanocatalysis and Sterically Controlled Site-
Selective Hydrogenation. ACS Catal. 2018, 8, 8441-8449.
(31) Tran, B. L.; Fulton, J. L.; Linehan, J. C.; Balasubramanian,
M.; Lercher, J. A.; Bullock, R. M. Operando XAFS Studies on
Rh(CAAC)-Catalyzed Arene Hydrogenation. ACS Catal. 2019, 9,
4106-4114.
(41) Kim, J.; Shin, K.; Jin, S.; Kim, D.; Chang, S. Oxidatively
Induced Reductive Elimination: Exploring the Scope and
Catalyst Systems with Ir, Rh, and Ru Complexes. J. Am. Chem.
Soc. 2019, 141, 4137-4146.
(42) Churcill, M. R.; Ni, S. W.-Y. Crystal Structure and Location
of the Bridging Hydride Ligand in -Chloro- -hydrido-
bis[chloro(pentamethylcyclopentadienyl)rhodium(III)],
a
Homogeneous Hydrogenation Catalyst. J. Am. Chem. Soc. 1973,
95, 2150-2155.
(43) Espinet, P.; Bailey, P. M.; Piraino,P.; Maitlis, P. M.
(Pentamethylcyclopentadienyl)rhodium
and
-iridium
Complexes. 24.1 Preparation, X-ray Crystal Structure, and
Properties of [Rh4(5-C5Me5)4H4]2+. Inorg. Chem. 1979, 18, 2706-
2710.
(44) Suzuki, H. Synthesis, Structure, and Chemistry of a
Dinuclear Tetrahydride-Bridged Complex of Ruthenium, (5-
C5Me5)Ru(-H)4Ru(5-C5Me5). C-H Bond Activation and
Coupling Reaction of Ethylene on Dinuclear Complexes.
Organometallics 1994, 13, 1129-1146.
(45) Ohki, Y.; Uehara, N.; Suzuki, H. Pentanuclear Polyhydride
Cluster of Ruthenium with Trigonal-Bipyramidal Geometry.
Synthesis and Fluxional Behavior. Organometallics 2003, 22, 59-
64.
(46) Nakajima, Y.; Kameo, H.; Suzuki, H. Cleavage of
Nitrogen-Hydrogen Bonds of Ammonia Induced by
Triruthenium Polyhydrido Clusters. Angew. Chem., Int. Ed. 2006,
45, 950-952.
(47) Shima, T.; Sugimura, Y.; Suzuki, H. Heterometallic
Trinuclear Polyhydrido Complexes Containing Ruthenium and a
Group 9 Metal, [Cp*3Ru2M(3-H)(-H)3] (M = Ir or Rh; Cp* = 5-
C5Me5): Synthesis, Structure, and Site Selectivity in Reactions
with Phosphines. Organometallics 2009, 28, 871-881.
(48) Shima, T.; Hu, S.; Luo, G.; Kang, X.; Luo, Y.; Hou, Z.
(32) Hu, Y.; Shaw, A. P.; Norton, J. R.; Sattler, W.; Rong, Y.
Synthesis, Electrochemistry, and Reactivity of New Iridium(III)
and Rhodium(III) Hydrides. Organometallics 2012, 31, 5058-
5064.
(33) Hu, Y.; Norton, J. R. Kinetics and Thermodynamics of H-
/H/H+ Transfer from a Rhodium(III) Hydride. J. Am. Chem. Soc.
2014, 136, 5938-5948.
(34) Pappas, I.; Chirik, P. J. Ammonia Synthesis by
Hydrogenolysis of Titanium-Nitrogen Bonds Using Proton
Coupled Electron Transfer. J. Am. Chem. Soc. 2015, 137, 3498-
3501.
(35) Pappas, I.; Chirik, P. J. Catalytic Proton Coupled Electron
Transfer from Metal Hydrides to Titanocene Amides, Hydrazides
and Imides: Determination of Thermodynamic Parameters
Relevant to Nitrogen Fixation. J. Am. Chem. Soc. 2016, 138,
13379-13389.
(36) Bezdek, M. J.; Chirik, P. J. Pyridine(diimine) Chelate
Hydrogenation in a Molybdenum Nitrido Ethylene Complex.
Organometallics 2019, 38, 1682-1687.
(37) Borowski, A. F.; Sabo-Etienne, S.; Donnadieu, B.;
Chaudret, B. Reactivity of the Bis(dihydrogen) Complex
[RuH2(2-H2)2(PCy3)2] toward N-Heteroaromatic Compounds.
Regioselective Hydrogenation of Acridine to 1,2,3,4,5,6,7,8-
Octahydroacridine. Organometallics 2003, 22, 1630-1637.
Dinitrogen Cleavage and Hydrogenation by a Trinuclear
Titanium Polyhydride Complex. Science 2013, 340, 1549-1552.
(49) Hu, S.; Shima, T.; Hou, Z. Carbon-carbon bond cleavage
and rearrangement of benzene by a trinuclear titanium hydride.
Nature 2014, 512, 413-415.
(50) Kameo, H.; Ito, Y.; Shimogawa, R.; Koizumi, A.; Chikamori,
H.; Fujimoto, J.; Suzuki, H.; Takao, T. Synthesis and
characterization of tetranuclear ruthenium polyhydrido clusters
with pseudo-tetrahedral geometry. Dalton Trans. 2017, 46,
5631-5643.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 12 of 13
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
ACS Paragon Plus Environment

Page 13 of 13
Journal of the American Chemical Society
Insert Table of Contents artwork here
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
13
ACS Paragon Plus Environment