Iridium-Catalyzed Hydrogenation and Dehydrogenation of N-Heterocycles in Water under Mild Conditions

Article abstract of DOI:10.1002/cssc.201900626

An efficient catalytic method is presented for the hydrogenation of N-heterocycles. The iridium-based catalyst operates under mild conditions in water without any co-catalyst or stoichiometric additives. The catalyst also promotes the reverse reaction of dehydrogenation of N-heterocycles, hence displaying appropriate characteristics for a future hydrogen economy based on liquid organic hydrogen carriers (LOHCs).

Full text of DOI:10.1002/cssc.201900626

Accepted Article
Title: Iridium Catalyzed Hydrogenation and Dehydrogenation of
N‑Heterocycles in Water under Mild Conditions
Authors: Shengdong Wang, Haiyun Huang, Christian Bruneau, and
Cedric Fischmeister
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10.1002/cssc.201900626
ChemSusChem
COMMUNICATION
Iridium Catalyzed Hydrogenation and Dehydrogenation of N‑
Heterocycles in Water under Mild Conditions
Shengdong Wang,[a],# Haiyun Huang,[a], # Christian Bruneau,[a] and Cédric Fischmeister*[a]
Dedication ((optional))
Abstract: In this communication is presented an efficient catalytic
method for the hydrogenation of N-heterocycles. The iridium-based
catalyst operates under mild conditions in water without any co-
catalyst or stoichiometric additives. The catalyst is also promoting
the reverse reaction of dehydrogenation of N-heterocycles hence
displaying appropriate characteristics for hydrogen-based energy
economy based on liquid hydrogen carriers.
latter performing the hydrogenation of quinoline under 5 bar of
hydrogen pressure at 90 °C in water and the reverse reaction at
100 °C in water. As revealed by these examples and despite
their higher cost as compared to other transition metals, iridium-
based complexes are predominant catalysts for the
hydrogenation/dehydrogenation of N-heterocycles. Of note,
reversible dehydrogenation/hydrogenation of N-heterocycles can
be performed using non-noble cobalt11a and iron11b pincer
complexes. However, these catalysts’ performances still need to
be improved as they require expensive pincer ligands, high
catalyst loadings and high temperatures to reach high efficiency.
Recently, we have been investigating the catalytic properties
of ruthenium and iridium complexes bearing underutilized
dipyridylamine ligands (dpa)12 in the valorization of the
biosourced levulinic acid (Figure 1).13 During these studies we
disclosed that the electron-rich complex Ir3 was very efficient for
the dehydrogenation of formic acid,14 another potential LOHC.15
In particular, Ir3 could perform the dehydrogenation of aqueous
and neat formic acid at low pH. This result prompted us to
investigate the catalytic performance of these complexes in the
hydrogenation/dehydrogenation of N-heterocycles.
The hydrogenation of N-heterocycles is of current interest as
many of these heterocycles are important building blocks in
organic synthesis with applications in drugs and agrochemicals.1
Recently, the hydrogenation and dehydrogenation of N-
heterocycles has been considered as a method for hydrogen
storage. Liquid organic hydrogen carrier’s (LOHC) have been
indeed proposed as convenient and safe solutions for hydrogen
storage.2 Several heterogeneous3 and homogeneous4 catalysts
have been reported for either hydrogenation or dehydrogenation
of N-heterocycles. Heterogeneous catalytic systems can in
general be recovered and reused but they require rather high
temperatures as compared to homogeneous catalysts. Recently,
Corma reported
a nanolayered cobalt-molybdenum sulfide
catalyst able to hydrogenate a broad range of substituted
quinolines at 120 °C under 12 bar of hydrogen pressure in
toluene with high chemo- and regioselectivity.5 In 2017, Toste
reported dendrimer-stabilized metal nanoparticles operating the
dehydrogenation of quinoline derivatives at 130 °C in toluene.
The reverse reaction was possible under milder conditions
(60 °C, 1 bar H2).6 Only very few homogeneous catalytic
systems
are
able
to
operate
both
hydrogenation/dehydrogenation of N-heterocycles. The first
example of homogeneous catalysts capable of carrying out both
hydrogenation and dehydrogenation of N-heterocycles was
reported by Yamagushi and Fujita7 in 2009. A Cp*Ir complex
containing
a
pyridonate ligand could perform
the
dehydrogenation of 1,2,3,4-tetrahydroquinolines in refluxing p-
xylene for 20 h. In 2014, the same group reported Cp*Ir
complexes bearing functional bipyridonate ligands for the
efficient perdehydrogenation and perhydrogenation of fused
Figure 1. DPA-based iridium complexes.
o
bicyclic N-heterocycles.8 However, harsh conditions (130 C, 70
bar H2) and 20 h in refluxing toluene were necessary. Other
iridium catalysts were reported by Crabtree9 and Albrecht,10 the
We initiated our investigations using quinoline 1a as a model
substrate. Several experimental parameters were screened and
optimized. As shown in Table 1, entry 1, the hydrogenation of 1a
was carried out with 0.5 mol% of Ir3 under 1 bar of dihydrogen
pressure at 90 oC in water for 17 h. Under these conditions,
1,2,3,4-tetrahydroquinoline 2a was cleanly obtained with almost
full conversion of 1a. Upon decreasing the temperature from 90
oC to room temperature, the conversions decreased from 99% to
[a]
S. Wang, H. Huang, Dr. C. Fischmeister, Dr. C. Bruneau
Institut des Sciences Chimiques de Rennes
Organometallics: Materials and Catalysis
UMR 6226 CNRS, Université de Rennes 1,Campus de Beaulieu, F-
35042 Rennes Cedex, France
E-mail: cedric.fischmeister@univ-rennes1.fr
o
less than 5% (Table 1, entry 2-5). 80 C was selected as the
+These two authors contributed equally to this work [b] Title(s),
temperature to further investigate the catalyst loading (Table 1,
entry 6-9). Interestingly, the catalyst loading could be reduced to
0.2 mol% without decreasing the reaction conversion (Table 1,
entry 8). Other catalysts Ir1, Ir2, Ir4 (Table 1, entry 10-12) have
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/cssc.201900626
ChemSusChem
COMMUNICATION
been evaluated but none of them led to higher performances
than Ir3.
Table 2. Iridium catalyzed hydrogenation of N-heterocycles[a]
Table 1. Ir-catalyzed hydrogenation of quinoline 1a: Investigation of Iridium
Entry
1
Substrate
Product
Yield[b]
98
complexes and Temperature. [a]
1a
1b
2a
2b
2
3
93
98
Entry
1
[Ir](mol%)
Ir3 (0.5)
Ir3 (0.5)
Ir3 (0.5)
Ir3 (0.5)
Ir3 (0.5)
Ir3 (0.4)
Ir3 (0.3)
Ir3 (0.2)
Ir3 (0.1)
Ir1 (0.2)
Ir2 (0.2)
Ir4 (0.2)
T (oC)
90
Conv.(%)[b]
99
99
93
81
<5
99
99
99
96
60
25
83
1c
1d
2c
2d
2
80
3
70
4
60
4
71
5
25
6
80
5
6
1e
1f
2e
2f
97
95
7
80
8
80
9
80
10
11
12
80
7
8
1g
1h
2g
2h
98
98
80
80
[a] Reaction conditions: quinoline (0.4 mmol), [Ir] (0.1-0.5 mol%), H2 (1 bar),
H2O (2 mL), 17 h. [b] Determined by 1H NMR analysis.
9
1i
1j
2i
2j
79
87
76
83
With the optimal conditions in hand, the scope of the iridium
catalysed hydrogenation of N-heterocycles was investigated as
described in Table 2. Numerous substituted quinoline derivatives
were subjected to hydrogenation. The hydrogenation of
quinoline derivatives substituted at the aryl ring i.e, 8-methyl 1b,
8-hydroxy- 1c and 8-bromo 1d (Table 2, entry 1-4) proceeded
smoothly giving the product in good to excellent yields (71-98%).
2-Alkyl 1e-1f and 2-aryl quinolines 1g-1m also led to the
corresponding products in good to excellent yields. Hence,
neither the steric hindrance nor the electronic properties of the
substituents had an impact on the reaction outcome. It must be
noted that dehalogenation of aryl-halide bonds was not
observed hence making the product valuable for further cross-
coupling reactions. 2-Heterocycle-substituted quinolines such as
2-(pyridin-2-yl) 1n, 2-(thiophen-2-yl) 1o and 2-(benzofuran-2-yl)
1p were also efficiently and selectively hydrogenated in good to
high yields. Interestingly, the polycyclic N-heterocycles 1q-1t
were also hydrogenated successfully leading to the
corresponding products 2q-2t in 53–94% yields. Very
interestingly, the 1,10-phenanthroline 1t can be selectively
reduced to 1,2,3,4-tetrahydro-1,10-phenanthroline 2t in 98%
yield. Finally, Ir3 could be further applied to the hydrogenation of
other types of N-heterocycles such as quinoxaline 1u, indole 1v
and isoquinoline 1s. However, the reaction temperature was
raised to 120 °C in order to achieve good yields of 2u and 2v.
10
11
12
1k
1l
2k
2l
13
1m
2m
95
14
15
1n
1o
2n
2o
93
96
16
1p
2p
71
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10.1002/cssc.201900626
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COMMUNICATION
17
18
19
1q
1r
2q
2r
79
75
60
1s
2s
20
21
1t
2t
98
1u
2u
95[c]
22
23
1v
2v
97[c]
53
Figure 3. Deuterium-labelling studies and proposed mechanism
1w
2w
Following these studies on the hydrogenation of quinolines, we
turned our attention to the reverse reaction using the same
catalyst Ir3. We were pleased to observe that the acceptorless
dehydrogenation of a number of tetrahydroquinolines took place
providing the corresponding quinolines in good to excellent
yields (Table 3). As generally required, higher temperature and
longer reaction time were required but Ir3 appeared to be
among the most active catalysts for this reaction. The release of
dihydrogen was confirmed using a vessel consisting of two
connected Schlenk tubes, as previously reported for the
dehydrogenation of formic acid.[13b] Using this experimental
setup, levulinic acid was quantitatively converted into γ-
valerolactone (see ESI).
[a] Reaction conditions: Substrate (0.4 mmol), Ir3 (0.2 mol%), H2 (1 bar), H2O
(2 mL), 80 oC, 17 h. [b] Isolated yield. [c] 120 oC.
Only very few studies on the mechanism of the
hydrogenation of quinoline have been reported.[4b,4e] These
proposed mechanisms depend on both the nature of the catalyst
and the reaction conditions. In order to get information on the
mechanism at play with our catalyst we have carried out two
experiments. First, we have monitored the activation of
1
hydrogen by Ir3 by H NMR. As depicted in Figure 2, when Ir3
was submitted to a hydrogen atmosphere, the clean formation of
a mono-hydride iridium complex was observed ( = -9.87 ppm).
We have then carried out the hydrogenation of quinoline in D2O.
This reaction led to the reduced product with 100% incorporation
of deuterium at C3 (Figure 3). This result is in line with the
proposed mechanisms, which involve hydride transfer at C2 and
C4 and protonation at C3 as described in Figure 3.
Table 3. Iridium catalyzed dehydrogenation of N-heterocycles[a]
Entry
1
Substrate
Substrate
Yield[b]
98
2a
2b
2e
1a
1b
1e
2
3
83
79
4
5
2g
2u
1g
1u
82
73
Figure 2. 1H NMR monitoring of the hydride intermediate.
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[a] Reaction conditions: Substrate (0.4 mmol), Ir3 (2 mol%), H2O (2 mL),
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In conclusion, we have developed an iridium-based catalyst
bearing an electron-enriched dipyridylamine ligand for the
reversible hydrogenation of quinoline derivatives. The catalyst
operates under mild reaction conditions in water without any
additive hence meeting the requirements for clean and
sustainable process. This catalyst is one of the few able to
promote both the hydrogenation and dehydrogenation of N-
heterocycles hence offering promising developments for the
reversible storage of hydrogen. Further efforts aiming at
improving the catalyst performances are in progress.
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Experimental Section
General procedure for the hydrogenation reactions
Quinolines (0.4 mmol), Ir3 (0.5-0.1 mol%), water (2 ml) were placed in a
20 ml thick wall Schlenk tube equipped with a Teflon screw cap. The
reaction mixture was degassed by 2 freeze-thaw cycles in liquid nitrogen.
After warming to r.t. the Schlenk tube was placed under 1 bar of
hydrogen and left upon stirring for 2 minutes before closing. The mixture
was stirred at the appropriate temperature for the desired time. After the
reaction, the vessel was cooled down and carefully depressurized. The
product mixture was analysed by 1H NMR. The mixture was purified by
flash column chromatography using petroleum ether and ethyl acetate as
eluent.
Acknowledgements
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The authors acknowledge the China Scholarship Council for a
grant to SW and M. Duo Wei for providing some reagents.
[6] C. Deraedt, R. Ye, W. T. Ralston, F. D. Toste, G. A. Somorjai, J. Am. Chem.
Soc. 2017, 139, 18084-18092
Keywords: homogeneous catalysis • Iridium • hydrogenation •
dehydrogenation• quinolines
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Entry for the Table of Contents (Please choose one layout)
Layout 1:
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The reversible
Author(s), Corresponding Author(s)*
hydrogenation/dehydrogenation of N-
heterocycles with an electron-enriched
iridium catalyst bearing a
Page No. – Page No.
Title
dimethylamino-substituted
dipyridylamine ligand is reported.
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