Hydrogenation/dehydrogenation of N-heterocycles catalyzed by ruthenium complexes based on multimodal proton-responsive CNN(H) pincer ligands

Article abstract of DOI:10.1039/d0dt02326d

Ru complexes based on lutidine-derived pincer CNN(H) ligands having secondary amine side donors are efficient precatalysts in the hydrogenation and dehydrogenation of N-heterocycles. Reaction of a Ru-CNN(H) complex with an excess of base produces the formation of a Ru(0) derivative, which is observed under catalytic conditions.

Full text of DOI:10.1039/d0dt02326d

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Hydrogenation/dehydrogenation of
N-heterocycles catalyzed by ruthenium complexes
Cite this: DOI: 10.1039/d0dt02326d
based on multimodal proton-responsive CNN(H)
pincer ligands†
Received 8th May 2020,
Accepted 3rd July 2020
Práxedes Sánchez, a Martín Hernández-Juárez, b Nuria Rendón,
*
a
Joaquín López-Serrano, a Laura L. Santos, a Eleuterio Álvarez,
a
DOI: 10.1039/d0dt02326d
a
rsc.li/dalton
Margarita Paneque a and Andrés Suárez
*
Ru complexes based on lutidine-derived pincer CNN(H) ligands of a Ru-PNN(H) complex with 2 equiv. of base produced the
having secondary amine side donors are efficient precatalysts in formation of an enamino anionic Ru(II) species,6 which accord-
the hydrogenation and dehydrogenation of N-heterocycles. ing to DFT calculations catalyzes the dehydrogenative coupling
Reaction of a Ru-CNN(H) complex with an excess of base produces of alcohols solely through amine-metal/amido-metal
the formation of a Ru(0) derivative, which is observed under cata- interconversion.8
lytic conditions.
On the other hand, hydrogenation and acceptorless dehy-
drogenation are low environmental impact processes for the
reduction of aromatic N-heterocycles to their corresponding
saturated derivatives and the oxidation of the latter products to
the parent N-heteroarenes, respectively.9 Although the prin-
ciple of microscopic reversibility dictates that species able to
catalyze the hydrogenation of N-heterocycles should also be
active in the reverse dehydrogenation process, the number of
catalytic systems that are able to perform both transformations
is scarce, being these mainly based on M-PNHP (M = Fe, Co)
complexes10 or costly CpIr derivatives.11
Pincer complexes based on N-heterocyclic carbenes (NHCs)
have received an increased attention as catalysts in hydrogen-
ation and dehydrogenation reactions.12 An interesting modifi-
cation of the structure of lutidine-derived PNP and PNN
ligands consists on the substitution of the P-donors by NHC
groups.13 Herein, we report a series of Ru complexes stabilized
with lutidine-derived CNN(H) pincer ligands incorporating sec-
ondary amino groups that are suitable catalytic precursors in
Following pioneering work by Noyori et al. on the use of metal
complexes based on ligands bearing primary or secondary
amine donors capable of getting involved in reversible metal-
amine/metal-amido interconversion,1 a considerable diversity
of ligands containing Brønsted acid/base functionalities have
been developed.2 Among others, lutidine-derived metal com-
plexes, which are readily deprotonated at the pincer methylene
arms with concomitant dearomatization of the pyridine
central moiety, have received significant attention.3 Both luti-
dine- and NH-containing pincer complexes have provided
highly active and selective catalysts for a broad variety of hydro-
genation4 and dehydrogenation reactions.5
Recently, the Milstein group has reported novel Ru com-
plexes incorporating lutidine-based PNN(H) ligands containing
secondary amines as side donors that are efficient catalysts in
the (de)hydrogenation of polar substrates.6,7 These complexes
are active ester and amide hydrogenation catalysts under very
mild conditions, and catalyze the dehydrogenative coupling of
alcohols to esters at low temperatures. Interestingly, reaction
both
the
hydrogenation
and
dehydrogenation
of
N-heterocycles. Because of the presence of two acidic function-
alities in the ligands, these complexes might exhibit metal–
ligand cooperation based on pyridine aromatization/dearoma-
aInstituto de Investigaciones Químicas (IIQ), Departamento de Química Inorgánica
and Centro de Innovación en Química Avanzada (ORFEO-CINQA). CSIC and
Universidad de Sevilla. Avda. Américo Vespucio 49, 41092 Sevilla, Spain.
E-mail: nuria@iiq.csic.es, andres.suarez@iiq.csic.es
bCentro de Investigaciones Químicas. Universidad Autónoma del Estado de Hidalgo.
Km. 14.5 Carretera Pachuca-Tulancingo. C.P. 42184, Mineral de la Reforma,
Hidalgo, Mexico
tization
or
amine-metal/amido-metal
interconversion.
However, preliminary NMR spectroscopic data revealed the
unexpected formation of a zero-valent Ru complex under cata-
lytic conditions.
Aiming to synthesize Ru-CNN(H) complexes, the imidazo-
lium salts 1a–c were made react with Ag2O in CH2Cl2 to yield
the silver complexes 2a–c (Scheme 1). Subsequent reactions of
2a–c with RuHCl(CO)(PPh3)3 in THF, followed by treatment
with NaBF4 and PPh3 in CH3CN, allowed the isolation of the
†Electronic supplementary information (ESI) available: Experimental pro-
cedures; X-ray diffraction analysis; and DFT calculations details. CCDC 1968868
[3a·CH2Cl2] and 1968869 [3b·2CH3OH]. For ESI and crystallographic data in CIF
or other electronic format see DOI: 10.1039/d0dt02326d
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Table 1 Hydrogenation of N-heterocycles catalyzed by 3a–c
Entry
Substrate
Product
Cat.
Yield (%)
1
2
3
3a
3b
3c
>99 (6 h)
23 (6 h)
22 (6 h)
4
3a
>99 (24 h)
Scheme 1 Synthesis of Ru–CNN(H) complexes.
5
6
3a
3a
98 (19 h)
92 (19 h)
Ru-CNN(H) complexes 3a–c in moderate to good yields
(33–85%). In the H NMR spectrum, the hydrido ligand of 3a
1
gives rise to a doublet resonance at −7.79 ppm with a large
2JHP of 114.0 Hz, evincing the trans arrangement of the
hydrido and PPh3 ligands. Similar NMR features are observed
for complexes 3b and 3c. This structural arrangement was
further confirmed in the solid state by an X-ray diffraction
study of 3a and 3b (ESI†).
7a,b
3a
3a
98 (48 h)
Next, the catalytic behavior of 3a–c in the hydrogenation of
N-heterocycles was examined (Table 1). In the presence of
KOtBu (5 mol%), complex 3a (0.5 mol%) catalyzed the hydro-
genation of quinoxaline (4a) under 4 bar of H2 at 80 °C leading
to full conversion in 6 h (entry 1). However, under the same
conditions, complexes 3b and 3c were found to be less active
than 3a (entries 2 and 3). Based on these results, complex 3a
was tested in the hydrogenation of a series of N-heterocycles.
For example, 2-methylquinoxaline (4b) was reduced under the
above conditions with high conversions in 24 h (entry 4).
Similarly, using 0.5 mol% of 3a, acridine (4c) and phenanthri-
dine (4d) were hydrogenated with elevated conversions in 19 h
(entries 5 and 6). However, the hydrogenation of quinazoline
(4e), quinoline (4f) and quinaldine (4g) required harsher reac-
tion conditions (1.0 mol% 3a, 95 °C, 48 h) to proceed to
higher than 95% conv (entries 7–9). Under the later con-
ditions, an increase of the H2 pressure to 10 bar was used for
the hydrogenation of isoquinoline (4h) (entry 10). Finally,
8a,b
>99 (48 h)
9a,b
3a
95 (48 h)
10a,b,c
3a
3a
74 (24 h)
11a,b
>99 (24 h)
12a,b,c
3a
93 (72 h) (+7% 5i)
under
4 bar of H2, selective reduction of one of the
N-containing rings of 4,7-phenanthroline (4i) was achieved,
while the hydrogenation of both N-heterocycles was accom-
plished at 10 bar of H2 (entries 11 and 12).
Reaction conditions: Unless otherwise noted:
4
bar H2, 80 °C,
2-methyltetrahydrofuran, 0.5 mol% Ru–CNN(H), 5 mol% KOtBu; [S] =
0.24 M. Yields were determined by 1H NMR spectroscopy using mesity-
lene as internal standard. a 95 °C. b 1.0 mol% 3a. c 10 bar H2.
The catalytic performance of 3a in the dehydrogenation of
the N-heterocycles 5 was also investigated (Table 2). Initially,
dehydrogenation of 1,2,3,4-tetrahydroquinoxaline (5a) was
examined using 4.0 mol% of 3a and 60 mol% of KOtBu in
2-methyltetrahydrofuran at 85 °C, leading to complete for-
mation of 4a after 24 h (entry 1). However, a higher tempera-
ture was required for the reaction of 5b (160 °C, o-xylene)
(entry 2). In addition, the oxidation of other N-heterocyclic
substrates was examined. 9,10-Dihydroacridine (5c) was dehy-
drogenated in refluxing o-xylene with moderate catalytic
activity (entry 3). Meanwhile, under the same conditions,
hydrogen release from 5d and 5e took place with higher than
94% conv. (entries 4 and 5). The dehydrogenation of 5f, 5g and
5h proceeded with only low to moderate conversions after 48 h
(entries 6–8); whereas 5i yielded 4,7-phenanthroline in 74%
NMR yield (entry 9). To the best of our knowledge, complex 3a
is the first example of a Ru derivative that catalyzes both the
hydrogenation and dehydrogenation of
a
series of
N-heterocycles. In addition, the catalytic activity of 3a in the
reduction of N-heteroarenes lies in the range of most CpIr
systems, although it is less efficient in the dehydrogenation
reactions (0.1–5 mol% Ir, 74–160 °C).11 Moreover, the perform-
ance of 3a is superior to that of the Fe-PNHP catalyst in the
hydrogenation of N-heterocycles (3 mol% Fe, 80 °C, 5 bar H2),
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Table 2 Dehydrogenation of N-heterocycles catalyzed by complex 3a
Entry
1a
Substrate
Product
Yield (%)
>99 (24 h)
2
85 (24 h)
3
4
76 (48 h)
94 (24 h)
Scheme 2 Generation of Ru complexes 6–8.
5
6
>99 (24 h)
50 (48 h)
to the methyne vCH–NHC bridge, and two doublets of doub-
3
lets at 3.43 (2JHH = 12.0 Hz, JHH = 12.0 Hz) and 3.09 (2JHH
=
3
12.0 Hz, JHH = 1.9 Hz) ppm, attributable to the CH2-NH
moiety. Subsequent treatment of the same THF-d8 solution of
complex 6 with an excess of KOtBu (10 equiv.) or KHMDS (3
equiv.) produced
a dark violet coloring of the sample
(Scheme 2). The NMR spectra of the reaction mixture pointed
out to the formation of the anionic complex 7, which is struc-
turally related to an enamino Ru(II) complex previously
reported by Milstein et al.6 The hydride and the enamino
vCH–NtBu hydrogens of the pincer ligand resonate as singlets
at −17.09 and 6.69 ppm, respectively, in the 1H NMR experi-
ment, while the inequivalent methylene protons of the CH2–
NHC bridge appear as mutually coupled doublets at 4.83 and
4.56 ppm (2JHH = 12.7 Hz). Also of note, the hydrogens of the
pincer dearomatized central ring produce upfield shifted reso-
nances in the range between 5.33 and 6.54 ppm.
7
27 (48 h)
8
9
27 (48 h)
74 (48 h)
THF-d8 solutions pressurized with H2 (3 bar) of the in situ
generated complexes 6 and 7 were analyzed by NMR spec-
troscopy in order to determine the potential of these species to
perform H2 activation. However, noticeable changes in their
1H NMR experiments were not observed. Alternatively, pressur-
ization of solutions of complexes 6 and 7 with D2 (3 bar) pro-
duced the H/D exchange of the hydride ligands and the
protons of the methylene and methyne bridges (ESI†), evincing
the ability of complexes 6 (after PPh3 decoordination) and 7 to
produce the reversible activation of H2 in a ligand-assisted
process or through the participation of an external base.
Unexpectedly, heating to 60 °C solutions of the in situ
formed species 6 or 7 produces the clean generation of a new
species, which has been spectroscopically characterized as the
Ru(0) imine complex 8 (Scheme 2).14 The 1H NMR spectrum of
the resulting dark blue solutions indicates the presence of the
imine moiety by the appearance of a doublet at 7.92 ppm (4JHP
= 3.7 Hz). The 13C{1H} NMR spectrum presents the resonances
Reaction conditions, unless otherwise noted: 160 °C, o-xylene,
4.0 mol% 3a, 60 mol% KOtBu. [S] = 0.12 M. Yields were determined by
1H NMR spectroscopy using mesitylene as internal standard. a 85 °C,
2-methyltetrahydrofuran. [S] = 0.06 M.
while it is slightly poorer in the dehydrogenation reactions
(3 mol% Fe, xylene reflux).10
To investigate the likely Ru species formed under catalytic
conditions, complex 3a was treated with KOtBu (1.3 equiv.) in
THF-d8 producing the instantaneous dark red coloring of the
initially clear solution. Formation of the deprotonated
complex
6
was ascertained by 1H NMR spectroscopy
(Scheme 2), which shows the hydrido ligand of 6 giving rise to
2
a broad doublet at −7.64 ppm with a large JHP of 140.2 Hz,
indicative of its trans coordination to PPh3. Selective deproto-
nation of the CH2-NHC arm of 3a was evident from the obser-
vation of a singlet signal at 4.38 ppm (integrating to 1H), due
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to determine the nature of the metal species participating in
the catalytic cycle are being carried out.
Conflicts of interest
Scheme 3 Complexes A and B reported by Keith, Chianese et al.
There are no conflicts to declare.
corresponding to the CO ligand and the C2–NHC carbon as
doublets at 216.1 (JCP = 10 Hz) and 191.3 (JCP = 7 Hz) ppm,
respectively. Finally, the coordination of PPh3 is manifested in
the 31P{1H} NMR experiment by the appearance of a singlet at
50.5 ppm. Complex 8 can be regarded as derived from 6 by the
formal loss of a H2 molecule.
Acknowledgements
Financial support (FEDER contribution) from the Spanish
Ministry of Science and Innovation (CTQ2016-80814-R) and
Junta de Andalucía (PY18-3208), and the use of computational
facilities of the Supercomputing Center of Galicia (CESGA) are
gratefully acknowledged. We thank support of the publication
fee by the CSIC Open Access Publication Support Initiative
through its Unit of Information Resources for Research
(URICI).
It is worth noting that imine Ru(0) complexes structurally
related to 8 have been recently reported by Keith, Chianese
et al. (Scheme 3).14 These derivatives (such as A), which were
shown to be highly active ester hydrogenation catalysts, were
isolated from the reactions with base of Ru–PNN and –CNN
complexes bearing dialkylamino side donors. Moreover, hydro-
gen activation by A led to the formation of a Ru dihydride
complex (B) in which the imine ligand fragment was hydrogen-
ated to amine. Interestingly, solutions of the Ru(0) derivative 8
were active in the hydrogenation of N-heterocycles.14,15 Thus,
THF-d8 solutions containing this complex were able to hydro-
genate (3 bar H2) 2-methylquinoxaline (10 equiv.) at 60 °C,
being 8 the only detectable metal species during the catalytic
reaction and suggesting that this is the catalyst resting state
(ESI†). Similarly, addition of 2-methylquinoxaline (10 equiv.)
to a THF-d8 solution of a 1 : 1 mixture of 6 and 7 produced the
instantaneous formation of 8. Subsequent pressurization with
H2 (3 bar) and heating to 65 °C the resulting solution brought
about the hydrogenation of the N-heteroarene (ESI†).
Notes and references
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dride species similar to B, a THF-d8 solution of complex 8 was
pressurized with H2 (4 bar) and analyzed by NMR spec-
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