A Solid Iridium Catalyst for Diastereoselective Hydrogenation

Article abstract of DOI:10.1002/chem.201703872

An Ir(NHC) supported catalyst is used in the selective hydrogenation of terpinen-4-ol to cis p-menthan-4-ol. Its activity, selectivity and stability are compared to those of a homogeneous homologue [IrCl(COD)MesImPr] and to a commercial Pd/C. The solid Ir

Full text of DOI:10.1002/chem.201703872

A Journal of
Accepted Article
Title: A solid iridium catalyst for diastereoselective hydrogenation
Authors: Iuliia Romanenko, Louis Jaffeux, Laurent Veyre, Emmanuel
Lacôte, Valérie Meille, and Chloé Thieuleux
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201703872
Link to VoR: http://dx.doi.org/10.1002/chem.201703872
Supported by

10.1002/chem.201703872
Chemistry - A European Journal
A solid iridium catalyst for diastereoselective
hydrogenation
Iuliia Romanenko1, Louis Jaffeux2, Laurent Veyre1, Emmanuel Lacôte1,
Valérie Meille2, and Chloé Thieuleux1
1Université de Lyon, Institut de Chimie de Lyon, Laboratoire de Chimie,
Catalyse, Polymères et Procédés (UMR 5265 CNRS-Université Lyon
1-CPE Lyon), Équipe Chimie Organométallique de Surface, 43 Bd du 11
Novembre 1918, 69616 Villeurbanne, France.
2Université de Lyon, Institut de Chimie de Lyon, Laboratoire de Génie des
Procédés Catalytiques (UMR 5285 CNRS-Université Lyon 1-CPE Lyon),
43 Bd du 11 Novembre 1918, 69616 Villeurbanne, France.
September 13, 2017
Abstract
An Ir(NHC) supported catalyst is used in the selective hydrogenation of
terpinen-4-ol to cis p-menthan-4-ol. Its activity, selectivity and stability are
compared to those of a homogeneous homologue [IrCl(COD)MesImPr] and
to a commercial Pd/C. The solid Ir catalyst is much more selective than the
Pd catalyst (92 vs. 42% at 80◦C) but also more active, more selective and
more stable than the iridium complex in solution. For the first time, a sup-
ported catalyst shows an enhanced activity with respect to a complex in a
diastereoselective hydrogenation reaction.
Keywords: diastereoselective hydrogenation; hybrid catalyst; heterogenized
complex; iridium
Many iridium complexes are known to be highly active catalysts for the hy-
drogenation of sterically hindered olefins. For example, [Ir(COD)(PCy)3(py)]+
–
(BF4 or PF6– ) often referred as the Crabtree’s catalyst, is able to hydrogenate
2,3-dimethyl-but-2-ene at high TOF (4000h−1 at 0 ◦C), when RhCl(PPh3)3 and
HRuCl(PPh3)3 are not active.[1] Besides its high activity, this catalyst was also
found to proceed with strongly directing effects.[2] When a strongly ligating group
is present on the alkene, then its association to the metal constrains the hydride
transfer. This generally results in it being directed selectively onto one side of the
double bond.[3] For example, a 99.9% cis-orientation was found during the hydro-
5
10 genation of terpinen-4-ol to p-menthan-4-ol (Figure 1).[2] This orientation was the
result of formation of a stable chelating complex of Ir center with the hydroxyl
1
This article is protected by copyright. All rights reserved.

10.1002/chem.201703872
Chemistry - A European Journal
group and the double bond of the substrate. The ability of Crabtree’s catalyst to
transfer hydrogen stereoselectivly was successfully utilized in total synthesis of
natural products.[4–11] It is worth mentioning that in some cases the use of Crab-
15 tree’s catalyst was the only possible way to reach targeted molecules.[12–14]
H
2
+
Catalyst
HO
HO
HO
TRANS
p−Menthan−4−ol
1−Isopropyl−4−methyl cyclohexanol
CIS
R+S enantiomers
Terpinen−4−ol
Figure 1: Hydrogenation of terpinen-4-ol.
In sharp contrast, the terpinen-4-ol hydrogenation performed under heteroge-
neous catalysis led to selectivities ranging from 20 to 53% depending on the solvent
polarity.[15] The authors concluded from their observations that a higher degree of
selectivity could not be reached with heterogeneous catalysts because the binding
20 to the OH group is not sufficiently strong. This means that to achieve high stere-
oselectivity, one needs to use homogeneous conditions or add a chiral modifier.[16]
Nevertheless, extented uses of the Ir(I) complexes are hampered by the complexity
of the systems or by the catalyst low stability as the complex rapidly deactivates in
solution via the formation of polynuclear clusters (or nanoparticles).
25
Immobilizing a homogeneous complex on a solid support may appear as a so-
lution to maintain the properties of the catalyst, but the authors of a recent publica-
tion declare: "...homogeneous catalysts are not stable and thus there is little point in
immobilizing them. Other problems are lower rates, sometimes lower selectivities
and metal leaching".[17]
30
Some of us recently published the preparation of an Ir(NHC)-based hybrid
material where the Ir centers are precisely positioned along the pore channels of
a silica framework.[18] This catalyst led to an increased rate and selectivity of the
trans-stilbene hydrogenation compared to its molecular Ir analogue.
As the coordination sphere of the surface Ir complex seems to be maintained on
35 the support, we tried to go further than the simple hydrogenation of non-functional
olefins[18] and studied the possibility to perform the diastereoselective hydrogena-
tion of terpinen-4-ol to cis p-menthan-4-ol (Figure 1) taking advantage of the ca-
pacity of such Ir complexes to direct hydrogenation of hydroxyl-functionalized
olefins while maintaining a high diastereoselectivity and avoiding deactivation as
40 encountered with molecular complexes in solution.
The hydrogenation of a solution of terpinen-4-ol in toluene with solid cata-
2
This article is protected by copyright. All rights reserved.

10.1002/chem.201703872
Chemistry - A European Journal
lyst (M-Ir or Pd/C) was performed in an 300mL autoclave at constant hydrogen
pressure (3 bars) and constant temperature (40, 60 or 80 ◦C). Pd/C was selected
to benchmark the typical selectivity of existing heterogeneous catalysts.[15,19] The
45 conversion was followed by GC (see Supplementary Informations). A 30mL lab-
reactor was also used to investigate the behavior of the non-immobilized complex,
[IrCl(COD)MesImPr], to compare its performance with to that of the heteroge-
nized catalyst. Figure 2 clearly shows that the initial activity of the complex at
40 ◦C (white squares) and 80 ◦C (white circles) is much lower than that of the het-
50 erogenized catalyst (black squares and circles).
100
M-Ir, 40˚C
[IrCl(COD)MesImPr], 40˚C
M-Ir, 80˚C
[IrCl(COD)MesImPr], 80˚C
80
60
40
20
0
-1
45 h , 100000 mol/mol
-1
7 h , 30000 mol/mol
-1
1.4 h , 17000 mol/mol
-1
0.6 h , 9000mol/mol
0
20
40
60
80
100 120 140 160 180
Time (h)
Figure 2: Terpinenol hydrogenation with iridium catalysts at 40 and 80 ◦C, 3 bars
hydrogen, in toluene (0.47mol/L). 30mL reactor. Molar ratio substrate/iridium is
1000, initial TOF and final TON provided.
During the terpinen-4-ol hydrogenation at 80 ◦C with [IrCl(COD)MesImPr],
we noticed the formation of a black deposit (Figure 3). TEM and EDX analysis
clearly showed it to be Ir particles. This explains the rapid selectivity decrease ob-
served when the hydrogenation is catalyzed by the complex (Figure 4, white curve
55 with triangles). A similar decrease of selectivity vs. conversion was also recorded
at 40 ◦C (white curve with pentagons) albeit it was less rapid at that temperature.
Again in contrast, the selectivity remained stable for the hybrid material (Figure 4,
black curves).
3
This article is protected by copyright. All rights reserved.

10.1002/chem.201703872
Chemistry - A European Journal
Figure 3: Photos of the [IrCl(CODMesImPr] catalytic solution before (a) and after
(b) catalytic reduction of Terpinen-4-ol at 80 ◦C with 0.1mol% of catalyst.
100
95
90
85
M-Ir, 40˚C
[IrCl(COD)MesImPr], 40˚C
80
M-Ir, 80˚C
[IrCl(COD)MesImPr], 80˚C
75
70
65
60
0
20
40
60
80
100
Conversion (%)
Figure 4: Selectivity vs. conversion during terpinenol hydrogenation at 40 and
80 ◦C, 3 bars hydrogen, in toluene (0.47mol/L). 30mL reactor. Molar ratio sub-
strate/iridium is 1000.
A decomposition of surface Ir sites may also happen in the case of heteroge-
60 neous M-Ir but to obviously a much lower extent, since no loss of activity and
selectivity was noticed during the hydrogenation reaction. In order to get more in-
sight into the deactivation process that could occur with the supported catalyst, the
latter was kept at 80 ◦C under H2 after full conversion of terpinen-4-ol. Some very
small Ir nanoparticles (ca. 2 nm) were observed by HRTEM at the surface of the
65 silica framework (Figure 5) thus showing that Ir may decoordinate under H2 from
heterogeneous carbene leading to clusters and nanoparticles.
4
This article is protected by copyright. All rights reserved.

10.1002/chem.201703872
Chemistry - A European Journal
Figure 5: STEM micrographs of the recovered solid after full terpinen-4-ol reduc-
tion at 80 ◦C with 0.1mol% of M-Ir in toluene.
The initial reaction rate (molproduct/molmetal/h) of the heterogeneous iridium
catalyst was also compared to that of a commercial Pd/C. It appears that a mol of Pd
is initially 4 times more active than a mol of Ir at 80 ◦C (Figure 6). Nevertheless, the
70 selectivity to cis p-menthan-4-ol is nearly 90% in the case of M-Ir whereas it only
reaches 40% in the case of Pd. Besides, the kinetic behavior of M-Ir is a zero order
with respect to the reactant, whereas an apparent first order can be observed with
Pd (for substrate/metal ratios from 400 to 1500). The zero order can be explained
by a strong adsorption of the molecules on the iridium center.[20] The apparent first
75 order rate with Pd was checked by changing the terpinenol initial concentration.
The kinetic order is not due to catalyst deactivation. Note that the results obtained
with M-Ir in a large volume autoclave (300mL) perfectly match those obtained in
a 30mL lab-reactor (Figure 6 vs. Figures 2 and 4).
5
This article is protected by copyright. All rights reserved.

10.1002/chem.201703872
Chemistry - A European Journal
100
80
60
40
20
0
-1
TOF = 115 h
0
Conversion with Pd/C
Cis-selectivity with Pd/C
Initial rate
0
1
2
3
4
5
6
7
8
Time (h)
100
80
60
40
20
0
-1
TOF = 28 h
0
Conversion with M-Ir
Cis-selectivity with M-Ir
Initial rate
0
10
20
30
40
50
60
70
80
Time (h)
Figure 6: Terpinenol hydrogenation at 80 ◦C, 3 bars hydrogen, in toluene
(0.63mol/L). 300mL reactor. Molar ratio substrate/metal is 400 for Pd/C and 2100
for M-Ir.
Interestingly, the diastereoselectivity was even higher at lower temperatures,
80 reaching 95% at 40 ◦C. Nevertheless, the activation energy was very high (ca.
75kJ/mol) for M-Ir, leading to a very slow reaction rate at 40 ◦C (1 h−1, see Figure
2). The activation energy for Pd/C was half that of M-Ir (ca. 35kJ/mol). This
is not limited to terpinen-4-ol: a similar kinetic behavior was observed for the
hydrogenation of trans-stilbene. In this case a zero order with respect to the reactant
85 for M-Ir and a first order for Pd/C were observed. The activation energy was also
twice higher for M-Ir.
In conclusion, we have reported the first example of a highly productive and
6
This article is protected by copyright. All rights reserved.

10.1002/chem.201703872
Chemistry - A European Journal
diastereoselective heterogeneous hydrogenation catalyst which does not rely on
additives to proceed. Stereoselectivity was achieved thanks to directed hydride
90 transfer, made possible by the coordination sphere of the catalytic sites. We believe
this opens great perspectives for asymmetric heterogeneous catalysis.
References
[1] R. Crabtree, Accounts of Chemical Research 1979, 12, 331–337.
[2] R. H. Crabtree, M. W. Davis, Organometallics 1983, 2, 681–682.
95
[3] J. M. Brown, Angewandte Chemie International Edition in English 1987,
26, 190–203.
[4] M. A. Arnold, K. A. Day, S. G. Durón, D. Y. Gin, Journal of the American
Chemical Society 2006, 128, 13255–13260.
[5] P. K. Koech, M. J. Krische, Tetrahedron, New applications of metal catalysis
in natural product synthesis 2006, 62, 10594–10602.
100
[6] W. Qi, M. C. McIntosh, Tetrahedron, Synthetic Advances in Transition Metal-
Catalyzed Bond-Forming Reactions 2008, 64, 7021–7025.
[7] K. C. Nicolaou, Q. Kang, S. Y. Ng, D. Y. Chen, Journal of the American
Chemical Society 2010, 132, 8219–8222.
105
[8] J. Ramharter, J. Mulzer, European Journal of Organic Chemistry 2012,
2012, 2041–2053.
[9] J. S. Clark, G. Yang, A. P. Osnowski, Organic Letters 2013, 15, 1464–1467.
[10] T. Sakai, A. Fukuta, K. Nakamura, M. Nakano, Y. Mori, The Journal of
Organic Chemistry 2016, 81, 3799–3808.
110 [11] G. Ernouf, J. Brayer, B. Folléas, J. Demoute, C. Meyer, J. Cossy, The Jour-
nal of Organic Chemistry 2017, 82, 3965–3975.
[12] S. Hanessian, E. Mainetti, F. Lecomte, Organic Letters 2006, 8, 4047–4049.
[13] T. J. Maimone, J. Shi, S. Ashida, P. S. Baran, Journal of the American Chem-
ical Society 2009, 131, 17066–17067.
115 [14] A. Shvartsbart, A. B. Smith, Journal of the American Chemical Society
2015, 137, 3510–3519.
[15] R. H. Crabtree, M. W. Davis, The Journal of Organic Chemistry 1986, 51,
2655–2661.
[16] M. Besson, S. Neto, C. Pinel, Chem. Commun. 1998, 1431–1432.
120 [17] S. Hubner, J. G. de Vries, V. Farina, Advanced Synthesis & Catalysis 2016,
358, 3–25.
[18] I. Romanenko, D. Gajan, R. Sayah, D. Crozet, E. Jeanneau, C. Lucas, L. Ler-
oux, L. Veyre, A. Lesage, L. Emsley, E. Lacôte, C. Thieuleux, Angewandte
Chemie International Edition 2015, 54, 12937–12941.
7
This article is protected by copyright. All rights reserved.

10.1002/chem.201703872
Chemistry - A European Journal
125 [19] A. Tungler, G. Fogassy, Journal of Molecular Catalysis A: Chemical, Catla-
ysis with Supported Palladium Metal at the Turn of the 21st Century 2001,
173, 231–247.
[20] D. Y. Murzin, P. Mäki-Arvela, E. Toukoniitty, T. Salmi, Catalysis Reviews
2005, 47, 175–256.
8
This article is protected by copyright. All rights reserved.