Rh(CAAC)-Catalyzed Arene Hydrogenation: Evidence for Nanocatalysis and Sterically Controlled Site-Selective Hydrogenation

Article abstract of DOI:10.1021/acscatal.8b02589

We report the arene hydrogenation of ethers, amides, and esters at room temperature and low hydrogen pressure, starting from [(CAAC)Rh(COD)Cl] (CAAC = cyclic alkyl amino carbene). Kinetic, mechanistic, and Rh K-edge XAFS studies showed formation of Rh nanoparticles from [(CAAC)Rh(COD)Cl], in contrast to a previous report of [(CAAC)Rh(COD)Cl] functioning as a homogeneous catalyst for arene hydrogenation. We determined that the site-selective arene hydrogenation catalyzed by this system is under steric control, as shown by detailed competition experiments with derivatives of ethers, amides, and esters bearing different aromatic rings of varying electronic and steric influence. This work illustrates the potential of CAAC ligands in the formation and stabilization of a colloidal dispersion of stable nanoparticle catalysts.

Full text of DOI:10.1021/acscatal.8b02589

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Article
Rh(CAAC)-Catalyzed Arene Hydrogenation: Evidence for
Nanocatalysis and Sterically Controlled Site-Selective Hydrogenation
Ba L. Tran, John L. Fulton, John C. Linehan, Johannes A. Lercher, and R. Morris Bullock
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b02589 • Publication Date (Web): 30 Jul 2018
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ACS Catalysis
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Rh(CAAC)-Catalyzed Arene Hydrogenation: Evidence for Nanocatal-
ysis and Sterically Controlled Site-Selective Hydrogenation
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Ba L. Tran, John L. Fulton, John C. Linehan, Johannes A. Lercher, and R. Morris Bullock*
Institute for Integrated Catalysis, Pacific Northwest National Laboratory, Richland, WA 99352, United States
ABSTRACT: We report arene hydrogenation of ethers, amides, and esters at room temperature and low hydrogen pressure, starting
from [(CAAC)Rh(COD)Cl] (CAAC = cyclic alkyl amino carbene). Kinetic, mechanistic, and Rh K-edge XAFS studies showed
formation of Rh nanoparticles from [(CAAC)Rh(COD)Cl], in contrast to a previous report of [(CAAC)Rh(COD)Cl] functioning as
a homogeneous catalyst for arene hydrogenation. We determined that the site-selective arene hydrogenation catalyzed by this system
is under steric control, as shown by detailed competition experiments with derivatives of ethers, amides, and esters bearing different
aromatic rings of varying electronic and steric influence. This work illustrates the potential of CAAC ligands in the formation and
stabilization of a colloidal dispersion of stable nanoparticle catalysts.
Keywords: rhodium, nanocatalysis, arene hydrogenation, site selectivity, XAFS
Introduction
tematic ligand design, which has been the key to success in tran-
sition metal catalysis, to the colloidal chemistry, reproducibly
generating hybrid nanomaterials from well-defined molecular
precursors.15a
Metal-catalyzed hydrogenations constitute crucially important
transformations in the production of commodity and specialty
chemicals, pharmaceuticals and bio-renewable formulations.1
Within that broad scope, hydrogenation of olefins,2 aldehydes,3
ketones3a, 3b esters,4 amides,5 carboxylic acids,6 imines,3a, 7 ni-
triles,8 and nitro9 groups have been studied extensively. In con-
trast, arene hydrogenation, despite its longstanding im-
portance,10 has been less explored; the variety of catalysts is
limited, and high reaction temperatures (>200 °C) are typically
required. The utility of arene hydrogenations is largely confined
to petroleum feedstocks, as sufficient selectivity in the presence
of functional groups is difficult to achieve. A prominent appli-
cation of arene hydrogenation is the conversion of benzene to
cyclohexane to produce Nylon, solvents, and plasticizers.11
Traditional arene hydrogenations use heterogeneous cata-
lysts (e.g., Ni, Pd, Ru, Rh, Pt) supported on a material to stabi-
lize the nanoparticles (NPs).12 Intense efforts seek to achieve
reproducible synthesis of colloidal materials.13 N-Heterocyclic
carbenes (NHCs)14 have been established as a new stabilizing
agents for colloidal catalysts.15 Applications of ionic liquids
containing NHC stabilize colloidal metals not only on the basis
of electrostatic interactions,16 but also stabilize colloidal metals
by covalent metal-carbene ligation.17
Scheme 1. Catalytic arene hydrogenations by Rh(CAAC)
systems.
Glorius (2017)
Rh
iPr
N
F
F
0.1-1.0 mol%
H2 (49 atm)
iPr
R
R
4 Å MS, hexane
25 ºC, 24 h
X
X
Rh
Cl
R2 = OH, OTBS, OMe, NHBoc, CO2Me, Bpin
X = O, NBoc
Zeng (2015)
Rh
O
OH
O
3.0 mol%
H2 (5-79 atm)
R1
R2
R1
4 Å MS, CF3CH2OH
25-70 ºC, 24-48 h
O
R = CO2H,
R1 = Me, OMe,
iPr, tBu
CH2COnBu,
CH2CO2Me,
CONHMe
R2
This work
Rh
These insights have led to interest in NHCs for modification
of nanoparticles catalysts 15a, 18 and functional materials; the ste-
ric and electronic profiles of NHCs are readily tunable.19 The
combination of chiral NHCs and Pd-Fe2O3 catalyzes, for exam-
ple, enantioselective a-arylation reactions.20 There is also grow-
ing evidence of electronic and steric effects of NHCs on the sta-
bility of metal particles15a, 21 and the activity of heterogeneous
systems such as Ni-catalyzed C-H borylation of arenes and het-
eroarenes,22 Buchwald-Hartwig C-N cross couplings,23 and
electrocatalytic reduction of CO2 to CO.24 These developments
illustrate the potential for a bottom-up approach to translate sys-
3.0 mol%
AgBF4 (3.0 mol%)
X
X
H2 (6.8 atm)
R3
R3
25 ºC, THF
6 h
X
= O, NHC(O), OC(O)
•
•
Kinetics, filtration, poisoning studies
Rh K-edge XAFS, STEM, IR
R3 = Me, Et, OMe, CF3
Herein, we report studies with Rh(CAAC) (CAAC = cyclic al-
kyl amino carbene)25 for the chemoselective hydrogenation of
aryl groups of ethers, amides, and esters at room temperature
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under low pressure of H2. While Rh(CAAC) complexes have
been reported for chemoselective arene hydrogenations of aryl
carbonyls26 and aryl fluorides27 (Scheme 1), the nature of the
active Rh catalysts have not been thoroughly examined. These
Rh(CAAC) complexes can potentially catalyze difficult, selec-
tive arene hydrogenations under mild conditions. We report a
combined study of kinetic, mechanistic, spectroscopic, and mi-
croscopic experiments that determine the nature of the active
Rh species for arene hydrogenation as Rh nanoparticles (Rh
NPs). In addition, we perform competition experiments to un-
derstand the site-selective hydrogenation of ethers, amides, and
esters by this Rh system.
Table 1. Reaction development for arene hydrogenation
1
2
3
4
5
6
7
8
O
Cy2O
L (6 mol%)
[Rh(COD)Cl]2 (1.5 mol%)
KOtBu (6 mol%)
+
O
PhOCy
O
H2 (6.8 atm)
+
HO
THF, 25 °C, 2 h
Ph2O
CyOH
Entry Ligand mol% Ligand Conv.ᵃ Cy2O % PhOCy % CyOH %ᵃ
9
1
NHC
cNHC
L1
3 to 6
0
0
10
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2
3
Results and Discussion
3
6
100
0
70
0
30
4
L2
6
6
Reaction Development. We initially studied arene hydro-
genation by evaluating the reaction of diphenyl ether (Ph2O) at
25 ºC with [Rh(COD)Cl]2, a series of NHCs, and KOtBu in THF
under H2 (6.8 atm). Results of the Rh-catalyzed hydrogenation
of Ph2O are presented in Table 1. No conversion of Ph2O at 2 h
was observed from the combination of several NHCs,28
[Rh(COD)Cl]2, and KOtBu in THF (Table 1, entry 1). Attempts
to stabilize the Rh with the bidentate NHC [bis(1-mesityl-3-im-
idazol-3-yl)methane] or the tridentate NHC [2,6-bis[(3-me-
sityl)imidazolium]pyridine] ligand (Table 1, entry 2) also led to
no conversion of Ph2O after 24 h. The lack of catalytic activity
using the tridentate NHC is readily understood, since the iso-
lated Rh(I) complex is inert towards the oxidative addition of
H2.29
5
L3
78
29
0
20
24
50
0
8
5
6
L4
6
7
L5
6
8b
9c
10d
11e
L1
6
35
93
0
10
45
22
34
3
L1
1.8
6
14
L1
L1
6
0
12
none
none
0
Conditions: 0.5 mmol Ph2O in 1 mL THF. aConversion and yields were
determined by GC analysis with dodecane as the internal standard. bH2
(1 atm), 24 h. c0.30 mol% [Rh(COD)Cl]2, 1.2 mol% L1, neat Ph2O, 24 h.
d1-2 equiv. MOtBu (M = Na, K) to Ph2O. eno [Rh(COD)Cl]2.
Ligands: NHC = IMes-HCl, IPr-HCl, IPr*-HCl, IPr-HBF4, SIPr-HBF4, ICy-
HBF4
We next explored cyclic alkyl amino carbenes (CAACs),
which are more electron-donating than NHCs25, 30 and which
confer a different spatial orientation around the metal center be-
n = 0, 1
2 Br
cNHC (3 mol%)
N
N
N
N
N
N
N
N
N
cause of their asymmetric characteristics, compared to symmet-
Mes
Mes
2 X = Br, BF4
14b, 25, 31
rical NHCs.14a,
Treating [Rh(COD)Cl]2 with L1 (4
R
R
R = Me, Mes
equiv) and KOtBu (4 equiv) under H2 (6.8 atm) provided quan-
titative conversion of Ph2O to dicyclohexyl ether (Cy2O, 70%)
and cyclohexanol (CyOH, 30%) in 2 h (Table 1, entry 3).
To elucidate the structure-activity relationship of CAACs on
Rh-catalyzed arene hydrogenations, we prepared a series of
CAAC derivatives (L2, L3, L4, L5) of varying steric influence
and substitution pattern at the nitrogen atom and the quaternary
carbon center. The Rh-catalyzed hydrogenations using L2-L5
(Table 1, entries 4-7) exhibited no activity to moderate activity
compared to L1. The structure-activity studies showed that the
cyclohexyl group at the quaternary carbon is crucial for high
activity, as replacing the cyclohexyl group with a phenyl and a
methyl in L2 thwarted catalysis (Table 1, entry 4). A smaller
mesityl group at the nitrogen (L3), compared to 2,6-diiso-
propylphenyl (L1), reduces catalytic activity to give Cy2O
(8%), PhOCy (50%), and CyOH (20%) at 78% conversion (Ta-
ble 1, entry 5). Increasing the steric demand at the aniline (i.e.,
2,6-bis(diphenylmethyl)-4-methylaniline) (L4) dramatically re-
duced activity, giving 29% conversion (Table 1, entry 6). Intro-
ducing a cyclohexyl group at the nitrogen (L5) completely shuts
down catalysis (Table 1, entry 7). Lastly, no conversion was
observed under the conditions used here [Ph2O (0.5 mM) under
6.8 atm H2 at 25 ºC] for 2 h in the presence of [Rh(COD)Cl]2
without L1, or without [Rh(COD)Cl]2 (Table 1, entry 11-12).
These results indicate that the combination of ligand and rho-
dium is required to effectively generate the catalyst.
CAACs
BF4
BF4
iPr
N
N
R1
Ph
iPr
R1
=
L2
L1 = Dipp L3 = Mes
L4 = Dipp* L5 = Cy
Dipp = 2,6-diisopropylphenyl
Dipp* = 2,6-bis(diphenylmethyl)4-methylphenyl
Hydrogenation of Ph2O at lower H2 pressure and low loading
of [Rh(COD)Cl]2 led to products, albeit with modest activity
and extended reaction time. Only 35% conversion was achieved
when the reaction was performed with [Rh(COD)Cl]2 and L1 at
1 atm of H2 for 24 h (Table 1, entry 8). Performing the catalysis
at 0.3 mol% of [Rh(COD)Cl]2 and L1 at 6.8 atm H2 for 24 h led
to 93% conversion (Table 1, entry 9). The pressure of hydrogen
clearly has a greater impact on the activity than low loading of
Rh and ligand.
We also investigated the effect of different bases on our cat-
alytic hydrogenations. Alkoxide bases (i.e., NaOtBu and
KOtBu) provided the best hydrogenation results compared to
NaN(SiMe)2, KN(SiMe)2, LiN(SiMe)2, or LiNiPr2 (see Support-
ing Information).14b, 14c, 31a, 32 We studied the effect of stoichio-
metric base to promote C-O cleavage without arene hydrogena-
tion. Hartwig, Chatani and their co-workers have demonstrated
that excess NaOtBu in NHC-Ni systems led to selective cleav-
age of C-O bonds.33 Accordingly, we performed catalysis with
MOtBu (M = Na, K) (1-2 equiv) with respect to Ph2O (Table 1,
entry 10). No conversion of Ph2O was found when using excess
MOtBu. We hypothesize that the excess base prevents for-
mation of the Rh catalyst, as homogeneity of the reaction mix-
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ACS Catalysis
ture was observed, in contrast to the appearance of black pre- Accordingly, we performed the reaction of Ph2O in water. The
1
2
3
4
5
6
7
8
cipitates when catalysis occurred. Observation of black precip-
itates during catalysis prompted the isolation of well-defined Rh
complexes to thoroughly investigate the identity of the active
Rh species for arene hydrogenation.
Speciation of Rhodium Complexes. The reaction of
[Rh(COD)Cl]2, L1, and KHMDS [KN(SiMe3)2] in THF/toluene
produced pure [(L1)Rh(COD)Cl] (1; 70%) (Scheme 2) after re-
crystallization from hexanes. Key to the easy purification of 1,
without the need for column chromatography previously re-
ported,26 is the use of excess ligand for complete consumption
of [Rh(COD)Cl]2.
major products remained Cy2O (79%) and CyOH (14%). More-
over, starting from PhOCy also yielded a similar ratio of
Cy2O:CyOH. These results and literature precedent strongly
suggest that C-O hydrogenolysis formed the CyOH in this sys-
tem.33a, 35
Kinetic studies showed that the end of the induction period
coincided with appearance of black particulate. We hypothesize
that the catalyst is a nanoparticle, in contrast to a recent report
attributing catalytic activity for arene hydrogenation of aryl car-
bonyls and phenols by 1 to homogeneous catalysis.26 Consider-
ing the controversy of homogeneous vs. heterogeneous cata-
lysts for arene hydrogenation,12c coupled with the reported ob-
servations, further studies were undertaken to understand the
nature of the active Rh species using filtration tests, controlled
poisoning experiments, and X-ray absorption fine structure
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Scheme 2. Synthesis of (L1)Rh(COD)Cl (1)
BF4
(XAFS) measurements.12b, 12c, 36
1 (3 mol%)
iPr
N
iPr
N
AgBF4 (3 mol%)
H2 (6.8 atm)
iPr
iPr
O
(3 equiv)
Cy2O + PhOCy + CyOH
KHMDS (3.1 equiv)
Rh
THF, 25 °C
[Rh(COD)Cl]2
Cl
PhMe, THF
1 without AgBF₄
-25 ºC
25 ºC, 3 h
70%
[(L1)Rh(COD)Cl] (1)
95
air- and moisture-stable
75
55
35
15
-5
To determine if 1 is an active pre-catalyst, we monitored the
time-dependence of hydrogenation of Ph2O. Conversion of
Ph2O was not observed after 24 hours (Figure 1). 1 was recov-
ered (80%) and its identity confirmed by comparison to an au-
thentic sample by 1H NMR spectroscopy. We hypothesized that
a cationic Rh species is the pre-catalyst, given the extensive lit-
erature on olefin hydrogenation with cationic Rh.1b In addition,
1 is a square-planar Rh complex that needs a vacant site for the
binding and activation of H2.
Accordingly, addition of AgBF4 (3 mol%) to 1 (3 mol%) pro-
duced Cy2O (8%) and PhOCy (27%) in 2 h, and 80% Cy2O and
20% CyOH in 6 h. The reaction profile for the conversion of
Ph2O revealed buildup of the PhOCy intermediate (22%) after
an induction period, with slower formation of Cy2O (6%) and
CyOH (3%) at 2 h (Figure 1). The concurrent onset of formation
of Cy2O and CyOH, and the higher concentration of PhOCy to
Cy2O at 2 h with respect to Cy2O, suggests the C-O cleavage to
form CyOH derives from PhOCy, or possibly from Ph2O, but
not from Cy2O. This observation was corroborated by the ab-
sence of CyOH formation when Cy2O was subjected to our hy-
drogenation conditions. The formation of cyclohexane was de-
tected by GC in these catalysis experiments, but its quantifica-
tion was not attempted because of its position near the solvent
peak.
Lastly, as the concentration of PhOCy reached its peak be-
tween the interval of 2 h and 3 h, there is a dramatic switch in
the rate of hydrogenation toward Cy2O relative to the steady
formation of CyOH. The reason for this behavior can be two-
fold: (1) PhOCy accumulates as an intermediate and (2) more
catalytically active species for arene hydrogenation are formed
over time from the slow hydrogenation of COD to COA from
complex 1. Detailed control experiments ruled out the possibil-
ity of a CAAC-Ag complex or CAAC-free cationic Rh as the
pre-catalyst (see Supporting Information).
0
1
2
3
Time (h)
4
5
6
Figure 1. Reaction profile for hydrogenation of Ph2O by 1
with AgBF4, and without AgBF4, to form Cy2O and CyOH.
Color codes in the plot are the same as the colors in the equa-
tion. No catalysis is observed without AgBF4.
Understanding the Identity of the Rh Catalyst by Filtration,
Poisoning, and XAFS Studies. To probe for soluble Rh spe-
cies, the reaction was filtered after complete consumption of 1
and Ph2O. The precipitate was removed under N2, and fresh
Ph2O was added to the filtrate. The precipitate was added to a
separate reaction vessel with fresh Ph2O and THF. The reaction
mixtures were again subjected to the same catalytic conditions.
Analysis of the reaction with the filtrate and fresh Ph2O re-
vealed no conversion of Ph2O (Scheme 3). Conversely, the re-
action with the precipitate and fresh Ph2O gave 80% conversion
of Ph2O after 8 h. These results provide evidence against soluble
catalysts for arene hydrogenation. We cannot entirely rule out
the possibility of a soluble Rh species leaching from the bulk
heterogeneous Rh, becoming active under catalytic condi-
tions.37
Significant accumulation of the PhOCy intermediate during
catalysis led us to question whether CyOH may form by reduc-
tive hydrolytic C-O cleavage due to adventitious moisture.34
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Scheme 3. Filtration experiments to probe for soluble Rh
species
similar to the hydrogenation of Ph2O to Cy2O and CyOH with-
out BT.
It might be argued that the stable interaction of Rh with BT
1
2
O
Filtrate
or DHBT, compared to that of Ph2O, leads to no conversion,
and that homogeneous catalysis is possible. If homogeneous
arene hydrogenation were operational, then Ph2O hydrogena-
tion should be observed under conditions of low concentrations
of BT or DHBT that cannot have 1 BT/DHBT : 1 Rh stoichi-
ometry. However, our results clearly indicate that arene hydro-
genation of Ph2O does not occur at low concentrations of BT,
in which the stoichiometry is 6 Rh : 1 BT.
For a direct study of the evolution of Rh, we turned to Rh K-
edge XAFS. These measurements were performed on Ph2O hy-
drogenations with 1 and AgBF4 to determine if Rh nanoparti-
cles, Rh clusters, or single-site Rh complexes are present. The
XAFS data were collected at intervals of 2 h and 6 h (Figure 2).
The transformation of the catalytic Rh species from the mixture
is compared to 1 and a Rh foil. At 2 h, 63% Ph2O was converted
to PhOCy (40%), Cy2O (14%), and CyOH (9%). At 6 h, Ph2O
was fully converted to Cy2O (80%) and CyOH (20%).
3
4
5
6
7
8
9
+ Ph2O
No conversion
H2 (6.8 atm)
8 h
3 mol% 1
Filtration
3 mol% AgBF4
H2 (6.8 atm)
THF, 25 °C, 8 h
Precipitate
+ Ph2O
Cy2O + CyOH
H2 (6.8 atm)
8 h
Cy2O + CyOH
80% conversion
100% conversion
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We turned to poisoning experiments to understand the dy-
namics of homogeneous and heterogeneous Rh species during
catalysis. Benzothiophene (BT) was used for fractional poison-
ing studies, as it offers several attractive features: (1) there are
two reactive sites, an olefin and aryl, that undergo distinctive
reactivity; (2) the sulfur atom of BT does not bind tightly to
molecular Rh, hence it should not interfere with H2 activation
for the formation of Rh NPs for arene hydrogenation; (3) sulfur-
containing heterocycles are known to poison heterogeneous hy-
drogenation catalysts,38 but are tolerated in homogeneous hy-
drogenations.39 The rationale for the fractional poisoning stud-
ies with BT is that if 1 aggregates toward the catalytically active
heterogeneous species, then the number of active Rh sites on
the surface will decrease, hence some Rh centers of larger par-
ticles must be inaccessible.12b Therefore, small amounts of BT
can poison an aggregated Rh species.
1 (3 mol%)
AgBF4 (3 mol%)
O
PhOCy + Cy2O + CyOH
H2 (6.8 atm)
THF, 25 °C
2 h: 40%
6 h: 0%
14%
80%
9%
20%
(0.5 mM)
Rh Foil
2h
6 h
(L1)Rh(COD)Cl
1.15
1.05
0.95
0.85
Scheme 4. Controlled poisoning studies with benzothio-
phene (BT)
S
0.5 - 6.0 mol%
1 (3 mol%)
AgBF4 (3 mol%)
No conversion of Ph2O
O
+
H2 (6.8 atm), 25 °C
6 h, THF
S
45-50%
30-60%
23225 23300 23375 23450 23525 23600
Dual reactive sites to probe hydrogenation
Energy (eV)
Rh Foil
6 h
2h
homogeneous
heterogeneous
(L1)Rh(COD)Cl
olefin
hydrogenation
arene
hydrogenation
6
5
4
3
2
1
0
S
iPr
iPr
N
Rh
Cl
Rh-Rh
2.6 Å
CN = 5
~ 0.8 nm
CN = 8
~ 2.0 nm
Fractional poisoning studies were performed for the reaction
of 1, AgBF4, and Ph2O at different loadings of BT (0.5, 1.5, 2.0,
3.0, 6.0 mol% with respect to 1). The results of the poisoning
studies are summarized in Scheme 4. No conversion of Ph2O
occurred at any loading of BT. As expected, BT did not interfere
with H2 activation, as evidenced by the hydrogenation of COD
and BT to cyclooctane (COA) and 2,3-dihydrobenzo[b]thio-
phene (DHBT) in 45-50% and 30-60% yields, respectively. Im-
portantly, olefin hydrogenation of COD and BT indicates ho-
mogeneous hydrogenation occurred under these conditions,
while arene hydrogenation of Ph2O or BT did not. This obser-
vation suggests that the active species for arene hydrogenation
is rapidly deactivated by BT or DHBT. Additional support for
the generation of the active species for arene hydrogenation is
that the conversion of COD to COA in the presence of BT is
0
2
4
6
R (Å)
Figure 2. Rh K-edge XAFS plot of energy vs. absorption (top);
Rh K-edge XAFS radial structure plot represents transfor-
mation of the active Rh species for Ph2O hydrogenation, com-
pared to 1 and Rh foil (bottom). The graphical scheme shows
the evolution of 1 to Rh NPs of different size as a function of
time.
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At 2 h, the Rh catalyst for arene hydrogenation is active, and
Understanding Site Selectivity of Rh-Catalyzed Arene Hy-
drogenation and Hydrogenolysis of the C-O Bond of Ethers,
Amides, and Esters. We determined the site selectivity of
arene hydrogenation with sterically and electronically unsym-
metrical aryl ethers, amides, and esters. We first examined a se-
ries of para-substituted diphenyl ethers containing an ethyl,
methoxy, or trifluoromethyl group, as well as ortho- and meta-
methoxy substituted diphenyl ethers (Table 2). All derivatives
of Ph2O showed faster hydrogenation at the unsubstituted
arenes than at the substituted arenes, with a ratio of 9-25 : 1,
regardless of the electronic properties of the substituent (OMe
or CF3) or the position of the substituents on the ring. These
results clearly indicate that steric effects dominate over elec-
tronic effects in the hydrogenation of unsymmetrical diphenyl
ethers.
1
has no resemblance to 1, as evidenced by the growing Rh-Rh
feature at ~2.6 Å that corresponds to the Rh-Rh distance in the
Rh metal foil, indicating the formation of Rh NPs (Figure 2,
bottom). The time-dependence of the change in magnitude at ~
2.6 Å indicates that the Rh NPs are growing. The size of these
Rh NPs, which can be estimated from the Rh-Rh coordination
numbers (CNs), yields approximately 0.8 nm (CN = 5) at 2 h
and 2.0 nm (CN = 8) at 6 h.40 Moreover, the disproportionately
higher amplitude of higher neighboring shells, in the range from
3.5-5.5 Å, indicates the presence of a fraction of much larger
Rh NPs. Therefore, the Rh K-edge XAFS results provide direct
evidence for the evolution of Rh NPs of different sizes from 1
under catalytic conditions, which is consistent with the increas-
ing rate of hydrogenation of Ph2O in the kinetic studies (see
above). Lastly, analysis of the radial structure plot (Figure 2,
bottom) does not support the presence of Rh4-6 clusters for arene
hydrogenation, which would contain a feature at ~2.71-2.73
Å.36a, 36c
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The selectivity for C-O hydrogenolysis of diphenyl ether de-
rivatives is similar to that of arene hydrogenation, with C-O
cleavage occurring at the less hindered arene (see Supporting
Information). Arene hydrogenation and C-O hydrogenolysis
appear to share a common preference for the interaction of Rh
with the less hindered arene.43 This preference is tentatively at-
tributed to the preferred adsorption of the less hindered arene to
Rh. Lastly, the influence of steric effects on the selectivity of
C-O hydrogenolysis of diphenyl ether derivatives of this
Rh(CAAC) catalyst is complementary to the electronic effect of
Ni(NHC)-catalyzed C-O hydrogenolysis, which favors C-O
bond cleavage at the electron-deficient arene.33a
Detection of Rh NPs in the reaction mixture by Rh K-edge
XAFS prompted further characterization of these nanoparticles
with scanning transmission electron microscopy (STEM) to de-
termine the size of the Rh NPs, and IR spectroscopy to detect
the presence of organic ligands decorating the Rh NPs. STEM
analysis of the reaction mixture for Ph2O hydrogenation with 1
and AgBF4 after 6 h showed the presence of Rh NPs of 5 nm
particle size (see Supporting Information). Additionally, the in-
soluble Rh nanoparticles were collected and washed thoroughly
with THF to remove unreacted Ph2O and hydrogenated prod-
ucts. Analysis of the isolated Rh NPs by IR spectroscopy15a, 24
showed bands characteristic of L1, suggesting that the Rh NPs
are stabilized by L1 (see Supporting Information). The for-
mation of nanoparticles stabilized by imidazolium salts from
well-defined metal complexes ligated by NHC ligands has been
reported.41 Loss of the NHC ligand from a metal center to form
nanoparticles has been proposed to occur by C-H coupling of
the NHC and hydride ligands bound to the same metal center.41a,
42 Thus, the combination of kinetic studies, filtration tests, poi-
soning experiments, XAFS measurements, and STEM charac-
terization provide conclusive evidence that the aromatic groups
of Ph2O are hydrogenated by Rh NPs derived from 1 and AgBF4
under the reaction conditions (Figure 3).
Table 2. Site-selective arene hydrogenation of usymmetrical di-
phenyl ethers
O
1 (3 mol%),
AgBF4 (3 mol%)
A
O
R
R
O
H2 (6.8 atm)
25 °C, THF, 3 h
R
B
Entry
R
% Conversionᵃ Ratio A/B (A+B%)
1
2
3
4
5
Et
63
57
86
55
60
11/1 (50%)
10/1 (52%)
25/1 (80%)
9/1 (40%)
OMe
CF3
o-Me
m-Me
8.7/1 (45%)
iPr
a Conversions and yields were determined by GC analysis with
dodecane as internal standard. The remaining mass balance is
fully hydrogenated and hydrogenolysis products.
iPr
XAFS
STEM
N
IR
+ AgBF4
Rh
Cl
iPr
N
iPr
4 BF4
iPr
iPr
N
N
iPr
iPr
iPr
iPr
N
Figure 3. Formation of Rh NPs stabilized by L1 from 1 and
AgBF4 is supported by the results of XAFS, STEM, and IR
spectroscopy
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Page 6 of 11
Table 3. Site-selective arene hydrogenation of usymmetrical di- Scheme 5. Site selectivity for Rh-catalyzed hydrogenation of
1
phenyl amides and esters
small molecules
R
R
2
3
4
5
6
7
8
9
R
Conditions: 1 (6 mol%), AgBF4 (6 mol%), H2 (6.8 - 20.5 atm), THF, 24 h, 25 ºC
Reported yield = conversion % (isolated %)
1 (3 mol%),
AgBF4 (3 mol%)
X
X
A
X
O
O
R1
O
O
Ph
Ar
H2 (6.8 atm)
25 °C, THF, 7 h
R1
O
O
O
+
N
5a
N
N
N
B
Ar
Ph
R1
MeO
MeO
2.5 : 1 (33%), 7 h
Entry
X
R
R1
H
% Conversionᵃ Ratio A/B (A+B%)
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11
12
13
14
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20
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60
Ar = C6H4OMe
12%, 7 h
99% (80%), 24 h
1
2
3
4
5
6
7
NH
H
94
99b
1.7/1.0 (52%)
B (90%)
A (44%)
A (35%)
A (42%)
B (93%)
A (48%)
NH CF3
H
O
O
MeO
MeO
MeO
OMe
NH
NH
NH
O
H
H
OMe
44
35
N
o-OMe
m-OMe
O
H
42
100b
N
O
O
CF3
H
H
Ac
N
Ac
O
OMe
48
5b
85% (60%)
5c
20% (6.8 atm H2)
25% (20.5 atm H2)
5d
94% (75%)
a Conversions and yields were determined by GC analysis with
dodecane as internal standard. The remaining mass balance is
fully hydrogenated products.b 24 h.
The insight that the arene hydrogenation is under steric con-
trol prompted us to investigate the site selectivity in small mol-
ecules with more than two reactive sites. The results for the Rh-
catalyzed arene hydrogenations of small molecules are summa-
rized in Scheme 5. In the hydrogenation of 5a, the two reactive
phenyl groups have a similar steric environment; however, the
electronic effect and flexibility are different. At 7 h, hydrogena-
tion of the benzyl group occurs faster than that of the acyl phe-
nyl group, with a ratio of 2.5 :1, at 45% conversion. This obser-
vation suggests that in addition to steric effects, flexible aryl
groups undergo faster hydrogenation between two similarly ac-
cessible arenes. At 24 h, quantitative hydrogenation of both aryl
groups has occurred, giving N-(cyclohexylmethyl)-N-(4-meth-
oxyphenyl)cyclohexane-carboxamide (80% isolated yield). For
5b, hydrogenation of the acyl phenyl is preferred over the un-
substituted phenyl, which is explained by the steric congestion
resulting from the adjacent proximity of the dimethoxy-substi-
tuted arene to the phenyl, thus rendering the acyl phenyl group
as more sterically accessible for arene hydrogenation. In 5c and
5d, arene hydrogenation occurs exclusively at the sterically ac-
cessible and unsubstituted phenyl group in the diphenyl ether
fragment, giving a single product and unreacted starting mate-
rial at 20-25% for 5c, but with good conversion (94%) and an
isolated yield of 75% for 5d. The identity of all hydrogenated
products has been confirmed by independent synthesis (see
Supporting Information).
To study the site-selective arene hydrogenation of esters and
amides, we first examined N-phenylbenzamide, because the
two aryl groups have a similar steric environments, yet their
electronic properties differ because of the amide linkage (Table
3, entry 1). Hydrogenation of N-phenylbenzamide formed N-
phenylcyclohexanecarboxamide and N-cyclohexylbenzamide
in a ratio of 1.7 : 1.0, for a combined yield of 52% at 94% con-
version. The remaining mass balance is the fully hydrogenated
product, N-cyclohexyl-cyclohexanecarboxamide, and unre-
acted starting material (Table 3, entry 12). In the hydrogenation
of N-phenylbenzamide, despite having equally accessible
arenes for hydrogenation, we observed faster hydrogenation at
the electron-poor arene adjacent to the carbonyl relative to the
electron-rich arene bonded to the nitrogen.
We also investigated the effects of para-, ortho-, and -meta
substitution for amides and esters, to compare to the diphenyl
ether derivatives (Table 3, entries 2-7). As found for the diphe-
nyl ether derivatives, unsubstituted arenes undergo faster hy-
drogenation than the substituted arenes for all amides and esters
in our studies. These combined results for diphenyl ethers, am-
ides, and esters reinforce the conclusion of the dominant steric
effect on arene hydrogenation, in which less hindered arenes are
hydrogenated faster than more hindered arenes.
Conclusions
Metal nanoparticles have been prepared from a small library
of carbene ligands in combination with [Rh(COD)Cl]2 for arene
hydrogenation at low H2 pressure and room temperature. We
have identified Rh-CAAC nanoparticles to be the active species
for arene hydrogenation under our experimental conditions.
This conclusion is supported by the induction period by kinetic
studies, mechanistic studies involving a filtration test, fractional
poisoning experiments, XAFS measurements, STEM character-
ization, and infrared spectroscopy. From site-selective studies
for the arene hydrogenation of ethers, amides, and esters with
different electronic and steric effects, we conclude that the site
selectivity for arene hydrogenation in this system markedly de-
pends on steric factors. We speculate that the high activity is
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ACS Catalysis
3070; (c) Knowles, W. S., Asymmetric Hydrogenations.
related to the presence of CAAC on the surface of the catalyti-
1
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cally active particles. Ongoing characterization of such cata-
lysts under operating conditions is expected to lead to new gen-
erations of catalysts at the interface between homogeneous and
heterogeneous catalysis.
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ASSOCIATED CONTENT
Supporting Information
Additional experimental data, synthetic procedures, characteriza-
tion of compounds, and spectroscopic data are included in the Sup-
porting Information. The Supporting Information is available free
of charge on the ACS Publications website.
3.
(a) Clapham, S. E.; Hadzovic, A.; Morris, R. H.,
9
Mechanisms of the H₂- and Transfer Hydrogenation of Polar
Bonds Catalyzed by Iron Group Hydrides. Coord. Chem. Rev.
2004, 248, 2201-2237; (b) Conley, B. L.; Pennington-Boggio,
M. K.; Boz, E.; Williams, T. J., Discovery, Applications, and
Catalytic Mechanisms of Shvo’s Catalyst. Chem. Rev. 2010,
110, 2294-2312; (c) Casey, C. P.; Guan, H., Efficient and
Chemoselective Iron Catalyst for Hydrogenation of Ketones.
J. Am. Chem. Soc. 2007, 129, 5816-5817.
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AUTHOR INFORMATION
Corresponding Author
morris.bullock@pnnl.gov
Author Contributions
All authors have given approval to the final version of the manu-
script.
4.
(a) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein,
D., Efficient Homogeneous Catalytic Hydrogenation of Esters
to Alcohols. Angew. Chem. Int. Ed. 2006, 45, 1113-1133; (b)
Saudan, L. A.; Saudan, C. M.; Debieux, C.; Wyss, P.,
Dihydrogen Reduction of Carboxylic Esters to Alcohols under
the Catalysis of Homogeneous Ruthenium Complexes: High
Efficiency and Unprecedented Chemoselectivity. Angew.
Chem. Int. Ed. 2007, 46, 7473-7476; (c) Kuriyama, W.;
Matsumoto, T.; Ogata, O.; Ino, Y.; Aoki, K.; Tanaka, S.;
Ishida, K.; Kobayashi, T.; Sayo, N.; Saito, T., Catalytic
Hydrogenation of Esters. Development of an Efficient Catalyst
and Processes for Synthesising (R)-1,2-Propanediol and 2-(L-
Menthoxy)Ethanol. Org. Process Res. Dev. 2012, 16, 166-
171; (d) Spasyuk, D.; Smith, S.; Gusev, D. G., From Esters to
Alcohols and Back with Ruthenium and Osmium Catalysts.
Angew. Chem. Int. Ed. 2012, 51, 2772-2775; (e) Spasyuk, D.;
Smith, S.; Gusev, D. G., Replacing Phosphorus with Sulfur for
the Efficient Hydrogenation of Esters. Angew. Chem. Int. Ed.
2013, 52, 2538-2542; (f) Chakraborty, S.; Dai, H.;
Funding Sources
We thank the U.S. Department of Energy, Office of Science, Office
of Basic Energy Sciences, Division of Chemical Sciences, Geosci-
ences and Biosciences for support. Pacific Northwest National La-
boratory is operated by Battelle for the U.S. Department of Energy.
This research used resources of the Advanced Photon Source, an
Office of Science User Facility operated for the U.S. Department
of Energy (DOE) Office of Science by Argonne National Labora-
tory, and was supported by the U.S. DOE under Contract No. DE-
AC02-06CH11357, and the Canadian Light Source and its funding
partners.
Notes
The authors declare no competing financial interest.
Bhattacharya, P.; Fairweather, N. T.; Gibson, M. S.; Krause, J.
A.; Guan, H., Iron-Based Catalysts for the Hydrogenation of
Esters to Alcohols. J. Am. Chem. Soc. 2014, 136, 7869-7872;
(g) Werkmeister, S.; Junge, K.; Wendt, B.; Alberico, E.; Jiao,
H.; Baumann, W.; Junge, H.; Gallou, F.; Beller, M.,
Hydrogenation of Esters to Alcohols with Well-Defined Iron
Complex. Angew. Chem. Int. Ed. 2014, 53, 8722-88726; (h)
Stein, T. v.; Meuresch, M.; Limper, D.; Schmitz, M.;
Hölscher, M.; Coetzee, J.; Cole-Hamilton, D. J.;
ACKNOWLEDGMENT
We thank Meng Wang for the sample preparation for the XAFS
measurements, Dr. Rosalie K. Chu for collection of the mass spec-
trometry data, and Dr. Libor Kovarik for the STEM characteriza-
tion.
Klankermayer, J.; Leitner, W., Highly Versatile Catalytic
Hydrogenation of Carboxylic and Carbonic Acid Derivatives
Using a Ru-Triphos Complex: Molecular Control over
Selectivity and Substrate Scope. J. Am. Chem. Soc. 2014, 136,
13217-13225.
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Graphic for Table of Contents
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X = O, NHC(O), OC(O)
Rh K-edge XAFS
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iPr
iPr
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AgBF4, H2, 25°C
Rh
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Energy
R
Sterically controlled arene hydrogenation
of ethers, amides, and esters
S
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