Chelating Bis(1,2,3-triazol-5-ylidene) Rhodium Complexes: Versatile Catalysts for Hydrosilylation Reactions

Article abstract of DOI:10.1002/adsc.201500875

NHC-rhodium complexes (NHC=N-heterocyclic carbenes) have been widely used as efficient catalysts for hydrosilylation reactions. However, the substrates were mostly limited to reactive carbonyl compounds (aldehydes and ketones) or carbon-carbon multiple bonds. Here, we describe the application of newly-developed chelating bis(tzNHC)-rhodium complexes (tz=1,2,3-triazol-5-ylidene) for several reductive transformations. With these catalysts, the formal reductive methylation of amines using carbon dioxide, the hydrosilylation of amides and carboxylic acids, and the reductive alkylation of amines using carboxylic acids have been achieved under mild reaction conditions.

Full text of DOI:10.1002/adsc.201500875

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DOI: 10.1002/adsc.201500875
Chelating Bis(1,2,3-triazol-5-ylidene) Rhodium Complexes:
Versatile Catalysts for Hydrosilylation Reactions
Thanh V. Q. Nguyen,a Woo-Jin Yoo,a and Shu¯ Kobayashia,*
a
Department of Chemistry, School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan
Fax: (+81)-3-5684-0634; phone: (+81)-3-5841-4790; e-mail: shu_kobayashi@chem.s.u-tokyo.ac.jp
Received: September 20, 2015; Revised: November 1, 2015; Published online: January 18, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500875.
Abstract: NHC-rhodium complexes (NHC=N- these catalysts, the formal reductive methylation of
heterocyclic carbenes) have been widely used as effi- amines using carbon dioxide, the hydrosilylation of
cient catalysts for hydrosilylation reactions. Howev- amides and carboxylic acids, and the reductive alky-
er, the substrates were mostly limited to reactive car- lation of amines using carboxylic acids have been
bonyl compounds (aldehydes and ketones) or achieved under mild reaction conditions.
carbon-carbon multiple bonds. Here, we describe the
application
of
newly-developed
chelating
bis(tzNHC)-rhodium complexes (tz=1,2,3-triazol-5- Keywords: carbene ligands; homogeneous catalysis;
ylidene) for several reductive transformations. With hydrosilylation; rhodium
Introduction
Since the common intermediates in metal-catalyzed
hydrosilylation reactions are believed to be the metal-
Over the last two decades, N-heterocyclic carbenes hydride species,[7] we hypothesized that the use of
(NHCs) have undergone rapid development into one strong electron-donating ligands would increase the
of the most popular classes of ligands for transition nucleophilicity of the metal-hydride intermediates
metal catalysis.[1] Metal complexes bearing NHC li- and facilitate the hydride transfer from the catalytic
gands are often quite stable and electron-rich, which intermediates to the substrates. With this in mind, we
enables them to be useful catalysts. In this context, have studied bis(imNHC) rhodium complexes 1 and
the combination of rhodium and NHCs can provide 2, and designed new bis(tzNHC) rhodium complexes
efficient catalysts and these have been extensively 3a–f (im=imidazole-2-ylidene, tz=1,2,3-triazol-5-yli-
studied for various organic transformations.[1,2] Since dene, Figure 1).[8] The use of tzNHC, as an exception-
the early report by Herrmann and co-workers,[3] the ally strong electron-donating ligand,[9] promoted the
hydrosilylation reaction has become one of the bench-
mark reactions for investigating the catalytic ability of
new NHC-rhodium complexes. The use of hydrosi-
lanes is attractive since they are stable and easy-to-
handle alternatives to traditional reductants, such as
hydrogen gas, boranes, and aluminum hydrides. Nev-
ertheless, the target substrates for NHC-rhodium cat-
alyzed hydrosilylation reactions were generally limit-
ed to reactive carbonyl compounds (such as alde-
hydes, ketones) and carbon-carbon multiple
bonds.[1,2a] In contrast, the reduction of more challeng-
ing, yet synthetically useful substrates, such as carbox-
ylic acid derivatives,[4] remained almost unexplored.[5]
This is in sharp contrast to several promising reports
on the use of phosphine-based rhodium catalysts for
the reduction of carboxylic acid derivatives.[6]
Figure 1. Bis(NHC) rhodium complexes studied in this
work.
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Chelating Bis(1,2,3-triazol-5-ylidene) Rhodium Complexes
Table 1. Reductive methylation of amines using CO2 and
unique catalytic activity of 3 towards the reductive
formylation of amines using CO2 and Ph2SiH2. The
substrate scope of this transformation was broad and
a variety of reducible functional groups could be tol-
erated. We believed that the excellent selectivity en-
joyed by our catalytic system was due to the use of
a high pressure of CO2 and in the absence of CO2, we
anticipated that our catalyst system could be useful
for the reduction of carbonyl compounds. Based on
several control experiments, we found that the inter-
action of 3c with Ph2SiH2 led to the formation of rho-
dium-silylene intermediates, which have been pro-
posed in the Hofmann–Gade-type mechanism.[7a,10]
Thus, carbonyl compounds could be activated via sili-
con–oxygen interaction, and the reduction could be
accelerated.
Ph2SiH2.[a]
Although such a mode of activation was suggested
for the hydrosilylation of ketones and CO2, we be-
lieved that such an interaction could also be applica-
ble for the reduction of carboxylic acids and their de-
rivatives. Herein, we describe our studies towards the
catalytic ability of our previously reported chelating
rhodium complexes 3 for several related hydrosilyla-
tion processes.
Results and Discussion
[a]
Reaction conditions: amines 4a–g (0.5 mmol), 3c (2.5
mmol), Ph2SiH2 (2.25 mmol), DCM (2 mL).
Yields of the isolated products 5a–g were based on 4a–g.
Reductive Methylation of Amines using CO2
[b]
At the outset of our investigation, we decided to
expand upon our previously reported reductive for-
mylation reactions of CO2.[8] Under the assumption Hydrosilylation of Amides
that these rhodium catalysts could facilitate the reduc-
tion of the resulting formamides in the absence of After confirming the ability of complex 3c to catalyze
CO2, the reductive methylation of amines was exam- the hydrosilylation of formamides, we began to inves-
ined. Following the complete formylation of dibenzyl- tigate the possibility of applying NHC-rhodium com-
amine (4a) after 4 h, the removal of CO2 and further plexes 3 for the general reduction of other amides. In
addition of 2 equivalents of Ph2SiH2 provided the de- the model reaction, the hydrosilylation of N,N-dime-
sired methylated amine 5a in 80% yield after 20 h at thylbenzamide (6a) to N,N-dimethylbenzylamine (7a)
258C under air, without the addition of more catalyst was studied using catalyst 3a. After extensive optimi-
(Table 1, entry 1). This result indicated the robustness zation,[12] the reaction was found to proceed efficient-
of NHC-rhodium complex 3c. Overall, the reaction ly in neat conditions at 308C using PhSiH3 as the re-
conditions were milder and the amount of Ph2SiH2 ductant with 0.25 mol% catalyst loading (Table 2,
was comparable to other reported catalyst systems of entry 1). We also found that only PhSiH3 and Ph2SiH2
this type.[11]
accelerated the reduction, while other monohydrosi-
Next, other amine substrates were investigated. In lanes were completely ineffective. Modifying the
general, the reactions proceeded smoothly for secon- NHC backbone to imNHC led to lower yields of 7a
dary amines (entries 2 and 3) and tolerated several re- (entries 2 and 3), while changing the counter anions
ducible functional groups such as amide (4d), ester to SbF6 (3b) or OTf (3c) improved the results (en-
(4e) and nitro (4f) (entries 4–6). The Boc-protected tries 4–7).[12] Finally, 3b was determined to be the best
piperazine 4g could also be methylated in a good catalyst.
yield without affecting the protecting group (entry 7).
This catalyst system was proven to be quite general
and effectively reduced various tertiary amides in
good yields (Table 3). Benzamides with different N-
substituents (6b–d) could be reduced smoothly to
their corresponding amines 7b–d in excellent yields
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Thanh V. Q. Nguyen et al.
Table 2. Optimization of the hydrosilylation of N,N-dime-
Table 3. Substrate scope for amide hydrosilylation.[a]
thylbenzamide (6a).[a]
Entry
Catalyst
Yield [%][b]
1
2
3
4
5
6
7
3a
1
2
3b
3c
3e
3f
75
42
36
94 (90)[c]
88
79
80
[a]
Reaction conditions: amide 6a (0.5 mmol), catalyst
(1.25 mmol), PhSiH3 (0.8 mmol).
Yields were determined by H NMR analysis using 1,3,5-
trimethoxybenzene as the internal standard.
Isolated yield in parenthesis.
[b]
[c]
1
(entries 1–3). It was found that various 4-substituted
aromatic amides (6e–g) could be utilized and reduci-
ble functional groups such as nitro (6h) or ester (6i)
were tolerated (entries 4–8). Amides containing het-
erocycles such as furan (6j) and thiophene (6k) were
also found to be good substrates (entries 9–10). Final-
ly, the amides derived from aliphatic carboxylic acids
(6l and m) or lactam (6n) were successfully reduced
using the NHC-rhodium/silane catalyst system (en-
tries 11–13).
On the other hand, the reduction of secondary
amides was found to be more challenging. When acet-
anilide (6o) was subjected to identical conditions as
for the hydrosilyation of tertiary amides, a stirring
problem partially prevented the reaction to proceed.
In order to overcome this problem, THF was added
as a solvent and the desired amine 7o was obtained in
a good yield after increasing the catalyst loading and
temperature (entry 14). Under similar conditions,
other acetanilide derivatives (6p–r) and secondary
amides (6s–u) could be effectively reduced to the cor-
responding amines 7p–u in moderate to excellent
yields (entries 15–20). Thus, rhodium complex 3b was
shown to effectively catalyze the hydrosilylation of
secondary amides.[13] Remarkably, it was found to be
a superior catalyst than previously reported rhodium
catalysts[6] and other NHC-metal catalysts[14] in terms
of catalyst loading, temperature, and substrate scope.
[a]
Reaction conditions: amides 6b–u (0.5 mmol), 3b
(1.25 mmol), PhSiH3 (0.8 mmol).
Yields of isolated products 7b–u were based on 6b–u.
1 mol% 3b.
PhSiH3 (2 mmol), THF (0.5 mL), 508C, quenched with
aqueous NaOH (15 wt%), 1 h.
[b]
[c]
[d]
[e]
1.5 mol% 3b.
Hydrosilylation of Carboxylic Acids
occurred smoothly in the presence of only 0.25 mol%
of 3a in THF at 308C (entry 1). Examination of the
Next, we examined the catalytic hydrosilylation of NHC backbone revealed a small difference in the re-
carboxylic acids to alcohols (Table 4). The model re- activity between tzNHC and imNHC ligands (en-
action of 4-bromophenylacetic acid (8a) with PhSiH3 tries 3 and 4). In addition, it was found that the re-
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Chelating Bis(1,2,3-triazol-5-ylidene) Rhodium Complexes
Table 4. Optimization of the hydrosilylation of 4-bromophe-
nylacetic acid (8a).[a]
Table 5. Substrate scope for amide hydrosilylation.[a]
Entry
Catalyst
Yield [%][b]
1
3a
3a
1
80
59
72
2[c]
3
4
2
61
5
6
7
8
3b
3c
3d
3e
3f
3c
3c
74
85
81
84
9
80
10[d]
11[d,e]
>95
94 (88)[f]
[a]
Reaction conditions: 8a (0.5 mmol), catalyst (1.25 mmol),
PhSiH3 (2.0 mmol), THF (0.5 mL).
Yields were determined by H NMR using 1,2,4,5-tetra-
[b]
1
methylbenzene as the internal standard.
0.1 mol% 3a.
0.5 mol% 3c.
3 equiv. of PhSiH3.
[c]
[d]
[e]
[f]
Isolated yield in parenthesis.
sults were not changed significantly upon varying the
counteranions (entries 5–9). Finally, 3c was chosen as
the best catalyst, and increasing the catalyst loading
to 0.5 mol% led to quantitative conversion of benzylic
acid 8a (entry 10). Moreover, the amount of the
silane could be reduced to 3 equivalents without sacri-
ficing the product yield (entry 11). Notably, under the
optimized reaction conditions, the desired alcohol 9a
could be selectively generated and only a trace
[a]
Reaction conditions: acids 8b–p (0.5 mmol), 3c
(2.5 mmol), PhSiH3 (1.5 mmol), THF (0.5 mL).
Yields of isolated products 9b–p were based on 8b–p.
1 mol% 3c.
22% of diol was also isolated.
The reaction was quenched with HCl (1N).
[b]
[c]
[d]
[e]
amount of the aldehyde could be observed in the reported ruthenium-based catalyst, with slightly lower
crude mixture.
catalyst loading and reaction temperature.[16]
Next, the substrate scope for the carboxylic acid re-
duction was examined using bis(tzNHC) rhodium 3c
as a catalyst (Table 5). It was found that various ali- Reductive Alkylation of Amines using Carboxylic
phatic carboxylic acids (8b–f) could be reduced to the Acids
corresponding alcohols 9b–f in modest to excellent
yields (entries 1–5). Notably, carboxylic acids bearing Since chelating bis(tzNHC) rhodium complexes 3
ketone (8g), phenol (8h) or alkene (8i) moieties could were found to be highly effective catalysts for hydro-
be tolerated to some extent to provide the corre- silylations of amides and carboxylic acids, we antici-
sponding alcohols 9g–i in modest yields (entries 6–8). pated that these catalysts could be utilized for the re-
Furthermore, benzoic acid derivatives bearing elec- ductive alkylation of amines with carboxylic acids,
tron-donating and electron-withdrawing substituents which was recently reported using platinum and
(8j–p) could be reduced to the desired benzyl alcohols boron catalysts.[17] After optimization of the reaction
9j–p in moderate to excellent yields (entries 9–15). It conditions,[12] it was found that the reaction between
is noteworthy that the over-reduced toluene deriva- acetic acid (8q) and p-toluidine (4h) occurred smooth-
tives, which were found to be problematic in a previ- ly to afford monoalkylated amine 10a in a high yield
ous report,[15] were not detected under our optimized under mild conditions (Table 6, entry 1). Although
conditions. In general, the efficiency of our catalyst aniline derivatives 4i and 4j were suitable substrates
system was comparable to that of the most recently (entries 2 and 3), the use of aliphatic amines led to
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Thanh V. Q. Nguyen et al.
Table 6. Substrate scope for amide hydrosilylation.[a]
expanded the broad application of rhodium catalysts
in hydrosilylation and related reductive reactions, as
well as the use of abnormal tzNHCs as effective li-
gands for transition metal complexes.
Experimental Section
General Information
1H and 13C NMR spectra were recorded on a JEOL ECX-
400, JEOL ECX-500 and a JEOL ECX-600 in CDCl3.
Chemical shifts of 1H and 13C were reported in parts per
million (ppm) from tetramethylsilane using the solvent reso-
nance as the internal standard (CDCl3: 7.26 ppm for
1H NMR and CDCl3: 77.0 ppm for 13C NMR). IR spectra
were measured on a JASCO FT/IR-610 spectrometer. High-
resolution mass spectrometry was carried out using a JEOL
JMS-T100TD (ESI and DART). Column chromatography
was carried out using silica gel obtained from Wako Pure
Chemical Industries, Ltd (neutral type) or Merck & Co.
(normal type).
Reagents
Unless stated otherwise, commercial organic chemicals were
purchase from Tokyo Chemical Industry Co. Ltd or Sigma
Aldrich and purified by distillation or recrystallization
before use. All organic solvents were purified by distillation
under dry argon atmospheres or purchased as anhydrous
solvents from Wako Pure Chemical Industries, Ltd. Amides
6b–l and 6t were prepared from the corresponding amines
and acid chlorides in DCM in the presence of Et3N.[13f] Rho-
dium complexes 1, 2 and 3a–f were synthesized following re-
ported procedures.[8]
[a]
Reaction conditions: acids (0.88 mmol), amines
(0.5 mmol), 3c (1.25 mmol), PhSiH3 (4 mmol), THF
(0.5 mL), quenched with aqueous NaOH (15 wt%), 1 h.
Yields of isolated products 10a–e and 6r were based on
the amine substrates.
0.5 mol% 3c.
1.5 mol% 3c.
Acid (2 equiv.), PhSiH3 (6 equiv.), 508C.
[b]
[c]
[d]
General Procedure for the Reductive Methylation of
Amines using CO2 (GP1)
[e]
To a 50-mL stainless steel reaction vessel was added 3c
(1.8 mg, 2.5 mmol), DCM (2 mL) and amines 4a–g
(0.5 mmol). The mixture was stirred under CO2 (25 atm) for
15 min, then Ph2SiH2 (0.23 g, 1.25 mmol) was added. The re-
action was carried out under CO2 (25 atm) for 4 h, upon
which TLC showed full conversion of the amine starting ma-
terial. Then, Ph2SiH2 (0.18 g, 1.0 mmol) was added and the
reaction mixture was stirred under air for 20 h. Next, the re-
action mixture was diluted to Et2O (10 mL) and acidified
with 1N HCl (15 mL). The aqueous phase was collected,
washed with Et2O (2”10 mL) and basified with NaOH solu-
tion (15 wt%) until the pH was greater than 10. Extraction
to DCM (3”10 mL), followed by drying over Na2SO4 and
removal of solvent under reduced pressure afforded the de-
sired products 5a–g. If necessary, the product was further
purified using preparative TLC (MeOH:DCM 5:95).
disappointingly poor results, even at higher catalyst
loading and temperature. When different carboxylic
acids were examined, it was found that higher catalyst
loadings were necessary to achieve good results (en-
tries 4–6).
Conclusions
In summary, we have demonstrated that the newly de-
veloped chelating bis(tzNHC) rhodium complexes 3
were versatile catalysts for several hydrosilylation re-
actions, such as the methylation of amines using CO2,
the reduction of amides and carboxylic acids, and the
reductive alkylation of amines using carboxylic acids.
Comparisons between the catalysts have been made
for each transformation, and in general, the rhodium
complexes bearing stronger electron-donating tzNHC
ligands were found to be more effective than rhodium
General Procedure for the Reduction of Tertiary
Amides (GP2)
In an argon-filled glove-box, a 5-mL microwave test tube
was charged with 3b (0.95 mg, 1.25 mmol), amides 6a–n
complexes ligated with imNHCs. These findings have (0.5 mmol), and PhSiH3 (0.086 g, 0.8 mmol). The tube was
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Chelating Bis(1,2,3-triazol-5-ylidene) Rhodium Complexes
sealed with a septum, brought out of the glove-box, placed
in a pre-heated oil bath at 308C and stirred for 20 h. Next,
the reaction mixture was diluted with Et2O (10 mL) and
acidified with 1N HCl (15 mL). The aqueous phase was col-
lected, washed with Et2O (2”10 mL) and basified with
NaOH solution (15 wt%) until the pH was greater than 10.
Extraction to DCM (3”10 mL), followed by drying over
Na2SO4 and removal of solvent under reduced pressure af-
forded the desired products 7a–n.
vation through Cooperation of Science and Engineering), the
University of Tokyo, the Japan Science and Technology
Agency (JST), and the Ministry of Education, Culture,
Sports, Science and Technology (MEXT, Japan).
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To a 10-mL tube were added 3b (3.6 mg, 5 mmol), amides
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General Procedure for the Reduction of Carboxylic
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To a 10-mL tube was added 3c (1.8 mg, 2.5 mmol), acids 8a–
p (0.5 mmol), THF (0.5 mL), and PhSiH3 (0.16 g, 1.5 mmol).
An argon balloon was attached and the reaction mixture
was stirred at 308C for 20 h. After the mixture had cooled
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(15 wt%, 1 mL) and stirred for 1 h. Then, the mixture was
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To a 10-mL tube were added 3c (0.9 mg, 1.25 mmol), amine
(4h–j) (0.5 mmol), THF (0.5 mL), acid (8f, 8j, 8q, 8r)
(0.88 mmol), and PhSiH3 (0.216 g, 2.0 mmol). An argon bal-
loon was attached and the reaction mixture was stirred at
308C for 20 h. After the reaction mixture had cooled to
room temperature, it was carefully quenched with NaOH 15
(wt%, 1 mL) and stirred for 1 h. Then, the mixture was di-
luted with water (10 mL) and extracted to DCM (3”
10 mL). The combined organic solution was dried over
Na2SO4 and the solvent was removed under reduced pres-
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Acknowledgements
This work was partially supported by a Grant-in-Aid for Sci-
ence Research from the Japan Society for the Promotion of
Science (JSPS), the Global COE Program (Chemistry Inno-
Adv. Synth. Catal. 2016, 358, 452 – 458
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