Asymmetric hydrogenation of thiophenes and benzothiophenes

Article abstract of DOI:10.1021/ja306622y

An efficient and highly asymmetric ruthenium-N-heterocyclic carbene-catalyzed hydrogenation of substituted thiophenes and benzothiophenes is described, providing a new strategy for the formation of valuable enantiomerically pure tetrahydrothiophenes and 2,3-dihydrobenzothiophenes.

Full text of DOI:10.1021/ja306622y

Communication
pubs.acs.org/JACS
Asymmetric Hydrogenation of Thiophenes and Benzothiophenes
Slawomir Urban,† Bernhard Beiring,† Nuria Ortega, Daniel Paul, and Frank Glorius*
Organisch-Chemisches Institut, Westfalische Wilhelms-Universitat Munster, Corrensstrasse 40, 48149 Munster, Germany
̈
̈
̈
̈
S
* Supporting Information
approaches developed to obtain these important compounds,
the formation of structurally diverse and enantiopure
derivatives is particularly challenging. Unlike for many other
chiral heterocyclic compounds, the asymmetric hydrogenation
of the corresponding aromatic organosulfur compounds was,
despite its attractiveness and due to the difficulties described
above, so far not entertained as a possible synthetic pathway.11a
Thus, the development of sulfur tolerant, highly reactive, and
enantioselective catalyst systems would allow the use of readily
available substituted aromatic organosulfur compounds as
starting materials for the synthesis of valuable optically active
dihydro- and tetrahydrothiophenes.
During the course of our investigation into the asymmetric
hydrogenation of arenes, we found that the combination of
ruthenium(II) and several monodentate NHCs (NHC = N-
heterocyclic carbene)12 led to the formation of selective
hydrogenation catalysts for quinoxalines7b and benzofurans6f,g
with very high levels of regio- and enantioselectivity. Herein we
report the asymmetric homogeneous hydrogenation of
substituted thiophenes and benzothiophenes using a Ru-NHC
complex. The use of a chiral NHC-ligand enables a new route
to biologically active dihydrobenzothiophenes and tetrahydro-
thiophenes of very high optical purity; both high levels of
reactivity and selectivity are remarkable.
The requirements for a suitable homogeneous catalyst for the
successful hydrogenation of substituted benzothiophenes and/
or thiophenes seem to differ dramatically from the ones
required for the hydrogenation of the corresponding
unsubstituted compounds.9 Indeed, none of the reported
reactive benzothiophene hydrogenation catalysts showed
reactivity toward substituted derivatives. Possible reasons for
this are that substituents at C(2) or C(3) reduce the π-acceptor
character of the olefin and also sterically hinder the η2-(C,C)-
coordination mode. In addition, electron-donating alkyl groups
enhance the donor ability of the sulfur atom, thereby favoring
S-coordination.13 Usually organosulfur hydrogenation catalysts
consist of phosphine, nitrogen, or Cp/Cp* type ligands. We
assumed that carbene ligands, due to their strong ability to
donate electron density to the metal center,12f might favor η2-
(C,C)-substrate−metal interactions through attractive π-back-
donation. The electron-rich metal should thereby show only
weak S-coordination. Furthermore, Ru(II)-complexes are
expected to show rather low thiophilicity, which is an important
requirement. This and the high reactivity of the previously
developed Ru-NHC catalyst system in the reduction of
heteroarenes6f,g,7b led us to test it in the hydrogenation of
substituted aromatic organosulfur compounds. In our initial test
ABSTRACT: An efficient and highly asymmetric ruthe-
nium-N-heterocyclic carbene-catalyzed hydrogenation of
substituted thiophenes and benzothiophenes is described,
providing a new strategy for the formation of valuable
enantiomerically pure tetrahydrothiophenes and 2,3-
dihydrobenzothiophenes.
he hydrogenation of (hetero)arenes provides a clean and
T
straightforward method to obtain the corresponding
saturated (hetero)cycles.1 Recently, a lot of progress has been
made in the asymmetric hydrogenation of (hetero)arenes, such
as quinolines,2 isoquinolines,3 quinoxalines,4 indoles,5 pyrro-
les,5j,k (benzo)furans,6 and naphthalenes.7a However, despite
great effort in this field in recent years, many challenges remain
and sulfur-containing arenes are particularly difficult substrates.
Extensive studies on the hydrogenation of unsubstituted
thiophene and benzothiophene have been executed by many
research groups in the past,8 due to its importance in the
hydrodesulfurization process (HDS). This effort led to the
identification of several catalysts for the catalytic hydrogenation
of unsubstituted benzothiophene, providing insight into
possible binding modes and kinetics.10 Thiophene, however,
is still a challenge for homogeneous catalysts, probably due to
its aromaticity and the strong coordination and poisoning
ability of the reduced tetrahydrothiophene.10d,f Thus, only one
example of catalytic thiophene hydrogenation has been
reported, by the groups of Borowski and Sabo-Etienne in
2003.10d However, the hydrogenation becomes even more
challenging for substituted thiophenes and benzothiophenes
(Scheme 1).8,9
(Optically active) dihydro- and tetrahydrothiophene deriva-
tives play an important role in organic, biological, and medicinal
chemistry and are widely distributed.11 Besides many
Scheme 1. Reactivity of Homogeneous Metal Complexes
toward Substituted Thiophene Derivatives under H2
Atmosphere
Received: July 6, 2012
Published: August 31, 2012
© 2012 American Chemical Society
15241
dx.doi.org/10.1021/ja306622y | J. Am. Chem. Soc. 2012, 134, 15241−15244

Journal of the American Chemical Society
Communication
reactions we investigated the performance of the catalyst
toward the hydrogenation of unsubstituted benzothiophene
(1a) and thiophene (3a). Gratifyingly, using 1 mol % of catalyst
prepared in situ from [Ru(cod)(2-methylallyl)2] and
SINpEt·HBF4 (5), both substrates could be quantitatively
reduced, even at room temperature (Tables 1 and 2).14 No side
reactions such as metal insertion into C−S bonds, hydro-
genolysis, or hydrodesulfurization were observed.
Table 2. Scope of the Asymmetric Hydrogenation of
Thiophenes
a
Table 1. Scope of the Asymmetric Hydrogenation of
a
Benzothiophenes
a
General conditions: [Ru(cod)(2-methylallyl)2] (0.015 mmol), KOt-
Bu (0.045 mmol), and 5 (0.032 mmol) were stirred at 70 °C in hexane
(1 mL) for 16 h, after which the mixture was added to thiophene (0.15
mmol), and hydrogenation was performed at shown conditions for 24
1
h. The yield was determined by GC or H NMR using CH2Br2 as an
internal standard. E.r. (given in brackets) was determined by HPLC on
b
a chiral stationary phase. Reaction time was 40 h; 70 bar H2 were
c
used. Signals of enantiomeres are not baseline separated in the HPLC
traces.
a
General conditions: [Ru(cod)(2-methylallyl)2] (0.015 mmol), KOt-
Bu (0.045 mmol), and 5 (0.032 mmol) were stirred at 70 °C in hexane
(1 mL) for 16 h, after which the mixture was added to benzothiophene
(0.30 mmol) and hydrogenation was performed at shown conditions
for 24 h. The yield was determined by GC or 1H NMR using CH2Br2
as internal standard. E.r. (given in brackets) was determined by HPLC
on a chiral stationary phase.
2-benzylbenzothiophene (1h) as substrates, but the high e.r.’s
were maintained. Unfortunately, no conversion of arylated
substrates was observed yet. Since the sign of the optical
rotation values for all the 2-substituted benzothiophenes
obtained in this study is the same (+), we assume that the
obtained stereochemistry should be similar to the one obtained
for (R)-2-methyl-2,3-dihydrobenzothiophene (2b) (see above).
Due to the unique performance of this complex in the
hydrogenation of various substituted benzothiophenes, we
wondered if the less reactive mono- and disubstituted
thiophenes could undergo hydrogenation. Using our standard
conditions, 2-alkylated and 2-arylated thiophenes such as 2-
ethylthiophene (3b) and 2-(4-fluorophenyl)thiophene (3d),
but also 3-methylthiophene (3c), could be reduced quantita-
tively (Table 2). Surprisingly, all of these monosubstituted
products were obtained in racemic form only.
Remarkably, even when disubstituted thiophenes were
tested, which have never been successfully applied in
homogeneous hydrogenation reactions before, the catalyst
still showed reactivity toward hydrogenation. Even though
lower yields were obtained for the phenyl substituted substrate
3e, moderate to excellent yields were obtained for thiophenes
bearing electron-withdrawing substituents (3f−h). Intriguingly,
in all cases, high enantio- (>95:5) and perfect diastereose-
lectivity (only cis-products) were obtained. Different re-
gioisomers such as 3,4-disubstituted thiophene 3i could also
be reduced with the same catalyst system under the standard
conditions, although the reaction proceeded with significantly
lower enantioselectivity (63:37 e.r.). Before this work, 2-
methylthiophene had been the only substituted (benzo)-
thiophene that was successfully hydrogenated (in only 11%)
To find out if our catalyst system might also be applicable for
substituted substrates, the hydrogenation of 2-methylbenzo-
thiophene (1b) as a model substrate was investigated.
Surprisingly, mild reaction conditions such as 10 bar of
hydrogen at room temperature were sufficient to obtain 83% of
the 2,3-dihydrobenzothiophene 2b in 18 h, without any
formation of side products. Remarkably, the product was
obtained in an enantiomeric ratio (e.r.) of 99:1. The conversion
could even be improved to 98% when the hydrogen pressure
was raised to 90 bar (Table 1). The absolute configuration of 2-
methyl-2,3-dihydrobenzothiophene (2b) was assigned as (R)
by comparison of optical rotation data with the literature
value.15 Similarly, the isomer 3-methylbenzothiophene (2i)
could also be smoothly reduced in a yield of 79% and 99:1 e.r.
These results represent the first examples of a catalytic
homogeneous hydrogenation of substituted benzothiophenes
to the corresponding 2,3-dihydro derivatives. In addition, the
high levels of enantioinduction of this transformation are
unparalleled, rendering this method an efficient route to
attractive optically active dihydrobenzothiophenes. The scope
of this reaction was further examined. Several alkyl substituted
benzothiophenes (1b−f) were reduced in good to high yields
and excellent e.r.’s ranging from 99:1 to 98:2. Modest yields
were obtained when using 2-isobutylbenzothiophene (1g) and
15242
dx.doi.org/10.1021/ja306622y | J. Am. Chem. Soc. 2012, 134, 15241−15244

Journal of the American Chemical Society
Communication
by a homogeneous catalyst (Scheme 1).10d Thus, the high level
of reactivity observed at room temperature with this Ru-NHC
complex is really remarkable. Intriguingly, [Ru(cod)(2-methyl-
allyl)2], which is a powerful catalyst for several arene
hydrogenations,16 fails to show significant levels of activity in
the hydrogenation of 2-methylbenzothiophene under our
standard conditions (<5% conversion after 24 h), when the
NHC SINpEt is left out. This is representative of the inability
of most Ru species to catalyze this challenging transformation
and shows the crucial role of the NHC ligands.
In summary we have developed the first asymmetric
hydrogenation of substituted thiophenes and benzothiophenes.
The efficient and enantioselective hydrogenation of S-
containing heterocycles provides a new strategy for the
formation of enantiomerically enriched tetrahydrothiophenes
and 2,3-dihydrobenzothiophenes, compounds of great interest.
These results lay the foundation to gain insight into the
previously difficult hydrogenation of substituted thiophenes
and benzothiophenes. The unique ability of the chiral Ru-NHC
complex and the surprising discrepancy between the very high
levels of enantioinduction in many cases and the formation of a
racemic product for other classes of substrates will be the
matter of further investigations.
M.; Bolm, C. Adv. Synth. Catal. 2008, 350, 1101−1105. (e) Wang, X.-
B.; Zhou, Y.-G. J. Org. Chem. 2008, 73, 5640−5642. (f) Zhou, H.-F.;
Li, Z.-W.; Wang, Z.-J.; Wang, T.-L.; Xu, L.-J.; He, Y.-M.; Fan, Q.-H.;
Pan, J.; Gu, L.-Q.; Chan, A. S. C. Angew. Chem., Int. Ed. 2008, 47,
8464−8467. (g) Guo, Q.-S.; Du, D.-M.; Xu, J. Angew. Chem., Int. Ed.
2008, 47, 759−762. (h) Wang, Z.-J.; Zhou, H.-F.; Wang, T.-L.; He, Y.-
M.; Fan, Q.-H. Green Chem. 2009, 11, 767−769. (i) Wang, D.-W.;
Wang, X.-B.; Wang, D.-S.; Lu, S.-M.; Zhou, Y.-G.; Li, Y.-X. J. Org.
Chem. 2009, 74, 2780−2787. (j) Tadaoka, H.; Cartigny, D.; Nagano,
T.; Gosavi, T.; Ayad, T.; Genet, J. P.; Ohshima, T.; Ratovelomanana-
Vidal, V.; Mashima, K. Chem.Eur. J. 2009, 15, 9990−9994.
(k) Eggenstein, M.; Thomas, A.; Theuerkauf, J.; Francio, G.;
̀
Leitner, W. Adv. Synth. Catal. 2009, 351, 725−732. (l) Tang, W.-J.;
Sun, Y. W.; Xu, L. J.; Wang, T.-L.; Fan, Q.-H.; Lam, K.-H.; Chan, A. S.
C. Org. Biomol. Chem. 2010, 8, 3464−3471. (m) Gou, F.-R.; Li, W.;
Zhang, X.; Liang, Y.-M. Adv. Synth. Catal. 2010, 352, 2441−2444.
(n) Wang, D.-W.; Wang, D.-S.; Chen, Q.-A.; Zhou, Y.-G. Chem.Eur.
J 2010, 16, 1133−1136. (o) Tang, W.-J.; Tan, J.; Xu, L.-J.; Lam, K.-H.;
Fan, Q.-H.; Chan, A. S. C. Adv. Synth. Catal. 2010, 352, 1055−1062.
(p) Wang, T.-L.; Zhuo, L. G.; Li, Z.-W.; Chen, F.; Ding, Z.-Y.; He, Y.-
M.; Fan, Q.-H.; Xiang, J.-F.; Yu, Z.-X.; Chan, A. S. C. J. Am. Chem. Soc.
2011, 133, 9878−9891. (q) Chen, Q.-A.; Gao, K.; Duan, Y.; Ye, Z.-S.;
Shi, L.; Yang, Y.; Zhou, Y.-G. J. Am. Chem. Soc. 2012, 134, 2442−2448.
(r) Zhang, D.-Y.; Yu, C.-B.; Wang, M.-C.; Gao, K.; Zhou, Y.-G.
Tetrahedron Lett. 2012, 53, 2556−2559. (s) Maj, A. M.; Suisse, I.;
́
Meliet, C.; Hardouin, C.; Agbossou-Niedercorn, F. Tetrahedron Lett.
2012, 53, 4747−4750.
(3) For examples of asymmetric hydrogenation of isoquinolines, see:
(a) Lu, S.-M.; Wang, Y.-Q.; Han, X.-W.; Zhou, Y.-G. Angew. Chem., Int.
Ed. 2006, 45, 2260−2263. (b) Shi, L.; Ye, Z.-S.; Cao, L.-L.; Guo, R.-N.;
Hu, Y.; Zhou, Y.-G. Angew. Chem., Int. Ed. 2012, DOI: 10.1002/
anie.201203647.
ASSOCIATED CONTENT
* Supporting Information
Experimental section and characterization details. This material
is available free of charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
glorius@uni-muenster.de
(4) For recent examples of asymmetric hydrogenation of quinoxa-
lines, see: (a) Tang, W.; Xu, L.; Fan, Q.-H.; Wang, J.; Fan, B.; Zhou,
Z.; Lam, K.-H.; Chan, A. S. C. Angew. Chem., Int. Ed. 2009, 48, 9135−
■
̌ ́
9138. (b) Mrsic, N.; Jerphagnon, T.; Minnaard, A. J.; Feringa, B. L.; de
Author Contributions
Vries, J. G. Adv. Synth. Catal. 2009, 351, 2549−2552. (c) Rueping, M.;
Tato, F.; Schoepke, F. R. Chem.Eur. J. 2010, 16, 2688−2691.
†These authors contributed equally.
̂
(d) Cartigny, D.; Nagano, T.; Ayad, T.; Genet, J. P.; Ohshima, T.;
Notes
Mashima, K.; Ratovelomanana-Vidal, V. Adv. Synth. Catal. 2010, 352,
1886−1891. (e) Wang, D.-S.; Zhou, Y.-G. Tetrahedron Lett. 2010, 51,
3014−3017. (f) Chen, Q.-A.; Wang, D.-S.; Zhou, Y.-G.; Duan, Y.; Fan,
H.-J.; Yang, Y.; Zhang, Z. J. Am. Chem. Soc. 2011, 133, 6126−6129.
(g) Cartigny, D.; Berhal, F.; Nagano, T.; Phanasavath, P.; Ayad, T.;
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This manuscript is dedicated to Professor Alois Furstner. We
■
̈
thank BASF (Prof. Dr. Klaus Ditrich) for the donation of
precious chiral amines (ChiPros). Generous financial support
by the Deutsche Forschungsgemeinschaft (SFB 858) and by
the European Research Council under the European
Community’s Seventh Framework Program (FP7 2007-
2013)/ERC Grant agreement no. 25936 is gratefully acknowl-
edged. The research of F.G. has also been supported by the
Alfried Krupp Prize for Young University Teachers of the
Alfried Krupp von Bohlen und Halbach Foundation.
̂
Genet, P.; Ohshima, T.; Mashima, K.; Ratovelomanana-Vidal, V. J. Org.
Chem. 2012, 77, 4544−4556.
(5) For recent examples of asymmetric hydrogenation of indoles/
pyrroles, see: (a) Kuwano, R.; Sato, K.; Kurokawa, T.; Karube, D.; Ito,
Y. J. Am. Chem. Soc. 2000, 122, 7614−7615. (b) Kuwano, R.; Kaneda,
K.; Ito, T.; Sato, K.; Kurokawa, T.; Ito, Y. Org. Lett. 2004, 6, 2213−
2215. (c) Kuwano, R.; Kashiwabara, M. Org. Lett. 2006, 8, 2653−2655.
̌ ́
(d) Mrsic, N.; Jerphagnon, T.; Minnaard, A. J.; Feringa, B. L.; de Vries,
J. G. Tetrahedron: Asymmetry 2010, 21, 7−10. (e) Baeza, A.; Pfaltz, A.
Chem.Eur. J. 2010, 16, 2036−2039. (f) Wang, D.-S.; Chen, Q.-A.; Li,
W.; Yu, C.-B.; Zhou, Y.-G.; Zhang, X. J. Am. Chem. Soc. 2010, 132,
8909−8911. (g) Wang, D.-S.; Tang, J.; Zhou, Y.-G.; Chen, M.-W.;
Duan, Y.; Jiang, G.-F. Chem. Sci 2011, 2, 803−806. (h) Duan, Y.;
Chen, M.-W.; Ye, Z.-S.; Wang, D.-S.; Chen, Q.-A.; Zhou, Y.-G.
Chem.Eur. J. 2011, 17, 7193−7197. (i) Duan, Y.; Chen, M.-W.;
Chen, Q.-A.; Yu, C.-B.; Zhou, Y.-G. Org. Biomol. Chem. 2012, 10,
1235−1238. (j) Kuwano, R.; Kashiwabara, M.; Ohsumi, M.; Kusano,
H. J. Am. Chem. Soc. 2008, 130, 808−809. (k) Wang, D.-S.; Ye, Z.-S.;
Chen, Q.-A.; Zhou, Y.-G.; Yu, C.-B.; Fan, H.-J.; Duan, Y. J. Am. Chem.
Soc. 2011, 133, 8866−8869.
REFERENCES
■
(1) For reviews on the hydrogenation of aromatic compounds, see:
(a) Dyson, P. J. Dalton Trans. 2003, 2964−2974. (b) Glorius, F. Org.
Biomol. Chem. 2005, 3, 4171−4175. (c) Zhou, Y. G. Acc. Chem. Res.
2007, 40, 1357−1366. (d) Kuwano, R. Heterocycles 2008, 76, 909−
922. (e) Wang, D.-S.; Chen, Q. A.; Lu, S. M.; Zhou, Y.-G. Chem. Rev.
2012, 112, 2557−2590. (f) Yu, Z.; Jin, W.; Jiang, Q. Angew. Chem., Int.
Ed. 2012, 51, 6060−6072.
(2) For recent examples of asymmetric hydrogenation of quinolines,
see: (a) Li, Z.-W.; Wang, T.-L.; He, Y.-M.; Wang, Z.-J.; Fan, Q.-H.;
(6) For examples of asymmetric hydrogenation of (benzo)furans, see:
(a) Ohta, T.; Miyake, T.; Seido, N.; Kumobayashi, H.; Takaya, H. J.
Org. Chem. 1995, 60, 357−363. (b) Studer, M.; Wedemeyer-Exl, C.;
Spindler, F.; Blaser, H. U. Monatsh. Chem. 2000, 131, 1335−1343.
(c) Maris, M.; Huck, W.-R.; Mallat, T.; Baiker, A. J. Catal. 2003, 219,
̌ ́
Pan, J.; Xu, L.-J. Org. Lett. 2008, 10, 5265−5668. (b) Mrsic, N.; Lefort,
L.; Boogers, J. A. F.; Minnaard, A. J.; Feringa, B. L.; de Vries, J. G. Adv.
Synth. Catal. 2008, 350, 1081−1089. (c) Rueping, M.; Theissmann, T.;
Raja, S.; Bats, J. W. Adv. Synth.Catal. 2008, 350, 1001−1006. (d) Lu, S.
15243
dx.doi.org/10.1021/ja306622y | J. Am. Chem. Soc. 2012, 134, 15241−15244

Journal of the American Chemical Society
Communication
52−58. (d) Feiertag, P.; Albert, M.; Nettekoven, U.; Spindler, F. Org.
Lett. 2006, 8, 4133−4135. (e) Kaiser, S.; Smidt, S. P.; Pfaltz, A. Angew.
Chem., Int. Ed. 2006, 45, 5194−5197. (f) Ortega, N.; Urban, S.;
Beiring, B.; Glorius, F. Angew. Chem., Int. Ed. 2012, 51, 1710−1703.
(g) Ortega, N.; Beiring, B.; Urban, S.; Glorius, F. Tetrahedron 2012,
68, 5185−5192.
(7) For the asymmetric hydrogenation of carbocyclic rings, see:
(a) Kuwano, R.; Morioka, R.; Kashiwabara, M.; Kameyama, N. Angew.
Chem., Int. Ed. 2012, 51, 4136−4139. (b) Urban, S.; Ortega, N.;
Glorius, F. Angew. Chem., Int. Ed. 2011, 50, 3803−3806.
(8) (a) Rodriguez, J. A.; Hrbek. J. Acc. Chem. Res. 1999, 32, 719−728.
(b) Bianchini, C.; Meli, A. Acc. Chem. Res. 1998, 31, 109−116.
́
(c) Sanchez-Delgado, R. A. Organometallic Modeling of the Hydro-
desulfurization and Hydrodenitrogenation Reactions; Kluwer Academic:
Dortrecht, Netherlands, 2002.
(9) (a) Topsøe, H.; Clausen, B. S.; Massoth, F. E. Hydrotreating
Catalysis; Springer-Verlag: Berlin, Germany, 1996. (b) Kabe, T.;
Ishihara, A.; Qian, W. Hydrodesulfurization and Hydrodenitrogenation;
Wiley-VCH: Tokyo, Japan, 1999.
(10) (a) Bianchini, C.; Meli, A.; Vizza, F. J. Organomet. Chem. 2004,
689, 4277−4290. (b) San
́
chez-Delgado, R. A.; Gonzal
1989, 8, 1431−1436. (c) Baralt, E.; Smith, S. J.; Hurwitz, I.; Horvat
́
ez, E. Polyhedron
́
h, I.
T.; Fish, R. H. J. Am. Chem. Soc. 1992, 114, 5187−5196. (d) Borowski,
A. F.; Sabo-Etienne, S.; Donnadieu, B.; Chaudret, B. Organometallics
2003, 22, 4803−4809. (e) Bianchini, C.; Meli, A.; Moneti, S.;
́
Oberhauser, W.; Vizza, F.; Herrera, V.; Fuentes, A.; Sanchez-Delgado,
R. A. J. Am. Chem. Soc. 1999, 121, 7071−7080. (f) Bianchini, C.; Dal
Santo, V.; Meli, A.; Moneti, S.; Moreno, M.; Oberhauser, W.; Psaro,
R.; Sordelli, L.; Vizza, F. J. Catal. 2003, 213, 47−62. (g) Bianchini, C.;
́
Meli, A.; Peruzzini, M.; Vizza, F.; Herrera, V.; Sanchez-Delgado, R. A.
Organometallics 1994, 13, 721−730.
(11) (a) Benetti, S.; De Risi, C.; Pollini, G. P.; Zanirato, V. Chem. Rev.
2012, 112, 2129−2163. (b) Hauptman, E.; Shapiro, R.; Marshall, W.
̀
Organometallics 1998, 17, 4976−4982. (c) Davoust, M.; Briere, J.-F.;
̀
Jaffres, P.-A.; Metzner, P. J. Org. Chem. 2005, 70, 4166−4169.
(d) Noh, J.; Jeong, Y.; Ito, E.; Hara, M. J. Phys. Chem. 2007, 111,
2691−2696.
(12) For the use of NHCs as ligands in transition-metal catalysis and
organometallic chemistry, see: (a) Nolan, S. P. N-Heterocyclic Carbenes
in Synthesis; Wiley-VCH: Weinheim, Germany, 2006. (b) Glorius, F.
N-Heterocyclic Carbenes in Transition Metal Catalysis; Springer: Berlin,
2007. (c) Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Angew.
Chem., Int. Ed. 2007, 46, 2768−2813. (d) Wurtz, S.; Glorius, F. Acc.
̈
́
Chem. Res. 2008, 41, 1523−1533. (e) Díez-Gonzalez, S.; Marion, N.;
Nolan, S. P. Chem. Rev. 2009, 109, 3612−3676. For a review on the
physicochemical properties of NHCs, see: (f) Droge, T.; Glorius, F.
̈
Angew. Chem., Int. Ed. 2010, 49, 6940−6952. For reviews on NHC
organocatalysis, see: (g) Bugaut, X.; Glorius, F. Chem. Soc. Rev. 2012,
41, 3511−3522. (h) Biju, A. T.; Kuhl, N.; Glorius, F. Acc. Chem. Res.
2011, 44, 1182−1195. (i) Vora, H. U.; Rovis, T. Aldrichimica Acta
2011, 44, 3−11. (j) Nair, V.; Menon, R. S.; Biju, A. T.; Sinu, C. R.;
Paul, R. R.; Jose, A.; Sreekumar, V. Chem. Soc. Rev. 2011, 40, 5336−
5346. (k) Chiang, P.-C.; Bode, J. W. In N-Heterocyclic Carbenes as
Organic Catalysts in N-Heterocyclic Carbenes: From Laboratory
́
Curiosities to Efficient Synthetic Tools; Díez-Gonzalez, S., Ed.; Royal
Society of Chemistry: 2011; p 399. (l) Moore, J. L.; Rovis, T. Top.
Curr. Chem. 2010, 291, 77−144. (m) Phillips, E. M.; Chan, A.; Scheidt,
K. A. Aldrichimica Acta 2009, 42, 55−66. (n) Enders, D.; Niemeier, O.;
Henseler, A. Chem. Rev. 2007, 107, 5606−5655.
(13) Choi, M.-G.; Angelici, R. J. Organometallics 1992, 11, 3328−
3334.
(14) Hg(0) poisoning experiments performed in our previous work
strongly indicate the homogeneous nature of this Ru-NHC catalyzed
hydrogenation. For more details, see ref 7b.
(15) See Supporting Information.
(16) Unpublished results from our group.
15244
dx.doi.org/10.1021/ja306622y | J. Am. Chem. Soc. 2012, 134, 15241−15244