Synthesis and reactivity of olefin metathesis catalysts bearing cyclic (alkyl)(amino)carbenes

Article abstract of DOI:10.1002/anie.200702085

(Chemical Equation Presented) All it's CAACed up to be! Cyclic (alkyl)-(amino)carbenes (CAACs) can be used as ligands for olefin metathesis catalysis. A dramatic steric effect of the N-aryl group of the CAAC on catalyst activity was observed and utilized

Full text of DOI:10.1002/anie.200702085

Communications
DOI: 10.1002/anie.200702085
Olefin Metathesis Catalysts
Synthesis and Reactivity of Olefin Metathesis Catalysts Bearing Cyclic
(Alkyl)(Amino)Carbenes**
Donde R. Anderson, Vincent Lavallo, Daniel J. OꢀLeary, Guy Bertrand, and Robert H. Grubbs*
The evolution of olefin metathesis into a reaction routinely
used to form new carbon–carbon double bonds has been
enabled by the development of well-defined transition-metal
catalysts.[1,2] Many metathesis catalysts based on the
exchange of the remaining PCy3 ligand with a chelating ether
moiety provides a more stable complex, catalyst 3.[6]
Recently, the synthesis of cyclic (alkyl)(amino)carbenes
(CAACs), in which one amino group from an NHC has been
replaced by an alkyl group, was reported.[12] The greater s-
donor ability of carbon versus nitrogen results in more
electron-donating ligands, as indicated by the nCO absorption
of cis-[Rh(Cl)(CO)2L] complexes (L = H2IMes, n˜CO = 1996,
2081 cmꢀ1; L = 5b, n˜CO = 1994, 2077 cmꢀ1).[13] The exchange of
an sp2-hybridized nitrogen atom for an sp3-hybridized carbon
atom also changes the steric environment relative to NHCs.
Although most NHCs are C2v-symmetric, the CAACs
reported to date are Cs- or C1-symmetric, which may have
implications for the microscopic reversibility of the olefin-
binding and cycloreversion steps in the metathesis catalytic
cycle.[14,15] The unique properties of CAACs led us to explore
the utility of this new class of stable carbenes as ligands in
olefin metathesis catalysts.
=
[L2X2Ru CHR] scaffold have been synthesized in an effort
to increase catalyst stability, activity, and substrate scope.[3–10]
A significant gain in these areas was achieved after exchang-
ing a single PCy3 ligand of 1 with H2IMes (H2IMes = 1,3-
dimesityl-4,5-dihydroimidazol-2-ylidene), an N-heterocyclic
carbene (NHC), to produce catalyst 2 (Figure 1).[5] These
We first chose to investigate carbenes 5a,b, which can be
prepared from their respective salts 4a,b (Scheme 1).[12,16]
These ligands each contain an N-DIPP (DIPP = 2,6-diisopro-
Figure 1. Commonly utilized ruthenium olefin metathesis catalysts.
Cy =cyclohexyl.
results are attributed to the increased s-donor ability of
H2IMes over PCy3, which increases the affinity for p-acidic
olefins relative to s-donating phosphines.[11] Additionally,
[*] D. R. Anderson, Prof. R. H. Grubbs
Arnold and Mabel Beckman Laboratories of Chemical Synthesis
Division of Chemistry and Chemical Engineering
California Institute of Technology
Pasadena, CA 91125 (USA)
Fax: (+1)626-564-9297
E-mail: rhg@caltech.edu
Scheme 1. Synthesis of carbenes 5a,b.
V. Lavallo, Prof. G. Bertrand
UCR-CNRSJoint Research Chem. Laboratory (UMI 2957)
Department of Chemistry, University of California
Riverside, CA 92521-0403 (USA)
Fax: (+1)951-827-2725
E-mail: gbertran@mail.ucr.edu
pylphenyl) group and vary the steric bulk at the quaternary
carbon adjacent to the carbene center, with either two Me
groups (5a) or a spiro-fused cyclohexyl group (5b). Upon
addition of potassium hexamethyldisilazide (KHMDS) to
salts 4a,b at 228C in benzene, the corresponding carbenes
5a,b are obtained in good conversion as observed by 1H NMR
spectroscopy.
Ruthenium olefin metathesis catalysts bearing a pyridine
ligand typically undergo facile ligand exchange with stronger
donors such as phosphines or NHCs.[17] Thus, upon addition of
pyridine complex 6[18] to an NHC, the resulting ruthenium
complex is typically coordinated by a carbene ligand and a
phosphine ligand (e.g. 2), rather than a pyridine ligand.
However, upon treatment of pyridine complex 6 with
carbenes 5a,b (generated in situ), no evidence for the
Prof. D. J. O’Leary
Department of Chemistry, Pomona College
645 North College Avenue
Claremont, CA 91711 (USA)
Fax: (+1)909-607-7726
E-mail: doleary@pomona.edu
[**] Lawrence M. Henling and Dr. Michael Day are acknowledged for X-
ray crystallographic analysis. D.R.A. acknowledges NSF and NDSEG
predoctoral fellowships. D.J.O. thanks the Mellon Foundation for
financial support. R.H.G. and G.B. were supported by the NSF
(CHE-0410425) and the NIH (R01 GM 68825).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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expected phosphine complexes was obtained by 1H or
31P NMR spectroscopy [Eq. (1)]. Instead, air-sensitive pyri-
dine adducts 7a,b were isolated in modest yields.
To obtain more stable complexes, we targeted complexes
12a,b. After addition of 5a,b (prepared in situ) to ruthenium
precursor 11,[8] catalysts 12a,b were isolated and purified in
good yields by column chromatography [Eq. (3)]. Chelating
ether complexes 12a,b are air- and moisture-stable com-
pounds.
X-ray crystallographic analysis of compounds 7a,b was
conducted. These complexes exhibit a distorted square-
pyramidal geometry with the benzylidene ligand in the
apical position (Figure 2). The bond lengths and angles of
Similar to complexes 7a,b, the solid-state structures of
12a,b show a distorted square-pyramidal structure with the
benzylidene moiety at the apical position (Figure 3). Com-
paring complexes 12a,b with the H2IMes-containing analogue
ꢀ
3, the Ru Ccarbene distances are ꢁ 0.04–0.05 Š shorter and the
ꢀ
Ru O distances are 0.04–0.09 Š longer than in complex 3 (see
the Supporting Information).[6] These observations are con-
sistent with the increased s-donating properties of ligands
5a,b over their NHC counterparts.
Figure 2. X-ray crystal structures of 7a (left) and 7b (right). Thermal
ellipsoids are drawn at 50% probability and hydrogen atoms are
omitted for clarity.
the pyridine catalysts 7a,b are similar to those of
=
[(H2IMes)(py)2(Cl)2Ru CHPh] (8) (see the Supporting Infor-
mation).[17] The Ru Ccarbene distance is ꢁ 0.05 Š shorter than
ꢀ
in 8 which is consistent with the increased s-donating ability
ꢀ
of CAACs relative to H2IMes. In addition, the Ru Cbenzylidene
Figure 3. X-ray crystal structures of 12a (left) and 12b (right). Thermal
ellipsoids are drawn at 50% probability and hydrogen atoms are
omitted for clarity.
bond length is ꢁ 0.03 Š shorter in 7a,b than in 8, possibly a
result of the trans influence of the additional pyridine ligand
in 8.
The efficiency of catalysts 7a,b was examined in the ring-
closing metathesis of diethyl diallylmalonate (9) [Eq. (2)].
In all solid-state structures obtained, the CAAC exhibits
the same orientation relative to the benzylidene group
(Figure 4). The N-aryl ring is located above the benzylidene
moiety, while the quaternary carbon adjacent to the carbene
center is positioned over an empty coordination site. In the
case of pyridine complexes 7a,b, this observed preference
may be due to p–p stacking between the N-aryl ring and the
benzylidene ring. For chelating ether complexes 12a,b this
structural preference may be a result of negative steric
interactions between the Me groups on the quaternary carbon
adjacent to the carbene carbon and the benzylidene proton
(Figure 4). From this side view, it is apparent that the
benzylidene proton would be in close contact with one Me
group on the quaternary carbon center if the ligand were
rotated 1808 relative to the remainder of the molecule.
Maximum conversions to cyclopentene 10 observed by
1H NMR spectroscopy were less than 50% after 24 h at
228C or 608C, which is attributed to catalyst decomposition.
These results are consistent with those obtained previously
with pyridine-containing catalysts.[19] For comparison, com-
plexes 2 and 3 can achieve 95% conversion to 10 in 30 and
20 min, respectively, at 308C and 1 mol% catalyst loading.[19]
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=
Figure 4. View of complex 12a looking down the Ru CHR bond. It can
be observed that rotating the carbene 1808 would place the protons on
the benzylidene and Me group on the quaternary carbon center in
close proximity.
observed and isolated. Similar to 12a,b, complex 18 is an air-
and moisture-stable solid. X-ray diffraction studies of catalyst
18 show similar bond lengths and angles to those in 12a,b
(Figure 5).
1H NMR spectroscopy data suggest that the solid-state
conformation of 12a,b is maintained in solution. 2D-ROESY
experiments performed on complexes 12a,b in C6D6 at 228C
demonstrate Overhauser effects between the benzylidene
resonance and the aryl protons on the N-DIPP moiety, the
equivalent methine resonances of the aryl isopropyl groups,
and the enantiotopic Me groups facing the benzylidene
proton (Figure 4b). Overhauser effects are not observed
between the benzylidene proton and the gem-dimethyl(ene)
groups adjacent to the carbene center. This interaction might
be expected if there is fast exchange between two orientations
of the carbene ligand relative to the ruthenium benzylidene.
The efficiency of catalysts 12a,b was examined in the ring-
closing metathesis of 9, 13a, and 13b [Eq. (4)]. At a catalyst
Figure 5. X-ray crystal structure of 18. Thermal ellipsoids are drawn at
50% probability and hydrogen atoms are omitted for clarity.
Catalyst 18, which differs from 12a only by replacement of
N-DIPP with N-DEP, demonstrates significantly increased
activity in the formation of di- and trisubstituted olefins. In
the presence of 1 mol% 18, 95% conversion of 9 to
substituted cyclopentene 10 is observed in 15 min at 308C,
as compared to 3 h at 608C required for catalyst 12a
(Table 1). Catalyst 18 achieves 95% conversion of 13a to
trisubstituted cyclopentene 14a at 308C in 1 h, which is
comparable to the performance of catalysts 2 and 3. However,
catalyst 18 showed no reactivity in the conversion of 13b to
14b.
The dramatic increase in activity observed after slightly
decreasing the steric bulk of the N-aryl group is attributed to
catalyst initiation. We postulate that catalyst initiation
requires dissociation of the ether moiety and rotation of the
benzylidene ring into a plane parallel to the N-aryl group to
open a coordination site for incoming olefin.[20] For complexes
12a,b this process may be sterically unfavorable, thus result-
loading of 1 mol% catalyst loading, chelating ether catalysts
12a,b achieved 97% and 95% conversion of diethyl diallyl-
malonate (9) after heating at 608C for 3.3 h and 10 h,
respectively. Uninitiated catalyst is observed for both cata-
lysts even at high conversions, indicating that only a fraction
of added catalyst is engaged in the reaction. Catalyst 12a
converts 13a to 95% of trisubstituted olefin 14a in 20 h at
608C, whereas catalyst 12b achieves 96% conversion after
48 h at 608C. However, catalysts 12a,b showed no reactivity in
the conversion of 13b to tetrasubstituted olefin 14b.
We hypothesized that sterics could be responsible for the
lower activity of catalysts 12a,b relative to 2 and 3. CAACs
without the quaternary carbon center adjacent to the carbene
carbon are not synthetically accessible; thus, decreasing the
steric bulk of the N-aryl ring was targeted. Both the N-
mesityl- and N-DEP (DEP = 2,6-diethylphenyl)-substituted
salts, 15 and 16, respectively, were synthesized; deprotonation
of 15 and 16 under a variety of conditions did not afford the
desired free carbenes [Eq. (5)]. In situ deprotonations of 15
and 16 with KHMDS at ꢀ788C in THF in the presence of
ruthenium precursor 11 were also attempted. Although 17
was not observed by NMR spectroscopy, complex 18 could be
Table 1: Comparison of the activities of catalysts 12a, 12b, 18, 2, and 3.
Catalyst
Conversion (9!10)
Conversion (9!14b)
12a
12b
18
2
97% (3.3 h at 608C)
95% (10 h at 608C)
95% (15 min at 308C)
95% (30 min at 308C)
95% (20 min at 308C)
95% (20 h at 608C)
96% (48 h at 608C)
95% (1 h at 308C)
95% (45 min at 308C)
95% (45 min at 308C)
3
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ing in poor initiation (Figure 6). The steric bulk of the ortho-
aryl substituents may have a significant effect on initiation for
[1] R. H. Grubbs, Handbook of Metathesis, Wiley-VCH, Weinheim,
2003.
ꢀ
two reasons. First, the Ru Ccarbene bond length is slightly
[2] K. J. Ivin, J. C. Mol, Olefin Metathesis and Metathesis Polymer-
ization, Academic Press, San Diego, CA, 1997.
[3] P. Schwab, R. H. Grubbs, J. W. Ziller, J. Am. Chem. Soc. 1996,
118, 100 – 110.
shorter than in NHC analogues, thus bringing the aryl ring in
closer proximity to the ruthenium center. Second, the
quaternary carbon adjacent to the N-aryl group restricts
ꢀ
[4] S. T. Nguyen, R. H. Grubbs, J. W. Ziller, J. Am. Chem. Soc. 1993,
115, 9858 – 9859.
[5] M. Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1,
953 – 956.
rotation around the N-aryl bond and the Caryl CiPr bond, as
indicated by NMR spectroscopy experiments discussed ear-
lier.
[6] S. B. Garber, J. S. Kingsbury, B. L. Gray, A. H. Hoveyda, J. Am.
Chem. Soc. 2000, 122, 8168 – 8179.
[7] J. Yun, E. R. Marinez, R. H. Grubbs, Organometallics 2004, 23,
4172 – 4173.
[8] E. Despagnet-Ayoub, R. H. Grubbs, Organometallics 2005, 24,
338 – 340.
[9] J. M. Berlin, K. Campbell, T. Ritter, T. W. Funk, A. Chlenov,
R. H. Grubbs, Org. Lett. 2007, 9, 1339 – 1342.
[10] I. C. Stewart, T. Ung, A. A. Pletnev, J. M. Berlin, R. H. Grubbs,
Y. Schrodi, Org. Lett. 2007, 9, 1589 – 1592.
[11] M. S. Sanford, J. A. Love, R. H. Grubbs, J. Am. Chem. Soc. 2001,
123, 6543 – 6554.
Figure 6. Proposed rotation required for catalyst initiation.
[12] V. Lavallo, Y. Canac, C. Prasang, B. Donnadieu, G. Bertrand,
Angew. Chem. 2005, 117, 5851 – 5855; Angew. Chem. Int. Ed.
2005, 44, 5705 – 5709.
[13] V. Lavallo, Y. Canac, A. DeHope, B. Donnadieu, G. Bertrand,
Angew. Chem. 2005, 117, 7402 – 7405; Angew. Chem. Int. Ed.
2005, 44, 7236 – 7239.
[14] L. Cavallo, J. Am. Chem. Soc. 2002, 124, 8965 – 8973.
[15] P. E. Romero, W. E. Piers, J. Am. Chem. Soc. 2007, 129, 1698 –
1704.
[16] R. Jazzar, D. Rian, J.-B. Bourg, B. Donnadieu, Y. Canac, G.
Bertrand, Angew. Chem. 2007, 119, 2957 – 2960; Angew. Chem.
Int. Ed. 2007, 46, 2899 – 2902.
[17] M. S. Sanford, J. A. Love, R. H. Grubbs, Organometallics 2001,
20, 5314 – 5318.
[18] E. L. Dias, PhD Thesis, California Institute of Technology,
Pasadena, CA (USA), 1998.
[19] T. Ritter, A. Hejl, A. G. Wenzel, T. W. Funk, R. H. Grubbs,
Organometallics 2006, 25, 5740 – 5745.
[20] A. H. Hejl, PhD Thesis, California Institute of Technology,
Pasadena, CA (USA), 2007.
Interestingly, replacement of the N-mesityl groups in
complex 3 with N-DIPP groups,[21] results in a catalyst with
increased activity for the ring-closing metathesis of 9 (97%
conversion in 13 min vs. 20 min).[20] However, this bulkier
catalyst differs from the CAAC complexes owing to the
absence of substitution at the carbon adjacent to the nitrogen
atom.
Our investigation of the use of CAACs as ligands for
olefin metathesis catalysts has shown promising results. By
tuning the steric bulk of the N-aryl group, the results of ring-
closing metathesis for the formation of di- and trisubstituted
olefins are comparable to those achieved with standard
catalysts 2 and 3.
Received: May 11, 2007
Published online: July 10, 2007
[21] F. C. Courchay, J. C. Sworen, K. B. Wagener, Macromolecules
2003, 36, 8231 – 8239.
Keywords: alkenes · carbenes · homogeneous catalysis ·
metathesis · ruthenium
.
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