Ruthenium olefin metathesis catalysts with frozen NHC ligand conformations

Article abstract of DOI:10.1021/om5001452

The catalytic behavior of Grubbs and Hoveyda-Grubbs II type ruthenium complexes bearing N-heterocyclic carbene (NHC) ligands with syn-phenyl groups on the backbone and syn- or anti-oriented o-tolyl N-substituents was evaluated in a series of olefin metath

Full text of DOI:10.1021/om5001452

Article
pubs.acs.org/Organometallics
Ruthenium Olefin Metathesis Catalysts with Frozen NHC Ligand
Conformations
Alessandra Perfetto, Chiara Costabile, Pasquale Longo, and Fabia Grisi*
Dipartimento di Chimica e Biologia, Universita
S Supporting Information
̀
di Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, Salerno, Italy
*
ABSTRACT: The catalytic behavior of Grubbs and Hoveyda−
Grubbs II type ruthenium complexes bearing N-heterocyclic
carbene (NHC) ligands with syn-phenyl groups on the
backbone and syn- or anti-oriented o-tolyl N-substituents was
evaluated in a series of olefin metathesis transformations.
Further advance in the synthesis of the best-performing syn
catalysts and a deeper investigation into the solution-state
structure of the Hoveyda−Grubbs type II complex with anti N-
tolyl groups by 2D-NMR and DFT studies are also reported. Of
particular interest, syn complexes emerged among the best-
performing catalysts in all of the explored metathesis reactions,
especially in the ring-closing metathesis (RCM) of hindered
olefins, allowing also for the difficult formation of macrocyclic
trisubstituted alkenes. An important unexpected result was
obtained in the RCM of linalool, where both syn and anti catalysts appeared to be involved in the dehydration reaction of the
cyclization product (1-methylcylopent-2-en-1-ol). This process allowed for the formation of well-defined mixtures of
methylcyclopentadiene isomers, which represent valuable precursors for the synthesis of renewable high-density fuels.
INTRODUCTION
(5 and 6) have been found to better perform ring-closing
metathesis (RCM) reactions of olefins in comparison to their
anti analogues (7 and 8) and, more significantly, the syn
complexes 5a and 6a with reduced bulk on the nitrogen atoms
■
Catalytic olefin metathesis has become one of the most powerful
carbon−carbon bond-forming reactions currently available to
1
the synthetic chemist. In particular, the development of well-
(
o-tolyl N-substituents) can be counted among the most efficient
defined ruthenium alkylidene complexes (e.g., 1−4, Chart 1) has
broadened the scope and utility of the olefin metathesis reaction
in the synthesis of small molecules, preparation of natural
8
catalysts in the RCM of sterically demanding substrates.
The role of the NHC backbone configuration has been
investigated through experimental and theoretical studies, and
the origin of the enhanced reactivity observed for syn catalysts has
been attributed to a preferential syn orientation of the N-tolyl
rings imposed by the syn disposal of methyl groups on the
backbone. This conformation of the NHC ligand provides a
more sterically accessible face of the catalyst that facilitates the
2,3
products, and construction of polymers.
To allow an even more extensive use of metathesis chemistry,
the design of effective catalysts that are readily available, easy to
handle, reliable, and highly selective continues to be crucial4.
Indeed, still diverse metathesis applications such as asymmetric,
5
6
sterically demanding, or aqueous transformations can be
improved by identifying more suitable catalysts. Recent progress
in ruthenium olefin metathesis catalysts is undoubtedly related to
the modification of the N-heterocyclic carbene (NHC) ligand
architecture of the classical Grubbs II and Hoveyda−Grubbs II
complexes, which has produced a vast amount of structural
motifs of NHCs directly influencing the catalyst’s performance.
For example, the fine tuning of the electronic and steric
properties of the substituents on the nitrogen atoms and/or the
backbone of NHCs has had a significant impact on catalyst
activity, stability, and selectivity in several metathesis applica-
8
,9
approach of hindered substrates. In a preliminary communi-
10
cation, we reported on the synthesis of novel ruthenium
catalysts featuring an NHC ligand with syn phenyl groups on the
backbone and o-tolyl N-substituents (9 and 10, Chart 3). The
increased steric pressure of the NHC-backbone phenyl
substituents on the N-tolyl rings allowed for the separation of
ruthenium complexes with different N-tolyl conformations and
different reactivity in RCM reactions.
The superior performance of the isomers with syn-oriented N-
tolyl groups (syn-9 and syn-10) furnished incontrovertible
evidence for the importance of correctly oriented N-aryl groups
4
b,f,7
tions.
Recent work in our laboratories has led to the identification of
a class of ruthenium catalysts bearing NHCs with different
8
backbone configuration (see 5−8, Chart 2). The complexes
Received: February 7, 2014
incorporating syn-related methyl groups on the NHC backbone
©
XXXX American Chemical Society
A
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Chart 1. Well-Defined Ruthenium Benzylidene Catalysts
Chart 2. NHC Backbone and N-Aryl-Substituted Ruthenium Complexes
Chart 3. Ruthenium Catalysts with Frozen NHC
Conformations
Scheme 1. Synthesis of Complexes 9 and 10
NMR analysis. Both these precatalysts are stable in a solid form as
well as in solution, where the retention of the benzylidene signal,
1
monitored by H NMR spectroscopy, is observed over the course
of 1 week for syn-9 and 3 days for anti-9.
Starting from these phosphine-based complexes, Ru precata-
lysts syn-10 and anti-10, bearing a chelating benzylidene ether
ligand, were readily obtained from the reaction with isopropox-
ystyrene in the presence of CuCl as phosphine scavenger
to successfully accomplish RCM reactions, leading to unprece-
dented results in the formation of tetrasubstituted alkenes.
To obtain a more complete picture on the catalytic behavior of
Ru complexes 9 and 10 with frozen NHC conformations, we give
herein a full overview on RCM studies as well as on other
metathesis transformations such as ring-opening metathesis
polymerization (ROMP) and cross-metathesis (CM). In
addition, we describe a facile and convenient access to the
highly stable and extremely active syn-9 and syn-10 isomers
through well-known synthetic protocols, thus rendering these
catalysts actually attractive for application in catalysis.
11
(Scheme 1). Complexes syn-10 and anti-10 are highly air and
moisture stable both in the solid state and in solution for
12
extended periods of time.
Solution-state structures of complex 10 were determined by
NMR analyses. Only one isomer for syn-10 was observed in
solution, which was unambiguously identified by X-ray structure
10
1
13
analysis. H and C NMR analysis of anti-10 revealed the
presence of two isomers, corresponding to the opposite
arrangement of the anti-oriented N-tolyl groups of the NHC
ring.
RESULTS AND DISCUSSION
Synthesis and Characterization of Catalysts 9 and 10.
As reported in our previous work, the synthesis of the
■
According to density functional theory (DFT) studies on the
complex stability, four minimum-energy structures were located
for complex 10. In Figure 1, the internal and free energies in
benzene are reported.
The lowest energy structure 10A corresponds to the most
abundant isomer, syn-10, characterized by X-ray diffraction as
well. Structure 10D is not experimentally observed very likely
10
phosphine-containing complex 9 was easily accomplished in
4d
three steps by following the synthetic procedure reported in
Scheme 1. Chromatographic workup allowed for the isolation of
two distinct isomers, which were identified as syn-9 and anti-9 by
B
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⧧
Figure 2. TS NHC rotational counterclockwise (left, 10BC− ) and
⧧
clockwise (right, 10BC+ ) structures. Distances are given in Å.
Table 1. Internal and Free Energies of B and C Isomers and of
⧧
TS NHC Rotational Clockwise (BC+ ) and Counterclockwise
⧧
(
BC− ) Barriers in the Gas Phase and Benzene Related to
a
Isomer B
structure
Egas
Ggas
Ebenzene
Gbenzene
B
0
0
0
0
C
2.8
3.3
2.4
2.9
⧧
BC−
BC+
16.0
16.5
16.7
17.9
15.7
16.5
16.4
18.0
⧧
a
Energies are in kcal/mol.
Figure 1. Isomers of complex 10. For each structure internal and free
energies in benzene, obtained by DFT calculations, are reported in kcal
mol .
between the above phenyl group and the chloride (see 10BC+⧧
in Figure 2). Differently, the same methyl in the counter-
clockwise rotation TS (10BC− in Figure 2) keeps longer
distances from the closest phenyl group and the alkylidene
carbon.
−1
⧧
because of its high energy. As for the remaining two isomers, 10B
10
was found to be more stable than 10C.
D-NOESY/EXSY experiments displayed chemical exchange
2
The slight difference of only 0.9 kcal/mol between the
calculated lowest TS rotational barrier in benzene (16.4 kcal/
mol) and the experimental value (17.3 kcal/mol), corresponding
to the 10B → 10C direct travel, supports the hypothesis that the
observed exchange of isomers 10B and 10C occurs through
NHC rotation around the C−Ru bond.
at room temperature between the major (10B) and minor (10C)
forms of anti-10. Exchange cross peaks observed in the EXSY
spectrum of anti-10 allowed us to evaluate as 1.35 s− the rate
constant for the 10B → 10C direct travel, corresponding to a free
1
−1
energy of activation of 17.3 kcal mol , while a rate constant of
−
1
⧧
3
1
.85 s was evaluated for the 10C → 10B inverse run (ΔG =
The evaluated NHC rotation barrier is lower than barriers
measured on Grubbs second-generation catalysts with both N-
−1
6.6 kcal mol ) (see the Supporting Information).
8
a,13
Exchange between 10B and 10C can, in principle, occur
aryl as well as N-alkyl substituents.
NHC rotation barrier was estimated to be 21.8 kcal/mol,
whereas for NHC-Ru complexes bearing N-phenylethyl groups
Indeed, for complex 3 the
13a,b
through rotation of the NHC ligand. More in detail, 180° NHC
rotation around the C−Ru bond would lead to isomer 10B, as
depicted in Figure 1, to the enantiomer of isomer C, as depicted
in the same figure. To support this hypothesis, experimental
exchange barriers were compared with theoretical NHC
rotational barriers calculated by DFT. Starting from the most
stable isomer, 10B, clockwise as well as counterclockwise NHC
rotational barriers were located, and transition state (TS)
structures have been reported in Figure 2. Internal and free TS
energies in the gas phase and benzene related to isomer 10B are
shown in Table 1.
8a
rotation barriers of about 20−21 kcal/mol were calculated.
decrease of rotation barrier was observed only in the case of an
A
unsymmetrical NHC bearing N-fluorophenyl N-mesityl sub-
13b
stituents down to 17.9 kcal/mol. Complex 10B differs from
the already investigated catalysts in being a phosphine-free
catalyst and presenting backbone substitution and mono-ortho
N-aryl substituents. The presence of an oxygen in place of a
phosphine in a position trans with respect to the NHC should
increase the π back-donation from the metal to the NHC,
increasing the rotation barrier, as also shown by Thiele et al.
investigating Ru bis-NHC complexes with NHC ligand bearing
According to our studies, the lowest NHC rotational barrier
⧧
corresponds to a counterclockwise (10BC− ) rotation of the
1
4
NHC around the C−Ru bond, which passes through a TS with
the backbone phenyl groups on the same side of the alkylidene
ligand. The calculated free energy barrier in benzene is 16.4 kcal/
mol. A clockwise rotational barrier requires about 1.6 kcal/mol
more, due to the steric interaction of one of the methyl groups of
the N-aryl group that get stuck at short distances (3.3−3.4 Å)
different electron-withdrawing groups. In principle, the
inductive electronic donation effect of phenyls on the backbone
of 10B should also increase the barrier, by increasing σ donation
and, as a consequence, the π back-donation from the metal to the
NHC. In contrast, complex 10B shows a lower barrier, possibly
due to the minor steric hindrance of mono-ortho N-aryl groups
C
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in comparison to diortho substitution. Furthermore, it was
unexpected and seems to indicate an important role of the base
((CF ) CH COK or KHMDS) which reacts with the NHC
15
recently shown by Cavallo et al. that direct electronic donation
can be observed by DFT calculations from the Cipso of the N-aryl
substituents on one side directly to the metal and on the other
side to the alkylidene group when correctly oriented. As for
complex 10B, we can expect scarce interaction with the
alkylidene due to the orientation characteristic of Hoveyda
type complexes as well as, on the other side, labile interaction
with the metal due to the N-aryl orientation induced by phenyl
groups on the backbone. Such minor NHC−metal interactions
with respect to Grubbs second-generation complexes could be
also responsible for the decreased barrier.
3
2
3
ligand precursor to determine the selectivity of the synthesis
reaction. A similar protocol was explored also for the preparation
7d
of the phosphine-free complex 10 (Scheme 2). Again, direct
reaction of the imidazolidinium salt with KHMDS and then with
Hoveyda−Grubbs II (2) at 70 °C led selectively to the isomer
syn-10 in 55% yield.
In light of the catalysis results, the possibility of obtaining
exclusively the most active syn isomers assumes particular
relevance. Indeed, the ease of synthesis of stable catalysts plays an
important role in determining the feasibility of large-scale
industrial applications.
In an attempt to obtain complex 9 in more satisfactory yields,
we decided to exploit an alternative route previously reported in
Ring-Closing Metathesis (RCM) Activity. The catalytic
behavior of 9 and 10 was first investigated in the RCM reactions
of diethyl diallylmalonate (15) and diallyltosylamine (16) by
1
6
the literature. Diamine 12 was converted to imidazolidinium
salt 14 by condensation with triethyl orthoformate. This salt was
deprotonated in situ by treatment with potassium hexamethyldi-
silazide (KHMDS) and then mixed with Grubbs I (1) in toluene
at room temperature to selectively afford the most active isomer,
syn-9, in 60% yield (see Scheme 2). This result was rather
1
monitoring the conversion of each substrate to product via H
NMR spectroscopy. For comparison, parallel reactions were
17
performed with the commercial benchmark catalysts GII-tol
18
and HGII-tol. As clearly shown by the kinetic plots of the RCM
of 15 and 16 (Figure 3), catalysts syn-9 and syn-10 were both
highly efficient in these cyclization reactions, performing better
than their anti analogues. The monophosphine complex syn-9
displayed a markedly higher initial reaction rate with respect to its
congener anti-9 in both of the ring-closure reactions (Figure
Scheme 2. Synthesis of Complexes syn-9 and syn-10
3
9
A,C). Indeed, syn-9 required 30 min to give 17 in more than
8% conversion and 25 min to quantitatively afford 18, whereas
anti-9 was not able to complete the cyclization reactions of both
5 and 16 within 60 min (70% and 90% conversions,
respectively).
1
8
b
Consistent with previous results, the phosphine-free
complexes syn- and anti-10 were found to be slow to initiate
Figure 3. RCM conversion of (A, B) 15 and (C, D) 16.
D
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Figure 4. RCM conversion of (A, B) 19 and (C, D) 20.
RCM reactions under the catalytic conditions (30 °C, CD Cl )
formations syn-9 gave better performances than the commercial
catalyst GII-tol. The increased steric hindrance of these RCM
transformations results in slower reaction rates and highlights
more clearly reactivity differences between the two isomeric
complexes. It is worth noting that, for the tosylamine derivative
20, a catalyst loading of 0.05 mol % of syn-10 allowed complete
conversion in 14 min (Figure 4D).
2
2
employed for the corresponding monophosphine complexes syn-
19
and anti-9 (30 °C, CD Cl ). Therefore, to promote their
2
2
activation, all of the examined RCM reactions were performed at
0 °C in C D . The plots reported in Figure 3B,D showed that
6
6
6
syn-and anti-10 were both able to promote the RCM of 15 and
6, with syn-10 behaving as HGII-tol. Also in this case, different
1
conformations of the NHC ligand imply different reactivities of
the corresponding ruthenium complexes. At a catalyst loading of
Our attention next focused on the challenging RCM of
hindered dienes 23 and 24 (Figure 5). Figure 5A shows the
results for the RCM of the most sterically demanding malonate
derivative 23 promoted by syn-9 and anti-9. For comparison, the
plots of two other efficient N-tolyl catalysts for encumbered
olefins, such as 5a and the commercially available GII-tol, are
also reported. Compound syn-9 not only clearly outperformed
anti-9 but was also found to be more efficient than complexes 5a
and GII-tol, reaching 92% conversion within 30 min. The latter
represents the best result achieved in the RCM of 23 with a
monophosphine Ru catalyst up to now. It should be noted that
complexes 5a and GII-tol exist as a mixture of inseparable syn and
1
1
mol % complete conversion of 15 was obtained with both syn-
0 and anti-10 in 5 and 12 min, respectively. When the amount of
precatalyst was reduced by 1 order of magnitude (0.1 mol %),
syn-10 was able to promote quantitative cyclization of 15 within
30 min, whereas anti-10 needed 60 min to nearly complete the
same reaction (97% conversion) (Figure 3B). Lower catalyst
loadings employed to perform the RCM of tosylamine 16
allowed us to observe a significant difference between catalyst
activities. Indeed, as emerges from the kinetic data of Figure 3D,
16 was efficiently transformed to product 18 (>99% conversion)
5
a,8a,9
in only 7 min using 0.05 mol % of syn-10, whereas precatalyst
anti-10 effected complete cyclization to product 18 in 5 min at
higher catalyst loading (1 mol %). Moreover, in the same RCM
reaction the latter complex was not able to overcome 94%
conversion within 60 min at a 10 times lower catalyst loading (0.1
mol %).
The comparison of the catalytic behavior of the syn and anti
conformers of 9 and 10 was then extended to the RCM of slightly
hindered malonate (19) and tosylamine derivatives (20). The
kinetic profiles of these experiments and of those performed with
GII-tol and HGII-tol are presented in Figure 4. Similar to the
RCM of 15 and 16, the syn complexes 9 and 10 showed higher
activity than their anti congeners. Moreover, in both trans-
anti NHC conformational isomers,
and this feature
accounts for their lower activity in contrast to syn-9, consisting
of solely syn-NHC conformation, which is the spatial arrange-
8
,9
ment beneficial for the RCM of challenging substrates.
We also performed the RCM of 23 with the chiral
monophosphine Ru complex bearing an NHC with anti phenyl
20
groups on the backbone and o-tolyl N-substituents (GII-C2),
which is supposed to preferentially assume the anti conforma-
21
tion. The activity of this complex was comparable to that of
complex anti-9 (32% vs 46% conversion, see Figure 5A),
providing further confirmation of the relevance of the correct N-
aryl orientation to successfully perform RCM reactions. The
slightly lower difference in activity of GII-C2 with respect to anti-
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Figure 5. RCM conversion of (A, B) 23 and (C, D) 24.
9
should arise from the symmetry of the NHC backbone
75% conversion and anti-10 just provided 31% conversion
(Figure 5D).
configuration, which has already been shown to be a key element
in the ruthenium-catalyzed RCM of olefins.
8b
The influence of the NHC conformation of 9 and 10 was
studied in the RCM of (±)-linalool (27), a naturally occurring
linear terpene alcohol. The skeleton of this diene is particularly
intriguing because it is characterized by one monosubstituted
and one trisubstituted double bond and bears a methyl
substituent on the allylic carbon. Despite the significant steric
deactivation, the RCM of 27 has proven to be facilitated by the
interaction of the allylic hydroxyl group with the catalytic
The results for the RCM of 23 to form the tetrasubstituted 25
ring, promoted by phosphine-free catalysts syn-10, anti-10, 6a,
and commercially available HGII-tol are depicted in Figure 5B.
Although the differences in overall activity were less evident than
for the corresponding phosphine-containing complexes, com-
pound syn-10 with correctly oriented N-tolyl groups showed the
highest activity, emerging as one of the most efficient catalysts in
the RCM of challenging diolefins. In addition, syn-10 allowed the
formation of tetrasubstituted olefin 25 at a catalyst loading as low
as 0.5 mol %, leading to almost full conversion (>96%) within 3
h. The graphs depicted in Figure 5B display that syn-10, with one-
tenth the catalyst loading, was able to reach the same conversion
of anti-10 (86%) within 60 min, despite the striking difference in
their initial rates (a pronounced induction period is indeed
observed using 0.5 mol % of syn-10). This experimental evidence
underlines once again the high efficiency of the syn conformer
with respect to the anti conformer.
A lower catalyst loading was employed to perform the RCM of
the sterically hindered tosylamine substrate 24 in comparison to
the malonate analogue 23 (Figure 5C,D). The general reactivity
trend is in line with that of previous RCM reactions performed in
the presence of the syn and anti isomers of 9 and 10. Notably, a
nearly quantitative yield (97% in 60 min) was registered at 0.1
mol % of syn-10 for the most difficult tosylamine derivative 24,
whereas under the same reaction conditions HGII-tol reached
22
center, resulting in the formation of 1-methylcylopent-2-en-1-
ol (28) and isobutylene (29) (see Scheme 3). Both of these
products represent valuable starting materials for the synthesis of
23−26
polymers and renewable fuels.
As depicted in Figure 6A, the monophosphine catalysts syn-9
and anti-9 efficiently catalyzed the ring closing of 27 at a loading
of 1 mol %. For comparison, the plot of the same reaction carried
out with the N-tolyl catalyst GII-tol is also reported. The RCM
reactivity trend confirms the superior performance of the syn
isomer, which reached full conversion in only 7 min (anti-9 and
GII-tol required 10 and 13 min, respectively). When the catalyst
amount was decreased to 0.1 mol % (Figure 6B), conversion of
27 was incomplete, ranging between 33% (anti-9) and 59% (syn-
9
) within 60 min. Prolonged reaction times (48 h) did not
significantly improve the yields (for anti-9 it reached 37%);
however, after this time, the complete and spontaneous
conversion of the so-formed cyclic alcohol 28 to dehydration
products was unexpectedly observed, while the amount of
unreacted linalool 27 was found to remain unchanged. In
F
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Scheme 3. Products Derived from the RCM of 27 Promoted
by 9 and 10
The RCM of 27 carried out with phosphine-free catalysts syn-
10 and anti-10 is reported in Figure 6C. The catalytic behavior of
the two conformers of 10 was compared to that of the
commercial benchmark catalyst HGII-tol. At 1 mol % of loading,
catalysts syn-10, anti-10, and HGII-tol showed the same activity,
effecting the quantitative ring closure of 27 in 6 min. A slight
difference in reactivity among syn-10, anti-10, and HGII-tol was
noted by lowering the catalyst loading to 0.1 mol %, as shown by
the graphs of Figure 6D. Once again, the syn isomer revealed the
highest efficiency (>98% conversion within 60 min). The
spontaneous conversion of the alcohol 28 obtained through
these latter RCM reactions into dehydration products required
longer reaction times. In effect, the initial formation of
methylcyclopentadiene isomers was observed after 1 day from
the completion of the RCM reaction. After 10 days, a complex
reaction mixture of alcohol 28, 2-MCPD, 1-MCPD, and methyl
cyclopentadiene dimers (MCPD dimers) arising from Diels−
Alder cycloadditions was detected (Scheme 3). The formation of
MCPD dimers is facilitated by the higher reaction temperature
required by phosphine-free catalysts (60 °C), with respect to
phosphine-containing complexes, to effectively perform RCM
reactions.
particular, a complex mixture of 27, 2-methylcyclopentadiene (2-
MCPD), and 1-methylcyclopentadiene (1-MCPD) was ob-
tained (Scheme 3). Although RCM reactions of 27 promoted by
ruthenium catalysts under dilute conditions have already been
7f,27
reported in the literature,
the authors did not make mention
Of particular significance is the obtainment of isobutylene and
of well-defined mixtures of methylcyclopentadiene isomers from
the RCM reactions described above. Indeed, isobutylene can be,
of a similar evolution of the RCM product 28.
To gain more insight into this interesting dehydration process,
the fate of the alcohol 28, quantitatively obtained in the RCM
reactions conducted at 1 mol % of catalyst, was monitored for
longer periods of time. About 5 min after the completion of the
RCM reactions promoted by catalysts syn-9, anti-9, and GII-tol,
23
for example, polymerized to polyisobutylene, dimerized to
24
produce high-octane gasoline, or trimerized to produce jet
25
fuel, whereas methylcyclopentadiene isomers can be dimerized
and subsequently hydrogenated to give specialized fuel
1
the H NMR signals due to the formation of 2-MCPD began to
26
be visible and within 2 h the RCM product 28 was totally
converted into 2-MCPD and a small amount of 1-MCPD.
Indeed, the preferentially formed isomer 2-MCPD underwent
slow isomerization to the less favored 1-MCPD, leading in 2 days
to a final 2-MCPD/1-MCPD ratio of 57/43 with the isomers of
products.
Recently, Harvey et al. reported on solvent-free RCM
reactions of linalool 27 conducted with three commercial Ru-
28
based catalysts (1, 4, and GII-tol). Among them, at 60 °C,
complexes 1 and 4 were found to furnish the cyclic alcohol 28
along with dehydrated products such as cyclopentenol ethers,
9
and 65/35 with GII-tol (see the Supporting Information).
Figure 6. RCM conversion of 27.
G
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Figure 7. RCM conversion of 30.
MCPD isomers, and MCPD dimers. This finding was explained
by considering 1 and 4 as able to dehydrate a tertiary alcohol. On
the other hand, complex 1 was previously found to be able to
(Figure 7). This class of RCM reactions is a powerful tool in
organic synthesis because it allows the atom-economical
formation of cyclic functionalized products, usually present in
many drugs and natural products. As depicted in Figure 7, both
catalysts 9 successfully performed the RCM of 30, as did the
benchmark catalyst GII-tol. At 1 mol %, syn-9 required only 2
min to totally cyclize 30, whereas anti-9 and GII-tol needed 4
and 5 min, respectively (Figure 7A). An appreciable difference in
reactivity was detected in the RCM conducted at 0.1 mol %,
where the syn isomer completed the cyclization in 13 min and the
anti isomer achieved the same result in 29 min. More then 35 min
is required by GII-tol to approach full conversion. With the
phosphine-free catalysts syn- and anti-10, no difference in activity
could be observed between the catalysts at 1 mol % of loading
(Figure 7B). Indeed, both complexes converted all the substrate
in less than 2 min. The same catalytic behavior was observed for
catalyst HGII-tol. A small amount of discrimination was instead
noticed at 0.1 mol % of catalyst loading; in this case, syn-10
employed only 8 min to quantitatively effect the cyclization
(Figure 7B), as did HGII-tol. Significantly, the overall reactivity
profile in the examined RCEYM reaction puts syn conformers of
29
promote the direct dehydration of an RCM alcohol product. By
consideration of the nature of the substrate 27, an alternative
interpretation of the experimental data was proposed. Accord-
ingly, the occurrence of a ligand exchange reaction at the
ruthenium center of the alkoxy group for chloride would release
catalytic amounts of HCl, sufficient to promote the dehydration
2
8
of the alcohol.
The dehydration process following the RCM reactions carried
out with complexes 9, 10, GII-tol, and HGII-tol appears to be
mediated by ruthenium catalyst, possibly by species derived from
catalyst decomposition. As a general remark, it is well known that
Ru complexes bearing NHCs with reduced bulk at the ortho
positions of N-aromatic substituents are rather unstable and are
susceptible to decomposition through C−H activation processes
30
of the N-aryl groups on the NHC ligand.
The above RCM results clearly indicate that the dehydration
process involving the cyclic alcohol 28 is much more favored in
the presence of the phosphine-containing catalysts 9 and GII-tol
with respect to the analogous phosphine-free complexes 10 and
31
9 and 10 among the most efficient catalysts known.
Among the RCM transformations, a special place is occupied
HGII-tol. Since the PCy ligand released in the reaction mixture
3
1d,3e,32
after the initial metathesis step is known to contribute to catalyst
by macrocyclic RCM reactions.
Indeed, macrocyclic
3
0a
degradation,
it is reasonable to suppose that alcohol 28
frameworks are commonly found in bioactive natural products
and pharmaceutical molecules and their construction by RCM
often represents a key step in the synthesis of natural products
containing large rings. The most active catalysts syn-9 and syn-10
were therefore tested in the RCM of the diene esters 32 and 33 to
form the 14-membered lactones 34 and 35, respectively (Scheme
4). The reactions were monitored by GC analysis over a period of
24 h, and the best results are reported in Table 2.
dehydration observed in the presence of complexes 9 and GII-tol
could be activated by species arising from decomposition of the
catalyst mediated by PCy . To support this hypothesis, the RCM
3
of 28 was performed in the presence of the phosphine-free
catalyst syn-10 in CD Cl at 30 °C. Full conversion of 27 was
2
2
reached after 4.5 h; however, the reaction mixture was further
monitored over the course of 1 week. No dehydration of the
product 28 was observed. After this time, an excess of PCy was
In the formation of the 14-membered lactone 34, syn-9 gave
nearly quantitative yields of the RCM product in only 30 min
(Table 2, entry 1), showing superior performance with regard to
the commercial monophosphine catalysts 2 and GII-tol (Table
2, entries 3 and 4). Moreover, syn-9 was found to be more
efficient than the analogous catalyst 5a with methyl groups on the
NHC backbone (Table 2, entry 5). The different macro-RCM
reactivities observed for syn-9, GII-tol, and 5a can be related to
the different substitution patterns of the NHC backbone. As
already reported, the presence of substituents on the NHC
backbone improves catalyst stability, because restriction of the
rotation of the N-aryl groups hinders the necessary proximity of
an aryl C−H bond and the ruthenium center to promote
3
added to the reaction mixture, and the formation of dehydrated
products began to be evident. A mixture of 28 (67%), MCPD
isomers (25%), and Diels−Alder adducts (8%) was obtained
after 6 days from the addition of PCy , thus indicating that the
3
presence of this component in the reaction mixture plays a role in
the alcohol dehydration process. Nevertheless, the influence of
the phosphine ligand as well as of the nature of the catalyst
employed on the composition of the final mixtures of the RCM
reaction of 27 is not at all clarified and is still under investigation.
To further explore the catalytic potential of the isomers of 9
and 10 in RCM reactions, ring-closing ene-yne metathesis
(
RCEYM) was investigated with the standard test substrate 30
H
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Organometallics
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Scheme 4. Macrocyclic RCM of 32 and 33
free energy difference calculated in CH Cl allowed us to
2
2
determine the relative thermodynamic stabilities of 35-E and 35-
Z. Indeed, calculated E:Z populations are 85% (35-E) and 15%
(
35-Z), very close to the experimental ratio obtained by RCM in
the presence of catalysts 2, syn-9, and syn-10. DFT calculations
confirm the tendency of the examined catalysts to give products
under thermodynamic control.
Ring-Opening Metathesis Polymerization (ROMP)
Activity. Afterward, the catalytic behavior of the conformers
of 9 and 10 was examined in the ROMP of 1,5-cyclooctadiene
(
36; COD). Time−conversion studies for the ROMP of 36 in
the presence of 0.1 mol % and 0.01 mol % of catalyst are depicted
in Figure 9, and the most significant results are summarized in
Table 3.
Table 2. Synthesis of Macrocyclic Lactones 34 and 35
a
b
c
On examination of these data, a remarkable difference in
overall activity between phosphine-containing catalysts syn-9 and
anti-9 emerged at both 0.1 and 0.01 mol % (Figure 9A; entries 1,
entry
substrate catalyst time (h) yield (%)
E:Z
E:Z calcd
1
2
32
32
32
32
32
33
33
33
syn-9
syn-10
2
0.5
0.5
2
96
99
97
54
73
76
47
57
90:10
94:6
2
, 4 and 5, Table 3). The syn orientation of the N-tolyl groups on
d
3
94:6
96.5:3.5
the NHC is revealed once again to be the best orientation to gain
high catalyst performance. As for E:Z selectivity, no relevant
influence could be attributed to the different NHC conforma-
tions of syn-9 and anti-9. Syn-9 gave conversions and E:Z ratios
d
4
d
GII-tol
5a
4
94:6
5
4
94:6
6
7
syn-9
syn-10
2
24
82:18
75:25
e
24
40
85:15
8a
similar to those for GII-tol under identical reaction conditions
f
8
87:13
(
entries 3 and 6, Table 3), underlining the negligible role of the
a
b
Reactions in CH Cl (4 mM) at reflux temperature. Isolated yield.
E:Z ratios were determined by GC and NMR spectroscopy. GC
yield, taken from ref 33. E:Z ratios obtained from DFT calculated
energies in CH Cl (for computational details see the Experimental
2
2
phenyl substituents on the NHC backbone in addressing activity
and stereoselectivity in the ROMP of COD, as already observed
for catalysts 5a and 7a with methyl substituents on the
c
d
e
2
2
8a
f
backbone.
Section). GC yield, taken from ref 34a.
It should be noted that in the same ROMP reaction no
difference in overall activity could be appreciated among the
phosphine-free complexes syn-10, anti-10, and HGII-tol. This
could be related to the high temperature required for the
activation of this class of catalysts, which, as already observed,
tends to even out reactivity differences.
7
a
degradation pathways. As a consequence, high activity deriving
from correct syn N-tolyl conformation, combined with increased
stability, renders syn-9 an excellent catalyst for this macro-
cyclization. The same result was obtained also in the presence of
syn-10; nonetheless, it usually requires higher reaction temper-
atures than the corresponding phosphine-containing complex
syn-9. The experimentally observed E:Z ratios are in good
agreement with the calculated E:Z populations, indicating a
mainly thermodynamically controlled RCM in the formation of
Cross-Metathesis (CM) Activity. Finally, the catalytic
performance of syn-9 and anti-9 was compared in the CM of
allyl benzene (37) and cis-1,4-diacetoxy-2-butene (38), illus-
trated in Scheme 5. Both conformers gave high conversions to
the desired heterocoupled product 39, with syn-9 (91% yield)
once again performing better than its anti analogue (81% yield).
The presence of phenyl groups on the NHC backbone increases
catalyst efficiency, as demonstrated by the improved yields
observed for complexes 9 with respect to that obtained with the
34, for all catalysts.
A more stringent test is the formation of the 14-membered
3
4
lactone 35, containing a trisubstituted double bond. In this
reaction, syn-9 was revealed as the most efficient catalyst known
to date, proving once again its superiority to the commercially
available catalyst 2 (Table 2, entry 6). The decreased efficiency of
syn-10 in the formation of 35 was not too surprising, since
increased steric hindrance of the reaction could necessitate
8a
benchmark catalyst GII-tol (60%). As for the stereoselectivity,
the E:Z ratios clearly appear to be not influenced by the NHC
conformation and the backbone substitution.
3
5
higher temperature to improve catalyst performance.
CONCLUSION
Molecular modeling of E and Z isomers of 35 was performed
to afford further information on catalyst behaviors. Minimum
energy structures of 35-E and 35-Z are shown in Figure 8. The
■
In summary, a systematic study on the catalytic behavior of
phosphine-containing and phosphine-free NHC ruthenium
catalysts incorporating syn phenyl groups on the backbone and
differently oriented N-tolyl groups (syn and anti) in several
metathesis transformations (such as RCM, RCEYM, ROMP, and
CM) of representative substrates was reported.
Complexes with frozen syn N-tolyl groups (syn-9 and syn-10)
were clearly identified as the most efficient in all of the examined
reactions, outperforming also the commercial N-tolyl catalysts
GII-tol and HGII-tol in almost all cases. This finding suggests
that the correct orientation of N-tolyl rings is a general
requirement to successfully accomplish olefin metathesis trans-
8b
formations. As shown for the RCM of hindered olefins, the
symmetric tilt of the N-tolyl groups induced by the syn-phenyl
substituents on the NHC backbone leads to a more sterically
Figure 8. Structures and free energies of the E and Z isomers of
compound 35 calculated in CH Cl . Energies are in kcal/mol, distances
are in Å.
2
2
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Figure 9. ROMP conversion of 36.
Table 3. ROMP of 36
(27). Indeed, this process leads to an exceptionally well-defined
distribution of methylcyclopentadiene isomers (2-MCPD and 1-
MCPD), which represent a viable route to specialized fuel
products. Work is in progress in order to rationalize the behavior
of N-tolyl catalysts in mediating the dehydration of the alcohol.
a
b
entry
catalyst
time (min)
poly(36) yield (%)
E:Z
c
1
syn-9
3
12
4
>99
>99
>99
>99
90
1.1
0.8
1.3
0.7
0.4
1.0
2.4
4.0
3.8
1.7
2.6
2.7
c
2
anti-9
c
3
GII-tol
syn-9
d
4
27
60
27
2
EXPERIMENTAL SECTION
d
■
5
anti-9
Synthesis of Imidazolinium Chloride 14. A diethyl ether solution
of 12 was treated with a solution of hydrogen chloride (2.0 M in diethyl
ether) to precipitate the diamine hydrochloride salt as an off-white
powder. The product was collected by filtration and washed with diethyl
ether. The diamine salt (1.94 mmol, 902 mg) and a large excess of
triethyl orthoformate (3.3 mL) was placed in a 50 mL round-bottom
flask equipped with a magnetic stirrer. The flask was fitted with a
condenser and heated to 135 °C in an oil bath for 2 h. When it was
cooled to room temperature, the solid product was washed several times
d
6
GII-tol
syn-10
anti-10
HGII-tol
syn-10
anti-10
>99
>99
>99
>99
>99
>99
>99
e
7
e
8
2
e
9
2
f
9
5
f
1
1
0
1
5
f
HGII-tol
6
a
1
b
1
Determined by H NMR. E/Z ratios were determined by H and
1
3
c
with hexane and then with Et O to give the desired imidazolinium
2
C NMR of isolated products. Conditions: reactions in CH Cl , at 30
2
2
chloride salt 14 as a pale yellow solid (1.52 mmol, 668 mg, 78.4% yield).
d
°
C, catalyst 0.1 mol %. Conditions: reactions in CH Cl , at 30 °C,
1
2
2
H NMR (250 MHz, CD CN): δ 9.41 (br s, 1H, NCHN); 7.52 (br s,
e
3
catalyst 0.01 mol %. Conditions: reactions in C D , at 60 °C, catalyst
0
6
6
2
H); 7.36−7.26 (br m, 6H); 7.14−7.10 (br m, 10H); 6.73 (br s, 2H, N-
f
.1 mol %. Conditions: reactions in C D , at 60 °C, catalyst 0.01 mol
13
6
6
CH(Ph)CH(Ph)-N), 2.6 (br s, 6H, PhCH ). C NMR (62.5 MHz,
3
%
.
CD Cl ): δ 161.1 (NCN), 133.9, 133.4, 132.4, 131.7, 130.0, 129.7,
2
2
1
28.6, 128.6, 127.9, 127.5, 72.3 (N-CH(Ph)CH(Ph)-N), 20.0 (Ph-
3
+
−
Scheme 5. CM of Substrates 37 and 38
CH ). ESI MS: m/z 403.1 [M + (Cl )].
Synthesis of Ru Complex syn-9. In a glovebox, a 10 mL Schlenk
tube was charged with imidazolinium salt 14 (0.341 mmol, 150 mg),
potassium hexamethyldisilazide (KHMDS; 0.341 mmol, 0.68 mL, 0.5 M
in toluene), and (PCy ) Ru(CHPh)Cl (0.227 mmol, 186 mg)
3
2
2
dissolved in 2 mL of toluene. The reaction mixture was stirred at room
temperature for 1 h; then toluene was evaporated under vacuum and a
small amount of MeOH was added with stirring. The precipitate was
filtered off, washed with MeOH, and dried in vacuo. The desired
complex syn-9 was obtained as a brown powder (0.136 mmol, 128 mg,
6
0%).
open space around the ruthenium. Very likely, this feature also
clears the way to the easy approach and reaction of different
metathesis substrates. This insight can contribute to inspire
further ligand design and modification strategies in order to
improve olefin metathesis ruthenium catalyst efficiency.
To render the most performing syn catalysts really attractive
for large-scale applications, more convenient and straightforward
syntheses of syn-9 and syn-10 were also reported. In particular,
syn-9 was selectively obtained in good yield, free from the less
active anti conformer without requiring chromatographic
purification.
1
H NMR (400 MHz, C D ): δ 19.83 (br s, 1H, RuCHPh); 9.07 (d,
6
6
3J
= 7.67 Hz; 1H); 7.22 (t, 1H); 6.96 (m, 6H); 6.87 (t, 2H); 6.80 (t,
H−H
3
3
H), 6.75−6.64 (overlapped m, 6H); 6.41 (t, J
= 7.28 Hz; 2H); 5.98
H−H
3
(d, J
= 10.03 Hz; 2H); 5.45 (br d, 2H, N-CH(Ph)CH(Ph)-N); 2.78
H−H
1
3
(s, 6H, Ph-CH ); 2.24−1.0 (33H). C NMR (100 MHz, C D ): δ 299.4
3
6
6
2
(br s, RuCHPh); 222.3 (iNCN, J
= 65.82 Hz); 151.1; 139.6;
C−P
138.6; 137.5; 136.1; 133.8; 133.1; 131.9; 130.3; 129.7; 129.5; 128.82;
1
3
25.9; 73.9 (N-CH(Ph)CH(Ph)-N); 73.2 (N-CH(Ph)CH(Ph)-N);
3.1; 33.0; 29.1; 28.0; 26.7; 20.8 (Ph-CH ); 19.3 (Ph-CH ). P NMR
3
1
3
3
(
(
161.97 MHz, C D ): δ 22.8. Anal. Calcd for C H Cl N PRu
944.33): C, 68.63; H, 6.93; N, 2.96. Found: C, 69.15; H, 6.98; N, 2.99.
6 6 54 65 2 2
Synthesis of syn-10. In a glovebox, to a suspension of 14 (0.752
An unexpected result with interesting implications is related to
the involvement of syn and anti N-tolyl catalysts, as well as of
commercial GII-tol, in the dehydration reaction of the 1-
methylcylopent-2-en-1-ol (28) produced by the RCM of linalool
mmol, 330 mg) in toluene was added KHMDS (0.827 mmol, 165 mg).
The reaction mixture was stirred for 15 min at room temperature, and
then (PCy )Ru(CH-o-OiPrC H )Cl (0.399 mmol, 239 mg) was
3
6
4
2
added. The flask was removed from the glovebox, and the contents were
J
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Organometallics
Article
stirred at 70 °C for 3.0 h. The reaction mixture was cooled to room
temperature and purified by column chromatography on TSI silica gel
1.25 (s) in CD Cl or 1.13 (br s) in C D , and those in the product, δ
2
2
6
6
1.35 (s) in CD Cl or 1.26 (br s) in C D .
2
2
6
6
(n-hexane/diethyl ether 2/1 to 1/1). The solvent was removed in vacuo
RCEYM of (1-(Allyloxy)prop-2-yne-1,1-diyl)dibenzene (30)
Figure 7). Runs at 1 mol %. An NMR tube with a screw-cap septum
(
to give syn-10 as a green powder (0.179 mmol, 129 mg, 45.0%). Crystals
suitable for X-ray analysis were grown by vapor diffusion of pentane into
a concentrated benzene solution of the complex at room temperature.
top was charged with 0.750 mL of a CD Cl or C D solution of 30 (21.3
2
2
6
6
mg, 0.080 mmol). After equilibration at the appropriate temperature of
the sample in the NMR probe, 50 μL of a 0.016 M solution of catalyst
was injected into the tube. The reaction was monitored as a function of
time, and the conversion to 31 was determined by integrating the
methylene protons in the starting material, δ 4.03 (m) in CD Cl or 4.11
1
H NMR (400 MHz, CD Cl ): δ 16.22 (s, 1H, RuCH-o-
2
2
3
OiPrC H ); 8.78 (d, 1H, J
= 7.64 Hz); 7.57 (t, 1 H); 7.54 (d, 1
6
4
H−H
3
H, J
= 7.90 Hz); 7.42−7.35 (m, 2H); 7.27−7.24 (m, 2H); 7.17−
H−H
7
1
.14 (m, 4H); 7.09−7.02 (m, 6H); 7.00−6.90 (m, 2H); 6.86−6.84 (m,
H); 6.03 (d, 2H, J
CH(Ph)CH(Ph)-N); 5.02 (q, 1H, J
s, 3H, Ph-CH ); 2.56 (s, 3H, Ph-CH ); 1.54 (d, 3H, J
2
2
3
3
(m) in C D , and those in the product, δ 4.75 (m) in CD Cl or 4.50 (m)
= 9.96 Hz); 5.93 (d, 2H, J
=9.96 Hz, N-
6
6
2
2
H−H
H−H
3
in C D .
6 6
= 6.15 Hz, CH(CH ) ); 2.66
H−H
3 2
3
Runs at 0.1 mol %. An NMR tube with a screw-cap septum top was
(
= 6.15 Hz,
3
3
H−H
13
3
charged with 0.80 mL of a CD Cl or C D solution of 30 (21.3 mg,
2
2
6
6
CH(CH ) ); 1.33 (d, 3H, J
= 6.15 Hz, CH(CH ) ). C NMR (75
3
2
H−H
3 2
0
.080 mmol). After equilibration at the appropriate temperature of the
MHz, C D ): δ 294.4 (RuCH-o-OiPrC H ); 215.3 (iNCN); 153.3;
6
6
6
4
sample in the NMR probe, the reaction was started, with injection of 5
μL of a 0.016 M catalyst solution.
1
1
44.6; 141.3; 140.6; 138.0; 137.5; 133.8; 132.2; 131.2; 130.8; 129.5;
22.34; 113.3; 75.0 (N-CH(Ph)CH(Ph)-N); 74.3 (N-CH(Ph)CH-
Macrocyclic RCM of Diene Esters 32 and 33 (Table 2). A 100
mL three-neck round-bottom flask was fitted with a condenser and two
additional funnels. Solutions of the ruthenium carbene (6.0 μmol) and
of the appropriate diene (32 or 33) (120 μmol), each in 10 mL of
CH Cl , were independently added dropwise to refluxing CH Cl (10
(
(
(
Ph)-N); 72.6 (CH(CH ) ); 22.4 (Ph-CH ); 22.0 (Ph-CH ); 20.6
3 2 3 3
CH(CH ) ); 18.9 (CH(CH ) ). Anal. Calcd for C H Cl N ORu
3
2
3
2
39 38
2
2
722.14): C, 64.81; H, 5.30; N, 3.88. Found C, 64,80; H, 5.27; N, 3.85.
General Procedures for RCM Reactions. An NMR tube with a
2
2
2
2
screw-cap septum top was charged with 0.80 mL of a CD Cl or C D
2
2
6
6
mL) over a period of 15 min under nitrogen. Aliquots were removed
periodically for GC analysis, and GC retention times and integrations
were confirmed with samples of authentic material. After 24 h, the
solvent was removed in vacuo and the residue purified by flash
chromatography to afford analytically pure compounds.
solution of catalyst (0.05−5%). After equilibration at the appropriate
temperature (30 °C for the reaction in CD Cl , 60 °C for the reaction in
2
2
C D ) of the sample in the NMR probe, 0.080 mmol of substrate was
6
6
injected into the tube (0.1 M substrate/solvent ratio). Conversions of
1
each substrate to product were monitored over time by H NMR.
ROMP of COD (36) (Figure 9, Table 3). Procedures are as
described for RCM reactions. A 49.1 μL portion (0.40 mmol) of 36 was
injected into the heated NMR tube containing 0.80 mL of catalyst
solution (0.01−0.1 mol %), and the conversion to poly(36) was
determined by integrating the methylene protons in the starting
monomer, δ 2.36 (m) in CD Cl or 2.22 (m) in C D , and those in the
RCM of Diethyl Diallylmalonate (15) (Figure 3). A 19.5 μL portion
0.080 mmol) of 15 was injected into a heated NMR tube containing
(
0
.80 mL of catalyst solution (0.1−1 mol %), and the conversion to 17
was determined by integrating the methylene protons in the starting
material, δ 2.61 (dt) in CD Cl or 2.84 (dt) in C D , and those in the
2
2
6
6
2
2
6
6
product, δ 2.98 (s) in CD Cl or 3.14 (s) in C D .
2
2
6
6
product, δ 2.09 (br m)−2.04 (br m) in CD Cl or 2.14 (br m)−2.10 (br
2
2
RCM of N-Tosyldiallylamine (16) (Figure 3). A 17.2 μL portion
0.080 mmol) of 16 was injected into a heated NMR tube containing
m) in CD Cl in C D .
2
2
6
6
(
CM of Allylbenzene (37) and cis-(1,4)-Diacetoxy-2-butene
(38) (Scheme 5). In an oven-dried 4 mL vial (equipped with a magnetic
stirrer) were added simultaneously a 33 μL amount of 37 (0.25 mmol)
and 80 μL of 38 (0.5 mmol) via syringe to a stirred solution of the
catalyst (0.0065 mmol) in 1.25 mL of CH Cl . The mixture was allowed
0
.80 mL of catalyst solution (0.05−1 mol %), and the conversion to 18
was determined by integrating the methylene protons in the starting
monomer, δ 3.70 (dt) in CD Cl or 3.71 (d) in C D , and those in the
2
2
6
6
product, δ 4.00 (s) in CD Cl or 3.90 (s) in C D .
2
2
6
6
2
2
RCM of Diethyl Allylmethallylmalonate (19) (Figure 4). A 20.5 μL
portion (0.080 mmol) of 19 was injected into the heated NMR tube
containing 0.80 mL of catalyst solution (0.1−1 mol %), and the
conversion to 21 was determined by integrating the methylene protons
in the starting material, δ 2.67 (s), 2.64 (dt) in CD Cl or 2.96 (d), 2.93
to react for 12 h at 40 °C. The reaction mixture was concentrated and
purified directly on a silica gel column (9/1 hexane/ethyl acetate). 39
was obtained as a pale oil. The E:Z ratio was determined by integration
of peaks at δ 4.73 and 4.55 (CDCl3).
2
2
(
3
s) in C D , and those in the product, δ 2.93 (s), 2.88 (m) in CD Cl or
ASSOCIATED CONTENT
Supporting Information
Text, figures, and an xyz file giving additional experimental
details, detailed NMR spectra, and Cartesian coordinates for the
optimized structures. This material is available free of charge via
the Internet at http://pubs.acs.org.
6
6
2
2
■
.18 (m), 3.07 (s) in C D .
6 6
*
S
RCM of N-tosylallylmethallylamine (20) (Figure 4). A 19.4 μL
portion (0.080 mmol) of 20 was injected into a heated NMR tube
containing 0.80 mL of catalyst solution (0.05−1 mol %), and the
conversion to 22 was determined by integrating the methylene protons
in the starting material, δ 3.63 (s), 2.64 (dt) in CD Cl or 3.70 (d), 3.67
2
2
(
3
s) in C D , and those in the product, δ 3.91 (s), 2.88 (m) in CD Cl or
6
6
2
2
.96 (m), 3.82 (s) in C D .
AUTHOR INFORMATION
Corresponding Author
E-mail for F.G.: fgrisi@unisa.it.
Notes
6
6
■
*
RCM of Diethyl Dimethallylmalonate (23) (Figure 5). A 21.6 μL
portion (0.080 mmol) of 23 was injected into a heated NMR tube
containing 0.80 mL of catalyst solution (0.5−5 mol %) and the
conversion to 25 was determined by integrating the methylene protons
in the starting material, δ 2.71 (s) in CD Cl or 2.98 (s) in C D , and
The authors declare no competing financial interest.
2
2
6
6
those in the product, δ 2.89 (s) in CD Cl or 3.15 (s) in C D .
2
2
6
6
RCM of N-Tosyldimethallylamine (24) (Figure 5). A 20.2 μL portion
0.080 mmol) of 24 was injected into a heated NMR tube containing
ACKNOWLEDGMENTS
■
(
This paper is dedicated to Professor Adolfo Zambelli on the
occasion of his 80th birthday. The authors thank Dr. Patrizia
Iannece and Patrizia Oliva for technical assistance. Computa-
tional support from CINECA-High Performance Computing
Portal in the framework of a class C awarded proposal to the
ISCRA programme (code RCMMSCMO - HP10C8VOGT)
0
.80 mL of catalyst solution (0.1−1 mol %), and the conversion to 26
was determined by integrating the methylene protons in the starting
material, δ 3.61 (s) in CD Cl or 3.69 (s) in C D , and those in the
2
2
6
6
product, δ 3.87 (s) in CD Cl or 3.90 (s) in C D .
2
2
6
6
RCM of (±)-Linalool (27) (Figure 6). A 14.3 μL portion (0.080
mmol) of 27 was injected into a heated NMR tube containing 0.80 mL
of catalyst solution (0.1−1 mol %), and the conversion to 28 was
determined by integrating the methyl protons in the starting material, δ
̀
and financial support from the Ministero dell’Universita e della
Ricerca Scientifica e Tecnologica are gratefully acknowledged.
K
dx.doi.org/10.1021/om5001452 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
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783−3785. (h) Grisi, F.; Costabile, C.; Gallo, E.; Mariconda, A.;
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35) This reaction proceeds through dimerization of substrate 33 at the
monosubstituted double bond, as already described in ref 34.
(
̈
4
̈
7
(
M
dx.doi.org/10.1021/om5001452 | Organometallics XXXX, XXX, XXX−XXX