Stable ruthenium olefin metathesis catalysts bearing symmetrical NHC ligands with primary and secondary: N -alkyl groups

Article abstract of DOI:10.1039/c8dt00619a

Four novel stable Hoveyda-Grubbs-type catalysts containing N,N′-dineopentyl- and N,N′-dicyclohexyl-substituted N-heterocyclic carbene (NHC) ligands with syn and anti phenyl groups on the ring backbone were synthesized and fully characterized. The catalytic potential of these complexes was investigated in metathesis reactions of both standard and renewable substrates. Compared to the Hoveyda-Grubbs second generation catalyst (HGII), all of the new catalysts showed high performances in most of the examined metathesis transformations. In particular, N,N′-dicyclohexyl catalysts gave improved results in the challenging ring-closing metathesis (RCM) reaction to form tetrasubstituted olefins, while catalysts with neopentyl N-groups were found to be more active and Z-selective in cross-metathesis (CM) reactions. Modest enantioselectivities in the asymmetric ring-closing metathesis (ARCM) of achiral trienes with different steric hindrance were observed in the presence of catalysts bearing chiral C₂-symmetric NHC ligands.

Full text of DOI:10.1039/c8dt00619a

Dalton
Transactions
View Article Online
View Journal
PAPER
Stable ruthenium olefin metathesis catalysts
bearing symmetrical NHC ligands with primary and
Cite this: DOI: 10.1039/c8dt00619a
secondary N-alkyl groups†
Chiara Ambrosio,a Veronica Paradiso,a Chiara Costabile, a Valerio Bertolasi,b
a
Tonino Carusoa and Fabia Grisi
*
Four novel stable Hoveyda–Grubbs-type catalysts containing N,N’-dineopentyl- and N,N’-dicyclohexyl-
substituted N-heterocyclic carbene (NHC) ligands with syn and anti phenyl groups on the ring backbone
were synthesized and fully characterized. The catalytic potential of these complexes was investigated in
metathesis reactions of both standard and renewable substrates. Compared to the Hoveyda–Grubbs second
generation catalyst (HGII), all of the new catalysts showed high performances in most of the examined meta-
thesis transformations. In particular, N,N’-dicyclohexyl catalysts gave improved results in the challenging
ring-closing metathesis (RCM) reaction to form tetrasubstituted olefins, while catalysts with neopentyl
N-groups were found to be more active and Z-selective in cross-metathesis (CM) reactions. Modest enantio-
selectivities in the asymmetric ring-closing metathesis (ARCM) of achiral trienes with different steric hin-
drance were observed in the presence of catalysts bearing chiral C2-symmetric NHC ligands.
Received 14th February 2018,
Accepted 11th April 2018
DOI: 10.1039/c8dt00619a
rsc.li/dalton
Introduction
Since their introduction more than 25 years ago,1
N-heterocyclic carbenes (NHCs) have emerged as an important
class of ligands in transition metal mediated processes and
have also been used as valuable nucleophilic organocatalysts
in a series of organic reactions.2 The tremendous success of
NHCs reflects their unique stereoelectronic properties and
finds maximum expression in their application as ancillary
ligands for ruthenium-based olefin metathesis catalysts.3
Indeed, due to the easy manipulation of the NHC scaffold of
classical second generation catalysts (e.g. GII and HGII,
Chart 1), many NHC ligands have been designed to confer
specific catalytic properties to the resulting ruthenium-based
catalysts in metathesis applications.4
In this context, a fair number of modifications of the NHC
ligand have been gained by varying the steric and electronic
properties of substituents on the backbone and/or the nitrogen
atoms, leading to the development of systems with improved
stability, activity and selectivity.5 While ruthenium olefin meta-
thesis complexes bearing saturated NHC ligands with aryl side
Chart 1 Grubbs and Hoveyda–Grubbs second generation catalysts.
chains have been thoroughly investigated,4,5 only a very few
number of analogous ruthenium complexes with aliphatic
amino side groups have been documented until now (see 1–3,
Chart 2).6 What is more, all of them present secondary N-alkyl
groups. The synthetic access to ruthenium complexes contain-
ing saturated NHCs with N-alkyl groups has been strongly
limited by the tendency of NHCs with small N-alkyl groups to
dimerize rather than to form the corresponding metal com-
plex7a and by the inability of NHCs presenting extremely bulky
aliphatic amino groups to be accommodated in the coordi-
nation sphere of the metal complex.7 In addition, some of
these complexes, albeit observed, were not stable enough to be
isolated.6a For all these reasons, an in-depth study of the cata-
lytic properties of this class of complexes and a full evaluation
of the influence exerted by the N-alkyl substituents on the
efficiency of catalysts have not been available to date.
aDipartimento di Chimica e Biologia “Adolfo Zambelli”, Università di Salerno,
Via Giovanni Paolo II 132, I-84084 Fisciano, Salerno, Italy. E-mail: fgrisi@unisa.it
bDipartimento di Chimica and Centro di Strutturistica Diffrattometrica, Università di
Ferrara, Via L. Borsari 46, I-44100 Ferrara, Italy
With this in mind, we aimed to develop stable N,N′-dialkyl
substituted ruthenium complexes by modifying the steric pro-
perties and flexibility of the NHC ring due to the presence of
†Electronic supplementary information (ESI) available. CCDC 1564122. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c8dt00619a
This journal is © The Royal Society of Chemistry 2018
Dalton Trans.

View Article Online
Paper
Dalton Transactions
lysts containing primary N-alkyl groups are bis(NHC) com-
plexes where the alkyl-substituted NHC is unsaturated.11
The steric and electronic features of newly developed com-
plexes 4–7 were assessed through both experimental and
theoretical studies, and their catalytic performances were eval-
uated in typical ring-closing metathesis (RCM), cross-meta-
thesis (CM) and ring-opening metathesis polymerization
(ROMP) reactions as well as in RCM and CM metathesis trans-
formations involving renewable compounds. Finally, the cata-
lytic potential of 5 and 7, possessing chiral C2-symmetric NHC
ligands, was also evaluated in the enantioselective desymme-
trization of achiral trienes via asymmetric ring-closing meta-
thesis (ARCM).
Chart 2 Ruthenium catalysts with aliphatic amino side groups.
Results and discussion
Synthesis and characterization of complexes 4–7
suitable substituents on the NHC backbone. We hypothesized
that, through this modification, the tendency of NHCs to
dimerize could be limited, allowing for the formation of the
desired metal complexes more easily. Furthermore, we reason-
ably expected that backbone substitution would have a positive
impact on the stability of complexes, as already observed for
both N,N′-diaryl5e,f,8 and N-alkyl/N′-aryl9 catalysts, and that
installation on the NHC backbone of groups with a precise
stereochemical relationship (syn or anti) could alter the pro-
perties of the resulting catalysts.10 Thus, in the present work
we report on the synthesis and characterization of four new
Hoveyda–Grubbs second generation type complexes decorated
with NHC ligands which combine different alkyl groups on the
nitrogen atoms (neopentyl or cyclohexyl) and syn- or anti-
related phenyl groups on the backbone (4–7, Chart 3). Notably,
metathesis ruthenium complexes bearing saturated NHC
ligands containing primary N-alkyl groups (4 and 5) are
described for the first time. Indeed, to the best of our knowl-
edge, the only known examples of NHC–olefin metathesis cata-
The synthesis of complexes 4–7 was easily accomplished start-
ing from commercial meso- or (R,R)-1,2-diphenylethyl-
enediamine, as depicted in Scheme 1. The dialkylated di-
amines A, B, and C were obtained by a condensation reaction
Scheme 1 Synthesis of ruthenium complexes 4–7. Reaction con-
ditions: (a) (1) meso-1,2-Diphenylethylenediamine (for A) or (R,R)-
diphenylethylenediamine (for B), pivalaldehyde, CH2Cl2, molecular
sieves, room temperature, 48 h; (2) NaBH4, CH3OH, room temperature,
3.5 h. (a’) For C: (1) meso-1,2-diphenylethylenediamine, cyclohexanone,
CH2Cl2, molecular sieves, room temperature, 48 h; (2) NaBH4, CH3OH,
room temperature, 3.5 h. For D: (1) (R,R)-diphenylethylenediamine,
cyclohexanone, CH2Cl2, molecular sieves, room temperature, 12 h; (2)
NaBH4, CH3OH, room temperature, 3.5 h; (3) cyclohexanone, HCOOH,
CHCl3, molecular sieves, 50 °C, 48 h; (4) NaBH4, CH3OH, room temp-
erature, 3.5 h. (b) NH4BF4, CH(OEt)3, 135 °C, 2 h. (c) (CF3)2CH3COK, HGI,
toluene, 65 °C, 2.5 h (for 5) or CH3CH2(CH3)2COK, HGI, toluene, 65 °C,
50 min (for 4, 6 and 7).
Chart 3 New ruthenium complexes with N,N’-dialkyl substituted NHC
ligands.
Dalton Trans.
This journal is © The Royal Society of Chemistry 2018

View Article Online
Dalton Transactions
Paper
with pivalaldehyde (A, B) or cyclohexanone (C) followed by complex 6 were grown by the slow diffusion of pentane into a
reduction in situ of the resulting diimines with sodium boro- concentrated solution of diethyl ether. The solid state structure
hydride (76–94% yields), whereas diamine D was prepared by of 6 was obtained by X-ray diffraction studies and is shown in
two subsequent steps of reductive amination with cyclohexa- Fig. 1. In this compound, the Ru center is penta-coordinated
none (64% yield), since following the same synthetic route and adopts a distorted square pyramidal coordination geome-
used for A–C lower yields of D (∼20%) were registered. The try. The Cl atoms are trans oriented in the basal plane and the
NHC precursors E–H were all obtained in high yields (87–91%) carbene C1 atom is in the trans position with respect to the O1
after reaction of the respective diamines with triethyl ortho- oxygen of the 2-iPrO substituent at the benzylidene ligand,
formate and ammonium tetrafluoroborate. The treatment of which is rotated by 22.23(4)° with respect to the NHC ring.
E–H with the appropriate base (potassium hexafluoro-t-but- Compound 6 crystallizes in the centro-symmetric P21/c space
oxide or potassium t-amylate) in the presence of RuCl2(vCH- group with the NHC phenyl groups in the cis position with
o-iPrO-Ph)(PCy3) (HGI) led to the desired complexes 4–7 as air- respect to the C2–C3 bond. Accordingly, the crystal contains a
and moisture-stable green solids (40–62% yields).12
racemic mixture of both the enantiomers having opposite con-
All the complexes were characterized by NMR spectroscopy, figurations (SR or RS) at the C2 and C3 asymmetric
elemental analysis and ESI-FT-ICR analysis. Single crystals of carbon atoms. The rotations of the cyclohexane rings at the
N1 and N2 NHC atoms are mainly determined by short
intramolecular interactions: H20⋯Ru1 = 2.9206(3) Å and
H14⋯Cl2 = 2.805(1) Å.
Despite numerous attempts, we were not able to grow crys-
tals of 4, 5 and 7 suitable for X-ray analysis due to their high
solubility in most common solvents.
To support characterization of 4–7, minimum energy struc-
tures were located for all complexes by density functional
theory (DFT) studies and are shown in Fig. 2 (see the ESI† for
further details).
Top and side views of minimum energy structures of 4–7,
displayed in Fig. 2, show how the orientation of N-substituents
is influenced by the phenyls on the backbone. It is worth
noting also that the torsion angles of the NHC planes with
respect to the alkylidene group are very pronounced for 6 and
7 (28.5° and −31.8°, respectively) due to the steric interactions
between the cyclohexyl and alkylidene groups.
Thermal stabilities of 4–7 were evaluated in C6D6 solutions
at 60 °C under nitrogen and monitored by 1H NMR spec-
troscopy over 40 days using tetrakis(trimethylsilyl)silane as an
internal standard. The degradation process of each complex
(20 days) is illustrated in Fig. 3.
Fig. 1 ORTEP13 view of 6 showing the thermal ellipsoids at the 40%
probability level.
Fig. 2 Top and side views of the calculated minimum energy structures of 4–7.
This journal is © The Royal Society of Chemistry 2018
Dalton Trans.

View Article Online
Paper
Dalton Transactions
meters were assessed by calculating percent buried volumes
(%VBur) and producing steric maps (Fig. 4) from the density
functional theory (DFT) optimized geometries of 4–7 (see
Fig. 2)14 (see the ESI† for computational details).
No remarkable differences could be appreciated between
the overall NHC %VBur of syn and anti isomers with the same
N-substituents, whereas complexes having N-neopentyl substi-
tuents present an overall %VBur higher than those with
N-cyclohexyl ones (see also Table 1). Moreover, complexes with
N-neopentyl substituents (4–5) show an asymmetrical hin-
drance located in a specific quadrant, which means that the
NHC ligand crowds the reacting side of the metal deeply just
in a small area (orange area of the map), whereas the steric
encumbrance is more diffuse as for complexes with
N-cyclohexyl substituents (6–7). Compared to HGII (Fig. 5),
4–7 have lower overall NHC %VBur values and a less symmetri-
cally distributed steric pressure around the metal.
Fig. 3 Stability tests of 4–7 in C6D6 at 60 °C under nitrogen.
Decomposition was monitored by 1H NMR spectroscopy using tetrakis
(trimethylsilyl)silane as an internal standard. The lines are intended as a
visual aid only.
As already reported in the literature,9c,15 differences in
Complexes 4 and 5 with neopentyl N-substituents were stability displayed by complexes 4–7 can be mainly related to
found to be more stable compared to 6 and 7 having cyclohexyl small differences in the steric demands of the corresponding
N-substituents. Moreover, although after 20 days the amount NHCs. In this view, complexes with bulkier ligands
of the residual complex was quite similar for both the couples are more stable than those with less encumbered ligands:
of syn and anti diastereomers, anti complexes showed higher HGII > 5 ≈ 4 > 7 ≈ 6.
stability than the corresponding syn isomers, mainly in the
To depict a complete description of 4–7, the electronic pro-
first 5–8 days of analysis. After 40 days, only 5 still persisted perties of the corresponding NHCs were assessed by experi-
(14% of unaltered complex). On the whole, 4–7 displayed good mental and theoretical investigations. More in detail, electro-
stabilities when compared to unsymmetrical systems bearing chemical studies were performed to evaluate the electron-
an analogous N-alkyl moiety,9c albeit they were all definitely donating abilities of the NHC ligands of 4–7.16 The Ru(II)/
less robust than the classical HGII complex with N-aromatic Ru(III) redox potentials determined by cyclic voltammetry are
substituents over a long period of time.
shown in Table 1.
To provide a more complete characterization of the newly
A slight influence of the N-alkyl substitution within the
developed complexes 4–7, the steric and electronic properties NHC framework on the electron density at the ruthenium
of the corresponding NHC ligands were investigated. Since center was proved by differences in redox potentials
crystal data were available only for complex 6, steric para- (24–50 mV) between complexes 4–5 and 6–7. In particular, the
Fig. 4 Topographic steric maps of 4–7. The iso-contour curves of steric maps are in Å. The maps were constructed starting from the minimum
energy structures of complexes optimized by DFT calculations. The complexes are oriented according to the complex scheme. Overall %VBur and
%VBur representative of each single quadrant are reported for each map.
Dalton Trans.
This journal is © The Royal Society of Chemistry 2018

View Article Online
Dalton Transactions
Paper
of a recent method that makes use of 13C NMR spectroscopy.17
It has been shown that the 1JCH coupling constant between the
carbon and the hydrogen atom of the precarbenic position in
the azolium salts can be used to evaluate the σ-electron donor
Table 1 Percent buried volumes, redox potentials and bond-dis-
sociation energies for 4–7
a
Complex
%VBur
ΔE1/2b (V)
BDEc (kcal mol−1
)
1
4
5
6
7
30.9
31.0
28.7
28.9
32.9
0.996
1.00
0.972
0.950
0.860d
−64.9
−66.0
−73.5
−71.5
−70.9
of the respective NHCs. The higher the JCH, the poorer the σ-
1
donation ability.18 The JCH values of 205 and 206 Hz were
measured for E and F, respectively, indicating that in this case
a different NHC backbone configuration has basically no effect
on the σ-donor properties of the carbene. On the other hand,
for G (1JCH = 201 Hz) and H (1JCH = 204 Hz) the presence of the
syn oriented phenyl groups on the backbone appears to
enhance the σ-donor ability of the corresponding NHC. By
comparison of these values with that reported for the NHC
precursor of the HGII (1JCH = 206 Hz),17a it appears that the
NHCs derived from salts E, F and H present quite similar σ-
donor properties, while the NHC generated from G is a slightly
better σ-donor. It must be noted, however, that the overall elec-
tron density of the metal depends on the σ-donation, as well
as on the π-donation to the metal and on the π-back donation
from the metal to the NHC ligand;19 therefore some inconsis-
HGII
a Percent buried volume obtained from DFT optimized structures.
b Redox potentials determined using cyclic voltammetry in CH2Cl2
under nitrogen; 1 mM analyte, 0.1 M NBu4PF6 as supporting electro-
lyte and 1 mM octamethylferrocene as an internal standard. Scan rate:
100 mV s−1 c Bond-dissociation energies are referred to the Ru–NHC
.
bond. d Redox potential reported in the literature16 is 0.850 V.
1
tencies in information deriving from JCH and redox potential
measurements are expectable.
Bond-dissociation energies (BDEs) of the Ru–NHC bonds in
complexes 4–7 were also evaluated by DFT calculations and are
shown in Table 1. While, once again, no correlation was found
among BDE values and electronic parameters (as ΔE1/2), BDEs
appear meaningful when compared with %VBur. In fact, less
hindered ligands, such as N-cyclohexyl substituted NHC, show
higher BDE values with respect to the more crowded neopentyl
N-substituted NHCs. Comparison with N-mesityl NHC is not
significant since N-substituents with sp2 N-carbons create a
different encumbrance around the metal.
Fig. 5 Topographic steric map of HGII. The iso-contour curves of steric
maps are in Å. The map was constructed starting from the minimum
energy structures of complex optimized by DFT calculations. The
complex is oriented according to the complex scheme. Overall %VBur
and %VBur representative of each single quadrant are reported in the
map.
Catalytic behaviours of 4–7
The catalytic performances of new complexes 4–7 were first
investigated in model RCM reactions of malonate derivatives
with increasing steric demand (8, 10, and 12). All the ring-
closures were monitored over time by 1H NMR spectroscopy
and the corresponding kinetic profiles are sketched in
presence of N-cyclohexyl substituents (6–7) confers better elec- Fig. 6–8. To put the results into a larger context, conversion–
tron donating properties to the corresponding NHCs. time curves for parallel RCM reactions carried out with the
Moreover, in the case of N-cyclohexyl complexes a small effect commercial catalyst HGII are also displayed.
of the NHC backbone configuration on the electron donor pro-
In the RCM of 8 (Fig. 6), 4–7 showed similar catalytic activi-
perties was observed, as revealed by a cathodic shift of 22 mV ties, with catalyst 4 performing slightly better than all the
registered moving from the syn isomer 6 to anti 7. This other ones (>98% conversion in 10 min) and disclosing a
shift implies an increased electron density at the metal center. higher reaction rate compared to its anti isomer 5. All the four
Compared to commercial N,N′-diaryl substituted HGII, all the complexes were found to be less efficient than commercial
complexes displayed anodic shifts of the Ru(II)/Ru(III) redox HGII at a tenfold lower catalyst loading. Reactivity differences
potentials (90–150 mV), suggesting lower electron donating among the newly developed catalysts can be better appreci-
abilities of the related NHCs. Since similar values of redox ated in the RCM of the more encumbered diethyl allylmethal-
potentials were observed for both ruthenium complexes lylmalonate (10). As shown by the kinetic plots in Fig. 7, 4 and
bearing symmetrical and unsymmetrical NHCs with phenyl 5 were able to nearly complete the cyclization reaction (>97%
groups on the backbone, it is reasonable to ascribe the lower conversion) within 30 min, outperforming 6 and 7 which
donor ability mainly to the backbone substitution rather than reached plateau conversion values of 88 and 86%, respectively,
to the presence of N,N-dialkyl substituents.5j,9c The σ-donor after roughly 10 min. Moreover, while it seems that the nature
character of the NHCs of 4–7 was also estimated on the basis of the N-alkyl substituents has a role in modulating catalytic
This journal is © The Royal Society of Chemistry 2018
Dalton Trans.

View Article Online
Paper
Dalton Transactions
Fig. 8 RCM conversion of 12.
Fig. 6 RCM conversion of 8.
gave only 20% conversion within 60 min. Moreover, they proved
to have activities superior to most of the catalysts supported by
symmetrical N,N′-diaryl substituted NHCs.20
The above results seem to suggest that the RCM catalytic
behavior shown by these catalysts is essentially controlled by
steric factors. Indeed, as already reported in the literature,
most of the catalysts with encumbered NHC ligands21,5j,8b
speed up the RCM of unhindered olefins (such as diethyl di-
allylmalonate and diethyl allylmethallylmalonate) and slow
down the RCM of hindered olefins (such as diethyl dimethallyl-
malonate). Comparison among catalysts 4–7 seems to show
the same trend. Complexes 4–5, which appear to be more hin-
dered from topographic maps and %VBur values (%VBur = 30.9
and 31.0), give faster RCM of unhindered olefins compared to
6–7 (%VBur = 28.7 and 28.9), as well as slower RCM of hindered
olefins. This hypothesis is supported by the behavior of the
highly encumbered HGII (%VBur = 32.9), that outperforms cata-
lysts 4–7 in the RCM of 8 and 10, whereas it shows signifi-
cantly lower efficiency in the RCM of 12. On the other hand,
no correlation between the electronic properties of different
NHCs of 4–7 and the catalytic results can be easily established.
The catalytic performances of the newly synthesized com-
Fig. 7 RCM conversion of 10.
behavior, the different NHC backbone configurations (syn or plexes 4–7 were also compared in the RCM of ( )-linalool (14),
anti) seem to somewhat have an influence only on the a naturally occurring terpene alcohol, to form 1-methyl-
initiation rates of the catalysts. Again, lower catalyst efficiency cyclopent-2-en-1-ol and isobutylene, both representing valu-
with respect to HGII was registered.
able starting materials for the production of renewable fuels
In the most sterically demanding RCM of diethyl dimethallyl- and polymer products.22 In line of principle, the RCM of this
malonate (12) (Fig. 8), differently from the previous cyclization diolefin shows a significant steric deactivation because one
reaction, the catalytic performances of catalysts 6 and 7 were of the double bonds is trisubstituted and the other one is
superior to those of 4 and 5, displaying faster initiation and flanked by a tetrasubstituted carbon. However, the reaction is
faster reaction rates. The maximum value conversion (80%) facilitated by the activating effect of the allylic hydroxyl
was observed in the presence of 6; in fact catalyst 7, despite group which is able to interact with the catalytic center.23
the higher initiation rate, showed a significant decrease in the Anti complexes 5 and 7 turned out to be highly competent in
reaction rate after the first 10 min, reaching a plateau at this cyclization, giving full conversion in less than 2 min,
74% conversion. Interestingly, all the new catalysts were found while syn 6 behaves as HGII completing the reaction within
to be more efficient than commercially available HGII which 3 min (Fig. 9). The catalytic behavior of syn 4 was found
Dalton Trans.
This journal is © The Royal Society of Chemistry 2018

View Article Online
Dalton Transactions
Paper
benzene (16) and cis-1,4-diacetoxy-2-butene (17) was investi-
gated and the results are summarized in Table 2.
All of the catalysts furnished the desired cross-coupling
product 18 in very high yields (85–97%), displaying better
activities and lower E/Z ratios with respect to HGII. While
changing the nature of the N-substituents did not affect the
outcome of the reaction for syn catalysts 4 and 6 (entries 1 and
3), a different behavior was observed for anti catalysts 5 and 7
(entries 2 and 4), which exhibited different activities and
Z-selectivities.
We then decided to probe the activity of 4–7 in cross-meta-
thesis reactions involving biorenewable feedstocks as sub-
strates to produce polyfunctional compounds. As an example,
we selected the CM of eugenol acetate (19), a constituent of
clove oil, with cis-1,4-dichloro-2-butene (20). This cross-meta-
thesis led to the allylic chloride derivative 21 which can be sub-
sequently transformed into a variety of useful chemicals.24,25
The reaction was carried out using 3 equivalents of 20 with
respect to 19 (0.2 M) in the presence of 2.7 mol% of catalysts
under refluxing CH2Cl2 for 12 h. All the results, including data
for the CM performed using the benchmark catalyst HGII, are
shown in Table 3.
In all cases, no undesired product arising from self-
metathesis as well as from double-bond migration reactions
was detected, as already observed in the analogous cross-meta-
thesis of 19 with allyl-chloride.24 Catalysts 4–7 were found to be
more efficient than HGII, confirming that the presence of alkyl
N-substituents is beneficial for this class of reactions. In more
detail, 4 and 5 with N-neopentyl groups gave very low E/Z ratios,
compared to HGII and previously reported catalytic systems.24
Ethenolysis of fatty acid esters represents another example
of a cross-metathesis reaction that allows the selective conver-
sion of renewable feedstock to useful products with extensive
applications.26 We therefore tested catalysts 4–7 in the etheno-
lysis of ethyl oleate (Table 4) comparing their performance to
that of HGII at 50 °C using 500 ppm catalyst loading and 10
bar of ethylene.
Fig. 9 RCM conversion of 14.
to be somewhat different, since it reached a plateau at 94%
conversion after the first minute of the reaction, suggesting a
minor stability of this system with respect to all the other
ones, very likely as a consequence of a deleterious interaction
of the active species with the substrate or the product.
We next turned our attention to exploring the catalytic
potential of 4–7 in CM reactions. First, the model CM of allyl
Table 2 CM of 16 and 17 promoted by catalysts 4–7
Entry
Catalyst
38 yielda (%)
E : Zb
1
2
3
4
5
4
5
6
7
88
97
90
85
69
5.5
4.0
6.0
7.1
8.6
As shown in Table 4 (entries 1–4), all the catalysts were scar-
cely active and selective, affording lower yields, selectivities
and TONs with respect to HGII. These results not only point
out that the introduction of alkyl instead of aryl groups as
HGII
a Isolated yield. b E : Z ratios were determined by 1H NMR spectroscopy.
Table 3 CM of 19 and 20 promoted by catalysts 4–7
Entry
Catalyst
38 yielda (%)
E : Zb
1
2
3
4
5
4
5
6
7
88
70
84
77
52
2.8
3.2
5.4
5.4
7.4
HGII
a Isolated yield. b E : Z ratios were determined by 1H NMR spectroscopy.
This journal is © The Royal Society of Chemistry 2018
Dalton Trans.

View Article Online
Paper
Dalton Transactions
Table 4 Ethenolysis of 22 promoted by catalysts 4–7
All complexes proved to be suitable catalysts for this reac-
tion, especially 4, 5 and 7 which showed no reactivity differ-
ences, converting COD quantitatively in less than 3 min and
rivaling the performance of HGII. Catalyst 6 turned out as a
less efficient system, completing the ROMP reaction within
9 min. The E/Z ratios of the double bonds in the polymer
1
chains, determined by H and 13C NMR spectroscopy, fall in a
range between 1.4 and 1.8.
As a final investigation, we focused on the application of
chiral anti catalysts 5 and 7 in the desymmetrization of achiral
trienes 28 and 30 through asymmetric ring closing metathesis
(ARCM), which represents a powerful means to obtain enantio-
enriched carbo- and heterocycles.3,29 The results are summar-
ized in Table 5.
The first chiral ruthenium-based metathesis catalysts
having chiral C2-symmetric NHC ligands were synthesized and
evaluated in ARCM reactions by the Grubbs group (e.g. GII-C2,
Fig. 11).30 In these systems, the chiral information is trans-
ferred from the backbone of the NHC ligand to the metal
center through the N-bound aryl rings (gearing effect).31
Conversion zb
Entry Catalysta (%)
Selectivityc
(%)
Yieldd
(%)
TONe
1
2
3
4
5
4
5
6
7
50
28
25
49
71
35
37
32
20
43
18
10
8
10
30
350
207
160
196
600
HGII
a The reactions were run neat using 5.4 mmol of ethyl oleate at 150 psi
of ethylene. Dodecane (150 μL) was used as an internal standard.
b Determined by GC analysis. Conversion = 100 − (final moles of 22) ×
100/[initial moles of 22]. c Determined by GC analysis. Selectivity =
100 × (moles of ethenolysis products 23 + 24)/[(moles of 23 + 24) + (2 ×
moles of 25 + 26)]. d Yield = conversion × selectivity/100. e TON =
yield × (initial moles of 22/moles of catalyst)/100.
Table 5 ARCM of 28 and 30 with catalysts 5 and 7
N-substituents is detrimental for the performance of the cata-
lyst in this kind of metathesis reaction, but they provide
further evidence that such transformation is accomplished
efficiently only in the presence of ruthenium catalysts bearing
cyclic alkylaminocarbene (CAAC) ligands27 or, to a lesser
extent, with unsymmetrical NHCs.9c,28
Then, the catalytic performances of 4–7 were evaluated in
the ROMP of 1,5-cyclooctadiene (COD) carried out in C6D6, at
30 °C, in the presence of 0.1 mol% of catalyst. The reactions
were monitored by 1H NMR spectroscopy and the results are
depicted in Fig. 10. For comparison, the kinetic profile of the
ROMP promoted by the benchmark catalyst HGII is included.
Entrya Substrate Catalyst (mol%) Additive Yieldb (%) eec (%)
1
28
28
28
28
28
28
30
30
5 (2.5)
5 (4.0)
None
NaI
>98
>98
>98
>98
>98
>98
>98
>98
36 (S)
15 (R)
36 (R)
13 (R)
35 (S)
90 (S)
7 (S)
2
3
7 (2.5)
7 (4.0)
GII-C2 (2.5)
GII-C2 (4.0)
5 (2.5)
None
NaI
None
NaI
None
None
4
5d
6d
7
8
7 (2.5)
33 (S)
a Reactions without an additive were performed in CH2Cl2 at 40 °C for
2 h; reactions with NaI were carried out in THF at 40 °C for 2 h, after
stirring 5 and 7 in solution of NaI for 1 h at RT. b Yields were based on
NMR analysis. c Enantiomeric excesses determined by chiral GC.
d Taken from ref. 30b.
Fig. 10 ROMP conversion of 27.
Fig. 11 Grubbs’ catalyst bearing a C2-symmetric NHC.
Dalton Trans.
This journal is © The Royal Society of Chemistry 2018

View Article Online
Dalton Transactions
Paper
It should be highlighted that complexes 5 and 7 have the sulphate and then the solvent was removed under vacuum.
same NHC backbone substitution and configuration as the The product, obtained as a yellow oil, was purified using
Grubbs chiral catalyst GII-C2 (Fig. 11), but they differ in the column chromatography on silica gel (hexane/ethyl acetate 9/1)
nature of the amino side groups (alkyl instead of aryl groups). to afford a white solid.
Table 5 describes the results for the ARCM of model trienes 28
A (MW = 352.6 g mol−1) yield 94%. 1H NMR (CD2Cl2,
and 30 promoted by 5 and 7. The available data for the ARCM 300 MHz): δ 7.24–7.19 (o m, 10H, Ar–H); 3.67 (s, 2H, N–CH–
of 28 performed with the catalyst GII-C2 are also reported. CH–N); 2.12 (d, 3J = 0.7 Hz, 2H, –CH2–C(CH3)3); 2.07 (d, 3J =
Both catalysts 5 and 7 provided dihydrofuran 29 in quantitative 1.6 Hz, 2H, CH2–C(CH3)3); 0.77 (s, 18H, CH2–C(CH3)3). 13C{H}
yield and 36% ee, albeit disclosing opposite enantioselectivity NMR (CD2Cl2, 75 MHz): δ 142.1; 128.5; 127.9; 127.0; 69.1; 59.9;
(entries 1 and 3, Table 5). In more detail, catalyst 5 with neo- 31.4; 30.8; 27.5. ESI + MS: m/z = 353.1 (MH+). Anal. calcd for
pentyl N-substituents formed the same enantiomer as GII-C2, C24H36N2 (352.56): C, 81.76, H, 10.29, N, 7.95. Found: C, 81.82,
while 7 with the cyclohexyl N-substituent catalyst gave the H, 10.38, N, 7.89.
opposite one. In an attempt to improve the enantioselectivity
of 5 and 7 by increasing the bulkiness of the halide ligands 300 MHz): δ 7.28–7.26 (o m, 3H, Ar–H); 7.16–7.13 (o m, 3H, Ar–
B (MW = 352.6 g mol−1) yield 76%. 1H NMR (CDCl3,
3
3
from chloride to iodide, as described for GII-C2 (entries 5 and H); 3.68 (s, 2H, N–CH–CH–N); 2.37–2.26 (q, J = 11.1 Hz, J =
6),30b lower enantiomeric excesses were obtained (entries 2 8.2 Hz, 4H, CH2–C(CH3)3); 1.07 (s, 18H, CH2–C(CH3)3). 13C{H}
and 4). Moreover, in the ARCM reaction carried out in the pres- NMR (CD2Cl2, 75 MHz): δ 142.3; 128.0; 127.8; 126.7; 70.7; 60.2;
ence of 5, the inversion of the absolute configuration of 29 was 31.8; 27.9. ESI + MS: m/z = 353.3 (MH+). [α]D20 = −6.9° (c = 0.5 in
observed.
CH2Cl2). Anal. calcd for C24H36N2 (352.56): C, 81.76, H, 10.29,
These results confirm that the chiral substitution of the N, 7.95. Found: C, 81.84, H, 10.41, N, 7.88.
backbone is a key factor to achieve enantioinduction, albeit
C (MW = 376.6 g mol−1) yield 77%. 1H NMR (CDCl3,
low. Even more, they suggest that a rigorously defined steric 300 MHz): δ 7.28–7.20 (o m, 10H, Ar–H); 3.90 (s, 2H, N–CH–
environment around the metal, deriving from the arrangement CH–N); 2.12–2.07 (br t, 2H, N–CH(Cy)); 1.75–1.73 (o m, 2H,
of the N-substituents (and in part from the bulkiness of the Cy–H); 1.55–1.44 (o m, 10H, Cy–H); 1.06–0.91 (o m, 6H, Cy–H);
halide ligands), is crucial to define the stereochemical 0.77–0.75 (o m, 2H, Cy–H). 13C{H} NMR (CDCl3, 75 MHz):
outcome of the reaction. Indeed, neopentyl and cyclohexyl δ 142.0; 128.5; 128.2; 127.3; 65.1; 53.1; 34.8; 32.4; 26.2; 25.1;
N-substituents exhibit different degrees of adaptability and 24.7. ESI + MS: m/z = 377.4 (MH+). Anal. calcd for C26H36N2
consequently they may contribute to delineate the shape of the (376.58): C, 82.93, H, 9.64, N, 7.44. Found: C, 83.01, H, 9.68, N,
reactive pocket in a very different way. This appears to be 7.58.
evident also in the more challenging ARCM of 30 to form a tet-
rasubstituted cycloolefin, where again different enantio-
Synthesis of D
selectivities between 5 and 7 were observed. It is worth noting For the synthesis of D, a two-step procedure was used. In the
that, to the best of our knowledge, this represents the first first step, the monoalkylated diamine was prepared as pre-
example of ARCM of 30 promoted by chiral ruthenium cata- viously reported.9a A round bottom flask was charged with the
lysts bearing a C2-symmetric NHC ligand. In fact, only chiral diamine (1 eq.), cyclohexanone (3 eq.) and anhydrous methyl-
complexes with the C1 symmetric NHC ligands have been ene chloride (C = 0.1 M). The reaction mixture was stirred for
tested so far, affording low to moderate enantioselectivities 12 hours at room temperature over activated molecular sieves.
(up to 42% ee).9,32
After filtration, the solvent was removed under reduced
pressure and anhydrous methanol was added (C = 0.1 M). The
resulting solution was stirred at room temperature for
30 minutes and then diluted with methanol (C = 0.05 M as
final concentration). NaBH4 (4 eq.) was added portionwise
under a nitrogen atmosphere and the reaction mixture was
Experimental section
Synthesis of diamines A–C
Into a round bottom flask, under an inert atmosphere, the stirred for 3.5 h. After extraction from dichloromethane–water,
amine (1 eq.), anhydrous methylene chloride (C = 0.1 M) and the organic layer was dried over anhydrous sodium sulphate
activated molecular sieves were introduced. Then, the alkylat- and then the solvent was removed under vacuum to afford the
ing agent (pivalaldehyde, 5 eq. for A, 3 eq. for B; cyclohexa- monoalkylated diamine as a colourless oil (92%). In the
none, 10 eq. for C) was added. The reaction mixture was second step, the monoalkylated product was dissolved in
stirred under nitrogen for 48 hours at room temperature.
CHCl3 (C = 0.1 M) and reacted with cyclohexanone (10 eq.) in
After filtration and removal of the solvent under reduced the presence of two drops of HCOOH at 50 °C for 48 h. To the
pressure, the crude reaction product was diluted with dry resulting imine, after filtration and removal of the solvent
methanol (C = 0.1 M) and treated with NaBH4 (equimolar with under reduced pressure, dry methanol (C = 0.1 M) and NaBH4
respect to the alkylating agent, added in three portions). The (equimolar with respect to cyclohexanone, added in three por-
mixture was stirred at room temperature for 3.5 hours under tions) were added. The mixture was stirred at room tempera-
nitrogen. The crude product was extracted with water and ture for 3.5 hours under nitrogen. The crude product was
methylene chloride. The organic layer was dried over sodium extracted with water and methylene chloride. The organic layer
This journal is © The Royal Society of Chemistry 2018
Dalton Trans.

View Article Online
Paper
Dalton Transactions
was dried over sodium sulphate and then the solvent was 1.29–1.11 (o m, 8H, Cy–H). 13C{H} NMR (CDCl3, 100 MHz):
removed under vacuum. The product was obtained as a white δ 155.0; 136.8; 130.1; 126.6; 72.3; 57.8; 32.1; 31.1; 25.2; 25.0;
powder after purification by column chromatography (hexane/ 24.7. ESI + MS: m/z = 389.1 (MH+ − BF4−).
ethyl acetate 9/1).
[α]2D0
= 152.5° (c = 0.5 in CH2Cl2). Anal. calcd for
D (MW = 376.6 g mol−1) yield 64%. 1H NMR (CDCl3, C27H35BF4N2 (474.38): C, 68.36, H, 7.44, N, 5.91. Found: C,
400 MHz): δ 7.15–7.08 (o m, 6H, Ar–H); 7.03–7.01 (o m, 4H, 68.48, H, 7.47, N, 6.02.
Ar–H); 3.73 (s, 2H, N–CH–CH–N); 2.19 (br t, 2H, N–CH(Cy));
General procedure for the synthesis of ruthenium complexes
4–7
1.90–1.85 (o m, 4H, Cy–H); 1.63–1.47 (o m, 9H, Cy–H);
1.11–1.00 (o m, 7H, Cy–H). 13C{H} NMR (CDCl3, 100 MHz):
δ 142.7; 128.0; 127.8; 126.6; 66.4; 53.9; 35.1; 32.7; 26.3; 25.5; Under an inert atmosphere, a Schlenk tube was charged with
24.8. ESI + MS: m/z = 378.2 (MH+).
the tetrafluoroborate salt (1.2 eq.), the base (CF3(CH3)2COK for
[α]2D0 = −26.8° (c = 0.5 in CH2Cl2). Anal. calcd for C26H36N2 5 and CH3CH2(CH3)2COK for 4, 6 and 7, 1.2 eq.) and dry
(376.58): C, 82.93, H, 9.64, N, 7.44. Found: C, 82.98, H, 9.70, N, toluene (C = 0.026 M for 4, 6 and 7, C = 0.1 M for 5). After a
7.54.
few minutes, the first generation Hoveyda–Grubbs catalyst (0.5
eq.) was added. The reaction mixture was heated to 65 °C for
two hours (5) or for 50 minutes (4, 6 and 7) and was then puri-
Synthesis of imidazolinium salts E–H
Into a flask containing the diamine (1 eq.), triethyl orthofor- fied with column chromatography on silica gel (hexane/diethyl
mate (8 eq.) and NH4BF4 (1.2 eq.) were introduced. The reac- ether from 9/1 to 2/1) to afford the ruthenium catalysts as
tion mixture was stirred at 135 °C for 4 hours. The crude green solids.
product obtained as a brownish oil was washed with diethyl
ether and purified on column chromatography (hexane/ethyl 400 MHz): δ 18.48 (s, 1H, RuvCH–oOiPrC6H4); 7.64 (br s, 3H,
4 (MW = 682.7 g mol−1) yield 40%. 1H NMR (C6D6,
3
3
acetate 1/1). Imidazolinium salts were obtained as white Ar–H); 7.45 (d, J = 7.6 Hz, 1H, Ar–H); 7.26 (t, J = 8.1 Hz, 1H,
solids.
3
Ar–H); 7.10–6.73 (o m, 7H, Ar–H); 6.55 (d, J = 8.1 Hz, 2H, Ar–
E (MW = 450.4 g mol−1) yield 87%. 1H NMR (CDCl3, H); 5.55 (br s, 3H, N–CH–CH–N and N–CH(H)–C(CH3)3);
400 MHz): δ 8.82 (s, 1H, N–CH–N); 7.15 (br s, 5H, Ar–H); 6.91 4.88–4.70 (o m, 2H, O–CH(CH3)2 and N–CH(H)–C(CH3)3); 3.51
(br s, 4H, Ar–H); 5.70 (s, 2H, N–CH–CH–N); 3.79 (d, J = 14.3 (d, 3J = 14.0 Hz, 2H, N–CH2–C(CH3)3); 1.79 (br s, 6H, O–CH
3
Hz, 2H, N–CH2–C(CH3)3); 2.91 (d, 3J = 14.3 Hz, 2H, –CH2–C (CH3)2); 1.37–0.98 (o m, 18H, CH2–C(CH3)3). 13C{H} NMR
(CH3)3); 1.00 (s, 18H, CH2–C(CH3)3). 13C{H} NMR (CDCl3, (C6D6, 75 MHz): δ 286.2 (RuvCH–oOiPrC6H4); 210.9; 154.2;
100 MHz): δ 162.6; 131.4; 130.5; 130.1; 129.7; 73.0; 58.7; 34.4; 144.9; 122.6; 122.1; 113.7; 75.3; 29.4; 22.1. Anal. calcd for
28.9. ESI + MS: m/z = 363.1 (MH+ − BF4−). Anal. calcd for C35H46Cl2N2ORu (682.73): C, 61.57, H, 6.79, N, 4.10. Found: C,
C25H35BF4N2 (450.36): C, 66.67, H, 7.83, N, 6.22. Found: C, 61.68, H, 6.84, N, 4.15. ESI-FT-ICR (4-Cl): m/z = calc. 647.2342,
66.75, H, 7.90, N, 6.31.
found 647.23338.
F (MW = 450.4 g mol−1) yield 87%. 1H NMR (CDCl3,
5 (MW = 682.7 g mol−1) yield 62%. 1H NMR (C6D6,
250 MHz): δ 8.98 (s. 1H, N–CH–N); 7.54–7.52 (o m, 6H, Ar–H); 600 MHz): δ 18.71 (s, 1H, RuvCH–oOiPrC6H4); 7.63 (br s, 4H,
3
7.24–7.23 (o m, 4H, Ar–H); 5.05 (s, 2H, N–CH–CH–N); 3.67 (d, Ar–H); 7.53 (d, J = 7.6 Hz, 1H, Ar–H); 7.30–7.24 (o m, 5H, Ar–
3
3
3J = 14.5 Hz, 2H, N–CH2–C(CH3)3); 2.92 (d, 3J = 14.5 Hz, 2H, N– H); 7.08 (t, J = 7.8 Hz, 2H, Ar–H); 6.78 (t, J = 7.4 Hz, 1H, Ar–
3
CH2–C(CH3)3); 0.97 (s, 18H, CH2–C(CH3)3). 13C{H} NMR H); 6.57 (d, J = 8.3 Hz, 1H, Ar–H); 5.66 (br d, 1H, N–CH(H)–C
(CDCl3, 62.5 MHz): δ 160.9; 135.4; 130.5; 126.6; 75.6; 57.4; (CH3)3); 4.91 (br s, 3H, N–CH–CH–N and N–CH(H)–C(CH3)3);
33.2; 27.9. ESI + MS: m/z = 363.2 (MH+ − BF4 ). [α]D20 = 417.9 (c 4.73 (m, 1H, O–CH(CH3)2); 3.66 (br d, 1H, N–CH(H)–C(CH3)3);
−
= 0.5 in CH2Cl2). Anal. calcd for C25H35BF4N2 (450.36): C, 3.00 (br d, 1H, N–CH(H)–C(CH3)3); 1.77 (dd, 3J = 6.2 Hz, 6H,
66.67, H, 7.83, N, 6.22. Found: C, 66.74, H, 7.92, N, 6.28.
O–CH(CH3)2); 1.11 (br s, 9H, CH2–C(CH3)3); 0.88 (br s, 9H,
286.8
G (MW = 474.4 g mol−1) yield 91%. 1H NMR (CDCl3, CH2–C(CH3)3). 13C{H} NMR (C6D6, 125 MHz):
δ
300 MHz): δ 9.51 (s, 1H, N–CH–N); 7.08–7.05 (o m, 6H, Ar–H); (RuvCH–oOiPrC6H4); 209.8; 153.9; 145.4; 139.6; 130.0; 129.9;
6.89–6.86 (o m, 4H, Ar–H); 5.81 (s, 2H, N–CH–CH–N); 3.22 (br 129.2; 129.0; 128.7; 127.7; 127.2; 123.2; 123.0; 114.1; 76.6; 75.6;
t, 2H, N–CH(Cy)); 2.18–2.11 (o m, 3H, Cy–H); 2.05–1.98 (o m, 74.2; 61.5; 58.1; 34.0; 33.5; 29.5; 29.4; 22.9; 22.8; 22.7; 22.6.
4H, Cy–H); 1.86–1.83 (o m, 2H, Cy–H); 1.70–1.66 (o m, 2H, Cy– Anal. calcd for C35H46Cl2N2ORu (682.73): C, 61.57, H, 6.79, N,
H); 1.52–1.41 (o m, 4H, Cy–H); 1.28–1.01 (o m, 5H, Cy–H). 13C 4.10. Found: C, 61.65, H, 6.86, N, 4.14. ESI-FT-ICR (5-Cl): m/z =
{H} NMR (CDCl3, 75 MHz): δ 157.0; 131.6; 128.9; 128.6; 128.2; calc. 647.2342, found 647.23335.
68.4; 57.4; 32.1; 31.3; 25.4; 25.1; 24.8. ESI + MS: m/z = 389.1
6 (MW = 706.8 g mol−1) yield 60%. 1H NMR (C6D6,
(MH+ − BF4−). Anal. calcd for C27H35BF4N2 (474.38): C, 68.36, 400 MHz): δ 18.25 (s, 1H, RuvCH–oOiPrC6H4); 7.72–7.35 (o m,
3
H, 7.44, N, 5.91. Found: C, 68.44, H, 7.41, N, 6.08.
3H, Ar–H); 7.28 (t, J = 7.5 Hz, 1H, Ar–H); 6.93–6.79 (o m, 8H,
H (MW = 474.4 g mol−1) yield 87%. 1H NMR (CDCl3, Ar–H); 6.60 (d, 3J = 8.3 Hz, 1H, Ar–H); 6.54 (br s, 1H, Ar–H);
400 MHz): δ 8.78 (s, 1H, N–CH–N); 7.50–7.47 (o m, 6H, Ar–H); 5.27 (br s, 1H, N–CH(Cy)); 5.15 (s, 2H, N–CH–CH–N); 5.04 (br
7.23–7.20 (o m, 4H, Ar–H); 4.86 (s, 2H, N–CH–CH–N); 3.39 (tt, s, 1H, N–CH(Cy)); 4.76 (m, 1H, O–CH(CH3)2); 2.88 (br s, 1H,
3J = 3.6 Hz, 3J = 3.6 Hz, 2H, N–CH(Cy)); 2.04–2.01 (o m, 2H, Cy– Cy–H); 2.31 (br s, 1H, Cy–H); 2.03–1.66 (o m, 11H, O–CH(CH3)2
H); 1.90–1.83 (o m, 5H, Cy–H); 1.78–1.69 (o m, 5H, Cy–H); and Cy–H); 1.54–0.68 (o m, 13H, Cy–H). 13C{H} NMR (C6D6,
Dalton Trans.
This journal is © The Royal Society of Chemistry 2018

View Article Online
Dalton Transactions
Paper
100 MHz): δ 284.2 (RuvCH–oOiPrC6H4); 217.8; 154.2; 144.7; trienes. Even if modest enantioselectivities were observed, this
137.5; 129.8; 129.2; 122.7; 122.1; 113.6; 75.1; 68.0; 62.9; 61.7; study confirms the relevance of the backbone configuration to
33.9; 26.4; 25.6; 22.2. Anal. calcd for C37H46Cl2N2ORu (706.75): give enantioinduction and suggests also that the different
C, 62.88, H, 6.56, N, 3.96. Found: C, 62.94, H, 6.79, N, 4.07. nature of N-alkyl groups may influence the stereochemical
ESI-FT-ICR (6-Cl): m/z = calc. 671.2342, found 671.2332.
outcome of the reaction. We are currently exploring alternative
7 (MW = 706.8 g mol−1) yield 53%. 1H NMR (C6D6, pathways for the synthesis of new N,N′-dialkyl NHC architec-
400 MHz): δ 18.43 (s, 1H, RuvCH–oOiPrC6H4); 7.53 (d, 3J = 6.5 tures, including the unsymmetrical ones, to provide new
3
Hz, 4H, Ar–H); 7.32–7.23 (o m, 6H, Ar–H); 7.10 (t, J = 7.4 Hz, opportunities in catalyst design and metathesis applications.
3
3
2H, Ar–H); 6.82 (t, J = 7.5 Hz, 1H, Ar–H); 6.59 (d, J = 8.4 Hz,
1H, Ar–H); 5.57 (br s, 1H, N–CH(Cy)); 5.05 (br s, 1H, N–CH
(Cy)); 4.75 (m, 1H, O–CH(CH3)2); 4.48 (s, 2H, N–CH–CH–N); Conflicts of interest
3
2.57 (br s, 2H, Cy–H); 2.04 (br s, 2H, Cy–H); 1.80 (dd, J = 6.1
There are no conflicts to declare.
Hz, 6H, O–CH(CH3)2); 1.67–0.63 (o m, 18H, Cy–H). 13C{H}
NMR (C6D6, 100 MHz): δ 286.2 (RuvCH–oOiPrC6H4); 211.0;
154.3; 145.0; 129.5; 129.3; 122.7; 122.2; 113.8; 29.5; 22.2; 21.7.
Anal. calcd for C37H46Cl2N2ORu (706.75): C, 62.88, H, 6.56, N,
Acknowledgements
3.96. Found: C, 62.96, H, 6.77, N, 4.05. ESI-FT-ICR (7-Cl): m/z =
calc. 671.2342, found 671.2349.
The authors thank Dr Patrizia Iannece and Dr Patrizia Oliva
for technical assistance. Mr Raffaele Contino, who performed
some experiments, is kindly acknowledged. This work was
financed by the Ministero dell’Università e della Ricerca
Conclusions
Scientifica e Tecnologica. Financial support from POR
CAMPANIA FESR 2007/2013 O.O. 2.1. – CUP B46D14002660009
“Il potenziamento e la riqualificazione del sistema delle infra-
strutture nel settore dell’istruzione, della formazione e della
ricerca” is gratefully acknowledged.
In conclusion, we have prepared four new stable Hoveyda–
Grubbs second generation catalysts featuring symmetrically
N-alkyl substituted NHCs with neopentyl or cyclohexyl groups
at the nitrogens and phenyl substituents on the backbone in a
syn or an anti stereochemical relationship (4–7). Synthetic
access to these complexes and their isolation were strongly
facilitated by the introduction of suitable backbone substi-
tution, which allowed obtaining, for the first time, olefin meta-
thesis ruthenium catalysts bearing saturated NHCs with
primary N-alkyl groups (4, 5). This finding opens the way to
the development of new ligands with significantly different
encumbrance around the metal. A detailed description of 4–7
was provided in terms of steric and electronic differences of
their NHC ligands. According to %VBur analysis, N,N′-dineo-
pentyl substituted NHCs of 4 and 5 were found to offer a more
pronounced and asymmetrically distributed steric hindrance
around the metal with respect to N,N′-dicyclohexyl NHCs of 6
and 7, which, on the other hand, exhibited better electron
donating properties, as evidenced by electrochemical studies.
As for the NHC backbone configuration, no remarkable effect
was observed. A comparison of the catalytic properties of 4–7
with those of the reference catalyst (HGII) revealed that they
give better performances in most of the explored transform-
ations. In particular, they were found to be more competent
for the RCM reactions leading to the formation of a tetrasub-
stituted double bond and for CM reactions, for which
improved Z-selectivities were also observed, especially in the
CM of eugenol acetate with cis-1,4-dichlorobutene. While RCM
activities appear to be mainly related to the bulkiness of the
N-groups, CM activities and selectivities seem to be dependent
also on the relative orientation of substituents on the NHC
backbone, although to a lesser extent and following a trend
more difficult to interpret. Catalysts 5 and 7 bearing chiral C2
symmetric NHCs were tested in the ARCM of model achiral
References
1 (a) H.-W. Wanzlick and H.-J. Schönherr, Angew. Chem., Int.
Ed. Engl., 1968, 7, 141; (b) K. Öfele, J. Organomet. Chem.,
1968, 12, P42.
2 (a) E. Peris, Chem. Rev., DOI: 10.1021/acs.chemrev.6b00695;
(b) D. Jansenn-Müller and F. Glorius, Chem. Soc. Rev., 2017,
46, 4845; (c) D. M. Flanigan, F. Romanov-Michailidis,
N. A. White and T. Rovis, Chem. Rev., 2015, 115, 9307;
(d)
N-Heterocyclic
Carbenes:
Effective
Tools
for
Organometallic Synthesis, ed. S. P. Nolan, Wiley-VCH, 2014;
(e) M. N. Hopkinson, C. Richter, M. Schedler and
F. Glorius, Nature, 2014, 510, 485; (f) C. S. J. Cazin,
N-Heterocyclic Carbenes in Transition Metal Catalysis and
Organocatalysis, Springer, 2011; (g) D. Enders, O. Niemeier
and A. Henseler, Chem. Rev., 2007, 107, 5606;
(h) N-Heterocyclic Carbenes in Transition Metal catalysis, ed.
F. Glorius, Springer-Verlag, Berlin, Germany, 2007;
(i) A. Correa, S. P. Nolan and L. Cavallo, Top. Curr. Chem.,
2011, 302, 131; ( j) N-Heterocyclic Carbenes, ed. S. Díez-
González, Royal Society of Chemistry, 2011; (k) D. Enders
and A. Grossmann, Angew. Chem., Int. Ed., 2012, 51, 314;
(l) L. Benhamou, E. Chardon, G. Lavigne, S. Bellemin-
Laponnaz and V. César, Chem. Rev., 2011, 111, 2705;
A. T. Biju, N. Kuhl and F. Glorius, Acc. Chem. Res., 2011, 44,
1182; (m) M. Fevre, J. Pinaud, Y. Gnanou, J. Vignolle and
D. Taton, Chem. Soc. Rev., 2013, 42, 2142.
3 (a) R. H. Grubbs, A. G. Wenzel, D. J. O’Leary and
E. Khosravi, Handbook of Metathesis, Wiley-VCH,
This journal is © The Royal Society of Chemistry 2018
Dalton Trans.

View Article Online
Paper
Dalton Transactions
Weinheim, Germany, 2nd edn, 2015; (b) Olefin Metathesis 13 M. N. Burnett and C. K. Johnson, ORTEP III, Oak Ridge
Theory and Practice, ed. K. Grela, J. Wiley & Sons, Hoboken,
NJ, 2014.
National Laboratory, Oak Ridge, TN, 1996; Report
ORNL-6895.
4 (a) G. C. Vougioukalakis and R. H. Grubbs, Chem. Rev., 14 L. Falivene, R. Credendino, A. Poater, A. Petta, L. Serra,
2010, 110, 1746; (b) C. Samojlowicz, M. Bieniek and
K. Grela, Chem. Rev., 2009, 109, 3708.
R. Oliva, V. Scarano and L. Cavallo, Organometallics, 2016,
35, 2286 %VBur is a parameter to quantify the steric hin-
drance of NHC ligands defined as the fraction of the total
volume of a sphere centered on the metal occupied by a
given ligand: (a) R. Dorta, E. D. Stevens, N. M. Scott,
C. Costabile, L. Cavallo, C. D. Hoff and S. P. Nolan, J. Am.
Chem. Soc., 2005, 127, 2485; (b) L. Cavallo, A. Correa,
C. Costabile and H. Jacobsen, J. Organomet. Chem., 2005,
690, 5407.
5 Selected examples: (a) T. J. Seiders, D. W. Ward and
R. H. Grubbs, Org. Lett., 2001, 3, 3225; (b) T. Ritter,
M. W. Day and R. H. Grubbs, J. Am. Chem. Soc., 2006, 128,
11768; (c) I. C. Stewart, T. Ung, A. A. Pletnev, J. M. Berlin,
R. H. Grubbs and Y. Schrodi, Org. Lett., 2007, 9, 1589;
(d) J. M. Berlin, K. Campbell, T. Ritter, T. W. Funk,
A. Chlenov and R. H. Grubbs, Org. Lett., 2007, 9, 1339;
(e) C. K. Chung and R. H. Grubbs, Org. Lett., 2008, 10, 15 M. M. Wu, A. M. Gill, L. Yunpeng, L. Falivene, L. Yongxin,
2693; (f) K. M. Kuhn, J.-B. Bourg, C. K. Chung, S. C. Virgil
and R. H. Grubbs, J. Am. Chem. Soc., 2009, 131, 5313;
R. Ganguly, L. Cavallo and F. Garcìa, Dalton Trans., 2015,
44, 15166.
(g) M. Gatti, L. Vieille-Petit, X. Luan, R. Mariz, E. Drinkel, 16 M. Süßner and H. Plenio, Chem. Commun., 2005, 43,
A. Linden and R. Dorta, J. Am. Chem. Soc., 2009, 131, 9498; 5417.
(h) L. Vieille-Petit, X. Luan, M. Gatti, S. Blumentritt, 17 (a) K. Verlinden, H. Buhl, W. Frank and C. Ganter,
A. Linden, H. Clavier, S. P. Nolan and R. Dorta, Chem.
Commun., 2009, 3783; (i) T. Savoie, B. Stenne and
Eur. J. Inorg. Chem., 2015, 2416; (b) M. Ruamps, N. Lugan
and V. César, Organometallics, 2017, 36, 1049.
S. K. Collins, Adv. Synth. Catal., 2009, 351, 1826; 18 H. A. Bent, Chem. Rev., 1961, 61, 275.
( j) A. Perfetto;, V. Bertolasi;, C. Costabile;, V. Paradiso;, 19 (a) H. Jacobsen, A. Correa, C. Costabile and L. Cavallo,
T. Caruso;, P. Longo; and F. Grisi, RSC Adv., 2016, 6, 95793.
6 (a) N. Ledoux, B. Allaert, S. Pattyn, H. V. Mierde,
C. Vercaemst and F. Verpoort, Chem. – Eur. J., 2006, 12,
4654; (b) N. Ledoux, A. Linden, B. Allaert, H. V. Mierde and
F. Verpoort, Adv. Synth. Catal., 2007, 349, 1692; (c) F. Grisi,
J. Organomet. Chem., 2006, 691, 4350; (b) H. Jacobsen,
A. Correa, A. Poater, C. Costabile and L. Cavallo, Coord.
Chem. Rev., 2009, 253, 687; (c) J. A. M. Lummiss,
C. S. Higman, D. L. Fyson, R. McDonald and D. E. Fogg,
Chem. Sci., 2015, 6, 6739.
C. Costabile, E. Gallo, A. Mariconda, C. Tedesco and 20 N. Mukherjee, S. Planer and K. Grela, Org. Chem. Front.,
P. Longo, Organometallics, 2008, 27, 4649. 2018, 82, 494.
7 (a) A. Poater, F. Ragone, S. Giudice, C. Costabile, R. Dorta, 21 T. Ritter, A. Hejl, A. G. Wenzel, T. W. Funk and
S. P. Nolan and L. Cavallo, Organometallics, 2008, 27, 2681; R. H. Grubbs, Organometallics, 2006, 25, 5740.
(b) M. B. Dinger, P. Nieczypor and J. C. Mol, 22 Selected examples: (a) H. A. Meylemans, R. L. Quintana,
Organometallics, 2003, 22, 5291.
B. R. Goldsmith and B. G. Harvey, ChemSusChem, 2011, 4,
465; (b) R. Alcántara, E. Alcántara, L. Canoira, M. J. Franco,
M. Herera and A. Navarro, React. Funct. Polym., 2000, 45,
19; (c) J. W. Yoon, S. H. Jhung, T.-J. Kim, H.-D. Lee,
N. H. Jang and J.-S. Chang, Bull. Korean Chem. Soc., 2007,
28, 2075; (d) Y. Li, Y. Wu, L. Liang, Y. Li and G. Wu,
Chin. J. Polym. Sci., 2010, 28, 55; (e) V. Vasilenko,
A. N. Frolov and S. V. Kostjuk, Macromolecules, 2010, 43,
5503; (f) J. S. Chickos, A. E. Wentz and D. Hillesheim-Cox,
Ind. Eng. Chem. Res., 2003, 42, 2874–2877.
8 (a) F. Grisi, A. Mariconda, C. Costabile, V. Bertolasi and
P. Longo, Organometallics, 2009, 28, 4988; (b) C. Costabile,
A. Mariconda, L. Cavallo, P. Longo, V. Bertolasi, F. Ragone
and F. Grisi, Chem. – Eur. J., 2011, 17, 8618; (c) A. Perfetto,
C. Costabile, P. Longo, V. Bertolasi and F. Grisi, Chem. –
Eur. J., 2013, 19, 10492; (d) A. Perfetto, C. Costabile,
P. Longo and F. Grisi, Organometallics, 2014, 33, 2747.
9 (a) V. Paradiso, V. Bertolasi and F. Grisi, Organometallics,
2014, 33, 5932; (b) V. Paradiso, V. Bertolasi, C. Costabile
and F. Grisi, Dalton Trans., 2016, 45, 561; (c) V. Paradiso, 23 T. R. Hoye and H. Zhao, Org. Lett., 1999, 1, 1123.
V. Bertolasi, C. Costabile, F. Grisi, T. Caruso, M. Dąbrowski, 24 H. Bilel, N. Hamdi, F. Zagrouba, C. Fischmeister and
K. Grela and F. Grisi, Organometallics, 2017, 36, 3692.
C. Bruneau, Catal. Sci. Technol., 2014, 4, 2064.
10 V. Paradiso, C. Costabile and F. Grisi, Molecules, 2016, 21, 117. 25 Some examples of functionalized allyl chlorides as value
11 (a) L. H. Peeck and H. Plenio, Organometallics, 2010, 29,
2761; (b) S. Wolf and H. Plenio, Green Chem., 2011, 13,
2008; (c) C. S. Higman, S. A. Rufh, R. McDonald and
D. E. Fogg, J. Organomet. Chem., 2017, 847, 162.
added chemical intermediates are reported in:
(a) M. Bandini, P. G. Cozzi, S. Licciulli and A. Umani-
Ronchi, Synthesis, 2004, 3, 409; (b) T. Jacobs, A. Rybak and
M. A. R. Meier, Appl. Catal., A, 2009, 353, 32.
12 The synthesis of 4–7 was accomplished by using both pot- 26 (a) J. C. Mol, Green Chem., 2002, 4, 5; (b) S. Chikkali and
assium hexafluoro-t-butoxide or potassium t-amylate for
the deprotonation in situ of the related NHC salts. In this
work, we reported the most successful synthetic route
identified for each catalyst.
S. Mecking, Angew. Chem., Int. Ed., 2012, 51, 5802;
(c) L. Montero de Espinosa and M. A. R. Meier, Top.
Organomet. Chem., 2012, 39, 1; (d) J. Bidange,
C. Fischmeister and C. Bruneau, Chem. – Eur. J., 2016, 22,
Dalton Trans.
This journal is © The Royal Society of Chemistry 2018

View Article Online
Dalton Transactions
Paper
12226; (e) J. Spekreijse, J. P. M. Sanders, J. H. Bitter and 28 R. M. Thomas, B. K. Keitz, T. M. Champagne and
E. L. Scott, ChemSusChem, 2017, 10, 470. R. H. Grubbs, J. Am. Chem. Soc., 2011, 133, 7490.
27 (a) D. R. Anderson, V. Lavallo, D. J. O’Leary, G. Bertrand 29 (a) T. Patrick Montgomery, A. M. Johns and R. H. Grubbs,
and R. H. Grubbs, Angew. Chem., Int. Ed., 2007, 46, 7262;
(b) D. R. Anderson, T. Ung, G. Mkrtumyan, G. Bertrand and
R. H. Grubbs, Organometallics, 2008, 27, 563; (c) Y. Schrodi,
Catalysts, 2017, 7, 87; (b) S. Kress and S. Blechert, Chem.
Soc. Rev., 2012, 41, 4389; (c) A. H. Hoveyda and
R. R. Schrock, Chem. – Eur. J., 2001, 7, 945.
T. Ung, A. Vargas, G. Mkrtumyan, W.-C. Lee, 30 (a) T. J. Seiders, D. W. Ward and R. H. Grubbs, Org. Lett.,
T. M. Champagne, R. L. Pederson and S. H. Hong, Clean:
Soil, Air, Water, 2008, 36, 669; (d) J. Zhang, S. Song,
2001, 3, 3225; (b) T. W. Funk, J. M. Berlin and
R. H. Grubbs, J. Am. Chem. Soc., 2006, 128, 1840.
X. Wang, J. Jiao and M. Shi, Chem. Commun., 2013, 49, 31 C. Costabile and L. Cavallo, J. Am. Chem. Soc., 2004, 126,
9491; (e) V. M. Marx, A. H. Sullivan, M. Melaimi, 9592.
S. C. Virgil, B. K. Keitz, D. S. Weinberger, G. Bertrand and 32 (a) B. Stenne, J. Timperio, J. Savoie, T. Dudding and
R. H. Grubbs, Angew. Chem., Int. Ed., 2015, 54, 1919;
(f) R. Gawin, A. Kozakiewicz, P. A. Guńka, P. Dąbrowski
and K. Skowerski, Angew. Chem., Int. Ed., 2017, 56, 981.
S. K. Collins, Org. Lett., 2010, 12, 2032; (b) V. Paradiso,
S. Menta, M. Pierini, G. Della Sala, A. Ciogli and F. Grisi,
Catalysts, 2016, 6, 177.
This journal is © The Royal Society of Chemistry 2018
Dalton Trans.