A versatile and highly Z -Selective olefin metathesis ruthenium catalyst based on a readily accessible N -heterocyclic carbene

Article abstract of DOI:10.1021/acscatal.8b00151

A ruthenium catalyst for Z-selective olefin metathesis has been synthesized from a readily accessible N-heterocyclic carbene (NHC) ligand that is prepared using an efficient, practical, and scalable multicomponent synthesis. The desired ruthenium complex

Full text of DOI:10.1021/acscatal.8b00151

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A Versatile and Highly Z-Selective Olefin Metathesis Ruthenium
Catalyst Based on a Readily Accessible N-Heterocyclic Carbene
Adrien Dumas, Robert Tarrieu, Thomas Vives, Thierry
Roisnel, Vincent Dorcet, Olivier Baslé, and Marc Mauduit
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ACS Catalysis
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A Versatile and Highly Z-Selective Olefin Metathesis Ruthenium
Catalyst Based on a Readily Accessible N-Heterocyclic Carbene.
Adrien Dumas, †,‡ Robert Tarrieu,† Thomas Vives, † Thierry Roisnel,§ Vincent Dorcet,§ Olivier Baslé*,†,
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and Marc Mauduit*,†
† Univ Rennes, Ecole Nationale Supérieure de Chimie de Rennes, CNRS, ISCR - UMR 6226, F-35000 Rennes, France.
‡ DEMETA SAS, 6 rue Pierre-Joseph Colin, 35000 Rennes, France
§ Univ Rennes, CNRS, ISCR - UMR 6226, F-35000 Rennes, France.
ABSTRACT: A ruthenium catalyst for Z-selective olefin metathesis has been synthesized from a readily accessible N-heterocyclic
carbene (NHC) ligand that is prepared thanks to an efficient, practical and scalable multicomponent synthesis. The desired rutheni-
um complex with cyclometalated NHC ligand is obtained by means of selective C(sp3)-H activation at the adamantyl fragment and
X-ray diffraction analysis unambiguously confirmed the structure of the precatalyst. The catalyst demonstrated attractive catalytic
performance in self- and cross-metathesis at low catalyst loading to afford the desired internal olefins with high conversion and
very high Z-selectivity (up to >99%). The versatility of the chelated catalyst is illustrated by the high cis-selectivity (up to >98%)
and high tacticity control (up to >98% syndiotactic) achieved in ring-opening-polymerization, allowing for the production of highly
microstructurally controlled norbornene, norbornadiene and cyclopropene-derived polymers.
KEYWORDS: Olefin metathesis, Z-selective catalyst, Syndiotactic polymers, NHC ligand, Ruthenium Complex.
During the last two decades, olefin metathesis has evolved
to become a highly versatile tool for the construction of C-C
double bonds.1 The development of efficient and robust transi-
tion metal-based catalysts for olefin metathesis has allowed
important applications in natural product synthesis,2 biochem-
istry3 and material science.4 Among the key advances, the
incorporation of N-heterocyclic carbenes (NHC) as ancillary
ligands has enabled new generations of ruthenium-based cata-
lysts with improved properties.5 In the recent years, particular
attention has been given to the development of Ru-based com-
plexes capable of Z-selective olefin metathesis,6, 2b as an alter-
native to more sensitive W-,7 and Mo-based catalysts.8 Attrac-
tive applications in selective olefin metathesis transformations
have been achieved with unsymmetrical NHC ligands,9 and
recent breakthrough works by Grubbs and co-workers evi-
denced the benefits provided by a chelating unsymmetrical
NHC ligand in ruthenium-catalyzed Z-selective olefin metath-
esis transformations,10 that opened the door to the develop-
ment of catalysts with improved activity and Z-selectivity.11
The most efficient cyclometalated Z-selective ruthenium cata-
lyst Ru-1 was recently obtained using the unsymmetrical
saturated NHC ligand combining a N-adamantyl and a bulky
N-2,6-diisopropylphenyl (Dipp) group (Figure 1).12 Indeed,
catalyst Ru-1 delivered exceptional level of Z-selectivity in
broad scope of transformations,6b with the exception of ring-
opening-cross metathesis.13 Nevertheless, and despite the
advantageous properties conferred to the cyclometalated-metal
species by this unsymmetrical NHC, the cost arising from the
multi-step synthesis of such ligands may render their use pro-
hibitive for industrial applications.14 In fact, the ligands sur-
rounding the metal are the most expensive component of a (Z-
selective) metathesis catalyst. This is reinforced by the fact
that despite the metal, the ligands cannot be recycled. There-
fore, the development of readily accessible NHC ligand for the
design of new ruthenium-based catalyst displaying high versa-
tility and high selectivity in the production of Z-olefins is of
high interest. Recently, we described a practical and efficient
multicomponent procedure for the highly selective synthesis
of unsymmetrical unsaturated NHC ligand precursors that
provide a cost-effective alternative to the multistep synthesis
of their saturated analogues.15 Notably, this approach allows
for the straightforward preparation at multi-gram scale in good
yield of the unsymmetrical imidazolium salt 1 bearing the N-
Dipp and N-adamantyl substituents (Figure 1). Herein, we
report on the synthesis of a new chelated ruthenium-based
catalyst incorporating an unsymmetrical unsaturated NHC,
which demonstrated its great versatility and high selectivity in
the construction of internal Z-olefins. Moreover, no modifica-
tion of the Ru-based catalyst is required to produce highly
tactic polymers (up to >98% syndiotactic) with very high cis-
content (up to >98%).
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Previous work (Grubbs et al.):
This work:
BF4
BF4
Glyoxal
Folmaldehyde, AcOH
10 min, 40°C
1
2
3
4
NH2
N
N
N
N
+
then KBF4
1
H2N
4 steps synthesis
Modest overall yield (<20%)
Multicomponant synthesis at multi-gram scale
95% selectivity, 75% yield
5
6
7
8
cost effective catalyst
with
improved performances
N
N
N
N
Reaction
Product
9
O
O
Ru
O
Ru
O
up to >99% cis
up to >98% cis
Figure 2. Solid-state structure of complex C1 (left) and complex
SM
CM
N
N
O
O
O
O
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Ru-2 (right) from single crystal X-ray diffraction. Displacement
ellipsoids are drawn at 50% probability. Most hydrogen atoms
have been omitted for clarity (N in blue, C in grey, Cl in green, O
in red, H in white. For complex C1: distance between C27 and Ru
= 2.89 Å. For complex Ru-2: distance between C27 and Ru =
2.06 Å.
up to >98% cis &
up to >98% syndiotactic
(Ru-2)
Z-selective catalyst
ROMP
(Ru-1)
Z-selective catalyst
Figure 1. Highly Z-selective ruthenium catalyst Ru-1 based on
the saturated unsymmetrical NHC precursor (left). New synthetic
approach to the lower-cost highly Z-selective ruthenium catalyst
Ru-2 (right). Self-metathesis (SM), cross-metathesis (CM), ring-
opening-cross metathesis (ROMP).
The efficiency of this new catalyst was first evaluated in the
self-metathesis of an unfunctionalized terminal olefin;11a i.e 1-
dodecene (Table 1). Interestingly, the catalyst Ru-2 demon-
strated excellent catalytic performances at low 0.1 mol% cata-
lyst loading and afforded after 2 hours the desired internal
olefin with 88% conversion and with very high >99% selectiv-
ity towards primary metathesis products (PMP).19 Further-
more, high 98% Z-selectivity could be maintained at high
conversion without any detectable amount of undesired olefin
walking product, suggesting good stability of the cyclomet-
alated catalyst Ru-2 (Table 1, entry 3).
We initiated our study by the preparation of complex Ru-2
incorporating our readily accessible unsymmetrical unsaturat-
ed NHC ligand combining the N-Dipp and N-adamantyl sub-
stituents. First, deprotonation of the tetrafluoroborate imidazo-
lium salt 1 with potassium bis(trimethylsilyl)amide (KHMDS)
followed by the addition of a stoichiometric amount of the first
generation Hoveyda-Grubbs complex (HGI) afforded the
expected second generation type complex C1 with good 78%
isolated yield (Scheme 1). X-ray diffraction analysis of this
new species allowed us to confirm the prerequisite close prox-
imity between the ruthenium center and the adamantyl C-H
bond (2.89 Å) (Figure 2, left).16 Serenely, the cyclometalation
procedure by means of carboxylate-assisted C-H bond activa-
tion strategy was engaged in the presence of an excess of
sodium pivalate (Scheme 1).17 Isolation and full characteriza-
tion, including X-ray crystallography of the stable nitrato-
complex Ru-2 confirmed the five-membered chelating archi-
tecture, which is critical for successful stereoselectivity in
catalysis (Figure 2, right).18
Table 1. Evaluation of Catalyst Ru-2 in the Self-Metathesis
of 1-Dodecenea
Ru-2 (0.1 mol%)
9
+
9
THF,
35 °C, time (h)
9
3
4
PMP-selectivity
(%)
entry
time (h) Conv. (%) Z:E ratio
1
2
3
4
1
2
76
88 (82)b
95
>99:1
>99:1
98:2
>99
>99
>99
>99
Scheme 1. NaOPiv-Mediated C(sp3)-H Activation at the
Adamantly Fragment to Form the Cyclometalated Ru-2
Complex
6
22
98
98:2
aConversions, molar ratio of E and Z isomers, and PMP-
selectivity were monitored by GC analysis using tetradecane as
internal standard. bIsolated yield
1) NaOPiv (10 equiv)
THF, MeOH, 55 °C
48h
N
N
N
N
1) KHMDS,
Tol, rt, 0.5h
Cl
Cl
O
Ru
O
1
The efficiency of our new catalyst was further evaluated in
the homometathesis of two more challenging substrates (Table
2). First, while modest reactivity is generally observed for
substrates with allylic functionality,11a,d the efficiency of the
catalyst was illustrated in the self-metathesis of allylacetate to
produce the desired self-metathesis product 6a in high conver-
sion (>98%) and high 97% Z-selectivity with very little al-
teration of the product configuration after an extended period
of time (table 2, entry 4). Regarding allylbenzene, which is
easily isomerized to β-methylstyrene, Ru-2 homometathesized
allylbenzene with full conversion and excellent 97% Z-
selectivity after 6h with very low amount (<5%) of allylben-
zene isomerization (Table 2, entry 7). It is important to note
that very similar behaviors were described with catalyst Ru-1,
which afforded the self-metathesis products 6a and 6b with
very comparable rate of conversion and selectivity.
Ru
O
2) NH4NO3 (15 equiv)
THF, 12h
N
O
2) HGI, Tol,
40 °C, 0.5h
O
Ru-2
C1
78% Isolated yield
43% yield over two steps
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Table 2. Self-Metathesis of Allylacetate and Allylbenzene
94% cis-epoxy content.25 While cyclometalated Ru-based
1
2
3
4
5
6
7
8
catalysts proved inefficient in reacting internal olefins with
trans configuration, the substrate scope for cross-metathesis
with this family of catalysts is not restricted to terminal ole-
fins.26 Indeed symmetrical internal Z-olefins can be useful
coupling partners in such transformations. The CM reaction
between allyl benzene (5b) and cis-1,4-diacetoxybutene (11)
afforded the desired unsymmetrical internal olefin 16 in good
yield and with high 95:5 Z:E ratio.
Ru-2 (0.1 mol%)
R
R
+
THF,
35 °C, time (h)
5
6
R
entry
substrate
time (h)
Conv. (%)a
70
Z:E ratiob
98:2
1
2
3
4
5
6
7
8
R = OAc (5a)
R = Ph (5b)
1
2
93
97:3
4
>98 (89)c
97:3
9
Scheme 2. Z-selective Cross-Metathesis with Ru-2
8
>98
96:4
10
11
12
13
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1
84
96(90)c
>99:1
98:2
Ru-2 (1 mol%)
R3
+
R2
R1
R1
R3
m
9
THF,
35 °C, time (h)
3
9: R1 = CH2-CH2OAc; R2 =H
10: R1 = BPin; R2 =H
11: R1 = R2 =CH2OAc
6
>98
97:3
20
>98
85:15
aDetermined by 1H NMR spectroscopy. bMolar ratio of E and Z
HO
B
O
O
AcO
3
9
9
2
7
12
13
isomers were determined by GC. cIsolated Yields.
14
3h, 73% yielda
6.5 h, 78% yielda
6 h, 66% yielda
95:5 Z:E b
97:3 Z:Eb
97:3 Z:E b
Ruthenium-based olefin metathesis catalysts have demon-
strated variable degree of stability in the presence of alco-
hols.20 In fact, the free hydroxyl-function may participate in
catalyst deactivation and/or decomposition into isomerization
active species such as ruthenium hydrides.21 Therefore, 4-
pentanol was established as a particularly challenging bench-
mark substrate for cylometalated ruthenium catalysts, which
demonstrated low activities and/or major erosion of Z-
selectivity.22 Interestingly, catalyst Ru-2 afforded good cata-
lytic activity in the self-metathesis of 4-pentenol (7), while
attaining and maintaining high Z-selectivity at high conver-
sion, surpassing all previously described Z-selective cyclomet-
alated catalysts, notably Ru-1 (Table 3).
Tenebrio molitor
pheromone
O
AcO
Ph
9
15
16
51% yield (3 steps)a
5h, 60% yielda
95:5 Z:E b
94:6 Z:E b
Disparlure pheromone
aIsolated yields. bDetermined by 1H NMR spectroscopy.
Recently, Z-selective Ru-based catalysts have demonstrated
their capacity to produce norbornene and norbornadiene-
derived polymers with specific microstructures.27 Neverthe-
less, while high cis-selectivity is often attained with cyclomet-
alated Ru-based catalyst, the production of polymers exhibit-
ing high tacticity is more challenging and requires special
catalyst design. In fact, Grubbs and co-workers demonstrated
that a modification of the chelating fragment by replacement
of the N-adamantyl substituent for the less encumbered N-tert-
butyl group allowed for lower unfavorable interactions that
resulted in higher syndioselectivity,13 but at the expense of
catalyst stability.27b A close look at the structural parameters of
complex Ru-2 and comparison with the crystal structure of the
previously reported complex Ru-1 evidenced no significant
difference.28 In fact, the planar geometry of the unsaturated
NHC ligand (N(42)-C(51)-C(42)-N(41) torsional angle of
0.63°) induced no dramatic change to the topographic steric
map of the catalytic pocket and the resulting calculated buried
volume for Ru-2 was only slightly lower than for complex
Ru-1 (45.9 vs 46.4) (Figure 3).29
Table 3. Self-Metathesis of 4-Pentenol by Catalyst Ru-2a
Ru-2 (0.1 mol%)
OH
3
OH
3
+
THF,
35 °C, time (h)
3
7
HO
8
Entry
Time (h)
Conversion (%)
Z:E ratio (%)
1
2
3
4
1
2
4
6
14
50(49)b
84
>98:2
97:3
93:7
93:7
84
aConversions and molar ratio of E and Z isomers were deter-
mined by 1H NMR spectroscopy. bIsolated Yield
The excellent selectivity obtained in self-metathesis
prompted us to further evaluate catalyst Ru-2 in cross-
metathesis (Scheme 2). The reaction between 3-butenyl ace-
tate (9) and 1-decene afforded the desired internal olefin prod-
uct 12, a Z-insect pheromone, in good 73% yield and with
high 97:3 Z:E ratio. While cross metathesis with vinyl boro-
nates catalyzed by non-cyclometalated Grubbs type complexes
leads to highly E isomer products,23 high 97% Z-selectivity
was observed with catalyst Ru-2 for the production in good
78% yield of the vinyl pinacol boronate cross product 13.24
Interestingly, 4-pentenol (7) could also be engaged efficiently
in cross-metathesis with 1-dodecene (3) to produce 14 in satis-
factory yield and high 95% Z-selectivity. The latter was con-
verted in three steps to the disparlure pheromone 15 with high
Figure 3. Steric map of complex Ru-2. The complex is oriented
according to the scheme on the left; the steric map is reported on
the right.
Because very small changes in the electronic and steric
properties of the ancillary NHC ligand can translate in dra-
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matic differences in catalytic properties, we decided to probe
Supporting Information
1
2
3
4
5
6
7
8
the potential benefit provided by our readily accessible cata-
lyst for the control of tacticity in ring-opening-polymerization
(Scheme 3). Our first attempt using catalyst Ru-2 (0.01 mol%)
in the ROMP of norbornene afforded a polymer material with
very low solubility that prevented its spectroscopic analysis.
On the other hand, norbornene ROMP with the addition of 2.5
mol % of 1-octene as a chain transfer agent, generated poly-17
with high cis-content (>98% Z-selectivity). Furthermore, the
13C NMR spectrum of the hydrogenated material was con-
sistent with highly syndiotactic polymer (>98%) (Scheme 3,
A). Under the same conditions, the norbornadiene ROMP
afforded the polymeric product poly-18 in high yield with the
same level of selectivity control (97% cis, >98% syndiotactic).
Moreover, the polymerization of the more complex monomer
19 using 1 mol% of Ru-2 produced a highly cis and syndiotac-
tic material (poly-19), which was isolated in 68% yield. Final-
ly, we turned our attention to the chiral cyclopropene mono-
mer 20 that was only previously considered with Mo- and W-
based catalysts.30 Once again, excellent stereogenic metal
control was observed with Ru-2 producing poly-20 with very
high cis,syndio-selectivity, since microstructural errors were
below the detection level (Scheme 3, B).
The Supporting Information is available free of charge on the
ACS Publications website.
NMR spectra of products, GC analyses, experimental procedures,
X-ray crystallographic data (PDF)
AUTHOR INFORMATION
Corresponding Author
9
* E-mail: olivier.basle@ensc-rennes.fr
* E-mail: marc.mauduit@ensc-rennes.fr
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Notes
The authors declare no competing financial interests
ACKNOWLEDGMENT
We are grateful to the CNRS, the Ecole Nationale Supérieure de
Chimie de Rennes. Umicore AG & Co is acknowledged for a
generous gift of M1 and M2 ruthenium complexes. This work was
supported by the ANRT and DEMETA S.A.S. (CIFRE no
2014/0702, grant to AD), the region Bretagne (ARED
n°COH14007 “NHC-MET” grant to RT) and the Agence Natio-
nale de la Recherche (N° ANR-15-CE07-0012-01 ”CHADOC”
grant to OB).
Scheme 3. Ring-Opening Metathesis Polymerization of
Norbornyl (Part A) and Cyclopropenyl Substrates (Part B)
REFERENCES
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(1) Handbook of Metathesis, Set, 2nd ed.; Grubbs, R. H., Wenzel, A.
G., O’Leary, D. J., Khosravi, E.; Wiley-VCH: Weinheim, Germany,
2015.
Ru-2 (0.01 to 1 mol%)
R
R
R
R
R
1-octene (2.5 mol%)
n
THF, rt, 1h
R
(2) (a) Metathesis in Natural Product Synthesis: Strategies, Sub-
strates, and Catalysts; Cossy, J., Arseniyadis, S., Meyer, C.; Wiley-
VCH: Weinheim, Germany, 2010. (b) Werrel, S.; Walker, J. C. L.;
Donohoe, T. J. Application of catalytic Z-selective olefin metathesis
in natural product synthesis. Tetrahedron. Lett. 2015, 56, 5261–5268.
(c) Meek, S. J.; O’Brien, R. V.; Llaveria, J.; Schrock, R. R.; Hoveyda,
A. H. Catalytic Z-selective olefin cross-metathesis for natural product
synthesis. Nature, 2011, 471, 461–466.
(3) Binder, J. B.; Raines, R. T. Olefin metathesis for chemical biolo-
gy. Curr. Opin. Chem. Biol. 2008, 12, 767–773.
(4) Slogovc, C. In Olefin Metathesis: Theory and Practice; Grela, K.;
John Wiley & Sons: Hoboken, N. J., 2014, pp. 329–348.
R
R
Norbornene (17), norbornadiene (18),
2,3-dicarbomethoxynorbornadiene (19)
poly-17,18,19
97% yielda
>98% cis,b >98% syndiotacticc,d
n
n
R = H: 99% yielda
97% cis,b >98% syndiotacticd
R
R
R
R
R = CO2Me: 68% yielda
98% cis,b >98% syndiotacticd
R
R
B
(5) Samojlowicz, C.; Bieniek, M.; Grela, K. Ruthenium-Based Olefin
Metathesis Catalysts Bearing N-Heterocyclic Carbene Ligands. Chem.
Rev. 2009, 109, 3708–3742.
Me Ph
Ph
Me
Me Ph
Me
Ru-2 (1 mol%)
Ph
THF, rt, 1.5h
80% yielda
n
>98% cis,b >98% syndiotacticd
20
(6) For reviews see: (a) Montgomery, T. P.; Ahmed, T. S.; Grubbs, R.
H. Stereoretentive Olefin Metathesis: An Avenue to Kinetic Selectivi-
ty. Angew. Chem. Int. Ed. 2017, 56, 11024–11036. (b) Montgomery,
T. P.; Johns, A. M.; Grubbs, R. H. Recent Advancements in Stereose-
lective Olefin Metathesis Using Ruthenium Catalysts. Catalysts,
2017, 7, 87. (c) Shahane, S.; Bruneau, C.; Fischmeister, C. Z Selectiv-
ity: Recent Advances in one of the Current Major Challenges of
Olefin Metathesis. ChemCatChem, 2013, 5, 3436–3459. For a very
recent example, see: d) Occhipinti, G.; Törnroos, K. W.; Jensen, V. R.
Pyridine-Stabilized Fast-Initiating Ruthenium Monothiolate Catalysts
for Z-Selective Olefin Metathesis. Organometallics, 2017, 36, 3284–
3292, (e) Ahmed, T. S.; Grubbs, R. H. A Highly Efficient Synthesis
of Z-Macrocycles Using Stereoretentive, Ruthenium-Based Metathe-
sis Catalysts. Angew. Chem. Int. Ed. 2017, 56, 11213–11216. For
recent examples of stereoretentive catalysts, see: (f) Xu, C.; Liu, Z.;
Torker, S.; Shen, X.; Xu, D.; Hoveyda, A. H. Synthesis of Z- or E-
Trisubstituted Allylic Alcohols and Ethers by Kinetically Controlled
Cross-Metathesis with a Ru Catechothiolate Complex. J. Am. Chem.
Soc. 2017, 139, 15640–15643. (g) Xu, C.; Shen, X.; Hoveyda, A. H.
In Situ Methylene Capping: A General Strategy for Efficient Stereore-
tentive Catalytic Olefin Metathesis. The Concept, Methodological
b
1
c
aIsolated yield; Determined by H NMR spectroscopy; Tac-
ticity of the hydrogenated polymer; Determinated by 13C spec-
d
troscopy (isotactic sequences were below the detection limit).
In summary, we have developed a new highly Z-selective
ruthenium catalyst based on a readily accessible unsaturated
unsymmetrical NHC ligand. The catalyst Ru-2 afforded a
stable catalytic system with excellent activities in the self-
metathesis and cross-metathesis of (functionalized) terminal
olefins, attaining and maintaining high Z-selectivity at high
conversion, with the capacity to surpass the efficiencies of
previously described Z-selective cyclometalated catalysts.
Moreover, no structural modification of the Ru-based catalyst
is required to achieve high tacticity (up to >98% syndiotactic)
and high cis-selectivity (up to >98%) in ring-opening-
polymerization allowing for the production of highly micro-
structurally controlled norbornene, norbornadiene and cyclo-
propene-derived polymers.
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ACS Catalysis
Implications, and Applications to Synthesis of Biologically Active
Compounds. J. Am. Chem. Soc. 2017, 139, 10919–10928.
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W.; Houk, K. N.; Grubbs, R. H. Decomposition Pathways of Z-
Selective Ruthenium Metathesis Catalysts. J. Am. Chem. Soc. 2012,
134, 7861–7866.
1
2
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(7) For selected examples with tungsten-based complexes, see: (a)
Peryshkov, D. V.; Schrock, R. R.; Takase, M. K.; Müller, P.; Hov-
eyda, A. H. Z-Selective Olefin Metathesis Reactions Promoted by
Tungsten Oxo Alkylidene Complexes. J. Am. Chem. Soc. 2011, 133,
20754–20757. (b) Marinescu, S. C.; Schrock, R. R.; Müller, P.; Ta-
kase, M. K.; Hoveyda, A. H. Room-Temperature Z-Selective Homo-
coupling of α-Olefins by Tungsten Catalysts. Organometallics, 2011,
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A. H. Highly Z-Selective Metathesis Homocoupling of Terminal
Olefins. J. Am. Chem. Soc. 2009, 131, 16630–16631.
(15) (a) Tarrieu, R.; Dumas, A.; Thongpaen, J.; Vives, T.; Roisnel, T.;
Dorcet, V.; Crévisy, C.; Baslé, O.; Mauduit, M. Readily Accessible
Unsymmetrical Unsaturated 2,6-Diisopropylphenyl N-Heterocyclic
Carbene Ligands. Applications in Enantioselective Catalysis. J. Org.
Chem. 2017, 82, 1880–1887. (b) Queval, P.; Jahier, C.; Rouen, M.;
Artur, I.; Legeay, J.-C.; Falivene, L.; Toupet, L.; Crévisy, C.; Cavallo,
L.; Baslé, O.; Mauduit, M. Multicomponent Synthesis of Unsymmet-
rical Unsaturated N-Heterocyclic Carbene Precursors and Their Re-
lated Transition-Metal Complexes. Angew. Chem. Int. Ed. 2013, 52,
14103–14107.
(16) Herbert, M. B.; Suslick, B. A.; Liu, P.; Zou, L.; Dornan, P. K.;
Houk, K. N.; Grubbs, R. H. Cyclometalated Z-Selective Ruthenium
Metathesis Catalysts with Modified N-Chelating Groups. Organome-
tallics, 2015, 34, 2858–2869.
(17) Cannon, J. S.; Zou, L.; Liu, P.; Lan, Y.; O’Leary, D. J.; Houk, K.
N.; Grubbs, R. H. Carboxylate-Assisted C(sp3)–H Activation in
Olefin Metathesis-Relevant Ruthenium Complexes. J. Am. Chem.
Soc. 2014, 136, 6733–6743.
(18) Endo, K.; Herbert, M. B.; Grubbs, R. H. Investigations into
Ruthenium Metathesis Catalysts with Six-Membered Chelating NHC
Ligands: Relationship between Catalyst Structure and Stereoselectivi-
ty. Organometallics, 2013, 32, 5128-5135.
(19) (a) For a recent paper regarding selective metathesis with α-
olefins, see reference (9a). (b) See supporting information for details.
(20) Tracz, A.; Matczak, M.; Urbaniak, K.; Skowerski, K. Nitro-
Grela-type complexes containing iodides – robust and selective cata-
lysts for olefin metathesis under challenging conditions. Beilstein J.
Org. Chem. 2015, 11, 1823−1832.
(21) (a) Manzini, S.; Poater, A.; Nelson, D. J.; Cavallo, L.; Slawin, A.
M. Z.; Nolan, S. P. Insights into the Decomposition of Olefin Metath-
esis Precatalysts. Angew. Chem. Int. Ed. 2014, 53, 8995−8999. (b)
Higman, C. S.; Plais, L.; Fogg, D. E. Isomerization During Olefin
Metathesis: An Assessment of Potential Catalyst Culprits. Chem-
CatChem 2013, 5, 3548−3551. (c) Beach, N. J.; Lummiss, J. A. M.;
Bates, J. M.; Fogg, D. E. Reactions of Grubbs Catalysts with Excess
Methoxide: Formation of Novel Methoxyhydride Complexes. Organ-
ometallics, 2012, 31, 2349–2356.
(22) Bronner, S. M.; Herbert, M. B.; Patel, P. R.; Marx, V. M.;
Grubbs, R. H. Ru-based Z-selective metathesis catalysts with modi-
fied cyclometalated carbene ligands. Chem. Science, 2014, 5, 4091–
4098.
(23) (a) Hemelaere, R.; Caijo, F. ; Mauduit, M.; Carreaux, F.; Car-
boni, B. Ruthenium-Catalyzed One-Pot Synthesis of (E)-(2-
Arylvinyl)boronates through an Isomerization/Cross-Metathesis
Sequence from Allyl-Substituted Aromatics. Eur. J. Org. Chem.
2014, 3328–3333. (b) Hemelaere, R.; Carreaux, F.; Carboni, B. Syn-
thesis of Alkenyl Boronates from Allyl-Substituted Aromatics Using
an Olefin Cross-Metathesis Protocol. J. Org. Chem. 2013, 78, 6786–
6792. (c) Morrill, C.; Grubbs, R. H. Synthesis of Functionalized Vinyl
Boronates via Ruthenium-Catalyzed Olefin Cross-Metathesis and
Subsequent Conversion to Vinyl Halides. J. Org. Chem. 2003, 68,
6031–6034.
(24) (a) Quigley, B. L.; Grubbs, R. H. Ruthenium-catalysed Z-
selective cross-metathesis of allylic-substituted olefins. Chem. Sci-
ence, 2014, 5, 501–506. (b) Kiesewetter, E. T.; O’Brien, R. V.; Tu, E.
C.; Meek, S. J.; Schrock, R. R.; Hoveyda, A. H. Synthesis of Z-
(Pinacolato)allylboron and Z-(Pinacolato)alkenylboron Compounds
through Stereoselective Catalytic Cross-Metathesis. J. Am. Chem.
Soc. 2013, 135, 6026–6029.
(25) (a) Herbert, M. B.; Marx, V. M.; Pederson, R. L.; Grubbs, R. H.
Concise Syntheses of Insect Pheromones Using Z-Selective Cross
Metathesis. Angew. Chem. Int. Ed. 2013, 52, 310–314. (b) The syn-
thesis of the disparlure pheromone 15 is described in the supporting
information.
(26) (a) Cannon, J. S.; Grubbs, R. H. Alkene Chemoselectivity in
Ruthenium-Catalyzed Z-Selective Olefin Metathesis. Angew. Chem.
Int. Ed. 2013, 52, 9001–9004. (b) With conjugated dienes, see: Luo,
9
(8) For selected examples with Molybdenum-based complexes, see:
(a) Lam, J. K.; Zhu, C.; Bukhryakov, K. V.; Müller, P.; Hoveyda, A.
H.; Schrock, R. R. Synthesis and Evaluation of Molybdenum and
Tungsten Monoaryloxide Halide Alkylidene Complexes for Z-
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Selective
Cross-Metathesis
of
Cyclooctene
and
Z-1,2-
Dichloroethylene. J. Am. Chem. Soc. 2016, 138, 15774–15783. (b)
Kiesewetter, E. T.; O’Brien, R. V.; Yu, E. C.; Meek, S. J.; Schrock, R.
R.; Hoveyda, A. H. Synthesis of Z-(Pinacolato)allylboron and Z-
(Pinacolato)alkenylboron Compounds through Stereoselective Cata-
lytic Cross-Metathesis. J. Am. Chem. Soc. 2013, 135, 6026–6029. (c)
Townsend, E. M.; Schrock, R. R.; Hoveyda, A. H. Z-Selective Me-
tathesis Homocoupling of 1,3-Dienes by Molybdenum and Tungsten
Monoaryloxide Pyrrolide (MAP) Complexes. J. Am. Chem. Soc.
2012, 134, 11334–11337. (d) Yu, M.; Ibrahem, I.; Hasegawa, M.;
Schrock, R. R.; Hoveyda, A. H. Enol Ethers as Substrates for Effi-
cient Z- and Enantioselective Ring-Opening/Cross-Metathesis Reac-
tions Promoted by Stereogenic-at-Mo Complexes: Utility in Chemical
Synthesis and Mechanistic Attributes. J. Am. Chem. Soc. 2012, 134,
2788–2799.
(9) (a) Rouen, M.; Queval, P.; Borré, E.; Falivene, L.; Poater, A.;
Berthod, M.; Hugues, F.; Cavallo, L.; Baslé, O.; Olivier-Bourbigou,
H.; Mauduit, M. Selective Metathesis of α-Olefins from Bio-Sourced
Fischer-Tropsch Feeds. ACS Catal. 2016, 6, 7970–7976. (b) Hamad,
F. B.; Sun, T.; Xiao, S.; Verpoort, F. Olefin metathesis ruthenium
catalysts bearing unsymmetrical heterocyclic carbenes. Coord. Chem.
Rev. 2013, 257, 2274–2292. (c) Tornatzky, J.; Kannenberg, A. Blech-
ert, S. New catalysts with unsymmetrical N-heterocyclic carbene
ligands. Dalton Trans. 2012, 41, 8215–8225.
(10) (a) Endo, K.; Grubbs, R. H. Chelated Ruthenium Catalysts for Z-
Selective Olefin Metathesis. J. Am. Chem. Soc. 2011, 133, 8525–
8527. (b) Keitz, B. K.; Endo, K.; Herbert, M. B.; Grubbs, R. H. Z-
Selective Homodimerization of Terminal Olefins with a Ruthenium
Metathesis Catalyst. J. Am. Chem. Soc. 2011, 133, 9686–9688.
(11) (a) Keitz, B. K.; Endo, K.; Patel, P. R.; Herbert, M. B.; Grubbs,
R. H. Improved Ruthenium Catalysts for Z-Selective Olefin Metathe-
sis. J. Am. Chem. Soc. 2012, 134, 693–699. (b) Liu, P.; Xu, X.; Dong,
X.; Keitz, B. K.; Herbert, M. B.; Grubbs, R. H.; Houk, K. N. Z-
Selectivity in Olefin Metathesis with Chelated Ru Catalysts: Compu-
tational Studies of Mechanism and Selectivity. J. Am. Chem. Soc.
2012, 134, 1464–1467. (c) Marx, V. M.; Herbert, M. B.; Keitz, B. K.;
Grubbs, R. H. Stereoselective Access to Z and E Macrocycles by
Ruthenium-Catalyzed Z-Selective Ring-Closing Metathesis and
Ethenolysis. J. Am. Chem. Soc. 2013, 135, 94–97. d) Pribisko, M. A.;
Ahmed, T. S.; Grubbs, R. H. Z-Selective ruthenium metathesis cata-
lysts: Comparison of nitrate and nitrite X-type ligands. Polyhedron
2014, 84, 144–149.
(12) (a) Herbert, M. B.; Grubbs, R. H. Z-Selective Cross Metathesis
with Ruthenium Catalysts: Synthetic Applications and Mechanistic
Implications. Angew. Chem. Int. Ed. 2015, 54, 5018–5024. (b) Rose-
brugh, L. E.; Herbert, M. B.; Marx, V. M.; Keitz, B. K.; Grubbs, R. H.
Highly Active Ruthenium Metathesis Catalysts Exhibiting Unprece-
dented Activity and Z-Selectivity. J. Am. Chem. Soc. 2013, 135,
1276–1279.
(13) Rosebrugh, L. E.; Ahmed, T. S.; Marx, V. M.; Hartung, J.; Liu,
P.; Lopez, J. G.; Houk, K. N.; Grubbs, R. H. Probing Stereoselectivity
in Ring-Opening Metathesis Polymerization Mediated by Cyclomet-
alated Ruthenium-Based Catalysts: A Combined Experimental and
Computational Study. J. Am. Chem. Soc. 2016, 138, 1394–1405.
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ACS Catalysis
Page 6 of 7
S.-X.; Cannon, J. S.; Taylor, B. L. H.; Engle, K. M.; Houk, K. N.;
(29) (a) Falivene, L.; Credendino, R.; Poater, A.; Petta, A.; Serra, L.;
Oliva, R.; Scarano, V.; Cavallo, L. SambVca 2. A Web Tool for
Analyzing Catalytic Pockets with Topographic Steric Maps. Organo-
metallics, 2016, 35, 2286–2293. (b) SambVca 2.0: a web application
Grubbs, R. H. Z-Selective Cross-Metathesis and Homodimerization of
3E-1,3-Dienes: Reaction Optimization, Computational Analysis, and
Synthetic Applications. J. Am. Chem. Soc. 2016, 138, 14039–14046.
(27) (a) Mikus, M. S.; Torker, S. Hoveyda, A. H. Controllable ROMP
Tacticity by Harnessing the Fluxionality of Stereogenic-at-Ruthenium
Complexes. Angew. Chem. Int. Ed. 2016, 55, 4997–5002. (b) Rose-
brugh, L. E.; Marx, V. M.; Keitz, B. K.; Grubbs, R. H. Synthesis of
Highly Cis, Syndiotactic Polymers via Ring-Opening Metathesis
Polymerization Using Ruthenium Metathesis Catalysts. J. Am. Chem.
Soc. 2013, 135, 10032–10035. (c) Keitz, B. K.; Fedorov, A.; Grubbs,
R. H. Cis-Selective Ring-Opening Metathesis Polymerization with
Ruthenium Catalysts. J. Am. Chem. Soc. 2012, 134, 2040–2043.
(28) The overlay of the crystal structures of Ru-1 and Ru-2 is dis-
closed in the supporting information.
1
2
3
4
5
6
7
8
for
analyzing
catalytic
pockets.
https://www.molnac.unisa.it/OMtools/sambvca2.0/.
(30) Flook, M. M.; Gerber, L. C. H.; Debelouchina, G. T.; Schrock,
R. R. Z-Selective and Syndioselective Ring-Opening Metathesis
Polymerization (ROMP) Initiated by Monoaryloxidepyrrolide (MAP)
Catalysts. Macromolecules, 2010, 43, 7515–7522.
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ACS Catalysis
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Readily Acessible NHC Ligand
Z-Selective Catalyst
with Improved Performances
N
N
BF4
8
9
Ru
O
Self-Metathesis
up to >99% cis
N
N
N
O
O
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Cross-Metathesis
up to >98% cis
O
up to >98% cis &
up to >98% syndiotactic
Multicomponent synthesis
ROMP
(at multi-gram scale)
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