Conducting Olefin Metathesis Reactions in Air: Breaking the Paradigm

Article abstract of DOI:10.1021/acscatal.5b00197

The first study of low catalyst loading olefin metathesis reactions in air is reported. TON values of up to 7000 were obtained using nondegassed solvents with commercially available precatalysts Caz-1, Hov-II, and Ind-II. The simple experimental condition

Full text of DOI:10.1021/acscatal.5b00197

Letter
pubs.acs.org/acscatalysis
Conducting Olefin Metathesis Reactions in Air: Breaking the
Paradigm
Stefano Guidone, Olivier Songis, Fady Nahra, and Catherine S. J. Cazin*
EaStCHEM School of Chemistry, University of St. Andrews, St. Andrews, KY16 9ST, United Kingdom
S
* Supporting Information
ABSTRACT: The first study of low catalyst loading olefin metathesis reactions in air is reported.
TON values of up to 7000 were obtained using nondegassed solvents with commercially available
precatalysts Caz-1, Hov-II, and Ind-II. The simple experimental conditions allow olefin metathesis
reactions to be carried out on the benchtop using technical grade solvents in air.
KEYWORDS: olefin metathesis, homogeneous catalysis, ruthenium, phosphite, air
he olefin metathesis reaction represents a powerful tool
T
for the formation of carbon−carbon bonds.1 Develop-
ment of precatalysts by modification of the original ruthenium
complex reported by Grubbs and co-workers has led to more
robust and active catalysts.2 Even if ruthenium precatalysts
display better tolerance toward water and oxygen than early
transition metal complexes,2b inert atmosphere and anhydrous
solvents are generally used to carry out such reactions.2 In the
past two decades, only a few studies have started to question
the catalytic performance of Ru systems in the presence of air.3
In 1991, Marciniec and Pietraszuck reported the catalytic
activity of [RuCl2(PPh3)3] in the self-metathesis of silicon-
containing olefins in air with 1 mol % Ru at 150 °C. Long
reaction times were necessary to obtain moderate to good
yields of 1,2 bis(silyl)ethenes (E/Z [5:1]−[10:1]).3a Some 10
years later, Dowden and Hoveyda independently reported the
use of modified Hoveyda−Grubbs-type precatalysts for ring-
closing metathesis (RCM) reactions affording disubstituted
olefins in air with nondegassed CH2Cl2 and THF using 5 mol
% Ru at 22−80 °C.3b,c Subsequently, Blechert and co-workers
described the use of commercially available G-II and Hov-II
(Figure 1) in nondegassed MeOH at 22 °C, affording
disubstituted olefins in high yields with 3−5 mol % of Ru.3d
To obtain systems suitable for use in protic solvents, the Raines
group isolated salycilaldimine-based benzylidene ruthenium
precatalysts active in the RCM of dienes and in enyne
metathesis. The precatalysts showed moderate to high
conversions in nondegassed methanol-d4 as well as benzene-
d6 in air with 5−10 mol % Ru at 55 °C.3e
Figure 1. Commercially available ruthenium precatalysts studied in
this work.
were reacted with the use of nondegassed CH2Cl2 in air and 10
mol % Ru at reflux.3f Inspired by the Raines work with
salycilaldimine derivatives,3e Verpoort and co-workers intro-
duced a Schiff base in the phosphine-containing indenylidene
ruthenium system. This system was shown active in ring-closing
metathesis (RCM) and cross-metathesis (CM) of allyl benzene
and cis-1,4-diacetoxy-2-butene in air with 1−2.5 mol % Ru at
40−80 °C.3g In 2010, Tew and co-workers described the ring-
opening metathesis polymerization (ROMP) of a hydrophilic
norbornene monomer, leading to the formation of hydrogels
using the pyridine-based Grubbs precatalyst in air at room
More recently, a Hoveyda-Grubbs type precatalyst immobi-
lized on polyethylene glycol able to perform RCM in air was
reported by Abell and co-workers. Di- and trisubstituted olefins
Received: January 30, 2015
Revised: March 18, 2015
© XXXX American Chemical Society
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Letter
temperature. Despite the living polymerization nature of this
specific transformation, the propagating catalyst attached to the
polymer chains was found to be inactive after 1 h under these
reaction conditions.3h
unexpected latent behavior displayed by Ru precatalysts under
aerobic conditions. To reduce this induction period, the
reactions were conducted at higher temperature (110 °C)
(Figure 2). Gratifyingly, short induction periods and good to
Recently, other modified Hoveyda−Grubbs type precatalysts
have been reported independently by Jensen and Grela.3i,j
Jensen and co-workers described the replacement of a chloride
anion with a 2,4,6-triphenylbenzenethiolate ligand affording a
highly Z-selective olefin metathesis catalyst. Despite the high
activity under typical reaction conditions, no activity was
observed when conducting the self-metathesis of 1-octene with
0.01 mol % Ru in air at 50 °C in neat substrate.3i In the search
for ruthenium precatalysts suitable for olefin metathesis in
water,4 Grela and co-workers reported the activity of a
ruthenium species containing quaternary ammonium chloride
tags in nondegassed CH2Cl2 in air with 1 mol % Ru at reflux.
The RCM of the easily reacting diethyl diallylmalonate led to
high yields of the five-membered ring product, and the
precatalyst could be recycled after extraction with D2O to
perform the isomerization of cis-2-butene-1,4-diol to the trans
isomer (94% isolated yield).3j
Figure 2. Comparison of commercially available Ru-based olefin
metathesis active complexes in air at 110 °C (lines are visual aids and
not curve fits). Reaction conditions: Ru cat (0.1 mol %), substrate 1
(0.25 mmol), reagent-grade toluene (1.5 mL), in air, 110 °C.
In early 2014, Grela and co-workers investigated the catalytic
efficiency of new mixed NHC/phosphine indenylidene
precatalysts. In this report, a slightly more comprehensive
study on the reactivity of ruthenium complexes in air was
carried out. Moderately challenging transformations were
performed using 1−5 mol % Ru.3k In contrast, Meier and co-
workers were the first to disclose a highly efficient metathesis
reaction performed in air and with low catalyst loading. Full
conversion of the easily cyclized diethyl diallylmalonate was
obtained with only 0.2 mol % of Hov-II (Figure 1).5a This is in
marked contrast with a report from Grubbs and co-workers that
concomitantly disclosed the very poor conversion (<10%) of
the same substrate under similar conditions using even higher
catalyst loadings and longer reaction times.6
More recently, reports by Skowerski and Olszewski showed
that metathesis reactions could be achieved in nondegassed
ACS grade green solvents (e.g., ethyl acetate, alcohols, dimethyl
carbonate, cyclopentyl methyl ether and 2-MeTHF), with
results comparable to those obtained with dichloromethane and
toluene.5b,c The diverging conclusions drawn from these
studies, as well as the robustness of Caz-1, incited us to
study low catalyst loading metathesis reactions in air using the
complexes shown in Figure 1.7
The RCM reaction profiles of the challenging substrate 1
using the commercially available precatalysts Caz-1, G-II,8b
Ind-II, and Hov-II were first recorded in air and in
nondegassed reagent-grade toluene.8 Whereas at least 90%
conversion of the challenging substrate 1 to product was
observed with 0.1 mol % of Caz-1 after 2 h at 80 °C under an
atmosphere of nitrogen,9a only traces of product were obtained
in air for all precatalysts tested at this temperature. Results
seemed to be in agreement with the presumed instability of Ru
species in air and in reagent-grade solvents. Surprisingly,
increasing the reaction time led to the unexpected activation of
the more thermally stable precatalysts Caz-1 and Hov-II,
allowing moderate conversions of the challenging substrate
(31% and 15% after 6 h, respectively).8 More strikingly, these
catalysts were found to remain active after 20 h.10 When the
more thermally sensitive complex G-II and the indenylidene
analogue Ind-II were employed, almost no conversion was
observed under these conditions. The long induction period
(∼1 h) observed at 80 °C for Caz-1 and Hov-II suggests an
moderate conversions of the challenging substrate 1 were
obtained for all thermally stable precatalysts under these
conditions. As shown in Figure 2, with the phosphine-based
complex Ind-II, more rapid catalyst activation was observed,
leading to 22% conversion in less than 3 min (at 80 °C, only
4% conversion was recorded after 1 h).8,10 When Hov-II was
employed, an activation period of ∼6 min was needed, leading
to 38% conversion after 1 h (at 80 °C, an activation time of 1 h
was required, with 28% conversion recorded after 27 h).8,10
With the robust and highly active precatalyst Caz-1, a short
activation time was also required (∼3 min) leading to more
than 60% conversion in less than 15 min.8,10
To gain more information about this latent behavior
displayed in air, further studies taking into account the
components of air separately were carried out (Figure 3).11
Contrary to popular belief, oxygen was found to be relatively
innocuous at this temperature because similar conversions of
the challenging substrate 1 were observed while carrying out
the reaction in parallel under nitrogen and under oxygen for all
precatalysts.12 Again, higher temperatures facilitate the
activation of the precatalysts, especially in the case of Caz-1,
for which the proposed isomerization from cis to trans
configuration and the release of the active species lead to
faster and more efficient reactions.9a
The presence of water was found to be very detrimental to
the phosphorus-based precatalysts Ind-II and Caz-1 because
8% and 15% conversion of the substrate were observed before
catalyst degradation in the presence of water (3 and 20 min
respectively, Figure 3a,b). Hov-II was found to be less sensitive
to water, with a 36% conversion recorded after 1 h (Figure 3c).
The deleterious effect of water is also reflected by the results
obtained when conducting the reaction in air and in dry air.
Indeed, although the latter did not affect the catalyst efficiency,
reactions carried out in “wet” air led to a substantially lower
catalyst activity. The relatively moderate activities observed in
the presence of water suggest why high catalyst loadings are
required when performing RCM reactions in water.4 The
influence of CO2 on the reaction outcome was also
investigated. For all catalysts, slightly lower catalyst efficiency
was observed. Therefore, the effect (detrimental) on catalyst
activity of the components of air decreases as follows: H2O >
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Figure 4. Catalytic properties of Caz-1, Hov-II, and Ind-II at different
temperatures in solvent-free conditions in air.14
latter on the catalytic system.15 Satisfactorily, no significant
difference was observed as a function of batch of reagent-grade
toluene and provider. As expected, a slight increase in
conversion was observed by drying the reagent-grade solvent
over activated 4 Å molecular sieves or by using anhydrous
degassed toluene (70% conversion of 1 using 0.1 mol % of Caz-
1 at 110 °C). This illustrates again the important effect of water
on the reaction outcome.
The scope of the reaction was next examined in air with
reagent-grade toluene or solvent-free conditions at 110 °C
(Figure 5). As expected, complex Caz-1 exhibited high activity
in air for a wide range of substrates in ring-closing, enyne and
cross-metathesis reactions. High to quantitative yields were
obtained using catalyst loadings of only 0.01 to 0.5 mol %.
These results are comparable or superior to what has previously
been reported for Caz-1 under inert atmosphere.9a More
surprisingly, Ind-II and Hov-II precatalysts were able to
perform the RCM of the substrates studied here under the
same conditions, with yields ranging from moderate to
excellent. All three catalysts performed well, except for the
formation of the challenging compound 3, for which Caz-1 was
largely superior. Of note is a TON of 7000 obtained in the
RCM leading to 4, which corresponds to a good yield using
only 100 ppm of catalyst, an unprecedented high activity for
RCM in air.
Figure 3. Reaction profiles of (a) Caz-1, (b) Ind-II, and (c) Hov-II
under N2, O2, dry air, CO2, and air and in the presence of H2O at 110
°C (lines are visual aids and not curve fits). Reaction conditions: (in
air) Ru cat (0.1 mol %), substrate 1 (0.25 mmol), reagent-grade
toluene (1.5 mL), in air, 110 °C; (under O2, CO2, dry air) Ru cat (0.1
mol %), substrate 1 (0.25 mmol), toluene saturated with adequate gas
(1.5 mL), under adequate gas, 80−110 °C; (in the presence of water)
Ru cat (0.1 mol %), substrate 1 (0.25 mmol), anhydrous toluene (1.5
mL), 100 μL of freshly distilled and degassed water, under nitrogen,
110 °C.
In conclusion, we have reported the first study of low catalyst
loading olefin metathesis reactions in air using commercially
available precatalysts and nondegassed reagent-grade solvents.
Water rather than oxygen or carbon dioxide was found to be
detrimental to the catalytic activity, suggesting the reason for
high catalyst loading when reactions are carried out in aqueous
media.4 This phenomenon is still poorly understood and is
currently under investigation in our group. Higher temper-
atures favor activation rather than degradation of the Ru species
under the conditions investigated. Complete conversions of
easily reacting substrates at low catalyst loading were achieved
at reflux of reagent grade toluene. Challenging substrates were
also converted in air with TONs comparable with the best
reported in the literature under inert atmosphere and
anhydrous conditions.9a,13 Ruthenium metathesis catalysts are
considered more tolerant toward water and oxygen than their
Mo counterparts; nevertheless, a rapid review of the most
recent studies reported in the field suggests that the community
is not yet fully aware that a number of ruthenium complexes are
CO2 ≥ O2. It is worth noting that the phosphite-based complex
Caz-1 led to the best catalyst efficiency.
As expected, although Caz-1 was the most active at 110 °C,
Ind-II and Hov-II, which are faster initiators, displayed better
activity than Caz-1 at lower temperatures (Figure 4). However,
only moderate to good conversions were reached using these
complexes, independently of the temperature, whereas
complete conversion was reached with Caz-1 (in air). This
result is comparable to the-state-of-the-art reaction carried out
under inert atmosphere (TON of 990 based on isolated
yield).9a,13
Solvent-free conditions are preferable (when reagents are
liquids) for efficient RCM in air (Figure 4) due to faster
kinetics and lower water content. It should be noted that the
water content relative to the substrate increases when the
reaction is carried out with a nonanhydrous solvent.14 Because
toluene is a solvent of choice in RCM, we carried out studies
using different sources of toluene to ascertain the effect of the
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ACKNOWLEDGMENTS
■
The authors gratefully acknowledge the Royal Society
(University Research Fellowship to CSJC) and the EC (CP-
FP 211468-2 EUMET) for funding, and Umicore for the
generous gift of ruthenium complexes.
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results (78% conversion observed, to be compared with <10%
published, ref 6)
Figure 5. Scope of the reaction using Caz-1, Hov-II, and Ind-II in air
at 110 °C.
air-stable tools for organic synthesis, or at least tools compatible
with fully aerobic conditions. The poor activity reported for
commercial Ru complexes in the course of experiments in
aqueous media and the belief that low-catalyst loading reactions
in air were problematic may have contributed to this way of
thinking.4,6 We hope that the present report exposes these
earlier conclusions as dogma and will encourage the use of
metathesis in more user-friendly conditions.
(8) (a) See Supporting Information section 2.3 page S5. (b)
Reactions with G-II were not carried out at 110°C because of the lack
of activity/stability observed at 80°C..
ASSOCIATED CONTENT
* Supporting Information
The following file is available free of charge on the ACS
■
S
(9) (a) Bantreil, X.; Schmid, T. E.; Randall, R. A. M.; Slawin, A. M.
Z.; Cazin, C. S. J. Chem. Commun. 2010, 46, 7115−7117. (b) Schmid,
T. E.; Bantreil, X.; Citadelle, C. A.; Slawin, A. M. Z.; Cazin, C. S. J.
Chem. Commun. 2011, 47, 7060−7062. (c) Songis, O.; Slawin, A. M.
Z.; Cazin, C. S. J. Chem. Commun. 2012, 48, 1266−1268. (d) Bantreil,
X.; Poater, A.; Urbina-Blanco, C. A.; Bidal, Y. D.; Falivene, L.; Randall,
R. A. M.; Cavallo, L.; Slawin, A. M. Z.; Cazin, C. S. J. Organometallics
2012, 31, 7415−7426. (e) Urbina-Blanco, C. A.; Bantreil, X.; Wappel,
J.; Schmid, T. E.; Slawin, A. M. Z.; Slugovc, C.; Cazin, C. S. J.
Organometallics 2013, 32, 6240−6247. (f) Leitgeb, A.; Wappel, J.;
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Publications website at DOI: 10.1021/acscatal.5b00197.
Experimental details, NMR of products of catalysis,
decomposition studies (PDF)
AUTHOR INFORMATION
Corresponding Author
*Fax: (+)44 (0) 1334 463808. E-mail: cc111@st-andrews.ac.uk.
Homepage: http://ch-www.st-andrews.ac.uk/staff/cc/group/.
■
Notes
(10) See Supporting Information, section 2.4, page S6.
The authors declare no competing financial interest.
(11) See Supporting Information, section 2.5, page S6.
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(12) See Supporting Information, section 4, page S24 for
decomposition study of Caz-1 under oxygen and section 5, page
S30 for stoichiometric reaction of Caz-1 with water.
(13) (a) Gatti, M.; Vieille-Petit, L.; Luan, X.; Mariz, R.; Drinkel, E.;
Linden, A.; Dorta, R. J. Am. Chem. Soc. 2009, 131, 9498−9499.
(b) Vorfalt, T.; Leuthaußer, S.; Plenio, H. Angew. Chem., Int. Ed. 2009,
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48, 5191−5194. (c) Clavier, H.; Urbina-Blanco, C. A.; Nolan, S. P.
Organometallics 2009, 28, 2848−2854.
(14) Precatalysts added as stock solution with the solvent evaporating
during the process. See Supporting Information, section 2.6, page S13.
(15) See Supporting Information, section 2.7, page S13 for Karl
Fischer titration data and graphical representation of the catalytic
activity of Caz-1.
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