Tandem catalysis: Versus one-pot catalysis: Ensuring process orthogonality in the transformation of essential-oil phenylpropenoids into high-value products via olefin isomerization-metathesis

Article abstract of DOI:10.1039/c5cy02038g

Conversion of essential-oil allylbenzenes (phenylpropenoids) to high-value fine chemicals via isomerization-metathesis is reported. The target reaction sequence involves isomerization of ArCH₂CH=CH₂1 into the corresponding conjugated olefins 2, and ensuing cross-metathesis with acrylates to generate ArCH=CHCO₂R 3. The second-generation Hoveyda catalyst HII was chosen for the metathesis step. A range of lead candidates was assessed for the isomerization step, of which most active was the Grotjahn catalyst [CpRu(PN)(MeCN)]PF₆([4]PF₆; PN = 2-PⁱPr₂-4-^tBu-1-Me-imidazole). The following order of isomerization activity was determined, using the isomerization of estragole 1a to anethole 2a (Ar = p-MeOC₆H₄) as a probe reaction: [CpRu(PN)(MeCN)]PF₆> RuHCl(CO)(PPh₃)₃> Ru(Me-allyl)₂(COD) > Pd₂Br₂(P^tBu₃)₂> RuHCl(PPh₃)₃> RuCl₃(μ₂-C)(μ₂,κ¹-C,η⁶-Mes-H₂IMes)Ru(H)(H₂IMes) (the "Grubbs hydride") > RuHCl(CO)(H₂IMes)(PCy₃) > RuHCl(CO)(IMes)(PCy₃) > RuHCl(CO)(PCy₃)₂. To maximize process efficiency, a systematic comparison of orthogonal tandem catalysis versus sequential catalyst addition was undertaken, using catalysts [4]PF₆and HII. The impact of each process type on product selectivity and catalyst compatibility was assessed. Selectivity was undermined in tandem isomerization-metathesis by competing metathesis of 1. Sequential catalyst addition eliminated this problem. The isomerization catalyst [4]PF₆adversely affected metathesis yields when equimolar with HII, an effect traced to the imidazole functionality in [4]PF₆. However, at the low catalyst loadings required for efficient isomerization (0.1 mol% [4]PF₆), negligible impact on metathesis yields was evident. The target cinnamates and ferrulates were obtained in quantitative yields by coupling these steps in a one-pot isomerization-metathesis protocol.

Full text of DOI:10.1039/c5cy02038g

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Tandem Catalysis versus One-Pot Catalysis: Ensuring Process
Orthogonality in the Transformation of Essential-Oil
Phenylpropenoids into High-Value Products via Olefin
Isomerization-Metathesis
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Carolyn S. Higman, Marcio P. de Araujo,† Deryn E. Fogg*
www.rsc.org/
Conversion of essential-oil allylbenzenes (phenylpropenoids) to high-value fine chemicals via isomerization-metathesis is
reported. The target reaction sequence involves isomerization of ArCH2CH=CH2 1 into the corresponding conjugated
olefins 2, and ensuing cross-metathesis with acrylates to generate ArCH=CHCO2R 3. The second-generation Hoveyda
catalyst HII was chosen for the metathesis step. A range of lead candidates was assessed for the isomerization step, of
which most active was the Grotjahn catalyst [CpRu(PN)(MeCN)]PF6 ([4]PF6; PN = 2-PiPr2-4-tBu-1-Me-imidazole). The
following order of isomerization activity was determined, using the isomerization of estragole 1a to anethole 2a (Ar = p-
MeOC6H4) as a probe reaction: [CpRu(PN)(MeCN)]PF6 > RuHCl(CO)(PPh3)3 > Ru(Me-allyl)2(COD) > Pd2Br2(PtBu3)2
>
RuHCl(PPh3)3 > RuCl3(µ2-C)(κ1-C,µ2,η6-Mes-H2IMes)Ru(H)(H2IMes) (the “Grubbs hydride”) > RuHCl(CO)(H2IMes)(PCy3) >
RuHCl(CO)(IMes)(PCy3) > RuHCl(CO)(PCy3)2. To maximize process efficiency, a systematic comparison of orthogonal tandem
catalysis versus sequential catalyst addition was undertaken, using catalysts [4]PF6 and HII. The impact of each process
type on product selectivity and catalyst compatibility was assessed. Selectivity was undermined in tandem isomerization-
metathesis by competing metathesis of 1. Sequential catalyst addition eliminated this problem. The isomerization catalyst
[4]PF6 adversely affected metathesis yields when equimolar with HII, an effect traced to the imidazole functionality in
[4]PF6. However, at the low catalyst loadings required for efficient isomerization (0.1 mol% [4]PF6), negligible impact on
metathesis yields was evident. The target cinnamates and ferrulates were obtained in quantitative yields by coupling these
steps in a one-pot isomerization-metathesis protocol.
elaborated into polyfunctional aromatic targets via olefin
metathesis.4-10 This approach can be seen as complementary
to strategies focused on metathetical degradation of biomass
Introduction
Notwithstanding recent advances in the discovery and
exploitation of fossil-fuel reserves,1 the long-term prospect is
one of dwindling supplies at increasing cost. Development of
synthetic methodologies based on renewable resources thus
remains an imperative.2,3 Among such resources, essential oils
stand out for the high proportion of functionalized, readily
modified aromatic compounds more typically available from
petrochemicals.4 Of particular note for their abundance are
functionalized allylbenzenes 1 (Fig. 1a), which serve as
important precursors to the conjugated phenylpropenoids 2.
We recently described the metathetical transformation of 2
into high-value antioxidants for the personal-care market (see,
e.g., 3a’; Fig 1b).5 More generally, conjugated arylpropenes of
type 2 are of interest as renewable feedstocks that can be
into simple building-blocks for commodity chemicals
manufacturing.11-13
MeO
HO
O
(a)
MeO
O
estragole (1a)
eugenol (1b)
safrole (1c)
(b)
MeO
2a
O
R
CM
O
O
MeO
octinoxate (3a')
+ 6
OR
Fig. 1. (a) Functionalized allylbenzenes (phenylpropenoids; 2-propenylbenzenes). (b)
Transformation of conjugated phenylpropenoids (1-propenylbenzenes) to high-value
cinnamates and ferulates.
In the present study, we sought to expand the scope of this
chemistry by coupling the metathesis step with a prior
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isomerization reaction, in order to harness the more abundant to isomerization-active species is rapid (IPr = 1,3-bis(2,6-
View Article Online
DOI: 10.1039/C5CY02038G
1-arylpropene feedstocks. Industrially, isomerization of diisopropylphenyl)imidazol-2-ylidene).26
estragole 1a to its conjugated isomer anethole 2a is reportedly Gooβen’s synthesis of functionalized styrenes via “isomerizing
effected by treatment with excess KOH at 200 °C.14,15 Much metathesis” embodies an alternative strategy, again based on
interest has focused on the development of alternative, orthogonal tandem catalysis.27,28 Here the terminal olefin in
catalytic routes, and a wide range of catalysts has now been the phenolic precursor is isomerized toward the more
reported.16
thermodynamically stable, conjugated site, following which
In considering routes from 1 to 3, we were particularly the styrenyl target is generated by cross-metathesis with
interested in one-pot processes, which eliminate the ethylene (“ethenolysis”; Scheme 2, top). Any incidence of
inefficiency and materials waste associated with the metathesis prior to complete isomerization is immaterial, as
intervening workup to isolate 2. Tandem catalysis, as a specific this simply results in stepwise shortening of the side-chain by
embodiment of this approach, is of added interest in moving ethenolysis, prior to another isomerization step (Scheme 2,
beyond stoichiometric methodologies.17 Tandem metathesis- bottom). Gooβen and Cole-Hamilton recently applied this
isomerization is now well established, and has recently been strategy to the synthesis of tsetse fly attractants,27 while Nolan
reviewed.18,19 Such processes typically rely on “assisted and co-workers utilized the same approach to convert 1 into
tandem catalysis”,17c involving the induced decomposition of a the corresponding styrenes.29
ruthenium metathesis catalyst into isomerization-active
OH
OH
species. Isomerization can be highly efficient, ambiguities in
(a)
(i)
the identity of the active catalyst notwithstanding.20
(ii)
Required here is the opposite sequence: that is, tandem
isomerization-metathesis. Early examples of success in such
methodologies were largely substrate-specific, in that ring
strain or steric constraints precluded metathesis prior to the
isomerization step.21-23 In the absence of such constraints,
tandem isomerization-metathesis is commonly hampered by
poor process orthogonality. Product selectivity is limited by
both premature metathesis, and isomerization of the product.
In an elegant example of orthogonal tandem catalysis17c
applied to olefin homologation, Grotjahn and Schrock resolved
this issue by deploying a metathesis catalyst that is unreactive
toward internal olefins, and an isomerization catalyst that was
found to be remarkably selective for reaction with trans-
olefinic linkages (see Scheme 1).24
OH
6
6
OH
OH
7
(i)
(ii)
(i)
(b)
6
5
Scheme 2. Example of selectivity in isomerization-metathesis, achieved by metathetical
excision of the extraneous alkyl chain. Shown are two extremes: (a) Multi-site
isomerization to the conjugated position, followed by ethenolysis. (b) Stepwise
isomerization-CM (CM = cross-metathesis). (i) Pd2Br(PtBu3)2 7; (ii) C2H4 + Ru metathesis
catalyst.
More generally, however, poor orthogonality between the two
processes can limit selectivity, and sequential catalyst addition
is used to control the process. Sequential addition has been
extensively deployed for the assembly of heterocyclic
compounds, including indoles and other benzo-fused
heterocycles.30,31 In a modified approach, the Hulea group
recently demonstrated the utility of serially linked,
differentially packed catalyst beds to effect the transformation
of ethylene to propylene via dimerization-isomerization-
metathesis.32
Anticipated as a challenge in the present work is the higher
metathesis reactivity of the terminal olefin, relative to the
internal olefin generated in the isomerization step.
Nevertheless, selectivity can be envisaged if the isomerization
catalyst is sufficiently reactive to promote initial isomerization
relative to metathesis. We therefore explored both tandem
and one-pot transformations in developing a methodology for
the transformation of essential-oil allylbenzenes into high-
value cinnamate and ferulate targets.
(ii)
– C2H4
(i)
X
iPr
iPr
O
iPr
iPr
Ru
PiPr2
N
MeCN
W
N
N
iPr
NMe
tBu
isomerization catalyst, [4]X
metathesis catalyst
Scheme 1. Selective homologation of Cn (E)-olefins into C2n−2 (Z)-olefins via orthogonal
tandem catalysis, involving concurrent processes of (i) isomerization; (ii) metathesis.
In related work, Consorti, Dupont, and co-workers achieved
selectivity by immobilizing the metathesis catalyst in an ionic
liquid phase, with an isomerization catalyst in the organic
phase. The preferential solubility of the olefinic substrates in
the organic layer accelerated isomerization relative to
metathesis.25 Finally, Mauduit and Carreaux employed a
system in which isomerization is promoted by choosing a Ru-
IPr metathesis catalyst, for which the onset of decomposition
Results and discussion
Initial experiments focused on the isomerization of estragole
1a, as a representative, abundant allylbenzene. In developing
methodologies for the transformation of 1a into cinnamate 3a,
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we considered a range of candidates for the isomerization metathesis catalyst and acrylate coupling partner are added
View Article Online
DOI: 10.1039/C5CY02038G
step, as discussed below. For the metathesis step, however, only once isomerization is complete.
we selected the second-generation Hoveyda catalyst HII, on
the basis of prior work.5,11,33,34 The dominant Grubbs-class
Isomerization of estragole
catalysts (that is, phosphine-stabilized pre-catalysts, of which
In the next phase of the study, we screened a range of known
isomerization catalysts (Fig. 2) for maximum activity in the
transformation of 1a to anethole 2a. Leading reviews have
described the isomerization activity of a large number of
GII is the exemplar) were rejected on the basis of their
incompatibility with acrylates.35 The incompatibility arises
from Michael reactions between the electron-deficient olefin
and the PCy3 ligand liberated from GII during catalyst
potential catalysts, with a particular focus on the impact of
initiation. Such reactions yield reactive enolates36 that were
substrate functional groups on activity.40-42 Additional
shown to trigger rapid catalyst decomposition.34
candidates were identified from the recent literature.16,42 As
well as the Grotjahn catalyst [4]PF6,39 which has previously
Attempted tandem catalysis
shown exceptional activity for isomerization of estragole and
eugenol to the (E)-olefins,38 we examined RuHCl(CO)(PPh3)3 5
and RuHCl(PPh3)3 6, the highest-performing isomerization
catalysts among several comparators recently examined.20
Other candidates emerge from the tandem catalysis studies
described in the Introduction, including dimeric Pd2Br(PtBu3)2
7,27,28 and Ru(COD)(methallyl)2 8.43
The first question explored was that of process efficiency:
specifically, the viability of orthogonal tandem catalysis. Prior
work aimed at the self-metathesis of estragole 1a using HII
demonstrated that unintended isomerization of 1a can
compete with metathesis,7 as indeed noted more broadly
elsewhere.37 We therefore considered it possible that
deliberate use of a highly reactive isomerization catalyst (e.g.
the Grotjahn catalyst [4]PF6),38,39 in conjunction with HII, could
promote initial isomerization relative to metathesis, and
enable selectivity for the target cinnamates. This proved
unsuccessful. As shown in Scheme 3, very poor selectivities
were observed under conditions previously established as
optimal for the CM reaction, when estragole and methyl
acrylate were present simultaneously with HII and [4]PF6.
Competing metathesis of 1a afforded homocoupled and cross-
products, among a multiplicity of other products (see ESI), and
yields of the target 3a were limited to 55%.
H
H
Cl
Cl
PF6
Ru
PPh3
CO
Ru
PPh3
PPh3
Ph3P
Ph3P
5
6
Ru
PPh3
PiPr2
MeCN
N
NMe
Br
tBu3P
Pd
Ru
tBu
2
[4]PF6
7
8
Fig. 2. Candidate complexes screened for isomerization activity in this work.
Isomerization experiments were carried out at 40 °C in
toluene, at a catalyst loading of 1 mol% (Fig. 3). Under these
conditions, the Grotjahn catalyst [4]PF6 exhibited highest
activity, delivering quantitative yields of 2a within 5 min.
Hydridochlorocarbonyl complex 5 and bis-allyl catalyst 8 were
also highly active, while dimeric 7 (0.5 mol%, i.e. 1 mol% Pd)
Ar
Ar
isom.
cross-metathesis
OMe
O
OMe
O
Ar
1a
required
1 h for complete reaction. In comparison,
cross-
metathesis
+ 6
OMe
isom.
Ar
OMe
RuHCl(PPh3)3 6 reached only ca. 50% conversion at 1 h. All
catalysts showed >95% selectivity for (E)-anethole 2a by 1 h,
with the sole exception of 5, for which 10% of (Z)-2a was
present at 100% yield. However, the proportion of (E)-2a
increases if reaction is continued after conversion to 2a is
complete.
Ar
O
O
2a
3a
+ HII (0.5 mol%)
+ [4]PF6 (0.1 mol%)
Ar
Ar
isom.
self-metathesis
Ar
Ar
%E at
100
Scheme 3. Target tandem isomerization-metathesis reaction (solid arrows; Ar = p-
MeOC6H4). Dashed arrows show representative, competing metathesis and metathesis-
isomerization processes. Conditions: C7H8, 70 °C, 6 h. Catalyst loadings are based on
literature precedents for both HII5 and [4]PF6,38,39 and validated below.
Catalyst 0.5 h* 1 h
4
5
8
7
[4]PF6
99
90
96
94
97
ND
96
96
97
97
5
6
7
8
50
0
6
While competing metathesis of 1 could potentially be
overcome by using higher loadings of [4]PF6, or a less reactive
metathesis catalyst, either comes at a price: that is, the
requirement for excess catalyst (with attendant issues of cost
and Ru removal), or slow throughput. We therefore accepted
the necessity of sequential catalytic processes, in which the
* %E at 100% yield for
[4]PF6 and 5 (ca. 15 min).
0
20
40
60
ꢀme (min)
Fig. 3. Assessing the activity of the candidate catalysts in isomerization of estragole.
Conditions: 1 mol% Ru or Pd, 40 °C, C7H8.
The relatively low isomerization activity of 6 is particularly
striking, given that in related work,20 this catalyst significantly
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out-performed others that have been regarded as potentially
potent isomerization catalysts, including RuHCl(CO)(L)(PCy3) (L
= PCy3 12, H2IMes 10),44 and the “Grubbs hydride” 9.45 All were
tested under the conditions shown in Fig. 3,20 permitting
extraction of the order of isomerization activity depicted in Fig.
4.
(a) Isomerization
0.1 mol% [4]PF6
(b) Metathesis
DOI: 10.1039/C5CY02038G
View Article Online
CO2Me
0.5 mol% HII
5 min, RT
0.5 h, RT
6 equiv MA
6 h, 70 ˚C
Ar
Ar
Ar
Ar
1a
2a
2a
3a
100
100
PF6
H
0
0
Cl
Ru
PiPr2
THF
DCE C7H8
THF
DCE C7H8
MeCN
>
>
>
Ru
CO
Ph3P
Ru
N
N
PPh3
NMe
5
PPh3
8
Fig. 5 Evaluating the impact of solvent on the isomerization and cross-metathesis steps.
tBu
[4]PF6
H
Compatibility of metathesis and isomerization catalysts
Br
Cl
N
Mes
tBu3P Pd
>
>
Ru
PPh3
Ph3P
A final question in developing the one-pot / dual catalyst
methodology lay in the potential sensitivity of the metathesis
step to the isomerization catalyst [4]PF6. To dissect out this
effect, we focused on metathesis of anethole 2a, the intended
product of estragole isomerization, and examined the impact
of added [4]PF6 on yields of 3a. Metathesis yields suffered
when [4]PF6 is present in amounts equimolar with HII (Table 1,
entries 1 vs. 2). The detrimental effect was traced to the
imidazole moiety by experiments in which free MeCN or
imidazole were added to the metathesis reaction, in molar
amounts equivalent to HII, in the absence of [4]PF6. Added
MeCN had essentially no effect, while added imidazole
strongly depressed CM yields (entry 3, 4). This behaviour is
consistent with the proposed hemilability of the phosphine-
imidazole ligand.50
Cl
Cl
2
Ru
6
7
PPh3
H2IMes
Ru
Cl
C
H
9
H
H
H
Cl
Cl
Cl
>
>
>
Ru
H2IMes
Ru
IMes
CO
Ru
12
PCy3
CO
Cy3P
Cy3P
Cy3P
CO
10
11
Fig. 4. Order of isomerization activity for catalysts surveyed in the reaction of Fig. 3.
Solvent compatibility
Isomerization using cationic [4]PF6 is normally carried out in
acetone.46 While a range of solvents is feasible for metathesis,
toluene and dichloromethane are generally most favourable.37
Acetone and other polar solvents have been reported to limit
catalyst productivity.47 Moreover, a relatively high-boiling
solvent is required for efficiency in the targeted metathesis
step, in which formation of cinnamate 3a is retarded by the
intermediate formation of stilbenes, which are slowly
consumed even at 70 °C.5 To identify a reaction medium that
balances the requirements for each reaction type, we
examined the solvent dependence for isomerization of 1a and
metathesis of 2a, in THF, toluene, and dichloroethane (DCE;
Fig. 5). Given the high activity of [4]PF6, isomerization was
undertaken at RT, with the metathesis step being carried out
at a bath temperature of 70 °C. As noted previously,5 efficient
volatilization of the propylene and ethylene byproducts from
metathesis is essential to promote selectivity for the desired
CM reaction. Metathesis reactions were therefore carried out
with efficient stirring in open vessels in a well-purged
glovebox.
Table 1. Evaluating the robustness of anethole–acrylate CM toward isomerization
catalyst [4]PF6 and its constituent ligands.
HII (0.5 mol%)
O
Ar
Ar
+ additive
OMe
+ 6
CO2Me
2a
3a
C7H8, 70 ˚C, 6 h
Entry
Additive
mol% additive
% conv
% yield
1
2
3
4
5
none
[4]PF6
---
100
100
100
81
100
73a
100
48a
100
0.5
0.5
0.5
0.1
MeCN
imidazole
[4]PF6
100
While isomerization was marginally faster in the polar solvent
THF (declining in the order THF > DCE > toluene; Fig. 5a),
reaction was complete in all cases within 0.5 h at RT. In
comparison, metathesis of 2a was considerably slower in THF
(Fig. 5b). Given the equivalent performance of DCE and
toluene, the latter was adopted as the less toxic,
environmentally less undesirable48 alternative, and used as a
good compromise solvent for both reactions.49
GC-FID analysis. aStilbenes resulting from self-metathesis constitute the balance
of material.
The negative impact of free imidazole is unsurprising. Not only
do imidazole51 and methyl imidazole52 function as effective
quenching agents in metathesis, but the metallacyclobutane
intermediate that carries metathesis was recently shown to be
highly sensitive to deprotonation by Bronsted base.53
Importantly, however, the relative rates of metathesis and
deactivation can be tuned by adjusting the ratio of HII to
[4]PF6. Thus, quantitative metathesis could be achieved by
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Conditions. (i) Isomerization: [4]PF6 (0.1 mol%), C7H8, RT, 0.5 h. Quantitative
reducing the proportion of [4]PF6 fivefold (to 0.1 mol%; Entry
5). The impact on isomerization rates is minor, as the
transformation of 1a to 2a was shown above to be complete
within 30 min at this catalyst loading, even at RT.
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formation of 2 confirmed prior to adding reagents for next step. (ii) Metathesis:
DOI: 10.1039/C5CY02038G
Addition of HII (0.5 mol%), acrylate (6 equiv); 70 °C, 6 h. Conversions of 2
1
assessed by GC-FID, yields of 3 by GC-FID or H NMR analysis; see Experimental.
Note: While no other products were evident, NMR yields are indicated merely as
>99%, given limits on the accuracy of NMR integration.
One-pot isomerization-metathesis.
Sequential isomerization-metathesis was carried out using the
optimized conditions identified above. Accordingly, a toluene
solution of estragole 1a and catalyst [4]PF6 (0.1 mol%) was
stirred for 0.5 h at RT under N2, following which methyl
acrylate and the metathesis catalyst HII (0.5 mol%) were
added, and the reaction was heated at 70 °C for 6 h. H NMR
analysis indicated quantitative yields of the desired cinnamate
3a (Table 2, entry 1).
This sequential isomerization-metathesis methodology shows
excellent tolerance for the unprotected phenolic functionality
in eugenol 1b, affording the ferulate target 3b in quantitative
yields (entry 2). Similar performance was also found for safrole
1c (entry 3). Likewise successful was the transformation of
estragole by isomerization and cross-metathesis with 2-
ethylhexyl acrylate (entry 4). This reaction is of particular
interest, given the high value of the octinoxate product 3a’, an
important sunscreen agent. CM of eugenol 1b and safrole 1c
proceeded correspondingly well (entries 5, 6). In all cases,
quantitative yields were achieved, irrespective of the
phenylpropenoid / acrylate combination.
Conclusions
The foregoing highlights the potential of olefin metathesis to
elaborate the conjugated phenolic structures that represent
key chemical motifs in naturally-occurring essential oils, and
expands the available pool of such resources by coupling
isomerization with metathesis catalysis. Thus, the renewable
phenylpropenoids estragole, eugenol, and safrole are
converted into cinnamate and ferulate products relevant to
fine-chemicals markets, via sequential processes of
isomerization and acrylate cross-metathesis.
The high propensity of the terminal olefins toward metathesis,
in competition with isomerization, hampered development of
orthogonal tandem catalysis methodologies. Such processes
are attractive for their operational simplicity; specifically,
“walk-away” operation, but are frequently constrained by such
imperfect orthogonality. Process efficiency was nevertheless
achieved by identifying conditions suitable for performing the
two reactions in a single vessel. Addition of the metathesis
catalyst following isomerization reduces waste by eliminating
the need for intervening workup and purification. Key to
overcoming the incomplete tolerance of the metathesis
process for the isomerization catalyst is the high activity of the
latter, which permits use of catalyst loadings sufficiently low
that metathesis proceeds unimpeded.
1
Table 2. One-pot isomerization-cross-metathesis of phenylpropenes with acrylates to
yield high-value cinnamates and ferulates.a
Ar
(ii)
(i)
CO2R
Ar
Ar
6
3: R = Me
1
2
CO2R
3': R = 2-ethylhexyl
Experimental
Materials and methods
entry
substrate
product
% conv
% yield
All reactions were carried out in an N2-filled glove-box. Dry, oxygen-
free C7H8 and THF were obtained using a Glass Contour solvent
purification system and stored in the glovebox in amber bottles
over 4 Å molecular sieves. Dichloroethane was dried over CaSO4 for
12 h under N2, then refluxed over P2O5 for 6 h prior to distillation,
and stored as above, over 5 Å molecular sieves. Anhydrous n-
decane (internal standard for gas chromatography) was purchased
from Sigma-Aldrich.
methyl acrylate
1
2
3
1a
1b
1c
3a
3b
3c
100
100
100
100
>99
>99
Substrates 1a (98%), 1b (99%), 1c (>97%), and 2a (99%) were
purchased from Sigma-Aldrich, and passed over neutral alumina
prior to use. Acrylates (Sigma-Aldrich; 99% (methyl) or 98% (2-
ethylhexyl)) were used without removing the phenolic stabilizers.
Acrylates and phenylpropenes were degassed by five freeze-pump-
thaw cycles, and stored protected from light under N2 in the
glovebox freezer (–35 °C). Catalysts [4]PF6, 7, and 8 were purchased
from Strem and used as received. Catalysts HII,54 5,55 and 656 were
synthesized by literature methods. Potassium hydrotris(1-
pyrazolyl)borate (KTp; >97%) was purchased from TCI and used as
received to quench the metathesis catalyst52 prior to workup and
analysis.
2-ethylhexyl acrylate
4
5
6
1a
1b
1c
3a’
3b’
3c’
100
100
100
>99
>99
>99
This journal was © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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Journal Name
NMR spectra were recorded on a Bruker Avance 300 or 500 MHz above for 6 h, after which an aliquot was quenched with KTp, then
View Article Online
DOI: 10.1039/C5CY02038G
air, and analyzed.
spectrometer at 298 K, and referenced to the residual proton or
carbon signals of the deuterated solvent (1H, 13C(1H) NMR). Signals
are reported in ppm, relative to TMS (1H, 13C) at 0 ppm. GC
quantification was performed on samples diluted with CH2Cl2 (ACS
reagent grade) on an Agilent 7890A Series GC equipped with a
flame ionization detector (FID), an Agilent 7683B Series
autosampler and an Agilent HP-5 polysiloxane column (30 m length,
320 μm diameter), using an inlet split ratio of 10:1, an inlet
temperature of 250 °C, and helium (UHP grade) as the carrier gas to
maintain column pressure at 11.512 psi. The FID response was
maintained between 50-2000 ρA, using analyte concentrations of
ca. 5 mM. Calibration curves (peak areas vs. concentration) were
constructed in the relevant concentration regime, to account for
the dependence on detector response for substrates, products and
decane (internal standard in catalytic runs). Conversions and yields
in catalytic runs were determined from the integrated peak areas,
referenced against decane, and compared to the initial substrate :
decane integration ratio. Conversions of 1 and 2, and yields of
products 2 and 3a, were assessed by GC-FID. Other product yields
Acknowledgements
This work was funded by the Natural Sciences and Engineering
Research Council of Canada. CSH thanks NSERC for a PGS-D
award. MPA thanks CNPQ of Brazil for a sabbatical fellowship
(PDE, Grant # 211399/2013-2).
Present Address
†Sabbatical visitor from Universidade Federal do Paraná,
Curitiba (PR), Brazil.
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Catalysis Science & Technology
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DOI: 10.1039/C5CY02038G
TOC text and graphic
One-pot and tandem catalysis methodologies are explored in developing efficient
isomerization-metathesis routes to high-value cinnamates and ferulates from
essential-oil allylbenzenes.