Dual Activity of Grubbs-Type Catalyst in the Transvinylation of Carboxylic Acids and Ring-Closing Metathesis Reactions

Article abstract of DOI:10.1021/acs.joc.0c02135

The development of a multifunctional catalyst, which mimics the promiscuity of enzymes, that would catalyze more than one chemical transformation in a single reaction vessel is one of the key points of modern sustainable chemistry. The results of our experiments indicated that Grubbs-type catalysts possess such multitask activity, catalyzing the transvinylation reaction of carboxylic acids without losing their original metathetic activity. This new activity of Grubbs catalysts was evidenced on several examples. It allows us to design a transvinylation/ring-closing metathesis (RCM) cascade reaction leading to the formation of endocyclic enol lactones from unsaturated carboxylic acids in an one-pot procedure. This unique ability of Grubbs catalyst to catalyze multiple mechanically distinct cascade reactions in a chemoselective way offers the new possibility for the synthesis of complex compounds from simple, easily accessible substrates.

Full text of DOI:10.1021/acs.joc.0c02135

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Article
Dual Activity of Grubbs-Type Catalyst in the Transvinylation of
Carboxylic Acids and Ring-Closing Metathesis Reactions
Anna Brodzka,* Dominik Koszelewski, and Ryszard Ostaszewski*
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ABSTRACT: The development of a multifunctional catalyst,
which mimics the promiscuity of enzymes, that would catalyze
more than one chemical transformation in a single reaction vessel is
one of the key points of modern sustainable chemistry. The results
of our experiments indicated that Grubbs-type catalysts possess
such multitask activity, catalyzing the transvinylation reaction of
carboxylic acids without losing their original metathetic activity.
This new activity of Grubbs catalysts was evidenced on several
examples. It allows us to design a transvinylation/ring-closing
metathesis (RCM) cascade reaction leading to the formation of
endocyclic enol lactones from unsaturated carboxylic acids in an
one-pot procedure. This unique ability of Grubbs catalyst to
catalyze multiple mechanically distinct cascade reactions in a
chemoselective way offers the new possibility for the synthesis of complex compounds from simple, easily accessible substrates.
special reaction conditions (such as the addition of ligands or
other reagents, thermal decomposition, etc.), which seriously
limits their applications.28
The majority of these nonmetathetic reactions were shown
in tandem with olefin metathesis. However, usually, the
metathesis is the first step of sequence, after which the catalyst
structure is irreversibly changed (losing its original activity).
Unfortunately, such modified catalysts are not active in
metathesis reactions.
The examples of tandem protocols where nonmetathesis
reaction is the first step of a cascade are very rare. Hodgson et
al. described a nonmetathesis−metathesis sequence, where in
the first step, the Grubbs second-generation Ru carbene
complex catalyzes the homocoupling of diazoacetates, and in
the next step, in the presence of an alkane, the metathesis
occurs.29−32 Thus, after the nonmetathetic transformation, the
catalyst retained its original activity.
Recently, we have reported the ring-closing metathesis
(RCM) of unsaturated carboxylic acids vinyl esters leading to
valuable endocyclic enol lactones.33 However, the syntheses of
substrates are difficult and based on nonefficient, toxic
protocols such as the transesterification of carboxylic acids
INTRODUCTION
■
The design and synthesis of new catalysts is a tedious and
time-consuming procedure. Usually, the catalyst can be applied
only for a single reaction. One of the major challenges for
organic chemists is to develop a multifunctional catalyst that
may catalyze more than one reaction in a single vessel. Such a
concept is also desired from the development of sustainable
chemistry to solve the environmental issues.1 Multiple
processes performed in an one-reaction vessel, where the
product of the first reaction is a substrate for the next
transformation known as the sequential tandem catalysis, are of
great importance for organic chemists.2,3 The one-pot
approach allows us to simplify the procedure and reduce
costs and toxicity by minimizing the purification steps, which is
economically and environmentally friendly.
Since the discovery of an air-stable ruthenium-based
metathesis catalyst by Grubbs,4 the metathesis reaction has
become one of the most powerful tools for the formation of
carbon−carbon double bond. However, the application of
these mediators is limited mostly to metathesis reactions. To
use such catalysts in other transformations, their structures
have to be modified. For example, several ruthenium-based
metathesis catalysts were found to be precatalysts for various
side reactions5,6 such as Kharasch addition,7,8 hydrogena-
tion,9−11 oxidation,12−14 isomerization,15−17 cyclization,18,19
and many others.20−27 However, to promote nonmetathetic
transformations, catalysts have to be converted to other Ru
species, e.g., Grubbs catalyst transformed to [Ru-H] by a
treatment with H2 is an efficient catalyst for the olefin
hydrogenation.9−11 Such modifications of catalysts require
Received: September 4, 2020
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© XXXX American Chemical Society
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with vinyl acetate using Hg(OAc)2.34,35 Other approaches are
based on Pd,36 Ir,37 Ag/Au,38 or Rh39 complexes as safer
analogues of mercury. However, the usage of a large excess of
vinyl acetate, which is a precursor of toxic acetaldehyde, makes
those procedures less attractive. Recently, the application of
ruthenium complexes as transvinylation catalysts has gained
much attention40 as they are less toxic and have a broad
substrate scope and wide functional-group tolerability.
indicates that only carboxylic acids undergo the studied
transvinylation.
In the next step, we explored the scope of transvinylation
reaction using Grubbs second-generation catalyst (Scheme 1).
In the studied cases, we used only such carboxylic acids, the
structures of which prevent the RCM reaction.
Scheme 1. Transvinylation Reaction
The versatility of Ru complexes encourages us to expand the
scope of Grubbs catalyst activities. During our studies, we
observed that the reaction of carboxylic acids with vinyl acetate
in the presence of metathesis catalysts gave the corresponding
carboxylic acid vinyl ester. This result led to the observation
that these catalysts may promote the transvinylation of
carboxylic acids. Herein, we present the details of our studies.
RESULTS AND DISCUSSION
■
In preliminary experiments, we have tested the reaction of
phenylacetic acid (1a) with 2 equiv of vinyl acetate in the
presence of several commonly used transvinylation catalysts as
well as metathesis catalysts (Table 1). Usually, the trans-
a
Table 1. Transvinylation of Phenylacetic Acid
In all cases, the appropriate vinyl esters 2b−e were obtained
in moderate to excellent yields. The application of biologically
relevant 2-arylpropionic acids42 provided the desired esters (as
the only products) in high yields. The transvinylation of 4-
methylcinnamic acid (1d) and 4-chlorocinnamic acid (1e)
gave esters 2d and 2e, respectively.
Next, we tested if the transvinylation reaction of unsaturated
carboxylic acids can be combined with subsequent RCM.
Unlike the previous works concerning the tandem metathesis/
nonmetathetic protocols,5−27 we postulate that the first step of
a cascade is a nonmetathetic reaction. Thus, the original
metathetic activity of the catalyst should be retained after the
transvinylation reaction.
b
entry
catalyst
yield (%)
1
2
Hg(OAc)2
Pd(OAc)2
Pd(OAc)2
Ru3(CO)12
(Ph3P)3RuCl2
12
35
38
28
<1
<1
18
41
86
c
3
4
5
6
7
8
9
[Ru-(p-cymene)Cl2]2
Grubbs first-generation
Grubbs−Hoveyda second-generation
Grubbs second-generation
a
Conditions: 1a (1 equiv), 4a (2 equiv), catalyst (5 mol %),
b
anhydrous toluene (c = 0.01), 16 h, inert atmosphere. Yield of
isolated product. Literature data:41 1a (1 equiv), 4a (11 equiv),
c
As a model substrate, we choose 3-phenyl-4-pentenoic acid
(1f). We have tested optimal cascade conditions (a catalyst, a
transvinylation agent, and temperature) (Table 2).
catalyst (1 mol %), tetrahydrofuran (THF), 60 °C, 16 h.
All reactions catalyzed by Grubbs second-generation catalyst
resulted in the formation of two products: vinyl ester (2f) and
4-phenyl-3,4-dihydro-2H-pyran-2-one (3f) (Table 2, entries
1−3). However, the best yield of tandem product was observed
when vinyl propionate (4b) was used as a transvinylation agent
at 80 °C (Table 2, entry 2). When vinylbenzoate (4c) was
applied, the yield of 2f was slightly lower, which can be
explained by the difficulty with the purification procedurethe
polarities of 4c and 2f are similar (Table 2, entry 3). We have
also tested other catalysts that were efficient in the trans-
vinylation reaction (Table 1, entries 2, 8) using donor 4b. The
reaction with Pd(OAc)2 resulted only in the formation of
product 2f (Table 2, entry 4). The Grubbs−Hoveyda second-
generation catalyst promoted both studied reactions leading to
the formation of ester 2f and lactone 3f (Table 2, entry 5).
However, the Grubbs second-generation catalyst proved to be
the most efficient for a studied cascade (Table 2, entry 2). To
demonstrate the practical utility of presented protocol, the
cascade was performed on a larger scale (1.5 mmol), resulting
in the formation of both desired products (Table 2, entry 6).
vinylation reaction requires the addition of strong acids or
bases. However, in our studies, to make the process
environmentally benign, the presence of these additives was
excluded. All reactions were conducted in toluene at 65 °C.
The reaction of 1a with vinyl acetate catalyzed by commonly
used transvinylation catalysts resulted in the formation of
desired product 2a in low yields (Table 1, entries 1−6).
Surprisingly, both Grubbs first- and Grubbs−Hoveyda second-
generation catalysts promoted the reaction; however, the yields
of product 2a were from low to moderate (Table 1, entries 7−
8). The best result was received in the presence of Grubbs
second-generation catalyst (86% yield) (Table 1, entry 9). In
all cases, the metathesis catalysts did not manifest their
metathetic activity as the formation of metathesis products
(dimers) was not observed. The only obtained product was
vinyl phenylacetate (2a). We have also performed similar
reactions of methyl phenylacetate with vinyl acetate and
palladium(II) acetate or Grubbs second-generation catalyst.
However, the progress of reactions was not observed, which
B
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a
a
Table 2. Tandem Reaction Parameters
Table 3. Substrate Scope
a
Conditions: 1f (1 equiv), 4 (2 equiv), catalyst (5 mol %), anhydrous
b
toluene (c = 0.01), 16 h, inert atmosphere. Yield of isolated product.
c
Reaction carried out on 1.5 mmol scale.
We have also examined the reaction of acid 1f with allyl acetate
(5). In this case 1,4-diacetoxybut-2-ene (6) (a product of
cross-metathesis of 5) was the only obtained product; acid 1f
was fully recovered from the reaction mixture (Table 2, entry
7).
Finally, we have examined the substrate scope for cascade
reaction employing various unsaturated carboxylic acids and
vinyl propionate (4b) in toluene at 80 °C (Table 3). The
yields of lactones 3 obtained via RCM reactions starting from
the corresponding vinyl esters 2 are given in parentheses.
First, we have tested 3-(alkyl or aryl)-4-pentenoic acids. In
all cases, the desired transvinylation and cascade products were
formed (Table 3, entries 1−3). When a diastereomeric mixture
of 2-methyl-3-phenyl-4-pentenoic acid (1i) was subjected to
the studied protocol, the corresponding vinyl ester 2i was
isolated in 1:1 diastereomeric ratio (dr) and its RCM product
3i, in 82:18 dr as a main isomer trans (Table 3, entry 3). This
phenomenon can be explained by the isomerization of the C
C bond by metathesis catalysts.45,46 The stirring of a minor cis-
3i isomer with Grubbs 2nd generation catalyst overnight
resulted in its full conversion to isomer trans. The acid 1j
underwent the transvinylation reaction and subsequent
domino ring-opening ring-closing metathesis reaction (ROM-
RCM) as it was also observed in our previous study33 (Table 3,
entry 4). The studied protocol was also successfully applied for
2-phenyl-4-pentenoic acid (1k) and 2-vinylbenzoic acid (1l)
(Table 3, entries 5 and 6). The reaction of 2-benzyl-3-butenoic
acid (1m) results in the formation of ester 2m and lactone 3m
(Table 3, entry 7). The structure of the obtained lactone 3m
differs from an expected RCM product of 2m and is in its
isomeric form.33 The application of carboxylic acids with
longer carbon chain than pentenoic results only in the
formation of transvinylation product (Table 3, entries 8 and
9), which is in accordance with our previous research.33 It is
also worth mentioning that in all studied cases, only the
transvinylation (2) and RCM (3) products were obtained.
Moreover, the obtained results show that both reactions are
catalyzed by the same catalyst, as after the transvinylation
reaction, the same catalyst successfully mediates the metathesis
a
Conditions: 1 (1 equiv), 4 (2 equiv), Grubbs second-generation
catalyst (5 mol %), anhydrous toluene (c = 0.01), 16 h, 80 °C inert
b
c
atmosphere. Yield of isolated product. The yields of products 3
obtained from RCM reaction starting from substrate 2 are given in
parentheses.
C
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reaction. The promotion of nonmetathetic reaction does not
result in the loss of metathetic activity of Grubbs catalyst.
We have also studied the mechanism of the newly developed
cascade reaction. Thus, we performed the reaction between 1f
and vinyl-13C2 acetate in the presence of the Grubbs second-
generation catalyst (Scheme 2). As a result, two 13C-labeled
amount of catalyst used; for the B reaction after the
completion of first step (transvinylation), the same amount
of catalyst was added (Table 4, entry 2). On the other hand,
both discussed reactions (A and B) proceeded much slower
than common RCM of 2f (Table 4, entry 3). The differences
in these values can be a result of complex reaction mixture.
The formation of vinyl esters would be reversible (the formed
propionic acid can undergo transvinylation); thus, a catalyst
can be also still involved in transvinylation. Nevertheless, the
obtained results indicate that the metathesis activity of Grubbs
second-generation catalyst is retained after the transvinylation
step.
Scheme 2. Reaction of 1f with Vinyl-13C2 Acetate
Based on the obtained results and literature data,47−49 we
have proposed the plausible mechanism of transvinylation
reaction mediated by Grubbs-type catalysts (Scheme 3).
In the first step, the Grubbs catalyst reacted with vinyl
acetate leading to the formation of Fischer carbene complex I.
As the decomposition of I in toluene proceeds slowly,49 we
assumed that in the next step, the transesterification with
carboxylic acid 1 occurs, leading to the formation of complex
II. Then, the complex II reacts with styrene molecule and the
ester bond toward the ruthenium center is cleaved, resulting in
the release of the vinyl ester 2 and catalyst, which can be used
in the next cycle. If the structure of carboxylic acid 1 enables
the RCM reaction, the formed ester 2 undergoes the
subsequent ring-closing metathesis.
products were obtainedvinyl-13C2 3-phenyl 4-pentenoate 2f
and 4-phenyl(6-13C)-3,4-dihydro-2H-pyran-2-one 3f. The
structures of products were confirmed by NMR analysis
(Supporting Information).
Next, we have also performed additional experiments to test
whether the metathesis activity of the Grubbs second-
generation catalyst is retained after the transvinylation step.
Thus, a set of experiments were designed (Table 4). First, the
Table 4. Studies on the Catalyst Activity
The previous studies50−52 suggested that complex I is not
involved in cross-metathesis; however, it can be applied for
RCM. This statement is in accordance with our results that the
only products of the proposed transformation are vinyl esters 2
and lactones 3; formation of dimers is not observed.
e
entry
reaction
VRCM (mol/L·s)
time (h)
TON
To support our hypothesis, an additional experiment was
performed. According to Johnson et al.49 Fischer carbene
complex I was prepared. The obtained compound I was added
to the solution of phenylacetic acid (1a) in toluene and stirred
at 80 °C. As a product, vinyl phenylacetate (2a) was obtained.
The result of the presented experiment confirms that the
transvinylation takes place through an acetoxycarbene I.
a
1
2
3
A
B
1.5 × 10−7
1.9 × 10−7
3.9 × 10−7
24
24
2
15
8.6
20
b
d
c
C
a
Conditions: 1a (0.1 mmol), 4b (0.2 mmol), Grubbs second-
generation catalyst (5 mol %), anhydrous toluene (c = 0.01), 2 h, 80
b
°C inert atmosphere, then 2f (0.1 mmol). Conditions: 1a (0.1
mmol), 4b (0.2 mmol), Grubbs second-generation catalyst (5 mol %),
anhydrous toluene (c = 0.01), 2 h, 80 °C inert atmosphere, then 2f
(0.1 mmol) and fresh Grubbs second-generation catalyst (5 mol %).
CONCLUSIONS
■
c
Conditions: 2f (0.1 mmol), Grubbs second-generation catalyst (5
In conclusion, our studies show a new type of nonmetathetic
activity of Grubbs-type catalyst in the transvinylation of
carboxylic acids. In comparison to classical methods involving
the application of toxic metal catalysts, the obtained protocol is
more efficient, less toxic, and works well for a broad range of
carboxylic acids under mild conditions. To the best of our
knowledge, the transvinylation reaction catalyzed by Grubbs-
type catalyst has no precedence in the literature. Since the
proposed mechanism of studied reaction indicates that
ruthenium catalyst did not lose its metathetic activity after
transvinylation reaction, attempts were made to combine
developed transvinylation protocol with subsequent metathesis
reaction. For selected unsaturated carboxylic acids, RCM
proceeds efficiently, leading to the formation of endocyclic
enol lactones. It is worth mentioning that both cascade
reactions are chemoselective, as the formation of side products
was not observed. Moreover, this is a rare example of cascade
protocol where a metathesis catalyst does not lose its
metathetic activity in a nonmetathetic step (transvinylation).
Vinyl esters of carboxylic acids as well as endocyclic enol
lactones are important building blocks for the synthesis of
biologically active compounds; thus, we expect that our newly
d
mol %), anhydrous toluene (c = 0.01), 2 h. The amount of catalyst
no
ncat
yield ×
e
used was 2-fold. Calculated from the equation: TON =
where no = initial moles of 2f; ncat = moles of catalyst used.
,
100
transvinylation reaction between phenylacetic acid 1a and vinyl
propionate 2a was performed. Then, upon the completion of
the transvinylation step, a cyclization precursor 2f was added
(reaction A). In the meantime, a similar reaction was carried
out; however, in this case, after the transvinylation, a certain
amount of fresh Grubbs second-generation catalyst was added
to the reaction mixture (reaction B). The rates (VRCM) as well
as turnover number (TON) of both RCM reactions were
measured and compared together with single RCM reaction
starting from 2f only (reaction C) (Table 4).
From the results (Table 4), it can be seen that the rates of
ring-closing metathesis of 2f, where in the first step, the
transvinylation of acid 1a occurs, are similar (Table 4, entry 1
and 2). The addition of a certain amount of fresh metathesis
catalyst did not significantly affect the reaction rate (reaction A
vs B). The differences in the TON values are due to the
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Scheme 3. Plausible Mechanism of the Studied Reaction
temperature and filtered over a Celite pad. The excess of solvent was
removed under reduced pressure. The crude product was purified by
column chromatography on silica gel (hexanes/ethyl acetate).
Vinyl 2-Phenylpropionate (2b). The product was isolated as a
colorless oil from a silica column eluted by EtOAc/hexanes (1:10) in
82% yield (57.5 mg); 1H NMR (400 MHz, CDCl3): δ 7.30−7.21 (m,
4H), 7.21−7.14 (m, 2H), 4.78 (dd, J = 14.0, 1.6 Hz, 1H), 4.47 (dd, J
= 6.3, 1.6 Hz, 1H), 3.70 (q, J = 7.2 Hz, 1H), 1.47 (d, J = 7.2 Hz, 3H);
13C{H} NMR (100 MHz, CDCl3): δ 171.6, 141.4, 139.7, 128.7,
developed protocol will gain access for the synthesis of the
pharmaceuticals and fine added-value chemicals.
EXPERIMENTAL SECTION
■
General. All of the chemicals were obtained from commercial
sources. The solvents were of analytical grade. Phenylacetic acid, 4-
chlorocinnamic acid, 4-methylcinnamic acid, 2-phenylpropionic acid,
Naproxen, 2-cyclopent-1-acetic acid, 2-vinylbenzoic acid, and oleic
acid were obtained from commercial source and used without further
purification. All yields refer to isolated compounds. NMR spectra
were recorded in CDCl3 with tetramethylsilane (TMS) as an internal
standard using Bruker 400 MHz spectrometers. The chemical shifts
are reported in ppm (δ scale), and the coupling constants (J) are
given in hertz (Hz). High-resolution mass spectra (HRMS) were
recorded on a Synapt G2:SHD apparatus with QqTOF analyzer. All
of the reactions were monitored by thin-layer chromatography (TLC)
on Merck silica gel Plates 60 F254. Column chromatography was
performed on Merck silica gel 60/230−400 mesh.
1
127.5, 127.3, 97.9, 45.3, 18.4. The H and 13C NMR data were in
accordance with those reported in the literature.43
Vinyl 2-(6-Methoxy-2-naphthyl)propionate (2c). The product was
isolated as white crystals from a silica column eluted by EtOAc/
hexanes (15:85) in 71% yield (73 mg); 1H NMR (400 MHz, CDCl3):
δ 7.65−7.59 (m, 3H), 7.33 (dd, J = 8.5, 1.9 Hz, 1H), 7.22−7.15 (m,
1H), 7.09−7.03 (m, 2H), 4.77 (dd, J = 14.0, 1.6 Hz, 1H), 4.47 (dd, J
= 6.3, 1.6 Hz, 1H), 3.84−3.81 (m, 4H), 1.54 (d, J = 7.1 Hz, 3H);
13C{H} NMR (100 MHz, CDCl3): δ 171.7, 157.8, 141.4, 134.8,
133.8, 129.3, 128.9, 127.3, 126.1, 119.1, 105.6, 97.9, 55.3, 45.2, 18.4.
The 1H and 13C NMR data were in accordance with those reported in
the literature.54
Vinyl 4-Methylcinnamate (2d). The product was isolated as white
crystals from a silica column eluted by EtOAc/hexanes (1:9) in 91%
yield (68.5 mg); 1H NMR (400 MHz, CDCl3): δ 7.68 (d, J = 15.9 Hz,
1H), 7.47−7.40 (m, 2H), 7.35 (dd, J = 14.0, 6.3 Hz, 1H), 6.88−6.81
(m, 2H), 6.25 (d, J = 16.0 Hz, 1H), 4.89 (dd, J = 14.0, 1.6 Hz, 1H),
4.54 (dd, J = 6.3, 1.6 Hz, 1H), 3.77 (s, 3H); 13C{H} NMR (100
MHz, CDCl3): δ 164.2, 161.8, 146.3, 141.4, 130.0, 126.9, 114.4,
114.0, 97.4, 55.4; HRMS (EI+, m/z): calcd. for C12H12O2 [M]+:
188.0837, found 188 0840.
General Procedure for the Transvinylation of Phenylacetic
Acid (1a). To a solution of phenylacetic acid 1a (0.4 mmol) and vinyl
acetate (0.8 mmol) in an anhydrous toluene (40 mL) under argon
atmosphere was added an appropriate catalyst (5 mol %). The
reaction mixture was heated in an oil bath at 65 °C for 16 h. The
reaction mixture was cooled to room temperature and filtered over a
Celite pad. The excess of solvent was removed under reduced
pressure. The crude product was purified by column chromatography
on silica gel (hexanes/ethyl acetate).
Vinyl Phenylacetate (2a). The product was isolated as an yellow
oil from a silica column eluted by EtOAc/hexanes (1:10) in 86% yield
1
(56 mg); H NMR (400 MHz, CDCl3): δ 7.29−7.21 (m, 5H), 7.18
Vinyl 4-Chlorocinnamate (2e). The product was isolated as white
crystals (mp 57 °C) from a silica column eluted by EtOAc/hexanes
(t, J = 3.2 Hz, 1H), 4.83 (dd, J = 13.9, 1.7 Hz, 1H), 4.52 (dd, J = 6.3,
1.7 Hz, 1H), 3.63 (s, 2H); 13C{H} NMR (100 MHz, CDCl3): δ
1
1
168.7, 141.3, 129.3, 128.7, 127.3, 98.0, 40.9. The H and 13C NMR
(1:9) in 45% yield (37.5 mg); H NMR (400 MHz, CDCl3): δ 7.67
data were in accordance with those reported in the literature.53
General Procedure for the Transvinylation of Carboxylic
Acids (1b−e). To a solution of the corresponding carboxylic acid
(1b−e) (0.4 mmol) and vinyl acetate (0.8 mmol) in an anhydrous
toluene (40 mL) under argon atmosphere was added Grubbs second-
generation catalyst (5 mol %). The reaction mixture was heated in an
oil bath at 65 °C for 16 h. The reaction mixture was cooled to room
(d, J = 16.0 Hz, 1H), 7.44−7.38 (m, 2H), 7.37−7.28 (m, 3H), 6.36
(d, J = 16.0 Hz, 1H), 4.91 (dd, J = 14.0, 1.7 Hz, 1H), 4.57 (dd, J =
6.2, 1.7 Hz, 1H); 13C{H} NMR (100 MHz, CDCl3): δ 163.7, 145.1,
141.3, 136.7, 132.6, 129.4, 129.3, 117.3, 97.9; HRMS (EI+, m/z):
calcd. for C11H9O2Cl [M]+: 208.0291, found 208,0298.
Synthesis of Carboxylic Acids. Carboxylic acids 1f,33,55 1g,33
1h,33 1i,33,56 1k,33,57 1m,58 and 1n59 were synthesized and purified
E
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1
according to the literature procedure. The H and 13C NMR data
δ 7.28−6.89 (m, 6H), 5.98−5.82 (m, 1H), 5.11−4.92 (m, 2H), 4.75
(ddd, J = 68.9, 13.9, 1.6 Hz, 1H), 4.44 (ddd, J = 55.7, 6.3, 1.6 Hz,
1H), 3.50−3.39 (m, 1H), 2.84−2.79 (m, 1H), 1.18 (d, J = 7.0 Hz,
2H), 0.94 (d, J = 6.9 Hz, 1H). 13C {H}NMR (100 MHz, CDCl3): δ
172.6, 172.2, 141.8, 141.2, 141.1, 140.9, 139.3, 138.1, 128.7, 128.5,
128.0, 127.6, 126.8, 126.7, 117.0, 115.8, 97.8, 97.6, 53.5, 53.4, 45.1,
44.8, 15.6, 15.2., HRMS (ESI+, m/z): calcd. for C14H16O2Na [M +
Na]+: 239.1048, found 21739.1040.
were in accordance with those reported in the literature.
General Procedure for Tandem Transvinylation/RCM Re-
action (2f−o, 3f−m). To a solution of an appropriate unsaturated
carboxylic acid (1f−o) (0.4 mmol) and vinyl propionate (0.8 mmol)
in an anhydrous toluene (40 mL) under argon atmosphere was added
Grubbs second-generation catalyst (5 mol %). The reaction mixture
was heated in an oil bath at 80 °C for 16 h. The reaction mixture was
cooled to room temperature and filtered over a Celite pad. The excess
of solvent was removed under reduced pressure. The crude product
was purified by column chromatography on silica gel (hexanes/ethyl
acetate).
Vinyl 3-Phenyl-4-pentenoate (2f). The product was isolated as a
colorless oil from a silica column eluted by EtOAc/hexanes (1:10) in
41% yield (33 mg); H NMR (400 MHz, CDCl3): δ 7.28−7.23 (m,
2H), 7.18−7.12 (m, 4H), 5.99−5.86 (m, 1H), 5.06−4.97 (m, 2H),
4.79 (dd, J = 14.0, 1.6 Hz, 1H), 4.48 (dd, J = 6.3, 1.6 Hz, 1H), 3.84
(q, J = 7.4 Hz, 1H), 2.82−2.69 (m, 2H); 13C{H} NMR (100 MHz,
CDCl3): δ 168.9, 142.1, 141.1, 139.9, 128.7, 127.5, 126.9, 115.1, 97.8,
45.3, 39.9; HRMS (EI+, m/z): calcd. for C13H14O2 [M]+: 202.0994,
found 202.0996.
4-Phenyl-3,4-dihydro-2H-pyran-2-one (3f). The product was
isolated as a colorless oil from a silica column eluted by EtOAc/
hexanes (1:9) in 41% yield (28 mg); 1H NMR (400 MHz, CDCl3): δ
7.31−7.20 (m, 3H), 7.17−7.12 (m, 2H), 6.61 (dd, J = 6.0, 1.8 Hz,
1H), 5.37 (dd, J = 6.0, 4.0 Hz, 1H), 3.79−3.69 (m, 1H), 2.91 (dd, J =
15.9, 6.5 Hz, 1H), 2.67 (dd, J = 16.0, 8.3 Hz, 1H); 13C{H} NMR
(100 MHz, CDCl3): δ 167.3, 141.6, 141.2, 129.1, 127.5, 126.8, 109.4,
37.3, 36.7; HRMS (ESI+, m/z): calcd. for C11H11O2 [M + H]+:
175.0759, found 175.0768.
Vinyl 3-Propyl-4-pentenoate (2g). The product was isolated as a
colorless oil from a silica column eluted by EtOAc/hexanes (1:10) in
10% yield (7 mg); 1H NMR (400 MHz, CDCl3): δ 7.19 (dd, J = 14.0,
6.3 Hz, 1H), 5.67−5.58 (m, 1H), 5.06−5.00 (m, 2H), 4.88 (dd, J =
14.0, 1.6 Hz, 1H), 4.54 (dd, J = 6.3, 1.4 Hz, 1H), 2.59−2.55 (m, 1H),
2.38 (ddd, J = 23.2, 15.0, 8.6 Hz, 2H), 1.35 (ddt, J = 20.4, 6.0, 5.4 Hz,
4H), 0.85 (t, J = 6.7 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3): δ
169.6, 141.2, 140.7, 115.3, 97.5, 39.9, 39.8, 36.6, 20.0, 13.9; HRMS
(EI+, m/z): calcd. for C10H16O2 [M]+: 168.1150, found 168,1147.
4-Propyl-3,4-dihydro-2H-pyran-2-one (3g). The product was
isolated as a colorless oil from a silica column eluted by EtOAc/
hexanes (1:9) in 83% yield (46.5 mg); 1H NMR (400 MHz, CDCl3):
δ 6.40 (dd, J = 6.0, 1.6 Hz, 1H), 5.18 (dd, J = 5.9, 4.0 Hz, 1H), 2.69−
2.59 (m, 1H), 2.51−2.42 (m, 1H), 2.34 (dd, J = 15.5, 8.0 Hz, 1H),
1.38−1.27 (m, 4H), 0.88−0.81 (m, 3H); 13C{H} NMR (100 MHz,
CDCl3) δ 168.5, 140.6, 110.4, 36.8, 34.9, 30.2, 19.5, 13.9; HRMS
(ESI+, m/z): calcd. for C8H12O2 [M + H]+: 140.0837, found
140.0849.
Vinyl 3-(Benzyloxymethyl)-4-pentenoate (2h). The product was
isolated as a colorless oil from a silica column eluted by EtOAc/
hexanes (1:10) in 20% yield (20 mg); 1H NMR (400 MHz, CDCl3):
δ 7.35−7.21 (m, 6H), 5.82−5.73 (m, 1H), 5.19−5.09 (m, 2H), 4.86
(dd, J = 14.0, 1.5 Hz, 1H), 4.55 (dd, J = 6.3, 1.6 Hz, 1H), 4.51 (s,
2H), 3.54−3.50 (m, 1H), 3.42−3.38 (m, 1H), 2.96−2.94 (m, 1H),
2.71−2.64 (m, 1H), 2.48−2.42 (m, 1H); 13C{H} NMR (100 MHz,
CDCl3): δ 169.5, 141.2, 138.2, 137.5, 128.4, 127.6, 127.5, 116.5, 97.6,
73.1, 72.6, 40.1, 36.3, HRMS (ESI+, m/z): calcd. for C15H18O3Na [M
+ Na]+: 269.1154, found 269.1157.
4-(Benzyloxymethyl)-3,4-dihydro-2H-pyran-2-one (3h). The
product was isolated as a colorless oil from a silica column eluted
by EtOAc/hexanes (1:9) in 68% yield (59 mg); 1H NMR (400 MHz,
CDCl3): δ 7.30−7.20 (m, 5H), 6.46 (dd, J = 6.0, 1.4 Hz, 1H), 5.16
(dd, J = 5.9, 4.2 Hz, 1H), 4.45 (s, 2H), 3.39−3.32 (m, 2H), 2.71−
2.68 (m, 1H), 2.66−2.52 (m, 2H); 13C{H} NMR (100 MHz,
CDCl3): δ 167.9, 141.9, 137.8, 128.4, 127.7, 127.5, 106.7, 73.3, 71.6,
32.2, 31.7; HRMS (ESI+, m/z): calcd. for C13H15O3 [M + H]+:
219.1021, found 219.1028.
Trans-4-Phenyl-5-methyl-3,4-dihydro-2H-pyran-2-one (3i). The
product was isolated as a colorless oil from a silica column eluted by
1
EtOAc/hexanes (1:9) in 36% yield (27 mg); H NMR (400 MHz,
CDCl3): δ 7.30−7.10 (m, 5H), 6.53 (dd, J = 6.0, 2.4 Hz, 1H), 5.21
(dd, J = 6.0, 2.9 Hz, 1H), 3.35 (dt, J = 10.6, 2.7 Hz, 1H), 2.68 (dq, J =
10.6, 6.9 Hz, 1H), 1.11 (d, J = 6.9 Hz, 3H). 13C{H} NMR (100 MHz,
CDCl3): δ 170.7, 141.3, 140.6, 128.9, 127.5, 127.5, 109.9, 44.3, 41.5,
14.2; HRMS (EI+, m/z): calcd. for C12H12O2 [M]+: 188.0837, found
188.00843.
cis-4-Phenyl-5-methyl-3,4-dihydro-2H-pyran-2-one (3i). The
product was isolated as a colorless oil from a silica column eluted
by EtOAc/hexanes (15:85) in 8% yield (6 mg); 1H NMR (400 MHz,
CDCl3): δ 7.24−7.01 (m, 5H), 6.62 (d, J = 5.9 Hz, 1H), 5.45 (t, J =
5.9 Hz, 1H), 3.53−3.47 (m, 1H), 3.08−2.99 (m, 1H), 0.94 (d, J = 7.0
Hz, 3H). 13C{H} NMR (100 MHz, CDCl3): δ 170.9, 141.2, 128.8,
128.1, 127.7, 109.9, 42.8, 39.4, 12.4. HRMS (EI+, m/z): calcd. for
C12H12O2 [M]+: 188.0837, found 188.00843.
Vinyl 2-Cyclopent-1-acetate (2j). The product was obtained from
commercially available 2-cyclopent-1-acetic acid, and it was isolated as
a colorless oil from a silica column eluted by EtOAc/hexanes (1:10)
in 50% yield (30 mg); 1H NMR (400 MHz, CDCl3): δ 7.23 (dd, J =
14.0, 6.3 Hz, 1H), 5.72 (td, J = 4.3, 2.0 Hz, 1H), 5.61 (ddd, J = 5.8,
4.1, 2.0 Hz, 1H), 4.82 (dd, J = 14.0, 1.4 Hz, 1H), 4.50 (dd, J = 6.3, 1.4
Hz, 1H), 3.13−2.99 (m, 1H), 2.46−2.18 (m, 4H), 2.16−2.03 (m,
1H), 1.47−1.38 (m, 1H); 13C{H} NMR (100 MHz, CDCl3): δ 169.9,
141.1, 133.3, 131.8, 97.5, 41.8, 40.0, 31.8, 29.6; HRMS (ES+, m/z):
calcd. for C9H12O2 [M]+: 152.0837, found 152.0842.
4-(But-3-en-1-yl)-3,4-dihydro-2H-pyran-2-one (3j). The product
was isolated as a colorless oil from a silica column eluted by EtOAc/
hexanes (1:9) in 35% yield (21 mg); 1H NMR (400 MHz, CDCl3): δ
6.41 (dd, J = 6.0, 1.5 Hz, 1H), 5.75−5.66 (m, 1H), 5.20 (dd, J = 5.9,
4.1 Hz, 1H), 5.17−4.92 (m, 2H), 2.68−2.63 (m, 1H), 2.48−2.46 (m,
1H), 2.42−2.33 (m, 1H), 2.06−2.02 (m, 2H), 1.48−1.43 (m, 2H);
13C{H} NMR (100 MHz, CDCl3): δ 168.3, 140.8, 137.3, 115.5,
110.1, 34.8, 33.7, 30.5, 29.8; HRMS (ESI+, m/z): calcd. for C9H13O2
[M + H]+: 153.0916, found 153.0921.
Vinyl 2-Phenyl-4-pentenoate (2k). The product was isolated as a
colorless oil from a silica column eluted by EtOAc/hexanes (1:10) in
32% yield (25.5 mg); 1H NMR (400 MHz, CDCl3): δ 7.27−7.19 (m,
5H), 7.16 (dd, J = 12.3, 4.6 Hz, 1H), 5.71−5.61 (m, 1H), 5.04−4.96
(m, 2H), 4.79 (dd, J = 14.0, 1.6 Hz, 1H), 4.48 (dd, J = 6.3, 1.6 Hz,
1H), 3.62 (dd, J = 8.4, 7.1 Hz, 1H), 2.82−2.71 (m, 1H), 2.51−2.44
(m, 1H); 13C{H} NMR (100 MHz, CDCl3): δ 178.3, 142.2, 140.2,
128.9, 127.8, 127.1, 115.3, 45.5, 40.2; HRMS (EI+, m/z): calcd. for
C13H14O2 [M]+: 202.0994, found 202.0998.
5-Phenyl-3,4-dihydro-2H-pyran-2-one (3k). The product was
isolated as a colorless oil from a silica column eluted by EtOAc/
hexanes (1:9) in 67% yield (46.5 mg); 1H NMR (400 MHz, CDCl3):
δ 7.30−7.17 (m, 5H), 6.49 (ddd, J = 5.9, 2.0, 1.2 Hz, 1H), 5.31 (ddd,
J = 5.8, 5.2, 3.6 Hz, 1H), 3.80−3.75 (m, 1H), 2.59−2.51 (m, 2H);
13C{H} NMR (100 MHz, CDCl3): δ 169.2, 141.6, 137.1, 128.7,
128.1, 127.7, 105.4, 45.3, 26.9; C11H11O2 [M + H]+: 175.0759, found
175.0767.
Vinyl 2-Vinylbenzoate (2l). The product was obtained from
commercially available 2-vinylbenzoic acid and isolated as a yellowish
oil from a silica column eluted by EtOAc/hexanes (1:10) in 15% yield
(10.5 mg); 1H NMR (400 MHz, CDCl3): δ 7.91 (dd, J = 7.9, 1.1 Hz,
1H), 7.53 (d, J = 7.9 Hz, 1H), 7.49−7.35 (m, 3H), 7.28 (td, J = 7.8,
1.2 Hz, 1H), 5.59 (dd, J = 17.4, 1.2 Hz, 1H), 5.31 (dd, J = 11.0, 1.2
Hz, 1H), 4.97 (dd, J = 14.0, 1.6 Hz, 1H), 4.63 (dd, J = 6.3, 1.6 Hz,
1H); 13C{H} NMR (100 MHz, CDCl3): δ 164.04, 141.38, 140.48,
1
Vinyl 2-Methyl-3-phenyl-4-pentenoate (2i). The product was
isolated as a colorless oil from a silica column eluted by EtOAc/
hexanes (1:10) in 35% yield (30 mg); 1H NMR (400 MHz, CDCl3):
F
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135.69, 132.79, 130.64, 127.50, 127.45, 127.08, 116.91, 98.24; HRMS
(EI+, m/z): calcd. for C11H10O2 [M]+: 174.0681, found 174.0681.
Isocumarin (3l). The product was isolated as a colorless oil from a
silica column eluted by EtOAc/hexanes (1:9) in 78% yield (45.5 mg);
1H NMR (400 MHz, CDCl3): δ 8.29 (d, J = 8.0 Hz, 1H), 7.70 (td, J =
7.7, 1.2 Hz, 1H), 7.56−7.49 (m, 1H), 7.41 (d, J = 7.8 Hz, 1H), 7.25
(d, J = 4.7 Hz, 1H), 6.48 (d, J = 5.6 Hz, 1H); 13C{H} NMR (100
MHz, CDCl3): δ 162.3, 144.7, 136.3, 134.8, 129.7, 128.6, 125.5,
121.6, 106.9.; HRMS (ESI+, m/z): calcd. for C9H7O2 [M + H]+:
147.0446, found 147.0450.
transvinylation step). Then, vinyl-3-phenyl-4-pentenoate (2f) (0.1
mmol) was added. The progress of the reaction was monitored on
high-performance liquid chromatography (HPLC; Kromasil SI 60/5
μm column); hexane/isopropanol (98:2), λ = 216 nm; 0.5 mL/min,
retention time (in min): t2a = 4.8, t2f = 5.1, t3f =11.3. Reaction B:
To a solution of a phenylacetic acid (1a) (0.1 mmol) and vinyl
propionate (0.2 mmol) in an anhydrous toluene (10 mL) under argon
atmosphere was added Grubbs second-generation catalyst (5 mol %).
The reaction mixture was heated in an oil bath at 80 °C for 2 h (upon
the completion of transvinylation step). Then, vinyl-3-phenyl-4-
pentenoate (0.1 mmol) and a certain amount of Grubbs second-
generation catalyst (5 mol %) were added. The progress of the
reaction was monitored on HPLC (Kromasil SI 60/5 μm column);
hexane/isopropanol (98:2), λ = 216 nm; 0.5 mL/min, retention time
(in min): t2a = 4.8, t2f = 5.1, t3f =11.3. Reaction C: To a solution of
vinyl 3-phenyl-4-pentenoate (0.1 mmol) in an anhydrous toluene (10
mL) under argon atmosphere was added Grubbs second-generation
catalyst (5 mol %). The reaction mixture was heated in an oil bath at
80 °C for 2 h. The progress of the reaction was monitored on HPLC
(Kromasil SI 60/5 μm column); hexane/isopropanol (98:2), λ = 216
nm; 0.5 mL/min, retention time (in min): t2f = 5.1, t3f =11.3.
Mechanistic Studies on the Tandem Transvinylation/RCM
Reaction. To a solution of 3-phenyl-4-pentenoic acid (1f) (0.15
mmol) and vinyl-13C2 acetate (0.3 mmol) in an anhydrous toluene (5
mL) under argon atmosphere was added Grubbs second-generation
catalyst (5 mol %). The reaction mixture was heated in an oil bath at
60 °C for 16 h. The reaction mixture was cooled to room temperature
and filtered over a Celite pad. The excess of solvent was removed
under reduced pressure. The products were purified by column
chromatography on silica gel (hexanes/ethyl acetate).
Vinyl 2-Benzyl-3-butenoate (2m). The product was isolated as a
colorless oil from a silica column eluted by EtOAc/hexanes (1:10) in
1
35% yield (28 mg); H NMR (400 MHz, CDCl3): δ 7.23−7.08 (m,
6H), 5.84−5.75 (m, 1H), 5.13−5.01 (m, 2H), 4.79 (dd, J = 14.0, 1.7
Hz, 1H), 4.49 (dd, J = 6.3, 1.7 Hz, 1H), 3.35−3.29 (m, 1H), 3.06 (dd,
J = 13.7, 7.7 Hz, 1H), 2.81 (dd, J = 13.7, 7.3 Hz, 1H); 13C{H} NMR
(100 MHz, CDCl3): δ 170.4, 141.2, 138.2, 134.5, 129.1, 128.4, 126.6,
118.3, 98.1, 51.7, 38.2; HRMS (EI+, m/z): calcd. for C13H15O2 [M]+:
202.0994, found 202.0997.
3-(Phenylmethyl)-2(5H)-furanone (3m). The product was isolated
as a colorless oil from a silica column eluted by EtOAc/hexanes (1:9)
in 26% yield (18 mg); 1H NMR (400 MHz, CDCl3): δ 7.34−7.22 (m,
5H), 6.98−6.89 (m, 1H), 4.75 (dd, J = 4.0, 2.2 Hz, 2H), 3.60 (d, J =
1.8 Hz, 2H); 13C{H} NMR (100 MHz, CDCl3): δ 173.9, 145.4,
137.4, 134.4, 128.9, 128.8, 126.8, 70.2, 31.8; HRMS (ESI+, m/z):
calcd. for C11H11O2 [M + H]+: 175.0759, found 175.0765.
Vinyl 2-Phenyl-5-hexenoate (2n). The product was isolated as a
colorless oil from a silica column eluted by EtOAc/hexanes (1:10) in
1
89% yield (80 mg); H NMR (400 MHz, CDCl3): δ 7.26−7.18 (m,
5H), 7.16 (dd, J = 10.0, 3.9 Hz, 1H), 5.75−5.65 (m, 1H), 4.95-4.76
(m, 2H), 4.78 (dd, J = 14.0, 1.6 Hz, 1H), 4.47 (dd, J = 6.3, 1.6 Hz,
1H), 3.55 (t, J = 7.6 Hz, 1H), 2.18-2.09 (m, 1H), 1.96 (dd, J = 14.3,
6.9 Hz, 2H), 1.87−1.76 (m, 1H); 13C{H} NMR (100 MHz, CDCl3):
δ 171.0, 141.3, 138.1, 137.3, 128.7, 128.0, 127.5, 115.6, 97.9, 50.5,
32.3, 31.4; HRMS (EI+, m/z): calcd. for C14H16O2 [M]+: 216.1150,
found 216.1157.
Vinyl-13C2 3-phenyl-4-pentenoate. The product was isolated as a
colorless oil from a silica column eluted by EtOAc/hexanes (1:10) in
1
40% yield (12 mg); H NMR (400 MHz, CDCl3): δ 7.37 (ddd, J =
14.0, 9.6, 6.3 Hz, 0.5H), 7.29−7.20 (m, 2H), 7.20−7.10 (m, 3H),
6.89 (ddd, J = 14.0, 9.6, 6.3 Hz, 0.5), 6.00−5.84 (m, 1H), 5.06−4.99
(m, 2H), 4.97 (ddd, J = 14.0, 8.2, 1.7 Hz, 0.5H), 4.67 (ddd, J = 7.8,
6.3, 1.6 Hz, 0.5H), 4.58 (ddd, J = 14.0, 8.2, 1.7 Hz, 0.5H), 4.26 (ddd,
J = 7.8, 6.3, 1.6 Hz, 0.5H), 3.83 (q, J = 7.4 Hz, 1H), 2.83−2.66 (m,
2H); 13C{H} NMR (100 MHz, CDCl3): δ 168.9, 142.1, 141.5 (13C-
labeled, J = 82.2 Hz), 139.9, 128.7, 127.5, 126.8, 115.1, 97.8 (13C-
labeled, J = 82.2 Hz), 45.3, 39.9. HRMS (EI+, m/z): calcd. for
C1113C2H14O2 [M]+: 204.1061, found 204.1059.
Vinyl Oleate (2o). The product was isolated as a colorless oil from
a silica column eluted by EtOAc/hexanes (1:10) in 87% yield (107
mg); 1H NMR (400 MHz, CDCl3): δ 7.21 (dd, J = 13.9, 6.2 Hz, 1H),
5.31−5.22 (m, 2H), 4.80 (dd, J = 13.9, 1.6 Hz, 1H), 4.48 (dd, J = 6.3,
1.6 Hz, 1H), 2.31 (t, J = 7.5 Hz, 2H), 1.94 (q, J = 6.5 Hz, 4H), 1.59
(t, J = 7.2 Hz, 2H), 1.29−1.19 (m, 20H), 0.81 (t, J = 6.8 Hz, 3H).;
13C{H} NMR (100 MHz, CDCl3): δ 170.8, 141.2, 130.0, 129.7, 97.4,
33.9, 31.9, 29.8, 29.7, 29.5, 29.3, 29.1, 29.1, 29.0, 27.2, 27.1, 24.6,
1
22.7, 14.1. H and 13C NMR data were in accordance with those
reported in the literature.60
4-Phenyl(6-13C)-3,4-dihydro-2H-pyran-2-one. The product was
isolated as a colorless oil from a silica column eluted by EtOAc/
1,4-Diacetoxybut-2-ene (6). The product was isolated as a
colorless oil from a silica column eluted by EtOAc/hexanes (1:10)
in 75% yield (51.5 mg); 1H NMR (400 MHz, CDCl3): δ 5.79 (dt, J =
3.0, 1.7 Hz, 2H), 4.56−4.45 (m, 4H), 2.01 (s, 6H); 13C{H} NMR
(100 MHz, CDCl3): δ 170.6, 128.0, 63.8, 20.8. 1H and 13C NMR data
were in accordance with those reported in the literature.61
Larger-Scale Tandem Transvinylation/RCM Reaction. To a
solution of 3-phenyl-4-pentenoic acid (1f) (1.5 mmol) and vinyl
propionate (3 mmol) in an anhydrous toluene (150 mL) under argon
atmosphere was added Grubbs second-generation catalyst (5 mol %).
The reaction mixture was heated in an oil bath at 80 °C for 16 h. The
reaction mixture was cooled to room temperature and filtered over a
Celite pad. The excess of solvent was removed under reduced
pressure. The crude product was purified by column chromatography
on silica gel (hexanes/ethyl acetate): vinyl 3-phenyl-4-pentenoate (2f)
was isolated as a colorless oil from a silica column eluted by EtOAc/
hexanes (1:10) in 52% yield (157 mg); 4-phenyl-3,4-dihydro-2H-
pyran-2-one (3f) was isolated as a colorless oil from a silica column
eluted by EtOAc/hexanes (1:9) in 33% yield (86 mg).
1
hexanes (1:9) in 17% yield (5 mg); H NMR (400 MHz, CDCl3): δ
7.32−7.23 (m, 3H), 7.24−7.12 (m, 2H), 6.86 (dd, J = 6.0, 1.8 Hz,
0.5H) 6.36 (dd, J = 6.0, 1.8 Hz, 0.5H), 5.37 (ddd, J = 8.4, 6.0, 4.0 Hz,
1H), 3.80−3.69 (m, 1H), 2.91 (dd, J = 15.9, 6.5 Hz, 1H), 2.67 (dd, J
= 16.0, 8.3 Hz, 1H).; 13C{H} NMR (100 MHz, CDCl3): δ 167.3,
141.6 (13C-labeled), 141.2, 129.1, 127.5, 126.8, 109.4, 37.1, 36.8.
HRMS (EI+, m/z): calcd. for C1013CH10O2 [M]+: 175.0714, found
175.0718.
Mechanistic Studies on the Transvinylation Reaction:
Complex 1. Complex 1 was prepared according to the literature
method.49 To a stirred solution of Grubbs second-generation catalyst
(0.05 mmol) in toluene (5 mL) was added excess vinyl acetate (1.02
mmol, 20.4 equiv). The solution was stirred for 1 h, over which time
the color changed from purple to orange. Then, the excess of vinyl
acetate was distilled off and a solution of phenylactetic acid 1a (0.1
mmol) in toluene (5 mL) was added. The reaction mixture was
heated in an oil bath at 80 °C for 2 h. The reaction mixture was
cooled to room temperature and filtered over a Celite pad. The excess
of solvent was removed under reduced pressure. The residue was
purified by column chromatography on silica gel (hexanes/ethyl
acetate) to give vinyl 2-phenylacetate (2a) in 85% yield.
Studies on Catalyst Activity: Reaction A. To a solution of
phenylacetic acid (1a) (0.1 mmol) and vinyl propionate (0.2 mmol)
in an anhydrous toluene (10 mL) under argon atmosphere was added
Grubbs second-generation catalyst (5 mol %). The reaction mixture
was heated in an oil bath at 80 °C for 2 h (upon the completion of
G
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Article
and Ruthenium Hydride Chemistry: Organometallic Aspects and
Applications to Organic Synthesis. Eur. J. Org. Chem. 2004, 2004,
1865−1880. (e) Nam, Y. H.; Snapper, M. L. Handbookof Matathesis.
In Applications in Organic Synthesis; Grubbs, R. H.; O’Leary, D. J.,
Eds.; Wiley: Weinheim, 2015; Vol. 2, pp 311−377.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02135.
■
sı
Studies on catalyst activityconversion, reaction rate,
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1
and TON calculation; H NMR and 13C NMR spectra
of all products; standard curves for compounds 2f and
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initial rates of RCM reactions; and calculation of TON
(PDF)
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AUTHOR INFORMATION
Corresponding Authors
Anna Brodzka − Institute of Organic Chemistry Polish
Academy of Sciences, 01-224 Warszawa, Poland;
orcid.org/0000-0002-6659-0758;
■
(10) Connolly, T.; Wang, Z.; Walker, M. A.; McDonald, I. M.;
Peese, K. M. Tandem ring-closing metathesis/transfer hydrogenation:
practical chemoselective hydrogenation of alkenes. Org. Lett. 2014, 16,
4444−4447.
Email: anna.brodzka@icho.edu.pl
Ryszard Ostaszewski − Institute of Organic Chemistry Polish
Academy of Sciences, 01-224 Warszawa, Poland;
orcid.org/0000-0002-3032-196X;
́
(11) Zielinski, G. K.; Majtczak, J.; Gutowski, M.; Grela, K. A
Selective and Functional Group-Tolerant Ruthenium-Catalyzed
Olefin Metathesis/Transfer Hydrogenation Tandem Sequence
Using Formic Acid as Hydrogen Source. J. Org. Chem. 2018, 83,
2542−2553.
Email: ryszard.ostaszewski@icho.edu.pl
Author
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Dominik Koszelewski − Institute of Organic Chemistry Polish
Academy of Sciences, 01-224 Warszawa, Poland
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02135
Author Contributions
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Polish National Science
Center project Preludium no. 2013/11/N/ST5/02723 and
Opus no. 2016/23/B/ST5/03307.
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