One-pot synthesis of α,β-unsaturated ketones through sequential alkyne dimerization/hydration reactions using the Hoveyda-Grubbs catalyst

Article abstract of DOI:10.1039/d1nj02410h

Herein we report a sequential one-pot alkyne dimerization/hydration protocol for the regioselective synthesis of α,β-unsaturated ketones in quantitative yields. The alkyne dimerization reactions of terminal arylacetylenes proceeded with high regioselectivity in the presence of the Hoveyda-Grubbs 2nd generation catalyst (1 mol%) and tricyclohexylphosphine (4 mol%). The hydration reactions ofin situformed 1-aryl-3-en-1-ynes proceeded very rapidly in the presence of CCl₃COOH/p-TsOH·H₂O, yielding the corresponding unsaturated ketones within 15 minutes in quantitative yields. Different arylacetylene derivatives were converted to the corresponding α,β-unsaturated ketones in quantitative yields (94-95%) using sequential one-pot alkyne dimerization/hydration reactions.

Full text of DOI:10.1039/d1nj02410h

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One-pot synthesis of a,b-unsaturated ketones
through sequential alkyne dimerization/hydration
reactions using the Hoveyda–Grubbs catalyst†
Cite this: DOI: 10.1039/d1nj02410h
Bengi O¨ zgun O¨ zturk, *a Begum Sarıaslan,ab Mina As-kun,a Zeynep Tunalıa and
¨
¨
¨
Solmaz Karabulut S- ehitoglu*a
˘
Herein we report a sequential one-pot alkyne dimerization/hydration protocol for the regioselective
synthesis of a,b-unsaturated ketones in quantitative yields. The alkyne dimerization reactions of terminal
arylacetylenes proceeded with high regioselectivity in the presence of the Hoveyda–Grubbs 2nd genera-
tion catalyst (1 mol%) and tricyclohexylphosphine (4 mol%). The hydration reactions of in situ formed
1-aryl-3-en-1-ynes proceeded very rapidly in the presence of CCl3COOH/p-TsOHÁH2O, yielding the
corresponding unsaturated ketones within 15 minutes in quantitative yields. Different arylacetylene
derivatives were converted to the corresponding a,b-unsaturated ketones in quantitative yields (94–95%)
using sequential one-pot alkyne dimerization/hydration reactions.
Received 16th May 2021,
Accepted 3rd August 2021
DOI: 10.1039/d1nj02410h
rsc.li/njc
through in situ formation of head-to-head dimerization of alkynes,
1. Introduction
followed by the generation of bis-carbene derivatives.17 The
Unsaturated ketones (enones) are important building blocks reaction then proceeds through oxidation of the intermediates,
for the synthesis of various functional molecules such as enols, yielding b,g-unsaturated ketone. This study showed that not only
a-siloxyamides, a-hydroxyamides, hydroborate derivatives and alkynes but 1,3-enynes can be used as starting materials for
chiral alcohols.1–4 To date, several different strategies have the synthesis of a,b- and b,g-unsaturated ketone derivatives.
been reported in the literature for the synthesis of a,b and b,g PtCl2/CO and IPrAuCl/AgOTf catalyzed hydration reactions of
unsaturated ketones.3–7 Various starting materials including 1-aryl-3-en-1-ynes selectively gave a,b- and b,g-unsaturated ketone
allyl alcohol, propargyl alcohol, saturated ketones, ketone- derivatives based on the catalyst and the reaction conditions.18
stabilized phosphonium ylides, enol ethers, and alkynes have In 2014, the same strategy was applied for the synthesis of 2-en-1,4-
been used in the construction of enone derivatives through dicarbonyl derivatives through hydrative oxidation of 1,3-enynes.19
catalytic or non-catalytic synthesis protocols.8–13 Among these
To date, several approaches have been reported in the literature
starting materials, alkynes emerge as valuable starting materi- for the selective synthesis of 1,3-enynes.20 Among the reported
als for the construction of unsaturated ketones through com- synthesis strategies, the dimerization of terminal alkynes emerges
bined catalytic transformation reactions.14 The early examples as an efficient catalytic reaction for the selective formation of
of unsaturated ketone synthesis protocols utilize isomerization 1,3-enynes. Several different transition metal complexes including
of propargylic alcohols to enones in the presence of a ruthe- Co, Ru, Fe, Zr, Pd and Au have been reported as efficient catalysts
nium catalyst.15 In 2012, hydroacylation of internal alkynes for the dimerization of terminal alkynes.21–27 Among these transi-
with aldehyde derivatives in the presence of Ru/CeO2 and tion metal-based catalysts, ruthenium exhibits high regio-
phosphine derivatives gave the corresponding a,b-unsaturated selectivity in the dimerization of alkynes.28–30 Ruthenium based
ketones in moderate yields.16 The reaction of terminal alkynes Grubbs type catalysts are known to catalyze various non-metathetic
and water in the presence of [CpRu(NCMe)3+PF6À] and para- reactions including alkyne dimerization, cyclotrimerization,
toluenesulfonic acid yielded b,g-unsaturated ketone derivatives alkyne–carboxylic acid addition reactions and reduction of
via a one-pot procedure. The reaction mechanism proceeds alkenes.31–42 During the last decade, our research group has
focused on non-metathetic tandem reactions using Grubbs type
catalysts.31–42 Grubbs 2nd and Grubbs 3rd generation catalysts are
a Hacettepe University, Faculty of Science, Chemistry Department, 06800, Beytepe-
efficient catalysts for alkyne dimerization reactions.36–39 Recent
Ankara, Turkey. E-mail: bengi04@hacettepe.edu.tr
b Hacettepe University, Graduate School of Science and Engineering, 06800,
studies proved that the addition of coordinating molecules such as
pyridine and phosphine can tune the chemoselectivity and regios-
Beytepe-Ankara, Turkey
† Electronic supplementary information (ESI) available. See DOI: 10.1039/d1nj02410h electivity of dimerization reactions.37,38
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(PCy3) (0.064 mmol, 0.018 g) under a nitrogen atmosphere. The
reactor was sealed with a rubber septum and taken to a pre-
heated oil bath at 120 1C. Aliquots were taken at 30 minute
intervals and analysed by GC-MS. The tip of a GC syringe was
plunged into the reaction mixture gently and the syringe tip was
purged in methanol (GC/HPLC grade) in vials for GC-MS
analysis. Once the conversion of phenylacetylene has reached
a plateau, the reaction mixture was cooled to room temperature
and the product was separated using dry column vacuum
chromatography (DCVC)44 using a gradient eluent (2% v/v),
starting from n-hexane (100%). The polarity of the solvent was
increased gradually by increasing the ethyl acetate content of
the mixture (2% v/v increment for each addition). The isolated
1
compound was characterized by H and 13C NMR analyses.
2.2. Representative procedure for hydration reactions of
1,3-enynes
Scheme 1 Different strategies for the synthesis of unsaturated ketones.
A Schlenk reactor was charged with (Z)-but-1-en-3-yne-1,4-
diyldibenzene (2a) (1.6 mmol, 0.33 g) and dissolved in dichlor-
oethane (4 mL). p-Toluenesulfonic acid monohydrate
(1.6 mmol, 0.30 g) and trichloroacetic acid (4.8 mmol, 0.78 g)
were added to the reactor and the reaction mixture was trans-
ferred to a pre-heated oil bath at 80 1C. After 15 minutes of
reaction time, enyne (2a) was completely consumed. The reac-
tor was cooled to room temperature. The reaction mixture was
diluted with dichloromethane (4 mL) and vacuum-filtrated. The
filtered reaction mixture was extracted with saturated NaHCO3
solution (20 mL Â 2) and deionized water (20 mL Â 1). The
organic layer was separated and the solvent was evaporated
using a rotary evaporator. The viscous yellow/brown oil was
dissolved in ethyl acetate (2 mL) and loaded on Celite. Celite
was added to a silica gel column and the final product was
purified using dry column vacuum chromatography using
n-hexane and ethyl acetate, starting from 100% n-hexane. The
polarity of the mobile phase was gradually increased (2%) using
To date, only a few studies utilized 1,3-enynes as starting
materials (or reaction intermediate) to build a,b- and
b,g-unsaturated ketone derivatives (Scheme 1).17–19 To the best
of our knowledge, there are no reports in the literature on the
synthesis of a,b-unsaturated ketones using sequential one-pot
alkyne dimerization/hydration reactions.
In this study, we have developed a novel strategy for the
synthesis of a,b-unsaturated ketones using sequential alkyne
dimerization/hydration reactions. The dimerization of arylalk-
ynes in the presence of the Hoveyda–Grubbs 2nd generation
catalyst (1% mol) and PCy3 (4% mol) yielded Z-selective dimers
(up to 99% Z isomer) within 2 hours of reaction time. The in situ
formed dimers were reacted with the p-toluenesulfonic acid/
trichloroacetic acid mixture to yield a,b-unsaturated ketones
within 15 minutes of reaction time. Different arylacetylene
derivatives were tested under optimized reaction conditions.
1
ethyl acetate. The isolated product was characterized using H
2. Experimental section
and 13C NMR.
All chemicals were purchased from Sigma-Aldrich and used as
received unless otherwise noted. The Z-selective Hoveyda–
Grubbs catalyst (Ru–Z) and Hoveyda–Grubbs 2nd generation
catalyst (HG2) were purchased from Sigma-Aldrich. The Grubbs
2nd generation analog [Ru = CHPhCl2(PCy3)(IPr)] was synthe-
sized according to the literature.43 Gas chromatography–mass
2.3. Representative procedure for one-pot synthesis of a,b-
unsaturated ketones
A Schlenk reactor was charged with phenylacetylene (1.6 mmol,
175 mL), Hoveyda–Grubbs 2nd generation catalyst (HG2)
(0.016 mmol, 0.01 g) and tricyclohexylphosphine (PCy3)
(0.064 mmol, 0.018 g) under a nitrogen atmosphere. The
reactor was sealed with a rubber septum and transferred to a
pre-heated oil bath at 120 1C. The aliquots were taken at regular
intervals from the reaction mixture and analyzed by GC-MS.
Once all the phenylacetylene was consumed, the temperature of
the oil bath was decreased to 80 1C and the viscous oily
dimerization product in the reactor was dissolved in dichlor-
oethane (4 mL). p-Toluenesulfonic acid monohydrate
(1.6 mmol, 0.30 g) and trichloroacetic acid (4.8 mmol, 0.78 g)
were added to the reactor and the reaction mixture was mag-
spectrometry (GC-MS) analyses were performed with
a
Shimadzu GC-MS 2010 Plus using a Restek Rxi-5Sil column
(30 m  0.25 mm  0.25 mm) in the temperature range of
1
50–320 1C with a constant helium flow rate of 1 mL minÀ1. H
and 13C NMR spectra were recorded at 25 1C with a Bruker
GmbH 400 MHz high performance digital FT-NMR spectro-
meter using CDCl3 as the NMR solvent.
2.1. Representative procedure for alkyne dimerization
reactions
A
Schlenk reactor was charged with phenylacetylene netically stirred. After 15 minutes, all the enyne product (2a)
(1a, 1.6 mmol, 175 mL), Hoveyda–Grubbs 2nd generation was converted to the desired a,b-unsaturated ketone (3a).
catalyst (HG2) (0.016 mmol, 0.01 g) and tricyclohexylphosphine The reaction mixture was cooled to room temperature and then
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dichloromethane (4 mL) was added to the reactor. The reaction within 8 h in the presence of 1 mol% PCy3 and 1 mol% HG2
mixture was filtered under vacuum. The filtered reaction mix- with a product selectivity ratio of Z/E/gem of 85/10/5 (mol/mol/
ture was extracted with saturated NaHCO3 solution (20 mL Â 2) mol). The increment of PCy3 loading to 4 mol% has drastically
and deionized water (20 mL Â 1). The organic layer was increased the Z-selectivity of the reaction and reduced the
separated and the solvent was evaporated using a rotary eva- reaction time to 2 h. The reaction yielded 2a with 99%
porator. The viscous yellow/brown oil was dissolved in ethyl Z-selectivity in the presence of 1 mol% HG2. The optimum
acetate (2 mL) and loaded on Celite. Celite was added to a silica phosphine loading was found to be 4 mol%, considering the
gel column and the final product was purified using dry reaction time, yield and regioselectivity of the reaction. As
column vacuum chromatography using n-hexane and ethyl shown in Fig. 1, the olefinic proton signal appearing as doub-
acetate, starting from 100% n-hexane. The polarity of the lets at 6.69–6.72 and 5.91–5.94 ppm with a J-value of 11.9 Hz
mobile phase was gradually increased (2%) using ethyl acetate. confirmed the presence of Z (cis)-configuration of double
The isolated product was characterized using 1H and 13C NMR. bonds. On the next trial, the effect of the phosphine structure
on the selectivity and yield of the reaction was investigated in
detail and the results are given in Table 2. In the absence of
phosphine, the reaction proceeded very slowly, yielding the
3. Results and discussion
cyclotrimerization product instead of the dimerization product
For the last decade, there has been tremendous interest in the
using HG2 (1 mol%). The addition of triphenylphosphine
development of atom-efficient tandem and one-pot catalytic
reactions.40 As a part of our ongoing efforts to develop efficient
(PPh3) has drastically switched the selectivity towards the
dimerization product, giving 2a in 99% yield with a 97%
Z-selectivity. The substitution of PPh3 with a better s-donor
one-pot sequential reactions to build advanced molecular
structures, our research group was focused on ruthenium
ligand, PCy3, has decreased the reaction time to 2h and
catalyzed alkyne dimerization reactions and alkyne hydration
reactions.38,39 The selective hydration of the a- or b-carbon of
increased the Z-selectivity of the reaction up to 99%. Therefore,
4 mol% PCy3 and 1 mol% Ru were used in further alkyne
the alkyne moiety of 1,3-enynes can give a,b- or b,g-unsaturated
ketones as reported in the literature.18,19 Therefore, the effec-
dimerization experiments.
The Grubbs 2nd generation analog (G2-1), Hoveyda–Grubbs
2nd generation catalyst (HG2) and Z-selective Hoveyda–Grubbs
catalyst (Ru–Z) were used in dimerization reactions of various
alkynes including 1-phenylacetylene (1a), 4-ethynyl toluene
tive combination of alkyne dimerization and hydration reac-
tions can be used for the efficient synthesis of unsaturated
ketone derivatives via a one-pot procedure. We have chosen
commercially available Grubbs type ruthenium catalysts for the
(1b), 2-ethynyl toluene (1c) and 4-tert-butylphenylacetylene
in situ generation of 1,3-enynes through dimerization reactions.
Instead of expensive gold-based hydration catalysts,45 the
p-toluenesulfonic acid/trichloroacetic acid binary mixture was
(1d) (Fig. 2). The effect of PCy3 on product selectivity can be
directly seen on HG2 and Ru–Z catalyzed reactions. In the
absence of PCy3, the reaction predominantly yielded cyclotri-
chosen for the alkyne hydration reactions based on their
effectiveness on the hydration reactions of various alkynes.42
merization products as the major reaction product. However,
the addition of 4 mol% PCy3 has switched the selectivity of the
reaction towards the dimerization product 2a. It is important to
note that HG2 exhibited high Z-selectivity (99%, Table 3-entry 2)
For this purpose, three different ruthenium catalysts: Grubbs
2nd generation (G2), Hoveyda–Grubbs 2nd generation (HG2),
and Z-selective Hoveyda–Grubbs catalysts (Ru–Z) were chosen
in the presence of 4 mol% PCy3. In contrast to HG2, Ru–Z
and tested in alkyne dimerization reactions of various alkynes
showed poor Z-selectivity under the same reaction conditions,
yielding 2a (85%) with a Z/E/gem selectivity of 61/36/3. The
alkynes 1a–d yielded the corresponding dimerization products
2a–d (up to 99% yield) with high Z-selectivity (91–99%) using
(Scheme 2). As reported in the literature, the reactions of
arylalkynes in the presence of the HG2 catalyst using various
solvents (toluene, THF, dichloromethane) have yielded cyclo-
trimerization products. However, the selectivity of HG2 can be
HG2 and G2 catalysts. The Ru–Z catalyst showed poor
tuned for the selective generation of dimerization products by
the introduction of s-donor ligands to the reaction media.38
Our first attempts were focused on the optimization of
alkyne dimerization reaction conditions using 1–8 mol% PCy3
and 1 mol% Hoveyda–Grubbs 2nd generation catalyst in the
Table 1 The effect of phosphine amount on the selectivity of the alkyne
dimerization reactions
absence of any solvents at 120 1C (Table 1). As can be seen in
Table 1, the reaction yielded the dimerization product (2a)
Entry
PCy3 (mol%)
Time (h)
Conversiona (%)
Z/E/gema
1
2
3
4
1
2
4
8
8
4
2
2
90
99
99
97
85/10/5
90/10/—
99/1/—
95/5/—
a
Scheme 2 Grubbs type ruthenium catalysts used in this study.
Determined by GC-MS using n-tetradecane as the internal standard.
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Table 3 Dimerization of arylalkynes in the presence of various ruthenium
catalysts
Entry Alkyne Cat.
PCy3% Time (h) % Yielda Z/E/gemb
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1b
1b
1b
1c
1c
1c
1d
1d
1d
G2
G2
—
4
—
4
—
4
4
4
4
4
4
24
2
36
2
24
2
2
2
2
2
2
80
97
60c
97
85d
96
97
97
96
97
96
90
97
98
95
85/10/5
99/1/—
80/20/—
99/1/—
61/36/1
73/26/1
92/8/—
93/7/—
74/24/4
91/6/3
92/7/1
61/36/1
96/2/2
99/1/—
55/41/4
HG2
HG2
Ru–Z
Ru–Z
G2
HG-2
Ru–Z
G2
HG-2
Ru–Z
G2
HG-2
Ru–Z
Fig. 1 1H NMR spectrum of the dimerization product (2a-Z) (400 MHz,
CDCl3)
9
10
11
12
13
14
15
4
4
4
4
4
4
4
4
Table 2 The effect of phosphine addition on the selectivity of the
dimerization reaction
a
b
Isolated yield of the dimerization product. Determined by GC-MS and
1H NMR. The cyclotrimerization (CT) product was formed as a side
product (40% GC yield). The CT product was formed (15% GC yield).
c
d
Entry
PR3 (mol%)
Time (h)
Conversiona (%)
Z/E/gema
before proceeding enyne hydration experiments, we have tested
the activity of acid mixtures on the hydration reaction of
diphenylacetylene, known as a challenging alkyne substrate
for hydration reactions. The results are given in Table 4.
The acidity of carboxylic acid has a huge effect on the
reactivity of the binary acid mixture in alkyne hydration reac-
tions. As shown in Table 4, the acetic acid catalyzed reaction
yielded the corresponding ketone 1,2-diphenylethanone in 24%
yield. In contrast to the acetic acid (pKa: 4.74)/p-toluenesulfonic
acid catalyzed hydration reactions, the yield of the hydration
product was increased to 55% when the same reaction was
conducted using the benzoic acid (pKa: 4.20)/p-toluenesulfonic
acid mixture. The trichloroacetic acid (pKa: 0.77)/p-toluenesulfonic
acid mixture yielded the corresponding hydration product quanti-
tatively within 15 minutes of reaction time. The most effective
binary acid mixture was found to be trichloroacetic acid/p-
toluenesulfonic acid and used in both hydration reactions of 1,3-
enynes and one-pot dimerization/hydration reactions.
1
2
3
4
—
12
4
2
80
99
99
97
85/10/5
97/3/—
99/1/—
95/5/—
PPh3
PCy3
P(iÀPr)3
2
a
Determined by GC-MS using n-tetradecane as the internal standard.
Fig. 2 1H NMR spectrum of 3a (400 MHz, CDCl3).
performance in terms of product selectivity, yielding a mixture
of Z- and E-isomers of the dimerization product.
Table 4 Hydration of diphenylacetylene in the presence of binary acid
Once the dimerization reaction conditions were optimized,
the hydration of the dimerization product 2a was studied using
different binary acid couples such as trichloroacetic acid/
p-toluenesulfonic acid, acetic acid/p-toluenesulfonic acid and
benzoic acid/p-toluenesulfonic acid under different reaction
conditions.
The activity of p-toluenesulfonic acid/acetic acid in alkyne
hydration reactions was previously reported by Liu et al.46
However, the performance of the acid catalyst system needs
to be improved for the hydration of 1,3-enynes. Therefore,
mixtures
Entry Acid
Solvent Time
Conversiona (%) Yieldb (%)
24
1
2
3
CH3COOH
DCE
C6H5COOH DCE
CCl3COOH DCE
4 hour 26
1 hour 59
15 min 99
55
95
a
b
Determined by GC-MS using n-tetradecane as the internal standard.
Isolated by simple extraction, isolated yield.
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To test the regioselectivity of the hydration reaction,
Paper
Table 5 One-pot sequential alkyne dimerization/hydration reactions
1,4-diphenylbut-1-en-3-yne (2a) with different Z/E contents:
Z-2a (99% Z, Table 3, entry 4) and Z/E-2a (61% Z, 36% E,
Table 3, entry 5) were used in the hydration reaction in the
presence of CCl3COOH/p-TsOH in DCE at 80 1C (Scheme 3). All
starting materials were consumed within 15 minutes of reac-
tion time as confirmed by both GC-MS and TLC analyses.
The isolated hydration product 3a was analyzed by 1H NMR.
It is interesting to note that, in both cases, the final
a,b-unsaturated ketone (3a) derivative was found to have
formed predominantly as an E-isomer (Fig. 2). The olefinic
proton signals appearing at 6.65–6.69 (J = 16.2 Hz, 1H) and 7.52
(J = 16.2 Hz, 1H) confirmed that the configuration of the double
bond was converted to an E-isomer during the hydration
reaction. Identical 1H NMR spectra were observed in both cases
using 99% Z-2a or 61% Z-36% E 2a isomers.
Entry
Alkyne
Time (h)
Conv.a (%)
Yieldb (%)
1
2
3
4
1a
1b
1c
1d
2.5
2.5
3
99
99
99
99
95
95
94
95
4.5
a
The conversion of alkynes (1a–d) was determined by GC-MS using
b
n-tetradecane as the internal standard. Isolated yields of 3a–d.
One-pot reactions were carried out under optimized reaction
conditions for alkyne dimerization and hydration reactions
using a variety of alkynes including phenylacetylene (1a),
4-ethynyltoluene (1b), 2-ethynyltoluene (1c) and 4-tert-butyl- Table 6 Hydration of isolated enynes using binary acid mixtures
phenylacetylene (1d) (Table 5). A Schlenk reactor was charged
with 1a and 1 mol% HG2 and 4 mol% PCy3 under a nitrogen
atmosphere and the reaction mixture was stirred at 120 1C
without any solvent. The progress of the reaction was moni-
tored by GC-MS. After complete conversion of the alkyne
substrate, the temperature of the reaction mixture was
decreased to 80 1C and the oily viscous dimer product (2a)
was dissolved in DCE, p-toluenesulfonic acid (1.0 mol equiva-
lent) and trichloroacetic acid (3.0 mol equivalent) and the
reaction mixture was stirred under a nitrogen atmosphere.
The progress of the reaction was monitored by both GC-MS
and TLC analyses. After 15 minutes, 2a was completely con-
sumed to produce 3a in quantitative yields. 3a was isolated in
95% yield. 4-Ethynyl toluene (1b) and 2-ethynyl toluene (1c)
were used in sequential dimerization/hydration reactions to
monitor the effect of para- and ortho-substituents on reaction
selectivity and yield. The hydration reaction proceeded
smoothly with both ortho- and para-substituted arylacetylenes,
giving unsaturated ketones in excellent yields.
To further investigate the possible role of ruthenium in
hydration reactions, a control-experiment was carried out in
the absence of HG2 (Table 6). For this purpose, isolated
1,3-enyne derivatives (2a–d) were reacted with CCl3COOH/
p-TsOHÁH2O in DCE at 80 1C under a nitrogen atmosphere.
In addition, different acid mixtures of CH3COOH/p-TsOHÁH2O
and C6H5COOH/p-TsOHÁH2O were also tested in hydration
reactions. In the case of the CH3COOH/p-toluenesulfonic acid
mixture, the conversion of 2a was 40% even after 24 h of
Entry
Dimer
Acid
Time
Conv.a (%)
Yieldb (%)
1
2
3
4
5
6
2a
2a
2a
2b
2c
2d
CH3COOH
C6H5COOH
CCl3COOH
CCl3COOH
CCl3COOH
CCl3COOH
24 h
24 h
15 min
15 min
20 min
15 min
40
50
99
99
99
99
33
48
95
96
95
96
a
Determined by GC-MS using n-tetradecane as the internal standard.
Isolated yield.
b
reaction time. The substitution of acetic acid with benzoic acid
yielded the a,b-unsaturated ketone (3a) in 48% yield after 24 h of
reaction time. As confirmed from previous experiments regard-
ing diphenylacetylene, trichloroacetic acid efficiently catalyzed
the hydration reaction, giving 3a in quantitative yields within 15
minutes. The reaction proceeds very rapidly in the presence of
trichloroacetic acid. It is important to note that sequential alkyne
dimerization/hydration reactions or direct hydration reactions of
isolated 1,3-enynes yielded the corresponding unsaturated
ketone 3a in quantitative yields in both cases. These results
strongly suggest that ruthenium does not have a significant
effect during the sequential reaction and is mainly responsible
for alkyne dimerization reactions as the key catalyst.
4. Conclusions
A novel sequential one-pot synthesis method utilizing alkyne
dimerization/hydration reactions is presented for the regiose-
lective synthesis of a,b-unsaturated ketones from arylalkyne
derivatives. The combination of HG2/PCy3 and CCl3COOH/
p-TsOHÁH2O through a one-pot sequential reaction gave the
Scheme 3 Synthesis of a,b-unsaturated ketone (3a) using isolated enynes
with different Z/E isomer contents.
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´
20 (a) S. E. Garcıa-Garrido, in Modern Alkyne Chemistry: Cata-
lytic and Atom-Economic Transformations, ed. B. M. Trost,
C. Li, Wiley-VCH, Weinheim-Germany, 2014, Ch. 11,
pp. 299–334; (b) B. M. Trost and J. T. Masters, Chem. Soc.
Rev., 2016, 45, 2212–2238; (c) Q. Teng, W. Mao, D. Chen,
Z. Wang, C.-H. Tung and Z. Xu, Angew. Chem., Int. Ed., 2020,
59, 2220–2224; (d) Q. Teng, N. Thirupathi, C.-H. Tung and
Z. Xu, Chem. Sci., 2019, 10, 6863–6867.
corresponding a,b-unsaturated ketones in quantitative yields
within 2.5–4 h. It is noteworthy that hydration reactions
of 1,3-enynes showed high regioselectivity and no trace of
b,g-unsaturated ketone was observed during the hydration
reactions.
Conflicts of interest
21 (a) O. N. Temkin, Kinet. Catal., 2020, 60, 689–732;
(b) R. H. Platel and L. L. Schafer, Chem. Commun., 2012,
48, 10609–10611.
There are no conflicts to declare.
22 O. Rivada-Wheelaghan, S. Chakraborty, L. J. W. Shimon,
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23 M. Kanaura, N. Endo, M. P. Schramm and T. Iwasawa, Eur.
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Acknowledgements
We would like to thank The Scientific and Technological
Research Council of TURKEY (TUBITAK) for supporting this
study through the KBAG-1002 program, Project No: 120Z006.
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