PtO2/PTSA system catalyzed regioselective hydration of internal arylalkynes bearing electron withdrawing groups

Article abstract of DOI:10.1039/c8ra00564h

A highly efficient PtO₂/PTSA catalyst system for the hydration of a wide array of alkynes was developed. This method proved to be compatible with a large range of functional groups and the ketone products were obtained in high yields. The scope of this methodology was also extended to the synthesis of 3-Aryl-isochromenones,-indoles and-benzofurans.

Full text of DOI:10.1039/c8ra00564h

RSC Advances
View Article Online
View Journal | View Issue
PAPER
PtO2/PTSA system catalyzed regioselective
hydration of internal arylalkynes bearing electron
Cite this: RSC Adv., 2018, 8, 11536
withdrawing groups†
*
Hsin-Ping Lin, Nada Ibrahim, Olivier Provot,
Mouad Alami
*
and Abdallah Hamze
Received 19th January 2018
Accepted 7th March 2018
A highly efficient PtO2/PTSA catalyst system for the hydration of a wide array of alkynes was developed. This
method proved to be compatible with a large range of functional groups and the ketone products were
obtained in high yields. The scope of this methodology was also extended to the synthesis of 3-aryl-
isochromenones, -indoles and -benzofurans.
DOI: 10.1039/c8ra00564h
rsc.li/rsc-advances
relatively high catalyst loadings. Recently, developing bulky N-
heterocyclic carbene gold (I) chloride complexes enabled
hydration not only under acid-free conditions7b but also at low
catalyst loadings (<10 ppm).12a Nevertheless, the reaction
required high temperature to proceed. In addition to the
aforementioned, regioselectivity is an important feature to be
considered; for example, the hydration of terminal alkyne
occurred via Markovnikov-type addition, while with unsym-
metrical internal alkynes, only moderate regioselectivities were
obtained.
A recent study showed the regiochemistry in these reactions
with a set of examples highlighting the challenges and survey of
some of the strategies engaged to address this problem, which
has remained a major concern up to now.13 We have no doubt
about the great advances achieved in this research area, but we
believe that there is still room for improvement, principally in
the area of the regioselective hydration and of internal alkynes
bearing electron withdrawing groups.
In these regards, our group reported previously the use of
PTSA in reuxing alcoholic media for the hydration of electron-
rich arylalkynes.14 As expected, no reaction was observed in the
presence of electron withdrawing groups (unpublished
results).15 With the aim of developing a general catalytic system
for carbon–carbon triple bond activation we demonstrated that
heterogeneous platinum oxide is a competent catalyst for
hydrosilylation of unsymmetrical internal arylalkynes.16
Depending on the source of the solvents used, we observed by
gas chromatography some traces of carbonyl compounds in the
crude mixture, particularly when solvents were not completely
dry, setting off clearly from the water addition to alkyne. We
have paid a very close attention to this reaction since hydration
of activated alkyne proceeded well with Pt (II)6a salts or Pt(IV)17
under carbon monoxide pressure (200 psi of CO) system but not
with the platinum oxide as far as we know.
1 Introduction
Alkyne, which is one of the widely used building blocks in
organic synthesis constitutes the toolbox of organic chemists,
biochemists, and materials scientists.1 Acetylene chemistry has
driven the development of numerous methodologies and
various synthetic procedures for many products such as
ketones, enynes, and metal acetylides of signicant interest to
both synthetic and medicinal chemists.2 Among these impor-
tant applications, the hydration of alkynes is one of the most
straightforward and largely studied reactions for the synthesis
of carbonyl compounds.3 Since these reactions require a long
time to be catalyzed under acidic conditions, they are suitable
only for electron-rich alkynes.4 The toxic mercury salt has served
as a catalyst for the addition of water and alcohol to unactivated
alkynes.5 Alternative and less harmful Au (III) and Pt (II) salts
have been used, but they have turned out to be less efficient.6
Regarding the substantial importance of this transformation,
the Teles et al. and Tanaka et al. have separately reported the
rst and very efficient method for hydration of alkynes using
cationic gold (I) complexes of [(PR3)Au]+ type.7 Nowadays,
a variety of catalytic systems including ruthenium,8 rhodium,9
iridium(III),10 and palladium11 have been well developed for
these transformations and have been shown to perform the
reaction at different levels of success; among these, gold might
be considered by now as the standard catalyst for terminal and
internal alkynes hydration with high degree of efficiency.7b,12
However, gold catalyzed hydration of alkynes has some short-
comings, for example, using high acid concentration and
´
´
´
BioCIS, Univ. Paris-Sud, CNRS, equipe Labellisee Ligue Contre le Cancer, Universite
ˆ
Paris-Saclay, 92290, Chatenay-Malabry, France. E-mail: abdallah.hamze@u-psud.fr;
mouad.alami@u-psud.fr
† Electronic supplementary information (ESI) available: For experimental details,
copies of 1H and 13C NMR spectra for all new compounds. See DOI:
10.1039/c8ra00564h
We wondered whether the catalytic activity of PtO2 would
achieve hydration of internal alkynes bearing EWG in
11536 | RSC Adv., 2018, 8, 11536–11542
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
Table 1 Optimization conditions for alkyne hydrationa
Entry
[M] (X mol%)
Additive (10 mol%)
Solvent
H2O (equiv.)
Yieldb (%)
1
2
3
—
—
PtO2 (5)
PtO2 (5)
PtO2 (5)
PtO2 (5)
PtO2 (5)
PtO2 (5)
PTSA
PTSA
—
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
Dioxane
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH/H2O (2 : 1)
MeOH
MeOH
—
0
0
5
3.3
3.3
—
4
PTSA
PTSA
H2SO4
CF3COOH
HCOOH
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
—
42
98
90
30
15
40
15
65
25
91
0
0
0
0
40
0
5c
3.3
3.3
3.3
3.3
3.3
3.3
3.3
3.3
3.3
3.3
3.3
3.3
3.3
3.3
6
7
8
9
PtO2 (5)
PtO2 (5)
10
11
12
13
14d
15
16
17
18e
19
20f
21d,g
H2PtCl6 (5)
Pt(acac)2 (5)
PtCl2 (5)
PdCl2 (5)
FeCl3 (5)
Cu(OTf)2 (5)
CoBr2 (5)
AgBF4 (5)
(IPr)AuCl (1)
(Ph3P)AuCH3 (1)
PtO2 (1)
H2SO4
PTSA
3.3
3.3
53
88
a
Reaction conditions: [catalyst] X mol%, PTSA 10 mol%, alkyne 1 mmol, H2O (3.3 equiv.), MeOH (2.2 mL), 90 ꢀC in a sealed tube. b Isolated yield of
2a. c Performing the reaction at 60 ꢀC furnished ketone 2a in 80% yield. d The reaction was performed overnight. e Conditions from Li et al.,19 the
reaction was performed at 110 ꢀC, 6 h. f Conditions from Tanaka et al.,7b reaction was performed at 70 ꢀC, 5 h. g Performing the reaction at a gram
scale (1.87 g) gave 2a in 80% isolated yield.
a regioselective manner and relatively low catalyst loading. (entry 2). The reaction between 1a and PtO2 (5 mol%) in MeOH
Moreover, we tended to consider the catalysis from an led to the formation of the desired product in a low yield (5%,
economical point of view with regards to recycling the catalyst entry 3). Performing this reaction in the presence of PtO2
and making scalable reactions and nally expanding the reac- (5 mol%) and with catalytic amount of PTSA (10 mol%) in
tion to the synthesis of useful heterocycles such as lactones, MeOH produced the desired compound 2a in a moderate yield
furans and indoles. In this study, we report that the use of PtO2/ (42%, entry 4). Next, we found that the combination of PtO2/
PTSA combination in MeOH/H2O serves as a general catalytic PTSA/MeOH in the presence of H2O had a drastic effect on
system for alkyne hydration with an improvement in activity for
diarylalkynes irrespective of the electronic nature of the
substituents (electron rich or poor) and regardless of their
position on the aromatic ring (ortho, meta, para).
2 Results and discussion
As previously mentioned, we started our optimization studies
on the hydration of diphenylacetylene 1a by relying on our
previous nding that PTSA promotes water addition-type reac-
tions. For the initial conditions, PTSA (10 mol%) with reuxing
in EtOH or MeOH was found to be inactive for the hydration of
1a (Table 1, entry1). The study of the reaction mechanism (vide
infra) revealed that water would be required for the hydrolysis of
the reaction intermediate; hence, we subsequently investigated
the addition of water to the reaction mixture. Indeed, addition
Fig. 1 Recycling of PtO2: the hydration of diphenylacetylene 1a
catalyzed by PtO2 (5 mol%), PTSA 10 mol% in MeOH (2.2 mL), H2O (3.3
of water to the methanolic solution did not improve the yield equiv.).
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 11536–11542 | 11537

View Article Online
RSC Advances
Paper
Table 2 Scope of the hydration of para- and meta-alkynes catalyzed
by the PtO2-PTSA system
Conditions
PtO2 X mol%/PTSAa 10 mol%,
PTSAb 10
Entry
1
yieldc
mol%, yieldc
Scheme 1 Plausible mechanism for hydration of electron rich 1,2-
diphenylethyne with PTSA.
NRd
NRd
the reaction efficiency and compound 1a was quantitatively
converted to ketone 2ꢀa (entry 5). Decreasing the temperature of
the reaction from 90 C to 60 ꢀC led to a slight decrease in the
yield (98% vs. 80%). Furthermore, we investigated the use of
other Brønsted acid sources such as H2SO4 (90%), which gave
a close yield to PTSA (entry 6). However, in the presence of
CF3COOH (entry 7) or HCOOH (entry 8), a low yield of 2a was
obtained as compared to the most effective Brønsted acid
(PTSA). The nature of the solvent signicantly affected the
hydration reaction since the use of EtOH or dioxane instead of
MeOH considerably decreased the yield (entries 9–10). As PtO2
proved to be the most effective catalyst for this transformation,
a variety of platinum catalysts were evaluated. Speier's catalyst
(H2PtCl6) and platinum(II) acetylacetonate Pt(acac)2 gave
moderate and low yields, respectively (entries 11–12). However,
a good yield was obtained with PtCl2 (entry 13). Most of the
starting material 1a was recovered with palladium, iron, copper,
and cobalt catalysts (entries 14–17) and a low yield of ketone 2a
2e
3f
4
NRd
NRd
NRd
5g,e
6
7
8e
NRd
NRd
NRd
9e
10
a
Reactions conditions: PtO2 X mol%, PTSA 10 mol%, alkyne 1 mmol,
b
H2O (3.3 equiv.), MeOH (2.2 mL), 90 ꢀC in a sealed tube. Same
conditions as before but without the addition of PtO2. c Isolated yield of
product 2. d NR: no reaction was observed without the addition of PtO2.
e
f
Reaction was carried out at 130 ꢀC. Obtained as separable 80/20
g
Scheme 2 Mechanism of hydration of arylalkynes with platinum/PTSA
catalyst system.
mixture with the other a-regioisomer. Obtained as separable 95/5
h
mixture with the other a-regioisomer. Reaction without PtO2 needs
heating under MWI at 150 ꢀC and the addition of 1 equiv. of PTSA.
11538 | RSC Adv., 2018, 8, 11536–11542
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
Table 3 Scope of the cyclization of ortho-alkynes catalyzed by Pt-PTSA system
Conditions
Entry
1
Alkyne 1
PtO2 Xa mol%, PTSA 10 mol%, yieldc
—b, PTSA 10 mol%, yieldc
NRe
2
NRe
3
4
5
a
Reactions conditions: PtO2 X mol%, PTSA 10 mol%, alkyne 1 mmol, H2O (3.3 equiv.), MeOH (2.2 mL), 90 ꢀC in a sealed tube. b Same conditions as before
but without the addition of PtO2. c Isolated yield of product 2. d Reaction was realized at 130 ꢀC. e NR: no reaction was observed without the addition of PtO2.
was obtained even with a prolonged reaction time when silver- liquid was poured out and the remaining solid catalyst was
catalyzed (AgBF4) was used (entry 18).18 Next, we examined the washed with hexane twice, dried and reused. PtO2 was used four
hydration of alkyne 1a under commercial AuI-catalyst system times without any signicant decrease of the catalytic activity.
(entries 19–20). No reaction occurred when 1,2-diphenylethyne
Next, we explored the scope of this reaction with various
1a was used as the substrate under cationic gold(I) species [(IPr) dissymmetrical alkynes (Table 2). Alkynes having EWGs on para
AuCl] as described by Li et al.19 in the presence of MeOH/H2O at position such as NO2, CN, and CF3 were efficiently converted to
110 ꢀC (entry 18). As with stable gold complex (Ph3P)AuCH3, 2a their corresponding ketones with complete b-regioselectivity
was obtained only in a 53% yield.7b In particular, with longer (entries 1–2 and 4). However, in the case of alkyne substituted
reaction time (12 h), we were able to decrease the catalyst with a para ester (CO2Me), a mixture of two separable
loading of PtO2 to 1 mol% with minor effect on the yield (Table regioisomers (80 : 20) was obtained, in which the b-regioisomer
1, entry 21).
In addition, the robustness of the catalytic conditions is
predominated (entry 3).
Alkyne having a meta nitro group was successfully regiose-
demonstrated through gram scale synthesis of the hydration lectively hydrated into the corresponding ketone 2fb with good
product 2a and reaction of 1a with the new catalytic system yield (entry 5). In comparison to 1,2-diphenylethyne, the
(entry 18) was successfully completed on a 1.87 g scale (10.5 hydration of the electron-poor alkynes (entries 1–5) requires the
mmol), giving rise to 2a with 80% yield.
addition of 5 mol% PtO2 to occur. Next, we applied our condi-
As the reusability and the recovery of the catalyst are very tions with electron-rich internal alkynes. Alkynes having free
important issues, we then studied the recycling of PtO2 in the amino or hydroxyl group in para-position were successfully
hydration reaction of diphenylacetylene 1a (Fig. 1). For this, converted into the corresponding a-ketone derivatives in
aer each run, the MeOH/water solvent was directly evaporated; excellent yields with only (1 mol%) of PtO2 (entries 6–7). It is
then, hexane was added at room temperature and the medium important to note for compound 2ga that without the use of
ꢀ
was stirred for 20 min. Aer sedimentation of the solid, the PtO2, the reaction needs heating under MWI at 150 C using 1
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 11536–11542 | 11539

View Article Online
RSC Advances
Paper
Table 4 Scope of the hydration of terminal-alkynes catalyzed by
PtO2-PTSA system
A possible reaction mechanism is proposed to account for
the hydration of arylalkynes catalyzed by PtO2/PTSA combina-
tion (Scheme 2). Activation of the triple bond can be explained
by the formation of p-complex (I) between platinum catalyst
and the triple bond, followed by the regioselective addition of
MeOH (species II). PTSA/H2O catalyzed proto-demetallation and
led to enol form (III), which rearranged into keto form 2.
The regioselectivity of hydration of dissymmetrical alkynes
depends on the nature of the substituent of the aromatic ring,
which will induce polarization of the triple bond.
Conditions
PtO2 1a mol%,
PTSA 10 mol%,
yieldc
—b, PTSA
10 mol%,
yieldc
Entry
1
Alkyne 1
Analysis of 13C NMR chemical shis of sp-carbon atoms of
alkyne 1 can provide a good approximation for electronic
polarization of para-alkyne derivatives. Indeed, for estimation
NRd
NRd
of the electronic effects for conjugated systems, analysis of 13
C
NMR chemical shis was routinely used.20 The presence of EWG
such as CN substituent in para-position increases the difference
in the 13C NMR chemical shi of the signal arising from the
DdCb–Ca atom from 0 ppm (R ¼ H, diphenylacetylene) to
6.1 ppm (Scheme 2). A similar situation was observed with other
EWG substituents such as NO2 or CF3.21 Accordingly, substitu-
ents on para-position such as CN, NO2, and CF3 polarize the
triple bond in the same way, making the a-sp-carbon more
electron-rich and the b-sp-carbon more electron-decient. The
catalytic cycle begins with the formation of Pt-p-alkyne complex
I by coordination between alkyne 1b and the platinum catalyst.
Nucleophilic attack by PTSA on complex I led to the formation
of intermediate II. Then, intermediate II evolved to enol III by
protodemetalation in the presence of water in acidic media.
Finally, isomerization of enol III produced the ketone 2bb. As
the reaction was performed in MeOH/water mixture, enol III can
also be formed by the hydrolysis of vinyl ether intermediate,
which can be obtained from the reaction between MeOH and
intermediate II.
2
3
4
5
NRd
NRd
NRd
6
NRd
a
Reaction conditions: PtO2 1 mol%, PTSA 10 mol%, alkyne 1 mmol,
b
H2O (3.3 equiv.), MeOH (2.2 mL), 90 ꢀC in a sealed tube. Same
conditions as before but without the addition of PtO2. Isolated yield
of product 2. NR: no reaction was observed without the addition of
c
d
The presence of EDGs in para-position such as NH2 induced
an inversion of the polarization of the carbon–carbon triple
bond (the Ca atom becomes more electron-decient than the
Cb atom). This resulted in the change of sign of DdCb–Ca
values, which become negative (DdCb–Ca ¼ ꢁ1.9 ppm, Scheme
2). This can explain the inversion of the hydration regiose-
lectivity in the case of para-EDG substituents.
We next examined the synthesis of an important class of
heterocyclic compounds under our standard conditions. Thus,
cylization of ortho-substituted diarylalkynes proceeded well
(Table 3) at 90 ꢀC. Diarylalkynes bearing an ortho-cyano
substituent on the aromatic ring 1l provided the cyclized 3-
phenyl-isochromen-1-one 2l with low isolated yield (30%).
Increasing the temperature of the reaction to 130 ꢀC led to
a signicant increase in the formation of cyclic product 2l in
a good overall yield of 65% (Table 3, entry 1). As expected
PtO2.
equiv. of PTSA.15a Performing the hydration of push–pull alkyne
led exclusively to the formation of a-regioisomer 2ia (entry 8). In
addition, our conditions were found to be efficient for the
hydration of heteroaryl-alkyne; the b-ketone 2jb was obtained
with moderate yield (50%, entry 9). Finally, arylalkyl alkyne was
easily hydrated under our conditions to give 2ka as a single
isomer with 82% yield (entry 10). Furthermore, these results
were reproducible as summarized in Table 2, which represents
the yields obtained from three parallel experiments.
2.1 Mechanism discussion
The PTSA-catalyzed hydration of alkyne requires the presence of reaction with alkyne 1m bearing an ortho-ester group (entry 2)
electron-donating substituent in para or in ortho-position gave again the same 3-phenyl-isochromen-1-one 2l in good
(Scheme 1). The methoxy-group in para-position could lead to yield.
an allene intermediate, followed by regioselective addition of
The scope of this cyclization was further examined with
ethanol to afford an enol form, which rearranges into ketone a variety of ortho-EDG-substituted diarylalkynes. Substrates
form aer hydrolysis. Thus, terminal alkynes as well as non- bearing an ortho-amino group were successfully transformed to
activated arylalkynes (EDG) did not react under the reaction the corresponding indoles derivatives 2m–n in good yields
conditions using only p-toluenesulfonic acid as the catalyst.
(entries 3–4). In the absence of PtO2, reaction of aniline
11540 | RSC Adv., 2018, 8, 11536–11542
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
derivatives (entries 3–4) results in the formation of the hydra-
tion products 2ma and 2na. Starting the reaction from ortho-
phenol alkyne 1p leads to the formation of benzofuran deriva-
tive 2o in 94% yield (entry 5), while on using only PTSA, product
2oa was obtained.
Notes and references
1 F. Diederich, P. J. Stang and R. R. Tykwinski, Acetylene
Chemistry: Chemistry, Biology, and Material Science, Wiley-
VCH Verlag GmbH & Co. KGaA, 2005.
Having succeeded in developing an efficient hydration
process of electron decient diarylalkynes, we next examined
this protocol with terminal alkynes so as to compare this system
to previously reported catalytic systems (Table 4). We were
however delighted to see a successful hydration at 1 mol% of
PtO2, regardless of the electronic nature of the terminal alkynes.
Thus, hydration of ethynylbenzene derivatives having electron-
donating or electron-withdrawing groups efficiently proceeded
to afford the corresponding ketones in good to excellent yields.
Also, aryl alkynes having a methoxyl group in meta-position of
the aryl ring reacted well and furnished the acetophenone
derivatives 2q in good yields. Additionally, terminal alkyne
having a heterocyclic aromatic substituent such as thiophene
reacts well under our standard conditions to afford the hydra-
tion product 2t in good yield (62%).
2 (a) D. R. Dreyer, H.-P. Jia and C. W. Bielawski, Angew. Chem.,
Int. Ed., 2010, 49, 6813; (b) M. Rubina, M. Conley and
V. Gevorgyan, J. Am. Chem. Soc., 2006, 128, 5818; (c)
V. P. Boyarskiy, D. S. Ryabukhin, N. A. Bokach and
A. V. Vasilyev, Chem. Rev., 2016, 116, 5894.
3 (a) L. Hintermann and A. Labonne, Synthesis, 2007, 1121; (b)
M. B. Smith and J. March, in March's Advanced Organic
Chemistry, John Wiley & Sons, Inc., 2006, p. 999.
4 A. D. Allen, Y. Chiang, A. J. Kresge and T. T. Tidwell, J. Org.
Chem., 1982, 47, 775.
5 M. Kutscheroff, Ber. Dtsch. Chem. Ges., 1881, 14, 1540.
6 (a) J. W. Hartman, W. C. Hiscox and P. W. Jennings, J. Org.
Chem., 1993, 58, 7613; (b) J. W. Hartman and L. Sperry,
Tetrahedron Lett., 2004, 45, 3787.
7 (a) J. H. Teles, S. Brode and M. Chabanas, Angew. Chem., Int.
Ed., 1998, 37, 1415; (b) E. Mizushima, K. Sato, T. Hayashi and
M. Tanaka, Angew. Chem., Int. Ed., 2002, 41, 4563.
8 (a) M. Tokunaga and Y. Wakatsuki, Angew. Chem., Int. Ed.,
1998, 37, 2867; (b) P. S. Mainkar, V. Chippala, R. Chegondi
and S. Chandrasekhar, Synlett, 2016, 27, 1969.
The latter substrate (2t) was studied under PtCl4–CO catalytic
system developed by Blum et al.22 However in their study, an
unsatisfactory yield of 30% was obtained. Furthermore, our
protocol was also efficient for the hydration of aliphatic
terminal alkyne and furnished the corresponding ketone 2u
with 66% yield.
9 J. Blum, H. Huminer and H. Alper, J. Mol. Catal., 1992, 75,
153.
10 S. Ogo, K. Uehara, T. Abura, Y. Watanabe and S. Fukuzumi, J.
Am. Chem. Soc., 2004, 126, 16520.
11 (a) Z. Zhang, L. Wu, J. Liao, W. Wu, H. Jiang, J. Li and J. Li, J.
Org. Chem., 2015, 80, 7594; (b) C. Xu, W. Du, Y. Zeng, B. Dai
and H. Guo, Org. Lett., 2014, 16, 948.
3 Conclusions
In summary, PtO2/PTSA in MeOH/H2O proved to be a highly
potent catalytic system for the transformation of non-activated
internal and terminal alkynes to ketones. Performing this
reaction in aqueous methanol enables the reaction to proceed
smoothly and to afford excellent yields of the resultant ketones
2. Furthermore, the results are highly reproducible and the
platinum catalyst is conveniently recovered. This system proved
to be compatible with a large range of functionalities including
nitrile, nitro, ester, amino and hydroxyl functional groups.
Additionally, the application of this methodology to internal
´
12 (a) N. Marion, R. S. Ramon and S. P. Nolan, J. Am. Chem. Soc.,
2009, 131, 448; (b) J. H. Teles, in Modern Gold Catalyzed
Synthesis, Wiley-VCH Verlag GmbH & Co. KGaA, 2012, p. 201.
13 J. A. Goodwin and A. Aponick, Chem. Commun., 2015, 51,
8730.
14 (a) N. Olivi, E. Thomas, J. F. Peyrat, M. Alami and J. D. Brion,
Synlett, 2004, 2175; (b) G. Le Bras, O. Provot, J. F. Peyrat,
M. Alami and J. D. Brion, Tetrahedron Lett., 2006, 47, 5497.
15 (a) M. Jacubert, O. Provot, J.-F. Peyrat, A. Hamze, J.-D. Brion
and M. Alami, Tetrahedron, 2010, 66, 3775; (b) G. Le Bras,
A. Hamze, S. Messaoudi, O. Provot, P.-B. Le Calvez,
J.-D. Brion and M. Alami, Synthesis, 2008, 1607.
16 (a) A. Hamze, O. Provot, M. Alami and J.-D. Brion, Org. Lett.,
2005, 7, 5625; (b) A. Hamze, O. Provot, J.-D. Brion and
M. Alami, Synthesis, 2007, 2007, 2025; (c) A. Hamze,
O. Provot, J.-D. Brion and M. Alami, J. Organomet. Chem.,
2008, 693, 2789.
ortho-alkynes
provides
exible
access
to
phenyl-
isochromenones, indoles, and benzofurans.
Conflicts of interest
There are no conicts to declare.
17 W. Baidossi, M. Lahav and J. Blum, J. Org. Chem., 1997, 62,
669.
Acknowledgements
Authors gratefully acknowledge the support of this project by
CNRS, Univ. Paris-Sud, as well as by La Ligue Nationale Contre
18 Z.-W. Chen, D.-N. Ye, Y.-P. Qian, M. Ye and L.-X. Liu,
Tetrahedron, 2013, 69, 6116.
´
le Cancer through an Equipe Labellisee 2014 grant. H.-P. L
19 F. Li, N. Wang, L. Lu and G. Zhu, J. Org. Chem., 2015, 80,
3538.
thanks the Taiwan Paris-Sud scholarship for a Ph.D. funding.
Our laboratory is a member of the laboratory of excellence
LERMIT supported by a grant from ANR (ANR-10-LABX-33).
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 11536–11542 | 11541

View Article Online
RSC Advances
Paper
20 (a) K. Itami, K. Mitsudo, K. Fujita, Y. Ohashi and
J.-i. Yoshida, J. Am. Chem. Soc., 2004, 126, 11058; (b)
F. Liron, M. Gervais, J. F. Peyrat and J. D. Brion, Angew.
Chem., Int. Ed., 2002, 41, 1578.
B. Happ, T. Bartik, C. Zucchi, M. C. Rossi, F. Ghel, 21 For more details on 13C NMR chemical shis of actetylenic
G. Palyi, G. Varadi, G. Szalontai, I. T. Horvath and
carbons of para alkynes please see the ESI part.†
C. Guastini, Organometallics, 1995, 14, 809; (c) M. Alami, 22 O. Israelsohn, K. P. C. Vollhardt and J. Blum, J. Mol. Catal. A:
Chem., 2002, 184, 1.
11542 | RSC Adv., 2018, 8, 11536–11542
This journal is © The Royal Society of Chemistry 2018