Ligand-free Pd/Ag-mediated dehydrogenative alkynylation of imidazole derivatives

Article abstract of DOI:10.1039/d1ra05303e

A variety of 2-alkynyl(benzo)imidazoles have been synthesized by dehydrogenative alkynylation of (benzo)imidazoles with terminal alkyne in NMP under air in the presence of Ag₂CO₃as the oxidant and Pd(OAc)₂as the catalyst precursor. The data obtained in this study support a reaction mechanism involving a non-concerted metalation deprotonation (n-CMD) pathway.

Full text of DOI:10.1039/d1ra05303e

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Ligand-free Pd/Ag-mediated dehydrogenative
alkynylation of imidazole derivatives†
Cite this: RSC Adv., 2021, 11, 25504
a
Matteo Biagetti,b Sara Guariento,b Marco Lessi,a Mattia Fausti,a
*
Fabio Bellina,
Paolo Ronchib and Elisabetta Rosadonia
Received 9th July 2021
Accepted 19th July 2021
A variety of 2-alkynyl(benzo)imidazoles have been synthesized by dehydrogenative alkynylation of (benzo)
imidazoles with terminal alkyne in NMP under air in the presence of Ag2CO3 as the oxidant and Pd(OAc)2 as
the catalyst precursor. The data obtained in this study support a reaction mechanism involving a non-
concerted metalation deprotonation (n-CMD) pathway.
DOI: 10.1039/d1ra05303e
rsc.li/rsc-advances
The development of synthetic protocols that enable the direct (decarboxylative direct arylation) (eqn (4), Scheme 1),26,49,50 the
2
and selective functionalization of Csp –H bonds are of primary CDA methodology makes it possible to use terminal alkynes
importance in the decoration of the imidazole scaffold.1–10 The without the need for preliminary activation.5,24
presence of two nitrogen atoms in the pentatomic structure of
Despite several papers having been dedicated to the dehy-
this important azole in fact introduces a differentiation in the drogenative alkynylation of pyrroles,27 indoles,27,31 oxa-
chemical behaviour of the three C–H bonds, allowing their zoles,27,30,32–34
selective involvement in carbon–carbon bond-forming reac- benzothiazoles,26,29,31,32,34 pyrazoles,25,27 1,3,4-oxadiazoles,33 imi-
tions as long as appropriate experimental conditions are dazopyridines,27,34 and N-substituted sydnones,28 to the best of
benzoxazoles,26,29,30,32,34
thiazoles,27,30
identied.
our knowledge a study specically devoted to the dehydrogen-
During our studies dedicated to the synthesis and investi- ative alkynylation of imidazoles has never been reported.
gation of azole-based uorophores featuring a p-conjugated However, careful reading the literature where alkynylation
backbone end-capped with electron-donating (EDG) and reactions involving azoles other than imidazole were described,
electron-acceptor (EWG) groups (the so-called “push–pull” it emerged that two papers reported the C-2 alkynylation of N-
systems),11–15 taking into account the structural characteristics benzylimidazole and N-benzylbenzimidazole with phenyl-
and synthetic versatility of a triple carbon–carbon bond16–23 that acetylene. In a study mainly devoted to the dehydrogenative
make it an excellent p-spacer, we recently decided to evaluate alkynylation of imidazo[1,5-a]pyridine, Shihabara, Dohke and
the possibility of obtaining alkynyl-substituted imidazoles by Murai employed the commercially unavailable Pd(II) complex
2
transition metal-catalyzed Csp –Csp bond-forming reactions. bi(4-nitropyridinyl)Pd(OAc)2, Ag2CO3 as the oxidant and AcOH
Among the synthetic procedures that allow the selective alky-
nylation of imidazoles and other ve-membered hetero-
arenes,5,24 there is no doubt that the possibility of forming the
new s carbon–carbon bond through the double activation of
two distinct carbon–hydrogen bonds through
a cross-
dehydrogenative alkynylation (CDA) represents the best
synthetic approach in terms of atom economy and functional
group tolerance (eqn (1), Scheme 1).25–34 In fact, when compared
2
with the transition metal-catalyzed direct Csp –H alkynylation
protocols involving 1-haloalkynes (the so-called “inverse Sono-
gashira coupling”) (eqn (2), Scheme 1),35–45 hypervalent iodine
reagents (eqn (3), Scheme 1),46–48 or a,b-ynoic acids
a
`
Dipartimento di Chimica e Chimica Industriale, Universita di Pisa, Via Moruzzi 13,
56124 Pisa, Italy. E-mail: fabio.bellina@unipi.it
bChemistry Research and Drug Design, Chiesi Farmaceutici S.p.A., Centro Ricerche,
Largo Belloli 11/A, 43122 Parma, Italy
† Electronic supplementary information (ESI) available: Experimental procedures
as well as 1H and 13C NMR spectra of the substrates and the products. See DOI:
10.1039/d1ra05303e
Scheme
1 Synthetic protocols for the transition metal-catalyzed
2
C
sp –H alkynylation of heteroarenes.
25504 | RSC Adv., 2021, 11, 25504–25509
© 2021 The Author(s). Published by the Royal Society of Chemistry

View Article Online
Paper
RSC Advances
dehydrogenative alkynylation with terminal alkynes (Scheme 2).
In particular, a careful screening allowed us to show how the
2
reactivity of Csp –H bond of imidazole derivatives and other
azoles can be enhanced simply by performing the alkynylation
using NMP as the reaction solvent, under air in non-anhydrous
conditions, and without the need for palladium ligands.
We decided to start our synthetic investigations by trying
Scheme 2 Pd/Ag-Promoted dehydrogenative alkynylation of imid-
azole derivatives.
a
cross-dehydrogenative
coupling
between
N-methyl-
benzimidazole (1) and phenylacetylene (2a), chosen as typical
coupling partners, under conditions very similar to those proposed
by Murai and co-workers for the regioselective C-3 dehydrogen-
ative alkynylation of 1-alkynyl-3-arylimidazo[1,5-a]-pyridines.34
Hence, to a mixture of 1.0 mmol 1, 5 mol% Pd(OAc)2, 1.5
equiv. Ag2CO3, and 1.0 equiv. AcOH in a 95 : 5 (v/v) mixture of
DMF and DMSO under argon 3.0 equiv. of 2a were added
dropwise over 90 min. However, aer 2 h at 120 ꢀC a 56% GLC
conversion of 1 was recorded, and the required 2-phenylethynyl-
N-methylbenzimidazole (3a) was obtained in only 34% GLC
yield (entry 1, Table 1).
Taking note of this unexpected negative result, we decided to
re-examine the reaction conditions, starting from the consid-
eration that even if Ag2CO3 can theoretically serve as the
oxidant, run the reaction in air (open ask) may be critical.28
Gratifyingly, when the coupling was performed under air there
as additive, in a 95 : 5 mixture of DMF and DMSO for 2 h at
120 C under argon.34 Due to the propensity of alkynes to give
ꢀ
Glaser-type homocoupling side-products in the presence of
silver(I) salts,51 phenylacetylene was slowly added over 90 min to
the reaction mixture. In 2015, Likhar, Kantam and co-workers
used a synthetic Pd(II) carbene complex. In this case Ag2O was
used as the oxidant, Cs2CO3 base, performing the coupling in
DMF at 85 C under air.26
ꢀ
Encouraged by these results but with the intention of
developing a simplied procedure that would allow the use of
a commercial Pd(II) pre-catalyst in the absence of any palladium
ligands, we decided to review the conditions of reaction and, in
this work, we are pleased to summarize the results obtained in
the synthesis
of 2-alkynylimidazole
derivatives
by
Table 1 Screening of the reaction conditions for the Pd/Ag-promoted dehydrogenative alkynylation of 1 with 2a a
Pd cat.
Entry (mol%)
Ag(I) salt
(equiv.)
Temp./react. timeb 1 GLC
3a GLC yieldd
(%)
RCOOH
Solvent
(ꢀC/h)
conversionc (%)
3a:4 AP%
1e
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19f
20g
Pd(OAc)2 (5)
Ag2CO3 (1.5)
Ag2CO3 (1.5)
Ag2CO3 (2.0)
—
Ag2CO3 (2.0)
Ag2CO3 (2.0)
Ag2CO3 (2.0)
Ag2CO3 (2.0)
Ag2CO3 (2.0)
Ag2CO3 (2.0)
AgOAc (2.0)
Ag2O (2.0)
Ag2CO3 (2.0)
Ag2CO3 (2.0)
Ag2CO3 (2.0)
Ag2CO3 (2.0)
Ag2CO3 (2.0)
Ag2CO3 (2.0)
Ag2CO3 (2.0)
Ag2CO3 (2.0)
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
—
DMF/DMSO (95 : 5)
DMF/DMSO (95 : 5)
DMF/DMSO (95 : 5)
DMF/DMSO (95 : 5)
DMF/DMSO (95 : 5)
DMF/DMSO (95 : 5)
DMF/DMSO (95 : 5)
DMF/DMSO (95 : 5)
AcOH
120/2
100/5.5
100/2
56
67
73
NR
73
67
72
53
0
76
55
66
80
45
43
75
81
85
82
83
34
66
70
—
69
63
68
23
—
69
48
62
71
45
40
70
57 : 43
32 : 68
34 : 66
—
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd2(dba)3 (2.5)
Pd(acac)2 (5)
PdCl2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (2.5)
Pd(OAc)2 (2.5)
Pd(OAc)2 (2.5)
Pd(OAc)2 (2.5)
Pd(OAc)2 (2.5)
Pd(OAc)2 (2.5)
Pd(OAc)2 (2.5)
Pd(OAc)2 (2.5)
Pd(OAc)2 (2.5)
Pd(OAc)2 (2.5)
Pd(OAc)2 (2.5)
100/3.5
100/3.5
100/3.5
100/3.5
100/3.5
100/3.5
100/3.5
100/3.5
100/3.5
100/3.5
100/3.5
80/3.5
100/3.5
100/3.5
100/3.5
100/3.5
100/3.5
30 : 70
27 : 73
35 : 65
72 : 28
0 : 100
30 : 70
25 : 75
28 : 72
35 : 65
22 : 78
17 : 83
34 : 66
33 : 67
36 : 64
40 : 60
36 : 64
—
AcOH
AcOH
AcOH
DMF/DMSO (95 : 5)
DMF/DMSO (95 : 5)
DMF/DMSO (95 : 5)
EtCOOH DMF/DMSO (95 : 5)
PivOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
DMF/DMSO (95 : 5)
DMF/DMSO (95 : 5)
DMF
DMA
NMP
NMP
NMP
75(68)
81(69)
66(51)
80
a
Reaction conditions: 2a (3.0 mmol) in the selected solvent (2.0 mL) was added dropwise over 45 min to a mixture of 1 (1.0 mmol), Pd cat., Ag(I) salt,
RCOOH (1.0 mmol) in the selected solvent (2.0 mL) under air, unless otherwise reported. b Aer the reported reaction time the GLC conversion of 2a
was quantitative. c GLC conversion of 1 vs. biphenyl. d GLC yield vs. biphenyl. In parentheses isolated yield. e This reaction was carried out under an
f
g
argon atmosphere. This reaction was carried out on a 10 mmol scale. This reaction was carried out in the presence of TEMPO (1.0 equiv.) as
radical scavenger.
© 2021 The Author(s). Published by the Royal Society of Chemistry
RSC Adv., 2021, 11, 25504–25509 | 25505

View Article Online
RSC Advances
Paper
was a marked increase in GLC yield, which went from 34% to
The satisfactory result obtained in the preparation of 3a from
66% (entry 2, Table 1). The use of a slightly more excess of 1 and 2a under the experimental conditions summarized in
Ag2CO3 resulted in a 70% GLC yield (entry 3, Table 1), while air entry 18 of Table 1 prompted us to extend this simple meth-
alone resulted ineffective in promoting the alkynylation (entry odology to the selective synthesis of 2-arylethynyl-1-methyl-1H-
4, Table 1). The use of palladium pre-catalysts different from imidazoles 6a–h and 2-arylethynyl-1-methyl-1H-benzimidazoles
Pd(OAc)2 did not give any signicant improvement in terms of 3a–e starting from 5 or 1 and terminal alkynes 2a–h. In details,
conversion and yield (entries 5–7, Table 1). The presence of 1.0 the slow addition over 45 min of 2 to a mixture of 5 or 1 in the
equiv. AcOH revealed to be essential for the coupling (entry 8, presence of 2.5 mol% Pd(OAc)2, 2.0 equiv. Ag2CO3, 1.0 equiv.
Table 1), but when the coupling was carried out using AcOH as AcOH in NMP as the solvent allowed us to recover the required
the reaction solvent 2a was entirely converted into the side- 2-alkynyl substituted derivatives 6a–h or 3a–e in 62–74% iso-
ꢀ
product 4 and no conversion of 1 into 3a was observed (entry lated yield aer 3.5 h at 100 C under air (Scheme 3).
9, Table 1).
Noteworthy, the reaction outcome was not inuenced by the
Continuing with the screening, we observed that halving the electronic nature of the aromatic moiety on the terminal alkyne.
palladium load did not lead to a loss of reaction efficiency (entry More importantly, several functional groups on the phenyl ring
10, Table 1), and that the use of silver(I) salts different from resulted well tolerated, including formyl and hydroxy groups
Ag2CO3 gave slightly worse results (entries 11 and 12, Table 1). that are potentially sensitive to the oxidative conditions
Propionic acid as additive gave results similar to AcOH (entry required by dehydrogenative couplings.
13, Table 1), while pivalic acid resulted less effective, giving rise
While good results were obtained when arylacetylenes were
to 3a in only 45% GLC yield (entry 14, Table 1). As already used as coupling partners, worse results were observed when
observed,31 the use of the right buffer system may be crucial for TIPS-acetylene 2i or 1-octyne (2j) were reacted with 5. In fact, the
the deprotonation of the terminal alkyne, and also for the expected 2-alkynyl substituted imidazoles 6i and 6j were iso-
reoxidation of Pd(0) to Pd(II).
lated in 30% and 11% yields, respectively (Scheme 4).25,31 The
With our delight the chemical yield went up to 69% when the low reactivity of these two terminal alkynes in respect to their
DMF/DMSO mixture was replaced by NMP (entry 18, Table 1), aryl analogues could be attributed, as already noted,31 to the
and the efficacy of this solvent was conrmed carrying out the decreased electrophilic nature of the corresponding alkynyl-
coupling on a ten times higher scale (entry 19, Table 1). A quite palladium(II) intermediates being generated during the
similar isolated yield was obtained performing the coupling in
DMA as the solvent (entry 17, Table 1), while DMF alone gave
a poorer result (entry 16, Table 1).
In contrast to what observed by Murai and co-workers,34 it
should be highlighted that the slow addition of phenylacetylene
never avoided in our hands the formation of Glaser side-
product 4.
Finally, when the reaction was performed in the presence of
1.0 equiv. of TEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyl as
radical scavenger, it still proceeded smoothly to afford 2-alky-
nylazole 3a in 80% GLC yield (entry 20, Table 1). This experi-
ment suggests that free radicals should be not involved in the
Scheme 4 Ligandless Pd/Ag-promoted dehydrogenative alkynylation
plausible catalytic cycle (see later).
of 1-methylimidazole 5 with terminal alkynes 2i and 2j.
Scheme 3 Ligandless Pd/Ag-promoted dehydrogenative alkynylation of 1-methylimidazole 5 or 1-methylbenzimidazole 1 with terminal alkynes
2a–h.
25506 | RSC Adv., 2021, 11, 25504–25509
© 2021 The Author(s). Published by the Royal Society of Chemistry

View Article Online
Paper
RSC Advances
Scheme 5 Ligandless Pd/Ag-promoted dehydrogenative alkynylation of 4,5-disubstituted 1-methylimidazole 7 or 9 with terminal alkynes 2a or
2d.
reaction. As a further proof of their lower reactivity, the slow while the corresponding C-5 or even the less probable C-4
addition of 2i and 2j was found to be unnecessary.
alkynyl-substituted regioisomers were never detected in the
Gratifyingly, the optimized Pd(OAc)2/Ag2CO3-promoted crude reaction mixtures.54 However, it is worth mentioning that
coupling conditions proved to be useful also for the C-2 dehy- when the alkynylation was tempted on 1,2-dimethyl-1H-imid-
drogenative alkynylation of 4,5-diphenyl-1-methylimidazole 7. azole 19, the C-5 alkynylated product 20 was obtained in 42%
In fact, this disubstituted azole gave the expected C-2 alkyny- isolated yield (eqn (1)).
lation product 8 in 70% isolated yield when reacted with phe-
nylacetylene (2a) (Scheme 5).
One of the main advantages of dehydrogenative cross-
coupling reactions is the tolerance, among others, of carbon–
halogen bonds that, hence, are available for subsequent trans-
formations. We were please to conrm this tolerance; in fact,
4,5-dibromo-1-methyl-1H-imidazole 9 was efficiently reacted
with alkynes 2a and 2d, giving rise to the required 2-alkynyl-4,5-
dibromoimidazoles 10a,b in 68 and 75% isolated yields,
respectively (Scheme 5). Notably, no conventional Sonogashira-
type coupling side-products were observed.
Similar satisfactory yields were obtained when 1-benzyl- and
1-phenyl-1H-imidazoles 11 and 12 when reacted with 2a. The
corresponding 2-phenylethynylimidazoles 13 and 14 were
recovered in 68% and 52% isolated yields, respectively (Scheme
6). In contrast, the C-2 alkynylation of thiazole (15) and oxazole
(16) with 2a gave the required products 17 and 18 in somewhat
lower yields (48 and 42%, respectively). It is noteworthy,
however, that the observed reactivity of 1-substituted imidazole
6, 11 and 12, i.e. 1-methyl > 1-benzyl > 1-phenyl, and that found
for the three 1,3-azoles 6, 13 and 14, i.e. 1-methylimidazole >
thiazole > oxazole, parallels that reported in the literature for
classical SEAr.52,53 As regards the regioselectivity, when the
reaction involved 1-substituted imidazoles 5, 11, and 12, thia-
zole 15 and oxazole 16 a clean C-2 alkynylation was observed,
(1)
Based on earlier reports and our observations, a possible
reaction mechanism for this Pd/Ag-promoted dehydrogenative
alkynylation of imidazoles is summarized in Fig. 1, using 1-
methylimidazole 5 as an example. Initial transmetallation
involving a Pd(II) complex and a (presumed) silver(I) acetylide
generates the alkynyl Pd(II) species A, which then affords the
imidazole–Pd–alkyne complex E through a sequence of base-
assisted carbanion generation from an azole–Pd complex (B /
C), followed by a C-palladation step via carbene D. This particular
C–H palladation mechanism, known as non-concerted
metalation-deprotonation (n-CMD) pathway, was initially
proposed by Hoarau and co-workers to justify the observed C-2
regioselectivity in the copper-free Pd-catalyzed direct arylation
of oxa(thia)zoles-4-carboxylate with aryl bromides.55–57
Although the comparison of the reactivity of 1-methyl-
imidazole 5 with both the other two 1-substituted imidazoles 11
and 12, and with thiazole (15) and oxazole (16) suggested a SEAr
Scheme 6 Ligandless Pd/Ag-promoted dehydrogenative alkynylation of 1-substituted imidazoles 5, 11, 12, thiazole (15), and oxazole (16) with
phenylacetylene (2a).
© 2021 The Author(s). Published by the Royal Society of Chemistry
RSC Adv., 2021, 11, 25504–25509 | 25507

View Article Online
RSC Advances
Paper
Fig. 1 Proposed n-CMD mechanistic pathway for the Pd(OAc)2/Ag2CO3-promoted dehydrogenative alkynylation of 1-methylimidazole 5.
mechanism (hence via a classic Wheland intermediate),58–60 it ligand. The experimental results point towards a non-concerted
should be noted that the most reactive position should have been metalation–deprotonation mechanistic pathway, that allows us
C-5, and not the position C-2 that instead has the most acidic to justify both the C-2 regioselectivity and the “SEAr-like” reac-
C–H bond. Similarly, a pure concerted metalation–deprotonation tivity of the azoles, as well as the higher reactivity of arylacety-
(CMD) pathway can reasonably be excluded considering that DFT lenes when compared with that of alkyl- or silyl-substituted
calculations have shown that in the case of 1,3-azoles position C- analogues. From the proposed mechanistic machinery it also
5 is, again, the most reactive.61 The n-CMD mechanism hypoth- emerged that Ag2CO3 plays not only as Pd(0) oxidant, but also has
esizes that the deprotonation occurs through the formation of an an active role in generating Ag(I) acetylide, and acts as an inner-
azole–Pd(II) complex and, therefore, justies the observed reac- sphere base in the C2–H deprotonation step. The application of
tivity by the most acidic C–H bond, i.e. the one in position 2 on this procedure to the preparation of new push–pull hetero-
the azole nucleus. On the other hand, one key step of this aromatic uorophores as functional materials is undergoing and
mechanism is the formation of N3–Pd complex C, which is the will be published in the next future.
more effective the more the terminal alkyne is electron-poor
(hence having the Csp–H bond more acid). That the steps of the
mechanism from A to E are certainly critical for the success of the
reaction is also proved by the benecial effect resulting from the
slow addition of the terminal alkyne 2 to the reaction mixture.
Conflicts of interest
There are no conicts to declare.
Finally, reductive elimination involving complex E gave the
coupling product 6, and reoxidation of Pd(0) to Pd(II) by Ag(I) or
air closed the catalytic cycle.
Acknowledgements
This research was supported by Chiesi Farmaceutici (Parma,
`
Italy) and Universita di Pisa (PRA_2020_219).
Conclusions
In this study we developed a simple and efficient ligandless Pd(II)
catalyzed dehydrogenative alkynylation of imidazoles with
terminal alkynes under air in non-anhydrous conditions, starting
from a preliminary screening of the role of silver(I) oxidant,
catalyst precursors, solvents, and reaction temperature on the
efficiency and selectivity of the alkynylation of 1-methyl-
benzimidazole (1). The optimized reaction conditions allowed us
to easily prepare several 2-alkynyl-substituted 1,3-azoles in good
isolated yields, working in an open vessel without any added
References
1 J. Roger, A. L. Gottumukkala and H. Doucet, ChemCatChem,
2010, 2, 20–40.
2 F. Bellina, R. Rossi, M. Lessi, C. Manzini and L. Perego,
Synthesis, 2014, 46, 2833–2883.
3 F. Bellina, in C-H Bond Activation and Catalytic
Functionalization I, ed. P. H. Dixneuf and H. Doucet,
Springer, Cham, 2016, vol. 55, pp. 77–102.
25508 | RSC Adv., 2021, 11, 25504–25509
© 2021 The Author(s). Published by the Royal Society of Chemistry

View Article Online
Paper
RSC Advances
4 R. Rossi, M. Lessi, C. Manzini, G. Marianetti and F. Bellina, 33 M. Kitahara, K. Hirano, H. Tsurugi, T. Satoh and M. Miura,
Adv. Synth. Catal., 2015, 357, 3777–3814.
5 B. Panda, Asian J. Org. Chem., 2020, 9, 492–507.
6 F. Bellina, Synthesis, 2021, 53(15), 2517–2544.
Chem.–Eur. J., 2010, 16, 1772–1775.
34 F. Shibahara, Y. Dohke and T. Murai, J. Org. Chem., 2012, 77,
5381–5388.
7 W. C. Lee, T. H. Wang and T. G. Ong, Chem. Commun., 2014, 35 I. V. Seregin, V. Ryabova and V. Gevorgyan, J. Am. Chem. Soc.,
50, 3671–3673. 2007, 129, 7742–7743.
8 Y. Yang, J. Lan and J. You, Chem. Rev., 2017, 117, 8787–8863. 36 Y. Gu and X.-m. Wang, Tetrahedron Lett., 2009, 50, 763–766.
9 H. Kim, Y. J. Hwang, I. Han and J. M. Joo, Chem. Commun., 37 E. Brachet and P. Belmont, J. Org. Chem., 2015, 80, 7519–
2018, 54, 6879–6882.
7529.
10 J. Le Bras and J. Muzart, Catalysts, 2020, 10, 571–618.
38 S. H. Kim and S. Chang, Org. Lett., 2010, 12, 1868–1871.
11 M. Lessi, C. Manzini, P. Minei, L. A. Perego, J. Bloino, 39 A. Mondal, H. Chen, L. Flamig, P. Wedi and M. van
F. Egidi, V. Barone, A. Pucci and F. Bellina, Chempluschem,
2014, 79, 366–370.
12 V. Barone, F. Bellina, M. Biczysko, J. Bloino, T. Fornaro,
Gemmeren, J. Am. Chem. Soc., 2019, 141, 18662–18667.
40 A. Mondal and M. van Gemmeren, Angew. Chem., Int. Ed.,
2021, 60, 742–746.
C. Latouche, M. Lessi, G. Marianetti, P. Minei, A. Panattoni 41 U. N. Patel and B. Punji, Asian J. Org. Chem., 2018, 7, 1390–
and A. Pucci, Phys. Chem. Chem. Phys., 2015, 17, 26710–
26723.
13 F. Bellina, C. Manzini, G. Marianetti, C. Pezzetta, E. Fanizza,
1395.
42 N. Matsuyama, K. Hirano, T. Satoh and M. Miura, Org. Lett.,
2009, 11, 4156–4159.
M. Lessi, P. Minei, V. Barone and A. Pucci, Dyes Pigm., 2016, 43 J. Aziz, T. Baladi and S. Piguel, J. Org. Chem., 2016, 81, 4122–
134, 118–128. 4133.
14 M. Lessi, G. Panzetta, G. Marianetti and F. Bellina, Synthesis, 44 T. Kawano, N. Matsuyama, K. Hirano, T. Satoh and
2017, 49, 4676–4686. M. Miura, J. Org. Chem., 2010, 75, 1764–1766.
15 G. Marianetti, M. Lessi, V. Barone, F. Bellina, A. Pucci and 45 F. Besselievre and S. Piguel, Angew. Chem., Int. Ed., 2009, 48,
P. Minei, Dyes Pigm., 2018, 157, 334–341. 9553–9556.
16 Modern Acetylene Chemistry, ed. P. J. Stang and F. Diederich, 46 J. P. Brand, J. Charpentier and J. Waser, Angew. Chem., Int.
VCH, Weinheim, 1995. Ed., 2009, 48, 9346–9349.
17 E. Negishi and L. Anastasia, Chem. Rev., 2003, 103, 1979– 47 J. P. Brand and J. Waser, Angew. Chem., Int. Ed., 2010, 49,
2017. 7304–7307.
18 F. Alonso, I. P. Beletskaya and M. Yus, Chem. Rev., 2004, 104, 48 Y. Li, J. P. Brand and J. Waser, Angew. Chem., Int. Ed., 2013,
3079–3159.
52, 6743–6747.
19 S. Toyota, Chem. Rev., 2010, 110, 5398–5424.
49 B. Zhao, Org. Biomol. Chem., 2012, 10, 7108–7119.
20 B. Godoi, R. F. Schumacher and G. Zeni, Chem. Rev., 2011, 50 J. Kim, D. Kang, E. J. Yoo and P. H. Lee, Eur. J. Org. Chem.,
111, 2937–2980. 2013, 2013, 7902–7906.
21 C. Liu, H. Zhang, W. Shi and A. Lei, Chem. Rev., 2011, 111, 51 X. Feng, Z. Zhao, F. Yang, T. Jin, Y. Ma and M. Bao, J.
1780–1824. Organomet. Chem., 2011, 696, 1479–1482.
22 J. P. Brand and J. Waser, Chem. Soc. Rev., 2012, 41, 4165– 52 L. I. Belen'kii and N. D. Chuvylkin, Chem. Heterocycl. Compd.,
4179. 1997, 32, 1319–1343.
23 R. Chinchilla and C. Najera, Chem. Rev., 2014, 114, 1783– 53 J. A. Joule and K. Mills, in Heterocyclic Chemistry at a Glance,
1826.
John Wiley & Sons, 2nd edn, 2013, ch. 12, pp. 107–121, DOI:
DOI: 10.1002/9781118380208.ch12.
54 M. R. Grimmett, in Advances in Heterocyclic Chemistry, 1970,
vol. 12, pp. 103–183, DOI: DOI: 10.1016/s0065-2725(08)
60973-3.
24 F. Bellina, M. La Manna and E. Rosadoni, Curr. Org. Chem.,
2021, 25, 1–26.
25 H. Ha, C. Shin, S. Bae and J. M. Joo, Eur. J. Org. Chem., 2018,
2018, 2645–2650.
26 T. Parsharamulu, P. Vishnuvardhan Reddy, P. R. Likhar and 55 L. Theveau, C. Verrier, P. Lassalas, T. Martin, G. Dupas,
M. Lakshmi Kantam, Tetrahedron, 2015, 71, 1975–1981.
27 X. Jie, Y. Shang, P. Hu and W. Su, Angew. Chem., Int. Ed.,
2013, 52, 3630–3633.
O. Querolle, L. Van Hije, F. Marsais and C. Hoarau,
Chem.–Eur. J., 2011, 17, 14450–14463.
´
56 L. Theveau, O. Querolle, G. Dupas and C. Hoarau,
28 C. Wu, P. Li, Y. Fang, J. Zhao, W. Xue, Y. Li, R. C. Larock and
F. Shi, Tetrahedron Lett., 2011, 52, 3797–3801.
29 S. S. Patil, R. P. Jadhav, S. V. Patil and V. D. Bobade,
Tetrahedron Lett., 2011, 52, 5617–5619.
30 S. H. Kim, J. Yoon and S. Chang, Org. Lett., 2011, 13, 1474–
1477.
31 L. Yang, L. Zhao and C. J. Li, Chem. Commun., 2010, 46, 4184–
4186.
32 N. Matsuyama, M. Kitahara, K. Hirano, T. Satoh and
M. Miura, Org. Lett., 2010, 12, 2358–2361.
Tetrahedron, 2013, 69, 4375–4380.
57 V. Gandon and C. Hoarau, J. Org. Chem., 2021, 86, 1769–
1778.
58 S. Pivsa-Art, T. Satoh, Y. Kawamura, M. Miura and
M. Nomura, Bull. Chem. Soc. Jpn., 1998, 71, 467–473.
59 F. Bellina, S. Cauteruccio, L. Mannina, R. Rossi and S. Viel,
Eur. J. Org. Chem., 2006, 2006, 693–703.
60 C. H. Park, V. Ryabova, I. V. Seregin, A. W. Sromek and
V. Gevorgyan, Org. Lett., 2004, 6, 1159–1162.
61 S. I. Gorelsky, Coord. Chem. Rev., 2013, 257, 153–164.
© 2021 The Author(s). Published by the Royal Society of Chemistry
RSC Adv., 2021, 11, 25504–25509 | 25509