Hydration of aromatic alkynes catalyzed by a self-assembled hexameric organic capsule

Article abstract of DOI:10.1039/c6cy00307a

The combination of a Br?nsted acid catalyst and a supramolecular organic capsule formed by the self-assembly of six resorcin[4]arene units efficiently promotes the mild hydration of aromatic alkynes to their corresponding ketones. The capsule provides a suitable nanoenvironment that favors protonation of the substrate and addition of water.

Full text of DOI:10.1039/c6cy00307a

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Hydration of aromatic alkynes catalyzed by a
self-assembled hexameric organic capsule†
Cite this: DOI: 10.1039/c6cy00307a
Giorgio La Sorella,a Laura Sperni,a Pablo Ballester,b Giorgio Strukula
a
*
and Alessandro Scarso
Received 12th February 2016,
Accepted 24th April 2016
The combination of a Brønsted acid catalyst and a supramolecular organic capsule formed by the self-
assembly of six resorcin[4]arene units efficiently promotes the mild hydration of aromatic alkynes to their
corresponding ketones. The capsule provides a suitable nanoenvironment that favors protonation of the
substrate and addition of water.
DOI: 10.1039/c6cy00307a
www.rsc.org/catalysis
vents as supramolecular catalysts for cycloaddition
reactions.8
Introduction
In recent years, supramolecular catalysis1 is growing as a new
cross-discipline that exploits the recognition properties of
host structures to promote reaction catalysis through the im-
plementation of weak intermolecular forces in the stabiliza-
tion of reaction intermediates and transition states. The role
of a catalytic host is to achieve high activity and both product
and substrate selectivity2 with the ultimate goal of enzyme
mimicking.3 While unimolecular host structures featuring
relatively small inner cavities, like cyclodextrins4 and
cucurbiturils,5 have been investigated as catalysts in the past,
more recently, supramolecular hosts displaying significantly
larger cavities have become interesting. The increase in vol-
ume size of a container host enabled co-encapsulation of mul-
tiple substrates, as well as the nesting of metal catalysts and
substrates. The inclusion of a metal complex catalyst can
drastically alter its properties compared to those exhibited in
bulk solution.6
Resorcin[4]arene 1 is an easy to prepare molecule that,
through hydrogen bonding interactions, spontaneously self-
assembles9 into hexameric 16·(H2O)8, stable both in the solid
state and in water saturated chloroform and benzene solu-
tions. The hexameric capsule is characterized by a large cavity
of about 1375 Å3,10 and encapsulates quaternary ammonium
compounds11 and some transition metal complexes by
establishing cation–π interactions with the electron-rich
internal lining of its aromatic rings.12 Alternatively, the cap-
sule interacts with hydrogen bonding species like alcohols13
or acids.14 These properties have been exploited to develop
supramolecular catalytic systems based on the resorcin[4]ar-
ene hexameric capsule. In particular, the capsule has been
used as (i) a reversible shield to control the activity of a
photo-catalyst,15 (ii) a nano-reactor to impart unique sub-
strate16 and product17 selectivities and (iii) a supramolecular
catalyst itself.18
As a function of solvent nature, different approaches were
considered in the development of synthetic supramolecular
catalysts. For example, water soluble capsular containers were
assembled through the hydrophobic effect and explored as
supramolecular catalysts for several chemical transforma-
tions in water.7 On the other hand, Rebek et al. introduced
the assembly of hydrogen bonded capsules in organic sol-
Some of the latter examples are related to the capsule me-
diated activation of water as a nucleophile towards the addi-
tion to different classes of substrates; in particular, the selec-
tive hydrolysis of acetals19 and the hydration of isonitriles to
formamides driven by encapsulation of the substrates in the
capsule that was recently disclosed by our group.20
Alkyne hydration is an atom efficient reaction that trans-
forms alkynes into carbonyl compounds such as ketones and
aldehydes.21 The reaction is usually carried out with the aid
of transition metal catalysts spanning from traditionally
employed Hg species22 to more recent examples based on
AuIJI),23 PtIJII)24 and RuIJII).25 Alternatively, the reaction can be
catalyzed by strong Brønsted acids like sulphuric acid in ex-
tremely large excess,26 as well as other strong organic acids
that require harsh experimental conditions and long reaction
times.27 For example, intrinsically electron rich internal aryl
alkynes require the presence of p-toluenesulfonic acid in
a Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca’ Foscari di
Venezia, via Torino 155, 30172, Mestre Venezia, ITALY. E-mail: alesca@unive.it;
Fax: +39 041 2340517; Tel: +39 041 2348569
b Institution for Research and Advanced Studies (ICREA) and Institut Català
d'Investigació Química (ICIQ), The Barcelona Institute of Science and Technology,
Avgda. Països Catalans 16, 43007, Tarragona, Spain. E-mail: pballester@iciq.es;
Fax: +34 977 920221
† Electronic supplementary information (ESI) available: Experimental details
and GC–MS spectra. See DOI: 10.1039/c6cy00307a
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ethanol solution under reflux conditions for several hours or
heating with MW irradiation.28 The use of microemulsion
conditions in water with the aid of surfactants and 0.33 M
HCl by heating the system from 100 to 140 °C for a few hours
is also competent for the hydrolysis of alkynes.29 Recently, it
was also disclosed that the combination of sulphuric acid
with an ionic liquid favoured the hydration of alkynes under
mild reaction conditions.30,31 Likewise, the combination of a
weak Brønsted acid as solvent with a strong Brønsted or
Lewis acid catalyst like GaIJOTf)3 enabled good yields of the
carbonyl compound by heating at 100 °C for a few hours with
reduced catalyst loading.32
and small amounts of products derived from acid addition
that were confirmed by GC–MS (Table 1, entries 5–6). Only
when catalytic amounts of the capsule 16·(H2O)8 were com-
bined with strong Brønsted acids did the quantitative hydra-
tion of 2a to its corresponding acetophenone 3a take place.
In particular, using 10 mol% of the capsule and 50 mol% of
HBF4 with respect to the substrate 2a catalyzed quantitative
hydration in slightly more than one hour (Table 1, entry 7).
Analogous results were obtained using longer reaction
times (18 hours) and by decreasing both the amount of the
capsule and the acid (Table 1, entry 8). Similarly, HCl and
methanesulfonic acid in combination with the capsule effi-
ciently promoted the hydration reaction of 2a. However, in
this case, a decrease in the amounts of both species had a
detrimental effect on the catalytic activity of the mixture
(Table 1, entries 9–10 and 12–13). Conversely, the use of
nitric acid as a Brønsted acid in the hydration reaction was
not improved by the addition of 16·(H2O)8 (Table 1, entry 11).
It is widely accepted that the hydration reaction of alkynes
occurs by water addition to a previously activated alkyne
through protonation or coordination to a metal center. Both
reaction mechanisms involve the enhancement of the electro-
philicity of the substrate, thus favoring the addition of water.
Recently, Tiefenbacher and co-workers demonstrated that the
resorcin[4]arene hexamer behaves as a weak acid with a pKa
of about 5.5,19 while free resorcinol, not bound as in 1a, has
a pKa of 9.15. The weak acidity of the capsule is not enough
to induce the protonation of the substrate to a significant ex-
tent, as shown by the lack of reactivity in the presence of the
capsule alone (Table 1 entry 1). The cooperation of the capsu-
lar hexamer with strong Brønsted acids like HBF4 and HCl
turned out to be much more efficient to catalyze the hydra-
tion reaction. As described above, it is well established that
the hexamer favors the encapsulation of cationic guests and
cationic reaction intermediates.18,33 Thus, a plausible, albeit
not proven, explanation of the catalytic effect exerted by the
capsule in the hydration of alkynes would possibly reside in
the stabilization of positively charged species that are formed
by Brønsted acid protonation of the triple bond.
Results and discussion
Herein, we present an example of very efficient supra-
molecularly promoted hydration of terminal aromatic alkynes
mediated by the combination of a strong Brønsted acid with
the self-assembled supramolecular organic capsule of resor-
cin[4]arene 16·(H2O)8 (Scheme 1). The capsule acts as an
organocatalyst and in the presence of a Brønsted acid effi-
ciently transforms aromatic alkynes into their corresponding
ketones at reaction temperatures of 60 °C or lower, within a
few hours. The catalytic effect was observed exclusively when
the capsule cavity was accessible. The addition of competitive
guests that preferentially encapsulate inhibited the catalytic
activity of the hexamer. This behaviour resembles the func-
tioning of the active sites of enzymes.
The hydration reaction of phenylacetylene 2a as model
substrate was monitored over time by means of 1H NMR
spectroscopy. The reaction was initially investigated at 60 °C
and for just a few hours. In the presence of the sole supramo-
lecular capsule 16·(H2O)8, no reaction was observed (Table 1,
entry 1). Similarly, in the presence of only strong Brønsted
acids such as HBF4, HCl or HNO3, the hydrolysis reaction did
not proceed (Table 1, entries 2–4). Only methanesulfonic
acid, as expected,27a and because of its better solubility in
chloroform, led to the partial formation of acetophenone 3a
In order to support this hypothesis, a series of control ex-
periments were carried out. In order to exclude the involve-
ment of the resorcinol moieties of 1 in the reaction, we re-
placed the hexameric capsule with 24 equivalents of resorcinol
with respect to the original amount of capsule. We observed
that under these reaction conditions, the formation of 3a was
negligible (Table 1, entry 16). We repeated the same control ex-
periment using 4-n-hexyl-resorcinol as a more soluble resor-
cinol derivative observing a 39% yield of 3a only after 24 h at
60 °C. These experiments were indicative of the minor effect
exerted by the resorcinol units to the reaction catalysis.
The hydration of 2a was also investigated in the presence of
HBF4, the capsule and tetraethylammonium tetrafluoroborate 4
as a competitive cationic guest for the capsule's interior.34 The
tetralkyl ammonium guest 4 was rapidly encapsulated as dem-
onstrated by the appearance of a broad resonance at −0.05 ppm
Scheme 1 Hydration reaction of terminal aromatic alkynes 2 leading
to their corresponding ketones 3 in the presence of tetrafluoroboric
acid and mediated by the capsule 16·(H2O)8 and the competitive guest
tetraethyl ammonium tetrafluoroborate 4.
1
in the H NMR spectrum (Fig. 1) with concomitant inactivation
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Table 1 Catalytic tests for the hydration of 2a
#
Brønsted Acid
Acid/2a
Time (h)
16·8H2O
4
3a (%)a
1
2
3
4
—
HBF4
HCl
HNO3
CH3SO3H
CH3SO3H
HBF4
HBF4
HCl
—
24
1
1
1
1
18
1.2
18
1.5
24
1
+
—
—
—
—
—
—
—
—
—
—
—
—
—
+
0
<2
<2
<2
0.5
0.5
0.5
0.5
0.2
0.5
0.2
0.5
0.2
0.5
0.5
0.2
0.5
0.5
0.5
0.1
0.5
—
—
—
—
—
+
+
+
+
+
+
+
+
—
—
+
5
57 (19)e
13 (3)e
>98
>98
>98
10
6b
7
8b
9
10b
11
12
13b
14
15
16c
17d
18f
HCl
HNO3
CH3SO3H
CH3SO3H
HBF4
HBF4
HBF4
18
1
>98
59 (17)e
<2
<2
<2
24
24
24
24
24
24
+
—
—
—
HBF4
HBF4
>98
39
—
Experimental conditions: [1] = 36 mM, [2a] = 60 mM, [Brønsted acid] = 30 mM, [4] = 60 mM (10 eq. with respect to the capsule), water saturated
a
b
chloroform-d = 1.5 mL, T = 60 °C. +: presence; −: absence. Determined by 1H-NMR. [1] = 18 mM, [2a] = 60 mM, [Brønsted acid] = 12 mM.
[resorcinol] = 140 mM (24 eq. with respect to 16·8H2O). d [1] = 18 mM, [2a] = 120 mM, [Brønsted acid] = 12 mM. e Amount of Brønsted acid ad-
c
dition products. f [4-n-hexyl-resorcinol] = 140 mM (24 eq. with respect to 16·8H2O).
of the catalytic activity of the hexamer (Table 1, entry 14 and
Fig. 1E).
is not the stabilization of the cationic species itself but the ef-
fect on the transition state yielding the charged intermediate;
hence, both the substrate and vinyl cation are expected to be
within the cavity even if the former is not macroscopically re-
vealed by NMR.
All the reported data suggest that the cavity of the
hexamer must be empty to allow the reaction to proceed. The
1H-NMR analysis of a solution containing the capsule, the
substrate phenylacetylene 2a or 2a and HBF4 did not show ev-
idence of encapsulated species (Fig. 1C). Most likely, the reac-
tion requires initial, rate-determining, alkyne protonation by
the strong Brønsted acid. The resulting cationic species is
stabilized by encapsulation followed by a rapid attack of wa-
ter that leads to the methyl ketone 3a. Indeed, what matters
The scope of the hydration reaction was investigated by ap-
plying the catalytic system obtained by the combination of
HBF4 and 16·8H2O to a wide range of aromatic terminal al-
kynes, as summarized in Table 2. With the aim of investigating
the turnover properties of the catalytic system under investiga-
tion, catalytic tests were performed with 50 mol% of HBF4 and
10 mol% of 16·8H2O at 60 °C for 1 h and with 10 mol% of
HBF4 and 5 mol% of 16·8H2O at the same temperature for 24 h.
The hydration reaction turned out to be extremely sensitive
to the electron density of the aromatic ring of the alkyne, pro-
viding higher yields for the more electron rich substrates.
Furthermore, N-protonable 3- and 4-ethynyl pyridine deriva-
tives did not produce their corresponding ketones in the pres-
ence of the capsule. On the other hand, extremely electron rich
substrates bearing methoxy substituents, i.e. p-methoxy-
phenylacetylene 2g and 4-methoxy-2-methyl-ethynylbenzene
2h, can react at 60 °C both in the presence of the free hexamer
and with the hexamer encapsulating the tetra-alkylammonium
salt 4. These results indicate that for these activated sub-
strates, the Brønsted acidity of HBF4 was enough to catalyze
the hydration reaction (Table 2, entries 6 and 7). In these
cases, the presence of the capsule either filled by the cationic
species 4 or in its free form is substantially not influencing the
reactivity of those activated substrates.
Fig.
1
1H NMR spectra in water saturated chloroform-d: (A)
phenylacetylene 2a (60 mM); (B) phenylacetylene 2a (60 mM) and 16
·8H2O (6 mM) after 18 h at 60 °C; (C) phenylacetylene 2a (60 mM) with
HBF4 (0.5 eq.) and 16·8H2O (6 mM); (D) phenylacetylene 2a (60 mM) with
HBF4 (0.5 eq.) and 16·8H2O (6 mM) after 70 minutes at 60 °C; (E)
phenylacetylene 2a (60 mM) with HBF4 (0.5 eq.), 16·8H2O (6 mM) and 4
(60 mM) after 24 h at 60 °C; encapsulated ammonium, acetophenone.
Substrates bearing alkyl substituents in the aromatic ring
showed a clear improvement of the hydration reaction in the
presence of the capsule, as reported in Table 2 (entries 1–5).
It is noteworthy that a gradual decrease in the yield of the
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Table 2 Hydration reaction of 2b–2m with HBF4 mediated by the cap-
sule 16·8H2O
Table 2 (continued)
#
Substrate
Product
Yield (%)a
#
1
Substrate
Product
Yield (%)a
10
50d, <2b,d
>98, 2b, >98c, 18b,c
2l
3l
2b
25d, <2b,d
3b
11
2
56, <2b, 78c, <2b,c
2m
2c
3m
3c
3
4
78, <2b, 40c, <2b,c
Experimental conditions: [1] = 36 mM, HBF4/substrate = 0.5, [2b–m] =
60 mM, water saturated chloroform-d = 1.5 mL, T = 60 °C, time = 1 h.
Determined by 1H NMR. Reaction in the presence of [4] = 60 mM.
a
c
b
[1] = 18 mM; HBF4/substrate = 0.1, T = 60 °C; time = 24 h. d [1] = 180
2d
3d
mM; HBF4/substrate = 0.5.
60, <2b, 98c, <2b,c
corresponding methyl ketone 3 was observed by increasing
the size of the aromatic substrate 2, regardless of its
electronic nature (Table 2, entries 1–5). This suggests that the
encapsulation of the protonated intermediate is size selective.
The cavity of the hexamer can accommodate about 6–8 chloro-
form or benzene molecules. The encapsulation of the cationic
intermediate of the reaction must occur together with a finite
number of solvent molecules. In all cases, an agreement
among the typical packing coefficient values observed for
host-guest systems in solution is mandatory.35 Further evi-
dence of the selective encapsulation of the cationic interme-
diate was provided by the hydration reactions of large sub-
strates such as 9-ethynyl-phenanthrene 2i and 1-ethynyl-4-
phenoxybenzene 2j that led to much lower conversion to the
corresponding ketone compared to the hydration of 2a under
similar experimental conditions (Table 2, entries 8 and 9). It
is noteworthy that even with some differences related to the
intrinsic reactivity of the different aromatic alkynes, the inhi-
bition effect imparted by the presence of the competitive am-
monium guest 4 was observed in almost all the substrates in-
vestigated, as shown in Table 2.
2e
3e
5
47, 7b, 83c, 8b,c
2f
3f
6
7
8
>98c, 72b,c
2g
3g
3h
>98, >98b
2h
40, <2b, 85c, 3b,c
Other
electron
poor
substrates
like
p-bromo-
phenylacetylene, 1-(4-ethynylphenyl)ethanone and methyl-4-
ethynylbenzoate failed to react in the presence of the capsule.
Finally, the hydration reaction was also tested using inter-
nal aromatic alkynes. We observed that 1-phenyl propine 2l
and 1-phenyl-hexyne 2m formed their corresponding ketones
with moderate yields and required the presence of higher
amounts of both the capsule and Brønsted acid (Table 2, en-
tries 10 and 11). Conversely, 1,1′-ethyne-1,2-diyldibenzene and
several terminal aliphatic alkynes did not show formation of
their corresponding hydration products.36
2i
3i
9
54, 17b
2j
3j
Conclusions
In conclusion, we have described another example of supra-
molecular catalysis in which catalytic amounts of the
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hexameric self-assembled capsule 16·8H2O in combination
with sub-stoichiometric amounts of HBF4 catalyzed the hy-
dration of aromatic alkynes 2 to their corresponding methyl
ketones 3 in a few hours using a water saturated chloroform
solution heated at 60 °C. The Brønsted acid induces the pro-
tonation of the substrate, while the supramolecular capsule
likely provides a suitable nano-environment to stabilize the
transition state leading to the positively charged vinyl cation
intermediate species,37,38 as would be expected with proton-
ation being the rate determining step of the reaction. More-
over, we demonstrated the inactivation of the supramolecular
catalyst by the addition of a competitive cationic ammonium
guest 4 that is preferentially encapsulated. We also proved
the sensitivity of the reaction to the size and shape of the
substrates. These findings clearly speak for the occurrence of
the hydration reaction within the cavity of the organocatalyst,
thus mimicking the active site of enzymes.
Chem. Commun., 2011, 47, 5368; (e) B. W. Purse and J.
Rebek, Proc. Natl. Acad. Sci. U. S. A., 2006, 103, 2530; ( f ) A.
Shivanyuk and J. Rebek, J. Am. Chem. Soc., 2003, 125, 3432;
(g) M. Yamanaka, A. Shivanyuk and J. Rebek, J. Am. Chem.
Soc., 2004, 126, 2939.
11 A. Shivanyuk and J. Rebek Jr., Proc. Natl. Acad. Sci. U. S. A.,
2001, 98, 7662.
12 D. A. Dougherty, Acc. Chem. Res., 2013, 46, 885.
13 (a) S. Slovak and Y. Cohen, Chem. – Eur. J., 2012, 18, 8515;
(b) S. Slovak, L. Avram and Y. Cohen, Angew. Chem., Int. Ed.,
2010, 49, 428; (c) B. Schnatwinkel, I. Stoll, A. Mix, M. V.
Rekharsky, V. V. Borovkov, Y. Inoue and J. Mattay, Chem.
Commun., 2008, 3873; (d) O. Ugono and K. Travis Holman,
Chem. Commun., 2006, 2144.
14 (a) Y. Aoyama, Y. Tanaka, Y. H. Toi and H. Ogoshi, J. Am.
Chem. Soc., 1988, 110, 634; (b) Y. Aoyama, Y. Nonaka, Y.
Tanaka, H. Toi and H. Ogoshi, J. Chem. Soc., Perkin Trans. 1,
1989, 2, 1025.
15 G. Bianchini, A. Scarso, G. La Sorella and G. Strukul, Chem.
Commun., 2012, 48, 12082.
Acknowledgements
AS acknowledges MIUR, Università Ca′ Foscari di Venezia and
16 (a) A. Cavarzan, J. N. H. Reek, F. Trentin, A. Scarso and G.
Strukul, Catal. Sci. Technol., 2013, 3, 2898; (b) S. Giust, G. La
Sorella, L. Sperni, G. Strukul and A. Scarso, Chem. Commun.,
2015, 51, 1658.
17 A. Cavarzan, A. Scarso, P. Sgarbossa, G. Strukul and J. N. H.
Reek, J. Am. Chem. Soc., 2011, 133, 2848.
18 (a) S. Shimizu, A. Usui, M. Sugai, Y. Suematsu, S. Shirakawa
and H. Ichikawa, Eur. J. Org. Chem., 2013, 4734; (b) G. La
Sorella, L. Sperni, G. Strukul and A. Scarso, ChemCatChem,
2015, 7, 291; (c) S. Giust, G. La Sorella, L. Sperni, F. Fabris,
G. Strukul and A. Scarso, Asian J. Org. Chem., 2015, 4, 217;
(d) L. Catti and K. Tiefenbacher, Chem. Commun., 2015, 51,
892; (e) Q. Zhang and K. Tiefenbacher, Nat. Chem., 2015, 7, 197.
19 Q. Zhang and K. Tiefenbacher, J. Am. Chem. Soc., 2013, 135,
16213.
Consorzio Interuniversitario Nazionale per la Scienza
e
Tecnologia dei Materiali for support. PB acknowledges the
Gobierno de Espana MINECO for Project CTQ2014-56295-R,
Severo Ochoa Excellence Accreditation (2014-2018 SEV-2013-
0319); FEDER funds (Project CTQ2014-56295-R), and the ICIQ
Foundation for funding.
Notes and references
1 (a) M. Raynal, P. Ballester, A. Vidal-Ferran and P. W. N. M.
van Leeuwen, Chem. Soc. Rev., 2014, 43, 1660; (b) M. Raynal,
P. Ballester, A. Vidal-Ferran and P. W. N. M. van Leeuwen,
Chem. Soc. Rev., 2014, 43, 1734.
2 P. W. N. M. van Leeuwen, Supramolecular Catalysis, Wiley-
VCH, 2008.
20 G. Bianchini, G. La Sorella, N. Canever, A. Scarso and G.
Strukul, Chem. Commun., 2013, 49, 5322.
3 (a) H. Wei and E. Wang, Chem. Soc. Rev., 2013, 42, 6060; (b)
Y. Lin, J. Ren and X. Qu, Acc. Chem. Res., 2014, 47, 1097.
4 R. Breslow and S. D. Dong, Chem. Rev., 1998, 98, 1997.
5 K. I. Assaf and W. M. Nau, Chem. Soc. Rev., 2015, 44, 394.
6 (a) P. Dydio and J. N. H. Reek, Chem. Sci., 2014, 5, 2135; (b)
S. H. A. M. Leenders, R. Gramage-Doria, B. de Bruin and
J. N. H. Reek, Chem. Soc. Rev., 2015, 44, 433; (c) J.-N. Rebilly,
B. Colasson, O. Bistri, D. Over and O. Reinaud, Chem. Soc.
Rev., 2015, 44, 467.
7 J. H. Jordan and B. C. Gibb, Chem. Soc. Rev., 2015, 44, 547.
8 (a) J. Kang and J. Rebek Jr, Nature, 1997, 385, 50; (b) J. Kang,
G. Hilmersson, J. Santamaría and J. Rebek, Jr., J. Am. Chem.
Soc., 1998, 120, 3650; (c) J. Kang, J. Santamaría, G.
Hilmersson and J. Rebek, Jr., J. Am. Chem. Soc., 1998, 120,
7389.
21 (a) L. Hintermann and A. Labonne, Synthesis, 2007, 8, 1121;
(b) L. Hintermann, ChemCatChem, 2012, 4, 321; (c) L.
Hintermann, Top. Organomet. Chem., 2010, 31, 123; (d) Y.
Yamamoto, I. D. Gridnev, N. T. Patil and T. Jin, Chem.
Commun., 2009, 5075; (e) B. Xu, W. Wang, L.-P. Liu, J. Han,
Z. Jin and G. B. Hammond, J. Organomet. Chem., 2011, 696,
269.
22 (a) G. A. Olah and D. Meider, Synthesis, 1978, 9, 671; (b) R. J.
Thomas, K. N. Campbell and G. F. Hennion, J. Am. Chem.
Soc., 1938, 60, 718.
23 (a) W. E. Brenzovich Jr., Angew. Chem., Int. Ed., 2012, 51,
8933; (b) N. Marion, R. S. Ramón and S. P. Nolan, J. Am.
Chem. Soc., 2009, 131, 448.
24 F. Trentin, A. M. Chapman, A. Scarso, P. Sgarbossa, R. A.
Michelin, G. Strukul and D. F. Wass, Adv. Synth. Catal.,
2012, 354, 1095.
9 L. R. MacGillivray and J. L. Atwood, Nature, 1997, 389, 469.
10 (a) L. Avram and Y. Cohen, J. Am. Chem. Soc., 2002, 124,
15148; (b) E. S. Barrett, T. J. Dale and J. Rebek Jr., J. Am.
Chem. Soc., 2008, 130, 2344; (c) L. Avram and Y. Cohen, Org.
Lett., 2002, 4, 4365; (d) L. Avram, Y. Cohen and J. Rebek,
25 (a) F. Boeck, T. Kribber, L. Xiao and L. Hintermann, J. Am.
Chem. Soc., 2011, 133, 8138; (b) L. Li, M. Zeng and S. B.
Herzon, Angew. Chem., Int. Ed., 2014, 53, 7892.
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Catalysis Science & Technology
26 A. D. Allen, Y. Chiang, A. J. Kresge and T. T. Tidwell, J. Org.
Chem., 1982, 47, 775.
27 (a) T. Tsuchimoto, T. Joya, E. Shirakawa and Y. Kawakami,
Synlett, 2000, 1777; (b) N. Olivi, E. Thomas, J.-F. Peyrat, M.
Alami and J.-D. Brion, Synlett, 2004, 2175; (c) N. Menashe
and Y. Shvo, J. Org. Chem., 1993, 58, 7434.
34 It is known that up to three molecules of tetraethylammonium
tetrafluoroborate 4 are accommodated in the cavity of the
resorcin[4]arene hexamer: L. C. Palmer, A. Shivanyuk, M.
Yamanaka and J. Rebek Jr., Chem. Commun., 2005, 857.
35 S. Mecozzi and J. Rebek Jr., Chem. – Eur. J., 1998, 4, 1016.
36 Diphenylacetylene and aliphatic alkynes like 4-phenyl-1-
butyne, 3,3-dimethyl-1-butyne and 1-octyne did not lead to
the formation of their corresponding ketones. Similarly, the
hydration reaction of benzonitrile was tested under identical
experimental conditions without observing the formation of
the corresponding benzamide.
28 M. Jacubert, O. Provot, J.-F. Peyrat, A. Hamze, J.-D. Brion and
M. Alami, Tetrahedron, 2010, 66, 3775.
29 Z. Nairoukh, D. Avnir and J. Blum, ChemSusChem, 2013, 6, 430.
30 W.-L. Wong, K.-P. Ho, L. Y. S. Lee, K.-M. Lam, Z.-Y. Zhou,
T. H. Chan and K.-Y. Wong, ACS Catal., 2011, 1, 116.
31 R. Kore and R. Srivastava, Tetrahedron Lett., 2012, 53, 3245.
32 S. Liang, G. B. Hammond and B. Xu, Chem. Commun.,
2015, 51, 903.
37 R. A. Cox, Adv. Phys. Org. Chem., 2012, 46, 1.
38 (a) A. D. Allen, Y. Chiang, A. J. Kresge and T. T. Tidwell,
J. Org. Chem., 1982, 47, 775; (b) V. Lucchini and G. Modena,
J. Am. Chem. Soc., 1990, 112, 6291.
33 L. Catti, Q. Zhang and K. Tiefenbacher, Synthesis, 2016, 48, 313.
Catal. Sci. Technol.
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