Tropylium Ion Catalyzes Hydration Reactions of Alkynes

Article abstract of DOI:10.1002/ejoc.201800579

The hydration of alkynes is one of the most atom-economic and versatile synthetic protocols to access carbonyl compounds. This fundamental reaction, however, often requires transition-metal catalysts or harsh reaction conditions to promote the addition of water to the carbon–carbon triple bond. In this work, it is demonstrated that the non-benzenoid aromatic tropylium ion can be used as an organic Lewis acid promoter for the hydration of alkynes under simple reaction conditions with excellent outcomes.

Full text of DOI:10.1002/ejoc.201800579

A Journal of
Accepted Article
Title: Tropylium Ion Catalyzes Hydration Reactions of Alkynes
Authors: Giulia Oss, Junming Ho, and Thanh Vinh Nguyen
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800579
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European Journal of Organic Chemistry
10.1002/ejoc.201800579
FULL PAPER
Tropylium Ion Catalyzes Hydration Reactions of Alkynes
[
a]
[a]
[a]
Giulia Oss, Junming Ho* and Thanh Vinh Nguyen*
Abstract: The hydration of alkynes is one of the most atom-
economic and versatile synthetic protocols to access carbonyl
compounds. This fundamental reaction, however, often requires
transition-metal catalysts or harsh reaction conditions to promote the
addition of water to the carbon-carbon triple bond. In this work, we
demonstrate for the first time that the non-benzenoid aromatic
tropylium ion can be used as an organic Lewis acid promoter for the
hydration of alkynes under simple reaction conditions with excellent
outcomes.
-
-
planar ring, fully conjugated
6π electrons
stable (aromatic) carbocation
soft organic Lewis acid
- positively charge
This work: Tropylium ion as organocatalyst for hydration reactions of alkynes
O
R2
R1
BF
(5 mol%)
4
R1
R
2
cat.
H H
27 examples
2
H O (2 equiv)
conditions: AcOH at 130 ºC, 1 h
or: TFE at rt, 48 h
35%-quant. yields
Previous hydration reactions of alkynes
R2
H O
2
O
Introduction
R1
R1
R2
cat. transition metal or strong Brønsted acid
H H
The fundamental hydration reaction of alkynes to carbonyl
compounds remain a versatile chemical process to access
valuable synthetic substrates as well as an interesting reactivity
complicated reaction setups
excess water
expensive metal/ligand catalyst or toxic solvent
possible
issues:
[
1]
probe for a range of catalytic systems. This reaction is
commonly utilized in organic synthesis due to its atom-economic
Figure 1. Tropylium-catalyzed hydration of alkynes.
[
1c]
nature. Although the reaction is exergonic, it often requires a
[
1]
catalyst to speed up the hydration of alkynes. In the past two
decades, the reaction has long departed from its original
[
15]
chemistry
and synthetic applications of Lewis acid/base
[
16]
[
2]
systems, we believe that tropylium ion could serve as a Lewis
mercury-promoted process with recent developments on more
[
15d]
[
1]
acid promoter for the hydration of alkynes.
Specifically, the
environmentally benign methods. These developments have
focused on two distinct angles of the reaction: activating alkyne
tropylium cation may enhance the Brønsted acidity of water or
[
1c]
[3]
the protic solvent, in a Lewis acid assisted Brønsted acid
substrate or stimulating the ‘hydrative’ reaction medium. The
first research direction typically involves activation of alkynes
[
17]
catalytic pathway, to facilitate the alkyne hydration reaction.
Previous Brønsted acid catalyzed hydration methods normally
[
4]
[5]
[6]
[7]
with transition-metal catalysts containing Au, Ag, Ru, Pd,
[
3c]
[
8]
[9]
[10]
[11]
employed strongly acidic conditions with special co-activators
Fe, Cu , Co
and other metals.
More recently, there has
[
3a,3b]
such as ionic liquid solvents,
perfluorinated reagents or
been a number of interesting hydration processes promoted by
[
12f]
[17]
[
12]
solvents
or metal Lewis acids. Herein, we demonstrate for
Brønsted acid catalytic systems. However, these methods are
[
18]
[
12c,12g,12h]
the first time that tropylium tetrafluoroborate
can be used as
generally limited in scope
or require complicated
[
7c,12c,12i]
an efficient organic promoter for the metal-free hydration
reaction of alkynes using a cheap solvent and simple reaction
setups. Our combined NMR and computational studies revealed
interesting activation mechanisms by the tropylium ion, which
will spur further research into the applications of tropylium ion in
catalytic chemistry.
reaction setups
expensive solvents.
with long reaction times in toxic or
Therefore, it is still of significant
[
12f,12h]
interest to develop new methods that do not involve precious
and toxic metal-catalysts and solvents, or have broader reaction
and substrate scopes. Herein, we report the successful
utilization of tropylium tetrafluoroborate, a readily available salt
of a stable carbocation, as an organic Lewis acid to efficiently
promote the hydration reaction of alkynes with excellent
outcomes (Figure 1).
Results and Discussion
[
13]
The non-benzenoid aromatic tropylium ion
and a positive charge fully delocalized on a conjugated planar
has 6π electron
Gratifyingly, our initial test reactions using tropylium
tetrafluoroborate (2) as a catalyst for the hydration reaction of
phenylacetylene (1a) met with instant success (Table 1). Under
pressurized microwave-assisted high temperature conditions in
toluene, 1a smoothly reacted with water to form acetophenone
[
14]
seven-carbon system.
It therefore fulfills Hückel's rule of
aromaticity and possesses a unique combination of stability and
reactivity. Based on our previous works with tropylium-promoted
(
2a) with 80% conversion within one hour in the presence of 5
[
a]
G. Oss; Dr J. Ho; Dr T. V. Nguyen
mol% catalyst 2 (entry 1, Table 1). We subsequently did a quick
[
19]
School of Chemistry, University of New South Wales
Sydney, Australia
solvent screening study and found that reactions in no solvent,
alcohols, dichloroethane, acetonitrile as well as toluene gave
unsatisfactory conversion of 1a to the product (entries 1-6).
Acetic acid, however, turned out to be a very good solvent for
this reaction (entry 7, Table 1). Variations of the tropylium
E-mail: t.v.nguyen@unsw.edu.au and junming.ho@unsw.edu.au
[**]
Experimental procedures, characterization data and spectroscopic
data are available free of charge.
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201800579
FULL PAPER
c
a
Conventional heating instead of MW irradiation gave similar results. 0.5 mL
Table 1. Optimization of tropylium-catalyzed hydration reaction
d
e
AcOH and 0.5 mL water were used. 0.5 mL AcOH and no water were used.
mol% of Brønsted acid (HBF or TfOH) was used instead of tropylium
5
4
H
O
f
g
cat.
BF4
catalyst. 5 mol% of 2,6-lutidine was used as proton sponge. 5 mol% of 2,6-
H
H
(2)
di(tert-butyl)pyridine was used as proton sponge.
H2O
+
H
solvent
1
a
(2.0 equiv)
Temperature, time
3a
catalyst loading, reaction temperature and reaction time (entries
7
-18) led to the conclusion that the reaction works optimally at
30 ºC after one hour of microwave irradiation or conventional
entry
mol% cat. 2
solvent
T (°C)
t (h)
conv (%)
80
1
[
20]
heating with 5 mol% tropylium tetrafluoroborate (entry 7).
A
1
2
3
4
5
6
5
5
toluene
MeOH
130
130
130
130
130
130
130
130
130
130
130
100
100
130
130
130
130
130
130
130
130
130
130
130
130
130
130
rt
1
1
control reaction without the catalyst showed no conversion of 1a
to product 3a (entry 11).
17
Interestingly, the use of an excess amount of water was not
favorable for the tropylium-catalyzed reaction (entry 17, Table 1).
When the reaction was carried out without the addition of water
5
EtOH
MeCN
DCE
1
40
5
1
37
(
entry 18, Table 1), the hydration reaction still took place with the
5
1
43
formation of acetic anhydride by-product from the sacrificial role
of acetic acid (see page S3 in the SI). Since the formation of
acetic anhydride is undesirable, the addition of water is deemed
necessary for the hydration reaction. Different counterions had
no effect on the performance of the tropylium catalysts (entries
5
no solvent
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
TFE
1
10
b
7
5
1
100
57
8
9
2
1
1
9-21, Table 1).
1
1
34
The use of strong Brønsted acids such as triflic acid (pKawater = -
[
21]
[22]
1
1
1
1
1
1
1
0
1
2
3
4
5
6
0.5
-
1
13
14.7)
or HBF
4
(pKawater = -0.44)
as catalysts can also
promote the smooth conversion of 1a to 3a (entries 22 and 23),
albeit only ~ 90% conversion in the later case. The weakly
(Brønsted) acidic ammonium tetrafluoroborate only gave a very
poor conversion (entry 24, Table 1). Potassium tetrafluoroborate
could not catalyze the reaction but the (Lewis) acidic tritylium
tetrafluoroborate resulted in a good conversion of alkyne 1a to
product 3a (entries 25-26).
1
n.r.
51
5
1
5
2
70
5
0.25
0.5
0.75
1
74
5
87
Li and co-workers recently reported in an interesting study that
triflic acid can facilitate the hydration reactions of alkyenes at
5
92
ambient temperature (reactive substrates) or 70 ºC (less reactive
c
1
7
5
38
[12f]
substrates) in TFE.
TFE solvent actually played a role in
d
1
8
5
1
100
100
100
100
100
~90
< 5
n.r.
~90
100
100
100
< 5
< 5
lowering the activation energy for these reaction compared to
[
12f]
ethanol.
using this perfluorinated solvent to carry out our catalytic
reactions under milder conditions. Gratifyingly, quick
Therefore, we decided to explore the possibility of
Trop Br
1
9
1
Trop PF6
a
2
2
0
1
1
optimization (entries 27-29, Table 1) showed that tropylium
catalyst 2 can also promote the hydration reaction of alkyne 1a
at room temperature in TFE with reaction time comparable to
Trop ClO
4
1
e
2
2
3
TfOH (5)
HBF (5)
NH BF (5)
KBF
TrBF
1
what reported by Li and co-workers with 20 mol% triflic acid
e
[12f]
2
4
1
catalyst.
Thus, we have developed two practical protocols to
facilitate the hydration reaction of alkynes, one at elevated
temperature in the inexpensive and abundantly available acetic
acid solvent (entry 7, Table 1) and the other at room
temperature in TFE (entry 29, Table 1).
2
4
4
4
1
2
2
2
2
2
5
6
7
8
9
4
(5)
(5)
1
4
1
Subsequent substrate scope studies using the first method
showed that this tropylium-catalyzed hydration protocol worked
5
5
1
[
20]
efficiently with a wide range of different alkynes (Scheme 1a).
TFE
72
48
1
All phenylacetylenes with electron-neutral or electron-donating
substituents were hydrated smoothly to their corresponding
acetophenones (3a-3q, Scheme 1a) in excellent yields using the
10
TFE
rt
f
3
0
5 + pyr1
5 + pyr2
TFE
130
130
optimized
reaction
conditions
(entry
7,
Table 1).
g
3
1
TFE
1
Phenylacetylenes with halogen substituents seemed to be less
reactive under the standard reaction settings; hence they were
converted to the acetophenone products using more forcing
a
Alkyne 1a (1 mmol), water (2 mmol), tropylium tetrafluoroborate (2, 0.1 or
b
0
.05 mmol) in solvent (0.5 mL) in a pressurized microwave (MW) reactor.
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European Journal of Organic Chemistry
10.1002/ejoc.201800579
FULL PAPER
(a) In AcOH at 130 ºC
[
§] 2.0 equiv of D2O in AcOD were used instead of H2O in AcOH
R2
O
BF4
(5 mol%)
R1
R1
R2
cat.
[
#] 20 mol% cat., 130 ºC (conventional heating), 48 h
(for less reactive substrates)
H
H
H2O (2 equiv), AcOH (0.5 mL), 130 ºC (MW), 1 h
O
O
Me
O
O
O
O
O
O
tBu
Me
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CHDx
nC H
5 11
tBu
2
< x < 3
Me
Me
Me
3d, 72%
nPr
3
b, 96%,
tBu 3h, 80%
3
aD, 86% [§]
3c, 94%
3e, 92%
3f, 96%
3g, 92%
3
.86 g (30 mmol scale)
O
O
OMe O
O
OMe O
O
O
O
MeO
MeO
MeO
MeO
HO
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
MeO
MeO
EtO
Me2N
3
i, 98%
3j, 95%
3k, 89%
3l, 91%
3m, 83%
O
3n, 93%
3o, 99%
3p, 92%
O
O
O
O
Br
O
O
O
Br
Br
Br
CH3
CH3
CH3
CH3
Cl
Br
Ph
3w, 88% [#]
3
q, 96%
3
r, 80% [#]
3s, 35% [#]
3t, 64% [#]
3u, 54% [#]
3v, 98% [#]
3x, 86% [#]
1
.96 g (12 mmol scale)
O
O
O
O
O
O
O
O
O
CH3
CH3
CH3
CH3
N
CH3
H3C
CH3
F3C
2
O N
3
y, 80% [#]
3z, 88% [#]
3Na, no reaction
3Nb, no reaction
3Nc, no reaction 3Nd, no reaction
3Ne, no reaction
3Nf, no reaction
(b) In TFE at room temperature
O
O
O
O
R2
O
BF4
R1
R1
R2
CH3
CH3
CH3
CH3
cat.
(10 mol%)
nPr
nC5H11
tBu
H
H
H2O (2 equiv), TFE (0.5 mL), rt, 48 h
3
a, 99%
3e, quant.
3f, 99%
3g, quant.
O
O
O
O
O
O
O
O
O
tBu
HO
CH3
CH3
Br
CH3
Me2N
CH3
CH3
Cl
CH3
CH3
CH3
CH3
EtO
F3C
2
O N
tBu
3r, 99%
with 20 mol% cat.
3
n, quant.
3o, 96%
3p, 85%
3s, 99%
3Na, no reaction
3Nb, no reaction 3Nc, no reaction
3
h, 99%
with 20 mol% cat
70 °C, MW
Scheme 1. Substrate scope of the tropylium-catalyzed hydration reaction
[
20]
conditions (3r-3u, Scheme 1a).
Similarly, non-terminal
of substrate 1a with deuterated water reagent and acetic acid
solvent also went smoothly to give deuterated acetophenone
3aD in high yields (Scheme 1a). There were more than two
aromatic alkynes required longer reaction times and higher
catalyst loading to afford the products in high to excellent yields
[
20]
(
3v-3z, Scheme 1a). Non-aromatic alkynes and aromatic
alkynes with strong electron-withdrawing substituents such as
the CF or nitro group could not be hydrated using this tropylium-
deuteriums incorporated into 3aD,
most likely due to further
deuteration via the enolization of the ketone under acidic
conditions.
3
catalyzed procedure (3Na-3Nf), hinting that a π electron-rich
aromatic system on the substrate is required for the tropylium
activation. This is consistent with a Brønsted acid catalyzed
pathway since the more electron-rich the substrate is, the higher
its proton affinity and the lower the thermodynamic barrier for
proton transfer. Despite this limitation, the substrate scope
clearly demonstrates the superior synthetic value and versatility
of the tropylium-catalyzed system in comparison to previous
Using the second method in TFE solvent at room temperature
(entry 29, Table 1), a number of randomly selected alkyne
substrates were hydrated smoothly and efficiently with 10 mol%
of tropylium catalyst (3a, 3e, 3f, 3g, 3h, 3n, 3o, 3p, Scheme 1b).
Chloro- and bromo-substituted phenylacetylene required higher
catalyst loading or elevated temperature to promote the
reactions (3r and 3s, Scheme 2c). Unfortunately the highly
electron-deficient aromatic or aliphatic substrates (3Na, 3Nb,
3Nc) still did not react, even with 20 mol% catalyst at 70 ºC.
Although these results showed that tropylium tetrafluoroborate
does not provide superior reactions outcomes to triflic acid as
[
12]
transition metal-free methods.
The first reaction protocol could also be easily employed in
multiple-gram scale reactions, as demonstrated by two
examples of alkynes 1b and 1q (Scheme 1a). These reactions
were very high yielding, which confirm the practicality of the
tropylium-catalyzed system. Furthermore, the hydration reaction
[
12f]
reported by Li and co-workers,
it is still synthetically
convenient to use such a stable solid organic catalyst to setup
this type of chemical transformation. The question remains as to
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European Journal of Organic Chemistry
10.1002/ejoc.201800579
FULL PAPER
what is the origin of the catalytic action of tropylium ion in this
type of reaction?
proton is initially transferred from acetic acid to phenylacetylene
(1a) to form the ion pair 6:OAc (Figure 2b). The potential energy
scans (Figure S4 – see page S6 in the SI) suggest that the
proton transfer is associated with spontaneous acetate addition,
Mechanistic Studies
(a) The first hypothesis of the reaction mechanism
There are two possible explanations for the catalytic activity of
tropylium tetrafluoroborate in the hydration reaction of alkynes:
OX
BF4
H
1
a
(
i) the tropylium ion acts as a ‘non-covalent’ Lewis acid to
7
cat. 2
activate the alkyne substrate (Figure 2a) or (ii) the tropylium ions
reacts with water or the solvent to facilitate the reaction via a
hidden Lewis acid assisted Brønsted acid catalytic pathway
X
BF4
BF4
(
vide infra). Our initial NMR studies (Figure 2b) revealed
O
π-π
interaction
complex
aromatic interactions between tropylium ion and
phenylacetylene, suggesting that tropylium might act as a non-
covalent catalyst. Specifically, when present in a 20:1 mixture (to
reflect the 5 mol% catalyst loading) with phenylacetylene 1a, the
tropylium ion signal showed an upfield shift, presumably due to
π−π interactions between tropylium ion and phenylacetylene
H
4
6
BF4
X
O
O
HOX
(X = H
or Ac)
Hδ+
CH3
(
spectrum 4, Figure 2a). Additionally, non-reactive substrates for
the tropylium-promoted hydration reaction, for example alkynes
Nb and 1Nc, showed much less significant chemical shift
3
a
5
1
1
3
(b) H NMR studies (CD CN, 400 MHz, 25 ºC)
movements (spectra 7 and 8, Figure 2b). The π−π interaction
between the tropylium ion to the benzene ring was also
evidenced in the cases of styrene and ethylbenzene, where a C-
C triple bond is absent (spectra 5 and 6, Figure 2b). At the NMR
temperature (25 ºC), tropylium tetrafluoroborate seemed to be
stable in the presence of water and acetic acid for several days
(
spectra 2 and 3).
Based on these NMR studies, we hypothesised that the
tropylium ion can simultaneously activate water/acetic acid
through electrostatic stabilization, and hold them in the close
proximity to the alkyne substrate (complex 5, Figure 2a) to
promote the reaction. Thus, we subsequently employed DFT
[
23]
(
M06-2X/6-31+G(d,p))
calculations (G3(MP2)-RAD(+))
of this process. Figure 2c illustrates the G3(MP2)-
and high-level ab initio composite
[
24]
to investigate the energetics
[
25]
[26]
-1
RAD(+)/SMD(Acetic Acid)
free energy profile
(in kJ mol )
for proton-coupled acetate addition to phenylacetylene in the
absence and presence of tropylium ion. The calculations
indicate that tropylium forms a very weak π−π complex with
(c) G3(MP2)-RAD(+)/SMD(acetic acid) free energy profile
-
1
phenylacetylene (ΔG complexation ca. 3.4 kJ mol ), which is
consistent with NMR studies. For this reason, the energies
reported in Figure 2(c) are relative to separate reactants. We
have located a concerted transition state where proton transfer
from acetic acid is coupled with acetate addition in an
asynchronous fashion. The free energy barrier associated with
TS-tropylium
62.3 kJ/mol
TS
60.0 kJ/mol
1
1
-
1
this transition state is about 160 kJ mol , which is thermally
inaccessible and is consistent with experimental observations
(
see entry 11, Table 1).
AcOH +
Surprisingly, the calculations further indicate that when tropylium
ion is present in a stacked conformation with phenylacetylene,
-
1
0
.0 kJ/mol
OAc
the free energy barrier is slightly raised by
2 kJ mol .
Presumably, the concerted nature of the transition state (no
charged intermediates) also means that electrostatic
stabilization is not likely to play a significant role. We have also
investigated the possibility of a stepwise process where the
-
60.1 kJ/mol
Figure 2. Mechanistic studies of the tropylium catalyzed hydration reaction.
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European Journal of Organic Chemistry
10.1002/ejoc.201800579
FULL PAPER
which refutes
a
stepwise mechanism when tropylium is
However, there was clear evidence that the tropylium ion
interacts weakly with water or AcOH, as indicated by the upfield
shifts of the tropylium signal when it was in 1:20 (equivalent to 5
mol% tropylium) mixtures with these nucleophilic molecules
(even at room temperature, also see spectra 2-3, Figure 2b).
Heating tropylium tetrafluoroborate to 130 ºC for one hour in
operating as a non-covalent catalyst. In brief, the results
presented in Figure 2 and discussed here indicate the non-
covalent catalytic pathway might not be the predominant route
for this tropylium-promoted alkyne hydration reaction.
The second proposed mechanism was based on the common
belief that tropylium tetrafluoroborate could react with water or
4 3
pure d -acetic acid (CD COOD) led to the formation of a small
[
27]
acetic acid (pKawater = 4.76) to form hydrogen tetrafluoroborate
HBF ) and OH/OAc substituted cycloheptatriene (also see
Figure 2),
amount (~ 5% of the original tropylium loading, i.e. in a catalytic
reaction with 5 mol% tropylium, only ~ 0.25 mol% converted to
this form) of cycloheptatriene adduct (see Eq. 4, spectrum 4,
Figure 3). Such reaction was not observed for water (Eq. 3,
spectrum 2).
(
4
[
13c]
thus catalyzing the reaction via a hidden Brønsted
acid catalytic pathway. During our optimization work discussed
in Table 1, we found that the addition of 2,6-lutidine or 2,6-
di(tert-butyl)pyridine as bulky Brønsted bases stopped the
Based on these collective NMR studies, we believe that the
presence of the tropylium ion in acetic acid might have led to the
formation of a small amount of a strong Brønsted acid (13,
Figure 3) through a Lewis acid assisted pathway. Figure 4
provides additional computed thermodynamic data to help shed
light on the mechanism of action of tropylium ion. Reactions (A)
to (C) shows that tropylium ion enhances the transfer of a proton
from acetic acid to phenylacetylene, forming vinyl cation
intermediate 14 (Figure 4), through electrostatic stabilization (B)
or adduct formation (C). In the former, the degree of stabilization
[
21]
reaction from working properly (entries 30 and 31, Table 1),
again hinting that this reaction might actually be Brønsted acid
HBF ) catalysis assisted by Lewis acid (tropylium salt). Would it
(
4
really be the case? To gain more insights into this hypothesis,
we carried out a range of mechanistic studies using NMR
spectroscopy (Figure 3) to look at how the tropylium ion interacts
with all reaction components.
Much to our surprise, tropylium tetrafluoroborate was found to
react directly with 2,6-lutidine (8) or 2,6-di(tert-butyl)pyridine (10)
to presumably form the corresponding cycloheptatrienyl
pyridinium salts (9 and 11, Figure 3). These chemical processes
ruled out the validity of the control experiments carried out in
entries 30-31 (Table 1) discussed above. The reaction with 2,6-
lutidine occurred quickly even at room temperature (Eq. 2,
spectrum 5) whereas 2,6-di(t-butyl)pyridine was more sluggish
but one hour at 130 ºC completely converted tropylium salt to
the inactive cycloheptatrienyl derivative (Eq. 1, spectrum 6).
Mixtures of tropylium tetrafluoroborate and water or acetic acid
-
1
is about 25 kJ mol ; however, the overall thermodynamic barrier
-
1
is still exceedingly high at 187 kJ mol . As such, tropylium ion is
unlikely to act as a non-covalent catalyst. By comparison, in
reaction (C) tropylium ion acts as a Lewis acid to stabilize the
resulting acetate anion via adduct formation, and this
-
1
significantly lowered the thermodynamic barrier by 90 kJ mol to
-
1
122 kJ mol , which is in the thermally accessible range.
Reactions (D), (E) and (F) provide some hints with regards to
the microspecies that may be involved in the proton transfer
process. Notably, the calculations indicate that the free energy
change for proton transfer from hydrogen tetrafluoroborate or
tropylium acetic acid adduct 13 to substrate 1a is approximately
3
in CD CN as NMR solvent remained unchanged after one hour
at 130 ºC (spectra 2-3, Figure 3; also see page S3 in the SI) or
several days at ambient temperature (see spectra 2 and 3,
Figure 2b) without the formation of hydrogen tetrafluoroborate.
-
1
30 kJ mol , which is a four-fold reduction compared to (C).
tBu
BF4
tBu
1
30 ºC
N
(Eq. 1)
N
BF4
tBu
tBu
1
0
2
2
1
1 (spectra 6)
Me
N
BF4
Me
N
rt
BF4
(Eq. 2)
Me
Me
8
9
(spectra 5)
H
H
H
H
BF4
O
BF4
X
O
(Eq. 3)
H
1
2
2
(
no evidence in NMR
also see page S2-4 in the SI)
H
O
O
∆
BF4
BF4
O
O
H
(Eq. 4)
1
3
H
2
pKa13 ~ pKaHBF4
1
3
Figure 3. Interactions of tropylium ion with acetic acid and water: (left) NMR studies [ H NMR, CD CN (except spectrum 4), 400 MHz, 25 ºC]; (right)
Corresponding chemical reactions
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European Journal of Organic Chemistry
10.1002/ejoc.201800579
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ΔG = 212 kJ/mol
ΔG = 187 kJ/mol
(
A)
AcOH
+
AcO
+
1
a
14
(
B)
+
+
O
O
1
5
1a
14
1
6
OH
O
ΔG = 122 kJ/mol
(C)
+
AcOH
+
OAc
+
1
4
1
a
1
7
2
+
AcOH
ΔG ~ -181 kJ/mol
HOH
ΔG ~ -168 kJ/mol
OAc
H+
+
+
7
-Ac
ΔG = 33 kJ/mol
(D)
BF
+
hydrolysis
HBF
4
+
4
O
1
4
1
a
+
H+
3a
O
AcO
(E)
HO
ΔG = 29 kJ/mol
ΔG = -182 kJ/mol
+
+
OAc
-Ac
+
1
3
1a
14
7
AcO
H
regenerated 2
ΔG
17
=
9
3
kJ/
mo
l
2
l
mo
kJ/
2
4
1
ΔG =
HOH
H
2
O
HO
regenerated 2
O
ΔG = 26 kJ/mol
ΔG = -207 kJ/mol
(F)
+
+
+
1
2
1a
14
3a
1
8
Figure 4. Thermodynamic data computed at the G3(MP2)-(RAD)(+)/SMD(acetic acid) level of theory.
As noted earlier, there is NMR evidence to support the presence
of (ca. 5% of the total tropylium loading) 13 in a heated mixture
of tropylium and acetic acid (see Figure 3). We hypothesise that
upon proton transfer from 13 (or 12, if any) to phenylacetylene
alkynes to the corresponding ketone derivative using simple
reaction setup with cheap and environmentally benign reagents
and solvents. This tropylium-promoted reaction is particularly
effective on aryl alkynes with excellent reaction outcomes,
prompting further investigations into new synthetic applications
of the tropylium ion in synthetic organic chemistry and
organocatalysis.
1
a to form vinyl cation 14, this intermediate can further react with
the generated by-products 17/18 to derive the product with the
regeneration of tropylium ion. Another plausible pathway is the
reaction of 14 with acetic acid or water (see reactions (D) in
Figure 5), with the regeneration of the proton, which will then
propagate the reaction. The data indicate that all of these
Experimental Section
-
1
General Methods: Reactions, unless otherwise stated, were conducted
under a positive pressure of dry nitrogen in oven-dried glassware.
Microwave reactions were carried out in pressurized 10 mL microwave
vials on CEM Discover – SP W/ACTIVENT 909155 or 10 mL vials on
Anton Paar Monowave 300. Commercially available reagents were used
as purchased unless otherwise noted. Analytical thin layer
chromatography was performed using silica gel plates pre-coated with
silica gel 60 F254 (0.2 mm). Flash chromatography employed 230-400
mesh silica-gel. Solvents used for chromatography are quoted as
volume/volume ratios.
processes are highly exergonic (ΔG < -160 kJ mol ), suggesting
that they all are likely to be feasible pathways for the subsequent
reactions after proton transfer.
To summarise, our combined experimental and computational
investigations support a Lewis acid assisted Brønsted acid
catalytic mechanism, where the Brønsted acidity of acetic acid
and water is significantly enhanced through adduct formation
with tropylium ion. We believe that the hydration reaction of
alkynes in TFE medium (reported in Scheme 1b) proceeded in a
similar fashion.
NMR spectroscopy was performed at 298 K using either a Bruker Avance
1
13
III 300 (300.13 MHz, H; 75.5 MHz, C; BBFO probe), a Avance I 300
1
13
(
300.13 MHz, H; 75.5 MHz, C; BBFO probe), a Avance III 400 (400.13
Conclusions
1
13
MHz, H; 100.6 MHz, C; BBFO probe or Prodigy cryoprobe), a Varian
1
1
Mercury 300 (300.13 MHz, H), a Varian Inova 400 (400.13 MHz, H;
1
3
1
We have developed a new reaction protocol involves the
tropylium ion as an organocatalyst to facilitate the conversion of
100.6 MHz, C), or a Varian Inova 600 (600.13 MHz, H; 150.0 MHz,
1
3
C). Data is expressed in parts per million (ppm) downfield shift from
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European Journal of Organic Chemistry
10.1002/ejoc.201800579
FULL PAPER
tetramethylsilane with residual solvent as an internal reference (δ 7.26
ppm for chloroform, 5.27 ppm for dichloromethane, 1.94 ppm for
acetonitrile, and 2.09 ppm for the toluene methyl group) and is reported
as position (δ in ppm), multiplicity (s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet), coupling constant (J in Hz) and integration
X Bond Formation, Vol. 31 (Ed.: A. Vigalok), Springer-Verlag Berlin, Berlin,
2
010, pp. 123-155..
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2] (a) M. Kutscheroff, Chem. Ber. 1881, 14, 1540-1542; (b) M. Kutscheroff,
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1
3
(
number of protons). C NMR spectra were recorded at 298 K with
complete proton decoupling. Data is expressed in parts per million (ppm)
downfield shift relative to the internal reference (δ 77.2 ppm for the
central peak of deuterated chloroform). Infrared spectra were obtained on
a ThermoNicolet Avatar 370 FT-IR spectrometer and are reported in
6
036.
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wavenumbers (cm ). HRMS were performed at the Bioanalytical Mass
Spectrometry Facility within the Mark Wainwright Analytical Centre at the
University of New South Wales on an Orbitrap LTQ XL (Thermo Fisher
Scientific, San Jose, CA, USA) ion trap mass spectrometer.
General Procedure for the Tropylium-Catalyzed Hydration Reactions
of Alkynes:
(
k) M. Gatto, P. Belanzoni, L. Belpassi, L. Biasiolo, A. Del Zotto, F. Tarantelli,
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Procedure A: A mixture of alkyne 1 (1 mmol), water (2 mmol), tropylium
tetrafluoroborate (0.05 mmol) and acetic acid (0.5 mL) was charged into
a microwave vial (10 mL volume). The reaction vial was programmed in
the microwave reactor to ramp rapidly from room temperature to the
reaction temperature (~2 min) then hold at that temperature for 1 hour.
The reaction vial was subsequently cooled down to room temperature.
The reaction mixture was partitioned between DCM (10 mL) and sat. aq.
2
[
(
2
017, 781-785.
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1
22-127; (f) J. Santhi, B. Baire, ChemistrySelect 2017, 2, 4338-4342.
NaHCO
3
. The aqueous phase was further extracted with DCM (2 x 5 mL).
SO and concentrated
[
6] D. B. Grotjahn, D. A. Lev, J. Am. Chem. Soc. 2004, 126, 12232-12233.
The combined organic phases were dried over Na
2
4
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under reduce pressure to give practically clean product 3.
Procedure B: A mixture of alkyne 1 (1 mmol), water (2 mmol), tropylium
tetrafluoroborate (0.2 mmol) and acetic acid (1 mL) was charged into a
two-neck flask. The resulting mixture was heated to 130 °C for 48 h. The
reaction was subsequently cooled down to room temperature. The
reaction mixture was partitioned between DCM (10 mL) and sat. aq.
[
8] (a) J. Park, J. Yeon, P. H. Lee, K. Lee, Tetrahedron Lett. 2013, 54, 4414-
4
5
417; (b) M. Bassetti, S. Ciceri, F. Lancia, C. Pasquini, Tetrahedron Lett. 2014,
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NaHCO
3
. The aqueous phase was further extracted with DCM (2 x 5 mL).
SO and concentrated
The combined organic phases were dried over Na
2
4
1
159.
under reduce pressure to give practically clean product 3.
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Procedure C: A mixture of alkyne 1 (1 mmol), water (2 mmol), tropylium
tetrafluoroborate (0.1 mmol) and 2,2,2-trifluoroethanol (0.5 mL) was
charged into a vial (4 mL volume). The reaction mixture was left stirring
at room temperature for 48 h. The reaction mixture was filtered a short-
plug of silica-gel then concentrated under reduce pressure to give
practically clean product 3.
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This work is financially supported by Australian Research
Council (grant DE150100517 awarded to TVN and grant
DE160100807 awarded to JH). The authors thank UNSW
Faculty of Science for additional support. JH acknowledges the
Australian National Computational Infrastructure and Intersect
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Bronsted acid impurities. .
[
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tropylium salts as it tends to ring-opening polymerize these solvent
compounds.
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European Journal of Organic Chemistry
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FULL PAPER
Entry for the Table of Contents
FULL PAPER
Giulia Oss, Junming Ho,* Thanh Vinh
Nguyen*
Page No. – Page No.
Tropylium Ion Catalyzes Hydration
Reactions of Alkynes
From Lewis to Brønsted: Tropylium ion acts as as Lewis acid to mediate the
transition metal-free hydration of alkynes.
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