Pinacol Rearrangement and Direct Nucleophilic Substitution of Allylic Alcohols Promoted by Graphene Oxide and Graphene Oxide CO2H

Article abstract of DOI:10.1002/cctc.201601362

Graphene oxide (GO) and carboxylic acid functionalized GO (GO–CO₂H) have been found to efficiently promote the heterogeneous and environmentally friendly pinacol rearrangement of 1,2-diols and the direct nucleophilic substitution of allylic alcohols. In general, high yields and regioselectivities are obtained in both reactions using 20 wt % of catalyst loading and mild reaction conditions.

Full text of DOI:10.1002/cctc.201601362

Accepted Article
Title: Pinacol Rearrangement and Direct Nucleophilic Substitution of
Allylic Alcohols promoted by Graphene Oxide and Graphene
Oxide-CO2H
Authors: Diego Antonio Alonso, Alejandro Baeza, and Melania Gómez-
Martínez
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ChemCatChem
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FULL PAPER
Pinacol Rearrangement and Direct Nucleophilic Substitution of
Allylic Alcohols promoted by Graphene Oxide and Graphene
Oxide-CO H
2
Melania Gómez-Martínez, Alejandro Baeza,* and Diego A. Alonso*
Dedication ((optional))
[
10]
Abstract: Graphene oxide (GO) and carboxylic acid-functionalized
GO (GO-CO H) have been found to efficiently promote the
as heterogeneous carbocation chemistry
catalysts, in
2
particular, for the pinacol rearrangement of 1,2-diols and the
direct nucleophilic substitution of allylic alcohols. This study
constitutes the first general application of graphene-like catalysts
to promote these reactions.
heterogeneous and environmentally friendly pinacol rearrangement
of 1,2-diols and the direct nucleophilic substitution of allylic alcohols.
In general, high yields and regioselectivities are obtained in both
reactions using 20 wt% of catalyst loading and mild reaction
conditions.
Results and Discussion
The pinacol rearrangement is a valuable process for the
synthesis of aldehydes or ketones through the elimination of
water and skeletal rearrangement of 1,2-diols. The reaction is
Introduction
[
11]
Graphene (G) is considered as one of the most promising
usually performed employing harsh Brønsted acids, such as
materials
in
nanotechnology,
electrochemistry,
and
[12]
H
2
SO
4
or HClO
4
although Lewis acids
as well as solid
[
1]
engineering. The significance of graphene in recent years has
involved an exponential increase in the number of studies into
graphene-based materials. Consequently, remarkable progress
has been accomplished in the development of new graphene
derivatives as benign, abundant, and readily available catalysts
and supports for organic transformations. Among graphene
[13]
[14]
catalysts such as zeolites
and silicoaluminophosphates,
have been also successfully used in this interesting organic
transformation. Table 1 shows the properties and materials
employed in the present study.
[
2]
derivatives, highly oxidized graphene oxide (GO), usually
produced from the exfoliation of graphite oxide, has emerged as
a new class of carbonaceous water-compatible heterogeneous
catalyst that promises green and economically viable routes to
different families of organic compounds. This is mainly due to its
unique aromatic nanostructure with a high surface area and the
presence of different oxygen-containing functional groups which
can be considered as the active sites operating as soft acids or
Table 1. Carbonaceous materials.
[a]
[b]
[c]
Material
O/C atomic ratio
%Mn
%S
[
d]
GO
0.655
0.09
0.16
0.8
0
[
d]
rGO
0.142
[d,e]
2
GO-CO H
0.664
0.003
0.05
0.2
5.2
[
3]
mild green oxidants. Furthermore, GO is easily functionalized
providing to the synthetic chemist a wide variety of graphene-like
[
f]
GiO
1.37
[
4]
carbocatalysts. Typical GO-catalyzed organic reactions are
substitutions, additions, hydrolyses, condensations, and redox
[
a] Determined by XPS. [b] Determined by ICP-MS. [c] Determined by
elemental analysis. [d] Provided by NanoInnova Technologies S.L. [e] 0.7
mmol CO H/g. [f] Provided by Applynano Solutions S.L.
[
5]
processes.
Graphene oxide’s usefulness as a solid state acid catalyst
2
[
6]
comes from its high acidity (pKa 3-4 in water)
as a
consequence of the sulfate or sulfonic acid groups present on its
surface. Prompted by previously studies on the use of GO as
The GO-catalyzed (20 wt%) pinacol rearrangement of 2,3-
diphenylbutane-2,3-diol was selected as model reaction in order
to perform the reaction conditions study (Table 2). Using toluene
[
7]
acid catalyst and as a part of our recent interest in carbon-
[8]
based materials, we report herein the successful use of few-
(
0.20 M) as solvent at 100 ˚C, only pinacol rearrangement with
[
9]
2
layer GO and a carboxylic acid-functionalized GO (GO-CO H)
phenyl migration was observed affording 3,3-diphenylbutan-2-
one (1) in a 95% isolated yield. Interestingly, the rearrangement
was highly chemoselective and no other side reactions, such as
[
15]
[
a]
M. Sc, M, Gómez-Martínez, Dr. A. Baeza, Dr. D. A. Alonso
the Nametkin rearrangement,
were observed in the crude
Organic Chemistry Department and Institute of Organic Synthesis
reaction mixture. The yield of the reaction clearly decreased
when reducing the temperature (Table 2, entries 2 and 3). The
reaction could also be performed under solvent-less conditions
to afford 1 in an 80% yield. No conversion towards 1 was
(
ISO)
Faculty of Sciences, University of Alicante
Apdo. 99, 03080 Alicante, Spain
E-mail:
detected when using H
acetophenone formed (8% conversion by GC) from the retro-
2
O as reaction medium, being only
Supporting information for this article is given via a link at the end of
the document.
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ChemCatChem
10.1002/cctc.201601362
FULL PAPER
[17]
pinacol coupling of the starting diol. This reaction is probably
carbocatalyst,
this material was not effective in the pinacol
catalyzed by traces of metal oxides, such as MnO
2
, contained in
rearrangement of 2,3-diphenylbutane-2,3-diol (Table 2, entry 10),
probably due to the markedly smaller specific surface area and
the absence of reactive sites to be a viable carbocatalyst. This
result was confirmed when graphite oxide (GiO) was used as
catalyst, which afforded 1 in a 80% isolated yield (Table 2, entry
11). Given the analytical properties of the employed GiO (see
Table 1), this result clearly indicated the important contribution to
[
16]
the carbocatalyst. Interestingly, microwave irradiation showed
a significant reduction in reaction time without compromising
performance (Table 2, entry 6). Regarding catalyst study, no
conversion was observed in the absence of GO (Table 2, entry
[
18]
7). The importance for catalysis of the functionality of GO was
demonstrated using rGO as catalyst in toluene, which resulted
inactive in the pinacol rearrangement (Table 2, entry 8). The
the process of both appropriate acidic sulfate groups (C-OSO
3
H)
2 2
carboxylic acid-functionalized GO-CO H (0.7 mmol CO H/g) was
and a high surface area. Catalytic contributions from metallic
[
19]
also unproductive as catalyst in the rearrangement. In fact, only
acetophenone was detected (10% conversion by GC) as a
consequence of the retro-pinacol coupling of the starting
material (Table 2, entry 9).
contaminants must be excluded. To discard the impact in GO
of residual manganese originated from its preparation process
(0.09% by ICP-MS, see Table 1), the model reaction was carried
out in the presence of an excess (0.1 mg) of MnO
2 2
and MnCl
(
Table 2, entries 12 and 13). The obtained results illustrate that
manganese species have no obvious catalytic activity for the
pinacol rearrangement under the optimized reaction conditions.
Furthermore, rGO (0.16% Mn by ICP-MS, 0% S by elemental
analysis, Table 1) had shown no activity in the reaction (Table 2,
entry 8) which definitively excluded any metal-catalyzed
contribution to the studied process and reinforced the role of the
sulfate groups as catalytic active sites in the material.
Table 2. Carbocatalyzed pinacol rearrangement of 2,3-diphenylbutane-2,3-
diol. Conditions study.
[
a]
90
Entry
Catalyst
GO
Solvent
Toluene
Toluene
Toluene

T (ºC)
100
50
Conv. (%)
95 (93)
82
100
7
5
7
1
80
60
40
20
0
1
2
3
4
5
6
7
8
9
5
2
yield (%)
C (%)
4
5
3
7
GO
2523
GO
rt
< 5
0.8
O (%)
0
GO
100
100
80
S (%)
[
b]
1
2
3
4
GO
H
2
O
< 5 [8]
Reaction cycle
[
c]
GO
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
1
100
92

100
100
100
100
100
100
100
< 5
Figure 1. GO recyclability and elemental analysis.
rGO
< 5
[
b]
2
GO-CO H
< 5 [10]
To test the recyclability of the catalyst, GO was recovered after
centrifugation, washed, and reused in four consecutive reaction
runs. As depicted in Figure 1, under the optimized loading
reaction conditions,
carbocatalyst was observed. Elemental analysis the GO
promoter after the fourth run showed a strong decrease in O and
S contents. Since GO-CO
the rearrangement, this result confirmed the central role of the -
OSO H groups as active sites for a good catalytic activity in the
pinacol rearrangement. In fact, some
10
11
12
13
Graphite
GiO
< 5
80
a
progressive deactivation of the
[
2
d]
[b]
[b]
MnO
< 5 [15]
[
2
d]
MnCl
< 5 [28]
2
H did not show any catalytic activity in
[
a] Conversion towards 1 determined by HNMR. In brackets, isolated yield
3
after flash chromatography. [b] In square brackets, reaction conversion
towards acetophenone detected by GC analysis in the crude reaction
mixture. [c] Reaction performed under MW irradiation (100 ˚C, 150 W, 1 h).
[d] 0.1 Milligrams were used as catalyst.
These results clearly showed the importance for catalytic
activity of a high-surface few-layer system with the appropriate
functionality. Although graphite has often been cited as effective
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10.1002/cctc.201601362
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partially nonspecific reduction of GO was observed during the
[
20,21]
catalytic cycle by XPS.
The importance for catalysis of the presence in the material of
attached hydrogen sulfate groups was confirmed performing
different tests. The first study consisted of the preparation of
Table 4. GO-catalyzed pinacol rearrangement. Substrate scope.
[
22]
sulfonated reduced graphene oxide
elemental analysis, see SI) from rGO (inactive catalytic material
in the pinacol rearrangement). The freshly prepared rGO-SO
3
(rGO-SO H, 3.29 %S by
3
H
showed good catalytic activity in two reaction cycles under the
optimized reaction conditions (Scheme 1).
Product(s)
[
a]
Entry
1
Starting diol
Structure No., yield (%)
2
3
3
Scheme 1. rGO-SO H-catalyzed pinacol rearrangement.
We also studied the activity of GO (25 mg) after three
washings/extraction cycles with ultrapure water (3 × 10 mL) to
remove sulfuric acid impurities. The catalytic activity of the
washed GO was tested in the pinacol rearrangement of 2,3-
diphenylbutane-2,3-diol resulting an 80% conversion in 20 h.
This result demonstrated that water removed some of the not so
strongly bonded active OSO H sites from GO sheets. Overall,
3
the performed control experiments are compatible with the
presence of hydrogen sulfate catalytic units bound to GO, as
4
5
6
[23]
[
5f,g]
previously demonstrated for other organic transformations.
In order to assess how important was the presence of OSO
groups for the reaction to proceed, we decided to test the
reaction using H SO and pTsOH as homogeneous catalysts in
equivalent amounts to that estimated from the elemental
3
H
2
4
[
24]
analysis of GO (see Table 1).
Thus, 2,3-diphenylbutane-2,3-
diol was allowed to react under the optimized conditions using
sulfuric acid (1.2 mol%) as catalyst. After 20 h no rearranged
product was observed (<5% conversion by GC), being only
detected a 17% of acetophenone from the retro-pinacol reaction
(
Table 3, entry 1). On the other hand, pTsOH (1.2 mol%)
afforded 15% conversion of along with 55% of
a
1
a
7
8
acetophenone (Table 3, entry 2). Interestingly, when this last
reaction was carried out in the presence of 20 wt% of rGO, only
starting material was detected by GC analysis, being no retro-
pinacol product observed. Thus, the role of the carbonaceous
surface on the selectivity of the process was then clearly
demonstrated. Finally, good conversion towards 1 were only
observed when the reaction was perfomed using 25 mol% of
pTsOH as homogeneous catalyst (Table 3, entry 4). All the
obtained results seems then to suggest a synergistic effect
[
a] Isolated yield after flash chromatography. [b] 50 wt% of GO was used.
1
involving, apart from the anchored OSO
sites present on the GO surface.
3
H groups, other active
[c] Isolated crude yield, >95% pure by HNMR. [d] Ratio determined by
1
HNMR over the crude reaction mixture. [e] A 10% of benzophenone was
also obtained. [f] Ratio determined by GC over the crude reaction mixture.
[
g] Reaction performed under neat conditions. An 87% yield of 10 was
obtained using toluene as solvent.
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carbonyl compounds from epoxides. Thus, treatment of 1-
phenyl-7-oxabicyclo[4.1.0]heptane with GO (50 wt%) under the
optimized conditions led to the formation of
1-
Table 3. Pinacol rearrangement of 2,3-diphenylbutane-2,3-diol. Role of the
OSO H active sites.
3
phenylcyclopentanecarbaldehyde (12) in a 56% isolated yield.
[
a]
Entry
Catalyst (mol%)
SO (1.2)
1 (%) / Acetophenone (%)
1
2
3
4
H
2
4
3 / 17
15 / 55
0 / 0
Scheme 2. Meinwald rearrangement.
pTsOH (1.2)
pTsOH (1.2) + rGO
pTsOH (25)
[
b]
The assumption of the formation of epoxide
9
as
intermediate in the pinacol rearrangement was reinforced
performing the GO-catalyzed rearrangement of benzopinacol in
90 / 0
[
a] Reaction conversion determined by GC analysis. [b] 20 wt% of rGO (0% S
2
the presence of two soft nucleophiles such as TsNH and
content, see Table 1) was used.
acetylacetone under the optimized conditions. As depicted in the
Scheme 3, apart from unreacted starting material,
benzophenone and the rearranged product 8, we could also
1
detect by GC and H-NMR analyses of the crude reaction
Next, we tested the pinacol rearrangement of a range of
structurally different 1,2-diols under the optimized reaction
conditions (Table 4). In general, good to excellent isolated yields
were obtained, being in many cases (compounds 3-7, 10)
unnecessary a purification step, since the rearranged crude
mixture compounds 13 and 14 in a 1:1 ratio. The presence of
such products can be explained from the direct attack of the
nucleophile onto a transient carbocation and/or from the epoxide
9
ring opening (Scheme 3), both possibilities pointing towards
the formation of a carbocationic intermediate.
1
products were highly pure (>95% by HNMR). As expected
when using weak acidic conditions such as those generated by
GO, we obtained those products formed from the most stable
carbocation involving the expected migration, as in the case of
2-methyl-1,1,3-triphenylpropane-1,2-diol
and
3-methoxy-2-
methyl-1,1-diphenylpropane-1,2-diol that afforded compounds 2
and 3 in 96 and 95% yield, respectively (Table 4, entries 2 and
3). 2-Methyl-1,1-diphenylpropane-1,2-diol afforded as major
product 3,3-diphenylbutan-2-one (4) although small amounts of
ketone 5 were also detected as a consequence of the good
migratory aptitude of the phenyl group (Table 4, entry 4).
Similarly, ketones 6 and 7 were obtained in a 78 and 15%
yield, respectively, from the rearrangement of 1,1,2-
triphenylethane-1,2-diol
Tetraphenylethan-1-one was isolated from benzopinacol in a
2% yield through a phenyl 1,2-shift (Table 4, entry 6). In this
case benzophenone (10%) and 2,2,3,3-tetraphenyloxirane 9
(Table
4,
entry
5).
1,2,2,2-
Scheme 3. Pinacol rearrangement mechanism elucidation experiments.
7
We next turned our attention to the use of the graphene-
[
25]
(
8%) were also detected in the crude reaction mixture. Finally,
based carbocatalysts in the intermolecular direct nucleophilic
ring-expansion of [1,1'-bi(cyclopentane)]-1,1'-diol
hydroxydiphenylmethyl)cyclopentan-1-ol
and 1-
afforded
[27]
substitution of activated allylic alcohols.
This well-known
(
transformation has been studied using different Lewis and
Brønsted acids but as far as we know it has no precedent using
such carbocatalysts. The reaction, which normally proceeds via
a carbocationic intermediate (S 1 pathway), can be considered
N
as a straightforward and environmentally benign way to get
spiro[4.5]decan-6-one (10) and 2,2-diphenylcyclohexan-1-one
(
11) in 99 and 80% isolated yield, respectively.
Alkene oxides such as 9, have been proposed as possible
intermediates in the pinacol rearrangement of sterically hindered
substrates as a consequence of the formation of a transient
access to new allylic entities, generating water as the sole by-
[
11a]
carbocationic intermediate.
This type of substrates are also
[28]
product.
As starting point, the reaction between (E)-1,3-
starting materials for the Meinwald rearrangement, reaction
diphenylprop-2-en-1-ol and p-toluensulfonamide as nucleophile
[26]
which is usually catalyzed by Brønsted or Lewis acids.
As
[29]
in water as solvent
was chosen as model reaction in the
depicted in Scheme 2, GO also promotes the synthesis of
search for the optimal conditions (Table 5). Firstly, GO (20 wt%)
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was selected as catalyst and at 80 ˚C the corresponding
amination product 15 was obtained in good yield (Table 5, entry
nucleophiles using (E)-1,3-diphenylprop-2-en-1-ol as -activated
allylic alcohol (Table 6). Firstly, 1,3-dicarbonyl compounds were
taken into account. Thus, acetyl acetone rendered the
corresponding allylic substitution product 16 in high yield even
when 1.25 equiv. of nucleophile were employed using both
approaches (Table 6, entries 1 and 2). Similarly, 1,3-diphenyl-
1,3-propanedione behaved well in both medias producing in
moderate yields (E)-2-(1,3-diphenylallyl)-1,3-diphenylpropane-
1,3-dione (17) (Table 6, entries 3 and 4). Asymmetrically
substituted 1-phenylbutane-1,3-dione gave rise to the desired
product 18 in high yields and a 58:42 diastereomeric mixture,
regardless the conditions employed (Table 6, entries 5 and 6).
Next, -ketoesters were essayed starting with ethyl
benzoylacetate. In this case, product 19 was achieved in
moderate yields at the best under both conditions (Table 6,
entries 7 and 8). Better results were obtained with a cyclic -keto
ester, reaching for compound 20 80% and 81% yield,
respectively (Table 6, entries 9 and 10). Electron-rich aromatics
were next evaluated as nucleophiles in a Friedel-Crafts type
reaction. Thus, when N,N-dimethylaniline was tested, product 21
was obtained as a sole regioisomer in high yields, especially
when water was employed as solvent (83%) (Table 6, entries 11
and 12). However, phenol showed an opposite trend. Thus,
whereas the reaction barely worked in water (<25%), high yield
was obtained under neat conditions (76%) (Table 6, entries 13
and 14).
1). Attempts to reduce the temperature resulted in detriment of
the yield (Table 5, entries 2 and 3). Good yields can be also
achieved at 50 ˚C but using 50 wt% of catalyst. It is worth to say
that in the absence of catalyst, the reaction did not work at all
(
Table 5, entry 4). Next, other carbocatalysts were examined
under the above mentioned conditions. Thus, whereas rGO or
graphite gave rise to 15 in low yields (Table 5, entries 5 and 7),
2
GO-CO H rendered the allylic substitution product in 83% yield
(
Table 5, entry 6). The fact that rGO produced a low yield in the
process, somehow ruled out a possible Mn-catalyzed process, in
agreement with the result observed in the pinacol rearrangement.
The solvent-free allylic amination reaction was also taken into
account using the most active GO-derived catalysts (Table 5,
entries 8 and 9). In concordance with the previous results in
2
water, GO-CO H turned out to be the best catalyst yielding the
corresponding product in 88% yield. The better performance of
this catalyst under both reaction conditions can be ascribed to
the presence of more Brønsted acidic functionalities on the
Table 5. Carbocatalyzed direct allylic substitution of (E)-1,3-diphenylprop-2-
[
a]
en-1-ol with 4-methylbenzenesulfonamide. Conditions study.
On the other hand, when allyltrimethylsilane was allowed to
react under the optimized conditions, low conversions at best
were observed even when higher amounts (3 equiv.) of
nucleophile were employed. Intrigued by these results we
decided to switch to another carbocatalyst since we speculate a
possible consumption of the nucleophile by means of the
reaction of some of the multiple oxygen atoms present in the
[
b]
Entry
Catalyst
GO
Solvent
T (ºC)
80
50
rt
Yield (%)
[
c]
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
2
O
2
O
2
O
2
O
2
O
2
O
2
O
81 (75)
[
d]
GO
28/88
GO-CO
assumption seemed to be true, since the reaction employing GO
20 wt%) rendered the corresponding allylation product in high
2
H
surface with the organosilicon species. The
GO
< 5
(

80
80
80
80
80
80
< 10
30
yields under solvent-free conditions (Table 6, entries 15 and 16).
In addition, rGO was also tested but no reaction was observed,
which point towards the need of acidic functionalities within the
graphene surface able to activate both the substrate and the
nucleophile and again rules out a possible metal catalyzed
process.
rGO
[
c]
2
GO-CO H
83 (82)
20
Graphite
GO
In order to study the regiochemical outcome of the reaction,


64
(
E)-4-phenylbut-3-en-2-ol was submitted to the allylic
[
c]
2
GO-CO H
88 (69)
substitution using acetyl acetone as nucleophile under the above
mentioned optimal reaction conditions (Scheme 4). When this
more challenging substrate, due to formation of a less stable
carbocation, was allowed to react under solvent free conditions,
a good 76% yield of a 70:30 regioisomeric mixture was obtained,
being the isomer with the most stable olefin 24 (conjugated with
the aromatic ring) the major regioisomer. Unfortunately, the
reaction in water gave very low yields.
[
a] Unless otherwise stated the reaction conditions were: alcohol (0.08
mmol), TsNH (2 equiv.) in H O (0.5 mL). [b] Isolated yield after flash
chromatography. [c] In brackets isolated yields using 1.25 equiv. of TsNH
d] Reaction performed using 50 wt% of GO.
2
2
2
.
[
surface of graphene which facilitates the allylic alcohol activation.
The reaction optimization study clearly showed that GO-CO
performed the best when using water as solvent and solvent-
free conditions (Table 5, entries and 9, respectively).
Therefore, these were the conditions of choice for testing other
2
H
6
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Scheme 4. Allylic substitution. Regiochemical study
Although the direct allylic substitution reaction over allylic
alcohols is a well-studied process which proceeds through the
[27]
formation of the corresponding allylic carbocation, we studied
the substitution of (E)-1,3-diphenylprop-2-en-1-ol in the
presence
of
equimolecular
amounts
of
4-
methylbenzenesulfonamide and acetylacetone. As depicted in
Scheme 5, under the optimized reaction conditions, a 37/63
mixture of compounds 15/16 was observed in the crude mixture
1
(
2
HNMR), supporting that also in the case of GO-CO H as
catalyst, the allylic substitution reaction occurs through fully
developed carbocations.
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[
a]
Table 5. Allylic substitution. Nucleophiles scope study..
Scheme 5. Allylic substitution mechanism elucidation experiments
[
b]
Entry
1
Nu
Solvent
Product
Yield (%)
2
H O
74
The recyclability of the carbonaceous catalyst in the direct
allylic substitution was next tackled. For this purpose, the
reaction between model allylic alcohol, (E)-1,3-diphenylprop-2-
en-1-ol and acetyl acetone without solvent and under the
optimized conditions (Table 6, entry 2) was chosen. As can be
observed in Figure 2, the yield of the product remained almost
unaltered until the third cycle. In the fourth run a slight decrease
in yield was obtained, which was more accused after the fifth
one. As in the case of the pinacol rearrangement, elemental
2
3
neat
90
60
2
H O
4
5
6
neat
60
91
90
2
analysis of GO-CO H after the last fifth run also showed a strong
2
H O
decrease in S contents, and hence a loss of acidic sulfur-
containing groups on the catalyst surface, but almost no change
on the oxygen content. These results could explain the partial
reduction of the catalytic activity, which is by far less accused
than in the pinacol rearrangement.
neat
7
8
9
H
2
O
60
56
9
5
8
8
89
1
00
8
1
7
2
neat
80
60
40
20
0
5
1
52
yield (%)
C (%)
4
6
4
5
]
H
2
O
80
0.2
O (%)
0
10
neat
81
83
75
S (%)
1
2
3
4
5
Reaction cycle
11
2
H O
2
Figure 2. GO-CO H recyclability and elemental analysis.
12
neat
3
Next, we decided to explore the role of the OSO H and
COOH groups in the reaction mechanism of the pinacol
rearrangement. For that purpose, we carried out 3 parallel
experiments consisting on the optimized reaction between (E)-
1
3
4
H
2
O
<25
76
1
neat
1
,3-diphenylprop-2-en-1-ol and acetyl acetone, using the
equivalent amount of PhCOOH, SO and pTsOH as
homogeneous catalysts according to the calculated carboxylic
acid and sulfur contents of GO-CO H (see Table 1). After 20 h,
when using PhCOOH (2.93 mol%) as acid catalyst, the allylation
H
2
4
,
[
d]
1
5
6
H
2
O
38
2
[d]
1
neat
85
[
30]
product was obtained in a 18% conversion (GC analysis). By
the contrary, H SO (0.26 mol%) and pTsOH (0.26 mol%) were
2
4
[
a] Unless otherwise stated the reaction conditions were: alcohol (0.3
mmol), nucleophile (1.25 equiv.) in H O (when corresponding, 2 mL). [b]
Isolated yield after flash chromatography. [c] Determined by
analysis from the crude reaction mixture. [d] The reaction was performed
using GO as catalyst.
able to catalyse the allylation of (E)-1,3-diphenylprop-2-en-1-ol
in a 68 and 97% conversion, respectively. These results are
somehow in concordance with the behaviour observed in the
2
1
H
NMR
3
recyclability test, in which the loss of OSO H groups did not
decrease considerably the catalyst activity. From all the
performed tests, both sulfonic and carboxylic acid moieties seem
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ChemCatChem
10.1002/cctc.201601362
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to be involved as active sites in the process with the former as
main actor.
was purified by flash chromatography (silica gel, Hexane/EtOAc
mixtures) to obtain the corresponding pure allylation products.
The same procedure was carried out under neat conditions.
Typical procedure for catalyst recovery
Conclusions
For the catalyst recovery experiment, acetyl acetone was chosen as
nucleophile under solvent-free conditions. Once the reaction was finished,
the mixture was diluted with 10 mL of EtOAc and it was stirred for 5
minutes. This mixture was then centrifuged (6000 rpm, 15 minutes) and
the solvent was eliminated using a syringe equipped with a 4 mm/0.2 μm
PTFE filter. The washing/centrifugation sequence was repeated five
additional times until no product was detected in the liquid phase by TLC.
The residual solvent present in the catalyst was completely removed
under reduced pressure. The recovered carbocatalyst was further dried
under vacuum at room temperature and it was directly used in the next
reaction cycle after adding fresh reagents. This procedure was repeated
for every reaction cycle, being the reaction conversion determined by GC
chromatography.
In summary, we have demonstrated that few-layers GO and
functionalized GO-CO
rearrangement and the direct nucleophilic substitution of allylic
alcohols, respectively. Generally good yields and
2
H are able to catalyze the pinacol
regioselectivities are observed in both processes. Several
studies about the active sites of the carbocatalysts revealed no-
metal species involvement in these transformations. Instead,
analytical and experimental data suggest that the sulfate groups,
introduced spontaneously during Hummers oxidation, and the
carboxylic acids play a decisive catalytic role in the studied
2
reactions. Only GO-CO H has shown good recyclability when
used in the direct nucleophilic substitution.
Characterization Data
Experimental Section
The physical and spectroscopic data shown below can be taken as
representative. For the whole catalysts and products characterization
data along with general and other experimental details and NMR charts
see supporting information.
Typical procedure for the carbocatalyzed pinacol rearrangement
A 10 mL glass vessel was charged with GO (20 wt%), the corresponding
diol (0.1 mmol) and toluene (0.5 mL). The vessel was sealed with a
pressure cap, and the mixture was stirred and heated at 100 ºC for 20 h.
Then, the mixture was cooled at room temperature and the mixture was
filtered using a syringe equipped with a 4 mm/0.2 μm PTFE filter. The
solvent was removed under reduced pressure. The crude residue was
purified by flash chromatography (silica gel, Hexane/EtOAc mixtures) to
give the pure compound.
3
,3,4-triphenylbutan-2-one (2).
Yellow oil; 96% yield; IR: 1703, 1594, 1495, 1446 cm ; HNMR (300
MHz, CDCl ): δ = 2.04 (s, 3H), 3.65 (s, 2H), 6.60 (d, J = 7.2 Hz, 2H),
-
1
1
3
13
6
2
2
.92-7.02 (m, 3H), 7.18-7.28 (m, 10H); CNMR (75 MHz, CDCl
7.4, 43.5, 68.7, 125.9, 127.1, 127.3, 128.0, 129.8, 130.9, 137.7, 140.3,
07.4; MS (EI): m/z 301 (M + 1, 0.2%), 300 (M , 0.6), 258 (22), 257
3
): δ =
+
+
(100), 209 (14), 179 (65), 178 (46), 165 (27); HRMS: Calcd for C20H
17
+
(
4
M -MeCO): 257.3484; Found 257.1329.
-methoxy-3,3-diphenylbutan-2-one (3).
Yellow solid; 95% yield; m.p. 78 ºC; IR: 1709, 1599, 1495, 1484, 1446,
Typical procedure for catalyst recovery
-
1 1
1
(
119, 1109, 1091 cm ; HNMR (300 MHz, CDCl
s, 3H), 4.20 (s, 2H), 7.18-7.21 (m, 4H), 7.25-7.37 (m, 6H); CNMR (75
MHz, CDCl ): δ = 28.1, 59.4, 66.2, 77.5, 127.1, 128.2, 129.0, 140.8,
3
): δ = 2.15 (s, 3H), 3.33
Once the reaction was finished, 10 mL of Et
2
O were added and the
13
resulting mixture was stirred for 5 minutes. After centrifugation (6000 rpm,
3
15 minutes), the solvent was separated using a syringe equipped with a
+
+
2
1
07.4; MS (EI): m/z 255 (M + 1, 0.1%), 254 (M , 0.3), 220 (4), 211 (25),
81 (21), 179 (48), 178 (33), 166 (11), 165 (55), 105 (17), 77 (12);
4
mm/0.2 μm PTFE syringe filter. The washing/centrifugation sequence
was repeated five additional times until no product was detected in the
liquid phase by TLC. Then, the residual solvent was completely removed
from the carbocatalyst under reduced pressure, being the material further
dried at room temperature under vacuum for 12 h. The recovered
catalyst was directly used in the next run after adding fresh reagents and
solvent. This procedure was repeated for every cycle, being the
conversion of the cycles determined by GC chromatography.
+
HRMS: Calcd for C15
H15O (M -MeCO): 211.1117; Found 211.1121.
[26]
(
E)-N-(1,3-diphenylallyl)-4-methylbenzenesulfonamide (15).
1
White solid; 82% yield; HNMR (300 MHz, CDCl
3
): δ = 2.35 (s, 3H), 5.06
(d, J = 7.2 Hz, 1H), 5.14 (t, J = 6.7 Hz, 1H), 6.10 (dd, J = 15.8, 6.6 Hz,
1
2
1
H), 6.37 (d, J = 15.9 Hz, 1H,) 7.15-7.29 (m, 12H), 7.68 (d, J = 8.3 Hz,
H); MS (EI): m/z 364 (M + 1, 0.5%), 363 (M , 2), 208 (100), 193 (12),
30 (11), 115 (18), 104 (35), 103 (10), 91 (42), 77 (13).
+
+
[
26]
(
E)-3-(1,3-diphenylallyl)pentane-2,4-dione (16).
1
Typical procedure for the carbocatalyzed allylation reactions
3
Off-White solid; 90% yield; HNMR (300 MHz, CDCl ): δ = 1.93 (s, 3H),
2
.25 (s, 3H), 4.33-4.35 (m, 2H), 6.19 (ddd, J = 15.8, 5.1, 2.8 Hz, 1H),
6.43 (d, J = 15.8 Hz, 1H,) 7.20-7.34 (m, 10H); MS (EI): m/z 249 (M+-
COCH , 91%), 274 (44), 232 (30) 231 (11), 194 (11), 193 (29), 191 (17),
A 10 mL glass vessel was charged with carbocatalyst GO-CO
mg, 20 wt%), (E)-1,3-diphenylprop-2-en-1-ol (63.07 mg, 0.3 mmol, 1eq),
and the corresponding nucleophile (0.375 mmol, 1.25 eq), and H O (2
2
H (12.61
3
189 (10), 178 (25), 128 (11), 115 (68), 91 (100).
2
mL). The vessel was sealed with a pressure cap, and the mixture was
stirred and heated at 80 ºC for 20 h. Then, the mixture was cooled at
room temperature and EtOAc (4 mL) was added. The resulting two-
phase mixture was filtered using a 4 mm/0.2 μm PTFE syringe filter.
Then, after phase separation, the aqueous phase was further extracted
with EtOAc (3 × 10 mL). The combined organic layers were dried over
Acknowledgements
Financial support from the University of Alicante (UAUSTI16-03,
MgSO
4
and concentrated under reduced pressure. The crude residue
VIGROB-173), and Spanish Ministerio de Economía
y
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ChemCatChem
10.1002/cctc.201601362
FULL PAPER
Competitividad (CTQ2015-66624-P) is acknowledged. We also
appreciated the generous gift of graphene based catalysts from
NanoInnova Technologies S. L. and Applynano Solutions S. L.
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Keywords: Graphene Oxide • Pinacol Rearrangement • Allylic
Substitution • Carbocatalysis • Green Chemistry
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4
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[
GO and GO-CO
2
H
catalysts were provided by NanoInnova
Technologies S.L and they have been fully characterized by FTIR,
Scanning Electron Microscopy (SEM), Elemental analysis, X-Ray
Diffraction (XRD), X-Ray Photoelectron Spectroscopy (XPS), Zeta-
2
012, 77, 7344-7354.
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For example, see: a) S. Shirakawa, S. Shimizu, Synlett 2008, 1539-
13
2
O as solvent.
potential, and solid state C-NMR.
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ChemCatChem
10.1002/cctc.201601362
FULL PAPER
1542; b) Y. L. Liu, L. Liu, Y. L. Wang, Y. C. Han, D. Wang, Y. J. Chen,
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J. García-Martínez, C. Nájera, ChemCatChem 2015, 7, 87-93.
employed GO-CO
2
H in a typical experiment (12.61 mg, 20 wt%) are:
-
4
-5
88×10
mmols (2.93 mol%) and 79×10 mmols (0.26 mol%),
respectively.
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FULL PAPER
Carbocatalysts for Carbocations.
The use of graphene oxide and
Melania Gómez-Martínez, Alejandro
Baeza,* and Diego A. Alonso*
2
graphene oxide-CO H as readily
available carbonaceous materials in
processes involving carbocationic
intermediates, such as the Pinacol
Page No. – Page No.
Pinacol Rearrangement and Direct
Nucleophilic Substitution of Allylic
Alcohols promoted by Graphene
rearrangement
and
direct
nucleophilic substitution is herein
disclosed. In general, high yields are
obtained in both transformations,
being the heterogeneous catalyst
recycled up to five times in the case
of the allylic substitution reaction.
2
Oxide and Graphene Oxide-CO H
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