Dehydrative Cross-Coupling of 1-Phenylethanol Catalysed by Palladium Nanoparticles Formed in situ under Acidic Conditions

Article abstract of DOI:10.1055/s-0037-1610246

A dehydrative cross-coupling of 1-phenylethanol catalysed by sugar derived, in situ formed palladium(0) nanoparticles under acidic conditions is realised. The acidic conditions allow for use of alcohols as a feedstock in metal-mediated coupling reactions via their in situ dehydration and subsequent cross-coupling. Extensive analysis of the size and morphology of the palladium nanoparticles formed in situ showed that the zero-valent metal was surrounded by hydrophilic hydroxyl groups. EDX-TEM imaging studies using a prototype silicon drift detector provided insight into the problematic role of molecular oxygen in the system. This increased understanding of the catalyst deactivation allowed for the development of the cross-coupling methodology. A 250-12,000 fold increase in molar efficiency was observed when compared to related two-step protocols that use alternative feedstocks for the palladium-mediated synthesis of stilbenes. This work opens up a new research area in which the active catalyst is formed, stabilised and regenerated by a renewable sugar.

Full text of DOI:10.1055/s-0037-1610246

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–M
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J. E. Camp et al.
Feature
Synthesis
Dehydrative Cross-Coupling of 1-Phenylethanol Catalysed by
Palladium Nanoparticles Formed in situ Under Acidic Conditions
Jason E. Camp*a,c
Thomas W. Bousfieldc
Jay J. Dunsforda
James Adamsa
Joshua Brittona
0
0
0
0
0-
0
0
1
7-
3
9
4
2-
1
0
1
Pd(OAc)2
glucose
OH
Ph
+
Ar
I
Ar
H2O–MeCN
Ph
(3:1, degassed)
150 °C, 16 h
14 examples
21–94% yield
Base Free
Acidic Conditions
pH = 2.95
Michael W. Fayb
Athanasios Angelis-Dimakisc
a School of Chemistry, University of Nottingham, Nottingham,
NG7 2RD, UK
b Nottingham Nanotechnology and Nanoscience Centre, Uni-
versity of Nottingham, Nottingham, NG7 2RD, UK
c Department of Chemical Sciences, University of Huddersfield,
Queensgate, Huddersfield, HD1 3DH, UK
Received: 29.06.2018
Accepted after revision: 24.07.2018
Published online: 27.08.2018
nous base has been shown to broaden their scope and in-
crease overall sustainability.9 In one of the rare instances of
using an alternative feedstock in the Mizoroki–Heck reac-
tion, Saiyed and Bedekar showed that benzylbromides, in
the presence of excess base, could be used in a domino pro-
cess to form stilbenes (Scheme 1b).8a,10 Importantly, this
work eliminated the need to preform and isolate the reac-
tive alkene intermediate. In addition, Colbon et al. recently
showed that aryl alcohols could be used in a two-step, one-
pot process for the in situ generation and reaction of sty-
renes to form stilbenes (Scheme 1c).11
DOI: 10.1055/s-0037-1610246; Art ID: ss-2018-z0442-fa
Abstract A dehydrative cross-coupling of 1-phenylethanol catalysed
by sugar derived, in situ formed palladium(0) nanoparticles under acid-
ic conditions is realised. The acidic conditions allow for use of alcohols
as a feedstock in metal-mediated coupling reactions via their in situ de-
hydration and subsequent cross-coupling. Extensive analysis of the size
and morphology of the palladium nanoparticles formed in situ showed
that the zero-valent metal was surrounded by hydrophilic hydroxyl
groups. EDX-TEM imaging studies using a prototype silicon drift detec-
tor provided insight into the problematic role of molecular oxygen in
the system. This increased understanding of the catalyst deactivation
allowed for the development of the cross-coupling methodology. A
250-12,000 fold increase in molar efficiency was observed when com-
pared to related two-step protocols that use alternative feedstocks for
the palladium-mediated synthesis of stilbenes. This work opens up a
new research area in which the active catalyst is formed, stabilised and
regenerated by a renewable sugar.
a) Typical Mizoroki-Heck reaction
Pd(OAc)2
NaOAc
Ph
Br
Ph
NMP, 135 °C
15 min, 99%
Ph
b) Dehalogenative Mizoroki-Heck reaction
Pd(OAc)2
oxazolinyl
K2CO3
Key words glucose, nanoparticles, catalysis, dehydrative heck, palla-
dium
Ph
I
Br
Ph
DMF, DMA
140 °C, 40 h
67%
Ph
Palladium-mediated cross-coupling reactions are some
of the most powerful methods for the controlled formation
of carbon–carbon bonds.1 Of these, the Mizoroki–Heck re-
action, is the method of choice for the formation of aryl–
alkenyl bonds from the reaction of aryl halides and
alkenes.2 Since its initial development in the 1970s, the
Mizoroki–Heck reaction has been optimised in terms of
catalyst,3 solvent4 and reaction parameters5 in order to ad-
dress limitations of the methodology and expand its sub-
strate scope (Scheme 1a).6 Two factors that have remained
relatively unexamined are the addition of an exogenous
base7 and the use of alkenes as the feedstock.8 For related
palladium-catalysed processes, the elimination of exoge-
c) Two-step, one-pot dehydrative Mizoroki-Heck reaction
O
4-bromoacetophenone
Pd(dba)2, P(t-Bu)3·HBF4
Et3N
H3PW12O40
OH
Ph
diglyme
100 °C, 1 h
Ph
DMF, 100 °C
4 h, 70%
Ph
d) This work: Dehydrative cross-coupling under acidic conditions
Pd(OAc)2
I
OH
Ph
glucose
+
R
H2O:MeCN
150 °C, 16 h
Ph
Ar
Scheme 1 Comparison of feedstocks in the Mizoroki–Heck reaction
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

B
J. E. Camp et al.
Feature
Synthesis
Biographical Sketches
Dr. Jason E. Camp is currently a Se-
nior Lecturer in the Department of
Chemical Sciences at the University of
Huddersfield, working on the use of
green solvents in organic synthesis as
well as on sugar-powered catalysis
protocols. Dr. Camp received his Bach-
elor of Science degree in Biochemistry
from the University of California, Davis
in June 2000. During his undergradu-
ate studies he conducted research as
an UCEAP Undergraduate Research
Fellow supervised by Prof. Geoffrey T.
Crisp (University of Adelaide, Austra-
lia) and completed an honours project
with the support of Prof. Alan L Balch
(UC Davis). Following graduate studies
with Prof. Robert Williams at Colorado
State University he completed his PhD
in 2007 under the supervision of Prof.
Steven M. Weinreb at The Pennsylva-
nia State University before undertak-
ing postdoctoral research with Prof.
Donald Craig (2008-2009) at Imperial
College London. Following his post-
doctoral work, he was appointed as a
lecturer at both the University of Not-
tingham (2009-2013) and Queen
Mary University of London (2013-
2014).
Thomas Bousfield is currently fin-
ishing his PhD at The University of
Huddersfield, which has focused on
the development of sugar-powered
catalysis methods as well as the use of
Cyrene as a green solvent. During his
PhD, Thomas was awarded COST
Short Term Scientific Mission funding
to work with Prof. Wim Thielemans at
the University of KU Leuven. He ob-
tained a MChem degree from Lough-
borough University, during which time
he worked with Dr Marc Kimber on the
synthesis of N-allenyl amides, ureas,
carbamates and sulfonamides.
Dr. Jay Dunsford is currently
a
cused on the synthesis of expanded
ring NHC carbene complexes and their
use in catalytic processes. He then un-
dertook post-doctoral research with
Dr Jason Camp at the University of
Nottingham followed by Dr Michael
Ingelson at the University of Manches-
ter.
chemist at the National Nuclear Labo-
ratory, UK. He completed his BSc and
PhD at Cardiff University. His doctoral
research with Prof. Kingsley Cavell fo-
James Adams is currently finishing
his BBSRC funded PhD at The Universi-
ty of Manchester, which resulted in
two publications and a prestigious SCI
scholarship (2015). He obtained a First
Class MSci degree in chemistry from
The University of Nottingham. During
his undergraduate studies he partici-
pated in numerous research projects,
which resulted in three publications.
James was the recipient of six different
undergraduate awards, including the
GSK Medal for Outstanding Work in
Medicinal Chemistry (2013) and the
BP Achievement Award (2012).
Dr. Joshua Britton earned his MSci
at Nottingham University, UK and his
PhD jointly at Flinders University and
The University of California, Irvine un-
der Colin L. Raston and Gregory A.
Weiss, respectively, in the area of con-
tinuous-flow synthesis and biocataly-
sis. He then undertook post-doctoral
studies at MIT with Prof. Tim Jamison,
which focused on the advancing of
multi-step continuous-flow synthesis
of active pharmaceutical ingredients.
After post-doctoral studies, he co-
founded Synthase,
a biotechnology
company focused on the continuous-
flow synthesis of pharmaceuticals and
high-value chemicals using biocataly-
sis and organic synthesis.
Dr. Michael Fay received his BSc de-
gree from the University of Leicester in
1994 followed by an MSc from the
University of Warwick in 1996 and a
PhD from the University of Sheffield in
2001. He has been at the University of
Nottingham since 2000, where he is
currently a Senior Research Fellow re-
sponsible for the operation of trans-
mission electron microscopes in the
Nanoscale and Microscale Research
Centre
Dr. Athanasios Angelis-Dimakis
received his undergraduate diploma in
Chemical Engineering from the Na-
tional Technical University of Athens in
Greece in 2005. He completed his PhD
in Chemical Engineering in 2011 at
the same university and then carried
out an EU funded post-doctoral re-
search on the life cycle assessment of
innovative and eco-efficient technolo-
gies. In 2015, he joined the Centre for
Environmental Policy at Imperial Col-
lege London, to participate in a proj-
ect, funded by Climate KIC and lead by
Covestro AG, on enabling carbon diox-
ide reutilization between industries. In
May 2016, he was appointed as a Lec-
turer in Chemical Engineering at the
University of Huddersfield. His re-
search interests include industrial
symbiosis, urban mining, and assess-
ment of the performance of novel
green processes using various indica-
tors; including the molar efficiency of
chemical processes.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

C
J. E. Camp et al.
Feature
Synthesis
This was accomplished by first reacting the aryl alcohol
with a catalytic amount of acid followed by the addition of
excess base under Mizoroki–Heck reaction conditions.
During the course of our study, Sinha and co-workers used
an ionic liquid for the dehydrative-Heck cross-coupling of
benzylic alcohols with aryl halides12 to form potential anti-
cancer compounds.13 This methodology was further ex-
tended to include a double dehydrative-Heck process for
the synthesis of lead compounds against Alzheimer’s dis-
ease.14 Aryl alcohol 1-phenylethanol (PE) is currently made
on an industrial scale as the byproduct of the reaction of
ethylbenzene hydroperoxide to form propylene oxide.15 The
majority of the alcohol is then dehydrated to form sty-
rene.16 Whilst styrene is a highly useful reagent, it is inher-
ently unstable and precautions must be taken to prevent
rapid exothermic polymerization.17 Importantly, the Inter-
national Agency for Research on Cancer recently classified
styrene in Group 2A ‘probably carcinogenic to humans’.18
Therefore, there are key safety, economic and green drivers
to develop cross-coupling methods that can eliminate the
issues associated with bulk styrene. Previously, it was
shown that the addition of reducing sugars, such as glucose,
to palladium-mediated cross-coupling reactions leads to in-
creased yields as well as facile catalyst recycling and in-
creased metal remediation.19–21 Herein, we report a dehy-
drative cross-coupling of 1-phenylethanol with aryl iodides
catalysed by palladium nanoparticles formed in situ under
base-free, acidic conditions in which the reducing sugars
form, stabilise and regenerate the active catalyst (Scheme 1d).
The Mizoroki–Heck reaction between iodobenzene and
styrene to form stilbene was used to assess the feasibility of
the removal of base (Table 1). It was found that merely re-
moving the base from the previously reported reaction con-
ditions did not afford any of the desired products (Table 1,
Table 1 Development of the Mizoroki–Heck Cross-Coupling under
Acidic Conditions
Pd(OAc)2 (4 mol%)
glucose (see, Table 1)
I
Ph
Ph
Ph
+
+
Ph
H2O–MeCN (3:1, degassed)
16 h
Ph
1
2b
3b
4b
Entry
Pd/sugar ratio
Temp. (°C)
Yield (%)b
Notes
Ref.18
1
2
3
4
5
6
7
1:2
100
100
150
150
150
150
150
97a
00
05
41
97
40
33
1:2
1:2
1:10
1:25
1:50
1:100
pH 2.95
a Et3N (1.5 equiv) was added
b 3b/4b were isolated in a ratio of >90:10.
entries 1 vs. 2).18 In order to eliminate the competing oxida-
tion of palladium by molecular oxygen22 (see below), the
solvents were degassed with nitrogen.23
Heating a solution of styrene (1) and iodobenzene (2b)
to 150 °C for 16 h, in the presence of Pd(OAc)2 and glucose,
gave alkenes 3b/4b as a 94:6 mixture in excellent yield (Ta-
ble 2, entry 5). The regiochemical distribution is in line
with previously reported high-temperature Mizoroki–Heck
cross-coupling reactions.24,25 The final pH of this solution
was determined to be 2.95. Additionally, it was found that
the ratio of sugar to palladium had a substantial effect on
the yield of the product, with a 1:25 ratio being optimal
(Table 2, entries 3–7).
Table 2 Optimization of the Dehydrative Cross-Coupling Reaction
Pd(OAc)2 (4 mol%)
glucose (1.0 equiv)
Ph
OH
+
+
I
H2O–MeCN
Ph
Ph
(3:1, degassed)
additive (1.1 equiv)
temperature, 16 h
5
2a
3a
4a
Entry
Temp (°C)
Additive
Ratio 3/4
Yield (%)
1
2
3
4
5
6
7
130
140
150
150
150
150
150
–
85:15
84:16
85:15
87:13
87:13
83:17
84:16
27
–
53
–
83
HCl
57a
16a
22b
93a
H2SO4
formic acid
formic acid
a 1.1 equiv of additive.
b 0.1 equiv formic acid used.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

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J. E. Camp et al.
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Synthesis
With a better understanding of the acidic cross-cou-
pling reaction in hand, the dehydrative cross-coupling of 1-
phenylethanol (5) with 4-iodotoluene (2a) was investigated
(Table 2 and Table S3). It was found that the reaction gave
the highest yield when 2 equivalents of alcohol 5 and 1
equivalent of glucose were used at 150 °C for 16 h (Table 2,
entry 3). The product alkenes were isolated as a 85:15 mix-
ture of linear 3a to branched isomers 4a. The equivalent of
glucose is required to both reduce the palladium and stabi-
lise the in situ formed nanoparticles (see below). To facili-
tate the dehydration of 1-phenylethanol (5), acidic addi-
tives were screened (Table 2, entries 5–8). The addition of
strong acids led to a decreased yield of alkenes 3a/4a (Table
2, entries 5 and 6). In contrast, the addition of 1.1 equiva-
lents of formic acid resulted in an increase in yield of the
desired product to 93%, but had no effect on the isomeric
ratio. In contrast, the addition of 10 mol% of formic acid
gave a deceased yield (Table 2, entry 7 vs. 6). Unfortunately,
neither 4-bromotoluene nor 4-chlorotoluene afforded any
of the desired cross-coupled products and only the starting
materials were isolated. A comparison of the molar efficien-
cy (Mol. E%)26,27 of this protocol versus related two-step
protocols that use alcohols or carboxylic acids for the palla-
dium-mediated synthesis of stilbenes showed a 250–
12,000 fold increase in efficiency.23 Importantly, we have
previously shown that palladium nanoparticles formed in
situ can readily be recycled without significant loss of cata-
lytic reactivity, which would mitigate the relatively high
catalyst loading required in this protocol.19
general, formic acid had either a beneficial or negligible ef-
fect on the dehydrative cross-coupling reaction, except in
cases where additional reactions may have occurred.
Pd(OAc)2 (4 mol%)
glucose (1.0 equiv)
formic acid (1.1 equiv)d
R
Ph
OH
+
I
R
Ph
H2O–MeCN
(3:1, degassed)
150 °C, 16 h
3
5
2
% yielda,b (linear:branched)c
Ph
Ph
Ph
3a
3b
3c
42% 88:12e
83% 85:15
93% 84:16
62% 94:06
79% 93:07
90% 93:07
94% 83:17
Ph
Ph
3d
Ph
3e
3f
3i
MeO
67% 88:12
37% 87:13
78% 88:12
21% 93:07
28% 93:07
48% 86:14
Ph
Ph
Ph
Ph
3g
3h
F
Cl
Br
60% 89:11
55% 90:10
55% 85:15
62% 85:15
66% 88:12
63% 88:12
Ph
Ph
H
F3C
3j
3k
3l
O
O
43% 91:09
61% 93:07
83% 90:10
58% 90:10
69% 89:11
89% 87:13
Ph
Ph
To assess the generality of these conditions, the reaction
of 1-phenylethanol (5) with a variety of aryl iodides 2 was
investigated. As there was some ambiguity in the initial
study with regard to the use of formic acid in the dehydra-
tive cross-coupling process, the substrate scope investiga-
tion was conducted in both its presence and absence
(Scheme 2). For comparison, base-free Mizoroki–Heck
cross-coupling reactions were also conducted to gain fur-
ther insights into the dehydrative process (Table S2). Whilst
the products were isolated as a mixture of regioisomers
3/4, the ratio of branched to linear was generally >85:15.
The reactions of 4-iodotoluene and iodobenzene with 1-
phenylethanol (5) in the presence of 4 mol% palladium ace-
tate and 1 equivalent of glucose proceeded in good yields to
form stilbenes 3a and 3b, respectively. For these substrates,
a substantial increase in yield was observed upon the addi-
tion of formic acid. The products of the reaction of 1-io-
donaphthalene, 3c, were formed in good yield under the
standard reaction conditions. The addition of formic acid to
the reaction of 2-iodotoluene resulted in an increased yield
of stilbene 3d. In contrast, the addition of formic acid had
little effect on the formation of the more sterically hindered
adduct 3e. Electron-rich substrate, 4-iodoanisole, was tol-
erated well under the reaction conditions. Iodobenzenes
with electron-withdrawing groups afforded the desired
cross-coupled adducts 3g–n in good to excellent yields. In
3m
3n
83% 90:10
NC
70% 90:10
51% 90:10
O2N
22% 90:10
Scheme 2 Substrate scope and role of formic acid in the dehydrative
cross-coupling reaction. a Isolated yield. b Reaction conditions: arylio-
dide (1.0 equiv), 1-phenylethanol (2.0 equiv), Pd(OAc)2 (4 mol %), glu-
cose (1.0 equiv), H2O/MeCN (3:1, degassed), 150 °C, 16 h. c
Linear/branched selectivity was determined by 1H NMR spectroscopy. d
Reaction conditions: aryliodide (1.0 equiv), 1-phenylethanol (2.0
equiv), Pd(OAc)2 (4 mol %), glucose (1.0 equiv), formic acid (1.1 equiv)
H2O/MeCN (3:1, degassed), 150 °C, 16 h. e Styrene (1.0 equiv) was used
in place of 1-phenylethanol.
For example, the nitro group of (E)-4-nitro-trans-stilbe-
ne 3n could have been reduced under the reaction condi-
tions,28 whereas the nitrile moiety of 3m could have been
hydrolysed in the presence of formic acid. Iodoarenes that
contained basic nitrogen centres, such as 4-iodoaniline and
3-iodopyridine, did not give any of the desired cross-cou-
pled products 3/4 under the optimised conditions. This re-
sult is in contrast to the related work by Liotta and co-
workers,7a who found that basic-nitrogen-containing sub-
strates were required for exogenous base-free Suzuki–Mi-
yaura reactions and furthermore highlights the importance
of the acidic conditions in our dehydrative cross-coupling
protocol.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

E
J. E. Camp et al.
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Synthesis
Transmission electron microscopy (TEM) analysis indi-
cated that nanoparticles were formed when the palladi-
um(II) pre-catalyst was subjected to the standard reaction
conditions. The less dense amorphous matter at the periph-
ery of the nanoparticles most likely contains the sugar resi-
dues (Figure 1a).23 Analysis of the sugar-derived nanoparti-
cles suspended in water at room temperature showed that
the nanoparticles aggregate into larger clusters of around
100 nm (Figure 1b).23 XPS analysis revealed that the palladi-
um was present only in the zero oxidation state (Figure
1c).23 A prototype EDX-TEM silicon drift detector was used
to determine the amount of carbon and oxygen on the sur-
face of the nanoparticles that were formed in both the ab-
sence and presence of oxygen (Figure 1d and Figure 1e, re-
spectively).23 It was found that there was a statistically sig-
nificant decrease in the amount of carbon and oxygen on
the surface of the nanoparticles that were formed in the
presence of oxygen, 5%, versus those that were formed in
the absence of oxygen, 37% (Figure 1f).23 This difference in
surface coverage is significant because if too little carbon
and oxygen are present on the surface of the metal then the
catalyst is unreactive (cf. Table 1). To our knowledge, this is
the first time that a EDX-TEM silicon drift detector has been
used to probe the difference in reactivity between in situ
formed catalysts.
Our mechanistic hypothesis for the dehydrative cross-
coupling reaction is predicated on the accepted mechanism
for the classical Mizoroki–Heck process2,29 as well as on the
wealth of information on both the formation of metal
nanoparticles20,30 from reducing sugars and the synthesis of
gluconic acid from glucose (Scheme 3).31 Initially, the palla-
dium(II) precatalyst is reduced by glucose to generate palla-
dium(0) nanoparticles (Pd0NP) with concomitant formation
of gluconic acid.19–21 The formation of gluconic acid was
confirmed by analysis of a truncated reaction by mass spec-
trometry. After this initial oxidation, the gluconic acid can
undergo a series of further palladium(II) mediated oxida-
tions to eventually afford carbon dioxide and water, whilst
simultaneously releasing additional reducing equivalents.32
It is the sequential oxidation of the glucose in combination
with the generation of one equivalent of hydrogen iodide
Figure 1 (a) TEM analysis (b) Nanosight analysis (c) XPS analysis (d)
EDX-TEM analysis of palladium-nanoparticles formed in the absence of
molecular oxygen (e) EDX-TEM analysis of palladium-nanoparticles
formed in the presence of molecular oxygen (f) Percentage of carbon
on the surface of palladium-nanoparticles formed in both the absence
and presence of oxygen.
per catalytic cycle that makes the aqueous solution acidic,
with a final pH 2.95. The acids generated in situ promote
the dehydration of 1-phenylethanol (5) to styrene (2). Un-
der the thermal conditions the in situ formed Pd0NPs may
be attacked by the arylating agent 1 to form a soluble an-
ionic complex.33 This species completes the desired Mizoro-
ki–Heck reaction to form cross-coupled products 3/4, with
concomitant generation of a palladium(II) species. The ac-
tive palladium(0) catalyst can be regenerated via reduction
of the palladium(II) species by glucose or an oxidized deriv-
ative of glucose. A competing oxidation process involving
molecular oxygen can short-circuit the catalytic cycle by
converting the Pd0NPs into a non-catalytically active palla-
dium(II) species, which would then have to be reduced to
re-enter the catalytic cycle. In aerated solvents we believe
that the molecular oxygen outcompetes the iodobenzene
for the Pd0NP catalyst, leading to recovery of the starting
material. It is believed that an increased temperature of
150 °C is needed to promote the requisite ring-opened con-
formation of glucose.34
In conclusion, a novel palladium-catalysed dehydrative
cross-coupling protocol for the conversion of 1-phenyletha-
nol into disubstituted alkenes was developed. The ability to
PdII
precatalyst
further
oxidation
OH
gluconic
acid
6CO2 + 6H2O
glucose
5
Ph
+
gluconic acid
HX or gluconic acid
Pd0NP
competing
oxidation
process
desired catalytic process
further
oxidation
Ar
I
+
conjugate base
Ph
O2
2
1
Ph
6CO2 + 6H2O
Ar
+ HI
Ar
+
Ph
PdIINP
3
4
Scheme 3 Proposed mechanism for the dehydrative cross-coupling reaction
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

F
J. E. Camp et al.
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Synthesis
run the process under acidic conditions and use a second-
ary aryl alcohol as starting material significantly expands
the scope and synthetic utility of the Mizoroki–Heck reac-
tion. The high yields of cross-coupled products were
achieved in an aqueous system, without the need to pre-
form and isolate the catalyst, through the simple addition
of a renewable reducing sugar. Mol.E% calculations showed
that the direct dehydrative cross-coupling of 1-phenyletha-
nol was significantly more efficient than previously report-
ed two-step protocols. This work opens up exciting oppor-
tunities for the use of reducing sugars to power catalytic re-
actions, sugar-powered catalysis.
focused (80 μm) beam generated by a single-mode laser diode with a
60 mW blue laser illumination (405 nm). The solution containing the
palladium(0) nanoparticles in a concentration of between 107 and 109
particles/mL was injected in a sample chamber of 0.5 mL size from
which a volume of 120×80×20 microns was visualised under the mi-
croscope. The sample concentration was adjusted to ensure statisti-
cally significant number of particles under analysis. The Brownian
motion of the nanoparticles was tracked at 30 frames/s. NTA 2.2 soft-
ware was used to evaluate the mean square displacements of each
visible particle (calibration 166 nm/pixel) and from the Strokes–Ein-
stein equation the particle sizes were determined. All experiments were
performed without filtering to ensure measurement of all particles.35
Dynamic Light Scattering (DLS): DLS experiments were performed
with a Malvern Zetasizer ZS equipped with a He-Ne (633 nm, 5 mW)
laser and an Avalanche photodiode detector at an angle of 173°. All
DLS data were processed using Dispersion Technology Software (Mal-
vern Instruments). All experiments were performed without filtering
to ensure measurement of all particles.36
Unless otherwise indicated, all commercially available reagents and
solvents were used directly from the supplier without further purifi-
cation. Acetonitrile and water were degassed by bubbling nitrogen
through the solvent at reflux for 1 h. Solvents used for column chro-
matography were of technical grade. For purification procedures us-
ing column chromatography, silica gel (60–120) mesh was used. Thin-
layer chromatography was carried out using Merck Kieselgel silica gel
60 F254 plates (0.2 mm) and visualisation was achieved using UV
light followed by dipping in a potassium permanganate solution and
heating. All reactions were performed in a Biotage 5 mL microwave
vial with Teflon coated cap.
1H NMR and 13C NMR were recorded with a Bruker AV400 (400 MHz)
spectrometer, Bruker AV(III)400 (400 MHz) spectrometer, Bruker
DPX400 (400 MHz) spectrometer or JOEL EX270 (270 MHz) spec-
trometer at ambient temperature using CDCl3 (7.26 ppm), DMSO-d6
(2.50 ppm), (CD3)2CO (2.05 ppm) or CD3OD (3.31 ppm) as the solvent.
Chemical shift values are expressed as parts per million (ppm) and J
values are in Hertz. Splitting patterns are indicated as s: singlet, d:
doublet, t: triplet, q: quartet or combination thereof, br.s: broad sin-
glet or m: multiplet. Solution IR spectra were recorded with a Perkin
Elmer 1600 series FTIR-spectrophotometer. Mass spectra were deter-
mined with a Bruker MicroTOF mass spectrometer. pH measurements
were recorded with a Philip Harris digital pH meter using a pH 7 stan-
dard buffer.
X-ray Photoelectron Spectroscopy (XPS): XPS spectra were recorded
with a Kratos AXIS ULTRA with a monochromated Al Kα X-ray source
(1486.6 eV) operated at 15mA emission current and 12kV anode po-
tential – 180 W. Hybrid (magnet/electrostatic) optics (300×700 μm
aperture), hemispherical analyser, multichannel plate and delay line
detector (DLD) with a take-off angle of 90° and an acceptance angle of
30°. All scans were acquired under charge neutralisation conditions
using a low-energy electron gun within the field of magnetic lens.
Survey scans were taken with a pass energy of 80 eV and high-resolu-
tion scans with a pass energy of 20 eV. Data analysis was carried out
using CASAXPS software with Kratos sensitivity factors to determine
atomic % values from the peak areas.
Scanning Ion Occlusion Sensing (SIOS): SIOS measurements were car-
ried out with a qNano instrument (Izon Science Ltd., Christchurch,
NZ). A standard electrolyte buffer (SEB) of 0.1 M KCl, 10 mM Tris buf-
fer, 0.01% Triton X-100, and 3 mM EDTA, pH 8.0, filtered through a
0.22 μm filter was used in all experiments. The membrane was wet-
ted prior to sampling by applying a voltage (typically 0.3 V) and man-
ually stretching the pore open (typically with a jaw stretch of 5 mm).
Once a stable background current achieved, the fluid in the top half of
the cell was replaced with a solution of the palladium(0) nanoparti-
cles in the SEB (30–70 μL). The magnitude and duration of changes in
the current signal were collected at a sampling frequency of 50 kHz.
The instrument was calibrated using a solution of polystyrene parti-
cles (3000 series, 100 nm) in SEB.37
Transmission Electron Microscopy (TEM): TEM analysis was performed
with a JEOL2100F field-emission gun microscope operating at 200 kV
and equipped with a Gatan Orius camera. The Pd(0) nanoparticles
were dispersed in water using an ultrasound bath and a suspension
(3.5 μL) was deposited onto a holey carbon grid (Agar Scientific),
which had previously been exposed to a low-temperature O2/Ar plas-
ma for five seconds in a Fischione Model 1020 Plasma Cleaner to
make them hydrophilic. TEM image simulations was carried out us-
ing spherical aberration coefficient (Cs) = 1 mm.
(E)-1-Methylstilbene38 (3a) and 1-Methyl-4-(1-phenylvinyl)ben-
zene39 (4a)
Method 1: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) and 4-iodotoluene (170 mg, 0.78 mmol)
in degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. was added
styrene (87 μL, 0.79 mmol). The vial was sealed and the mixture was
heated at 150 °C for 16 h. The mixture was cooled to r.t. and water (10
mL) and dichloromethane (10 mL) were added. The combined organic
extracts were dried over Na2SO4 and the solvent was removed under
reduced pressure. The crude residue was purified by flash column
chromatography (silica gel, n-hexane/EtOAc, 5%) to give (E)-1-methyl-
stilbene (3a) and 1-Methyl-4-(1-phenylvinyl)benzene (4a, 80 mg, ra-
tio 88:12, 42% combined yield) as a white solid.
EDX Transmission Electron Microscopy (EDX-TEM): EDX analysis was
performed with a prototype Oxford Instruments Light Element
100 mm silicon drift detector with a JEOL 2100F operating at 200kV
and the Aztec software. All spectra are acquired from regions not con-
taining amorphous carbon supporting film. Cr, Fe and Co signals can
originate from scatter from the polepiece and holder; Au signal can
originate from scatter from the sample holder; Cu signal from the
TEM supporting grid has been de-convolved from the quantification.
Nanoparticle Tracking Analysis (NTA): NTA was performed with a
Nanosight LM10-HS instrument equipped with an electron multipli-
cation charge coupled device camera mounted on an optical micro-
scope system to track light scattered by particles that are present in a
Method 2: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodotoluene (85 mg, 0.39 mmol) in
degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. were added
1-phenylethanol (97 mg, 0.79 mmol). The vial was sealed and the
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

G
J. E. Camp et al.
Feature
Synthesis
mixture was heated at 150 °C for 16 h. The mixture was cooled to r.t.
and water (10 mL) and dichloromethane (10 mL) were added. The
combined organic extracts were dried over Na2SO4 and the solvent
was removed under reduced pressure. The crude residue was purified
by flash column chromatography (silica gel, n-hexane/EtOAc, 5%) to
give (E)-1-methylstilbene (3a) and 1-methyl-4-(1-phenylvinyl)ben-
zene (4a, 63 mg, ratio 85:15, 83% combined yield) as a white solid.
by flash column chromatography (silica gel, n-hexane/EtOAc, 5%) to
give (E)-stilbene (3b) and 1,1-diphenylethene (4b, 44 mg, ratio 94:6,
62% combined yield) as a white solid.
Method 3: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 1-phenylethanol (97 mg, 0.79 mmol),
iodobenzene (44 μL, 0.39 mmol) and formic acid (33 μL, 0.87 mmol).
The vial was sealed and the mixture was heated at 150 °C for 16 h.
The mixture was cooled to r.t. and water (10 mL) and dichlorometh-
ane (10 mL) were added. The combined organic extracts were dried
over Na2SO4 and the solvent was removed under reduced pressure.
The crude residue was purified by flash column chromatography (sil-
ica gel, n-hexane/EtOAc, 5%) to give (E)-stilbene (3b) and 1,1-di-
phenylethene (4b, 55 mg, ratio 93:7, 79% combined yield) as a white
solid.
Method 3: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodotoluene (85 mg, 0.39 mmol) in
degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. were added
1-phenylethanol (97 mg, 0.79 mmol) and formic acid (33 μL, 0.87
mmol). The vial was sealed and the mixture was heated at 150 °C for
16 h. The mixture was cooled to r.t. and water (10 mL) and dichloro-
methane (10 mL) were added. The combined organic extracts were
dried over Na2SO4 and the solvent was removed under reduced pres-
sure. The crude residue was purified by flash column chromatogra-
phy (silica gel, n-hexane/EtOAc, 5%) to give (E)-1-methylstilbene (3a)
and 1-methyl-4-(1-phenylvinyl)benzene (4a, 71 mg, ratio 84:16, 93%
combined yield) as a white solid.
(E)-Stilbene (3b) and 1,1-Diphenylethene (4b)
1H NMR (400 MHz, CDCl3): δ = 7.60–7.58 (m, 4 H), 7.45–7.39 (m,
5.57 H), 7.35–7.31 (m, 2 H), 7.18 (s, 2 H), 5.54 (s, 0.26 H).
13C NMR (100 MHz, CDCl3): δ (stillbene) = 137.4, 128.8, 127.7, 126.6.
(E)-1-Methylstilbene (3a)
IR (CHCl3): 3021, 2915, 1494, 1451, 983, 808, 688 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.53 (d, J = 7.4 Hz, 2 H), 7.44 (d,
J = 8.1 Hz, 2 H), 7.37 (t, J = 7.6 Hz, 2 H), 7.26 (m, 1 H), 7.18 (d,
J = 7.9 Hz, 2 H), 7.13 (d, J = 16.4 Hz, 1 H), 7.08 (d, J = 16.5 Hz, 1 H), 2.38
(s, 3 H).
HRMS (APPI): m/z calcd. for C14H12: 180.0934; found: 180.0932.
(E)-1-Styrylnaphthalene42 (3c) and 1-(1-Phenylethenyl)naphtha-
lene43 (4c)
13C NMR (100 MHz, CDCl3): δ = 137.5 (2 × C), 134.6, 129.4 (2 × C),
128.7 (2 × C), 128.6, 127.7, 127.4, 126.5 (2 × C), 126.4 (2 × C), 21.3.
IR (CHCl3): 3020, 2915, 1593, 1508, 1493, 1448, 969, 803, 706 cm–1
HRMS (APPI): m/z calcd. for [C15H14]+: 194.1090; found: 194.1087.
Method 2: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 1-phenylethanol (97 mg, 0.79 mmol)
and 1-iodonaphthalene (57 μL, 0.78 mmol). The vial was sealed and
the mixture was heated at 150 °C for 16 h. The mixture was cooled to
r.t. and water (10 mL) and dichloromethane (10 mL) were added. The
combined organic extracts were dried over Na2SO4 and the solvent
was removed under reduced pressure. The crude residue was purified
by flash column chromatography (silica gel, n-hexane/EtOAc, 5%) to
give (E)-1-styrylnaphthalene (3c) and 1-(1-phenylethenyl)naphtha-
lene (4c, 45 mg, ratio 93:17, 90% combined yield) as a colourless oil.
.
1-Methyl-4-(1-phenylvinyl)benzene (4a)
1H NMR (400 MHz, CDCl3): δ = 7.35–7.32 (m, 5 H), 7.25 (d, J = 8.1 Hz,
2 H), 7.15 (d, J = 7.9 Hz, 2 H), 5.44 (d, J = 1.1 Hz, 2 H), 5.41 (d,
J = 1.2 Hz, 2 H), 2.38 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 149.9, 141.7, 138.6, 137.5, 128.9 (2 ×
C), 128.3 (2 × C), 128.2 (2 × C), 128.1 (2 × C), 127.6, 113.7, 21.2.
Method 3: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 1-phenylethanol (97 mg, 0.79 mmol), 1-
iodonaphthalene (57 μL, 0.78 mmol) and formic acid (33 μL, 0.87
mmol). The vial was sealed and the mixture was heated at 150 °C for
16 h. The mixture was cooled to r.t. and water (10 mL) and dichloro-
methane (10 mL) were added. The combined organic extracts were
dried over Na2SO4 and the solvent was removed under reduced pres-
sure. The crude residue was purified by flash column chromatogra-
phy (silica gel, n-hexane/EtOAc, 5%) to give (E)-1-styrylnaphthalene
(3c) and 1-(1-phenylethenyl)naphthalene (4c, 85 mg, ratio 83:17, 94%
combined yield) as a colourless oil.
(E)-Stilbene40 (3b), 1,1-Diphenylethene41 (4b)
Method 1: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added iodobenzene (87 μL, 0.78 mmol) and
styrene (87 μL, 0.79 mmol). The vial was sealed and the mixture was
heated at 150 °C for 16 h. The mixture was cooled to r.t. and water (10
mL) and dichloromethane (10 mL) were added. The combined organic
extracts were dried over Na2SO4 and the solvent was removed under
reduced pressure. The crude residue was purified by flash column
chromatography (silica gel, n-hexane/EtOAc, 5%) to give (E)-stilbene
(3b) and 1,1-diphenylethene (4b, 136 mg, ratio 94:6, 97% combined
yield) as a white solid.
(E)-1-Styrylnaphthalene (3c)
Method 2: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 1-phenylethanol (97 mg, 0.79 mmol)
and iodobenzene (44 μL, 0.39 mmol). The vial was sealed and the
mixture was heated at 150 °C for 16 h. The mixture was cooled to r.t.
and water (10 mL) and dichloromethane (10 mL) were added. The
combined organic extracts were dried over Na2SO4 and the solvent
was removed under reduced pressure. The crude residue was purified
1H NMR (500 MHz, CDCl3): δ = 8.25 (d, J = 8.3 Hz, 1 H), 7.93–7.88 (m,
2 H), 7.83 (d, J = 8.2 Hz, 1 H), 7.77 (d, J = 7.1 Hz, 1 H), 7.63 (d,
J = 7.3 Hz, 2 H), 7.58–7.50 (m, 3 H), 7.43 (t, J = 7.7 Hz, 3 H), 7.34–7.31
(m, 1 H), 7.18 (d, J = 16.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 137.7, 135.1, 133.8, 131.8, 131.4,
128.8 (2 × C), 128.7, 128.1, 127.8, 126.7 (2 × C), 126.1, 125.9, 125.8,
125.7, 123.8, 123.5.
IR (CHCl3): 3056, 2928, 2852, 1493, 1263, 959, 774, 734, 692 cm–1
HRMS (APPI): m/z calcd. for [C18H14]+: 230.1090; found: 230.1089.
.
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H
J. E. Camp et al.
Feature
Synthesis
1-(1-Phenylethenyl)naphthalene (4c)
(E)-2,6-Dimethylstilbene46 (3e) and 1,3-Dimethyl-2-(1-phenylvi-
nyl)benzene46 (4e)
1H NMR (500 MHz, CDCl3): δ = 7.86–7.84 (m 2 H), 7.77–7.75 (m, 1 H),
7.51–7.48 (m, 1 H), 7.44–7.41 (m, 2 H), 7.34–7.30 (m, 3 H), 7.27–7.24
(m, 3 H), 5.98 (d, J = 1.4 Hz, 2 H), 5.39 (d, J = 1.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 148.3, 141.1, 139.8, 133.7, 131.9,
128.4 (2 × C), 128.2, 128.0, 127.7, 127.2, 126.6 (2 × C), 126.4, 125.9,
125.7, 125.4, 116.3.
Method 2: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 1-phenylethanol (97 mg, 0.79 mmol)
and 2-iodo-1,3-dimethylbenzene (57 μL, 0.39 mmol). The vial was
sealed and the mixture was heated at 150 °C for 16 h. The mixture
was cooled to r.t. and water (10 mL) and dichloromethane (10 mL)
were added. The combined organic extracts were dried over Na2SO4
and the solvent was removed under reduced pressure. The crude resi-
due was purified by flash column chromatography (silica gel, n-hex-
ane/EtOAc, 5%) to give (E)-2,6-dimethylstilbene (3e) and 1,3-dimeth-
yl-2-(1-phenylvinyl)benzene (4e, 17 mg, ratio 93:7, 21% combined
yield) as a colourless oil.
(E)-2-Methylstilbene44 (3d) and 1-Methyl-2-(1-phenylvinyl)ben-
zene45 (4d)
Method 1: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 2-iodotoluene (99 μL, 0.78 mmol) and
styrene (99 μL, 0.79 mmol). The vial was sealed and the mixture was
heated at 150 °C for 16 h. The mixture was cooled to r.t. and water (10
mL) and dichloromethane (10 mL) were added. The combined organic
extracts were dried over Na2SO4 and the solvent was removed under
reduced pressure. The crude residue was purified by flash column
chromatography (silica gel, n-hexane/EtOAc, 5%) to give (E)-2-methyl-
stilbene (3d) and 1-methyl-2-(1-phenylvinyl)benzene (4d, 71 mg, ra-
tio 88:12, 47% combined yield) as a colourless oil.
Method 3: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 1-phenylethanol (97 mg, 0.79 mmol), 2-
iodo-1,3-dimethylbenzene (57 μL, 0.39 mmol) and formic acid (33 μL,
0.87 mmol). The vial was sealed and the mixture was heated at 150 °C
for 16 h. The mixture was cooled to r.t. and water (10 mL) and di-
chloromethane (10 mL) were added. The combined organic extracts
were dried over Na2SO4 and the solvent was removed under reduced
pressure. The crude residue was purified by flash column chromatog-
raphy (silica gel, n-hexane/EtOAc, 5%) to give (E)-2,6-dimethylstilbene
(3e) and 1,3-dimethyl-2-(1-phenylvinyl)benzene (4e, 23 mg, ratio
93:7, 28% combined yield) as a colourless oil.
Method 2: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 1-phenylethanol (97 mg, 0.79 mmol)
and 2-iodotoluene (50 μL, 0.39 mmol). The vial was sealed and the
mixture was heated at 150 °C for 16 h. The mixture was cooled to r.t.
and water (10 mL) and dichloromethane (10 mL) were added. The
combined organic extracts were dried over Na2SO4 and the solvent
was removed under reduced pressure. The crude residue was purified
by flash column chromatography (silica gel, n-hexane/EtOAc, 5%) to
give (E)-2-methylstilbene (3d) and 1-methyl-2-(1-phenylvinyl)ben-
zene (4d, 28 mg, ratio 87:13, 37% combined yield) as a colourless oil.
(E)-2,6-Dimethylstilbene (3e)
1H NMR (400 MHz, CDCl3): δ = 7.54 (d, J = 7.3 Hz, 2 H), 7.40 (t,
J = 7.9 Hz, 2 H), 7.31 (t, J = 7.3 Hz, 1 H), 7.17–7.11 (m, 4 H), 6.64 (d,
J = 16.8 Hz, 1 H), 2.40 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 137.6, 137.0, 136.3 (2 × C), 134.0,
128.7 (2 × C), 127.7 (2 × C), 127.6, 127.0, 126.8, 126.3 (2 × C), 21.1 (2 ×
C).
Method 3: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 1-phenylethanol (97 mg, 0.79 mmol), 2-
iodotoluene (50 μL, 0.39 mmol) and formic acid (33 μL, 0.87 mmol).
The vial was sealed and the mixture was heated at 150 °C for 16 h.
The mixture was cooled to r.t. and water (10 mL) and dichlorometh-
ane (10 mL) were added. The combined organic extracts were dried
over Na2SO4 and the solvent was removed under reduced pressure.
The crude residue was purified by flash column chromatography (sil-
ica gel, n-hexane/EtOAc, 5%) to give (E)-2-methylstilbene 3d and 1-
methyl-2-(1-phenylvinyl)benzene 4d (59 mg, ratio 88:12, 78% com-
bined yield) as a colourless oil.
IR (CHCl3): 3023, 2922, 2853, 1595, 1464, 968, 766, 690 cm–1
.
HRMS (APPI): m/z calcd. for [C16H16]+: 208.1247; found: 208.1248.
(E)-4-Methoxystilbene47 (3f) and 1-Methoxy-4-(1-phenylvi-
nyl)benzene47 (4f)
Method 1: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) and 4-iodoanisole (183 mg, 0.78 mmol)
in degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. was added
styrene (87 μL, 0.79 mmol). The vial was sealed and the mixture was
heated at 150 °C for 16 h. The mixture was cooled to r.t. and water (10
mL) and dichloromethane (10 mL) were added. The combined organic
extracts were dried over Na2SO4 and the solvent was removed under
reduced pressure. The crude residue was purified by flash column
chromatography (silica gel, n-hexane/EtOAc, 5%) to give (E)-1-me-
thoxystilbene (3f) and 1-methoxy-4-(1-phenylvinyl)benzene (4f, 152
mg, ratio 84:16, 93% combined yield) as a white solid.
(E)-2-Methylstilbene (3d)
1H NMR (400 MHz, CDCl3): δ = 7.65 (d, J = 7.1 Hz, 1 H), 7.58 (d,
J = 7.5 Hz, 2 H), 7.41 (t, J = 7.6 Hz, 3 H), 7.37–7.23 (m, 5 H), 7.06 (d,
J = 16.2 Hz, 1 H), 2.49 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 137.8, 136.5, 135.9, 130.5, 130.1,
128.8 (2 × C), 127.7, 127.6, 126.64 (2 × C), 126.61, 126.3, 125.4, 20.0.
Method 2: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodoanisole (91 mg, 0.39 mmol) in de-
gassed acetonitrile / degassed water (1:3, 4 mL) at r.t. were added 1-
phenylethanol (97 mg, 0.79 mmol). The vial was sealed and the mix-
ture was heated at 150 °C for 16 h. The mixture was cooled to r.t. and
water (10 mL) and dichloromethane (10 mL) were added. The com-
bined organic extracts were dried over Na2SO4 and the solvent was
removed under reduced pressure. The crude residue was purified by
IR (CHCl3): 3023, 2923, 1540, 1494, 959, 756, 711 cm–1
.
HRMS (APPI): m/z calcd. for [C15H14]+: 194.1090; found: 194.1088.
1-Methyl-2-(1-phenylvinyl)benzene (4d)
1H NMR (400 MHz, CDCl3): δ = 7.32–7.17 (m, 9 H), 5.77 (d, J = 1.3 Hz,
1 H), 5.22 (d, J = 1.3 Hz, 1 H), 2.05 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 137.8, 136.5, 130.5, 130.1, 128.8 (2 ×
C), 127.7, 127.6, 126.64 (2 × C), 126.61, 126.3, 125.4, 20.0.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

I
J. E. Camp et al.
Feature
Synthesis
flash column chromatography (silica gel, n-hexane/EtOAc, 5%) to give
(E)-1-methoxystilbene (3f) and 1-methoxy-4-(1-phenylvinyl)ben-
zene (4f, 64 mg, ratio 88:12, 67% combined yield) as a white solid.
sure. The crude residue was purified by flash column chromatogra-
phy (silica gel, n-hexane/EtOAc, 5%) to give (E)-4-fluoro-trans-stilbe-
ne (3g) and 1-fluoro-4-(1-phenylvinyl)benzene (4g, 42 mg, ratio
90:10, 55% combined yield) as a white solid.
Method 3: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodoanisole (91 mg, 0.39 mmol) in de-
gassed acetonitrile / degassed water (1:3, 4 mL) at r.t. were added 1-
phenylethanol (97 mg, 0.79 mmol) and formic acid (33 μL, 0.87
mmol). The vial was sealed and the mixture was heated at 150 °C for
16 h. The mixture was cooled to r.t. and water (10 mL) and dichloro-
methane (10 mL) were added. The combined organic extracts were
dried over Na2SO4 and the solvent was removed under reduced pres-
sure. The crude residue was purified by flash column chromatogra-
phy (silica gel, n-hexane/EtOAc, 5%) to give (E)-1-methoxystilbene
(3f) and 1-methoxy-4-(1-phenylvinyl)benzene (4f, 43 mg, ratio
86:14, 48% combined yield) as a white solid.
(E)-4-Fluorostilbene (3g)
1H NMR (400 MHz, CDCl3): δ = 7.53–7.48 (m, 4 H), 7.39 (t, J = 7.6 Hz,
2 H), 7.29 (t, J = 7.30 Hz, 1 H), 7.12–7.02 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 162.4 (d, J = 246.3 Hz), 137.2, 133.5 (d,
J = 3.4 Hz), 128.7, 128.5 (d, J = 2.4 Hz), 128.0 (d, J = 8.0 Hz), 127.7,
127.5, 126.5, 115.6 (d, J = 21.7 Hz).
19F NMR (376 MHz, CDCl3): δ = –114.2 (s, 1 F).
IR (CHCl3): 3022, 2923, 2851, 1592, 1504, 1226, 999, 822, 751 cm–1
.
HRMS (APPI): m/z calcd. for C14H12F: 198.0839; found: 198.0835.
(E)-1-Methoxystilbene (3f)
(E)-1-Chloro-4-styrylbenzene40 (3h), 1-Chloro-4-(1-phenylvi-
1H NMR (400 MHz, CDCl3): δ = 7.53–7.48 (m, 3 H), 7.37 (t, J = 7.6 Hz,
2 H), 7.28–7.22 (m, 2 H), 7.10 (d, J = 16.3 Hz, 1 H), 7.00 (d, J = 16.3 Hz,
1 H), 6.93 (d, J = 8.7 Hz, 2 H), 3.86 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.3, 137.7, 130.2, 128.7 (2 × C),
128.2, 127.7 (2 × C), 127.2, 126.6, 126.3 (2 × C), 114.1 (2 × C), 55.3.
nyl)benzene41 (4h)
Method 2: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-chloroiodotoluene (93 mg, 0.39
mmol) in degassed acetonitrile / degassed water (1:3, 4 mL) at r.t.
were added 1-phenylethanol (97 mg, 0.79 mmol). The vial was sealed
and the mixture was heated at 150 °C for 16 h. The mixture was
cooled to r.t. and water (10 mL) and dichloromethane (10 mL) were
added. The combined organic extracts were dried over Na2SO4 and
the solvent was removed under reduced pressure. The crude residue
was purified by flash column chromatography (silica gel, n-hex-
ane/EtOAc, 5%) to give (E)-1-chloro-4-styrylbenzene (3h) and 1-
chloro-4-(1-phenylvinyl)benzene (4h, 46 mg, ratio 85:15, 55% com-
bined yield) as a white solid.
IR (CHCl3): 3022, 3002, 2933, 2836, 1600, 1508, 1266, 1028, 811, 686
cm–1
.
HRMS (APPI): m/z calcd. for [C15H14O]+: 210.1039; found: 210.1039.
(E)-4-Fluorostilbene44 (3g) and 1-Fluoro-4-(phenylvinyl)benzene43
(4g)
Method 1: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 4-fluoroiodobenzene (90 μL, 0.78 mmol)
and styrene (87 μL, 0.79 mmol). The vial was sealed and the mixture
was heated at 150 °C for 16 h. The mixture was cooled to r.t. and wa-
ter (10 mL) and dichloromethane (10 mL) were added. The combined
organic extracts were dried over Na2SO4 and the solvent was removed
under reduced pressure. The crude residue was purified by flash col-
umn chromatography (silica gel, n-hexane/EtOAc, 5%) to give (E)-4-
fluorostilbene (3g) and 1-fluoro-4-(1-phenylvinyl)benzene (4g, 83
mg, ratio 94:6, 54% combined yield) as a white solid.
Method 3: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-chloroiodotoluene (93 mg, 0.39
mmol) in degassed acetonitrile / degassed water (1:3, 4 mL) at r.t.
were added 1-phenylethanol (97 mg, 0.79 mmol) and formic acid (33
μL, 0.87 mmol). The vial was sealed and the mixture was heated at
150 °C for 16 h. The mixture was cooled to r.t. and water (10 mL) and
dichloromethane (10 mL) were added. The combined organic extracts
were dried over Na2SO4 and the solvent was removed under reduced
pressure. The crude residue was purified by flash column chromatog-
raphy (silica gel, n-hexane/EtOAc, 5%) to give (E)-1-chloro-4-styryl-
benzene (3h) and 1-chloro-4-(1-phenylvinyl)benzene (4h, 52 mg, ra-
tio 85:15, 62% combined yield) as a white solid.
Method 2: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 1-phenylethanol (97 mg, 0.79 mmol)
and 4-fluoroiodobenzene (45 μL, 0.39 mmol). The vial was sealed and
the mixture was heated at 150 °C for 16 h. The mixture was cooled to
r.t. and water (10 mL) and dichloromethane (10 mL) were added. The
combined organic extracts were dried over Na2SO4 and the solvent
was removed under reduced pressure. The crude residue was purified
by flash column chromatography (silica gel, n-hexane/EtOAc, 5%) to
give (E)-4-fluorostilbene (3g) and 1-fluoro-4-(1-phenylvinyl)benzene
(4g, 60 mg, ratio 89:11, 60% combined yield) as a white solid.
(E)-1-Chloro-4-styrylbenzene (3h)
1H NMR (400 MHz, CDCl3): δ = 7.52 (d, J = 7.4 Hz, 2 H), 7.45 (d,
J = 8.5 Hz, 2 H), 7.40–7.27 (m, 5 H), 7.12–7.03 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 137.0, 135.9, 133.2, 129.3, 128.9 (2 ×
C), 128.8 (2 × C), 127.9, 127.7 (2 × C), 127.4, 126.6 (2 × C).
IR (CHCl3): 3055, 2987, 2928, 1558, 1540, 1264, 730, 701, 669 cm–1
GCMS (EI): m/z calcd. for [C14H11Cl]+: 214.1; found: 214.0.
.
Method 3: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 1-phenylethanol (97 mg, 0.79 mmol), 4-
fluoroiodobenzene (45 μL, 0.39 mmol) and formic acid (33 μL, 0.87
mmol). The vial was sealed and the mixture was heated at 150 °C for
16 h. The mixture was cooled to r.t. and water (10 mL) and dichloro-
methane (10 mL) were added. The combined organic extracts were
dried over Na2SO4 and the solvent was removed under reduced pres-
1-Chloro-4-(1-phenylvinyl)benzene (4h)
1H NMR (400 MHz, CDCl3): δ = 7.33–7.26 (m 10 H), 5.47 (s, 1 H), 5.45
(s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 149.0, 141.02, 140.0, 133.6, 129.6 (2 ×
C), 128.4 (2 × C), 128.3 (2 × C), 128.2 (2 × C), 237.9, 114.7.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

J
J. E. Camp et al.
Feature
Synthesis
(E)-4-Bromostilbene48 (3i) and 1-(4-Bromophenyl)-1-phenyle-
Method 2: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodobenzaldehyde (85 mg, 0.39
mmol) in degassed acetonitrile / degassed water (1:3, 4 mL) at r.t.
were added 1-phenylethanol (97 mg, 0.79 mmol). The vial was sealed
and the mixture was heated at 150 °C for 16 h. The mixture was
cooled to r.t. and water (10 mL) and dichloromethane (10 mL) were
added. The combined organic extracts were dried over Na2SO4 and
the solvent was removed under reduced pressure. The crude residue
was purified by flash column chromatography (silica gel, n-hex-
ane/EtOAc, 5%) to give (E)-4-styrylbenzaldehyde (3j) and 4-(1-
phenylvinyl)benzaldehyde (4j, 35 mg, ratio 91:9, 43% combined yield)
as a white solid.
thene49 (4i)
Method 1: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodobromobenzene (221 mg, 0.78
mmol) in degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. was
added styrene (87 μL, 0.79 mmol). The vial was sealed and the mix-
ture was heated at 150 °C for 16 h. The mixture was cooled to r.t. and
water (10 mL) and dichloromethane (10 mL) were added. The com-
bined organic extracts were dried over Na2SO4 and the solvent was
removed under reduced pressure. The crude residue was purified by
flash column chromatography (silica gel, n-hexane/EtOAc, 5%) to give
(E)-4-bromo-stilbene (3i) and 1-bromo-4-(1-phenylvinyl)benzene
(4i, 176 mg, ratio 86:14, 87% combined yield) as a white solid.
Method 3: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodobenzaldehyde (85 mg, 0.39
mmol) in degassed acetonitrile / degassed water (1:3, 4 mL) at r.t.
were added 1-phenylethanol (97 mg, 0.79 mmol) and formic acid (33
μL, 0.87 mmol). The vial was sealed and the mixture was heated at
150 °C for 16 h. The mixture was cooled to r.t. and water (10 mL) and
dichloromethane (10 mL) were added. The combined organic extracts
were dried over Na2SO4 and the solvent was removed under reduced
pressure. The crude residue was purified by flash column chromatog-
raphy (silica gel, n-hexane/EtOAc, 5%) to give (E)-4-styrylbenzalde-
hyde (3j) and 4-(1-phenylvinyl)benzaldehyde (4j, 50 mg, ratio 93:7,
61% combined yield) as a white solid.
Method 2: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodobromobenzene (110 mg, 0.39
mmol) in degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. was
added 1-phenylethanol (97 mg, 0.79 mmol). The vial was sealed and
the mixture was heated at 150 °C for 16 h. The mixture was cooled to
r.t. and water (10 mL) and dichloromethane (10 mL) were added. The
combined organic extracts were dried over Na2SO4 and the solvent
was removed under reduced pressure. The crude residue was purified
by flash column chromatography (silica gel, n-hexane/EtOAc, 5%) to
give (E)-4-bromostilbene (3i) and 1-bromo-4-(1-phenylvinyl)ben-
zene (4i, 67 mg, ratio 88:12, 66% combined yield) as a white solid.
Method 3: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodobromobenzene (110 mg, 0.39
mmol) in degassed acetonitrile / degassed water (1:3, 4 mL) at r.t.
were added 1-phenylethanol (97 mg, 0.79 mmol) and formic acid (33
μL, 0.87 mmol). The vial was sealed and the mixture was heated at
150 °C for 16 h. The mixture was cooled to r.t. and water (10 mL) and
dichloromethane (10 mL) were added. The combined organic extracts
were dried over Na2SO4 and the solvent was removed under reduced
pressure. The crude residue was purified by flash column chromatog-
raphy (silica gel, n-hexane/EtOAc, 5%) to give (E)-4-bromostilbene (3i)
and 1-bromo-4-(1-phenylvinyl)benzene (4i, 64 mg, ratio 88:12, 63%
combined yield) as a white solid.
(E)-4-Styrylbenzaldehyde (3j)
1H NMR (400 MHz, CDCl3): δ = 10.00 (s, 1 H), 7.87 (d, J = 8.2 Hz, 2 H),
7.66 (d, J = 8.1 Hz, 2 H), 7.55 (d, J = 7.5 Hz, 2 H), 7.40 (t, J = 7.5 Hz, 2 H),
7.34–7.25 (m, 2 H), 7.15 (t, J = 16.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 191.6, 143.4, 136.6, 135.3, 132.2,
130.3, 128.9, 128.5, 127.3, 126.9 (2 × C).
IR (CHCl3): 3028, 2820, 2729, 1692, 1590, 1209, 1166, 968, 816, 759,
688 cm–1
.
HRMS (Dual ESI): m/z calcd. for [C15H13O]+: 209.0961; found:
209.0961.
(E)-1-(4-Styrylphenyl)ethan-1-one48 (3k) and 1-(4-(1-Phenylvi-
(E)-4-Bromostilbene (3i)
1H NMR (400 MHz, CDCl3): δ = 7.53–7.46 (m, 4 H), 7.40–7.34 (m, 4 H),
nyl)phenyl)ethan-1-one51 (4k)
Method 1: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) and 4-iodotoluene (170 mg, 0.78 mmol)
in degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. was added
styrene (87 μL, 0.79 mmol). The vial was sealed and the mixture was
heated at 150 °C for 16 h. The mixture was cooled to r.t. and water (10
mL) and dichloromethane (10 mL) were added. The combined organic
extracts were dried over Na2SO4 and the solvent was removed under
reduced pressure. The crude residue was purified by flash column
chromatography (silica gel, n-hexane/EtOAc, 5%) to give (E)-1-(4-sty-
rylphenyl)ethan-1-one (3k) and 1-(4-(1-phenylvinyl)phenyl)ethan-
1-one (4k, 78 mg, ratio 93:7, 45% combined yield) as a white solid.
7.30–7.25 (m, 1 H), 7.07 (dd, J = 16.4 Hz, J = 28.3 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 137.0, 136.3, 131.8, 129.4, 128.8,
128.0, 127.9, 127.4, 126.6, 121.3.
IR (CHCl3): 3025, 2921, 2852, 1485, 1072, 964, 840, 688 cm–1
.
HRMS (APPI): m/z calcd. for [C14H11Br]+: 258.0039; found: 258.0029.
(E)-4-Styrylbenzaldehyde50 (3j) and 4-(1-Phenylvinyl)benzalde-
hyde43 (4j)
Method 1: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) and 4-iodobenzaldehyde (170 mg, 0.78
mmol) in degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. was
added styrene (87 μL, 0.79 mmol). The vial was sealed and the mix-
ture was heated at 150 °C for 16 h. The mixture was cooled to r.t. and
water (10 mL) and dichloromethane (10 mL) were added. The com-
bined organic extracts were dried over Na2SO4 and the solvent was
removed under reduced pressure. The crude residue was purified by
flash column chromatography (silica gel, n-hexane/EtOAc, 5%) to give
(E)-4-styrylbenzaldehyde (3j) and 4-(1-phenylvinyl)benzaldehyde
(4j, 63 mg, ratio 90:10, 39% combined yield) as a white solid.
Method 2: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodotoluene (85 mg, 0.39 mmol) in
degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. was added 1-
phenylethanol (97 mg, 0.79 mmol). The vial was sealed and the mix-
ture was heated at 150 °C for 16 h. The mixture was cooled to r.t. and
water (10 mL) and dichloromethane (10 mL) were added. The com-
bined organic extracts were dried over Na2SO4 and the solvent was
removed under reduced pressure. The crude residue was purified by
flash column chromatography (silica gel, n-hexane/EtOAc, 5%) to give
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

K
J. E. Camp et al.
Feature
Synthesis
(E)-1-(4-styrylphenyl)ethan-1-one (3k) and 1-(4-(1-phenylvi-
nyl)phenyl)ethan-1-one (4k, 50 mg, ratio 90:10, 83% combined yield)
as a white solid.
dried over Na2SO4 and the solvent was removed under reduced pres-
sure. The crude residue was purified by flash column chromatogra-
phy (silica gel, n-hexane/EtOAc, 5%) to give (E)-4-trifluoromethylstil-
bene (3l) and 1-(1-phenylvinyl)-4-(trifluoromethyl)benzene (4l, 86
mg, ratio 87:13, 89% combined yield) as a white solid.
Method 3: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodotoluene (85 mg, 0.39 mmol) in
degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. were added
1-phenylethanol (97 mg, 0.79 mmol) and formic acid (33 μL, 0.87
mmol). The vial was sealed and the mixture was heated at 150 °C for
16 h. The mixture was cooled to r.t. and water (10 mL) and dichloro-
methane (10 mL) were added. The combined organic extracts were
dried over Na2SO4 and the solvent was removed under reduced pres-
sure. The crude residue was purified by flash column chromatogra-
phy (silica gel, n-hexane/EtOAc, 5%) to give (E)-1-(4-styrylphe-
nyl)ethan-1-one (3k) and 1-(4-(1-phenylvinyl)phenyl)ethan-1-one
(4k, 50 mg, ratio 90:10, 58% combined yield) as a white solid.
(E)-4-Trifluoromethylstilbene (3l)
1H NMR (400 MHz, CDCl3): δ = 7.64–7.59 (m, 4 H), 7.55 (d, J = 7.04 Hz,
2 H), 7.41 (t, J = 7.48 Hz, 2 H), 7.33 (t, J = 7.28 Hz, 1 H), 7.21 (d,
J = 16.4 Hz, 1 H), 7.13 (d, J = 16.3 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 140.8, 136.6, 131.2, 129.7, 129.4,
129.1, 128.8, 127.1, 126.8, 126.6, 125.7 (q, 2 × C), 122.9, 123.2.
19F NMR (376 MHz, CDCl3): δ = –62.4 (s, 3 F).
IR (CHCl3): 3028, 2928, 2854, 1612, 1450, 1321, 1164, 1105, 1066,
843, 756, 692 cm–1
.
HRMS (APPI): m/z calcd. for [C15H11F3]+: 248.0807; found: 248.0809.
(E)-1-(4-Styrylphenyl)ethan-1-one (3k)
1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.3 Hz, 2 H), 7.59 (d,
J = 8.3 Hz, 2 H), 7.54 (d, J = 7.5 Hz, 2 H), 7.39 (t, J = 7.5 Hz, 2 H), 7.33–
7.29 (m, 1 H), 7.26–7.22 (m, 1 H), 7.14 (d, J = 16.4 Hz, 1 H), 2.61 (s,
3 H).
13C NMR (100 MHz, CDCl3): δ = 197.5, 136.7, 136.0, 131.5, 128.9 (2 ×
C), 128.8 (2 × C), 128.3, 127.5, 126.8 (2 × C), 126.5 (2 × C), 26.6.
1-(1-Phenylvinyl)-4-(trifluoromethyl)benzene (4l)
1H NMR (400 MHz, CDCl3): δ = 7.62 (d, J = 8.2 Hz, 2 H), 7.47 (d,
J = 8.1 Hz, 2 H), 7.39–7.32 (m, 5 H), 5.58 (s, 1 H), 5.54 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 149.0, 140.6, 128.8, 128.6 (2 × C),
128.4 (2 × C), 128.2 (2 × C), 128.1, 126.8, 126.6, 125.2 (q, 2 × C), 115.9.
IR (CHCl3): 3010, 2922, 2853, 1673, 1633, 1410, 1356, 1260, 999, 843,
19F NMR (376 MHz, CDCl3): δ = –62.5 (s, 3 F).
753, 688, 610 cm–1
.
HRMS (APPI): m/z calcd. for [C16H14O]+: 222.1039; found: 222.1039.
(E)-4-Styrylbenzonitrile40 (3m) and 4-(1-Phenylvinyl)benzoni-
trile45 (4m)
(E)-4-Trifluoromethylstilbene40 (3l) and 1-(1-Phenylvinyl)-4-tri-
Method 2: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodotoluene (85 mg, 0.39 mmol) in
degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. was added 1-
phenylethanol (97 mg, 0.79 mmol). The vial was sealed and the mix-
ture was heated at 150 °C for 16 h. The mixture was cooled to r.t. and
water (10 mL) and dichloromethane (10 mL) were added. The com-
bined organic extracts were dried over Na2SO4 and the solvent was
removed under reduced pressure. The crude residue was purified by
flash column chromatography (silica gel, n-hexane/EtOAc, 5%) to give
(E)-4-styrylbenzonitrile (3m) and 4-(1-phenylvinyl)benzonitrile (4m,
56 mg, ratio 90:10, 70% combined yield) as a white solid.
fluoromethylbenzene41 (4l)
Method 1: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 4-iodobenzotrifluoride (114 μL, 0.78
mmol) and styrene (87 μL, 0.79 mmol). The vial was sealed and the
mixture was heated at 150 °C for 16 h. The mixture was cooled to r.t.
and water (10 mL) and dichloromethane (10 mL) were added. The
combined organic extracts were dried over Na2SO4 and the solvent
was removed under reduced pressure. The crude residue was purified
by flash column chromatography (silica gel, n-hexane/EtOAc, 5%) to
give (E)-4-trifluoromethylstilbene (3l) and 1-(1-phenylvinyl)-4-(tri-
fluoromethyl)benzene (4l, 172 mg, ratio 87:13, 89% combined yield)
as a white solid.
Method 3: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodotoluene (85 mg, 0.39 mmol) in
degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. were added
1-phenylethanol (97 mg, 0.79 mmol) and formic acid (33 μL, 0.87
mmol). The vial was sealed and the mixture was heated at 150 °C for
16 h. The mixture was cooled to r.t. and water (10 mL) and dichloro-
methane (10 mL) were added. The combined organic extracts were
dried over Na2SO4 and the solvent was removed under reduced pres-
sure. The crude residue was purified by flash column chromatogra-
phy (silica gel, n-hexane/EtOAc, 5%) to give (E)-4-styrylbenzonitrile
(3m) and 4-(1-phenylvinyl)benzonitrile (4m, 41 mg, ratio 90:10, 51%
combined yield) as a white solid.
Method 2: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 1-phenylethanol (97 mg, 0.79 mmol)
and 4-iodobenzotrifluoride (57 μL, 0.78 mmol). The vial was sealed
and the mixture was heated at 150 °C for 16 h. The mixture was
cooled to r.t. and water (10 mL) and dichloromethane (10 mL) were
added. The combined organic extracts were dried over Na2SO4 and
the solvent was removed under reduced pressure. The crude residue
was purified by flash column chromatography (silica gel, n-hex-
ane/EtOAc, 5%) to give (E)-4-trifluoromethylstilbene (3l) and 1-(1-
phenylvinyl)-4-(trifluoromethyl)benzene (4l, 67 mg, ratio 89:11, 69%
combined yield) as a white solid.
(E)-4-Styrylbenzonitrile (3m)
1H NMR (400 MHz, CDCl3): δ = 7.67–55 (m, 6 H), 7.44 (t, J = 7.4 Hz,
2 H), 7.37–7.33 (m, 1 H), 7.24 (d, J = 16.4 Hz, 1 H), 7.11 (d, J = 16.3 Hz,
1 H).
13C NMR (100 MHz, CDCl3): δ = 141.9, 136.3, 132.5 (2 × C), 132.4,
128.9 (2 × C), 128.7, 126.93 (2 × C), 126.88 (2 × C), 126.7, 119.1, 110.6.
Method 3: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol) and
glucose (70 mg, 0.39 mmol) in degassed acetonitrile / degassed water
(1:3, 4 mL) at r.t. were added 1-phenylethanol (97 mg, 0.79 mmol), 4-
iodobenzotrifluoride (57 μL, 0.78 mmol) and formic acid (33 μL, 0.87
mmol). The vial was sealed and the mixture was heated at 150 °C for
16 h. The mixture was cooled to r.t. and water (10 mL) and dichloro-
methane (10 mL) were added. The combined organic extracts were
IR (CHCl3): 3023, 2920, 2854, 2223, 1600, 1503, 972, 823, 756, 689
cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

L
J. E. Camp et al.
Feature
Synthesis
HRMS (APPI): m/z calcd. for [C15H11N]+: 205.0886; found: 205.0890.
Supporting Information
Supporting information for this article is available online at
(E)-4-Nitro-stilbene52 (3n) and 1-Nitro-4-(1-phenylvinyl)ben-
https://doi.org/10.1055/s-0037-1610246.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
zene45 (4n)
Method 1: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodonitrobenzene (194 mg, 0.78
mmol) in degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. was
added styrene (87 μL, 0.79 mmol). The vial was sealed and the mix-
ture was heated at 150 °C for 16 h. The mixture was cooled to r.t. and
water (10 mL) and dichloromethane (10 mL) were added. The com-
bined organic extracts were dried over Na2SO4 and the solvent was
removed under reduced pressure. The crude residue was purified by
flash column chromatography (silica gel, n-hexane/EtOAc, 5%) to give
(E)-1-nitrostilbene (3n) and 1-nitro-4-(1-phenylvinyl)benzene (4n,
159 mg, ratio 92:8, 90% combined yield) as a yellow solid.
References
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Method 2: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodonitrobenzene (97 mg, 0.39 mmol)
in degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. was added
1-phenylethanol (97 mg, 0.79 mmol). The vial was sealed and the
mixture was heated at 150 °C for 16 h. The mixture was cooled to r.t.
and water (10 mL) and dichloromethane (10 mL) were added. The
combined organic extracts were dried over Na2SO4 and the solvent
was removed under reduced pressure. The crude residue was purified
by flash column chromatography (silica gel, n-hexane/EtOAc, 5%) to
give (E)-1-nitrostilbene (3n) and 1-nitro-4-(1-phenylvinyl)benzene
(4n, 62 mg, ratio 90:10, 83% combined yield) as a yellow solid.
Method 3: To a stirred solution of Pd(OAc)2 (3.5 mg, 0.016 mmol), glu-
cose (70 mg, 0.39 mmol) and 4-iodonitrobenzene (97 mg, 0.39 mmol)
in degassed acetonitrile / degassed water (1:3, 4 mL) at r.t. were add-
ed 1-phenylethanol (97 mg, 0.79 mmol) and formic acid (33 μL, 0.87
mmol). The vial was sealed and the mixture was heated at 150 °C for
16 h. The mixture was cooled to r.t. and water (10 mL) and dichloro-
methane (10 mL) were added. The combined organic extracts were
dried over Na2SO4 and the solvent was removed under reduced pres-
sure. The crude residue was purified by flash column chromatogra-
phy (silica gel, n-hexane/EtOAc, 5%) to give (E)-1-nitrostilbene (3n)
and 1-nitro-4-(1-phenylvinyl)benzene (4n, 19 mg, ratio 90:10, 22%
combined yield) as a yellow solid.
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(E)-1-Nitrostilbene (3n)
1H NMR (400 MHz, CDCl3): δ = 8.22 (d, J = 8.8 Hz, 2 H), 7.64 (d,
J = 8.8 Hz, 2 H), 7.56 (d, J = 7.3 Hz, 2 H), 7.42 (t, J = 7.4 Hz, 2 H), 7.36–
7.32 (m, 1 H), 7.28 (d, J = 16.3 Hz, 2 H), 7.15 (d, J = 16.3 Hz, 2 H).
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C), 128.8, 127.0 (2 × C), 126.9 (2 × C), 126.3, 124.2 (2 × C).
IR (CHCl3): 3089, 2920, 1593, 1569, 1505, 1336, 1105, 849, 692 cm–1
HRMS (APPI): m/z calcd. for [C14H11NO2]+: 225.0784; found: 225.0778.
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Funding Information
This work was supported by the University of Nottingham, the EPSRC
(First-Grant EP/J003298/1) and the University of Huddersfield (PhD
studentship for T.W.B).
)(
Acknowledgment
The authors thank Dr Christopher Parmenter (Nanosight) and Dr Em-
ily Smith (XPS) for their efforts.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

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