A deacetylation-diazotation-coupling sequence: Palladium-catalyzed C-C bond formation with acetanilides as formal leaving groups

Article abstract of DOI:10.1002/adsc.201200929

Acetanilides can be deacetylated and diazotized in situ, and subsequently used in Pd-catalyzed coupling reactions without isolation of the diazonium intermediate. Heck reactions, Suzuki crosscoupling reactions, and a Pd-catalyzed [2+2+1] cycloaddition hav

Full text of DOI:10.1002/adsc.201200929

FULL PAPERS
DOI: 10.1002/adsc.201200929
A Deacetylation–Diazotation–Coupling Sequence: Palladium-
À
Catalyzed C C Bond Formation with Acetanilides as Formal
Leaving Groups
Bernd Schmidta,* and Renꢀ Bergera
a
Universitꢁt Potsdam, Institut fuer Chemie (Organische Synthesechemie), Karl-Liebknecht-Straße 24-25, D-14476
Potsdam-Golm, Germany
Fax : (+49)-331-977-5059; e-mail: bernd.schmidt@uni-potsdam.de
Received: October 19, 2012; Published online: February 1, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200929.
Abstract: Acetanilides can be deacetylated and di- sequence does not require the exchange of solvents
azotized in situ, and subsequently used in Pd-cata- or removal of by-products between the individual
lyzed coupling reactions without isolation of the di- steps, but proceeds by addition of reagents and cata-
azonium intermediate. Heck reactions, Suzuki cross- lysts in due course.
coupling reactions, and a Pd-catalyzed [2+2+1]cy-
À
cloaddition have been investigated as terminating C
C bond-forming steps of this one-flask sequence. The geneous catalysis; palladium; Suzuki coupling
Keywords: diazo compounds; Heck reaction; homo-
Introduction
spontaneous or thermally induced decomposition,
which can be overcome to some extent by the devel-
Over the past few years there has been a renewed in- opement of innovative flow processes[31] and limited
terest in arenediazonium salts as reagents for Pd-cata- stability upon storage and toxicity.[32] For these rea-
lyzed coupling reactions[1–4] and for Meerwein-type ar- sons, tactics have been developed to avoid the isola-
ylation reactions.[5–7] While for the latter class of reac- tion of diazonium salts and conduct consecutive trans-
tions arenediazonium halides are often more suited, formations in one flask. For example, Doyle et al. de-
the Pd-catalyzed reactions generally require the pres- veloped an in situ diazotation–Meerwein arylation of
ence of larger, non-nucleophilic counterions, such as electron-deficient alkenes,[33] and Beller et al. de-
BF4À or PF6À,[8] to avoid catalyst inhibition.
scribed a tandem diazotation–Heck reaction of ani-
À
Palladium-catalyzed C C bond-forming reactions lines with ethylene as a method for the synthesis of
that have been successfully conducted using arenedia- styrenes.[34] More recently, the Beller group published
zonium salts include, inter alia, Heck reactions,[9–20] a carbonylative Sonogashira coupling of anilines with
Suzuki–Miyaura cross-coupling reactions[21–27] and So- in situ diazotation, leading to aryl alkynyl ketones.[35]
nogashira reactions.[28,29] In many cases these diazoni- Examples for the synthesis of stilbenes through in situ
um compounds display enhanced reactivities com- diazotation of anilines and Heck reaction were pub-
pared to the analogous aryl halides or triflates, and lished by Andrus et al.,[36] whereas Coy and Sefkow
often undesired side reactions, such as olefin isomeri- described a Larock annulation[37] via in situ diazota-
zation, can be suppressed. These improved selectivi- tion of ortho-aminophenols.[38,39] Very recently, Felpin
ties can be attributed to the occurrence of cationic Pd and co-workers presented an interesting variant of
species in the catalytic cycle,[30] because the Pd hy- the one-flask diazotation–coupling sequence, which
dride intermediate responsible for isomerization reac- relies on two interacting catalytic cycles and is catalyt-
tions is destabilized in the absence of coordinating ic both in palladium and in the acid required for the
counter ions. In spite of these beneficial properties diazotation step.[40] The in situ formation of diazonium
arenediazonium salts have, as electrophiles in Pd-cat- salts and their subsequent use in Pd-catalyzed cou-
alyzed coupling reactions, still not attracted the same pling reactions is also a key element in the cleavage
degree of attention as aryl halides or triflates. The re- of triazene linkers, which have been extensively stud-
luctance to use these reagents might originate from ied in combinatorial chemistry by Brꢁse et al.[41] Poly-
their actual or alleged hazardous properties, such as mer-bound triazenes are “concealed diazonium
Adv. Synth. Catal. 2013, 355, 463 – 476
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463

Bernd Schmidt and Renꢀ Berger
FULL PAPERS
salts”,[42] which are in turn synthesized from a diazoni- ionic Pd-s-aryl complex obtained via oxidative addi-
um salt and a polymer-bound benzylamine. tion to such an extent that this intermediate is stabi-
All the aforementioned strategies eventually use lized without being catalytically inhibited.[47]
anilines as starting materials for the diazotation reac- These considerations led us to investigate a deacety-
tion. These are, however, sometimes prone to oxida- lation method for the initiating step of the projected
tion; occasionally to such an extent that their use is one-flask sequence that proceeds in methanol and in
highly impractical because the aniline needs to be the absence of Brønsted acids with strongly coordinat-
freshly synthesized prior to use. The presence of an ing counter ions, such as hydrochloric acid. The latter
unprotected and therefore highly nucleophilic amino aspect is particularly important because, as outlined
group may also cause problems if a derivatization of in the introduction, halides are known to coordinate
the aniline (e.g., by electrophilic substitution or Pd- to the Pd catalyst and reduce the catalytic activity.
catalyzed coupling at the aromatic core, or by alkyla- For these reasons we chose Sihlbohmꢃs deacetylation
tion of other nucleophilic groups) is required.
conditions,[48] using BF3·MeOH complex as a Lewis
To address these problems, we have recently devel- acid and anhydrous methanol as a solvent. Similar
oped a one-flask deacetylation–diazotation sequence reasoning led us to abandon the traditional diazota-
which uses acetanilides as starting materials for the tion method, NaNO2 in combination with hydrochlo-
synthesis of stable and isolable arenediazonium tetra- ric acid. We also did not consider NOBF4 or NOPF6
fluoroborates.[19,43–45] Several acetanilides are commer- as diazotizing reagents due to their high costs, al-
cially available at low cost, but unlike many of their though there is no obvious reason why these reagents
parent anilines air stable, less toxic, crystalline and should not be compatible with the reaction conditions.
conveniently synthetically modified. Herein, we de- Instead, we focused on the implementation of Doyleꢃs
scribe that the deacetylation–diazotation sequence diazotation method[49] in our one-flask sequence. This
can be extended by various Pd-catalyzed reaction method furnishes arenediazonium tetrafluoroborates
steps (Scheme 1). This means that in practice acet- from anilines, alkyl nitrites and BF3·OEt2 and is typi-
amides can be used as arylating agents.
cally conducted using dichloromethane as a solvent.
For our purpose, it is an additional advantage that the
same Lewis acid can be used for the deacetylation
and the diazotation step. We started our investigation
with the acetanilide 1a, which was successively treated
with BF3·MeOH in methanol under reflux conditions,
followed by treatment with tert-butyl nitrite at 08C
and then with methyl acrylate and a catalytic amount
of PdACTHNUTRGNE(UNG OAc)2 (Table 1). Under these ligand- and base-
free conditions (procedure A), a moderate yield of
45% of 4a could be obtained with a catalyst loading
of 2.5 mol% (entry 1). With the double amount of
precatalyst only a minor improvement of the yield
could be achieved under otherwise identical condi-
tions (entry 2). Further increasing the catalyst loading
was considered as uneconomical, and therefore other
parameters were investigated.
Scheme 1. Deacetylation–diazotation–coupling sequence.
Results and Discussion
Initial Considerations and Optimization Studies
Next, several additives were tested. With the bases
NaOAc and NEt3, the reaction failed completely and
One of the most important challenges in the develop- only the dediazonation product acetophenone was
ment of practical one-flask sequences is the compati- isolated (entries 3 and 4). We reasoned that addition
bility of all steps with one solvent or solvent mixture. of KF might facilitate the formation of the stabilizing
The majority of Heck reactions with arenediazonium tetrafluoroborate ion and thereby suppress undesired
salts are conducted either in methanol or in acetoni- dediazonation reactions. Remarkably, we observed
trile. The choice of solvent depends very much on the indeed a significantly improved yield of 68% when
electronic nature of the alkene. Correia et al.[46] and three equivalents of KF were added after addition of
our group[17] obtained high yields with electron-rich tert-butyl nitrite (entry 5). We thought that, if the un-
alkenes, such as enamides and enol ethers, respective- derlying assumption on the role of this additive is cor-
ly, in acetonitrile, whereas Felpin et al. showed that rect, a further improvement might be reached by
methanol is much better suited for Heck reactions adding KF before the diazotation reaction starts (pro-
with electron-deficient alkenes, such as acrylates.[47] cedure C, entries 6–9). Gratifyingly, this procedure al-
The latter result was rationalized by DFT calculations, lowed us to improve the yield to 78% with a catalyst
which suggest that methanol coordinates to the cat- loading of 2.5 mol% (entry 6) or to 89% with
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A Deacetylation–Diazotation–Coupling Sequence: Palladium-Catalyzed C C Bond Formation
Table 1. Optimization of conditions for Heck coupling.
sence of the alkene coupling partner. This s-complex
was found to be a highly active catalyst for the Heck
coupling. We assumed that the formation of such
a particularly active catalyst should be further facili-
tated by increasing the initial concentration of 1a, and
we could indeed obtain a quantitative yield of cou-
pling product 4a with a concentration of 0.6M
(entry 11).
Entry Additive
Cat. loading Procedure[a] Yield
1
2
3
4
5
6
7
8
none
none
2.5 mol%
5.0 mol%
A
A
B
B
B
C
C
C
C
D
D
45%
57%
<5%
<5%
68%
78%
66%
45%
89%
89%
99%
Having established optimum conditions for the 4-
acetyl-substituted acetanilide 1a, we wanted to check
whether or not these were also applicable to an acet-
anilide with an electron-donating group in the para-
position. To this end, 4-methoxy derivative 1b was re-
acted under standard conditions, but surprisingly the
desired coupling product 4b was not observed. Inter-
estingly, this failure could not be attributed to a limit-
ed stability of the transient diazonium salt 3b: a pre-
cipitate formed after keeping the reaction mixture for
24 h at ambient temperature in the presence of the Pd
catalyst and the coupling partner methyl acrylate was
unambigously identified as 4-methoxybenzene diazo-
nium salt 3b,[44] which could be isolated in 72% yield.
As we know from previous investigations, the Heck
reaction of this particular diazonium salt 3b with
methyl acrylate is normally a facile process and gives
the corresponding cinnamate derivative 4b in high
yield.[19] This could indeed be verified using the diazo-
nium salt 3b isolated from the failed experiment: ap-
plication of the Heck reaction conditions from stan-
NaOAc (3 equiv.) 2.5 mol%
NEt3 (3 equiv.)
KF (3 equiv.)
KF (3 equiv.)
KF (2 equiv.)
KF (1 equiv.)
KF (3 equiv.)
none
2.5 mol%
2.5 mol%
2.5 mol%
2.5 mol%
2.5 mol%
5.0 mol%
5.0 mol%
5.0 mol%
9
10
11[a]
none
[a]
Reagents and conditions: Procedure
A
–
methanol
(0.3M); BF3·MeOH (3.0 equiv.); 658C; then 08C; tert-
BuONO (1.5 equiv.); then 208C; add methyl acrylate
(1.5 equiv.); PdACHTUNGTRENNUNG(OAc)2 (n mol%). Procedure B – as for
procedure A, but add additive prior to methyl acrylate.
Procedure C – as for procedure A, but add additive prior
to tert-BuONO. Procedure D – as for procedure A, but
add PdACHTUNGTRENNUNG(OAc)2 first, stir for 15 min. at 208C, then add
methyl acrylate.
Substrate concentration: 0.6M.
[b]
5.0 mol% of PdACHTUNGTRENNUNG(OAc)2 (entry 9). This is an improve- dard procedure D (see Table 1) to isolated 3b gave 4b
ment of ca. 30% compared to the analogous additive- in nearly quantitative yield (Table 2, entry 1). This
free conditions (procedure A, entries 1 and 2). While result suggests that either one of the reagents used in
reducing the amount of added KF (entries 7 and 8) excess for the deacetylation–diazotation–coupling se-
led to considerably lower yields, further improve- quence or one of the by-products formed in the
ments could not be achieved. However, these results course of the reaction sequence interferes with the
and the interesting effect of the order in which the re-
agents are added prompted us to revisit the base-free
conditions (procedure A) described in entries 1 and 2.
We modified this procedure by inverting the order of
addition of the coupling partner methyl acrylate and
Table 2. Optimization of conditions for 1b.
the precatalyst PdACHTNUGTRNEUNG(OAc)2 to the in situ generated di-
azonium salt. Thus, the precatalyst was added first,
and the reaction mixture was kept at ambient temper-
ature for 15 min, before the coupling partner was
added (procedure D). Remarkably, this resulted in
a yield of 89% of 4a (entry 10), compared to 57% ob-
tained with the conventional addition sequence
(entry 2). This result is in line with observations previ-
ously described by Correia et al., who found im-
proved yields if a Pd precatalyst, in their case
Pd2ACHTUNGTRENNUNG(dba)3·CHCl3, was treated with a catalytic amount
Entry
Additive
Equivalents
Yield of 4b
of the diazonium salt for a certain period of time,
before stoichiometric quantities of the diazonium salt
and the alkene were added.[30] The authors explained
this result, based on ESI-MS studies, by the selective
formation of a cationic Pd-s-aryl species from the
Pd(0) precursor and the diazonium cation in the ab-
1
2
3
4
5
none
–
98%
96%
56%
93%
95%
BF3·MeOH
tert-BuONO
tert-BuOH
H2O
1.3
0.5
1.3
1.0
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Bernd Schmidt and Renꢀ Berger
FULL PAPERS
Table 3. Scope of the deacetylation–diazotation–coupling se-
quence for acetanilides 1.
Heck reaction. To check this hypothesis, the Heck re-
action of 3b and methyl acrylate was repeated in the
presence of each of these reagents or by-products. As
can be seen from Table 2, entries 2, 4 and 5, neither
excess Lewis acid nor the diazotation by-products
tert-butyl alcohol and water affect the isolated yield
of 4b, whereas the yield decreases significantly if the
reaction is run in the presence of tert-butyl nitrite
(entry 3).
Entry
1
R1
R2
R3
4
Yield[a] Yield[b]
1
1a
1b
1b
1c
1d
1e
1f
1g
1h
1i
Ac
OMe
OMe
H
CN
H
NO2
H
Cl
H
H
OH
OMe NO2
Br
OMe Br
H
H
H
H
H
CF3
H
H
H
H
H
H
H
H
H
H
4a
4b
4b
4c
4d
4e
4f
99%
<5%
–
95%
36%
72%
49%
87%
92%
86%
93%
69%
86%
99%
76%
74%
71%
80%
The adverse effect of excess tert-butyl nitrite can
probably be explained by its oxidizing properties.
While most Pd-catalyzed coupling and cross-coupling
reactions rely on a facile cycling between Pd(0) and
Pd(II), a higher oxidation state Pd chemistry [in par-
ticular the couple [Pd(II)/Pd(IV)] is not unknown and
has recently attracted some attention in catalysis.[50] In
a typical catalytic cycle of a Heck reaction, an oxidant
might interfere at different stages. If, as in the present
case, a Pd(II) precatalyst is used, the necessary reduc-
tion to the catalytically active Pd(0) species might be
suppressed or at least retarded. Although this as-
sumption appears to be plausible, it does not explain
why the Heck reaction leading to 4a proceeds virtual-
ly unaffected by excess of oxidant with quantitative
yield, while it fails completely in the case of 4b under
otherwise identical conditions. This remarkable differ-
ence suggests that the oxidant interferes at the stage
of the Pd-s-aryl complex, which according to Cor-
reiaꢃs investigations plays a prominent role in Heck
reactions with arenediazonium salts (Scheme 2). Most
likely, oxidation of the 4-methoxyphenyl complex B
will be facilitated by the electron-donating substituent
2
3[c]
4
40%
86%
47%
83%
77%
55%
74%
84%
–
5
6
7
8
NO2 4g
9
H
H
Cl
H
H
H
H
4h
4i
4j
4k
4l
4m
4n
10
11
12
13
14
15
Cl
H
NO2
1j
1k
1l
26%
–
–
1m OH
1n
[a]
Reagents and conditions: Procedure
(0.6M); BF3·MeOH (3.0 equiv.); 658C; then 08C; tert-
BuONO (1.5 equiv.); 1 h; Pd(OAc)2 (5.0 mol%); 0.25 h;
methyl acrylate (1.5 equiv.); 208C.
Reagents and conditions: Procedure E – as for procedure
D, but with tert-BuONO (1.0 equiv.).
D
–
methanol
AHCTUNGTRENNUNG
[b]
[c]
Reaction mixture was heated to 608C after addition of
methyl acrylate.
in para-position, whereas the electron-withdrawing 1 under the optimized conditions of procedure D
acetyl group in complex A should lower the energy of (Table 3). Due to the interesting different outcome
all orbitals and reduce the sensitivity towards oxida- for acetanilides 1a and 1b and the putative effects of
tion.
electron-withdrawing and electron-donating substitu-
ents discussed above, we also varied the amount of
tert-butyl nitrite and repeated the experiments with
1.0 equivalent (procedure E).
As can be seen from Table 3, the para-methoxy-
substituted derivative 1b reacts to afford 4b in 36%
Scope of the Deacetylation–Diazotation–Heck
Sequence
The observations and conclusions outlined in the pre- yield if the amount of tert-butyl nitrite is reduced to
vious section prompted us to investigate the one-flask 1 equivalent (entry 2). For this example, the yield can
sequence for a variety of substituted acetanilides be improved to 72% by heating the reaction mixture
to reflux during the coupling step (entry 3). Deriva-
tives with electron-withdrawing substituents in the 4-
position (1a, d, f, entries 1, 5 and 7) react to give the
corresponding cinnamates 4a, d, f in good yields. In
these cases the results are not affected by the excess
of tert-buyl nitrite. A remarkable difference between
procedures D and E was also observed for 1e
(entry 6) and 1l (entry 13), although both derivatives
carry electron-withdrawing substituents. These are,
however, located in the meta-position. Notably, phe-
nols are tolerated under the conditions of procedure
E and the coupling products 4k and 4m (entries 12
and 14) could be isolated in good yields.
Scheme 2. Cationic Pd-s-aryl complexes.
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Adv. Synth. Catal. 2013, 355, 463 – 476

À
A Deacetylation–Diazotation–Coupling Sequence: Palladium-Catalyzed C C Bond Formation
Table 4. Stilbenes from acetanilides 1 via deacetylation–diaz-
mocoupling has been translated into a catalytic
method for the synthesis of biaryls[60,61] and was more
recently mechanistically elucidated: the reaction pro-
ceeds via [k2-O2PdL2] complexes, which are attacked
by the Lewis acidic areneboronic acids.[62] The forma-
tion of homocoupling products is significantly less
pronounced with organotrifluoroborates as coupling
partners. Lloyd-Jones et al. proposed that the slow re-
lease of areneboronic acids from these reagents leads
to a low concentration of boronic acids and hence an
efficient suppression of this undesired pathway.[63,64]
Taking these considerations and our observation
that alkyl nitrites obviously have a certain potential
as oxidants in Pd-catalyzed coupling reactions into ac-
count, we decided to avoid any excess of tert-butyl ni-
trite for the envisaged deacetylation–diazotation–
Suzuki coupling sequence. In addition, for the reasons
outlined above we focused on organotrifluoroborates
as nucleophilic coupling partners. For an initial opti-
mization study acetanilide 1a and potassium phenyl-
trifluoroborate (7a) were chosen (Table 5). When we
adapted the conditions previously established for the
deacetylation–diazotation–Heck sequence, the desired
biaryl 8aa was obtained in 47% yield, along with 39%
of biphenyl (9a), resulting from an oxidative homo-
coupling (Table 5, entry 1). The comparatively high
otation–coupling sequence.[a]
Entry
1
R1
R2
R3
5
R4
6
Yield
1
2
3
4
1a
1d
1a
1d
1j
Ac
CN
Ac
CN
H
H
H
H
H
H
H
H
H
H
5a
5a
H
H
6aa
6da
47%
50%
73%
–
81%
35%
5b NO2 6ab
5b NO2 6db
[b]
5
Cl 5b NO2 6jb
6[c]
7[c]
8
1k
OH NO2
H
H
H
5b NO2 6kb
5b NO2 6mb 48%
5b NO2 6ob
1m OH Br
1o OH
[d]
H
–
[a]
Reagents and conditions: Procedure
F
–
methanol
(0.6M); BF3·MeOH (3.0 equiv,); 658C; then 08C; tert-
BuONO (1.0 equiv,); 1 h; Pd(OAc)2 (5.0 mol%); 0.25 h;
AHCTUNGTRENNUNG
styrene 5a or 5b (1.0 equiv.); 208C.
Complex mixture of products.
As for procedure F, but with 0.5 equivalents of 5b.
No conversion after deacetylation and diazotation.
[b]
[c]
[d]
In the next step we investigated the transfer of the Table 5. Optimization of Suzuki coupling.
deacetylation–diazotation–Heck coupling procedure
to the synthesis of stilbenes (Table 4).
While only mediocre yields were obtained with sty-
rene (5a) and electron-deficient acetanilides 1a, d (en-
tries 1 and 2), 4-nitrostyrene (5b) appeared to be
more reactive, as yields of 73% and 81%, respectively,
were observed with acetanilides 1a, j (entries 3 and
5). Surprisingly, the combination of acetanilide 1d and
the more reactive styrene 5b did not result in the for-
mation of notable amounts of the desired stilbene,
but led to a complex mixture of products (entry 4).
As illustrated in entries 6 and 7 for the phenol deriva-
tives 1k, m a protecting group-free coupling with 5b is
in principle possible, although the parent acetanilide
paracetamol (1o) does not react under these condi-
tions.
Entry Pd
G
7
8aa
9a
A
E
ACHTUNGTRENN(UNG equiv.)
1
2
3
4
5
6
7
8
5.0
5.0
5.0
5.0
2.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.25
0.1
0.5
0.5
0.5
0.1
0.5
0.5
0.5
0.5
0.5
0.5
7a (1.0)
7a (1.0)
7a (1.0)
7a (1.5)
7a (1.5)
7a (1.5)
7a (1.5)
47%
47%
49%
52%
58%
62%
54%
39%
35%
36%
24%
14%
11%
11%
13%
12%
<5%
6%
Deacetylation–Diazotation–Suzuki Coupling
7a (0.67) 56%
9
7a (1.0)
7a’ (1.0)
7a (1.0)
7a (1.0)
7a (1.0)
58%
39%
56%
54%
Suzuki cross-coupling reactions using arenediazonium
salts as electrophiles have been reported for arenebor-
onic acids,[22,51–54] boronates,[55,56] and for organotri-
fluoroborates[21,26,57,58] as nucleophilic coupling part-
ners. Suzuki reactions in general are often complicat-
ed by the formation of symmetrical side products, re-
sulting from an oxidative dimerization of the boronic
acids if oxygen is not rigorously excluded.[59] This ho-
10
11[a]
12[b]
13[c]
6%
<5%[d] <5%
[a]
With addition of NaOAc (1.0 equiv.).
With addition of NaOAc (1.3 equiv.).
With addition of NaOAc (3.0 equiv).
Acetophenone isolated in 47% yield.
[b]
[c]
[d]
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Bernd Schmidt and Renꢀ Berger
FULL PAPERS
yield of biphenyl may be explained by assuming that only to a slightly improved yield of 8aa, whereas the
the tert-butyl nitrite was not fully consumed in the di- amount of biphenyl could be significantly reduced to
azotation step and thus triggers the undesired oxida- 24%. In the next step, the catalyst loading was varied,
tive homocoupling. However, considering the very while the amount of borate 7a was maintained. Inter-
high yield observed for the Heck coupling of the estingly, reducing the catalyst loading to 2.5 mol%
same acetanilide 1a and methyl acrylate (Table 3, (entry 5) and 0.5 mol% (entry 6) leads to significantly
entry 1) under similar deacetylation–diazotation con- improved yields of 8aa and decreased yields of the
ditions, it appears to be more likely that the presence side product 9a. Obviously, higher catalyst loadings
of the Lewis acid BF3·MeOH in combination with the accelerate the oxidative homocoupling much more
protic solvent methanol foils the slow release mecha- than the intended Suzuki coupling. No further im-
nism[64] of the organotrifluoroborate reagent. This provement could be achieved by reducing the initial
would lead to a high stationary concentration of a bor- substrate concentration to 0.1M (entry 7) and using
onate, which might ultimately result in an accelerated the diazonium salt in excess (entry 8). For economical
oxidative homocoupling.
reasons, the amount of borate was then reduced to
To mitigate the extent of this side reaction, several 1.0 equivalents (entry 9), which resulted in the forma-
parameters were varied. First, an observation previ- tion of 8aa and 9a in yields similar to those obtained
ously reported by Felpin et al. for the heterogeneous- with 1.5 equivalents of 7a. When 7a was replaced by
ly catalyzed Suzuki coupling of boronic acids and are- phenylboronic acid (7a’), the yield of Suzuki coupling
nediazonium salts was investigated for our system.[24] product 8aa dropped to 39%, however, quite surpris-
These authors reported a significant effect of the ini- ingly no biphenyl was formed (entry 10). Finally, we
tial substrate concentration on the yield of the desired tested the addition of NaOAc as a base. If the forma-
coupling products, with 0.1M being the optimum con- tion of homocoupling product 9a can indeed be attrib-
centration, whereas higher or lower dilution resulted uted to a Lewis acid-accelerated solvolysis of the or-
in lower yields. For these reasons the comparatively ganotrifluoroborate, it should be possible to retard
high concentration of 0.5M used in previous experi- this effect by neutralizing the Lewis acid. On the
ments was reduced to 0.25M (entry 2) and 0.1M other hand, nucleophiles and bases have a detrimental
(entry 3), however, the product distribution and iso- effect on the stability of many arenediazonium salts
lated yields remained virtually unchanged. Increasing and lead to decreased yields in most Pd-catalyzed
the amount of borate 7a to 1.5 equiv. (entry 4) led coupling and cross-coupling reactions.[19] This dichoto-
Table 6. Scope of deacetylation–diazotation–Suzuki coupling.
Entry
1
R1
R2
7
R3
R4
8
9
1
2
3
4
5
6
7
8
1a
1b
1d
1e
1f
1m
1n
1a
1d
1a
1d
1f
Ac
H
H
H
CF3
H
Br
Br
H
H
H
7a
7a
7a
7a
7a
7a
7a
7b
7b
7c
7c
7c
7d
7e
H
H
H
H
H
H
H
OMe
OMe
F
F
F
H
H
H
H
H
H
H
H
H
H
H
H
8aa (58%)
8ba (19%)
8da (56%)
8ea (22%)
8fa (47%)
8ma (20%)
8na (32%)
8ab (41%)
8db (27%)
8ac (63%)
8dc (65%)
8fc (61%)
8hd (24%)
8ae (51%)
9a (12%)
9a (36%)
9a (<5%)
9a (35%)
9a (<5%)[a]
9a (23%)
9a (23%)
9b (13%)
9b (13%)
9c (<5%)
9c (10%)
9c (10%)
9d (16%)[b]
9e (<5%)[c]
OMe
CN
H
NO2
OH
OMe
Ac
CN
Ac
CN
NO2
Cl
9
10
11
12
13
14
H
H
H
H
1h
1a
H
NO2
À
Ac
-CH=CH CH=CH-
[a]
Nitrobenzene (15%) was isolated as an additional side product.
4,4’-Dichlorobiphenyl (9h, 15%) was isolated as an additional side product.
Several unidentified side products are formed.
[b]
[c]
468
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Adv. Synth. Catal. 2013, 355, 463 – 476

À
A Deacetylation–Diazotation–Coupling Sequence: Palladium-Catalyzed C C Bond Formation
my might explain why the addition of 1.0 or 1.3 equiv-
alents of NaOAc results in a lower amount of homo-
coupling product without improving the yield of
Suzuki coupling product (entries 11 and 12). Addition
of three equivalents of base (entry 13) inhibits the for-
mation of both products. Under these conditions, only
acetophenone resulting from reductive dediazonation
of the intermediate diazonium salt 3a was isolated in
47% yield.
The conditions listed in Table 5, entry 9 appeared
to be the best compromise with respect to yield, selec-
tivity and economical considerations and were there-
fore applied to other examples (Table 6). In summary,
acetanilides with electron-withdrawing substituents in
the para-position (entries 1, 3, 5) react in considerably
higher yields to the desired biaryls 8 than those with
Scheme 3. Deacetylation–diazotation–Suzuki coupling se-
quence with styrenyl trifluoroborate 7f.
electron-donating groups (entries 2, 6, 7). Strongly lated naphthalenes.[65] In the course of this study we
electron-withdrawing substituents in the meta-position investigated whether a termination of the deacetyla-
appear to be ineffective and lead to product distribu- tion–diazotation sequence by a Pd-catalyzed formal
tions similar to those observed with electron-donating [2+2+1] cycloaddition reaction is possible, which
groups (entry 4). The highest yields of Suzuki-cou- means that isolated diazonium salts can be replaced
pling products were obtained for acetanilides with by acetanilides as starting materials.
electron-withdrawing groups in para-position and the
Starting from the 4-hydroxyacetanilides 1k, m, p
4-fluoro-substituted borate 7c (entries 10–12). In most the expected spirocyclic products 11k, m, p were ob-
cases the symmetrical products 9 resulting from oxi- tained in fair yields, using the deacetylation–diazota-
dative dimerization of the organotrifluoroborates are tion conditions previously established for the Heck
the only side products. Notable exceptions are listed and Suzukicoupling sequences. Surprisingly, the
in entries 5, 13 and 14: in the case of 1f, a significant methyl ether 1b and the benzyl ether 1q undergo the
quantity of the hydrodediazonation product nitroben- cycloaddition reaction in comparable yields, furnish-
zene was isolated (entry 5), whereas for the 4-chloro ing the same product 11b (Table 7). This result points
derivative 1h the symmetrical side product 4,4’-di- at a facile ether cleavage under the reaction condi-
chlorobiphenyl (9h), obviously formed via reductive tions.
dimerization of the intermediate diazonium salt, was
isolated in 15% yield (entry 13). For the coupling re-
action of 1a and 2-naphthyltrifluoroborate 7e no oxi- Conclusions
dative homocoupling product could be isolated, be-
cause a complex mixture of side products was formed In conclusion, we have shown that conveniently avail-
along with the desired product 8ae (entry 14).
able, crystalline and air-stable acetanilides can be
The best yield for a deacetylation–diazotation– used as starting materials for Pd-catalyzed deacetyla-
Suzuki–coupling sequence was observed with an
alkenACHTUNGTRENNUNGyltrifluoroborate. The combination of 4-acetyl
Table 7. Deacetylation–diazotation–[2+2+1] cycloaddition
sequence.
derivative 1a and the styrenyltrifluoroborate 7f fur-
nished the stilbene 6aa in 74% yield. This derivative
is also available from 1a and styrene (5a) via a deace-
tylation–diazotation–Heck
coupling
sequence
(Table 4, entry 1), albeit in significantly lower yield
(Scheme 3).
Deacetylation–Diazotation–[2+2+1]Cycloaddition
Sequence
Entry
1
R1
R2
11
1
2
3
4
5
1k
1m
1p
1b
1q
H
H
H
Me
Bn
NO2
Br
CO2Me
H
11k (60%)
11m (39%)
11p (38%)
11b (34%)
11b (37%)
Recently, we described a Pd-catalyzed formal [2+2+
1]cycloaddition reaction which yields densely func-
tionalized spirocycles from 4-phenoldiazonium salts
and two equivalents of an alkyne. The products are
valuable starting materials for the synthesis of perary-
H
Adv. Synth. Catal. 2013, 355, 463 – 476
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
469

Bernd Schmidt and Renꢀ Berger
FULL PAPERS
105–1088C. 1H NMR (300 MHz, CDCl3): d=7.94 (d, J=
8.4 Hz, 2H), 7.68 (d, J=16.1 Hz, 1H), 7.58 (d, J=8.3 Hz,
2H), 6.50 (d, J=16.1 Hz, 1H), 3.80 (s, 3H), 2.59 (s, 3H);
13C NMR (75 MHz, CDCl3): d=197.3 (0), 166.9 (0), 143.3
(1), 138.7 (0), 138.1 (0), 128.9 (1), 128.2 (1), 120.4 (1), 51.9
(3), 26.7 (3); MS (EI): m/z=102 (16%), 189 (100%), 204
([M]+, 32%); HR-MS (EI): m/z=204.0802, calcd. for
C12H12O3 [M]+: 204.0786.
tion–diazotation–coupling sequences that proceed in
one flask without exchange or removal of solvents or
by-products, simply by adding the appropriate re-
agents in due course. Thus, from acetanilides cinna-
mates, stilbenes, biaryls and spirocyclic ketones
become available via formal substitution of the acet-
amide moiety. Extension of the method by imple-
menting further Pd-catalyzed steps is currently under
investigation. Although the use of acetanilides instead
of anilines makes an additional in situ deacetylation
necessary, which might result in somewhat lower over-
all yields, this disadvantage is outweighed by the op-
portunity of an easier functionalization of the acetani-
lides by electrophilic substitution, and by a higher ef-
ficiency of the Pd-catalyzed step due to the absence
of inhibiting aniline oxidation products.
(E)-Methyl 3-(4-methoxyphenyl)acrylate (4b):[66] Follow-
ing the general procedure, 4b was obtained from 1b
(500 mg, 3.0 mmol) after heating the mixture to reflux for
12 h upon addition of methyl acrylate as a colourless solid;
yield: 423 mg (72%); mp 88–918C. 1H NMR (300 MHz,
CDCl3): d=7.64 (d, J=16.0 Hz, 1H), 7.46 (d, J=8.8 , 2H),
6.89 (d, J=8.8 Hz, 2H), 6.30 (d, J=16.0 Hz, 1H), 3.82 (s,
3H), 3.78 (s, 3H); 13C NMR (75 MHz, CDCl3): d=167.6 (0),
161.3 (0), 144.4 (1), 129.6 (1), 127.1 (0), 115.2 (1), 114.3 (1),
55.3 (3), 51.5 (3); MS (ESI): m/z=147 (25%), 161 (100%),
193 ([M+H]+, 44%); HR-MS (ESI): m/z=193.0870, calcd.
for C11H13O3 [M+H]+: 193.0865.
(E)-Methyl 3-phenylacrylate (4c):[67] Following the general
procedure, 4c was obtained from 1c (409 mg, 3.0 mmol) as
Experimental Section
1
General Remarks
a colourless solid; yield: 238 mg (49%); mp 378C. H NMR
(300 MHz, CDCl3): d=7.70 (d, J=16.0 Hz, 1H), 7.57–7.48
(2H), 7.45–7.33 (3H), 6.45 (d, J=16.0 Hz, 1H), 3.81 (s,
3H); 13C NMR (75 MHz, CDCl3): d=167.5 (0), 145.0 (1),
134.5 (0), 130.4 (1), 129.0 (1), 128.2 (1), 118.0 (1), 51.8 (3);
MS (EI): m/z=103 (64%), 131 (23%), 162 ([M]+, 64%);
HR-MS (EI): m/z=162.0684, calcd. for C10H10O2 [M]+:
162.0681.
All experiments were conducted in dry reaction vessels
under an atmosphere of dry argon. Solvents were purified
by standard procedures. H NMR spectra were obtained at
1
300 MHz in CDCl3 with CHCl3 (d=7.26 ppm) as an internal
standard, in DMSO-d6 with DMSO-d5 (d=2.50 ppm) as an
internal standard, or in acetone-d6 with acetone-d5 (d=
2.05 ppm) as an internal standard. Coupling constants (J)
are given in Hz. Signal assignments refer to numbering
schemes which are detailed in the Supporting Information.
13C NMR spectra were recorded at 75 MHz in CDCl3 with
CDCl3 (d=77.0 ppm) as an internal standard, in DMSO-d6
with DMSO-d6 (d=39.5 ppm) as an internal standard, or in
acetone-d6 with CD3C(O)CD3 (d=29.9 ppm) as an internal
standard. IR spectra were recorded as films on NaCl or KBr
(E)-Methyl 3-(4-cyanophenyl)acrylate (4d):[68] Following
the general procedure, 4d was obtained from 1d (485 mg,
3.0 mmol) as a colourless solid; yield: 495 mg (87%); mp
122–1268C. 1H NMR (300 MHz, CDCl3): d=7.67 (d, J=
8.4 Hz, 2H), 7.66 (d, J=16.1 Hz, 1H), 7.60 (d, J=8.3 Hz,
2H), 6.51 (d, J=16.0 Hz, 1H), 3.82 (s, 3H); 13C NMR
(75 MHz, CDCl3): d= 166.6 (0), 142.5 (1), 138.8 (0), 132.7
(1), 128.5 (1), 121.5 (1), 118.4 (0), 113.6 (0), 52.0 (3); MS
(EI): m/z=128 (9%), 156 (100%), 187 ([M]+, 63%); HR-
MS (EI): m/z=187.0621, calcd. for C11H9NO2 [M]+:
187.0633.
plates or as KBr discs. Wave numbers (n) are given in cmÀ1
.
Mass spectra were obtained at 70 eV
General Procedure for the Deacetylation–
Diazotation–Heck Reaction Sequence with Methyl
Acrylate
(E)-Methyl 3-[3-(trifluoromethyl)phenyl]acrylate (4e):[47]
Following the general procedure, 4e was obtained from 1e
(615 mg, 3.0 mmol) as a colourless solid; yield: 640 mg
1
(92%); mp 38–428C. H NMR (300 MHz, CDCl3): d=7.78–
To a solution of acetanilide 1 (3.0 mmol) in anhydrous
MeOH (5 mL) was added BF3·MeOH complex (0.98 mL,
9.1 mmol). The solution was stirred at reflux temperature
until the acetanilide was fully consumed, and subsequently
cooled to 08C. After addition of tert-BuONO (0.36 mL,
3.0 mmol) the solution was stirred for 1 h at this tempera-
7.60 (4H), 7.51 (dd, J=7.8, 7.8 Hz, 1H), 6.50 (d, J=16.1 Hz,
1H), 3.82 (s, 3H); 13C NMR (75 MHz, CDCl3): d=166.9 (0),
143.1 (1), 135.4 (0), 131.7 (q, 2JC,F =32.8 Hz, 0), 131.2 (1),
3
3
129.6 (1), 126.8 (q, JC,F =3.7 Hz, 1), 124.7 (q, JC,F =3.8 Hz,
1
1), 124.0 (q, JC,F =272.5 Hz, 0), 120.0 (1), 52.0 (3); MS (EI):
m/z=151 (87%), 199 (100%), 230 ([M]+, 46%); HR-MS
(EI): m/z=230.0551, calcd. for C11H9O2F3 [M]+: 230.0555.
(E)-Methyl 3-(4-nitrophenyl)acrylate (4f):[16] Following
the general procedure, 4f was obtained from 1f (545 mg,
3.0 mmol) as a yellow solid; yield: 542 mg (86%); mp 158–
ture. To the reaction mixture was added PdACTHNURGTNEUNG(OAc)2 (34 mg,
5 mol%). After 15 min methyl acrylate (0.41 mL, 4.5 mmol)
was added. The solution was stirred for 12 h at ambient tem-
perature. The reaction was quenched with water (20 mL)
and extracted with MTBE (60 mL). The combined organic
layers were dried with MgSO4, filtered and concentrated
under reduced pressure. The residue was purified by column
chromatography on silica using hexane-MTBE (5:1) mix-
tures as eluent.
1
1608C. H NMR (300 MHz, CDCl3): d=8.24 (d, J=8.8 Hz,
2H), 7.71 (d, J=16.0 Hz, 2H), 7.67 (d, J=8.9 Hz, 2H), 6.55
(d, J=16.0 Hz, 1H), 3.83 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=166.5 (0), 148.6 (0), 142.0 (1), 140.6 (0), 128.7
(1), 124.3 (1), 122.2 (1), 52.1 (3); MS (EI): m/z=130 (16%),
176 (100%), 207 ([M]+, 73%); HR-MS (EI): m/z=207.0521,
calcd. for C10H9NO4 [M]+: 207.0532.
(E)-Methyl 3-(4-acetylphenyl)acrylate (4a):[66] Following
the general procedure, 4a was obtained from 1a (536 mg,
3.0 mmol) as a colourless solid; yield: 590 mg (95%); mp
470
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ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 463 – 476

À
A Deacetylation–Diazotation–Coupling Sequence: Palladium-Catalyzed C C Bond Formation
(E)-Methyl 3-(2-nitrophenyl)acrylate (4g):[16] Following
the general procedure, 4g was obtained from 1g (545 mg,
3.0 mmol) as a yellow solid; yield: 542 mg (93%); mp 70–
(1), 127.2 (0), 125.0 (1), 118.6 (1), 114.0 (1), 56.8 (3), 51.9
(3); MS (EI): m/z=102 (41%), 206 (39%), 237 ([M]+,
100%); HR-MS (EI): m/z=237.0617, calcd. for C11H11NO5
[M]+: 237.0637.
1
738C. H NMR (300 MHz, CDCl3): d=8.11 (d, J=15.8 Hz,
(E)-Methyl 3-(3-bromo-4-hydroxyphenyl)acrylate (4m):[19]
Following the general procedure, 4m was obtained from 1m
(697 mg, 3.0 mmol) as a colourless solid; yield: 551 mg
(71%); mp 109–1148C. 1H NMR (300 MHz, CDCl3): d=
7.63 (d, J=2.0 Hz, 1H), 7.54 (d, J=16.0 Hz, 1H), 7.38 (dd,
J=8.5, 2.0 Hz, 1H), 7.00 (d, J=8.5 Hz, 1H), 6.28 (d, J=
16.0 Hz, 1H), 5.86 (s, 1H), 3.78 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=167.6 (0), 154.2 (0), 143.2 (1), 132.0 (1), 129.3
(1), 128.9 (0), 117.0 (1), 116.7 (1), 111.0 (0), 51.9 (3); MS
(ESI): m/z=146 (41%), 225 (100%), 257 ([M+H]+, 16%);
HR-MS (ESI): m/z=256.9813, calcd. for C10H10O3Br [M+
H]+: 256.9807; anal. calcd. for C10H9O3Br: C 46.7%, H 3.5%;
found: C 46.6%, H 3.4%; IR (KBr): n=3312 (m), 1688 (s),
1H), 8.06–7.98 (m, 1H), 7.69–7.58 (2H), 7.54 (m, 1H), 6.36
(d, J=15.8 Hz, 1H), 3.82 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=166.3 (0), 148.4 (0), 140.2 (1), 133.6 (1), 130.6
(0), 130.4 (1), 129.2 (1), 125.0 (1), 123.0 (1), 52.1 (3); MS
(EI): m/z=65 (100%), 130 (23%), 207 ([M]+, 2%); HR-MS
(EI): m/z=207.0545; calcd. for C10H9NO4 [M]+: 207.0532.
(E)-Methyl 3-(4-chlorophenyl)acrylate (4h):[69] Following
the general procedure, 4h was obtained from 1h (513 mg,
3.0 mmol) as a colourless solid; yield: 408 mg (69%); mp
1
748C. H NMR (300 MHz, CDCl3): d=7.63 (d, J=16.0 Hz,
1H), 7.44 (d, J=8.5 Hz, 2H), 7.35 (d, J=8.6 Hz, 2H), 6.40
(d, J=16.0 Hz, 1H), 3.80 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=167.2 (0), 143.4 (1), 136.3 (0), 133.0 (0), 129.3
(1), 129.3 (1), 118.5 (1), 51.8 (3); MS (EI): m/z=102 (33%),
165 (100%), 196 ([M]+, 81%); HR-MS (EI): m/z=196.0281,
calcd. for C10H9O235Cl [M]+: 196.0291.
1631 (s), 1600 (s), 1430 (s) cmÀ1
.
(E)-Methyl 3-(3-bromo-4-methoxyphenyl)acrylate (4n):[19]
Following the general procedure, 4n was obtained from 1n
(739 mg, 3.0 mmol) as a colourless solid; yield: 551 mg
(71%); mp 115–1168C. 1H NMR (300 MHz, CDCl3): d=
7.72 (d, J=2.1 Hz, 1H), 7.55 (d, J=16.0 Hz, 1H), 7.41 (dd,
J=8.5, 2.1 Hz, 1H), 6.87 (d, J=8.6 Hz, 1H), 6.29 (d, J=
16.0 Hz, 1H), 3.90 (s, 3H), 3.77 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=167.5 (0), 157.6 (0), 143.2 (1), 132.8 (1), 129.1
(1), 128.7 (0), 116.9 (1), 112.5 (0), 112.0 (1), 56.6 (3), 51.9
(3); MS (ESI): m/z=160 (68%), 239 (100%), 271 ([M+H]+,
15%); HR-MS (ESI): m/z=270.9984, calcd. for C11H12O3Br
[M+H]+: calcd 270.9970; anal. calcd. for C11H11O3Br: C
48.7%, H 4.1%; found: C 48.6%, H 3.9%; IR (KBr): n=
(E)-Methyl 3-(3-chlorophenyl)acrylate (4i):[70] Following
the general procedure, 4i was obtained from 1i (513 mg,
3.0 mmol) as a colourless solid; yield: 510 mg (86%); mp
42–448C. 1H NMR (300 MHz, CDCl3): d=7.61 (d, J=
16.0 Hz, 1H), 7.49 (m, 1H), 7.41–7.27 (3H), 6.43 (d, J=
16.0 Hz, 1H), 3.80 (s, 3H); 13C NMR (75 MHz, CDCl3): d=
167.0 (0), 143.3 (1), 136.3 (0), 135.0 (0), 130.2 (1), 130.2 (1),
127.9 (1), 126.3 (1), 119.4 (1), 51.9 (3); MS (EI): m/z=102
(57%), 165 (100%), 196 ([M]+, 60%); HR-MS (EI): m/z=
196.0277, calcd. for C10H9O235Cl [M]+: 196.0291.
(E)-Methyl 3-(2-chlorophenyl)acrylate (4j):[71] Following
the general procedure, 4j was obtained from 1j (513 mg,
3.0 mmol) as a colourless liquid; yield: 596 mg (99%).
1H NMR (300 MHz, CDCl3): d=8.07 (d, J=16.0 Hz, 1H),
7.59 (m, 1H), 7.38 (m, 1H), 7.32–7.19 (2H), 6.40 (d, J=
16.0 Hz, 1H), 3.79 (s, 3H); 13C NMR (75 MHz, CDCl3): d=
167.0 (0), 140.7 (1), 135.1 (0), 132.8 (0), 131.1 (1), 130.3 (1),
127.7 (1), 127.2 (1), 120.6 (1), 51.9 (3); MS (EI): m/z=101
(40%), 161 (100%), 196 ([M]+, 12%); HR-MS (EI): m/z=
196.0274, calcd. for C10H9O235Cl [M]+: 196.0291.
3438 (m), 1704 (s), 1633 (s), 1497 (s), 1265 (s) cmÀ1
.
General Procedure for the Deacetylation–
Diazotation–Heck Reaction Sequence with Styrenes
To a solution of acetanilide 1 (1.5 mmol) in anhydrous
MeOH (5 mL) was added BF3·MeOH complex (0.50 mL,
4.5 mmol). The solution was stirred at reflux temperature
until the acetanilide 1 was fully consumed, and subsequently
cooled to 08C. After addition of tert-BuONO (0.18 mL,
1.5 mmol) the solution was stirred for 1 h at this tempera-
(E)-Methyl 3-(4-hydroxy-3-nitrophenyl)acrylate (4k):[19]
Following the general procedure, 4k was obtained from 1k
(594 mg, 3.0 mmol) as a colourless solid; yield: 423 mg
(72%); mp 142–1488C. 1H NMR (300 MHz, CDCl3): d=
10.70 (s, 1H), 8.23 (d, J=2.2 Hz, 1H), 7.75 (dd, J=8.8,
2.2 Hz, 1H), 7.61 (d, J=16.0 Hz, 1H), 7.19 (d, J=8.8 Hz,
1H), 6.39 (d, J=16.0 Hz, 1H), 3.80 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=167.0 (0), 156.3 (0), 141.8 (1), 136.1
(1), 133.9 (0), 127.5 (0), 125.1 (1), 121.0 (1), 119.0 (1), 52.1
(3); MS (ESI): m/z=146 (28%), 192 (100%), 223 ([M]+,
85%); HR-MS (ESI): m/z=223.0491, calcd. for C10H9NO5
[M]+: 223.0481; anal. calcd for C10H9NO5: C 53.8%, H,
4.1%, N, 6.3%; found: C 54.2%, H 4.2%, N 6.2%; IR (KBr):
ture. To the reaction mixture was added PdACTHNURGTNEUNG(OAc)2 (17 mg,
5 mol%). After 15 min, styrene (1.5 mmol) was added and
the solution was stirred at ambient temperature for 12 h.
The reaction was quenched with water (20 mL), and extract-
ed with MTBE (60 mL). The combined organic layers were
dried with MgSO4, filtered and concentrated under reduced
pressure. The residue was purified by column chromatogra-
phy on silica using hexane-MTBE (5:1) mixtures as eluent.
(E)-1-(4-Styrylphenyl)ethanone (6aa):[72] Following the
general procedure, 6aa was obtained from 1a (266 mg,
1.5 mmol) and 5a (156 mg, 1.5 mmol) as a colourless solid;
yield: 158 mg (47%); mp 140–1468C. 1H NMR (300 MHz,
CDCl3): d=7.96 (d, J=8.4 Hz, 2H), 7.59 (d, J=8.3 Hz, 2H),
7.57–7.51 (2H), 7.42–7.35 (2H), 7.30 (m, 1H), 7.24 (d, J=
16.2 Hz, 1H), 7.13 (d, J=16.3, 1H), 2.61 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=197.5 (0), 142.1 (0), 136.8 (0), 136.1
(0), 131.6 (0), 129.0 (1), 128.9 (1), 128.4 (0), 127.6 (0), 126.9
(1), 126.6 (1), 26.7 (3); MS (EI): m/z=152 (10%), 178
(54%), 207 (100%), 222 ([M]+, 66%); HR-MS (EI): m/z=
222.1051, calcd. for C16H14O [M]+: 222.1045.
n=3262 (m), 2924 (m), 1724 (s), 1620 (s), 1533 (s) cmÀ1
.
(E)-Methyl 3-(4-methoxy-3-nitrophenyl)acrylate (4l):[19]
Following the general procedure, 4l was obtained from 1l
(636 mg, 3.0 mmol) as a colourless solid; yield: 530 mg
(74%); mp 129–1308C. 1H NMR (300 MHz, CDCl3): d=
8.00 (d, J=2.2 Hz, 1H), 7.68 (dd, J=8.8, 2.2 Hz, 1H), 7.60
(d, J=16.0 Hz, 1H), 7.11 (d, J=8.8 Hz, 1H), 6.38 (d, J=
16.0 Hz, 1H), 3.99 (s, 3H), 3.80 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=167.0 (0), 154.1 (0), 141.9 (1), 140.0 (0), 133.5
Adv. Synth. Catal. 2013, 355, 463 – 476
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
471

Bernd Schmidt and Renꢀ Berger
FULL PAPERS
(E)-4-Styrylbenzonitrile (6da):[72] Following the general
procedure, 6da was obtained from 1d (240 mg, 1.5 mmol)
and 5a (156 mg, 1.5 mmol) as a colourless solid; yield:
(d, J=2.1 Hz, 1H), 7.81 (d, J=8.8 Hz, 2H), 7.52 (dd, J=8.5,
2.1 Hz, 1H), 7.42 (d, J=16.4 Hz, 1H), 7.27 (d, J=16.4 Hz,
1H), 7.05 (d, J=8.4 Hz, 1H); 13C NMR (75 MHz, acetone-
d6): d=155.5 (0), 147.5 (0), 145.3 (0), 132.7 (1), 132.6 (1),
131.1 (0), 128.6 (1), 127.8 (1), 125.8 (1), 124.8 (1), 117.6 (1),
111.0 (0); MS (EI): m/z=165 (100%), 194 (40%), 319
([M]+, 43%); HR-MS (EI): m/z=for 318.9840, calcd. for
1
153 mg (50%); mp 114–1168C. H NMR (300 MHz, CDCl3):
d=7.70–7.49 (6H), 7.46–7.28 (3H), 7.22 (d, J=16.4 Hz,
1H), 7.09 (d, J=16.4 Hz, 1H); 13C NMR (75 MHz, CDCl3):
d=141.9 (0), 136.4 (0), 132.6 (1), 132.5 (1), 128.9 (1), 128.7
(1), 127.0 (1), 126.9 (1), 126.8 (1), 119.1 (0), 110.7 (0); MS
(EI): m/z=89 (16%), 176 (19%), 190 (44%), 205 ([M]+,
100%); HR-MS (EI): m/z=205.0896, calcd. for C15H11N
[M]+: 205.0891.
C14H10NO3Br
[M]+:
318.9844;
anal.
calcd.
for
C14H10NO379Br: C 52.5%, H 3.1%, N 4.4%; found: C 52.4%,
H 2.9%, N 4.6%; IR (KBr): 3445 (s), 1588 (s), 1496 (s), 1341
(s) cmÀ1.
(E)-1-[4-(4-Nitrostyryl)phenyl]ethanone (6ab): Following
the general procedure, 6ab was obtained from 1a (266 mg,
1.5 mmol) and 5b (224 mg, 1.5 mmol) as a yellow solid;
yield: 292 mg (81%), contaminated with ca. 10% of the Z-
General Procedure for the Deacetylation–
Diazotation–Suzuki Coupling Sequence with
Organotrifluoroborates
1
isomer. H NMR (300 MHz, CDCl3): d=8.26 (d, J=8.8 Hz,
2H), 8.01 (d, J=8.3 Hz, 2H), 7.68 (d, J=8.8 Hz, 2H), 7.65
(d, J=8.8 Hz, 2H), 7.32 (d, J=16.3 Hz), 7.24 (d, J=16.3 Hz,
1H), 2.64 (s, 3H); 13C NMR (75 MHz, CDCl3): d=197.4,
143.2, 140.8, 137.1, 132.1, 129.1, 129.1, 127.4, 127.2, 124.4,
26.7; MS (EI): m/z=206 (16%), 252 (100%), 267 ([M]+,
74%); HR-MS (EI): m/z=267.0882, calcd. for C16H13NO3
[M]+: 267.0895. Selected data for Z-6ab obtained from the
To a solution of acetanilide 1 (1.5 mmol) in anhydrous
MeOH (3 mL) was added BF3·MeOH complex (0.50 mL,
4.5 mmol). The solution was stirred at reflux temperature,
until the acetanilide was fully consumed, and subsequently
cooled to 08C. After addition of tert-BuONO (0.18 mL,
1.5 mmol) the solution was stirred for 1 h at this tempera-
1
mixture: H NMR (300 MHz, CDCl3): d=8.11 (d, J=8.8 Hz,
ture. To the reaction was added PdACTHNUTRGENUN(G OAc)2 (1.7 mg, 0.5
2H), 7.87 (d, J=8.3 Hz, 2H), 7.37 (d, J=8.9 Hz, 2H), 7.28
(d, J=8.3 Hz, 2H), 6.85 (d, J=12.3 Hz, 1H), 6.76 (d, J=
12.3 Hz, 1H), 2.60 (s, 3H).
mol%). After 15 min the appropriate organotrifluoroborate
7 (1.5 mmol) was added. The solution was stirred for 12 h at
ambient temperature. The reaction was quenched with
water (20 mL) and extracted with MTBE (60 mL). The com-
bined organic layers were dried with MgSO4, filtered and
concentrated under reduced pressure. The residue was puri-
fied by column chromatography on silica using hexane-
MTBE (20:1) mixtures as eluent.
(E)-1-Chloro-2-(4-nitrostyryl)benzene (6jb): Following the
general procedure, 6jb was obtained from 1j (256 mg,
1.5 mmol) and 5b (224 mg, 1.5 mmol) as a yellow solid;
yield: 326 mg (81%); mp 125–1288C. 1H NMR (300 MHz,
CDCl3): d=8.23 (d, J=8.8 Hz, 2H), 7.70 (m, 1H), 7.68 (d,
J=16.3 Hz, 1H), 7.67 (d, J=8.8 Hz, 2H), 7.43 (dd, J=8.3,
2.0 Hz, 1H), 7.35–7.23 (2H), 7.12 (d, J=16.3, 1H);
13C NMR (75 MHz, CDCl3): d=147.2 (0), 143.6 (0), 134.5
(0), 134.1 (0), 130.2 (1), 129.8 (1), 129.4 (1), 128.9 (1), 127.3
(1), 127.2 (1), 126.9 (1), 124.2 (1); MS (EI): m/z=178
(54%), 207 (27%), 259 ([M]+, 100%); HR-MS (EI): m/z=
259.0396, calcd. for C14H10NO235Cl [M]+: 259.0400; anal.
calcd. for C14H10NO2Cl: C 64.7%, H 3.9%, N 5.4%; found:
C 64.8%, H 3.7%, N 5.8%; IR (KBr): n=1590 (s), 1510 (s),
1321 (s), 1107 (s) cmÀ1.
1-(Biphenyl-4-yl)ethanone (8aa):[73] Following the general
procedure, 8aa was obtained from 1a (266 mg, 1.5 mmol)
and 7a (276 mg, 1.5 mmol) as a colourless solid; yield:
170 mg (58%); mp 1208C, along with 9a [yield: 28 mg
1
(12%)]. H NMR (300 MHz, CDCl3): d=8.04 (d, J=8.5 Hz,
2H), 7.69 (d, J=8.5 Hz, 2H), 7.64 (dd, J=7.0, 1.5 Hz, 2H),
7.52–7.36 (3H), 2.64 (s, 3H); 13C NMR (75 MHz, CDCl3):
d=197.7 (0), 145.9 (0), 140.0 (0), 136.0 (0), 129.0 (1), 129.0
(1), 128.3 (1), 127.3 (1), 127.3 (1), 26.7 (3); MS (EI): m/z=
43 (60%), 152 (84%), 181 (100%), 196 ([M]+, 54%); HR-
MS (EI): m/z=196.0882, calcd. for C14H12O+ [M]+: 196.0888.
4-Methoxybiphenyl (8ba):[73] Following the general proce-
dure, 8ba was obtained from 1b (248 mg, 1.5 mmol) and 7a
(276 mg, 1.5 mmol) as a colourless solid; yield: 53 mg
(19%); mp 85–898C, along with 9a [yield: 83 mg (36%)].
1H NMR (300 MHz, CDCl3): d=7.64–7.49 (4H), 7.43 (dd,
J=7.5, 7.5 Hz, 2H), 7.32 (t, J=7.3 Hz, 1H), 7.00 (d, J=
8.7 Hz, 2H), 3.87 (s, 3H); 13C NMR (75 MHz, CDCl3): d=
159.2 (0), 140.9 (0), 133.9 (0), 128.8 (1), 128.2 (1), 126.8 (1),
126.7 (1), 114.3 (1), 55.4 (3); MS (EI): m/z=115 (68%), 141
(58%), 169 (51%), 184 ([M]+, 100%); HR-MS (EI): m/z=
184.0898; calcd. for C13H12O+ [M]+: 184.0888.
(E)-2-Nitro-4-(4-nitrostyryl)phenol (6kb): Following the
general procedure, 6kb was obtained from 1k (294 mg,
1.5 mmol) and 5b (224 mg, 1.5 mmol) as a yellow solid;
yield:75 mg /35%), mp 220–2238C. 1H NMR (300 MHz,
CDCl3): d=10.66 (s, 1H), 8.26 (d, J=2.2 Hz, 1H), 8.24 (d,
J=8.9 Hz, 2H), 7.81 (dd, J=8.8, 2.2Hz, 1H), 7.64 (d, J=
8.8 Hz, 2H), 7.24 (d, J=8.8 Hz, 1H), 7.20 (d, J=16.3 Hz,
1H), 7.11 (d, J=16.3, 1H); 13C NMR (75 MHz, CDCl3): d=
155.3 (0), 147.3 (0), 143.1 (0), 135.4 (1), 133.9 (0), 130.3 (1),
129.3 (0), 127.4 (1), 127.1 (1), 124.4 (1), 123.3 (1), 120.8 (1);
MS (EI): m/z=69 (86%), 165 (73%), 286 ([M]+, 100%);
HR-MS (EI): m/z=286.0578, calcd. for C14H10N2O5 [M]+:
286.0590; anal. calcd. for C14H10N2O5: C 58.7%, H 3.5%; N
9.8%; found: C 58.4%; H 3.3%; N 9.9%; IR (KBr) n=1624
Biphenyl-4-carbonitrile (8da):[73] Following the general
procedure, 8da was obtained from 1d (240 mg, 1.5 mmol)
and 7a (276 mg, 1.5 mmol) as a colourless solid; yield:
150 mg (56%); mp 86–898C. 1H NMR (300 MHz, CDCl3):
d=7.73 (d, J=8.5 Hz, 2H), 7.68 (d, J=8.6 Hz, 2H), 7.61–
7.57 (2H), 7.52–7.46 (2H), 7.43 (tt, J=7.2, 1.3, 1H);
13C NMR (75 MHz, CDCl3): d=145.8 (0), 139.3 (0), 132.6
(1), 129.2 (1), 128.7 (1), 127.8 (1), 127.3 (1), 119.0 (0), 111.1
(s), 1531 (s), 1504 (s), 1337 (s) cmÀ1
.
(E)-2-Bromo-4-(4-nitrostyryl)phenol (6mb): Following the
general procedure, 6mb was obtained from 1m (345 mg,
1.5 mmol) and 5b (224 mg, 1.5 mmol) as a yellow solid;
yield: 115 mg (48%); mp 202–2038C. 1H NMR (300 MHz,
acetone-d6): d=9.37 (s, 1H), 8.22 (d, J=8.9 Hz, 2H), 7.84
472
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ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 463 – 476

À
A Deacetylation–Diazotation–Coupling Sequence: Palladium-Catalyzed C C Bond Formation
(0); MS (EI): m/z=76 (5%), 151 (12%), 179 ([M]+, 100%);
HR-MS (EI): m/z=179.0725; calcd. for C13H9N+ [M]+:
179.0735.
4’-Methoxybiphenyl-4-carbonitrile (8db):[77] Following the
general procedure, 8db was obtained from 1d (240 mg,
1.5 mmol) and 7b (321 mg, 1.5 mmol) as a colourless solid;
yield: 85 mg (27%); mp 108–1118C, along with 9b [yield:
3-(Trifluoromethyl)biphenyl (8ea):[74] Following the gener-
al procedure, 8ea was obtained from 1e (305 mg, 1.5 mmol)
and 7a (276 mg, 1.5 mmol) as a colourless liquid; yield:
1
42 mg (13%)]. H NMR (300 MHz, CDCl3): d=7.69 (d, J=
8.6 Hz, 2H), 7.63 (d, J=8.6 Hz, 2H), 7.54 (d, J=8.8 Hz,
2H), 7.01 (d, J=8.8 Hz, 2H), 3.86 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=160.3 (0), 145.3 (0), 132.6 (1), 131.6
(0), 128.4 (1), 127.2 (1), 119.1 (0), 114.7 (1), 110.2 (0), 55.5
(3); MS (EI): m/z=166 (28%), 194 (25%), 209 ([M]+,
100%); HR-MS (EI): m/z=209.0842, calcd. for C14H11NO+
[M]+: 209.0841.
1
72 mg (22%), along with 9a [yield: 81 mg (35%)]. H NMR
(300 MHz, CDCl3): d=7.85 (s, 1H), 7.78 (d, J=7.5 Hz, 1H),
7.74–7.30 (6H); 13C NMR (75 MHz, CDCl3); d=142.2 (0),
3
139.9 (0), 131.2 (q, JCF =32.0, 0), 130.5 (1), 129.3 (1), 129.1
1
(1), 128.1 (1), 127.3 (1), 124.4 (q, JC,F =272 Hz, 0), 124.2–
123.9 (2C, 1); MS (EI): m/z=152 (24%), 201 (18%), 222
([M]+, 100%); HR-MS (EI): m/z=222.0665, calcd. for
1-(4’-Fluorobiphenyl-4-yl)ethanone (8ac):[78] Following the
general procedure, 8ac was obtained from 1a (266 mg,
1.5 mmol) and 7c (303 mg, 1.5 mmol) as a colourless solid;
yield: 201 mg (63%); mp 100–1048C. 1H NMR (300 MHz,
CDCl3): d=8.03 (d, J=8.5 Hz, 2H), 7.63 (d, J=8.5 Hz, 2H),
7.62–7.55 (m, 2H), 7.16 (dd, J=8.7, 8.7 Hz, 2H), 2.64 (s,
3H); 13C NMR (75 MHz, CDCl3): d=197.7 (0), 163.0 (d,
+
C13H9F3 [M]+: 222.0656.
4-Nitrobiphenyl (8fa):[73] Following the general procedure,
8fa was obtained from 1f (270 mg, 1.5 mmol) and 7a
(276 mg, 1.5 mmol) as a colourless solid; yield: 170 mg
(47%); mp 1138C, along with nitrobenzene [yield: 27 mg
1
(15%)]. H NMR (300 MHz, CDCl3): d=8.30 (d, J=8.5 Hz,
4
1JC,F =248 Hz, 0), 144.8 (0), 136.1 (d, JC,F =3.3 Hz, 2C, 1),
2H), 7.74 (d, J=8.5 Hz, 2H), 7.70–7.57 (2H), 7.57–7.40
(3H); 13C NMR (75 MHz, CDCl3): d=147.7 (0), 147.2 (0),
138.9 (0), 129.2 (1), 129.0 (0), 127.9 (1), 127.5 (1), 124.2 (1);
MS (EI): m/z=115 (10%), 152 (64%), 169 (29%), 199
([M]+, 100%); HR-MS (EI): m/z=199.0633, calcd. for
136.0 (0), 129.1 (1), 129.0 (d, 3JC,F =7.7 Hz, 1), 127.2 (1),
116.0 (d, 2JC,F =21.6 Hz, 0), 26.7 (3); MS (EI): m/z=85
(7%), 170 (43%), 199 (100%), 214 ([M]+, 50%); HR-MS
(EI): m/z=214.0792, calcd. for C14H11OF+ [M]+: 214.0794.
4-Fluoro-4’-cyanobiphenyl (8dc): Following the general
procedure, 8dc was obtained from 1d (240 mg, 1.5 mmol)
and 7c (303 mg, 1.5 mmol) as a colourless solid; yield:
193 mg (65%); mp 110–1158C, along with 9c [yield: 28 mg
+
C12H9NO2 [M]+: 199.0633.
3-Bromobiphenyl-4-ol (8ma):[26] Following the general
procedure, 8ma was obtained from 1m (345 mg, 1.5 mmol)
and 7a (276 mg, 1.5 mmol) as a colourless solid; yield: 76 mg
(20%); mp 94–998C, along with 9a [yield: 53 mg (23%)].
1H NMR (300 MHz, CDCl3): d=7.71 (d, J=2.1, 1H), 7.57–
7.49 (2H), 7.49–7.38 (3H), 7.34 (tt, J=7.2, 2.3, 1H), 7.10 (d,
J=8.4, 1H), 5.54 (s, 1H); 13C NMR (75 MHz, CDCl3): d=
151.8 (0), 139.5 (0), 135.5 (0), 130.5 (1), 128.9 (1), 128.0 (1),
127.3 (1), 126.8 (1), 116.4 (1), 110.7 (0); MS (EI): m/z=115
(28%), 139 (80%), 170 (11%), 248 ([M]+, 100%); HR-MS
(EI): m/z=247.9820, calcd. for C12H9O79Br+ [M]+: 247.9837.
3-Bomo-4-methoxybiphenyl (8na):[75] Following the gener-
al procedure, 8na obtained from 1n (366 mg, 1.5 mmol) and
7a (276 mg, 1.5 mmol) as a colourless solid; yield: 128 mg
(32%), mp 808C; along with 9a [yield: 53 mg (23%)].
1H NMR (300 MHz, CDCl3): d=7.80 (d, J=2.2 Hz, 1H),
7.59–7.47 (3H), 7.43 (m, 2H), 7.33 (m, 1H), 6.97 (d, J=
8.5 Hz, 1H), 3.94 (s, 3H); 13C NMR (75 MHz, CDCl3): d=
155.4 (0), 139.5 (0), 135.3 (0), 132.0 (1), 128.9 (1), 127.3 (1),
127.1 (1), 126.8 (1), 112.2 (1), 112.1 (0), 56.4 (3); MS (EI):
m/z=139 (48%), 219 (25%), 247 (43%), 262 ([M]+, 100%);
HR-MS (EI): m/z=261.9978, calcd. for C13H11OBr+ [M]+:
261.9993; anal. calcd. for C13H11OBr: C 59.3%, H 4.2%;
found: C 59.4%, H 4.0%; IR (KBr): n=1595 (m), 1484 (s),
1282 (s), 1270 (s) cmÀ1.
1
(10%)]. H NMR (300 MHz, CDCl3): d=7.72 (d, J=8.6 Hz,
2H), 7.64 (d, J=8.6 Hz, 2H), 7.56 (dd, J=8.9, 5.2 Hz, 2H),
7.17 (dd, J=8.7, 8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3):
4
d=163.3 (d, 1JC,F =249 Hz, 0), 144.7 (0), 135.4 (d, JC,F
=
3.3 Hz, 0), 132.7 (1), 129.1 (d, 3JC,F =8.3 Hz, 1), 127.6 (1),
118.9 (0), 116.2 (d, JCF =21.7, 1), 111.0 (0); MS (EI): m/z=
2
85 (5%), 98 (4%), 170 (9%), 197 ([M]+, 100%); HR-MS
(EI): m/z=197.0636, calcd. for C13H8NF+ [M]+: 197.0641.
4-Fluoro-4’-nitrobiphenyl (8fc):[73] Following the general
procedure, 8fc was obtained from 1f (270 mg, 1.5 mmol)
and 7c (303 mg, 1.5 mmol) as a colourless solid; yield:
200 mg (61%), mp 124–1288C, along with 9c [yield: 28 mg
1
(10%)]. H NMR (300 MHz, CDCl3): d=8.29 (d, J=8.9 Hz,
2H), 7.69 (d, J=8.9 Hz, 2H), 7.60 (dd, J=8.9 Hz, 5.2, 2H),
7.19 (dd, J=8.6, 8.6 Hz, 2H); 13C NMR (75 MHz, CDCl3):
1
d=163.4 (d, JC,F =250 Hz, 0), 147.2 (0) 146.7 (0), 135.0 (d,
3
4JC,F =3.3 Hz, 0), 129.3 (d, JC,F =8.3 Hz, 1), 127.7 (1), 124.3
2
(1), 116.3 (d, JC,F =21.7 Hz, 1); MS (EI): m/z=159 (33%),
170 (79%), 187 (40%), 217 ([M]+, 100%); HR-MS (EI):
m/z=217.0544, calcd. for C12H8NO2F+ [M]+: 217.0539.
4’-Chloro-3-nitrobiphenyl (8hd):[79] Following the general
procedure, 8hd was obtained from 1h (255 mg, 1.5 mmol)
and 7d (344 mg, 1.5 mmol) as a colourless solid; yield:
84 mg (24%), mp 90–938C, along with 9d [yield: 59 mg
(16%)]. 1H NMR (300 MHz, CDCl3): d=8.39 (dd, J=1.9,
1.9 Hz, 1H), 8.20 (ddd, J=8.2, 2.2, 1.0 Hz, 1H), 7.87 (ddd,
J=7.8, 1.7, 1.0 Hz, 1H), 7.61 (dd, J=8.0, 8.0 Hz, 1H), 7.55
(d, J=8.7 Hz, 2H), 7.45 (d, J=8.7 Hz, 2H); 13C NMR
(75 MHz, CDCl3): d=148.8 (0), 141.6 (0), 137.1 (0), 134.9
(0), 132.9 (1), 129.9 (1), 129.4 (1), 128.4 (1), 122.4 (1), 121.8
(1); MS (EI): m/z=126 (8%), 152 (100%), 187 (9%), 233
([M]+, 61%); HR-MS (EI): m/z=233.0250, calcd. for
C12H8NO235Cl+ [M]+: 233.0244.
1-(4’-Methoxybiphenyl-4-yl)ethanone (8ab):[76] Following
the general procedure, 8ab was obtained from 1a (266 mg,
1.5 mmol) and 7b (321 mg, 1.5 mmol) as a colourless solid;
yield: 138 mg (41%); mp 155–1588C, along with 9b [yield:
1
42 mg (13%)]. H NMR (300 MHz, CDCl3): d=8.01 (d, J=
8.5 Hz, 2H), 7.64 (d, J=8.5 Hz, 2H), 7.58 (d, J=8.8 Hz,
2H), 7.00 (d, J=8.8 Hz, 2H), 3.86 (s, 3H), 2.63 (s, 3H);
13C NMR (75 MHz, CDCl3): d=197.8 (0), 160.0 (0), 145.5
(0), 135.4 (0), 132.4 (0), 129.0 (1), 128.5 (1), 126.7 (1), 114.5
(1), 55.5 (3), 26.7 (3); MS (EI): m/z=139 (26%), 211
(100%), 226 ([M]+, 76%); HR-MS (EI): m/z=226.0980,
+
calcd. for C15H14O2 [M]+: 226.0994.
Adv. Synth. Catal. 2013, 355, 463 – 476
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
473

Bernd Schmidt and Renꢀ Berger
FULL PAPERS
1-[4-(Naphthalen-2-yl)phenyl]ethanone (8ae):[80] Follow-
ing the general procedure, 8ae was obtained from 1a
(266 mg, 1.5 mmol) and 7e (351 mg, 1.5 mmol) as a colourless
solid; yield: 189 mg (51%); mp 136–1398C. 1H NMR
(300 MHz, CDCl3): d=8.11–8.05 (3H), 7.99–7.85 (3H), 7.82
(d, J=8.5 Hz, 2H), 7.76 (dd, J=8.5, 1.8 Hz, 1H), 7.60–7.48
(2H), 2.66 (s, 3H); 13C NMR (75 MHz, CDCl3): d=197.7
(0), 145.6 (0), 137.1 (0), 135.8 (0), 133.5 (0), 133.0 (0), 128.9
(1), 128.7 (1), 128.3 (1), 127.6 (1), 127.4 (1), 126.5 (1), 126.4
(1), 126.3 (1), 125.1 (1), 26.6 (3); MS (EI): m/z=116 (13%),
202 (72%), 231 (100%), 246 ([M]+, 78%); HR-MS (EI): m/
z=246.1036, calcd. for C18H14O+ [M]+: 246.1045.
After addition of tert-BuONO (0.18 mL, 1.5 mmol) the solu-
tion was stirred for 1 h at this temperature. To the reaction
was added PdACTHUNRGTNEUNG(OAc)2 (17 mg, 5 mol%). After 15 min. tolane
(535 mg, 3.0 mmol) was added. The solution was stirred for
12 h at room temperature. The reaction was quenched with
water (20 mL) and extracted with MTBE (60 mL). The com-
bined organic layers were dried with MgSO4, filtered and
concentrated under reduced pressure. The residue was puri-
fied by column chromatography on silica using hexane-
MTBE (5:1) mixtures as eluent.
7-Nitro-8-oxo-1,2,3,4-tetraphenyl-spiroACTHNUTRGNE[NUG 4.5]deca-1,3,6,9-
tetraene (11k): Following the general procedure, 11k was
obtained from 1k (294 mg, 1.5 mmol) as a yellow solid;
yield: 444 mg (60%); mp 2098C. Analytical data are identi-
cal to those reported previously.[65]
(E)-1-(4-Styrylphenyl)ethanone (6aa):[72] Following the
general procedure, 6aa was obtained from 1a (266 mg,
1.5 mmol) and 7f (315 mg, 1.5 mmol) as a colourless solid;
yield: 247 mg (74%); mp 140–1468C. All analytical data are
identical to those reported above for the product obtained
via deacetylation–diazotation–Heck reaction.
7-Bromo-8-oxo-1,2,3,4-tetraphenyl-spiroACTHNUTRGNE[NUG 4.5]deca-1,3,6,9-
tetraene (11m): Following the general procedure, 11m was
obtained from 1m (345 mg, 1.5 mmol) as a colourless solid;
yield: 308 mg (39%); mp 2438C. Analytical data are identi-
cal to those reported previously.[65]
Analytical Data for the Side Products 9
Methyl
8-oxo-1,2,3,4-phenyl-spiroACTHUGNETRNNU[G 4.5]deca-1,3,6,9-tet-
Biphenyl (9a):[73] colourless solid; mp 698C. 1H NMR
(300 MHz, CDCl3): d=7.62 (m, 4H), 7.46 (m, 4H), 7.36 (tt,
J=7.3, 2.2 Hz, 2H); 13C NMR (75 MHz, CDCl3): d=141.4
(0), 128.8 (1), 127.3 (1), 127.3 (1); MS (EI): m/z=57 (54%),
98 (13%), 154 ([M]+, 100%); HR-MS (EI): m/z=154.0770,
calcd. for C12H10+ [M]+: 154.0783.
raene-7-carboxylate (11p): Following the general procedure,
11p was obtained from 1p (313 mg, 1.5 mmol) as a colour-
less; solid; yield: 288 mg (38%); mp 1268C. Analytical data
are identical to those reported previously.[65]
8-Oxo-1,2,3,4-tetraphenyl-spiroACTHNUGTRNEUNG[4.5]deca-1,3,6,9-tetraene
(11b): Following the general procedure, 11b was obtained
from 1b (248 mg, 1.5 mmol) as a colourless solid; yield:
229 mg (34%). Alternatively, 11b was obtained from 1q
(362 mg, 1.5 mmol) as a colourless solid; yield: 249 mg
(37%); mp 2438C. Analytical data are identical to those re-
ported previously.[65]
4,4’-Dimethoxybiphenyl (9b):[81] colourless solid; mp 179–
1
1838C. H NMR (300 MHz, CDCl3): d=7.48 (d, J=8.8 Hz,
4H), 6.96 (d, J=8.8, 4H), 3.85 (s, 6H); 13C NMR (75 MHz,
CDCl3): d=158.8 (0), 133.6 (0), 127.8 (1), 114.3 (1), 55.5 (3);
MS (EI): m/z=171 (27%), 199 (76%), 214 ([M]+, 100%);
+
HR-MS (EI): m/z=214.0987, calcd. for C14H14O2 [M]+:
214.0994.
4,4’-Difluorobiphenyl (9c):[82] colourless solid; mp 90–
928C. 1H NMR (300 MHz, CDCl3): d=7.51 (dd, J=8.8,
5.3 Hz, 4H), 7.14 (dd, J=8.7, 8.7 Hz, 4H); 13C NMR
Acknowledgements
1
(75 MHz, CDCl3): d=162.2 (d, JC,F =246 Hz, 0), 136.5 (d,
3
2
4JC,F =3.3 Hz, 0), 128.7 (d, JC,F =8.1 Hz, 1), 115.8 (d, JC,F
=
We thank Evonik Oxeno for generous donations of solvents
and Umicore (Hanau, Germany) for generous donations of
palladium precatalysts.
21.5 Hz, 1); MS (EI): m/z=57 (100%), 149 (94%), 190
([M]+, 22%); HR-MS (EI): m/z=190.0581, calcd. for
+
C12H8F2 [M]+: 190.0594.
3,3’-Dinitrobiphenyl (9d):[83] colourless solid; mp 202–
2038C. 1H NMR (300 MHz, CDCl3): d=8.57 (dd, J=1.9,
1.9 Hz, 2H), 8.35–8.24 (4H), 7.82 (dd, J=8.0, 8.0 Hz, 2H);
13C NMR (75 MHz, CDCl3): d=148.4 (0), 139.4 (0), 133.6
(1), 130.6 (1), 123.1 (1), 121.7 (1); MS (EI): m/z=152
(59%), 198 (19%), 244 ([M]+, 100%); HR-MS (EI): m/z=
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