Exploring the selectivity of the Suzuki-Miyaura cross-coupling reaction in the synthesis of arylnaphthalenes

Article abstract of DOI:10.1016/j.tet.2010.11.081

A series of 1-arylnaphthalenes and 1,8-diarylnaphthalenes were synthesized by the Suzuki-Miyaura cross-coupling methodology showing significant differentiation in the yields and selectivity between aryl rings with electron donating (higher yields), and el

Full text of DOI:10.1016/j.tet.2010.11.081

Tetrahedron 67 (2011) 689e697
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Exploring the selectivity of the SuzukieMiyaura cross-coupling reaction
in the synthesis of arylnaphthalenes
*
ꢀ
Carlos F.R.A.C. Lima, Jose E. Rodriguez-Borges, Luís M.N.B.F. Santos
ˇ
~
Centro de Investigac¸ ao em Química, Departamento de Química e Bioquímica, Faculdade de Ciencias da Universidade do Porto, Rua do Campo Alegre, 687, P-4169-007 Porto, Portugal
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 October 2010
Received in revised form 18 November 2010
Accepted 25 November 2010
Available online 1 December 2010
A series of 1-arylnaphthalenes and 1,8-diarylnaphthalenes were synthesized by the SuzukieMiyaura
cross-coupling methodology showing significant differentiation in the yields and selectivity between aryl
rings with electron donating (higher yields), and electron withdrawing substituents (lower yields). These
results strongly support the relation between the nucleophilicity of the boronate complex and its re-
activity, and emphasize the importance of the transmetalation step in the overall efficiency of this cross-
coupling reaction. The results obtained with non-symmetric 1,8-diarylnaphthalenes indicate preference
for arylation of an already arylated species (the 1-aryl-8-bromonaphthalene intermediate) over mono-
Keywords:
SuzukieMiyaura cross-coupling
Selectivity
Arylnaphthalenes
Substituent effect
Nucleophilicity
arylation of 1,8-dibromonaphthalene. Evidences for the existence of intramolecular Pd/p and aromatic
interactions in some Pd(II) complexes were found.
Ó 2010 Elsevier Ltd. All rights reserved.
Aromatic interactions
1. Introduction
The SuzukieMiyaura cross-coupling reaction has received much
attention in the past years due to it’s versatility in the formation of
CeC bonds.1,2 The reaction is generally green, with good yields and
selectivity. The great variety of commercially available boron and
halogenated compounds enables the very attractive building-blocks
philosophy. In this work, a systematic study on the synthesis of
some 1-arylnaphthalenes and structurally symmetric and non-
symmetric 1,8-diarylnaphthalenes was carried out (Figs. 1 and 2).
Fig. 2. SuzukieMiyaura reaction scheme for the synthesis of 1,8-diarylnaphthalenes.
The work of Liu et al.,3 respecting the synthesis of biaryls and
polyaryls, served as a basis for the conditions employed in this
study. The general accepted reaction mechanism2 involves three
main steps: an oxidative addition of the halogenated species to the
Pd catalyst, followed by a transmetalation step, where the organic
group attached to the activated boron species is transferred to the
metal, and finally a reductive elimination that yields the coupling
product and regenerates the catalyst. In the transmetalation step,
the boron species must be activated with a base, in order to increase
its nucleophilicity and give a clean reaction.2,4 Thus, the trans-
metalation reaction between the Pd catalyst and the organoboron
species may be fastened by the increased nucleophilicity of the later.
Fig. 3 depicts the reaction’s catalytic cycle for the case of mono-
arylation of 1-bromonaphthalene, with the conditions employed in
this work. It is important to keep in mind that the role of the base in
Fig. 1. SuzukieMiyaura reaction scheme for the synthesis of 1-arylnaphthalenes.
* Corresponding author. Tel.: þ351 220402536; fax: þ351 220402520; e-mail
address: lbsantos@fc.up.pt (L.M.N.B.F. Santos).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.11.081

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C.F.R.A.C. Lima et al. / Tetrahedron 67 (2011) 689e697
Table 1
Reaction yield (%) for the mono-arylation of 1-bromonaphthalene and symmetric
di-arylation of 1,8-dibromonaphthalene by the SuzukieMiyaura cross-coupling, and
Hammett constants, smeta and spara, as a function of the R group in the phenyl-
boronic acid
P
R
Yielda (%)
Mono-
smeta
spara
s
Di-
4-N(CH3)2
3-OCH3
4-OCH3
4-Ph
71
77
85
81
87
d
d
ꢀ0.83
d
ꢀ0.83
0.12
ꢀ0.27
ꢀ0.01
0
0.12
d
71
55
60
ꢀ0.27
ꢀ0.01
0
d
H
76
d
4-CHO
4-COOH
4-CN
3,4-diOCH3
3-CHO-4-OCH3
Ar]C6F5
56
59
58
75
57
d
d
0.42
0.45
0.66
ꢀ0.27
ꢀ0.27
d
0.42
0.45
0.66
ꢀ0.15
0.08
d
d
30
76
53
d
0.12
0.35
d
66
no reaction
no reaction
a
Isolated yield corrected for sample purity.
Fig. 3. The SuzukieMiyaura reaction catalytic cycle adapted to the conditions
employed in this work.
this mechanism is not yet fully understood.2,4 The di-arylation of
1,8-dibromonaphthalene has analogous reaction mechanisms, one
for each arylation step. The main objective of this study is to explore
the effect of the substituent R in the reaction outcome and use
these findings to gain some insights on the mechanistic pathway.
Thus, it was imperative to keep all the other reaction variables
(stoichiometry, solvent, temperature, reaction time, base, catalyst,
and extraction methodology) as constant as possible. In this way
the transmetalation step will be the main focus of our attention,
since it is expected that the substituents R will not influence the
other catalytic steps to any considerable extent. Additionally, the
1,8-diarylnaphthalene system is particularly interesting due to
the existence of two equivalent adjacent coupling positions that
can be used to explore the effect of intramolecular interactions in
the reaction mechanism.
Fig. 4. Homocoupling reaction involving the boronic acid derivatives. The condensa-
tion product was identified in some cases.
keeping the reaction conditions essentially constant. Table 1 sum-
marizes these results. As can be seen the % yield of the reaction is
larger for electron donating groups (EDG) and lower to electron
withdrawing groups (EWG). The R¼H compound, 1-phenyl-
naphthalene, establishes the scale’s zero, so EDG’s improve the
reaction outcome relative to the neutral situation, whereas, EWG’s
have the opposite effect. This effect is substantially enhanced for
the pentafluorophenyl case, where no detectable 1-(penta-
fluorophenyl)naphthalene was formed. The trend observed in re-
action yield with the susbtituent’s electron/donor character can in
principle be correlated with a Hammett plot. These results are
presented in Fig. 5. The % yield of the SuzukieMiyaura reaction in
the experimental conditions adopted in this work clearly have
some dependency with substituent electron/donor strength, how-
ever this is not the only factor affecting the reaction outcome.
Solubility aspects and competing undesirable side reactions may
also play a role in defining the trend observed in Fig. 5. For example,
in the synthesis of the dimethylamino derivative (the strongest
EDG), it was observed that the reaction mixture acquired a green
tone, in addition to the custom dark-grey color. During the ex-
tractions, the aqueous phase was green, suggesting the formation
of a hydrophilic impurity. This is an indication that the % yield of
N,N-dimethyl-4-(naphthalene-1-yl)aniline (R¼N(CH3)2) may be
lowered by the presence of a significant side-reaction, what could
explain the deviation from the correlation trend. Steric interactions
in 1-arylnaphthalenes, relative to the naphthylephenyl torsion,
prevent a significant conjugation between the aryl and naphthyl
moieties. Thus, the 1-arylnaphthalene molecule can roughly be
viewed as two independent, non-interacting aromatic groups.
Sustain for this statement comes from the 1H NMR spectra of the
1-arylnaphthalenes synthesized in this work. They are very alike in
what concerns the naphthalene protons, presenting similar
chemical shifts and coupling constants. This fact supports the ob-
servation that thermodynamic considerations aren’t important for
the trend observed in the reaction % yield. By this reasoning we can
2. Results and discussion
The global results obtained for the SuzukieMiyaura cross-cou-
pling reaction, concerning the mono- (Fig. 1) and diary-
lnaphthalenes (Fig. 2) are presented in Table 1, alongside with the
substituent Hammett constants, smeta and spara, for the groups
P
considered in this work.5
s is the sum of all the substituents
contributions, considered additive for the cases where more than
one R group is presented. The Hammett constants are referred to
the arylboronic acids. In some cases the presence of the homo-
coupling product of the boronic acid (Fig. 4) was detected by 1H
NMR and by GC (gas chromatography) analysis against a known
sample of the compound. This is not surprising since the reactions
were carried out in the presence of air, hence with O2, which is
known to induce homocoupling in boronic acids.6 For example,
biphenyl was formed in the synthesis involving phenylboronic acid,
and p-quaterphenyl was detected in the synthesis were biphen-4-
ylboronic acid was used.
2.1. 1-Arylnaphthalenes
Starting from 1-bromonaphthalene the reaction outcome with
various para-substituted phenylboronic acids was monitored,

C.F.R.A.C. Lima et al. / Tetrahedron 67 (2011) 689e697
691
argue that kinetic factors play the main role in defining the ob-
served trend. In a mechanistically point of view, a perfect correla-
tion was only to be expected if the influence of the substituent
group is in the same way in every steps of the global synthetic
process (reaction of interestþside reactionsþother physical/chem-
ical features), or is active in one-step and silent in all the others.
dubious; however its addition doesn’t disturb the correlation to any
significant extent. In 1,8-diarylnaphthalenes the two parallel aryl
rings can interact via intramolecular interactions, stabilizing or
destabilizing the reaction product.7ꢀ9 Nevertheless, this fact alone
should not be responsible for the observed reaction outcomes, and
in analogy with the results obtained for 1-arylnaphthalenes, the
kinetic factors appear to be the more determinant ones in defining
the trends observed in this work so far. As for 1-arylnaphthalenes,
100
95
2
R
= 0.802
2
R
85
90
80
70
60
50
= 0.832
75
65
55
45
35
25
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
0.8
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
0.8
Hammett
Hammett
P
P
Fig. 5. Isolated reaction yield (%) as a function of
1-arylnaphthalenes by the SuzukieMiyaura reaction.
s (Hammett) for the synthesis of
Fig. 6. Isolated reaction yield (%) as a function of
1,8-diarylnaphthalenes by the SuzukieMiyaura reaction.
s (Hammett) for the synthesis of
the starting product 1,8-dibromonaphthalene was never detected
in considerable amounts; %(m/m) <1 by GC analysis of the impure
products obtained. This fact, together with the high yields obtained
in the work of Liu et al.3 using similar reaction conditions, are
a strong indication that practically all the brominated reagent re-
acts completely. Hence, the existence of side reactions should be
responsible for not achieving yields (%) near 100%. In this way the
presence of EDGs have the effect of increasing the rate of the de-
sired SuzukieMiyaura coupling reaction relative to the unknown
side reactions. One possible important side-reaction may be the
homocoupling of the boronic acid, which removes it from the re-
action media at a definite rate, competing kinetically with the
transmetalation step.
The present results and the direct comparison between the
outcomes for 3-methoxy (yield (%)¼77) and 4-methoxy (yield (%)¼
85) substituents are a good sign of the importance of conjugation
effects in reaction intermediates involving the substituted aryl.
These intermediates only participate in the transmetalation and
reductive elimination steps. Hence, R can only cause significant
kinetic differentiation in these steps, the transmetalation one being
the more obvious choice. The starting reagent 1-bromonaph-
thalene was not detected in any significant amount in all the re-
actions that were carried out: %(m/m)<1 by GC analysis of the
impure products obtained.
2.2. 1,8-Diarylnaphthalenes
As for mono-aryl naphthalenes the same approach was con-
sidered for the synthesis of 1,8-diarylnaphthalenes. Table 1 sum-
marizes the experimental results. Clearly, the same dependence of
2.3. Non-symmetric 1,8-diarylnaphthalenes
Various approaches were used in order to explore the synthesis
of structurally non-symmetric 1,8-diarylnaphthalenes. In these
situations three different products can be produced: the two pos-
sible symmetric diarylnaphthalenes and the non-symmetric dia-
rylnaphthalene (Fig. 7). The molar fraction of each product was
determined by GC. For each symmetric 1,8-diarylnaphthalene the
peak area was related to molar concentration by calibrating the
signal with solutions of known concentrations. The non-symmetric
compound was taken to be the one corresponding to the peak
between the two known peaks (intermediate retention time). Our
only concern was to access the selectivity of the SuzukieMiyaura
reaction when more than one coupling product is possible. In this
% yield with the substituent identity was found. Correlation with
P
s
(Hammet) constant is statistically relevant, as shown in Fig. 6.
Again, we must be aware of the existence of competing side re-
actions, or other unexpected phenomenon’s when analyzing this
data. For example, in the case of 1,8-di([1,10-biphenyl]-4-yl)naph-
thalene (R¼Ph), the synthesis was carried out in a different solvent,
toluene/water/EtOH (2:1:1), rather than in DMF/water (1:1). In the
last case the yield was only of 40%. The use of a more apolar media
increased the yield to 55%. This fact may be associated with solu-
bility issues of reaction intermediates. The difference in reaction
solvent makes the inclusion of this case in the Hammet correlation
Fig. 7. SuzukieMiyaura reaction scheme for the synthesis of non-symmetric 1,8-diarylnaphthalenes. The indices f1, f2 and f3 represent the molar fraction of each possible coupling
product.

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C.F.R.A.C. Lima et al. / Tetrahedron 67 (2011) 689e697
fashion, the final mixture was extracted with ethyl acetate and the
organic phase washed, as it was made for all the other synthesis,
except for the separation of the different reaction products, which
was not carried out. We assume that equal retention times in GC
and the success in the preceding synthetic approaches (Sections 2.1.
and 2.2.) suffice to prove the product identity. By chromatographic
considerations it seems justifiable to ascribe the middle peak to the
non-symmetric product.
2.3.1. Effect of addition sequence. First, we began by exploring the
effect of addition sequence of the boronic acid on the synthesis
of non-symmetric diarylnaphthalenes. These results are pre-
sented in Table 2. In entry 1, 1,2 equiv of phenylboronic acid was
added first, and after 3 h 3 equiv of biphen-4-ylboronic acid was
added. The reaction was allowed to continue at 100 ꢁC for 4 h. In
entry 2 the same procedure was employed, but toggling the
addition sequence. Entry 3 is the normal case of simultaneous
addition. As shown in Table 2, the sequence of addition in-
fluences the reaction outcome, clearly favoring the first addition
product. Another interesting observation is that the second ad-
dition product was formed in very low quantities, even given the
fact that the corresponding boronic acid was presented in higher
molar equivalents (3 equiv compared to 1.2 equiv). This is a clear
indication that thermodynamics alone is not capable of
explaining the observed results, and that the reverse reaction
occurs in a very small extent. Also, we must conclude that di-
arylation of 1,8-dibromonaphthalene is preferred over mono-
arylation, or else the non-symmetric product would be formed
with higher selectivity.
Fig. 8. The results obtained show preferred arylation of the 1-aryl-8-bromonaph-
thalene species over 1,8-dibromonaphthalene.
with care due to the presence of significant amounts of unreacted
1,8-dibromonaphthalene. This subject will be discussed in more
detail in a following section.
Table 2
Reaction selectivity (mol %) for the non-symmetric di-arylation of 1,8-di-
bromonaphthalene by the SuzukieMiyaura cross-couplingeeffect of addition
sequence
2.3.2. Effect of temperature. Second we have studied the effect of
temperature on the reaction selectivity. These reactions were car-
ried out in the usual way, changing only the temperature at which
the reaction mixture was heated after addition of all the reactants.
By a qualitative inspection of Table 3 we can conclude that, in the
interval considered, temperature has no meaningful effect on se-
lectivity. Since, in all the cases, the reaction mixture was heated to
the desired temperature only after addition of the base, K2CO3, we
may conclude that the reaction proceeds rapidly at room temper-
ature and the reverse reaction occur in a negligible extent. The
mol % of unreacted 1,8-dibromonaphthalene was negligible in all
the cases.
Entry
1
Addition sequence
1steHePheB(OH)2
2ndePhePheB(OH)2
Ratioa/mol %
PheH/PheHe81
PhePh/PhePhe1
PheH/PhePhe18
Unreacted 1,8-diBrbꢀ11
PheH/PheHe11
PhePh/PhePh-74
PheH/PhePhe15
Unreacted 1,8-diBrbꢀ17
PheH/PheHe18
1stePhePheB(OH)2
2ndeHePheB(OH)2
2
3
Simultaneous
PhePh/PhePhe34
PheH/PhePhe48
Unreacted 1,8-diBrbꢀ1
a
Table 3
Measured by GC analysis of the reaction mixture after extraction with AcOEt.
Calculated excluding all the other peaks.
Reaction selectivity (mol %) for the non-symmetric di-arylation of 1,8-di-
bromonaphthalene by the SuzukieMiyaura cross-couplingeeffect of temperature
b
mol % of unreacted 1,8-dibromonaphthalene (relative to the three products
formed).
Temperature/ꢁC
25
Ratioa/mol %
PheH/PheHꢀ17
PhePh/PhePhꢀ36
PheH/PhePhꢀ47
PheH/PheHꢀ19
PhePh/PhePhꢀ33
PheH/PhePhꢀ48
PheH/PheHꢀ18
PhePh/PhePhꢀ33
PheH/PhePhꢀ49
A statistical analysis, assuming irreversible reaction steps and
the above cited stoichiometry, predicts an outcome of 36% for the
symmetric product formed by di-arylation from the first addition of
boronic acid, 16% for the symmetric product formed from the sec-
ond addition, and 48% for the non-symmetric product.
As can be seen in Table 2 the ratio observed is of 81/1/18 for
entry 1 and 74/11/15 for entry 2, significantly differing from the
statistically unbiased prediction of 36/16/48 (detailed statistical
analysis is presented in the Supplementary data). This fact shows
a preference for the formation of the symmetric first addition
product, indicating the existence of some feature that favors the
arylation of an already arylated bromonaphthalene (the 1-aryl-8-
bromonaphthalene species) in comparison with 1,8-dibromo-
naphtalene (Fig. 8). Nonetheless these results should be regarded
70
120
a
Measured by GC analysis of the reaction mixture after extraction with AcOEt.
Calculated excluding all the other peaks.
2.3.3. Effect of the substituent R. Third, we have inspected the effect
of the substituent R. The results are given on Table 4. All the re-
actions were carried out by the previously described procedure,
and with simultaneous addition of the two boronic acids, in

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693
Table 4
Reaction selectivity (mol %) for the non-symmetric di-arylation of 1,8-di-
bromonaphthalene by the SuzukieMiyaura cross-couplingeeffect of substituent
R1/R2
H/Ph
Ratioa/mol %
PheH/PheHe18
PhePh/PhePhe34
PheH/PhePhe48
OCH3/CHO
N(CH3)2/CN
PheOCH3/PheOCH3ꢀ87
PheCHO/PheCHOe0
PheOCH3/PheCHOe13
PheN(CH3)2/PheN(CH3)2ꢀ89
PheCN/PheCNe0
PheN(CH3)2/PheCNe11
a
Measured by GC analysis of the reaction mixture after extraction with AcOEt.
Calculated excluding all the other peaks.
equimolar amounts. These conditions allow for a good competition
scenario with respect to arylation. The statistically unbiased out-
come is easily demonstrated to be 25/25/50 for R1,R1/R2,R2/R1,R2,
respectively, as the formation of the non-symmetric product (R1,R2)
is twice as probable as the formation of each symmetric product
(R1,R1 and R2,R2). In this way, for the case of PheH/PhePh, where
the distinction between the two substituents in terms of electronic
effects are less pronounced, the observed ratio was not very far
from the statistical outcome, with, however some preference for
the PhePh/PhePh product relative to the PheH/PheH one. This fact
can be related with the weak donor character of the phenyl group,
increasing a little the rate of the transmetalation step. For the other
two cases the observed outcome is radically different from the
expected ratio, with a clearly preference for the formation of the
products that correspond to the electron donor substituent, eOCH3
and eN(CH3)2. This is in agreement with the results obtained so far,
supporting the view that the transmetalation step is significantly
fastened by the presence of electron donor substituents in the para-
position of phenylboronic acids.
These results also make less favorable the hypothesis of the
distinction to be noted in the reductive elimination step, where the
formation of the coupling product from the corresponding complex
intermediate would be fastened by the presence of EDGs. This is so,
because this step does not impose any selectivity in the reaction,
considering that it is relatively fast compared with the total re-
action time. If we regard the transmetalation step as independent
of the R group, the respective Pd complexes would be populated in
a pure statistical ratio and the corresponding products formed at
different rates by reductive elimination but in a finite time,
reflecting the statistical outcome, which is not the case.
Fig. 9. Homodesmic schemes for the evaluation of the energetic preference for mono-
or di-arylation, at the SCS-MP2 level of theory.
overall reaction and the selected homodesmic schemes can be
made since the only differences between the two complete cycles
(neglecting reaction intermediates) are the brominated reagent and
the arylated product. Looking at the reaction mechanism (Fig.1) the
most reasonable explanation for the preference of di-arylation
should reside in the oxidative addition step, where the brominted
reagent complexes with Pd(0).
The results obtained point to a faster reaction for the addition of
the mono-arylated species (1-aryl-8-bromonaphthalene) relative
to the addition of the non-arylated species (1,8-dibromonaph-
thalene), yielding a trans Pd(II) complex,2,11 involving the formation
of a metal complex with the aryl ring in close proximity to the Pd
atom, versus one with the bromine atom in close contact to the
metal center. This indicates that either an attractive Pd/
p intra-
molecular interaction, or a Pd/Br repulsive interaction, or a com-
bination of both, exists and are responsible for the observed
reaction selectivity (Fig. 10), by differentiating energetically the
respective reaction intermediates and transition states. Another
2.4. Mechanistic insights
An ab-inito computational study using the SCS-MP2/cc-pVDZ
level of theory10 was performed in order to provide some support
for the experimental results, concerning the observed preference
for di-arylation over mono-arylation (Section 2.3.1, see Fig. 8). The
results for the gas phase homodesmic schemes, presented in Fig. 9,
indicate that the energetic distinction between the two outcomes
should be of little importance. In this scheme we picture the two
possible reaction pathways for a molecule of 1-phenylnaphthalene,
here mimicking the arylboronic acid. This molecule can either
arylate 1,8-dibromonaphthalene or the mono-arylated 1-bromo-8-
phenylnaphthalene, to yield the respective products of reaction.
The relative energies of the two possible arylation products (dif-
ference of ca. 2 kJ/mol) do not justify the observed selectivity based
on the energetic differentiation. This is an indication that the cyclic
mechanism for mono-arylation (yielding 1-bromo-8-phenyl-
naphthalene) is not thermodynamically significantly distinguished
from the cyclic mechanism for di-arylation (yielding 1,8-diphe-
nylnaphthalene). A direct relation between the SuzukieMiyaura
Fig. 10. Schematic representation of the intramolecular interactions that can favor
oxidative addition of the mono-arylated naphthalene over 1,8-dibromonaphthalene.

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C.F.R.A.C. Lima et al. / Tetrahedron 67 (2011) 689e697
However, for this hypothesis to be valid one must assume that
the oxidative addition step is reversible to the extent that the
equilibrium is rapid enough to ensure a dynamic distribution of
BrePd(II)eAr species ready to undergo transmetalation. If this is
not so and we assume that no kinetic distinction is made in the
oxidative addition step, kOAzk’OA, then, even if kTsk’T, (1) and (2)
will form in the statistical ratio, and eventually react via trans-
metalation, yet at different rates (see Fig. 12). Nevertheless, virtu-
ally all of them will react and yield the respective products
according to the statistical expected outcome.
The irreversibility of the oxidative addition step is a very plau-
sible scenario for aryl halides and Pd,14,15 making more likely the
hypothesis that considers the existence of significant kinetic dif-
ferentiation in this step, in agreement with the results obtained in
this work. However, for explaining the preference for the formation
of the PhePh/PhePh product over the PheH/PheH one, when si-
multaneous addition of the boronate reagents is considered, as
noted in Section 2.3.3 (see Table 4), this hypothesis is more feasible,
since in this case differentiation is meaningful in transmetalation.
In this case, the formation of the Pd complex presented in Fig. 13
will be favored relative to the other possible complexes, because
the two additional aromatic rings enhance the intramolecular ar-
omatic interactions, thus increasing the amount of the PhePh/
PhePh product formed.
Fig. 11. Schematic representation of the intramolecular aromatic interaction in the
trans intermediate formed after transmetalation for the mono-arylated species.
3. Conclusions
It was found that the nucleophilicity of the boronate species
strongly influences the reaction yield and selectivity when the re-
action conditions employed in this work are considered. Electron
donor substituents in the boronic acid improve the reaction out-
come, whereas electron withdrawing substituents show the op-
posite trend. The effect of addition sequence, temperature and the R
group in boronic acid was explored using a competitive arylation
methodology. The more consistent conclusions that can be drawn
from this study are:
Fig. 12. Schematic representation of the two mechanistic pathways that lead to the
formation of the mono- and di-arylated products.
possible explanation may be the existence of an intramolecular
aromatic interaction in the trans Pd(II) complex2,11 formed after
transmetalation, that is, present only in the mono-arylated species
and would increase the rate of this step relative to the one involving
the dibromo species. The geometry of the complex permits the
phenyl rings to interact in a parallel displaced fashion, as illustrated
in Fig. 11. Although the geometric positioning between the two
- A preference for the arylation of the 1-aryl-8-bromonaphthalene
species over 1,8-dibromonaphthalene was observed, that can be
due to specific intramolecular aromatic interactions in some Pd
(II) intermediates. Thermodynamic considerations are unable to
justify the observed selectivity. The stepwise addition of boronic
acids is therefore a bad strategy for the synthesis of non-sym-
metric 1,8-diarylnaphthalenes by this methodology.
benzene rings is not the ideal alignment for a p/p interaction (the
displacement between the ring centers is too large), it has still as-
sociated significant stabilizing interaction energy.12,13
Fig. 13. The four possible trans intermediates formed after transmetalation for the SuzukieMiyaura reaction involving phenylboronic acid (R¼H) and biphen-4-ylboronic acid
(R¼Ph). The observed outcome ratio was of 18/34/48 for PheH/PheH, PhePh/PhePh, and PheH/PhePh, respectively.

C.F.R.A.C. Lima et al. / Tetrahedron 67 (2011) 689e697
695
- The reaction seems to take place very rapidly at room tem-
perature and the reverse reaction occurs in a negligible extent.
- The reaction mechanism clearly favors the formation of aryl-
naphthalenes with EDGs, in detriment of arylnaphthalenes
with EWGs.
under reduced pressure to yield white crystals of the titled com-
1
pound; H NMR (400 MHz, CDCl3, 300 K, TMS) 8.07 (1H, d, 80-H,
J¼8.4 Hz), 7.94 (1H, d, 20-H, J¼7.6 Hz), 7.85 (1H, d, J¼8.2 Hz),
7.57e7.44 (6H, m), 6.92 (2H, d, 2-H, J¼8.7 Hz), 3.08 [6H, s, N(CH3)2];
13C NMR (100.6 MHz, CDCl3, 300 K) 150.7, 141.4, 134.9, 132.9, 131.7,
129.7, 129.1, 127.8, 127.7, 127.3, 126.6, 126.5, 126.4, 113.2, 41.6. CCDC
718939.
The results obtained in this work are an experimental insight
concerning the mechanism of the SuzukieMiyaura cross-coupling
reaction, that represent an experimental support for the current
view that increased nucleophilicity of the boronate species in-
creases the rate of the transmetalation step, and contribute to
a better overall understanding of this synthetic methodology.
4.2.1.4. 1-(3-Methoxyphenyl)naphthalene. The brown liquid
obtained (0.63 g, 77%) was treated with MeOH, precipitating
a white solid that was recrystallized from MeOH and sublimed
under reduced pressure to yield white crystals of the titled com-
pound; 1H NMR (400 MHz, CDCl3, 300 K, TMS) 7.97e7.92 (2H, m, 2-
Hþ8-H), 7.89 (1H, d, J¼8.2 Hz), 7.57e7.42 (5H, m), 7.13e7.07 (2H,
m), 7.01 (1H, ddd, 2-H, J1¼8.3 Hz, J2¼2.6 Hz, J3¼0.9 Hz), 3.89 (3H, s,
OCH3); 13C NMR (100.6 MHz, CDCl3, 300 K) 160.4, 143.1, 141.0, 134.7,
132.5, 130.1, 129.2, 128.6, 127.7, 126.9, 126.7, 126.2, 123.5, 116.5,
113.8, 56.2.
4. Experimental section
4.1. General
1-Bromonaphthalene, 1,8-diaminonaphthalene, all the boronic
acids, and Pd(OAc)2 were commercially obtained from Sigmae
Aldrich. 1,8-dibromonaphthalene was synthesized as previously
described by Kuroda et al.16,17 Melting points were measured in an
IA9200 Melting Point Apparatus. 1H and 13C NMR spectra were
recorded on a Bruker Avance III 400 spectrometer, equipped with
a 5 mm broad band observe (bbo) prove. The spectra were all ref-
erenced to TMS. Reaction yields (%) are calculated from the mass of
isolated product obtained, corrected for the sample %(m/m) degree
of purity, measured by GC analysis, using an HP 4890 apparatus
equipped with an HP-5 column, cross-linked, 5% diphenyl and 95%
dimethylpolysiloxane. Crystallographic data (excluding structure
factors) for some structures in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplementary
publication. For each one of those compounds, the CCDC code
number is indicated.
4.2.1.5. 1-(4-Methoxyphenyl)naphthalene. The yellowish solid
obtained (2.35 g, 85%) was recrystallized from MeOH and sublimed
under reduced pressure to yield white crystals of the titled com-
pound (mp¼114.2e114.7 ꢁC); 1H NMR (400 MHz, CDCl3, 300 K,
TMS) 7.92 (1H, d, 8-H, J¼8.3 Hz), 7.89 (1H, d, 2-H, J¼8.0 Hz), 7.82
(1H, d, J¼8.2 Hz), 7.52e7.39 (6H, m), 7.02 (2H, d, 2-H, J¼8.6 Hz), 3.88
(3H, s, OCH3); 13C NMR (100.6 MHz, CDCl3, 300 K) 159.9, 140.8,
134.8, 134.1, 132.8, 132.0, 129.2, 128.3, 127.8, 127.0, 126.9, 126.6,
126.3, 114.7, 56.3.
4.2.1.6. 4-(Naphthalen-1-yl)benzaldehyde. The yellowish solid
obtained (1.37 g, 56%) was recrystallized from EtOH and sublimed
under reduced pressure to yield white crystals of the titled com-
pound (mp¼86.5e87.4 ꢁC); 1H NMR (400 MHz, CDCl3, 300 K, TMS)
10.12 (1H, s, CHO), 8.01 (2H, d, 2-H, J¼8.1 Hz), 7.94e7.90 (2H, m, 2-
Hþ8-H), 7.83 (1H, d, J¼8.7 Hz), 7.67 (2H, d, 3-H, J¼8.1 Hz), 7.56e7.42
(4H, m);13C NMR (100.6 MHz, CDCl3, 300 K) 192.9,148.2,139.7,136.2,
134.7,132.0,131.7,130.7,129.5,129.4,127.9,127.4,127.0,126.4,126.3.
4.2. Synthesis of 1-arylnaphthalenes
4.2.1. General synthesis of 1-arylnaphthalenes. A solution of K2CO3
(1.4 mol/equiv) in 12 ml of water per 1 mmol of the limiting re-
actant was added to a solution of 1-bromonaphthalene (1 mol/
equiv), arylboronic acid (1.2 mol/equiv) and Pd(OAc)2 (2 mol %) in
the same volume of DMF. The resultant mixture was heated at
100 ꢁC for 8 h under stirring. The final solution was allowed to cool
to room temperature, and extracted with ethyl acetate. The organic
layer was washed with water and aqueous 0.1 M NaOH, dried over
anhydrous sodium sulfate and evaporated, yielding the product as
impure mono-arylnaphthalene.
4.2.1.7. 4-(Naphthalen-1-yl)benzoic acid. The white flakes
obtained (0.73 g, 59%) were washed with Et2O and sublimed under
reduced pressure to yield white crystals of the titled compound
(mp¼235.2e236.1 ꢁC); 1H NMR (400 MHz, CDCl3, 300 K, TMS) 13.04
(1H,br s, COOH), 8.11 (2H, d, 2-H, J1¼8.8 Hz), 8.05e7.99 (2H, m, 2-
Hþ8-H), 7.79 (1H, d, J¼8.4 Hz), 7.62 (2H, d, 3-H, J¼8.4 Hz), 7.60e7.47
(4H, m); 13C NMR (100.6 MHz, CDCl3, 300 K) 171.9,147.4,139.9,134.7,
132.1,131.2,131.2,129.4,129.3,128.9,127.9,127.3,126.9,126.5,126.3.
The X-ray structure of this compound was published elsewhere.18
4.2.1.1. 1-Phenylnaphthalene. The brown oil obtained (2.73 g,
76%) was distilled under reduced pressure to yield a colorless liq-
uid; 1H NMR (400 MHz, CDCl3, 300 K, TMS) 7.90e7.81 (3H, m),
7.50e7.39 (9H, m); 13C NMR (100.6 MHz, CDCl3, 300 K) 141.8, 141.3,
134.9, 132.7, 131.1, 129.3 (two peaks), 128.7, 128.3, 128.0, 127.1 (two
peaks), 126.8, 126.4.
4.2.1.8. 4-(Naphthalen-1-yl)benzonitrile. The
brown
solid
obtained (0.45 g, 58%) was recrystallized from MeOH and sublimed
under reduced pressure to yield white crystals of the titled com-
pound; 1H NMR (400 MHz, CDCl3, 300 K, TMS) 7.98e7.92 (2H, m, 2-
Hþ8-H), 7.81 (2H, d, 2-H, J¼8.2 Hz), 7.84e7.78 (1H, m), 7.64 (2H, d,
3-H, J¼8.2 Hz), 7.61e7.40 (4H, m); 13C NMR (100.6 MHz, CDCl3,
300 K) 146.6, 139.1, 134.7, 133.0, 131.9, 131.7, 129.7, 129.5, 127.9,
127.6, 127.1, 126.3, 126.1, 119.8, 112.1.
4.2.1.2. 1-([1,10-Biphenyl]-4-yl)naphthalene. The brown solid
obtained (4.91 g, 81%) was washed with boiling MeOH and sublimed
under reduced pressure to yield white crystals of the titled com-
pound; 1H NMR (400 MHz, CDCl3, 300 K, TMS) 7.98 (1H, d, 8-H,
J¼8.2 Hz), 7.92 (1H, d, 2-H, J¼8.0 Hz), 7.87 (1H, d, J¼8.1 Hz), 7.73e7.68
(4H, m), 7.59e7.36 (9H, m); 13C NMR (100.6 MHz, CDCl3, 300 K) 141.8,
141.0,140.8,140.7,134.8,132.5,131.4,129.8,129.2,128.6,128.3,128.1,
127.92, 127.87, 127.0, 126.9, 126.7, 126.3. CCDC 698100.
4.2.1.9. 1-(3,4-Dimethoxyphenyl)naphthalene. The greenish solid
obtained (0.77 g, 75%) was recrystallized from MeOH and sublimed
under reduced pressure to yield white needles of the titled com-
pound (mp¼120.3e121.2 ꢁC); 1H NMR (400 MHz, CDCl3, 300 K, TMS)
7.94 (1H, d, 8-H, J¼8.4 Hz), 7.89 (1H, d, 2-H, J¼8.4 Hz), 7.84 (1H, d,
J¼8.2 Hz), 7.53e7.40 (4H, m), 7.07e6.97 (3H, m), 3.96 (3H, s, OCH3),
3.89 (3H, s, OCH3); 13C NMR (100.6 MHz, CDCl3, 300 K) 149.6, 149.3,
141.0,134.8,134.4,132.8,129.2,128.4,127.8,127.0,126.9,126.7,126.3,
123.2, 114.3, 112.0, 56.9, 56.9. CCDC 781816.
4.2.1.3. N,N-Dimethyl-4-(naphthalen-1-yl)aniline. The
brown
solid obtained (0.72 g, 71%) was washed with MeOH and sublimed

696
C.F.R.A.C. Lima et al. / Tetrahedron 67 (2011) 689e697
4.2.1.10. 2-Methoxy-5-(naphthalen-1-yl)benzaldehyde. The light
titled compound; 1H NMR (400 MHz, CDCl3, 300 K, TMS) 7.96 (2H,
dd, 2-H, J1¼8.2 Hz, J2¼1.0 Hz), 7.59e7.53 (2H, m, 3-H), 7.44 (2H, dd,
4-H, J1¼7.1 Hz, J2¼1.0 Hz), 6.89 (4H, d, 20-H, J¼8.6 Hz), 6.52 (4H, d,
30-H, J¼8.6 Hz), 3.75 (6H, s, OCH3); 13C NMR (100.6 MHz, CDCl3,
300 K) 158.6, 141.0, 136.7, 136.4, 131.8, 131.6, 130.6, 129.3, 126.0,
113.7, 56.2.
brown solid obtained (0.94 g, 66%) was recrystallized from MeOH
and sublimed under reduced pressure to yield white crystals of the
titled compound (mp¼92.6e93.9 ꢁC); 1H NMR (400 MHz, CDCl3,
300 K, TMS) 10.59 (1H, s, CHO), 8.01 (1H, d, 6-H, J¼2.4 Hz), 7.94 (1H,
d, 80-H, J¼7.5 Hz), 7.89 (1H, d, 20-H, J¼8.2 Hz), 7.85 (1H, d, J¼8.6 Hz),
7.72 (1H, dd, 4-H, J1¼8.6 Hz, J2¼2.4 Hz), 7.57e7.40 (4H, m), 7.15 (1H,
d, 3-H, J¼8.6 Hz), 4.05 (3H, s, OCH3); 13C NMR (100.6 MHz, CDCl3,
300 K) 190.7, 162.1, 139.4, 138.3, 134.7, 134.2, 132.4, 130.9, 129.3,
128.8, 128.0, 127.2, 126.8, 126.5, 126.3, 125.6, 112.6, 56.8.
4.3.1.5. 4,40-(Naphthalen-1,8-diyl)dibenzaldehyde. The yellowish
solid obtained (0.35 g, 57%) was washed with MeOH, boiling EtOH
and sublimed under reduced pressure to yield white crystals of the
titled compound; 1H NMR (400 MHz, CDCl3, 300 K, TMS) 9.82 (2H,
s, CHO), 8.05 (2H, d, 20-H, J¼8.3 Hz), 7.64 (2H, dd, 30-H, J1¼8.3 Hz,
J2¼7.1 Hz), 7.47 (4H, d, 2-H, J¼8.4 Hz), 7.49e7.45 (2H, 40-H, m), 7.18
(4H, d, 3-H, J¼8.0 Hz); 13C NMR (100.6 MHz, CDCl3, 300 K) 192.4,
150.2, 139.5, 136.3, 135.0, 132.2, 131.3, 130.5, 129.7, 129.6, 126.4.
4.3. Synthesis of 1,8-diarylnaphthalenes
4.3.1. General synthesis of 1,8-diarylnaphthalenes. A solution of
K2CO3 (6 mol/equiv) in 15 ml of water per 1 mmol of the limiting
reactant was added to a solution of 1,8-dibromonaphthalene
(1 mol/equiv), arylboronic acid (4 mol/equiv), and Pd(OAc)2
(2 mol %) in the same volume of DMF. The resultant mixture was
heated at 100 ꢁC for 8 h under stirring. The final solution was
allowed to cool to room temperature, and extracted with ethyl
acetate. The organic layer was washed with water and aqueous
0.1 M NaOH, dried over anhydrous sodium sulfate and evaporated,
yielding the product as impure diarylnaphthalene.
4.3.1.6. 4,40-(Naphthalen-1,8-diyl)dibenzonitrile. The pale grey
solid obtained (0.13 g, 30%) was recrystallized from AcOEt, and
sublimed under reduced pressure to yield white crystals of the ti-
tled compound; 1H NMR (400 MHz, CDCl3, 300 K, TMS) 8.06 (2H,
dd, 20-H, J1¼8.3 Hz, J2¼1.3 Hz), 7.64 (2H, dd, 30-H, J1¼8.3 Hz,
J2¼7.1 Hz), 7.43 (2H, dd, 40-H, J1¼7.1 Hz, J2¼1.3 Hz), 7.31 (4H, d, 3-H,
J¼8.4 Hz), 7.12 (4H, d, 2-H, J¼8.4 Hz); 13C NMR (100.6 MHz, CDCl3,
300 K) 148.5, 138.7, 136.3, 132.3, 132.1, 131.3, 130.8, 129.3, 126.5,
119.3, 110.9.
4.3.1.1. 1,8-Diphenylnaphthalene. The yellowish solid obtained
(1.10 g, 60%) was recrystallized from AcOEt and sublimed under
reduced pressure to yield white crystals of the titled compound
(mp¼143e145 ꢁC); 1H NMR (400 MHz, CDCl3, 300 K, TMS) 7.98 (2H,
dd, 2-H, J1¼8.3 Hz, J2¼1.3 Hz), 7.59 (2H, dd, 3-H, J1¼8.3 Hz,
J2¼7.0 Hz), 7.45 (2H, dd, 4-H, J1¼7.0 Hz, J2¼1.3 Hz), 7.03e6.93 (10H,
m); 13C NMR (100.6 MHz, CDCl3, 300 K) 144.0, 141.4, 136.3, 132.0,
130.7, 130.1, 129.5, 128.0, 126.6, 126.0.
4.3.1.7. 1,8-Bis(3,4-dimethoxyphenyl)naphthalene. The brown oil
obtained was treated with MeOH, precipitating a yellow solid
(0.64 g, 76%), that was washed with boiling MeOH and sublimed
under reduced pressure to yield white crystals of the titled com-
pound (mp¼132.1e133.2 ꢁC); 1H NMR (400 MHz, CDCl3, 300 K,
TMS), equilibrium of syn/anti conformers, 7.96 (2H, d, 2-H,
J¼8.1 Hz), 7.59e7.54 (2H, m, 3-H), 7.46 (2H, d, 4-H, J¼6.8 Hz),
6.82e6.32 (6H, m), 3.84, 3.81, 3.75, and 3.70 (12H, s, OCH3); 13C
NMR (100.6 MHz, CDCl3, 300 K) 148.2, 141.1, 137.4, 136.4, 131.6,
129.4, 126.0, 122.3, 114.8, 111.9, 111.5, 57.1, 56.5, 56.2. CCDC 769513.
4.3.1.2. 1,8-Di([1,10-biphenyl]-4-yl)naphthalene. A solution of
K2CO3 (6 mol/equiv) in a 40 ml solution of water/EtOH (1:1) was
added to a solution of 1,8-dibromonaphthalene (1 mol/equiv),
arylboronic acid (4 mol/equiv), and PdCl2(dppe) (2 mol %) in 40 ml
of toluene. The resultant mixture was heated at 120 ꢁC for 52 h
under stirring. The final solution was allowed to cool to room
temperature, and the aqueous phase extracted with toluene. The
mixed organic layers were washed with water and aqueous 0.1 M
NaOH, dried over anhydrous sodium sulfate and evaporated,
yielding a greenish solid (0.50 g, 55%) that was recrystallized from
cyclohexane, washed with boiling MeOH, and sublimed under re-
duced pressure to yield white crystals of the titled compound; 1H
NMR (400 MHz, CDCl3, 300 K, TMS) 8.02 (2H, dd, 2-H, J1¼8.2 Hz,
J2¼1.4 Hz), 7.62 (2H, dd, 3-H, J1¼8.2 Hz, J2¼7.0 Hz), 7.53 (2H, dd, 4-H,
J1¼7.0 Hz, J2¼1.4 Hz), 7.36e7.25 (10H, m, Ph), 7.17 (4H, d, 30-H,
J¼8.4 Hz), 7.08 (4H, d, 20-H, J¼8.4 Hz); 13C NMR (100.6 MHz, CDCl3,
300 K) 143.1, 141.9, 141.0, 139.7, 136.3, 131.8, 131.2, 130.4, 129.7,
129.3, 128.1, 127.7, 126.8, 126.1. CCDC 668280.
4 . 3 .1. 8 . 5 , 5 0- ( Na p h t h a l e n - 1, 8 - d i yl ) b i s (2 - m e th o x y -
benzaldehyde). The brown solid obtained (0.74 g; 53%) was washed
with boiling MeOH and sublimed under reduced pressure to yield
white crystals of the titled compound (mp¼206.6e207.9 ꢁC); 1H
NMR (400 MHz, CDCl3, 300 K, TMS), equilibrium of syn/anti con-
formers; syn conformer: 10.54 (2H, s, CHO), 8.06 (2H, d, 6-H,
J¼2.5 Hz), 7.99 (2H, dd, 20-H, J1¼8.3 Hz, J2¼1.2 Hz), 7.82 (2H, dd, 4-H,
J1¼8.8 Hz, J2¼2.5 Hz), 7.57 (2H, dd, 30-H, J1¼8.3 Hz, J2¼6.8 Hz), 7.40
(2H, dd, 40-H, J1¼6.8 Hz, J2¼1.2 Hz), 7.10 (2H, d, 3-H, J¼8.8 Hz), 4.00
(6H, s, OCH3); anti conformer: 10.32 (2H, s, CHO), 7.99 (2H, dd, 20-H,
J1¼8.3 Hz, J2¼1.2 Hz), 7.57 (2H, dd, 30-H, J1¼8.3 Hz, J2¼6.8 Hz), 7.40
(2H, dd, 40-H, J1¼6.8 Hz, J2¼1.2 Hz), 7.34 (2H, d, 6-H, J¼2.3 Hz), 7.19
(2H, dd, 4-H, J1¼8.6 Hz, J2¼2.3 Hz), 6.60 (2H, d, 3-H, J¼8.6 Hz), 3.85
(6H, s, OCH3); 13C NMR (100.6 MHz, CDCl3, 300 K) 190.4, 160.9,
139.1, 138.4, 136.6, 136.3, 131.6, 130.5, 130.0, 126.1, 124.2, 111.7, 56.7.
4.3.1.3. 4,40-(Naphthalen-1,8-diyl)bis(N,N-dimethylaniline). The
yellowish solid obtained (0.58 g, 87%) was recrystallized from
AcOEt, washed with boiling MeOH, and sublimed under reduced
pressure to yield white crystals of the titled compound; 1H NMR
(400 MHz, CDCl3, 300 K, TMS) 7.92 (2H, dd, 20-H, J1¼8.2 Hz,
J2¼1.4 Hz), 7.55 (2H, dd, 30-H, J1¼8.2 Hz, J2¼7.0 Hz), 7.47 (2H, dd, 40-
H, J1¼7.0 Hz, J2¼1.4 Hz), 6.85 (4H, d, 3-H, J¼8.8 Hz), 6.36 (4H, d, 2-H,
J¼8.8 Hz), 2.88 [12H, s, N(CH3)2]; 13C NMR (100.6 MHz, CDCl3,
300 K) 149.5, 141.8, 136.5, 133.0, 131.4, 131.3, 130.7, 128.8, 125.9,
112.8, 41.7. CCDC 721267.
4.4. Synthesis of non-symmetric 1,8-diarylnaphthalenes
4.4.1. First addition: phenylboronic acid. A solution of K2CO3
(0.75 mmol, 1.5 mol/equiv) in 10 ml of H2O was added, at ambient
temperature, to a solution of 1,8-dibromonaphthalene (0.50 mmol,
1 mol/equiv), phenylboronic acid (0.60 mmol,1.2 mol/equiv) and Pd
(OAc)2 (2 mol %) in 10 ml of DMF. The resultant mixture was heated
at 100 ꢁC under stirring, and after 3 h a solution of biphen-4-
ylboronic acid (1.51 mmol, 3 mol/equiv) and Pd(OAc)2 (1 mol %) in
10 ml of DMF, and a solution of K2CO3 (1.75 mmol, 3.5 mol/equiv) in
10 ml of H2O, were added. The reaction was allowed to proceed for
4 h at 100 ꢁC. The final solution was allowed to cool to room tem-
perature, and extracted with ethyl acetate. The organic layer was
4.3.1.4. 1,8-Bis(4-methoxyphenyl)naphthalene. The light brown
solid obtained (0.42 g, 71%) was washed with boiling MeOH and
sublimed under reduced pressure to yield white crystals of the

C.F.R.A.C. Lima et al. / Tetrahedron 67 (2011) 689e697
697
washed with water and aqueous 0.1 M NaOH, dried over anhydrous
sodium sulfate, and filtered for GC analysis.
Community Support Framework (CSF) for the award of a Ph.D.
Research Grant (SRFH/BD/29394/2006).
4.4.2. First addition: biphen-4-ylboronic acid. A solution of K2CO3
(0.77 mmol, 1.5 mol/equiv) in 10 ml of H2O was added, at ambient
temperature, to a solution of 1,8-dibromonaphthalene (0.50 mmol,
1 mol/equiv), biphen-4-ylboronic acid (0.60 mmol, 1.2 mol/equiv)
and Pd(OAc)2 (2 mol %) in 10 ml of DMF. The resultant mixture was
heated at 100 ꢁC under stirring, and after 3 h a solution of phe-
nylboronic acid (1.50 mmol, 3 mol/equiv) and Pd(OAc)2 (1 mol %) in
10 ml of DMF, and a solution of K2CO3 (1.75 mmol, 3.5 mol/equiv) in
10 ml of H2O, were added. The reaction was allowed to proceed for
4 h at 100 ꢁC. The final solution was allowed to cool to room tem-
perature, and extracted with ethyl acetate. The organic layer was
washed with water and aqueous 0.1 M NaOH, dried over anhydrous
sodium sulfate, and filtered for GC analysis.
Supplementary data
Detailed statistical analysis for the mono- and di-arylation of
1,8-dibromonaphthalene. 1H and 13C NMR spectra for all the syn-
thesized compounds. Detailed computational results. Supplemen-
tary data related to this article can be found online version, at
doi:10.1016/j.tet.2010.11.081. These data include MOL files and
InChIKeys of the most important compounds described in this
article.
References and notes
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7 mol/equiv) in 20 ml of H2O was added, at ambient temperature, to
a solution of 1,8-dibromonaphthalene (0.50 mmol, 1 mol/equiv),
phenylboronic acid (1.50 mmol, 3 mol/equiv), biphen-4-ylboronic
acid (1.50 mmol, 3 mol/equiv), and Pd(OAc)2 (2 mol %) in 20 ml of
DMF. The resultant mixture was heated at 100 ꢁC for 8 h under
stirring. The final solution was allowed to cool to room tempera-
ture, and extracted with ethyl acetate. The organic layer was
washed with water and aqueous 0.1 M NaOH, dried over anhydrous
sodium sulfate, and filtered for GC analysis.
3. Liu, L.; Zhang, Y.; Xin, B. J. Org. Chem. 2006, 71, 3994.
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4.5. Computational details
15. Fitton, P.; Rick, E. A. J. Organomet. Chem. 1971, 28, 287.
16. Kuroda, M.; Nakayama, J.; Hoshino, M. Tetrahedron 1993, 49, 3735.
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All theoretical calculations were performed using the Gaussian
03 software package.19 The full geometry optimizations were per-
€
formed using the MollerePlesset perturbation theory with a sec-
19. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken,
V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A.
J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G.
A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.;
Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Fores-
man, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov,
B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.;
Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P.
M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian
03, Revision C.02; Gaussian: Pittsburgh, PA, 2004.
ond order perturbation (MP2) and the correlation consistent basis
set cc-pVDZ, using the SCS-MP2 method for evaluation of the
electronic energies.10
Acknowledgements
ˇ
~
Thanks are due to Fundac¸ ao para a Ciencia e Tecnologia (FCT)
ˇ
~
and Programa Operacional Ciencia e Inovac¸ ao 2010 (POCI 2010)
supported by the European Community Fund FEDER for the fi-
nancial support to Project POCI/QUI/61873/2004. C.F.R.A.C.L. also
thanks FCT and the European Social Fund (ESF) under the third