Aryne-mediated fluorination: Synthesis of fluorinated biaryls via a sequential desilylation-halide elimination-fluoride addition process

Article abstract of DOI:10.1016/j.jfluchem.2011.02.017

An unusual aryne-mediated fluorination of aromatic ring systems during the desilylation of ortho-bromo-biphenyl-trimethylsilanes with tetrabutylammonium fluoride (TBAF) is described. In situ formation of an aryne and addition of fluoride affords fluorinat

Full text of DOI:10.1016/j.jfluchem.2011.02.017

Journal of Fluorine Chemistry 134 (2012) 146–155
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Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Aryne-mediated fluorination: Synthesis of fluorinated biaryls via a sequential
desilylation–halide elimination–fluoride addition process
*
´ ´
Vincent Diemer, Juan Sanz Garcia, Frederic R. Leroux , Franc¸oise Colobert
CNRS/Universite´ de Strasbourg (ECPM), UMR 7509, 25 Rue Becquerel, F-67087 Strasbourg Cedex 2, France
A R T I C L E I N F O
A B S T R A C T
Article history:
An unusual aryne-mediated fluorination of aromatic ring systems during the desilylation of ortho-
bromo-biphenyl-trimethylsilanes with tetrabutylammonium fluoride (TBAF) is described. In situ
formation of an aryne and addition of fluoride affords fluorinated biphenyls. The structures have been
undoubtfully confirmed by synthesis of authentic samples via Suzuki–Miyaura cross-coupling and X-ray
analysis. In situ trapping experiments with furan proved the transient formation of aryne by fluoride-
induced displacement of the TMS group and subsequent bromide elimination.
Received 17 January 2011
Received in revised form 16 February 2011
Accepted 27 February 2011
Available online 15 March 2011
Keywords:
Desilylation
Silane
ß 2011 Elsevier B.V. All rights reserved.
Fluorination
Aryne
Nucleophilic addition
Biaryl
mon heterocycles bearing fluorinated substituents like a-fluor-
´ ´
The ‘‘Laboratoire de stereochimie’’ belongs to a mixed CNRS-
University of Strasbourg research group (UMR CNRS 7509)
implemented at the European School of Chemistry, Polymers
and Material Sciences (ECPM) in Strasbourg. Our research
focuses on the development of new organic and organometallic
methodologies and find their application in the synthesis of
biologically active compounds, new ligands for asymmetric
catalysis and pharmacophores as well as agrochemical targets.
One of the principal research activities of the group lies in the
total synthesis of natural products. The second research topic
focuses on the control of axial chirality in biaryls employing
atropo-diastereo- and enantioselective Suzuki–Miyaura cross-
coupling reactions, C–H activation or transition-metal free aryl–
aryl ARYNE coupling reactions. This expertise has been success-
fully applied in the synthesis of biaryl-based ligands for C–C, C–
N, C–O and, more recently, C–F coupling protocols. The use of
fluorinated ligands being intensively studied in this field. The
third research area concerns the development of new fluorina-
tion methodologies with application in the synthesis of uncom-
oethers with application in Life Science oriented research. The
group succeeded recently in the first modular synthesis of
trifluoromethoxy pyridine building-blocks.
1. Introduction
Arynes (1,2-dehydrobenzenes) and their heterocyclic analo-
gues (heteroarynes) are highly reactive intermediates in organic
chemistry and have attracted in recent years increasing interest
due to their wide synthetic applications [1,2]. They react with a
variety of N-, S-, O-, Se- [3–11], and P-nucleophiles [12] as well as
with carbanions [13–19]. With alkenes they undergo Diels–Alder-
type cycloaddition reactions [20–22], [2 + 2] cycloaddition [23,24],
1,3-dipolar cycloaddition [25,26] and transition-metal catalyzed
reactions making them powerful tools in organic synthesis [27–
31]. Note that aryl–aryl couplings using arynes as key inter-
mediates have been described in the literature in some cases
[14,32–35]. In this research area, our group made intensive
researches and reported very recently on the efficient synthesis of
ortho,ortho0-tri- and tetrasubstituted bromobiphenyls via a transi-
tion metal free cross-coupling procedure. This so-called ‘‘ARYNE
coupling’’ methodology is based on the reaction of thermodynam-
* Corresponding author. Tel.: +33 368852640; fax: +33 368852742.
E-mail address: frederic.leroux@unistra.fr (F.R. Leroux).
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.02.017

V. Diemer et al. / Journal of Fluorine Chemistry 134 (2012) 146–155
147
Fig. 1. ARYNE coupling methodology.
ically stable organolithium intermediates with arynes [13,14]
generated in situ by reaction with symmetrical [13], and more
recently, unsymmetrical 1,2-dibromobenzenes (Fig. 1) [36]. The
latter became accessible due to highly complementary transition-
metal catalyzed and polar organometallic protocols [37]. We could
show that unsymmetrical arynes undergo with perfect regios-
electivity the ARYNE coupling by using sterically demanding silyl-
groups in the ortho-position of the aryne functionality [36]. The
advantage of trialkylsilyl groups is, beside their sterical crowding,
that they can be easily displaced by protodesilylation [38,39],
bromodesilylation [38,40], or iododesilylation [38,41–43].
In the ARYNE cross coupling, 1,2-dibromobenzenes are used as
aryne precursors, but various other methods for the in situ
generation of an aryne are known. They imply most oftenly the
elimination of a leaving group such as halide, tosylate, triflate,
diazonium, trialkyl-ammonium, etc. from the ortho-position of a
metalated aromatic ring [44–50].
elimination process with subsequent fluoride addition allows the
access to fluorinated aromatic scaffolds.
2. Results and discussion
2.1. Desilylation of biaryls 1a–d with TBAF
The ortho-bromobiaryls 1a–d were prepared by applying the
ARYNE cross-coupling methodology [13,36] starting from 2,6-
dimethoxy aryllithium and functionalized 1,2-dibromobenzenes
2a–d (Scheme 1a). As outlined previously, the trimethylsilyl group
(TMS) has been chosen in order to guarantee a perfect control of
the regioselectivity during the addition of the aryllithium
nucleophile onto the aryne by virtue of its steric hindrance
(Scheme 1b). Moreover, the TMS group can be easily introduced on
the starting material by means of selective ortho-metalation
reactions [37].
For example, ortho-metalations on aromatic triflates [51] as
well as halogen/metal permutations on ortho-halotriflates [52] or
1,2-dibromobenzenes (as shown in Fig. 1 in the mechanism of the
ARYNE cross-coupling) have been successfully applied to produce
arynes. Beside these well-established organometallic methods, an
alternative strategy has emerged starting from trimethylsilyl
triflate precursors (Kobayashi reagent). In that case, the elimina-
tion of the leaving group is induced under mild conditions by
displacement of the trimethylsilyl group with fluoride anions [53].
This approach requires, however, the synthesis of aryl trimethyl-
silyl triflates [54].
In the context of our researches dedicated to the removal of the
directing silyl-group in the ARYNE coupling methodology, we
describe now the generation of aryne by fluoride induced
elimination of bromide on ortho-trimethylsilyl-bromoarenes. It
will be shown that the combination of this new desilylation–halide
Classically, the TMS group can be removed with tetrabuty-
lammonium fluoride (TBAF) in THF at 25 8C. However, in case of the
ortho-bromobiaryls 1a–d, the expected desilylated biaryls 3a–d
were obtained in mixture with the fluorinated derivatives 4a–d
(Scheme 2). The isolated yields as well as the ratio of desilylated
and fluorinated products depended on the substitution pattern of
the aryl silane moiety. Starting from the non-substituted
compound 1a, a mixture that mainly contained the fluorinated
derivative 4a (70%) was isolated in 49% yield. When a phenyl group
was present in meta-position of the silane, the yield of the reaction
was increased to 72% and the ratio between fluoro and
bromobiaryls increased in favor of the latter one (3d/
4d = 74:26). Crystallization from MeOH provided the analytically
pure terphenyl 3d in 40% yield. An intermediate situation was
observed with biaryls 1b–c substituted with a methyl group either
at the 50- or 60-position of the biaryl ring system.
Scheme 1. Synthesis of biaryls 1a–d by ARYNE cross-coupling. (a) Experimental results. (b) Regioselectivity of the addition.

148
V. Diemer et al. / Journal of Fluorine Chemistry 134 (2012) 146–155
Scheme 2. Main products obtained by desilylation of biaryls 1a–d.
In order to elucidate the chemical structure of all fluorinated
confirm the structure of compound 9, a pure sample was prepared
in two steps starting from 1,3,5-tribromobenzene (Scheme 3) via
Suzuki–Miyaura cross-coupling with 2,6-dimethoxyphenylboro-
nic acid affording biaryl 11 (47% yield). Lithiation followed by
trapping with methyl iodide gave biaryl 9 in 74% yield.
side products, authentic samples of 4a–d were synthesized via
Suzuki–Miyaura cross-coupling reactions (Scheme 3). The biaryls
4a and 4b were prepared in one step starting from 1-fluoro-3-iodo-
benzene and 2-bromo-4-fluoro-1-methyl-benzene, respectively.
Heating at reflux these halogenated compounds with the 2,6-
dimethoxyphenyl boronic acid in a mixture of toluene, ethanol and
aqueous Na2CO3 in the presence of catalytic amount of Pd(PPh3)4
cleanly gave the expected products 4a and 4b in 55% and 76% yield,
respectively. In the case of compound 4c we prepared also the
regioisomer 5 with fluorine at the 20-position in order to confirm
the relative position of the fluorine atom on the aromatic ring. The
20-fluoro regioisomer 5 was synthesized analogously as compound
4a with 49% yield, starting from 2-bromo-1-fluoro-4-methylben-
zene. On the other hand, a two-step procedure was needed to
access compound 4c. 1,3-Dibromo-5-fluorobenzene was con-
verted by Suzuki–Miyaura coupling into biaryl 6 in a yield of
59%. Subsequent bromine/lithium permutation with BuLi in THF at
ꢀ78 8C followed by electrophilic trapping with methyl iodide led to
the 30-fluoro regioisomer 4c. The comparison of the NMR data
unambiguously proved that the fluorine atom was introduced in
the 30-position relative to the biaryl bond. The regioselectivity of
the fluorination was also confirmed in the case of 1d by the
synthesis of the terphenyl 4d. A three-step procedure converted
1,3-dibromo-5-fluoro benzene into terphenyl 4d with 40% overall
yield. First, magnesiation of the starting material at ꢀ40 8C in THF
using iPrMgCl followed by trapping with 2-isopropoxy-4,4,5,5-
tetramethyl-[1,3,2]dioxaborolane afforded the boronic ester 7 in
53%. A first Suzuki–Miyaura cross-coupling with an excess of
iodobenzene in a mixture of EtOH, toluene and aqueous Na2CO3 in
presence of Pd(PPh3)4 provided the biaryl 8 with 90% yield. Due to
the perfect chemoselectivity of iodide vs. bromide, no homocou-
pling of 7 was observed. Finally, a second Suzuki–Miyaura cross-
coupling under similar conditions afforded terphenyl 4d in 79%
yield.
2.2. Trapping with furan
In order to elucidate further the regioselective fluorination
during the desilylation reaction of ortho-bromobiaryls 1a–d, we
performed the reaction in presence of an excess of furan
(10 equiv.). Under these conditions, possible aryne intermediates
can be trapped via their [4 + 2] Diels–Alder cycloaddition. As
described previously in the absence of furan, mixtures of biaryls
3a–c and 4a–c were isolated by column chromatography in 22%,
23% and 33% yield, respectively. Crystallization from MeOH
provided pure samples of methylated 2-bromobiaryls 3b and 3c.
However, a new product, the polycyclic compound 12 was now
detected as major product beside compounds 3 and 4 (Table 2). The
sterically more hindered cycloadduct 12b was obtained in a lower
yield (34%) compared to 12a and 12c (51% and 45%, respectively).
The structure of the cycloaddition product could be undoubtfully
confirmed by single-crystal X-ray analysis in the case of 12c
(Fig. 3).
The formation of compound 12 revealed that after fluoride-
induced desilylation, the intermediate carbanion eliminates
bromide affording the corresponding aryne. At the same time,
the presence of furan dramatically decreased the ratio of 30-
fluorinated derivative 4 (Table 2). The ratio of 4 did not exceed 11%
in the mixture whatever the substitution pattern of the starting 2-
bromosilane 1. These results imply that the formation of biaryl 4 is
due to the nucleophilic addition of the fluoride anion on the
transient aryne species (Fig. 4). When furan is present in excess, the
cycloaddition becomes faster than the nucleophilic fluoride
addition onto the aryne intermediate leading to a decreased
formation of the 30-fluorinated derivative 4.
In addition, we succeeded to obtain from biaryl 4a single
crystals for X-ray analysis (Fig. 2). Although the fluorine atom is
disordered on two positions (60% on C11 and 40% on C13 (F1b)) the
X-ray determination confirmed the structure of biaryl 4a.
The formation of 30-bromobiaryl 9 (Table 1) starting from
bromosilane 1c can be explained in
a similar manner by
regioselective addition of the bromide anion onto the aryne
(Fig. 4). Bromide anions are formed during the aryne formation.
However, their concentration remains low until the end of the
reaction. As a consequence, fluoride addition leading to 30-
fluorobiaryl 4c largely dominates even in presence of furan. This
selectivity was amplified when the initial concentration of TBAF
with respect to [TBAF]0 was increased in the reaction mixture by
the addition of 5 and 10 equiv. of TBAF. In this case, the amount of
3-bromobiaryl 9 decreased from 12% to 7% in favor of the 30-
fluorinated derivative 4c (Table 1, Entries 1, 3 and 4). On the other
hand, addition of tetrabutylammonium bromide (TBABr)
Next, we studied more in detail the outcome of the desilylation/
fluorination reaction on compound 1c as model (Table 1, Entry 1).
Combined NMR and GC–MS analysis confirmed the main presence
of biaryls 3c (41%) and 4c (41%) and revealed the formation of other
side products in smaller quantities. The 30-bromo regioisomer 9 of
biaryl 3c and the benzofuran 10 were present in 12% and 6%,
respectively. At the same time, the 20-fluoro regioisomer 5 (Scheme
3) was not at all detected in the reaction mixture. Small amounts of
benzofuran 10 were isolated and NMR (1H, 13C) and GC–MS
analysis were in agreement with the heterocyclic structure. To

V. Diemer et al. / Journal of Fluorine Chemistry 134 (2012) 146–155
149
Scheme 3. Synthesis of reference compounds 4a–d, 5 and 9 via Suzuki–Miyaura-cross coupling reactions.
completely reversed the composition of the reaction mixture
(Table 1, Entry 7). Starting material was mainly converted into 3-
bromobiaryl 9 (40%) and the 30-fluorinated derivative 4c was only
detected as minor products (26%) at the end of the reaction. These
experimental data confirm that compounds 4c and 9 result from a
competitive addition of bromide and fluoride anions on the aryne
via an intermolecular processes. The kinetics of these two reactions
are mainly controlled by the relative concentration of the
halogenated anions. In parallel, an intramolecular pathway
involving a demethylation–cyclisation sequence provided, as
depicted in Fig. 4 the benzofuran 10 from bromosilane 1c.
The attack of fluoride at the TMS group first promotes the
cleavage of the Ar–Si bond. Due to the leaving group ability of the
neighboring bromide anion, the removal of the TMS group induces
the partial elimination of bromide and leads, besides the classical
desilylation pathway, to the formation of the aryne intermediate.
Efficient precursors like 2-(trimethylsilyl)phenyl triflates [53,56]
and (phenyl)[2-(trimethylsilyl)phenyl]iodonium triflates [57,58]
have already been described in the literature to generate aryne by
fluoride displacement of a TMS group. Due to the high leaving
group ability of triflate and iodonium, the intermediate carbanion
forms quantitatively the transient aryne species. Triflate and
iodonium groups being better leaving groups than iodide anions
[58], we can assume similar properties for the bromide anion.
However, its weaker nucleofugacity is responsible for the partial
conversion of the ortho-bromobiaryls 1 into aryne. Note, as shown
in the case of compound 1c, that neither increasing the
temperature of the reaction (Table 1, Entries 5 and 6) nor changing
the concentration of TBAF (Table 1, Entries 2–4) or the nature of the
nucleophile (Table 1, Entry 7) modified the product ratios resulting
from the classical desilylation (3c, 30–40%) and aryne-mediated
reactions (4c, 9, and 10, 60–70%). These results confirmed that the
proportion of aryne in the reaction mixture is mainly controlled by
the nature of leaving group.

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V. Diemer et al. / Journal of Fluorine Chemistry 134 (2012) 146–155
Fig. 2. Thermal ellipsoid drawing of 4a with ellipsoids drawn to the 50% probability level (ORTEP plot) [55].
Table 1
Although arynes are widely used for aryl-carbon and aryl-
heteroatom bond formation as outlined in the introduction,
information on aryne-mediated fluorination is scarce and lacking
in detail. Carbon–fluorine bond formation via arynes has been
observed by Schwesinger’s group, although this type of fluorina-
tion is only mentioned in one brief sentence in the conclusion [59].
Otherwise, the fluoride induced aryne formation from a trimethyl-
silyl aryl triflate and successive fluoride addition has been reported
Desilylation of biaryl 1c under different experimental conditions.
Entry TBABr
TBAF
[TBAF]0
(in M)
Reaction
Composition of
the reaction
conditions
mixture (in %)a,c
10 3c/9/4cb
1
2
–
–
3 equiv.
3 equiv.
0.23
0.23
25 8C, 18 h
25 8C, 18 h
reverse
6
5
41/12/41 (81)
42/13/40 (77)
´
by Perez [60,61]. Grushin nicely showed during their studies on
addition
N,N- and S,S-chelate-stabilized aryl palladium fluorides that aryne-
mediated fluorination of nonactivated haloarenes with Me4NF in
DMSO is possible [61].
Although there are few precedents in the literature, trapping
experiments with furan clearly demonstrate that the mechanism
leading to the fluorinated product 4 is based on the addition of the
fluoride anion onto the transient aryne. Steric hindrance generated
by the 2,6-dimethoxyphenyl group in ortho position of the aryne
favors this addition in 30-position of the biaryl ring. This steric
3
4
5
6
7
–
–
–
–
5 equiv.
0.50
25 8C, 3 h
4
5
5
5
2
40/7/49 (75)
39/7/49
10 equiv. 0.77
3 equiv. 0.23
10 equiv. 0.77
0.23
25 8C, 18 h
At reflux 3 h
At reflux 3 h
25 8C, 18 h
33/18/44 (72)
38/15/42 (70)
32/40/26 (71)
10 equiv. 3 equiv.
Ratio of 3c, 4c, 9 and 10 determined by 1H NMR analysis of the reaction mixture.
Isolated yields of 3c +4c +9 in brackets.
a
b
c
No starting material was detected in the reaction mixture.
Fig. 3. Thermal ellipsoid drawing of 12c with ellipsoids drawn to the 50% probability level (ORTEP plot) [55].

V. Diemer et al. / Journal of Fluorine Chemistry 134 (2012) 146–155
151
Fig. 4. Aryne-mediated mechanism leading to side products 4c, 9, 10 and 12c.
literature procedures, pertinent references are given. Air- and
moisture-sensitive materials were stored in Schlenk tubes. They
were protected by and handled under an atmosphere of argon,
using appropriate glassware. Tetrahydrofuran was dried by
distillation from sodium after the characteristic blue color of
sodium diphenyl ketyl (benzophenone-sodium ‘‘radical-anion’’)
had been found to persist. Melting ranges (mp) given were
determined on a Kofler heated stage and found to be reproducible
after recrystallization, unless stated otherwise (‘‘decomp.’’), and
are uncorrected. If melting points are missing, it means all
attempts to crystallize the liquid at temperatures down to ꢀ75 8C
failed. Column chromatography was carried out on a column
Table 2
Desilylation of biaryls 11a–c in presence of furan.
Entry
R1
R2
Ratioa
Yield of 3 + 4 (in %)e
Yield of 12 (in %)
4/3/12
1
2
3
H
H
11/30/59b
4/36/60c
9/32/59d
22 (72/28)
23 (85/15)
33 (77/23)
51
34
45
Me
H
H
Me
a
Ratios of 3, 4 and 12 determined by NMR analysis of the reaction mixture.
13% of starting material (1a) was recovered at the end of the reaction.
35% of starting material (1b) was recovered at the end of the reaction.
13% of starting material (1c) was recovered at the end of the reaction.
Values in brackets ratios of 3 and 4 determined by NMR analysis of the isolated
b
c
d
e
mixture.
packed with silica-gel 60 N spherical neutral size 63–210
m
m. 1H
and (1H decoupled) 13C and 19F nuclear magnetic resonance (NMR)
spectra were recorded at 400 or 300 and 101 or 75 MHz and
repulsion, amplified by the bulky tetrabutylammonium counter-
ion of the nucleophile, prevented, as unambiguously proven in the
case of bromosilane 1c, the formation of 20-fluorobiaryls 5. Such a
regioselectivity observed with ortho-substituted arynes
[62,63,51,64] constitutes an additional proof for the aryne-
mediated mechanism of the fluorination reaction.
282 MHz, respectively. Chemical shifts are reported in
d units,
parts per million (ppm) and were measured relative to the signals
for residual chloroform (7.26 ppm for 1H NMR and 77.16 ppm for
13C NMR). Coupling constants J are given in Hz. Coupling patterns
are abbreviated as, for example, s (singlet), d (doublet), t (triplet), q
(quartet), quint (quintet), sp (septuplet), td (triplet of doublets), m
(multiplet), app. s (apparent singlet) and br (broad). Tetrabuty-
lammonium fluoride (TBAF) was used as commercially available
1 M solution in THF.
3. Conclusion
Fluoride displacement of the TMS group on (2-bromobiphenyl-
3-yl)trimethylsilanes led to the partial conversion of the starting
material into arynes. Regioselective and nucleophilic addition on
this highly reactive intermediate provided, besides the expected
desilylated product, uncommon fluorinated derivatives. So far, in
contrast to aryl-carbon and aryl-heteroatom bond formations
involving arynes, only scarce information on aryne-mediated
fluorination is described in the literature. Starting from more
efficient aryne precursor this process might be used as fluorination
method of aromatic rings. In light of the importance of fluorinated
arenes and the practical limitations of current methods for their
preparation, the conversion of easy accessible aryl halide (Br, I) or
sulfonate (e.g., triflate BB ꢁOTf) with a nucleophilic fluorine source
(such as an alkali metal fluoride) to yield the corresponding aryl
fluoride is a highly desirable transformation [65–67].
Compounds 1a–d and 2a–d were prepared as previously
described in the literature [36,37].
4.1. Synthesis of fluoro and bromo derivatives 4a-d, 5 and 9
4.1.1. 30-Fluoro-2,6-dimethoxy-biphenyl (4a)
To 2,6-dimethoxyphenylboronic acid (4.50 mmol, 819 mg) in a
mixture of toluene (45.0 mL), 2 M aqueous Na2CO3 (18.0 mL) and
EtOH (9 mL) were successively added under Argon 1-fluoro-3-
iodo-benzene (3.00 mmol, 666 mg) and Pd(PPh3)4 (0.15 mmol,
173 mg). This well-stirred mixture was heated at reflux for 18 h
and then diluted at 25 8C with water (100 mL) and toluene (50 mL).
The aqueous layer was separated and washed with CH2Cl2
(2 ꢂ 100 mL). All the organics layers were combined, dried over
Na2SO4 and concentrated under reduced pressure. Purification of
the residue by column chromatography (cyclohexane/CH2Cl2
75:25) followed by crystallization from MeOH afforded biaryl 4a
as a colorless solid (380 mg, 55%). mp 81–83 8C. 1H NMR (300 MHz,
4. Experimental
Starting materials, if commercial, were purchased and used as
such, provided that adequate checks (melting ranges, refractive
indices, and gas chromatography) had confirmed the claimed
purity. When known compounds had to be prepared according to
CDCl3):
7.14 (m, 3H, Ar–H), 7.27–7.39 (m, 2H, Ar–H); 13C NMR (100 MHz,
CDCl3):
56.0 (2 ꢂ CH3), 104.3 (2 ꢂ CH), 113.7 (d, JCF = 21 Hz, CH),
d
3.75 (s, 6H, 2 ꢂ OCH3), 6.66 (d, J = 8.4 Hz, 2H, Ar–H), 6.98–
d

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V. Diemer et al. / Journal of Fluorine Chemistry 134 (2012) 146–155
118.1 (d, JCF = 22 Hz, CH), 118.4 (C), 126.8 (d, JCF = 3 Hz CH), 129.0
(d, JCF = 8 Hz, CH), 129.2 (CH), 136.5 (d, JCF = 8 Hz, C), 157.7 (2 ꢂ C),
residue by column chromatography (cyclohexane/CH2Cl2 75:25)
followed by crystallization from MeOH afforded biaryl 5 as a
colorless solid (0.61 g, 49%). mp 85–87 8C. 1H NMR (300 MHz,
162.5 (d, JCF = 241 Hz, C); 19F NMR (282 MHz, CDCl3):
d
ꢀ114.6 (m).
Anal. Calcd for C14H13FO2: C, 72.40; H, 5.64. Found: C, 72.53; H,
5.67.
CDCl3):
d
2.35 (s, 3H, Ar–CH3), 3.76 (s, 6H, 2 ꢂ OCH3), 6.65 (d,
J = 8.4 Hz, 2H, Ar–H), 7.00 (t, J = 8.4 Hz, 1H, Ar–H), 7.06–7.12 (m,
2H, Ar–H), 7.31 (t, J = 8.3 Hz, 1H, Ar–H); 13C NMR (75 MHz, CDCl3):
4.1.2. 5-Fluoro-20,60-dimethoxy-2-methyl-biphenyl (4b)
d
20.9 (CH3), 56.2 (2 ꢂ CH3), 104.2 (2 ꢂ CH), 113.6 (C), 115.0 (d,
Prepared analogously as biaryl 4a, starting from 2-bromo-4-
fluoro-toluene (5.00 mmol, 0.95 g) and 2,6-dimethoxyphenylboro-
nic acid (7.50 mmol, 1.37 g). Purification of the residue by column
chromatography (cyclohexane/CH2Cl2 75:25) followed by crystal-
lization from hexane at ꢀ78 8C afforded biaryl 4b as a colorless
JCF = 22 Hz, CH), 121.5 (d, JCF = 17 Hz, C), 129.5 (CH), 129.5 (d,
JCF = 8 Hz, CH), 132.7 (d, JCF = 3 Hz, C), 133.3 (d, JCF = 4 Hz, CH),
158.2 (2 ꢂ C), 158.7 (d, JCF = 242 Hz, C); 19F NMR (282 MHz, CDCl3):
d
ꢀ118.9 (m). Anal. Calcd for C15H15FO2: C, 73.15; H, 6.14. Found: C,
73.15; H, 6.19.
solid (0.94 g, 76%). mp 79–80 8C. 1H NMR (300 MHz, CDCl3)
d 2.02
(s, 3H, Ar–CH3), 3.72 (s, 6H, 2 ꢂ OCH3), 6.64 (d, J = 8.4 Hz, 1H, Ar–
H), 6.86 (dd, J = 9.6, 2.7 Hz, 1H, Ar–H), 6.93 (dt, J = 8.4, 2.8 Hz, 1H,
Ar–H), 7.20 (dd, J = 8.2, 6.1 Hz, 1H, Ar–H), 7.31 (t, J = 8.3 Hz, 1H, Ar–
4.1.6. 50-Bromo-30-fluoro-2,6-dimethoxy-biphenyl (6)
Prepared analogously as biaryl 4a, starting from 1,3-dibromo-5-
fluoro-benzene (5.00 mmol, 1.27 g) and 2,6-dimethoxyphenyl-
boronic acid (5.50 mmol, 1.00 g). Purification of the residue by
column chromatography (cyclohexane/CH2Cl2 8:2) afforded biaryl
6 as a colorless solid (0.92 g, 59%) mp 127–128 8C. 1H NMR
H); 13C NMR (75 MHz, CDCl3):
d
19.0 (CH3), 55.9 (2 ꢂ CH3), 104.1
(2 ꢂ CH), 113.9 (d, JCF = 21 Hz, CH), 117.6 (d, JCF = 21 Hz, CH), 118.1
(C), 129.2 (CH), 130.6 (d, JCF = 8 Hz, CH), 133.1 (d, JCF = 3 Hz, C),
136.1 (d, JCF = 8 Hz, C), 157.7 (2 ꢂ C), 160.9 (d, JCF = 241 Hz, C); 19
F
(300 MHz, CDCl3):
Ar–H), 7.01 (dm, J = 9.5 Hz, 1H, Ar–H), 7.18 (td, J = 8.3, 2.0 Hz, 1H,
Ar–H), 7.27 (m, 1H, Ar–H), 7.29 (t, 1H, J = 8.4 Hz, Ar–H); 13C NMR
d
3.75 (s, 6H, 2 ꢂ OCH3), 6.64 (d, J = 8.4 Hz, 2H,
NMR (282 MHz, CDCl3):
73.15; H, 6.14. Found: C, 73.19; H, 6.18.
d
ꢀ119.1 (m). Anal. Calcd for C15H15FO2: C,
(75 MHz, CDCl3):
d
56.0 (2 ꢂ CH3), 104.2 (2 ꢂ CH), 117.0 (d,
4.1.3. 30-Fluoro-2,6-dimethoxy-50-methyl-biphenyl (4c)
JCF = 1 Hz, C), 117.3 (d, JCF = 21 Hz, CH), 117.4 (d, JCF = 24 Hz, CH),
121.6 (d, JCF = 10 Hz, C), 129.8 (CH), 130.0 (d, JCF = 3 Hz, CH), 137.9
(d, JCF = 9 Hz, C), 157.6 (2 ꢂ C), 162.3 (d, JCF = 247 Hz, C); 19F
To a solution of biaryl 6 (2.00 mmol, 622 mg) in THF (8.00 mL)
was added dropwise, under Argon and at ꢀ78 8C, a solution of BuLi
(2.20 mmol) in hexane (1.37 mL). The mixture was stirred at
ꢀ78 8C for 2 h and methyl iodide (2.40 mmol, 0.15 mL) was added
dropwise. The mixture was warmed to 25 8C overnight, hydrolyzed
with water (100 mL) and extracted with CH2Cl2 (3 ꢂ 100 mL). The
combined organic layers were dried over Na2SO4 and concentrated
under reduced pressure. Crystallization from MeOH at ꢀ20 8C gave
biaryl 4c (242 mg, 49%) as a colorless solid. mp 86–88 8C. 1H NMR
(282 MHz, CDCl3):
d
ꢀ112.6 (t, J = 8.8 Hz). Anal. Calcd for
C14H12BrFO2: C, 54.04; H, 3.89. Found: C, 54.01; H, 4.09.
4.1.7. 2-(3-Bromo-5-fluoro-phenyl)-4,4,5,5-tetramethyl-
[1,3,2]dioxaborolane (7)
To 1,3-dibromo-5-fluoro-benzene (40.0 mmol, 10.2 g) in THF
(100 mL) was added dropwise, under inert atmosphere and at
ꢀ40 8C, a solution of isopropyl magnesium chloride (44.0 mmol) in
THF (22.0 mL). After 3 h at ꢀ40 8C, 2-isopropoxy-4,4,5,5-tetra-
methyl-[1,3,2]dioxaborolane (48.0 mmol, 8.93 g) was added drop-
wise. The reaction mixture was warmed to 25 8C overnight,
hydrolyzed with saturated ammonium chloride solution (300 mL)
and extracted with Et2O (3 ꢂ 200 mL). The combined organic
layers were dried over Na2SO4 and solvents were removed by
evaporation under reduced pressure. Purification by distillation (1
mbar, 102 8C) afforded boronic ester 7 as a colorless oil (6.34 g,
(300 MHz, CDCl3):
6.65 (d, J = 8.3 Hz, 2H, Ar–H), 6.82–6.85 (m, 2H, Ar–H), 6.94 (br s,
1H, Ar–H), 7.29 (t, J = 8.4 Hz, 1H, Ar–H); 13C NMR (75 MHz, CDCl3):
d
2.39 (s, 3H, Ar–CH3), 3.75 (s, 6H, 2 ꢂ OCH3),
d
21.6 (CH3), 56.1 (2 ꢂ CH3), 104.3 (2 ꢂ CH), 114.6 (d, JCF = 21 Hz,
CH), 115.0 (d, JCF = 21 Hz, CH), 118.6 (d, JCF = 2 Hz, C), 127.4 (d,
JCF = 3 Hz, CH), 129.1 (CH), 136.0 (d, JCF = 9 Hz, C), 139.3 (d,
JCF = 8 Hz, C), 157.7 (2 ꢂ C), 162.5 (d, JCF = 242 Hz, C); 19F NMR
(282 MHz, CDCl3):
d
ꢀ118.9 (br s). Anal. Calcd for C15H15FO2: C,
73.15; H, 6.14. Found: C, 73.24; H, 6.07.
53%). 1H NMR (300 MHz, CDCl3):
J = 8.3, 2.1 Hz, 1H, Ar–H), 7.40 (dd, J = 8.5, 2.3 Hz, 1H, Ar–H), 7.71 (s,
1H, Ar–H); 13C NMR (75 MHz, CDCl3):
119.9 (d, JCF = 19 Hz, CH), 121.8 (d, JCF = 24 Hz, CH), 122.5 (d,
JCF = 8 Hz, C), 133.4 (d, JCF = 3 Hz, CH), 162.5 (d, JCF = 250 Hz, C) (C–B
not observed); 19F NMR (282 MHz, CDCl3):
d
1.34 (s, 12H, 4 ꢂ CH3), 7.31 (td,
4.1.4. 50-Fluoro-2,6-dimethoxy-[1,10;30,100]terphenyl (4d)
Prepared analogously as biaryl 4a, starting from 5-bromo-3-
fluoro-biphenyl 8 (5.00 mmol, 1.26 g) and 2,6-dimethoxyphenyl-
boronic acid (7.50 mmol, 1.37 g). Purification of the residue by
column chromatography (cyclohexane/CH2Cl2 7:3) followed by
crystallization from cyclohexane afforded terphenyl 4d as a
colorless solid (1.22 g, 79%). mp 112–113 8C. 1H NMR (300 MHz,
d
25.0 (4 ꢂ CH3), 84.6 (2 ꢂ C),
d
ꢀ111.5 (t, J = 8.3 Hz).
4.1.8. 5-Bromo-3-fluoro-biphenyl (8)
CDCl3):
d
3.78 (s, 6H, 2 ꢂ OCH3), 6.69 (d, J = 8.4 Hz, 2 H, Ar–H), 7.08
Prepared analogously as biaryl 4a, starting from iodobenzene
(20.0 mmol, 4.08 g) and boronic ester 7 (10.0 mmol, 3.01 g).
Purification of the residue by column chromatography (cyclohex-
ane) afforded biaryl 8 as a colorless oil (2.26 g, 90%). 1H NMR
(dm, J = 9.9 Hz, 1H, Ar–H), 7.26 (td, J = 9.9, 1.8 Hz, 1H, Ar–H), 7.33
(t, J = 8.4 Hz, 1H, Ar–H), 7.34–7.47 (m, 4H, Ar–H), 7.61–7.64 (m, 2H,
Ar–H); 13C NMR (75 MHz, CDCl3):
d
56.1 (2 ꢂ CH3), 104.3 (2 ꢂ CH),
112.5 (d, JCF = 22 Hz, CH), 116.9 (d, JCF = 21 Hz, CH), 118.3 (d,
JCF = 2 Hz, C), 125.8 (d, JCF = 2 Hz, CH), 127.4 (2 ꢂ CH), 127.7 (CH),
128.9 (2 ꢂ CH), 129.3 (CH), 136.6 (d, JCF = 9 Hz, C), 140.5 (d,
JCF = 2 Hz, C), 142.3 (d, JCF = 8 Hz, C), 157.7 (2 ꢂ C), 162.9 (d,
(100 MHz, CDCl3):
d
7.21–7.25 (m, 2H, Ar–H), 7.37–7.48 (m, 3H,
113.2
Ar–H), 7.52–7.56 (m, 3H, Ar–H); 13C NMR (75 MHz, CDCl3):
d
(d, JCF = 22 Hz, CH), 117.8 (d, JCF = 24 Hz, CH), 123.0 (d, JCF = 10 Hz,
C), 126.3 (d, JCF = 3 Hz, CH), 127.2 (2 ꢂ CH), 128.6 (CH), 129.2
(2 ꢂ CH), 138.7 (d, JCF = 2 Hz, C), 145.0 (d, JCF = 8 Hz, C), 163.1 (d,
JCF = 242 Hz, C); 19F NMR (282 MHz, CDCl3):
d
ꢀ114.8 (t, J = 9.9 Hz).
Anal. Calcd for C20H17FO2: C, 77.90; H, 5.56. Found: C, 77.46; H,
5.54.
JCF = 248 Hz, C); 19F NMR (282 MHz, CDCl3):
d
ꢀ110.6 (m). HRMS
(EI) calcd for: C12H879BrF (M+) 249.9793, found: 249.9814; calcd
for: C12H881BrF (M+) 251.9773, found: 251.9795.
4.1.5. 2-Fluoro-20,60-dimethoxy-5-methyl-biphenyl (5)
Prepared analogously as biaryl 4a, starting from 2-bromo-1-
fluoro-4-methyl-benzene (5.00 mmol, 0.95 g) and 2,6-dimethox-
yphenylboronic acid (6.00 mmol, 1.09 g). Purification of the
4.1.9. 50-Bromo-2,6-dimethoxy-30-methyl-biphenyl (9)
Prepared analogously as biaryl 4c, starting from compound 11
(3.76 mmol, 1.40 g). Purification of the residue by column

V. Diemer et al. / Journal of Fluorine Chemistry 134 (2012) 146–155
153
chromatography (cyclohexane/CH2Cl2 85:15) afforded biaryl 9
(0.85 g, 74%) as a colorless solid. mp 141–142 8C. 1H NMR
113.7 (C), 123.0 (CH), 123.7 (C), 127.3 (CH), 127.7 (CH), 132.4 (C),
153.9 (C), 156.0 (C), 157.7 (C). GC–MS (EI) Calcd for: C14H12O2 (M+)
212.1, Found: 212.2.
(300 MHz, CDCl3):
6.63 (d, J = 8.4 Hz, 2H, Ar–H), 7.07 (br s, 1H, Ar–H), 7.25–7.30 (m,
3H, Ar–H); 13C NMR (75 MHz, CDCl3):
d
2.35 (s, 3H, Ar–CH3), 3.74 (s, 6H, 2 ꢂ OCH3),
d
21.4 (CH3), 56.1 (2 ꢂ CH3),
4.2.4. Desilylation of 1d
104.2 (2 ꢂ CH), 118.3 (C), 121.6 (C), 129.2 (CH), 130.5 (CH), 130.6
(CH), 131.0 (CH), 136.1 (C), 139.3 (C), 157.7 (2 ꢂ C). Anal. Calcd for
To (40-bromo-200,600-dimethoxy-[1,10;30,100]terphenyl-50-yl)tri-
methylsilane 1d (1.50 mmol, 663 mg) in THF (15.0 mL) was added
under Argon and at 25 8C a solution of TBAF (4.50 mmol) in THF
(4.50 mL). The mixture was stirred at 25 8C for 16 h, hydrolyzed
with water (100 mL) and extracted with Et2O (100 mL). The
organic layer was washed with water (2 ꢂ 100 mL) and dried over
Na2SO4. After evaporation of the solvent under reduced pressure, a
mixture of 3d and 4d (3d/4d 74:26, 382 mg, 72%) was isolated by
column chromatography (cyclohexane/CH2Cl2 8:2).
C
15H15BrO2: C, 58.65; H, 4.92. Found: C, 58.29; H, 4.73.
4.1.10. 30,50-Dibromo-2,6-dimethoxy-biphenyl (11)
Prepared analogously as biaryl 4a, starting from 1,3,5-
tribromobenzene (10.0 mmol, 3.15 g) and 2,6-dimethoxyphenyl-
boronic acid (11.0 mmol, 2.00 g). Purification of the residue by
column chromatography (cyclohexane/CH2Cl2 75:25) followed by
crystallization from acetonitrile afforded biaryl 11 as a colorless
solid (1.73 g, 47%). mp 181–183 8C. 1H NMR (300 MHz, CDCl3):
d
4.2.4.1. 40-Bromo-200,600-dimethoxy-[1,10;30,100]terphenyl (3d). Crys-
tallization from MeOH at ꢀ20 8C afforded 3d as a colorless solid
3.75 (s, 6H, 2 ꢂ OCH3), 6.63 (d, J = 8.4 Hz, 2H, Ar–H), 7.30 (t,
J = 8.4 Hz, 1H, Ar–H), 7.42 (d, J = 1.8 Hz, 2H, Ar–H), 7.59 (t,
(220 mg, 40%). mp 102–105 8C. 1H NMR (300 MHz, CDCl3):
d 3.76
J = 1.8 Hz, 1H, Ar–H). 13C NMR (75 MHz, CDCl3):
d
56.0
(s, 6H, 2 ꢂ OCH3), 6.67 (d, J = 8.4 Hz, 2H, Ar–H), 7.26–7.48 (m, 6H,
Ar–H), 7.59–7.61 (m, 2H, Ar–H), 7.71 (d, J = 8.2 Hz, 1H, Ar–H). 13
NMR (75 MHz, CDCl3):
(2 ꢂ CH3), 104.2 (2 ꢂ CH), 116.8 (C), 122.1, 129.8, 132.3, 132.9
(2 ꢂ CH), 137.9 (C), 157.6 (2 ꢂ C) ppm. Anal. Calcd for C14H12Br2O2:
C, 45.20; H, 3.25. Found: C, 44.87; H, 3.43.
C
d
56.2 (2 ꢂ CH3), 104.2 (2 ꢂ CH), 118.9 (C),
124.5 (C), 127.2 (2 ꢂ CH), 127.3 (CH), 127.5 (CH), 128.9 (2 ꢂ CH),
129.7 (CH), 131.2 (CH), 132.8 (CH), 136.5 (C), 140.0 (C), 140.4 (C),
157.9 (2 ꢂ C). Anal. Calcd for C20H17BrO2: C, 65.05; H, 4.64. Found:
C, 65.45; H, 4.55.
4.2. Desilylation of ortho-bromobiarylsilanes 1a–d
4.2.1. Desilylation of 1a
To (2-bromo-20,60-dimethoxy-biphenyl-3-yl)trimethylsilane 1a
(1.50 mmol, 548 mg) in THF (15.0 mL) was added under Argon and
at 25 8C a solution of TBAF (4.50 mmol) in THF (4.50 mL). The
mixture was stirred at 25 8C for 16 h, hydrolyzed with water
(100 mL) and extracted with Et2O (100 mL). The organic layer was
washed with water (2 ꢂ 100 mL) and dried over Na2SO4. After
evaporation of the solvent under reduced pressure, a mixture of 3a
and 4a (3a/4a 30:70, 183 mg, 49%) was isolated by column
chromatography (cyclohexane/CH2Cl2 8:2). Spectroscopic data of
3a were in agreement with literature [36,68].
4.3. Desilylation of ortho-bromobiarylsilanes 1a-c in presence of furan
4.3.1. Desilylation of 1a in presence of furan
To a mixture of (2-bromo-20,60-dimethoxy-biphenyl-3-yl)tri-
methylsilane 1a (0.87 mmol, 318 mg) and furan (8.70 mmol,
0.63 mL) in THF (9.00 mL) was added under Argon and at 25 8C
a solution of TBAF (2.61 mmol) in THF (2.61 mL). The mixture was
stirred at 25 8C for 3 h, hydrolyzed with water (75 mL) and
extracted with Et2O (75 mL). The organic layer was washed with
water (2 ꢂ 50 mL) and dried over Na2SO4. After evaporation of the
solvent under reduced pressure, compounds 3a, 4a, and 12a
contained in the residue (3a/4a/12a 30:11:59 according to NMR
analysis) were separated by column chromatography (cyclohex-
ane/CH2Cl2 80:20 for 3a and 4a then cyclohexane/EtOAc 75:25 for
12a). 12a was isolated as colorless solid (124 mg, 51%) whereas 3a
was recovered in mixture with 4a (3a/4a 72:28 according to NMR
analysis, 53 mg, 22%). Spectroscopic data of 3a were in agreement
with literature [36,68].
4.2.2. Desilylation of 1b
To
(2-bromo-20,60-dimethoxy-6-methyl-biphenyl-3-yl)tri-
methylsilane 1b (1.50 mmol, 568 mg) in THF (15.0 mL) was added
under Argon and at 25 8C a solution of TBAF (4.50 mmol) in THF
(4.50 mL). The mixture was stirred at 25 8C for 16 h, hydrolyzed
with water (100 mL) and extracted with Et2O (100 mL). The
organic layer was washed with water (2 ꢂ 100 mL) and dried over
Na2SO4. After evaporation of the solvent under reduced pressure, a
mixture of 3b and 4b (3b/4b 46:54, 200 mg, 49%) was isolated by
column chromatography (cyclohexane/CH2Cl2 8:2).
4.3.1.1. 3-(2,6-Dimethoxyphenyl)-11-oxa-tricyclo[6.2.1.02,7]undeca-
2(7),3,5,9-tetraene (12a). Analytic pure sample was obtained by
crystallization from cyclohexane. 1H NMR (300 MHz, CDCl3):
d 3.74
4.2.3. Desilylation of 1c
(s, 3H, OCH3), 3.75 (s, 3H, OCH3), 5.39 (s, 1H, bridgehead), 5.74 (s,
1H, bridgehead), 6.67 (t-like, J = 7.6 Hz, 2H, Ar–H), 6.96–7.08 (m,
4H, Ar–H + vinyl), 7.20 (d, J = 6.5 Hz, 1H, Ar–H), 7.31 (t, J = 8.3 Hz,
To
(2-bromo-20,60-dimethoxy-5-methyl-biphenyl-3-yl)tri-
methylsilane 1c (1.00 mmol, 379 mg) in THF (10.0 mL) was added
under Argon and at 25 8C a solution of TBAF (3.00 mmol) in THF
(3.00 mL). The mixture was stirred at 25 8C for 16 h, hydrolyzed
with water (100 mL) and extracted with Et2O (100 mL). The
organic layer was washed with water (2 ꢂ 100 mL) and dried over
Na2SO4. After evaporation of the solvent under reduced pressure,
purification of the residue by column chromatography (cyclohex-
ane/CH2Cl2 8:2) afforded a small amount of dibenzofuran 10
(15 mg, 7%) and a mixture of 3c and 4c (3c/4c 47:53, 150 mg, 55%).
1H, Ar–H); 13C NMR (75 MHz, CDCl3):
d 55.8 (CH3), 56.0 (CH3), 82.3
(CH), 82.7 (CH), 103.9 (CH), 104.6 (CH), 116.7 (C), 118.8 (CH), 124.3
(CH), 126.9 (C), 128.2 (CH), 129.2 (CH), 142.6 (CH), 143.3 (CH),
148.4 (C), 149.2 (C), 157.6 (C), 157.9 (C). HRMS (EI) calcd for:
C
18H16O3 (M+) 280.1099, found: 280.1149.
4.3.2. Desilylation of 1b in presence of furan
To a mixture of (2-bromo-20,60-dimethoxy-6-methyl-biphenyl-
3-yl)trimethylsilane 1b (2.43 mmol, 921 mg) and furan
(24.3 mmol, 1.77 mL) in THF (25.0 mL) was added under Argon
and at 25 8C a solution of TBAF (7.29 mmol) in THF (7.29 mL). The
mixture was stirred at 25 8C for 3 h, hydrolyzed with water
(100 mL) and extracted with Et2O (100 mL). The organic layer was
washed with water (2 ꢂ 100 mL) and dried over Na2SO4. After
evaporation of the solvent under reduced pressure, compounds 3b,
4.2.3.1. 1-Methoxy-8-methyl-dibenzofuran
(10). 1H
NMR
(300 MHz, CDCl3): 2.51 (s, 3H, Ar–CH3), 4.06 (s, 3H, OCH3),
d
6.78 (d, J = 8.1 Hz, 1H, Ar–H), 7.16 (d, J = 8.2 Hz, 1H, Ar–H), 7.21 (dd,
J = 8.3, 1.5 Hz, 1H, Ar–H), 7.36 (t, J = 8.2 Hz, 1H, Ar–H), 7.41 (d,
J = 8.4 Hz, 1H, Ar–H), 7.93 (br s, 1H, Ar–H); 13C NMR (100 MHz,
CDCl3): d 21.5 (CH3), 55.8 (CH3), 103.8 (CH), 104.6 (CH), 110.6 (CH),

154
V. Diemer et al. / Journal of Fluorine Chemistry 134 (2012) 146–155
4b, and 12b contained in the residue (3b/4b/12b 36:4:60 according
to NMR analysis) were separated by column chromatography
(cyclohexane/CH2Cl2 80:20 for 3b and 4b then cyclohexane/EtOAc
75:25 for 12b). 12b was isolated as colorless solid (245 mg, 34%)
whereas 3b was recovered in mixture with 4b (3b/4b 85:15
according to NMR analysis, 170 mg, 23%).
(CH), 82.7 (CH), 103.9 (CH), 104.6 (CH), 116.8 (C), 120.4 (CH), 126.4
(C), 128.1 (CH), 129.1 (CH), 133.9 (C), 142.4 (CH), 143.6 (CH), 146.4
(C), 148.7 (C), 157.7 (C), 157.9 (C). Anal. Calcd for C19H18O3: C,
77.53; H, 6.16. Found: C, 77.42; H, 6.12.
Acknowledgements
4.3.2.1. 60-Bromo-2,6-dimethoxy-20-methyl-biphenyl (3b). Analyti-
cally pure sample of 3b was obtained by crystallization from MeOH
at ꢀ20 8C. Colorless solid; mp 104–106 8C. 1H NMR (300 MHz,
`
We are grateful to the CNRS, the ‘‘Ministere de l’Education
Nationale et de la Recherche’’, and the Agence Nationale pour la
Recherche (ANR Program 07-BLAN-0292-01, MetChirPhos) for its
financial support and a postdoctoral grant to V.D.
CDCl3): d 2.05 (s, 3H, Ar–CH3), 3.74 (s, 6H, OCH3), 6.66 (d, J = 8.4 Hz,
2H, Ar–H), 7.09 (t, J = 7.7 Hz, 1H, Ar–H), 7.21 (br d, J = 7.5 Hz, 1H,
Ar–H), 7.35 (t, J = 8.4 Hz, 1H, Ar–H), 7.49 (d, J = 7.8 Hz, 1H, Ar–H);
13C NMR (75 MHz, CDCl3):
d
= 20.7 (CH3), 56.0 (2 ꢂ CH3), 104.1
Appendix A. Supplementary data
(2 ꢂ CH), 118.1 (C), 125.5 (C), 128.4 (2 ꢂ CH), 129.4 (CH), 129.6
(CH), 135.7 (C), 139.7 (C), 157.4 (2 ꢂ C) ppm. HRMS (EI) calcd for:
C15H1579BrO2 (M+): 306.0255, found: 306.0296; calcd for:
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jfluchem.2011.02.017.
C
15H1581BrO2 (M+) 308.0235, found: 308.0277.
4.3.2.2. 3-(2,6-Dimethoxy-phenyl)-4-methyl-11-oxa-tricy-
clo[6.2.1.02,7]undeca-2(7),3,5,9-tetraene (12b). mp 146–148 8C. 1H
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bridgehead), 6.65 (d, J = 8.4 Hz, 1H, Ar–H), 6.66 (d, J = 8.4 Hz, 1H,
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(CH3), 55.7 (CH3), 55.9 (CH3), 82.2 (CH), 82.8 (CH), 103.8 (CH),
104.2 (CH), 115.5 (C), 119.0 (CH), 125.6 (CH), 127.5 (C), 129.3 (CH),
134.8 (C), 142.9 (CH), 143.2 (CH), 145.7 (C), 149.7 (C), 157.8 (2 ꢂ C).
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To a mixture of (2-bromo-20,60-dimethoxy-5-methyl-biphenyl-
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d
2.33 (s, 3H, Ar–CH3), 3.74 (s, 6H, 2 ꢂ OCH3), 6.65 (d, J = 8.3 Hz, 2H,
Ar–H), 6.99–7.04 (m, 2H, Ar–H), 7.33 (t, J = 8.3 Hz, 1H, Ar–H), 7.52
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21.1 (CH3),
d
56.2 (2 ꢂ CH3), 104.3 (2 ꢂ CH), 119.2 (C), 122.0 (C), 129.5 (CH),
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NMR (300 MHz, CDCl3):
d 2.34 (s, 3H, Ar–CH3), 3.74 (s, 3H, OCH3),
3.76 (s, 3H, OCH3), 5.37 (s, 1H, bridgehead), 5.70 (s, 1H,
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13C NMR (75 MHz, CDCl3):
d 21.5 (CH3), 55.8 (CH3), 56.0 (CH3), 82.1

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