An exploration of Suzuki aryl cross coupling chemistry involving [2.2]paracyclophane derivatives

Article abstract of DOI:10.1039/b415764h

Suzuki aryl cross coupling reactions using derivatives of [2.2]paracyclophane were examined. A variety of aryl boronic acids and pinacolate esters were successfully cross coupled with 4-bromo[2.2] paracyclophane under standard Suzuki conditions. Whilst an

Full text of DOI:10.1039/b415764h

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A R T I C L E
An exploration of Suzuki aryl cross coupling chemistry involving
[2.2]paracyclophane derivatives†
Alex J. Roche* and Belgin Canturk
Rutgers, The State University of New Jersey, Department of Chemistry, 315 Penn St, Camden,
NJ, 08102-1411, USA. E-mail: alroche@crab.rutgers.edu
Received 13th October 2004, Accepted 17th November 2004
First published as an Advance Article on the web 22nd December 2004
Suzuki aryl cross coupling reactions using derivatives of [2.2]paracyclophane were examined. A variety of aryl
boronic acids and pinacolate esters were successfully cross coupled with 4-bromo[2.2]paracyclophane under standard
Suzuki conditions. Whilst an excellent tolerance for electron donating and withdrawing groups was observed, cross
coupling reactions with highly sterically demanding borates (e.g. mesityl) were unsuccessful. The preparation and
stability of the previously unreported [2.2]paracyclophanyl-4-boronic acid, -pinacolate ester and -dimethyl ester are
described, along with the utility of these systems in Suzuki aryl cross coupling reactions. Application of this
methodology led to a dicyclophane containing two [2.2]paracyclophane units separated by a 4–4ꢀconnected biphenyl
spacer group.
Introduction
Even though [2.2]paracyclophane (PCP)1 was first prepared
more than half a century ago, the chemistry and utility of this
compound and its derivatives are still active fields of research.2
PCP compounds find application in a multitude of areas, includ-
ing unique polymers3 and materials,4 and catalysts with planar
chirality.5 As part of the ongoing development of the chemistry
of 1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane (OFP),6–8 we
had previously described the preparation of the boronic acid of
OFP,9 and studied its potential in Suzuki aryl cross coupling
reactions.9,10 In order to probe the influence that the octafluori-
nated bridges impart on such systems, we had to compare the
preparation and reactivity of the boronic acids (and esters) of
PCP and OFP. We were slightly surprised to find no literature
reports concerning the boronic acid of PCP. Indeed at outset of
this project, there were no literature reports of either substituted
or unsubstituted PCP boronic acids/esters, or even Suzuki aryl
cross coupling reactions on a PCP skeleton, although Heck
couplings have been reported.11 However, last year Rozenberg
and coworkers reported Suzuki coupling reactions of several
hetero- and homo-annularly substituted PCP systems en route to
a selection of planar chiral bidentate ligands.12 Our interest lay in
the use of Suzuki aryl cross coupling methodology to introduce
a variety of functionalized aryl groups into the 4-position of
paracyclophanes to prepare more exotic monomers for Parylene
type polymers and also with the aim of generating dicyclophanes
(compounds containing two paracyclophane units connected
through an aryl–aryl linkage).
ditions (Table 1, entry 5). The results from reactions employing
either aryl boronic acids (method A) or boronic acid pinacol
esters (method B) displayed no considerable differences. The
same protocol was followed for all the aryl cross couplings; the
reagents and catalyst were added into the reaction vessel under
a counter-current of dry nitrogen, the solvent was added via
syringe and then the reaction mixture was warmed to reflux
for 48 h. TLC was used to monitor the reaction progress and
then ether/water workup was followed by product isolation
using column chromatography on silica gel. After establishing
this ground work, we sought to compare the effectiveness of
the same cross coupling transformations, but with interchanged
functionalities, i.e. reacting PCP–B(OH)2, 7, with a selection of
aryl bromides.
The synthesis of boronic acid 7 is not reported in the literature
and our initial attempts to prepare and isolate 7 using standard
synthetic methods met with disappointment. Compound 7
appears to be unstable in air and exposure to silica gel led
to the production of PCP–OH 813 and PCP. However, the
formation of 8 was taken as evidence that the desired boronic
acid was generated at least to some extent. Indeed, following
the established literature preparation of 8,13 deliberate oxidation
(using alkaline hydrogen peroxide) of our reaction mixture
afforded product 8 in 79% isolated yield (Scheme 1). This can
be taken as a lower limit for the yield of formation of 7. The
instability of boronic acid 7 is in contrast to its octafluorinated
bridge analogue, with the latter being oxidatively stable in air
and able to be stored and used in reactions without special
precautions.9 Our inability to isolate compound 7 left us with
two alternatives; try to prepare a more stable analogue (such as
boronate ester), or try to generate and react the boronic acid
in situ.
Results and discussion
In order to examine the scope of Suzuki aryl cross coupling
reactions on the [2.2]paracyclophane skeleton, coupling reac-
tions using 4-bromo[2.2]paracyclophane 1 and a selection of
aryl boronic acids (method A) and pinacolate esters (method B)
were performed.
As shown in Table 1, an excellent tolerance of electronically
different substituents on the phenyl group was observed. We
observed that an ortho tolyl group could be cross coupled
successfully (Table 1, entry 2), but that the sterically larger
mesityl could not be cross coupled onto PCP using these con-
Both the dimethyl and diisopropyl borate esters of PCP were
found to be similarly unstable. However, the boronic acid pinacol
ester of PCP 9 which was easily prepared by the reaction of 1
with butyllithium and bis(pinacolato)diboron, was found to be
† Electronic supplementary information (ESI) available: 13C and 1H
NMR spectra of compounds 3–5, 9 and 11. See http://www.rsc.org/
suppdata/ob/b4/b415764h/
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 5 1 5 – 5 1 9
5 1 5
©

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Table 1 Suzuki reactions leading to aryl-substituted cyclophanes
Isolated yields
Method A/%
Entry
Y
Product
Method B/%
Method C/%
1
2
3
4
5
H
2
3
4
5
6
84
81
87
80
0
87
86
83
88
0a
79
82
87
85
0
2-Me
4-CN
3-OH
2,4,6-Me3
a Bis(pinacol) ester used.
signals.15 The 13C NMR spectra of these systems were fully
consistent with the product structures, but spectroscopically
unremarkable, as indeed were the mass spectra which displayed
the characteristic cyclophane–xylylene fragmentation patterns.2
There are a variety of dicyclophane compounds where two
cyclophanes are linked through an aryl–aryl linkage, including
the parent system diPCP,16 its bridge fluorinated analogue,8
and a number of systems containing organic, inorganic17 and
transition metal18 spacer groups. Due to the planar chirality
of mono-substituted [2.2]paracyclophanes,2 there is interest in
the diastereoselectivity of dicyclophane formation and in NMR
chemical shift differences between diastereomers of this type.
Such compounds are also of interest as they serve as monomers
for cross linked Parylene type polymers.19
Scheme 1 Reaction conditions: (i) BuLi, B(OMe)3, ether, then H3O+;
(ii) air, or H2O2, NaOH, THF, H2O.13
stable in air and could be isolated in 71% yield as a colorless
solid using column chromatography on silica gel (Scheme 2).
Product 9 could also be formed by transesterification of the
initially formed dimethyl boronate, using pinacol.
Our initial attempts to use the above Suzuki methodology to
prepare diPCP, or PCP–OFP dicyclophanes were not successful,
with sterics being the most likely cause. So we turned our
attention to the formation of a dicyclophane with a spacer group.
In an attempt to prepare a dicyclophane with a phenyl spacer
group, we reacted p-phenyldiboronic acid with an excess of 1
under Suzuki conditions. Surprisingly, the only dicyclophane
product observed in the reaction was identified as 11, in 44%
isolated yield (Scheme 4). It is presumed that this product arises
from a homocoupling of boronic acids. The same product with
similar yield (33%) was also observed employing the dipinacolate
ester. Such homocouplings of arylboronic acids (and esters)
during Suzuki reactions are known to occur when the cross
coupling reaction is very slow.20 A similar product was also
reported in the case of the bridge-fluorinated analogue.9
Scheme 2 Reaction conditions: (i) BuLi, bis(pinacolato)diboron, THF.
The enhanced stability of 9 was demonstrated by exposure to
alkaline hydrogen peroxide, which resulted in only a 10% con-
version to 8 after 24 h, with 2 weeks required for full conversion.
However, this extra stability unfortunately precluded the efficient
use of 9 in Suzuki cross coupling experiments, as the reaction
of 9 with aryl bromides under standard Suzuki conditions gave
only low conversions (<10%) to desired products after one week
under reflux.
Alternatively, as shown in Scheme 3, the in situ formation
and reaction of PCP–B(OMe)2, 10 with aryl bromides was
much more productive (Table 1, method C). These two-step,
one-pot Suzuki reactions gave cross coupled products in high
yields comparable to the yields of the arylboronic acid/PCP–Br
approach.
Scheme 4
Scheme 3 Reaction conditions: (i) BuLi, B(OMe)3; (ii) BrC6H4-Y,
Pd(PPh3)2Cl2, K2CO3, THF, H2O.
Product 11 showed analytical data characteristically similar
to the aryl derivatives 2–5 described above. In the H NMR
1
The various aryl-substituted paracyclophanes prepared were
spectrum, the biphenyl hydrogens appeared as a doublet of
doublets at dH = 7.7 and 7.9 ppm and the cyclophane aryl
hydrogens were clustered together around dH = 6.6 ppm. We were
not able to convincingly resolve the meso and (DL) diastereomers
of 11 by any GC or HPLC techniques available to us. Such
diminutive diastereomeric differences imply that the planar
chiral units are significantly alienated from each other by the
large distance andorientation away from one another, as dictated
by the 4,4ꢀ biphenyl spacer group.
1
identified and confirmed from their H and 13C NMR data.14
1
In the H NMR spectrum of compounds 2–5 it was observed
that the aryl substituents did not exert either a significant
ortho or geminal shift on the cyclophane aryl hydrogens. Thus
compounds 2–5 displayed their substituent aryl C–H signals
at much lower field than the cyclophane aryl C–H resonances.
For example, compound 3 displayed dH = 7.2–7.7 ppm for
the substituent and dH = 6.5–6.7 ppm for the cyclophane aryl
5 1 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 5 1 5 – 5 1 9

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Further investigations into the syntheses of other related cy-
clophane and dicyclophane systems, including their diastereose-
lectivity of formation, spectroscopic properties and applications,
are ongoing in our laboratory.
(Rf = 0.29) 8 (0.31 g, 79%): dH (300 MHz; CDCl3; Me4Si) 6.98
(1 H, dd, 3J 7.8, 4J 1.9), 6.44–6.35 (4 H, m), 6.24 (1 H, dd, 3J 7.7,
4J 1.6), 5.54 (1 H, d, 4J 1.6) (aryl C–Hs); 4.40 (1 H, br s, OH); 3.39
(1 H, m), 2.66–3.27 (6 H, m), 2.59 (1 H m) (bridge CH2s); m/z
(EI) 224 (M+, 50%), 104 (50), 120 (100). Such characterization
is in excellent agreement with literature values.13
Experimental
General details
4-(3-Hydroxyphenyl)[2.2]paracyclophane (5)
All NMR spectra were obtained on a Varian Mercury Plus
300 MHz spectrometer with 5 mm ATB probe at ambient
temperature. Coupling constants are given in Hz. All products
were colorless solids, except where specified otherwise in the text.
All reagents, unless otherwise specified, were used as purchased
from Aldrich or Fisher. Column chromatography was performed
using chromatographic silica gel 200–425 mesh, as supplied by
Fisher. Melting points are uncorrected. Low-resolution mass
spectrometry was performed at the Center for Advanced Food
Technology, New Brunswick, NJ and high-resolution mass
spectrometry was performed at the University of Pennsylvania,
Philadelphia, PA.
The aryl bromides, boronic acids and boronic acid pinacol
esters used were purchased from commercial sources except
for the following: 4-bromo[2.2]paracyclophane, 1, was prepared
from PCP according to a literature method.21 2-Phenyl-4,4,5,5-
tetramethyl-1,3-dioxaborolane, 2-(2-methylphenyl)-4,4,5,5-tetra-
methyl-1,3-dioxaborolane and 2,2ꢀ-(1,4-phenylene)bis[4,4,5,5-
tetramethyl-1,3-dioxaborolane] were prepared as described
previously.9
Method A. Under a counter-current of nitrogen gas, a
round-bottomed flask was charged with 4-bromo[2.2]para-
cyclophane, 1, (0.20 g, 0.70 mmol), 3-hydroxyphenylboronic
acid (0.13 g, 0.94 mmol), bis(triphenylphosphine)palladium(II)
chloride (23 mg, 0.04 mmol), potassium carbonate (0.26 g,
1.88 mmol), THF (6 mL) and water (1.5 mL). The vessel
was thoroughly flushed with N2 and the mixture heated under
reflux for 48 h. The reaction mixture was then cooled to room
temperature, extracted with ether (3 × 20 mL), the extracts were
dried (MgSO4) and evaporated under reduced pressure. The
crude product was chromatographed (hexane–ether 1 : 1, Rf =
0.46) to give 5 (168 mg, 80%); mp = 185–189 ◦C (from ether); dH
(300 MHz; d6-acetone; Me4Si) 8.40 (1 H, s), 7.30 (1 H, t, 3J 7.4),
6.97 (1 H, d, 3J 7.4), 6.85 (1 H, d, 3J 7.4), 6.68–6.52 (7 H, m) (aryl
C–Hs); 3.37–3.50 (m, 2H), 2.83–3.21 (m, 4H), 2.58–2.70 (m, 2H)
(bridge CH2s); dC (75 MHz; d6-acetone; Me4Si) 136.00, 133.25,
132.75, 132.35, 132.28, 132.17, 129.94, 129.59, 121.09, 116.70,
13.90 (aryl C–Hs); 157.79 (C–OH); 140.00, 139.83, 139.68,
139.59, 137.38, 137.01 (quaternary); 35.46, 35.16, 34.92, 34.26
(CH2s); m/z (EI) 300 (M+, 90%), 181 (90), 195 (100). HRMS
(CI+) 300.1511 (M+. C22H20O requires 300.1515).
Method B. Under a counter-current of nitrogen gas, a
round-bottomed flask was charged with 4-bromo[2.2]paracy-
clophane, 1, (0.20 g, 0.70 mmol), 3-hydroxyphenylboronic acid
pinacol ester (0.23 g, 1.05 mmol), bis(triphenylphosphine)-
palladium(II) chloride (23 mg, 0.04 mmol), potassium carbonate
(0.26 g, 1.88 mmol), THF (6 mL) and water (1.5 mL). The vessel
was thoroughly flushed with N2 and the mixture heated under
reflux for 48 h. The reaction mixture was then cooled to room
temperature, extracted with ether (3 × 20 mL), the extracts
were dried (MgSO4) and evaporated under reduced pressure.
The crude product was chromatographed (hexane–ether 1 : 1,
Rf = 0.46) to give 5 (185 mg, 88%) spectroscopically identical
with the sample prepared above.
Method C. 4-Bromo[2.2]paracyclophane, 1, (0.20 g,
0.70 mmol) and ether (30 mL) were cooled to −78 ◦C under
an N2 atmosphere. n-Butyllithium (0.86 mL of 1.6 M in hexane,
1.38 mmol) was added and the solution was stirred at this
temperature for 1 h. Trimethyl borate (0.17 mL, 1.39 mmol)
was syringed into the solution and the solution was left to
stir for an additional hour whilst warming to 0 ◦C. Through
a pressure-equalizing dropping funnel, a THF (6 mL) solution
of 3-bromophenol (0.24 g, 1.39 mmol) and bis(triphenyl-
phosphine)palladium(II) chloride (23 mg, 0.04 mmol) were
added, followed by an aqueous solution (1.5 mL) of potassium
carbonate (0.26 g, 1.88 mmol). The vessel was thoroughly flushed
with N2 and the mixture was heated under reflux for 48 h.
The reaction mixture was then cooled to room temperature,
extracted with ether (3 × 20 mL) and the extracts were dried
(MgSO4) and evaporated under reduced pressure. The crude
product was chromatographed (hexane–ether 1 : 1, Rf = 0.46)
to give 5 (179 mg, 85%) spectroscopically identical with the
sample prepared above.
[2.2]Paracyclophanyl-4-boronic acid pinacol ester (9)
4-Bromo[2.2]paracyclophane, 1, (1.47 g, 5.10 mmol) in THF
◦
(47 mL) was cooled to −78 C under a dry N2 atmosphere. n-
Butyllithium (4.7 mL of 1.6 M in hexane, 7.52 mmol) was added
dropwise and the solution was stirred for 1 h at this temperature.
A solution of bis(pinacolato)diboron (2.55 g, 10.04 mmol) in
THF (10 mL) was slowly syringed into the reaction mixture
and the mixture was left to stir for an additional 1 h at this
temperature. The reaction mixture was then allowed to warm
to room temperature overnight. The mixture was extracted
with ether (3 × 20 mL), the extracts were dried (MgSO4)
and evaporated under reduced pressure. The solid residue was
subjected to column chromatography (hexane–chloroform 1 :
1) to give (Rf = 0.55) 9 (1.21 g, 71%); mp 104–106 ◦C (from
chloroform); dH (300 MHz; d6-acetone; Me4Si) 6.86 (1 H, d,
3
4J 1.5), 6.43 (1 H, d, J 9.9), 6.28–6.34 (4 H, m), 6.23 (1H,
3
d, J 7.8) (aryl C–Hs); 2.71–2.89 (8 H, m, bridge CH2s) 1.27
(12 H, s, CH3s); dC (75 MHz; d6-acetone; Me4Si) 139.60, 134.51,
133.18, 132.52, 132.30, 131.84, 131.45 (aryl C–Hs); 34.93, 34.72,
34.59, 34.45 (CH2s); 146.37, 138.93, 138.75, 137.44 (cyclophane
bridgeheads); 82.37 (quaternary); 23.95, 23.76 (CH3s); m/z (EI)
334 (M+, 90%), 83 (40), 130 (60), 229 (40), 203 (100). HRMS
(CI+) 334.2089 (M+. C22H27BO2 requires 334.2104).
4-Hydroxy[2.2]paracyclophane (8)
4-Bromo[2.2]paracyclophane, 1, (0.50 g, 1.77 mmol) and ether
(22 mL) were cooled to −78 ◦C under an atmosphere of dry N2.
n-Butyllithium (2.31 mL of 1.6 M in hexane, 3.70 mmol) was
added dropwise and the solution was stirred as it warmed to
room temperature for 20 min. The temperature of the reaction
mixture was brought down to 0 ◦C and then trimethyl borate
(0.39 mL, 3.46 mmol) was syringed into the solution and the
mixture was left to stir for an additional 1 h. To the reaction
mixture was added an aqueous solution of 0.5 M sodium
hydroxide (0.86 mL, 0.43 mmol) and 30% hydrogen peroxide
(0.74 mL, 6.49 mmol) and the mixture was heated at 40 ◦C
for 2 h. The solution was acidified with dilute HCl, extracted
with ether (3 × 20 mL) and the extracts were dried (MgSO4)
and evaporated under reduced pressure. The solid residue
was subjected to column chromatography (chloroform) to give
4-(4-Cyanophenyl)[2.2]paracyclophane (4)
At the same scale and according to the same procedure
as described in method A, 4-cyanophenylboronic acid, after
column chromatography (hexane–dichloromethane 1 : 1), gave
(Rf = 0.44) 4 (188 mg, 87%); mp = 107–108 ◦C (from
dichloromethane); dH (300 MHz; d6-acetone; Me4Si) 7.87 (2 H,
3
4
3
4
dd, J 6.0 and J 1.5), 7.74 (2 H, dd, J 6.6 and J 2.1), 6.53
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 5 1 5 – 5 1 9
5 1 7

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(1 H, d, 3J 8.1), 6.60 (1 H, d, 3J 7.5), 6.62 (1 H, d, 3J
9.3), 6.66–6.69 (4 H) (aryl C–Hs); 3.39 (1 H, m), 2.76–3.20
(6 H, m), 2.53–2.62 (1 H m) (bridge CH2s); dC (75 MHz; d6-
acetone; Me4Si) 136.44, 133.50, 133.39, 132.92, 132.50, 132.26,
132.23, 130.77, 129.76 (aryl C–Hs); 34.47, 34.27, 33.98, 33.21
(CH2s); 139.51, 139.34, 138.85, 138.65 (cyclophane bridge-
heads); 147.18, 145.10, 109.61 (quaternary); 117.78 (CN); m/z
(EI) 309 (M+, 34%), 104 (42), 105 (100). HRMS (CI+) 309.1519
(M+. C23H19N requires 309.1518).
Acknowledgements
The National Science Foundation is gratefully acknowledged
for allowing the purchase of an NMR system through a Major
Research Instrumentation grant (NSF CHE-0116145). Rutgers,
The State University of New Jersey, Campus at Camden, is
also acknowledged for generously providing startup funds.
Additionally, Shirin Modarai is thanked for her laboratory
assistance.
Method B using 4-cyanophenylboronic acid pinacol ester gave
4 in 83%; Method C using 4-bromobenzonitrile gave 4 in 87%.
References
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4-Phenyl[2.2]paracyclophane (2)
At the same scale and using the same procedure as described in
method A with phenylboronic acid, after column chromatogra-
phy (hexane–chloroform 8 : 1), gave (Rf = 0.35) 2 (167 mg, 84%);
dH (300 MHz; d6-acetone; Me4Si) 7.46 (2 H, d, 3J 7.5), 7.35 (2 H,
t, 3J 7.2), 7.29 (1 H, t, 3J 7.4), 6.59–6.91 (7 H, m) (aryl C–Hs);
2.66–3.20 (7 H, m) 3.40–3.51 (1 H, m) (bridge CH2s); m/z (EI)
284 (M+, 27%), 180 (100), 104 (76). Such data is in agreement
with previously reported data.22,23
Method B using phenylboronic acid pinacol ester gave 2 in
87%; Method C using bromobenzene gave 2 in 79%.
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4-(2-Methylphenyl)[2.2]paracyclophane (3)
At the same scale and using the same procedure as described
in method A, 2-methylphenylboronic acid, after column chro-
matography (hexane–chloroform 7 : 1), gave (Rf = 0.33) 3
◦
(169 mg, 81%); mp = 105–110 C (from chloroform) (lit.23
=
114–116 ◦C); dH (300 MHz; d6-acetone; Me4Si) 7.71 (1 H, d,
3
3
3J 7.5), 7.41 (1 H, d, J 7.2), 7.23 (1 H, d, J 7.5), 7.29 (1 H,
3
3
d, J 7.5), 6.72 (1 H, d, J 7.8), 6.60–6.67 (3 H, m), 6.50–6.57
(3 H, m) (aryl C–Hs); 3.02–3.16 (6 H, m), 2.75–2.89 (2 H, m)
(bridge CH2s), 2.09 (3 H, s, CH3); dC (75 MHz; d6-acetone;
Me4Si) 133.65, 132.44, 132.20, 131.68, 131.59, 131.55, 129.14,
129.14, 129.01, 126.18, 125.37 (aryl C–Hs); 34.52, 34.35, 34.31,
32.66 (CH2s); 140.62, 139.90, 138.86, 138.78, 127.58, 136.30,
135.26 (quaternary); 18.93 (CH3); m/z (EI) 298 (M+, 50%), 104
(40), 178 (50), 179 (70), 193 (100). HRMS (CI+) 298.1718 (M+.
C23H22 requires 298.1722). Such data agrees with and expands
upon, the reported spectroscopic data.23
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7216.
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(b) A. J. Roche and W. R. Dolbier, Jr., J. Org. Chem., 2000, 65, 5282;
(c) W. R. Dolbier, Jr., J. X. Duan, K. Abboud and B. Ameduri,
J. Am. Chem. Soc., 2000, 122, 12083; (d) L. Guyard, P. Audebert,
W. R. Dolbier and J. X. Duan, J. Electroanal. Chem., 2002, 537, 189;
(e) W. R. Dolbier, Jr., J. X. Duan and A. J. Roche, US Pat. , 6392097,
2002; (f) W. R. Dolbier, Jr. and W. F. Beach, J. Fluorine Chem., 2003,
122, 97; (g) M. A. Battiste, J. X. Duan, Y. A. Zhai, I. Ghiviriga, K.
Abboud and W. R. Dolbier, Jr., J. Org. Chem., 2003, 68, 3078.
8 A. J. Roche, J. X. Duan, W. R. Dolbier, Jr. and K. A. Abboud, J. Org.
Chem., 2001, 66, 7055.
Method B using 2-methylphenylboronic acid pinacol ester
gave 3 in 86%; Method C using 2-bromotoluene gave 3 in 82%.
4,4ꢀ-Bis([2.2]paracyclophan-4-yl)biphenyl (11)
Under a counter-current of nitrogen gas, a round-bottomed
flask was charged with 4-bromo[2.2]paracyclophane
1
(0.24 g, 0.84 mmol), phenylene-1,4-diboronic acid (34 mg,
0.20 mmol), bis(triphenylphosphine)palladium(II) chloride
(14 mg, 0.02 mmol), potassium carbonate (0.32 g, 2.32 mmol),
THF (8.5 mL) and water (1.5 mL). The vessel was thoroughly
flushed with N2 and the mixture was heated under reflux for 48 h.
The reaction mixture was then cooled to room temperature,
extracted with ether (3 × 20 mL) and the extracts were dried
(MgSO4) and evaporated under reduced pressure. The crude
product was subjected to column chromatography (hexane–
chloroform 2 : 1) to give (Rf = 0.59) 11 (25 mg, 44%); mp = 103–
106 ◦C (from chloroform); dH (300 MHz; d6-acetone; Me4Si) 7.79
(4 H, d, 3J 8.4), 7.59 (4 H, d, 3J 8.4), 6.53–6.66 (14 H, m) (aryl
C–Hs); 3.53 (2 H, m), 2.67–3.22 (12 H, m), 2.58–2.63 (2 H, m)
(bridge CH2s); dC (75 MHz; d6-acetone; Me4Si) 135.27, 132.38.
131.93, 131.61, 131.42, 131.28. 129.53. 128.97, 126.12 (aryl C–
Hs); 141.53, 140.70, 140.67, 140.05 (cyclophane bridgeheads);
139.70, 139.67. 137.13 (quaternary); 34.54, 34.27, 33.99, 33.44
(CH2s). m/z (EI) 566 (M+, 100%), 119 (40), 357 (50). HRMS
(CI+) 566.3002 (M+. C44H38 requires 566.2974).
9 A. J. Roche and B. Canturk, J. Fluorine Chem.,
DOI: 10.1016/j.jfluchem.2004.11.008.
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12 V. I. Rozenberg, D. Y. Antonov, R. P. Zhuravsky, E. V. Vorontsov
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14 For an excellent review of cyclophane NMR spectroscopy see: L.
Ernst, Prog. Nucl. Magn. Reson. Spectrosc., 2000, 37, 47.
15 This convenient “separation” of substituent and cyclophane aryl C–
H NMR signals was useful since it assisted us in the elucidation
1
of the corresponding H NMR spectra from the bridge fluorinated
OFP analogues. In these cases, the electron withdrawing fluorines
force the OFP hydrogens to lower field, which often overlapped with
the substituent aryl C–H resonances. See ref. 9.
Using phenylene-1,4-diboronic acid bis-pinacol ester gave 11
in 33%.
5 1 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 5 1 5 – 5 1 9

View Article Online
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O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 5 1 5 – 5 1 9
5 1 9