Competitive pathways in Pd-catalyzed synthesis of arylphenols

Article abstract of DOI:10.1016/j.tet.2013.02.029

Novel developments are described, which have been achieved in the framework of the studies of sequential palladium-catalyzed reactions, involving palladacycle formation with norbornene or norbornadiene via aromatic C-H activation. The use of o-bromophenols as partners of iodobenzenes has led to ring formation after norbornene deinsertion, or to arylphenols, containing a pendant norbornenyl or norbornadienyl group or to vinylarylphenols. The availability of a reductive elimination step drives the reaction course toward a preferential product.

Full text of DOI:10.1016/j.tet.2013.02.029

Tetrahedron 69 (2013) 4421e4428
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Competitive pathways in Pd-catalyzed synthesis of arylphenols
,
Elena Motti a, Nicola Della Ca’ a, Di Xu a b, Simone Armani a, Brunella Maria Aresta c,
,
Marta Catellani a
*
a
ꢀ
Dipartimento di Chimica and CIRCC, Universita di Parma, Parco Area delle Scienze, 17/A, I-43124 Parma, Italy
b R&D Centre for Pharmaceuticals, School of Chemical Engineering and the Environment, Beijing Institute of Technology, Beijing 100081, PR China
c CNR-IC, Via Amendola 122/O, I-70126 Bari, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel developments are described, which have been achieved in the framework of the studies of se-
quential palladium-catalyzed reactions, involving palladacycle formation with norbornene or norbor-
nadiene via aromatic CeH activation. The use of o-bromophenols as partners of iodobenzenes has led to
ring formation after norbornene deinsertion, or to arylphenols, containing a pendant norbornenyl or
norbornadienyl group or to vinylarylphenols. The availability of a reductive elimination step drives the
reaction course toward a preferential product.
Received 3 December 2012
Received in revised form 30 January 2013
Accepted 5 February 2013
Available online 14 February 2013
Keywords:
Palladacycles
Catalysis
Ó 2013 Elsevier Ltd. All rights reserved.
CeH activation
Sequential reaction
1. Introduction
caused to react further with olefins, in particular methyl acrylate, to
terminate the process with liberation of palladium(0) (Scheme 1).2c
Direct CeH activation of Csp2 and Csp3 bonds has opened a va-
riety of synthetic pathways involving CeC bond formation.1 Our
studies in this area have been aimed at working out new methods
to achieve ordered reaction sequences by means of palladium and
norbornene joint catalysis involving palladacycle formation
through CeH bond activation. We have previously shown that bi-
phenyl derivatives can be prepared by reaction of ortho-substituted
iodoarenes with bromoarenes, followed by a variety of irreversible
intermolecular steps, such as Heck and Suzuki coupling leading to
the final organic products.2 The key for the success of these re-
actions is the use of iodoarenes, containing electron-releasing
substituents, in conjunction with bromoarenes, bearing electron-
withdrawing groups. If the latter substituents are present in
iodoarenes, they render iodoarene reactivity too high, so that sec-
ondary reactions, not involving the bromoarene, predominate.
Bromoarenes with donor substituents cannot be generally used
because of their low reactivity.
Scheme 1. Palladium/norbornene catalyzed synthesis of o-vinylbiaryl derivatives.
In continuation of this work we observed that also other
bromoarenes, not containing electron-withdrawing substituents
but having chelating properties, such as bromophenols, could be
used as partners of the iodoarenes.3 Our research thus led us to
the synthesis of an important class of compounds, containing the
base structure of cannabinoids. The one-pot reaction of an ortho-
substituted iodoarene with an o-bromophenol and an electron
poor olefin, such as an acrylic ester in the presence of Pd(OAc)2
and norbornene as catalysts, potassium carbonate as a base in
DMF as solvent at 80 ꢀC for 24 h afforded the corresponding
dibenzopyran derivative in good to excellent yields (Scheme 2).
This result was achieved because the base present in the reaction
mixture acted as a third catalyst to cause the phenolic group to
Using this methodology some years ago we worked out a pro-
cedure leading to biaryl-bonded palladium complexes, which were
* Corresponding author. Tel.: þ39 0521 905415; fax: þ39 0521 905472; e-mail
address: marta.catellani@unipr.it (M. Catellani).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.02.029

4422
E. Motti et al. / Tetrahedron 69 (2013) 4421e4428
add to the double bond of the arylacrylate formed according to
an intramolecular Michael reaction.3
on this point. The situation appeared much more complex than
expected, however, because the presence of the phenolic group
allowed competitive ways to be at work.
In the present paper we shall analyze the iodoarene/bromo-
phenol/norbornene/palladium system and we shall see that the
reaction can be driven toward different products by suitable ter-
mination steps.
2. Results and discussion
Scheme 2. Synthesis of dibenzopyran derivatives.
We expected that the reaction between iodides 1 and bromo-
phenols 2, when carried out in the absence of an electron-poor
olefin, such as methyl acrylate, could give rise to dibenzofurans 3
as a result of the attack of the phenolic hydroxyl on the arylpalla-
dium bond of complex VI (Scheme 4).
The following Schemes 2 and 3 show the stoichiometry of the
reaction and the corresponding reaction pathway, which is sup-
ported by the isolation of products and intermediates.3,2a,b
Scheme 4. Formation of dibenzofurans.
Under the adopted conditions dibenzofuran 3 was obtained only
to a limited extent (conditions for improving yields will be shown
later in this text), the main product being a hydroxybiphenyl, still
bonded to the dehydrogenated norbornyl group. Thus the reaction of
o-iodotoluene and o-bromophenol with norbornene in the presence
of Pd(OAc)2 as catalyst, potassium carbonate as a base in DMF as
solvent at 105 ꢀC for 24 h gave dibenzofuran 3 (R1¼Me; R2, R3, R4¼H)
in only 5% yield together with the arylphenol resulting from
hydrogenolysis of complex VI (4; 2%) (Scheme 4), the main product
being compound 5 (61% yield, Scheme 5). Formation of compound 5
meant that (a) norbornene was not deinserted, as usually observed;
Scheme 3. Proposed reaction pathway to dibenzopyrans (L¼solvent or any co-
ordinating species present in the reaction mixture).
The initial oxidative addition of the iodoarene to the in situ
formed palladium(0) species4 is followed by stereoselective nor-
bornene insertion into the arylpalladium bond of I leading to
complex II with the aryl ring and the palladium group cis and exo to
the norbornyl moiety.5 This species, containing the palladium
center weakly bound to the aromatic ring, readily undergoes pal-
ladacycle formation6 through activation of the aromatic ortho CeH
bond.7 The subsequent oxidative addition of bromophenol to the
palladium(II) metallacycle III to form palladium(IV) complex IV,8 is
followed by selective migration of the phenolic unit onto the aro-
matic site of the metallacycle to give the palladium(II) species V.9
Norbornene deinsertion, likely due to the steric hindrance created
by the two ortho substituents, affords the o-biarylpalladium bro-
mide VI, which readily reacts with the terminal electron-poor
olefin according to the Heck coupling. The resulting organic prod-
uct undergoes Michael-type reaction to the dibenzopyran de-
rivative. Both norbornene insertion (from I to II) and deinsertion
(from V to VI) are equilibrium steps. It is worth noting that the
deinsertion step is favored by the irreversible Heck coupling to
yield the organic product and regenerate the palladium(0) catalyst.
Considering Scheme 3 the question arose of what would happen
in the absence of the added olefin. Another pathway leading to
reaction of the hydroxyl function with the palladium-bonded biaryl
of complex VI seemed to be possible and we set out to gain insight
(b) there was a new type of termination, based on
b-hydrogen
elimination from the palladium-bonded norbornyl group.
Scheme 5. Palladium-catalyzed reaction of o-iodotoluene, o-bromophenol with
norbornene.
Observation (a) arises the question of why norbornene was not
eliminated, contrary to what usually observed. It can be readily
answered considering the coordinating effect of the phenolic group
on the norbornyl-bonded palladium, possibly through formation of
an eight-membered oxapalladacycle. Other type of oxapalladacycle
complexes have been reported.10
The latter observation (b) also leads to the question of why b-
hydrogen elimination occurred on the palladium-bonded nor-
bornyl. As Sicher first observed many years ago11 this elimination in

E. Motti et al. / Tetrahedron 69 (2013) 4421e4428
4423
Table 1
the rigid norbornane system cannot occur intramolecularly because
the correct stereochemical arrangement cannot be reached. We
could show, however, that this becomes possible using an alkali
phenoxide in a bimolecular reaction (Scheme 6).12
Reaction of o-substituted iodoarenes and o-bromophenols with norbornene (ZeZ]
CH2eCH2) or norbornadiene (ZeZ]CH]CH) in the presence of Pd(OAc)2 and K2CO3
in DMF at 105 ꢀCa
Scheme 6. Effect of PhOK in a palladium-catalyzed reaction of bromobenzene with
norbornene.
Entry
R1
R2
R3
R4
ZeZ
Yield of 5 (%)b,c
1
2
3
Me
Me
Me
Me
Me
(CH]CH)2
(CH]CH)2
(CH]CH)2
H
H
H
H
H
Me
H
OMe
OMe
H
Me
OMe
H
H
H
Me
H
H
H
H
H
H
CH2eCH2
CH2eCH2
CH2eCH2
CH2eCH2
CH2eCH2
CH2eCH2
CH2eCH2
CH2eCH2
CH2eCH2
CH]CH
61
62
71
64
74
45
56
60
45
75
72
62
Another instance of b-hydrogen elimination occurring in a rigid
4d
5e
6f
7
molecule has been reported by Dyker,13 who caused 1-
iodonaphthalene to react with acenaphthylene and obtained 1-
(naphthalene-1-yl)acenaphthylene (Scheme 7). This is a special
case, however, where double bond formation is favored by the
particular aromatic structure of the molecule formed.
OMe
8
9g
10
11
12
CF3
Me
Me
H
H
H
H
H
H
H
Me
H
CH]CH
CH]CH
(CH]CH)2
a
Reaction conditions: molar ratio of the reaction components in the order re-
ported in the title 25:25:30 (60 for norbornadiene):1:80; 105 ꢀC for 24 h. DMF as
solvent, under N2; 2.2ꢁ10ꢂ3 mmol Pd(OAc)2/mL DMF.
b
Isolated yield based on the amount of iodoarene put in reaction.
Unless otherwise indicated benzofurans 3 and the corresponding arylphenols
c
are each present in the range 2e10%. Other by-products, mainly derived from re-
action of aryl iodide with norbornene/norbornadiene, have been reported
previously.2a,c,15
Scheme 7.
b-Hydrogen elimination in the rigid structure of the acenaphthylene.
d
48 h.
66 h.
e
f
16% yield of 3 (R1, R2¼(CH]CH)2; R3, R4¼H).
g
45% yield of 3 (R1¼CF3; R2, R3, R4¼H).
The formation of the double bond in the norbornenylarylphenol
of Scheme 5 clearly appears to be analogous to that shown in
Scheme 6. One can wonder, however, why a bimolecular b-hydro-
We can observe that the reaction works satisfactorily with var-
ious substrates both with norbornene and norbornadiene. Yields of
dibenzofurans 3 were in general modest and only using the o-CF3
group in the iodoarene could a satisfactory yield be obtained.16 This
result is likely due to the presence of an electron-withdrawing
group in complex VI (Scheme 4) favoring the final cyclization
step. Table 2 shows that although dibenzofuran formation through
CeO coupling remains difficult in most cases,17 it is enhanced by
raising the temperature and decreasing the ratio between norbor-
nene and palladium to half the stoichiometric amount, thus fa-
voring norbornene expulsion.
gen elimination did not occur earlier, when the arylnorbornylpal-
ladium complex was present together with bromophenoxide.
Apparently the latter is not able to abstract a proton at this stage
and the system acquires the ability to do so only when the phen-
oxide can act intramolecularly. The process is depicted in Scheme 8
starting from intermediate V (Scheme 3), which, in place of un-
dergoing norbornene deinsertion, retains norbornene through co-
ordination of the hydroxyl group to palladium, possibly as in
complex VII.
Table 2
Reaction of o-substituted iodoarenes and o-bromophenols in the presence of nor-
bornene, Pd(OAc)2 and K2CO3 in DMF at 120 ꢀCa
Entry
R1
R2
R3
R4
Yield of 3 (%)b
Yield of 5 (%)b,c
1
2
3
Me
(CH]CH)2
CF3
H
H
H
H
H
H
H
45
24
75
36
37
15
H
a
Reaction condition: molar ratio of the reaction components in the order re-
ported in the title 25:25:12:1:80; 120 ꢀC for 24 h. DMF as solvent, under N2;
2.2ꢁ10ꢂ3 mmol Pd(OAc)2/mL DMF.
Scheme 8. Oxapalladacycle formation preventing norbornene deinsertion and favor-
ing b-H elimination.
b
Isolated yield based on the amount of iodoarene put in reaction.
c
Two diastereoisomers in 1.1:1 molar ratio.
We observed a similar behavior with norbornadiene, which was
previously shown to give rise to analogous palladium complexes.14
Table 1 shows some norbornenyl- and norbornadienyl-substituted
arylphenols, obtained in satisfactory yields as a mixture of two
diastereoisomers. The molar ratio of the latter (determined by
NMR) was 1.4:1 working at 105 ꢀC in the case of norbornenyl-
substituted arylphenols while the corresponding norbornadienyl
derivatives were in the 1.1:1 molar ratio.
Going back to Scheme 8 we could expect a termination step
consisting of reductive elimination leading to the formation of
a ring joining the phenolic to the norbornyl group in oxapallada-
cycle VII. We did not observe this process, but ascertained that in
the presence of a catalytic amount of acid, such as the p-toluene-
sulfonic one it is possible to convert these norbornenyl-substituted
phenols quantitatively into oxaspiro compounds (Scheme 9).

4424
E. Motti et al. / Tetrahedron 69 (2013) 4421e4428
Dehydrogenation of alkyl groups in iodoarenes had been re-
ported18 but we did not expect that it could occur after the formation
of the biphenyl structure, with the hydroxyl group still free to un-
dergo intramolecular cyclization. Apparently dibenzofuran ring
formation is rather difficult and subject to competitive reactions.17
A general consideration is appropriate at this point. The elimi-
nation of norbornene from the (o-hydroxyphenyl)arylnorbornyl-
palladium complex (V, Scheme 3) resulting from aryl coupling
depends on the availability of irreversible steps leading to a final
product with concomitant liberation of palladium(0). If we compare
Schemes 5 and 11 where the starting iodoarenes differ only by
a methylene group we notice that in the latter norbornene is dein-
serted (from V to VI (R1¼Et)) to a significant extent because there is
the possibility of hydrogen elimination from the ethyl group, which
is absent in the case of Scheme 5. In the latter case the norbornyl
group is preserved and undergoes another type of elimination,
leading to norbornenylbiphenylphenol 5 predominantly. Similarly
the addition of methyl acrylate (Scheme 2) causes the complete
elimination of norbornene to allow the biarylpalladium complex
thus formed to undergo the irreversible step consisting of a Heck
reaction. Norbornene elimination to form dibenzofurans does not
occur so easily because ring formation by CeO coupling is more
difficult and requires less norbornene and higher temperature.
Scheme 9. Acid-catalyzed quantitative conversion of 5 into oxaspiro compounds 6.
The X-ray structure of compound 6 (R1¼Me; R2, R3¼OMe;
R4¼H) reveals the presence of only one stereoisomer (Fig. 1). It is
further supported by NMR determinations.
Fig. 1. X-ray structure of compound 6 (R1¼Me; R2, R3¼OMe; R4¼H).
Another surprising result consisted of the unexpected de-
hydrogenation of alkyl groups present in the ortho position of the
starting iodoarene (Scheme 10). The reaction of o-iodoethylbenzene
and o-bromophenol with norbornene, under the conditions re-
ported in Table 1, gave compound 5 (R1¼Et; R2, R3, R4¼H) together
with the vinylphenylphenol 7 and compound 8 in 28%, 18%, and 16%
yield, respectively. Compound 8 results from a secondary reaction,
which takes place by arylation of the first formed vinyl group by
another molecule of palladium-bonded biaryl.
Scheme 11. Proposed pathways for ethyl dehydrogenation and vinyl arylation.
3. Conclusions
In conclusion the reactions of bromoarenes containing a phe-
nolic function with iodoarenes under palladium/norbornene ca-
talysis, involving palladacycle formation via CeH activation, offer
versatile systems allowing to steer reactivity in different directions.
4. Experimental section
4.1. General
Scheme 10. Dehydrogenation of an aryl-bonded ethyl group.
The reaction proceeds as in Scheme 3 until complex V (R1¼Et) is
formed. At this point the steric hindrance generated by the pres-
ence of the two ortho substituents causes norbornene deinsertion
and the resulting arylpalladium bromide VI (R1¼Et) forms the
palladacycle ring VIII, which undergoes reductive elimination to
vinylphenylphenol 7. A secondary Heck type reaction with complex
IX leads to compound 8. The combined yields of 7 and 8 shows that
dehydrogenation represents the majority of the reaction outcome.
Most starting materials were commercially available and were
used without further purification. 2,5-Norbornadiene was dis-
tilled through a Vigreux column prior to use. 4-Methoxy-2-
methyliodobenzene was prepared starting from the correspond-
ing aniline by diazotization procedure.19 3,4-Dimethoxy-2-
methyliodobenzene,20 1-iodo-4-methylnaphthalene,21 and 1-
iodo-4-methoxynaphthalene22 were prepared according to re-
ported procedures.

E. Motti et al. / Tetrahedron 69 (2013) 4421e4428
4425
All reactions were carried out under nitrogen using standard
Schlenk techniques. DMF was dried and stored over 4 A molecular
(B), ]CH), 5.04, 4.98 (2 br s, 1H (A), 1H (B), OH), 2.88, 2.79 (2 br s,
1H (A), 1H (B), H4), 2.54, 2.47 (2 br s, 1H (B), 1H (A), H1), 2.35 (br s,
3H (A), 3H (B), CH3), 2.30, 2.27 (2s, 3H (B), 3H (A), CH3), 1.71e1.37
(m, 2H (A), 2H (B), H5exo, H6exo), 1.22e0.78 (m, 4H (A), 4H (B),
ꢁ
sieves under nitrogen. Gas chromatography analyses were per-
formed with an Agilent Technologies 7820A GC System using
a 30 m SE-30 capillary column. Flash column chromatography was
carried out on Merck Kieselgel 60 and TLC on Merck 60F254 plates.
Mass spectra (EI) were obtained with a Hewlett Packard instrument
working at 70 eV ionization energy. NMR spectra were recorded in
CDCl3 on Bruker AC-300 and AVANCE 300 spectrometers, unless
otherwise indicated. Chemical shifts are reported in parts per
million using the solvent as internal reference (7.26 and 77.00 ppm,
respectively for 1H and 13C). The reported assignments are based on
2D experiments (COSY and NOESY). Melting points were de-
termined with an Electrothermal apparatus and are uncorrected.
Elemental analyses were performed with a Carlo Erba EA 1108-
Elemental Analyzer.
H7syn, H7anti, H5endo, H6endo); 13C NMR:
d 152.8, 152.3, 145.4,
144.7, 137.8, 137.2, 137.1, 136.7, 136.3, 135.1, 134.9, 133.8, 133.6,
133.1, 131.14, 131.07, 130.9, 130.7, 129.5, 129.0, 128.8, 128.7, 128.3,
120.1, 119.6, 116.1, 114.7, 48.7, 48.3, 47.8, 43.0, 42.8, 26.03, 25.97,
24.0, 23.9, 20.94, 20.89, 20.77; MS (EI, 70 eV): Mþ 290 (38), m/z
275 (84), 247 (100), 233 (43), 222 (52), 209 (62), 189 (40), 165
(53), 152 (32). Anal. Calcd for C21H22O: C, 86.85; H, 7.64. Found: C,
86.58; H, 7.57.
4.3.3. 20-(Bicyclo[2.2.1]hept-2-en-2-yl)-30,5-dimethyl-[1,10-bi-
phenyl]-2-ol (5, R1¼Me, R2, R3¼H, R4¼Me, ZeZ]CH2eCH2; Table 1,
entry 3). From 2-iodotoluene (122 mg, 0.56 mmol), 2-bromo-4-
methylphenol (105 mg, 0.56 mmol), and norbornene (63 mg,
0.67 mmol), product 5 was obtained in 71% (115 mg) yield. Eluent:
hexane/EtOAc 95:5. Colorless oil. A 1.4:1 mixture of two stereo-
4.2. General procedure for the reaction of ortho-substituted
aryl iodides with 2-bromophenols and norbornene/
norbornadiene
isomers indicated as A and B. 1H NMR:
d 7.29e7.21 (m, 2H (A), 2H
(B)), 7.16e7.10 (m, 1H (A), 1H (B)), 7.08e6.98 (m, 2H (A), 1H (B)),
6.87e6.78 (m, 1H (A), 2H (B)), 6.04, 5.84 (2d, J¼3.0 Hz, 1H (A), 1H
(B)), 4.91, 4.82 (2 br s, 1H (A), 1H (B)), 2.91, 2.81 (2 br s, 1H (A), 1H
(B)), 2.58, 2.51 (2 br s, 1H (B), 1H (A)), 2.34, 2.33, 2.30, 2.25 (4s, 3H
(B), 3H (A), 3H (A), 3H (B)), 1.74e1.40 (m, 2H (A), 2H (B)),
A Schlenk-type flask, equipped with a magnetic stirring bar, was
charged under nitrogen with K2CO3 (246 mg, 1.78 mmol) and with
a DMF solution (5 mL) of Pd(OAc)2 (5 mg, 0.022 mmol). A DMF
solution (5 mL) of the ortho-substituted aryl iodide (0.56 mmol),
the 2-bromophenol (0.56 mmol), and norbornene (63 mg,
0.67 mmol) or norbornadiene (123 mg, 1.34 mmol) was then added.
The resulting mixture was stirred in an oil bath at 105 ꢀC for
24e66 h. After cooling to room temperature, the mixture was di-
luted with EtOAc (30 mL) and washed with a saturated solution of
NaCl (3ꢁ25 mL). The organic layer was dried over anhydrous
Na2SO4, the solvent was removed under reduced pressure and the
products were isolated by flash column chromatography on silica
gel using mixtures of hexaneeEtOAc as eluent.
1.31e0.78 (m, 4H (A), 4H (B)); 13C NMR:
d 150.4, 149.9, 145.6,
144.7, 137.7, 137.5, 136.4, 136.2, 135.3, 134.9, 133.7, 132.2, 131.4,
131.2, 130.1, 129.9, 129.4, 129.2, 129.0, 128.7, 128.5, 128.1, 127.5,
127.4, 127.3, 126.8, 116.0, 114.4, 48.8, 48.1, 47.5, 43.0, 42.7, 25.9,
25.8, 23.9, 23.7, 20.9, 20.8, 20.5, 20.2; MS (EI, 70 eV): Mþ 290 (29),
m/z 275 (100), 247 (55), 245 (52), 233 (49), 222 (34), 209 (54), 178
(21), 165 (23). Anal. Calcd for C21H22O: C, 86.85; H, 7.64. Found: C,
87.12; H, 7.71.
4.3.4. 20-(Bicyclo[2.2.1]hept-2-en-2-yl)-50-methoxy-30-methyl-[1,10-
biphenyl]-2-ol (5, R1¼Me, R3¼OMe, R2, R4¼H, ZeZ]CH2eCH2; Table
1, entry 4). From 4-methoxy-2-methyliodobenzene (139 mg,
0.56 mmol), 2-bromophenol (97 mg, 0.56 mmol), and norbornene
(63 mg, 0.67 mmol), product 5 was obtained in 64% (110 mg) yield.
Eluent: hexane/EtOAc 95:5. Mp (hexane): 94 ꢀC. A 1.4:1 mixture of
4.3. Characterization data
4.3.1. 20-(Bicyclo[2.2.1]hept-2-en-2-yl)-30-methyl-[1,10-biphenyl]-2-ol
(5, R1¼Me, R2, R3, R4¼H, ZeZ]CH2eCH2; Table 1, entry 1). From 2-
iodotoluene (122 mg, 0.56 mmol), 2-bromophenol (97 mg,
0.56 mmol), and norbornene (63 mg, 0.67 mmol), product 5 was
obtained in 61% (94 mg) yield. Eluent: hexane/EtOAc 95:5. Colorless
oil. A 1.4:1 mixture of two stereoisomers indicated as A and B. 1H
two stereoisomers indicated as A and B. 1H NMR:
d 7.34e7.20 (m,
2H (A), 1H (B)), 7.09 (d, J¼6.9 Hz, 1H (B)), 7.05e6.83 (m, 3H (A), 3H
(B)), 6.76e6.68 (m, 1H (A), 1H (B)), 6.02, 5.84 (2d, J¼2.4 Hz, 1H (A),
1H (B)), 5.16 (br s,1H (A),1H (B)), 3.84, 3.83 (2s, 3H (A), 3H (B)), 2.92,
2.82 (2 br s, 1H (A), 1H (B)), 2.56, 2.48 (2 br s, 1H (B), 1H (A)), 2.35,
2.32 (2s, 3H (B), 3H (A)),1.76e1.40 (m, 2H (A), 2H (B)), 1.31e0.80 (m,
NMR:
d 7.29e7.17 (m, 4H (A), 3H (B)), 7.15e7.08 (m, 1H (A), 1H (B)),
7.04 (d, J¼7.0 Hz, 1H (B)), 7.00e6.81 (m, 2H (A), 2H (B)), 6.02, 5.84
(2 d, J¼2.8 Hz, 1H (A), 1H (B), ]CH), 4.97, 4.90 (2 br s, 1H (A), 1H (B),
OH), 2.89, 2.79 (2 br s, 1H (A), 1H (B), H4), 2.55, 2.48 (2 br s, 1H (B),
1H (A), H1), 2.33, 2.30 (2s, 3H (B), 3H (A)), 1.71e1.37 (m, 2H (A), 2H
(B), H5exo, H6exo), 1.22e0.78 (m, 4H (A), 4H (B), H7syn, H7anti,
4H (A), 4H (B)); 13C NMR (100 MHz, CDCl3):
d 158.4, 158.0, 152.7,
152.2, 145.1, 144.5, 139.3, 138.5, 138.0, 136.4, 134.9, 133.5, 130.9,
130.8, 130.6, 129.4, 129.2, 129.1, 128.8, 128.5, 120.2, 119.6, 116.2,
116.02, 115.98, 114.8, 113.6, 112.6, 55.2, 48.6, 48.5, 48.3, 47.8, 43.0,
42.7, 26.04, 25.96, 23.9, 23.8, 21.2, 21.1; MS (EI, 70 eV): Mþ 306 (69),
m/z 291 (63), 289 (24), 278 (28), 263 (46), 261 (100), 249 (22), 238
(23), 225 (18), 165 (13). Anal. Calcd for C21H22O2: C, 82.32; H, 7.24.
Found: C, 82.65; H, 7.30.
H5endo, H6endo); 13C NMR:
d 152.8, 152.3, 145.4, 144.8, 138.3, 137.7,
137.2, 136.4, 135.3, 135.0, 133.7, 132.7, 132.5, 131.1, 130.8, 130.5, 130.2,
130.1, 129.3, 129.2, 129.0, 128.8, 127.7, 127.4, 126.9, 120.1, 119.6, 116.1,
114.8, 48.8, 48.3, 47.7, 43.0, 42.8, 26.0, 25.9, 24.0, 23.9, 21.0, 20.8; MS
(EI, 70 eV): Mþ 276 (53), m/z 261 (78), 248 (30), 233 (30), 219 (43),
195 (41),178 (20),165 (21). Anal. Calcd for C20H20O: C, 86.92; H, 7.29.
Found: C, 87.23; H, 7.32.
4.3.5. 20-(Bicyclo[2.2.1]hept-2-en-2-yl)-40,50-dimethoxy-30-methyl-
[1,10-biphenyl]-2-ol (5, R1¼Me, R2, R3¼OMe, R4¼H, ZeZ]CH2eCH2;
Table 1, entry 5). From 3,4-dimethoxy-2-methyliodobenzene
(156 mg, 0.56 mmol), 2-bromophenol (97 mg, 0.56 mmol), and
norbornene (63 mg, 0.67 mmol), product 5 was obtained in 74%
(139 mg) yield. Eluent: hexane/EtOAc 9:1. Mp (hexane): 118 ꢀC. A
1.4:1 mixture of two stereoisomers indicated as A and B. 1H NMR:
4.3.2. 20-(Bicyclo[2.2.1]hept-2-en-2-yl)-30,50-dimethyl-[1,10-bi-
phenyl]-2-ol (5, R1, R3¼Me, R2, R4¼H, ZeZ]CH2eCH2; Table 1, entry
2). From 2,4-dimethyliodobenzene (130 mg, 0.56 mmol), 2-
bromophenol (97 mg, 0.56 mmol), and norbornene (63 mg,
0.67 mmol), product 5 was obtained in 62% (101 mg) yield. Eluent:
hexane/EtOAc 95:5. Colorless oil. A 1.4:1 mixture of two stereo-
d
7.32e7.18 (m, 2H (A), 1H (B)), 7.06 (d, J¼6.9 Hz, 1H (B)), 7.02e6.83
isomers indicated as A and B. 1H NMR:
d
7.29e7.17 (m, 2H (A), 1H
(m, 3H (A), 3H (B)), 6.72 (br s,1H (A),1H (B)), 5.98, 5.81 (2d, J¼2.7 Hz,
1H (A), 1H (B)), 5.16 (br s, 1H (A), 1H (B)), 3.88, 3.86 (2s, 6H (A), 6H
(B)), 2.90, 2.80 (2 br s, 1H (A), 1H (B)), 2.59, 2.49 (2 br s, 1H (B), 1H
(B)), 7.12e7.08 (br s, 1H (A), 1H (B)), 7.04 (dd, J¼7.2, 1.7 Hz, 1H (B)),
7.00e6.81 (m, 3H (A), 3H (B)), 6.00, 5.82 (2 d, J¼3.0 Hz, 1H (A), 1H

4426
E. Motti et al. / Tetrahedron 69 (2013) 4421e4428
(A)), 2.27, 2.23 (2s, 3H (B), 3H (A)), 1.75e1.36 (m, 2H (A), 2H (B)),
1.34e0.73 (m, 4H (A), 4H (B)); 13C NMR:
153.0, 152.3, 151.7, 151.2,
152.1, 144.0, 143.3, 136.0, 134.8, 133.7, 132.9, 131.7, 130.9, 130.6,
129.5, 129.1, 128.8, 128.6, 127.0, 126.8, 126.1, 125.6, 125.3, 125.2,
121.9, 120.1, 119.7, 116.1, 114.8, 106.6, 105.6, 55.4, 48.8, 48.7, 48.6,
48.4, 43.1, 42.9, 26.1, 26.0, 23.6; MS (EI, 70 eV): Mþ 342 (86), m/z
313 (26), 301 (15), 285 (31), 273 (44), 261 (100), 202 (22). Anal.
Calcd for C24H22O2: C, 84.18; H, 6.48. Found: C, 84.37; H, 6.43.
d
147.0, 145.1, 144.4, 134.9, 133.5, 132.6, 132.0, 131.8, 131.0, 130.8, 130.5,
130.2, 129.3, 129.0, 128.7, 128.6, 120.0, 119.5, 116.1, 114.7, 112.3, 111.4,
60.0, 55.6, 48.6, 48.3, 47.8, 42.9, 42.7, 26.0, 25.8, 23.74, 23.65, 13.8,
13.7; MS (EI, 70 eV): Mþ 336 (79), m/z 321 (100), 308 (31), 291 (65),
277 (19), 255 (26), 178 (13), 165 (18). Anal. Calcd for C22H24O3: C,
78.54; H, 7.19. Found: C, 78.79; H, 7.26.
4.3.9. 20-(Bicyclo[2.2.1]hept-2-en-2-yl)-30-trifluoromethyl-[1,10-bi-
phenyl]-2-ol (5, R1¼CF3, R2, R3, R4¼H, ZeZ]CH2eCH2; Table 1, entry
9). From 1-iodo-2-(trifluoromethyl)benzene (152 mg, 0.56 mmol),
2-bromophenol (97 mg, 0.56 mmol), and norbornene (63 mg,
0.67 mmol), product 5 was obtained in 45% (83 mg) yield. Eluent:
hexane/EtOAc 95:5. Colorless oil. A 1.4:1 mixture of two stereo-
4.3.6. 2-(1-(Bicyclo[2.2.1]hept-2-en-2-yl)naphthalen-2-yl)phenol (5,
R1, R2¼(CH]CH)2, R3, R4¼H, ZeZ]CH2eCH2; Table 1, entry 6). From
1-iodonaphthalene (142 mg, 0.56 mmol), 2-bromophenol (97 mg,
0.56 mmol), and norbornene (63 mg, 0.67 mmol), product 5 was
obtained in 45% (87 mg) yield. Eluent: hexane/EtOAc 95:5. Col-
orless oil. A 1.4:1 mixture of two stereoisomers indicated as A and
isomers indicated as A and B. 1H NMR:
d 7.80e7.72 (m, 1H (A), 1H
(B)), 7.49e7.39 (m, 2H (A), 2H (B)), 7.33e7.21 (m, 1H (A), 1H (B)),
7.18 (dd, J¼7.5, 1.5 Hz, 1H (A)), 7.06e6.85 (m, 2H (A), 3H (B)), 6.21,
6.06 (2 br s, 1H (A), 1H (B), ]CH), 4.80, 4.73 (2 br s, 1H (A), 1H (B),
OH), 2.84, 2.76 (2m, 1H (A), 1H (B), H4), 2.57, 2.53 (2m, 1H (B), 1H
(A), H1), 1.68e1.48 (m, 1H (A), 1H (B), H5exo), 1.42e1.22 (m, 1H (A),
1H (B), H6exo), 1.20e0.80 (m, 4H (A), 4H (B), H5endo, H6endo,
B. 1H NMR:
d 8.10e7.97 (m, 1H (B), 1H (A)), 7.94e7.80 (m, 2H (A),
2H (B)), 7.59e7.49 (m, 2H (A), 2H (B)), 7.44 (d, J¼8.4 Hz, 1H (A), 1H
(B)), 7.35e7.27 (m, 2H (A), 2H (B)), 7.16 (d, J¼7.8 Hz, 1H (B)),
7.13e6.92 (m, 2H (A), 1H (B)), 6.30, 6.12 (2 d, J¼2.8 Hz, 1H (A), 1H
(B)), 5.12, 4.90 (2 s, 1H (A), 1H (B), OH), 3.05, 2.95 (2 br s, 1H (A),
1H (B)), 2.77, 2.65 (2 br s, 1H (B), 1H (A)), 1.89e1.49 (m, 2H (A), 2H
H7syn, H7anti); 13C NMR:
d 152.5, 152.3, 142.6, 142.1, 137.0 (q,
(B)), 1.49e0.89 (m, 4H (A), 4H (B)); 13C NMR:
d
153.0, 152.3, 144.2,
JC,F¼2.5 Hz), 135.9 (q, JC,F¼1.9 Hz), 134.9, 134.1, 131.6, 131.0, 129.7,
129.4, 128.3, 127.5, 127.1, 126.4, 126.3 (2 q, JC,F¼5.7 Hz), 124.0, 123.9
(2 q, JC,F¼273.8 Hz), 120.5, 120.1, 116.7, 115.3, 50.1, 49.9, 49.0, 48.6,
42.9, 42.7, 25.2, 25.1, 23.4, 23.3; MS (EI, 70 eV): Mþ 330 (63), m/z
302 (84), 285 (70), 261 (50), 249 (53), 233 (100), 215 (50), 202
(25). Anal. Calcd for C20H17F3O: C, 72.72; H, 5.19. Found: C, 73.00;
H, 5.16.
143.5, 136.5, 136.4, 134.8, 133.8, 133.3, 132.9, 132.0, 131.3, 130.9,
129.2, 129.0, 128.7, 128.1, 128.0, 127.8, 127.6, 126.6, 126.5, 126.4,
126.1, 125.9, 120.2, 119.9, 116.2, 114.9, 49.2, 49.1, 48.7, 48.5, 43.3,
43.1, 26.2, 26.0, 23.8; MS (EI, 70 eV): Mþ 312 (100), m/z 295 (9),
284 (44), 267 (49), 255 (31), 231 (28), 215 (13), 202 (13). Anal.
Calcd for C23H20O: C, 88.43; H, 6.45. Found: C, 88.67; H, 6.51.
4.3.7. 2-(1-(Bicyclo[2.2.1]hept-2-en-2-yl)-4-methylnaphthalen-2-yl)
phenol (5, R1, R2¼(CH]CH)2, R3¼Me, R4¼H, ZeZ]CH2eCH2; Table 1,
entry 7). From 1-iodo-4-methylnaphthalene (150 mg, 0.56 mmol),
2-bromophenol (97 mg, 0.56 mmol), and norbornene (63 mg,
0.67 mmol), product 5 was obtained in 56% (109 mg) yield. Eluent:
hexane/EtOAc 97:3. Mp (hexane): 131 ꢀC. A 1.7:1 mixture of two
4.3.10. 20-(Bicyclo[2.2.1]hepta-2,5-dien-2-yl)-30-methylbiphenyl-2-ol
(5, R1¼Me, R2, R3, R4¼H, ZeZ]CH]CH; Table 1, entry 10). From 2-
iodotoluene (122 mg, 0.56 mmol), 2-bromophenol (97 mg,
0.56 mmol), and norbornadiene (123 mg, 1.34 mmol), product 5
was obtained in 75% (115 mg) yield. Eluent: hexane/EtOAc 95:5.
Colorless oil. A 1.1:1 mixture of two stereoisomers indicated as A
and B. 1H NMR: 7.33e7.06 (m, 5H (A), 5H (B)), 7.00e6.85 (m, 2H (A),
2H (B)), 6.67, 6.60 (2m, 1H (A), 1H (B)), 6.55e6.49 (m, 1H (A), 1H
(B)), 6.45 (d, J¼2.7 Hz, 1H (B)), 6.21 (m, 1H (A)), 4.95, 4.85 (2 br s, 1H
(A), 1H (B)), 3.57 (br s, 1H (A), 1H (B)), 3.22 (br s, 1H (A), 1H (B)), 2.29
(s, 3H (B)), 2.22 (s, 3H (A)),1.89,1.83 (2 d, J¼5.7 Hz, 2H (B)),1.79,1.70
stereoisomers indicated as A and B. 1H NMR:
d 8.14e8.03 (m, 2H (A),
2H (B)), 7.64e7.51 (m, 2H (A), 2H (B)), 7.36e7.26 (m, 3H (A), 2H (B)),
7.17 (dd, J¼7.5, 1.2 Hz, 1H (B)), 7.08e6.98 (m, 2H (A), 1H (B)), 6.95 (t
further split, J¼7.5 Hz, 1H (B)), 6.27, 6.10 (2d, J¼2.7 Hz, 1H (A), 1H
(B)), 5.14, 4.95 (2 br s, 1H (A), 1H (B)), 3.05, 2.95 (2 br s, 1H (A), 1H
(B)), 2.78 (br s, 1H (B)), 2.76 (s, 3H (A), 3H (B)), 2.67 (br s, 1H (A)),
1.86e1.41 (m, 2H (A), 2H (B)), 1.39e0.91 (m, 4H (A), 4H (B)); 13C
(2 d, J¼5.7 Hz, 2H (A)); 13C NMR:
d 154.6, 154.3, 152.5, 142.9, 142.7,
142.6, 141.8, 140.2, 140.1, 138.82, 138.77, 136.9, 136.6, 135.6, 135.0,
130.9, 130.7, 130.1, 130.0, 128.94, 128.88, 128.83, 128.6, 128.3, 128.2,
127.2, 127.1, 120.1, 119.9, 115.4, 115.3, 73.7, 56.6, 56.4, 50.9, 50.7, 21.3,
21.2; MS (EI, 70 eV): Mþ 274 (12), m/z 259 (10), 208 (100), 189 (11),
178 (16), 165 (33). Anal. Calcd for C20H18O: C, 87.56; H, 6.61. Found:
C, 87.33; H, 6.64.
NMR:
d 152.9, 152.3, 144.3, 143.5, 136.3, 135.1, 134.8, 134.3, 134.0,
133.3, 133.1, 132.9, 132.5, 132.4, 132.1, 131.4, 131.1, 130.8, 129.5, 129.2,
129.1, 128.9, 128.7, 128.5, 127.1, 126.5, 126.2, 126.02, 125.97, 125.95,
124.15, 124.12, 120.1, 119.8, 116.1, 114.8, 49.1, 49.0, 48.8, 48.6, 43.2,
43.1, 26.1, 26.0, 23.7, 23.6, 19.4, 19.3; MS (EI, 70 eV): Mþ 326 (100),
m/z 311 (10), 298 (29), 283 (39), 281 (47), 269 (26), 257 (15), 245
(29), 239 (12). Anal. Calcd for C24H22O: C, 88.31; H, 6.79. Found: C,
88.02; H, 6.86.
4.3.11. 20-(Bicyclo[2.2.1]hepta-2,5-dien-2-yl)-30,5-dimethylbiphenyl-
2-ol (5, R1¼Me, R2, R3¼H, R4¼Me, ZeZ]CH]CH; Table 1, entry
11). From 2-iodotoluene (122 mg, 0.56 mmol), 2-bromo-4-
methylphenol (105 mg, 0.56 mmol), and norbornadiene (123 mg,
1.34 mmol), product 5 was obtained in 72% (116 mg) yield. Eluent:
hexane/EtOAc 95:5. Colorless oil. A 1.1:1 mixture of two stereo-
4.3.8. 2-((1-Bicyclo[2.2.1]hept-2-en-2-yl)-4-methoxynaphthalen-2-
yl)phenol (5, R1, R2¼(CH]CH)2, R3¼OMe, R4¼H, ZeZ]CH2eCH2;
Table 1, entry 8). From 1-iodo-4-methoxynaphthalene (159 mg,
0.56 mmol), 2-bromophenol (97 mg, 0.56 mmol), and norbornene
(63 mg, 0.67 mmol), product 5 was obtained in 60% (115 mg)
yield. Eluent: hexane/EtOAc 95:5. Mp (hexane): 137 ꢀC. A 1.7:1
mixture of two stereoisomers indicated as A and B. 1H NMR:
isomers indicated as A and B. 1H NMR:
d 7.27e7.17 (m, 2H (A), 2H
(B)), 7.14e7.06 (m, 1H (A), 1H (B)), 7.05e6.96 (m, 1H (A), 1H (B)),
6.90e6.84 (m, 1H (A), 1H (B)), 6.80 (d, J¼8.0 Hz, 1H (A)), 6.74 (d,
J¼8.0 Hz, 1H (B)), 6.64 (m, 1H (A)), 6.54 (m, 1H (B)), 6.50 (d,
J¼2.7 Hz,1H (A)), 6.45 (m,1H (A)), 6.40 (d, J¼2.7 Hz,1H (B)), 6.16 (m,
1H (B)), 4.79, 4.63 (2 br s, 1H (A), 1H (B)), 3.54 (br s, 1H (A), 1H (B)),
3.20, 3.16 (2 partially overlapped br s, 1H (B), 1H (A)), 2.28 (s, 3H
(B)), 2.26 (s, 3H (A), 3H (B)), 2.17 (s, 3H (A)), 1.89, 1.81 (2 d, J¼5.7 Hz,
d
8.36e8.28 (m, 1H (A), 1H (B)), 8.02e7.89 (m, 1H (B), 1H (A)),
7.56e7.48 (m, 2H (A), 2H (B)), 7.36e7.25 (m, 2H (A), 1H (B)), 7.15
(dd, J¼7.2, 1.2 Hz, 1H (B)), 7.06e6.95 (m, 2H (A), 1H (B)), 6.92 (t
further split, J¼7.5 Hz, 1H (B)), 6.74 (s, 1H (A), 1H (B)), 6.21, 6.01
(2d, J¼2.7 Hz, 1H (A), 1H (B)), 5.19, 4.96 (2 br s, 1H (A), 1H (B)),
4.00, 3.98 (2s, 3H (A), 3H (B)), 3.00, 2.89 (2 br s, 1H (A), 1H (B)),
2.71, 2.58 (2 br s, 1H (B), 1H (A)), 1.81e1.36 (m, 2H (A), 2H (B)),
2H (B)), 1.76, 1.70 (2 d, J¼5.7 Hz, 2H (A)); 13C NMR:
d 154.8, 154.4,
150.2, 143.0, 142.7, 142.4, 141.7, 140.2, 140.0, 138.7, 138.5, 136.8,
136.5, 135.9, 135.3, 131.31, 131.26, 130.0, 129.9, 129.3, 129.2, 129.1,
128.9, 128.6, 128.3, 128.2, 128.1, 127.1, 127.0, 115.3, 115.1, 73.7, 56.6,
1.34e0.74 (m, 4H (A), 4H (B)); 13C NMR:
d 154.7, 154.5, 152.9,

E. Motti et al. / Tetrahedron 69 (2013) 4421e4428
4427
56.4, 50.9, 50.7, 21.35, 21.28, 20.4; MS (EI, 70 eV): Mþ 288 (9), m/z
222 (100), 207 (11), 179 (22), 178 (19), 165 (9). Anal. Calcd for
C21H20O: C, 87.46; H, 6.99. Found: C, 87.21; H, 6.91.
247 (51), 233 (49), 222 (32), 209 (42), 165 (15). Anal. Calcd for
21H22O: C, 86.85; H, 7.64. Found: C, 86.97; H, 7.61.
C
4.3.17. 8,9-Dimethoxy-7-methylspiro[benzo[c]chromene-6,20-bicyclo
[2.2.1]heptane] (6, R1¼Me, R2, R3¼OMe, R4¼H; Scheme 9). From the
corresponding compound 5 (100 mg, 0.30 mmol) and p-toluene-
sulfonic acid (25 mg, 0.15 mmol) in MeCN (2 mL) at room temper-
ature for 1.5 h, product 6 was obtained quantitatively. Mp (hexane):
4.3.12. 2-(1-(Bicyclo[2.2.1]hepta-2,5-dien-2-yl)naphthalen-2-yl)phe-
nol (5, R1, R2,¼(CH]CH)2, R3, R4¼H, ZeZ]CH]CH; Table 1, entry
12). From 1-iodonaphthalene (142 mg, 0.56 mmol), 2-
bromophenol (97 mg, 0.56 mmol), and norbornadiene (123 mg,
1.34 mmol), product 5 was obtained in 62% (108 mg) yield. Eluent:
hexane/EtOAc 95:5. Colorless oil. A 1.1:1 mixture of two stereo-
165 ꢀC. Eluent: hexane/EtOAc 9:1. 1H NMR (400 MHz, CDCl3):
d 7.68
(dd, J¼7.8,1.5 Hz,1H), 7.23 (td, J¼7.8,1.2 Hz,1H), 7.17 (s,1H), 7.05 (td,
J¼7.5, 1.2 Hz, 1H), 6.97 (dd, J¼7.8, 1.2 Hz, 1H), 3.95 (s, 3H), 3.80 (s,
3H), 3.00 (dd, J¼14.1, 1.8 Hz, 1H), 2.55e2.46 (m, 4H), 2.40 (d,
J¼4.8 Hz, 1H), 2.05e1.96 (m, 2H), 1.62e1.45 (m, 2H), 1.35e1.20 (m,
isomers indicated as A and B. 1H NMR:
d
8.04 (d, J¼7.8 Hz, 1H (B)),
7.98e7.75 (m, 3H (A), 2H (B)), 7.63e7.39 (m, 3H (A), 3H (B)),
7.37e7.17 (m, 2H (A), 2H (B)), 7.09e6.92 (m, 2H (A), 2H (B)),
6.91e6.69 (m, 2H (A), 2H (B)), 6.65 (br s, 1H (A)), 6.25 (br s, 1H (B)),
5.04, 4.89 (2 br s,1H (A),1H (B)), 3.73 (br s,1H (A),1H (B)), 3.34 (br s,
1H (A), 1H (B)), 2.09, 1.96 (2 d, J¼5.7 Hz, 2H (B)), 1.91, 1.86 (2 d,
1H), 1.10e0.95 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 152.2, 151.7,
147.0, 129.8, 128.6, 128.2, 127.3, 125.3, 122.8, 121.4, 117.5, 105.8, 89.0,
60.1, 55.5, 44.6, 39.4, 36.9, 35.6, 29.2, 21.5, 14.5; MS (EI, 70 eV): Mþ
336 (40), m/z 321 (100), 295 (9), 281 (7), 255 (44), 253 (28). Anal.
Calcd for C22H24O3: C, 78.54; H, 7.19. Found: C, 78.38; H, 7.26.
J¼5.7 Hz, 2H (A)); 13C NMR:
d 153.5, 153.2, 152.5, 152.3, 143.1, 142.9,
142.8, 142.1, 141.8, 141.7, 133.3, 132.05, 132.00, 131.9, 131.6, 131.0,
130.8, 129.2, 129.10, 129.05, 128.4, 128.2, 128.1, 128.0, 127.9, 127.7,
127.6, 126.8, 126.64, 126.57, 126.4, 126.2, 125.5, 125.4, 120.2, 120.1,
115.6, 115.5, 73.9, 57.3, 57.1, 51.3, 51.1; MS (EI, 70 eV): Mþ 310 (16),
m/z 243 (100), 215 (15), 213 (10). Anal. Calcd for C23H18O: C, 89.00;
H, 5.85. Found: C, 88.69; H, 5.91.
4.3.18. 120-Methoxyspiro[bicyclo[2.2.1]heptane-2,50-naphtho[1,2-c]
chromene] (6, R1, R2¼(CH]CH)2, R3¼OMe, R4¼H; Scheme 9). From
the corresponding compound 5 (103 mg, 0.30 mmol) and p-tol-
uenesulfonic acid (25 mg, 0.15 mmol) in MeCN (2 mL) at room
temperature for 1.5 h, product 6 was obtained quantitatively. Mp
4.3.13. 4-Methyldibenzo[b,d]furan23 (3, R1¼Me, R2, R3, R4¼H; Table 2,
entry 1). From 2-iodotoluene (122 mg, 0.56 mmol), 2-bromophenol
(97 mg, 0.56 mmol), and norbornene (25 mg, 0.27 mmol), product 3
was obtained in 45% (46 mg) yield. Eluent: hexane/EtOAc 95:5.
(hexane): 230 ꢀC. Eluent: hexane/EtOAc 95:5. 1H NMR:
d 8.41 (d,
J¼8.7 Hz, 1H), 8.37 (dd, J¼8.1, 1.8 Hz, 1H), 7.76 (dd, 7.8, 1.5 Hz, 1H),
7.55e7.41 (m, 2H), 7.29 (td, J¼7.5, 1.8 Hz, 1H), 7.19 (s, 1H), 7.11 (td,
J¼7.5, 1.2 Hz, 1H), 7.03 (dd, J¼7.8, 1.2 Hz, 1H), 4.09 (s, 3H), 3.34 (dd,
J¼14.7, 2.1 Hz, 1H), 2.68 (br s, 1H), 2.61 (br s, 1H), 2.22e2.12 (m, 2H),
1.92e1.79 (m, 1H), 1.73e1.58 (m, 1H), 1.38e1.22 (m, 2H), 1.18e1.09
4.3.14. Benzo[d]naphtho[1,2-b]furan23 (3, R1, R2¼(CH]CH)2, R3, R4¼H;
Table 2, entry 2). From 1-iodonaphthalene (142 mg, 0.56 mmol), 2-
bromophenol (97 mg, 0.56 mmol), and norbornene (25 mg,
0.27 mmol), product 3 was obtained in 24% (29 mg) yield. Eluent:
hexane/EtOAc 95:5.
(d further split, J¼9.6 Hz, 1H); 13C NMR:
d 155.0, 152.9, 133.0, 130.2,
129.0, 126.0, 125.9, 125.4, 124.6, 124.2, 124.1, 123.5, 122.5, 121.6,
117.4, 100.5, 89.0, 55.4, 44.9, 41.4, 37.2, 36.4, 28.5, 21.8; MS (EI,
70 eV): Mþ 342 (99), m/z 341 (96), 313 (28), 301 (17), 285 (33), 273
(36), 261 (100), 202 (19). Anal. Calcd for C24H22O2: C, 84.18; H, 6.48.
Found: C, 84.29; H, 6.55.
4.3.15. 4-(Trifluoromethyl)dibenzo[b,d]furan (3, R1¼CF3, R2, R3, R4¼H;
Table 2, entry 3). From 1-iodo-2-(trifluoromethyl)benzene (152 mg,
0.56 mmol), 2-bromophenol (97 mg, 0.56 mmol), and norbornene
(25 mg, 0.27 mmol), product 3 was obtained in 75% (99 mg) yield.
4.3.19. 20-(Bicyclo[2.2.1]hept-2-en-2-yl)-30-ethyl-[1,10-biphenyl]-2-ol
(5; Scheme 10). From 2-iodoethylbenzene (130 mg, 0.56 mmol), 2-
bromophenol (97 mg, 0.56 mmol), and norbornene (63 mg,
0.67 mmol), product 5 was obtained in 28% (45 mg) yield. Eluent:
hexane/EtOAc 95:5. Colorless oil. A 1.4:1 mixture of two stereo-
Eluent: hexane/EtOAc 95:5. 1H NMR:
d
8.12 (d further split, J¼7.9 Hz,
1H, H1), 7.97 (d further split, J¼7.0 Hz,1H, H9), 7.69, 7.67 (two partly
overlapping d, 2H, H3, H6), 7.53 (ddd, J¼8.5, 7.3, 1.2 Hz, 1H, H7),
7.45e7.36 (m, 2H, H2, H8); 13C NMR:
d
156.4 (C5a), 152.1 (q,
isomers indicated as A and B. 1H NMR:
d 7.40e6.80 (m, 7H (A), 7H
JC,F¼1.9 Hz, C4a), 128.1 (C7), 126.0, 124.3 (C1), 123.9 (q, JC,F¼4.7 Hz,
C3), 123.4 (C8), 123.3 (q, JC,F¼272.1 Hz, CF3), 122.9, 122.3 (C2), 120.7
(C9), 115.0 (q, JC,F¼33.8 Hz, C4), 112.1 (C6); MS (EI, 70 eV): Mþ 236
(100), m/z 217 (17), 186 (13), 139 (14). Anal. Calcd for C13H7F3O: C,
66.11; H, 2.99. Found: C, 66.31; H, 3.03.
(B)), 5.99, 5.85 (2 d, J¼2.9 Hz, 1H (A), 1H (B), ]CH), 4.93, 4.91 (2
partially overlapped br s, 1H (A), 1H (B), OH), 2.95, 2.80 (2 br s, 1H
(A), 1H (B)), 2.63, 2.60 (2 partially overlapped q, J¼7.5 Hz, 2H (A), 2H
(B), CH2), 2.56, 2.50 (2 br s, 1H (B), 1H (A)), 1.72e1.38 (m, 2H (A), 2H
(B)), 1.33e0.76 (m, 7H (A), 7H (B)); MS (EI, 70 eV): Mþ 290 (32), m/z
261 (100), 247 (25), 233 (58), 219 (24), 207 (26), 189 (14). Anal.
Calcd for C21H22O: C, 86.85; H, 7.64. Found: C, 87.04; H, 7.56.
4.3.16. 2,7-Dimethylspiro[benzo[c]chromene-6,20-bicyclo[2.2.1]hep-
tane] (6, R1, R4¼Me, R2, R3¼H; Scheme 9). From the corresponding
compound 5 (87 mg, 0.30 mmol) and p-toluenesulfonic acid
(25 mg, 0.15 mmol) in MeCN (2 mL) at room temperature for 1.5 h,
product 6 was obtained quantitatively. Mp (hexane): 114 ꢀC. Eluent:
4.3.20. 30-Vinylbiphenyl-2-ol (7; Scheme 10). From 2-iodoethyl-
benzene (130 mg, 0.56 mmol), 2-bromophenol (97 mg,
0.56 mmol), and norbornene (63 mg, 0.67 mmol), product 7 was
hexane/EtOAc 95:5. 1H NMR:
d
7.61 (d further split, J¼7.7 Hz, 1H,
obtained in 18% (20 mg) yield. 1H NMR: 7.05 (br s, 1H, H20),
d
H10), 7.54 (d, J¼1.5 Hz, 1H, H1), 7.24 (t, J¼7.7 Hz, 1H, H9), 7.09 (d
further split, J¼7.5 Hz, 1H, H8), 7.05 (dd, J¼8.2, 1.9 Hz, 1H, H3), 6.87
(d, J¼8.1 Hz, 1H, H4), 2.96 (dd, J¼14.2, 2.1 Hz, 1H, H30endo), 2.59 (s,
3H, CH3(C7)), 2.52e2.48 (m, 1H, H40), 2.42 (br d, J¼5.1 Hz, 1H, H10),
2.39 (s, 3H, CH3(C2)), 2.07e1.94 (m, 2H, H70syn, H30exo), 1.60e1.48
(m, 2H, H50exo, H50endo), 1.34e1.17 (m, 1H, H60exo), 1.08e0.96 (m,
7.49e7.43 (m, 2H), 7.38e7.33 (m, 1H), 7.31e7.22 (m, 2H), 7.04e6.96
(m, 2H), 6.77 (dd, J¼17.6, 10.9 Hz, 1H), 5.82 (dd, J¼17.6, 0.6 Hz, 1H),
5.32 (dd, J¼10.9, 0.6 Hz, 1H), 5.21 (br s, 1H, OH); 13C NMR:
d 152.4,
138.6, 137.3, 136.3, 130.1, 129.4, 129.2, 128.4, 127.9, 126.9, 125.7,
120.8, 115.8, 114.8; MS (EI, 70 eV): Mþ 196 (100), m/z 181 (32), 165
(21), 152 (19), 139 (11). Anal. Calcd for C14H12O: C, 85.68; H, 6.16.
Found: C, 85.54; H, 6.19.
2H, H60endo, H70anti); 13C NMR:
d 150.2 (C4a), 134.7 (C7), 133.8
(C6a), 132.5 (C10a), 132.1 (C8), 130.6 (C2), 129.6 (C3), 127.3 (C9),
125.1 (C10b), 123.7 (C1), 122.3 (C10), 117.2 (C4), 88.9 (C20), 44.3
(C10), 39.4 (C30), 36.9 (C40), 35.6 (C70), 29.4 (C50), 24.7 (CH3(C7)), 21.6
(C60), 21.0 (CH3(C2)); MS (EI, 70 eV): Mþ 290 (34), m/z 275 (100),
4.3.21. 30-(2-(20,3-Diethylbiphenyl-2-yl)vinyl)biphenyl-2-ol (8; Scheme
10). From 2-iodoethylbenzene (130 mg, 0.56 mmol), 2-bromophenol
(97 mg, 0.56 mmol), and norbornene (63 mg, 0.67 mmol), product 8

4428
E. Motti et al. / Tetrahedron 69 (2013) 4421e4428
5. (a) Horino, H.; Arai, M.; Inoue, N. Tetrahedron Lett. 1974, 15, 647; (b) Li, C.-S.;
was obtained in 16% (45 mg) yield. 1H NMR:
d
7.95e6.95 (m, 16H),
Cheng, C.-H.; Liao, F.-L.; Wang, S.-L. J. Chem. Soc., Chem. Commun. 1991, 710; (c)
Portnoy, M.; Ben-David, Y.; Rousso, I.; Milstein, D. Organometallics 1994, 13,
3465; (d) Catellani, M.; Mealli, C.; Motti, E.; Paoli, P.; Perez-Carreno, E.; Pre-
gosin, P. S. J. Am. Chem. Soc. 2002, 124, 4336.
6. (a) Catellani, M.; Chiusoli, G. P. J. Organomet. Chem. 1988, 346, C27; (b) Liu, C.-H.;
Li, C.-S.; Cheng, C.-H. Organometallics 1994, 13, 18; (c) Malinakova, H. C. Top.
Organomet. Chem. 2011, 35, 85.
7. (a) Dyker, G. Angew. Chem., Int. Ed. 1999, 38, 1698; (b) Dyker, G. In Handbook of
CeH Transformation; Dyker, G., Ed.; Wiley-VCH: Weinheim, Germany, 2005;
Vol. 2, p 465; (c) Kakiuchi, F.; Chatani, N. Adv. Synth. Catal. 2003, 345, 1077; (d)
Livendahl, M.; Echavarren, A. M. Isr. J. Chem. 2010, 50, 630; (i) De Mendoza, P.;
Echavarren, A. M. In Modern Arylation Methods; Ackermann, L., Ed.; Wiley-VCH:
Weinheim, Germany, 2009; p 363; (f) Gorelsky, S.; Lapointe, D.; Fagnou, K. J. Am.
Chem. Soc. 2008, 130, 10848; (g) Rousseaux, S.; Davi, M.; Sofack-Kreutzer, J.;
Pierre, C.; Kefalidis, C. E.; Clot, E.; Fagnou, K.; Baudoin, O. J. Am. Chem. Soc. 2010,
132, 10706.
6.23 (d, J¼17.7 Hz,1H), 5.14 (1H, br s, OH), 2.83, 2.40 (2 q further split,
J¼7.60 Hz, 4H, CH2), 1.28, 1.03 (2 t, J¼7.60 Hz, 6H, CH3); MS
(EI, 70 eV): Mþ 404 (100), m/z 375 (47), 346 (16), 221 (85), 193 (54),
178 (35).
Crystallographic data (excluding structure factors) for the
structures in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication nos.
CCDC 915263. Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax:
þ44-(0)1223-336033 or e-mail: deposit@ccdc.cam.ac.UK).
Acknowledgements
8. (a) Canty, A. J. Acc. Chem. Res. 1992, 25, 83; (b) Powers, D. C.; Lee, E.;
Ariafard, A.; Sanford, M. S.; Yates, B. F.; Canty, A. J.; Ritter, T. J. Am. Chem. Soc.
2012, 134, 12002; (c) Hickman, A. J.; Sanford, M. S. Nature, 484, 177. (d)
This work was supported by MIUR and Parma University. The
NMR instrumentation was provided by Centro Interdipartimentale
‘Giuseppe Casnati’ of Parma University. D.X. was recipient of a fel-
lowship from the Beijing Institute of Technology, Beijing, PR China.
We thank Giuliano Ferri for the preparation of starting materials.
ꢂ
ꢂ
Vicente, J.; Arcas, A.; Julia-Hernandez, F.; Bautista, D. Angew. Chem., Int. Ed.
2011, 50, 6896; (e) Catellani, M.; Fagnola, M. C. Angew. Chem., Int. Ed. Engl.
1994, 33, 2421; (f) Catellani, M.; Mann, B. E. J. Organomet. Chem. 1990, 390,
251; (g) Bocelli, G.; Catellani, M.; Ghelli, S. J. Organomet. Chem. 1993, 458,
C12; (h) Amatore, C.; Catellani, M.; Deledda, S.; Jutand, A.; Motti, E. Organ-
ometallics 2008, 27, 4549.
9. (a) Maestri, G.; Motti, E.; Della Ca’, N.; Malacria, M.; Derat, E.; Catellani, M. J. Am.
Chem. Soc. 2011, 133, 8574; (b) Catellani, M.; Motti, E. New J. Chem. 1998, 22, 759;
(c) Catellani, M.; Motti, E.; Baratta, S. Org. Lett. 2001, 3, 3611.
Supplementary data
10. (a) Alsters, P. L.; Boersma, J.; Smeets, W. J. J.; Spek, A. L.; van Koten, G. Organo-
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.02.029.
These data include MOL files and InChIKeys of the most important
compounds described in this article.
ꢂ
ꢂ
metallics 1993, 12, 1639; (b) Fernandez-Rivas, C.; Cardenas, D. J.; Martín-Matute,
ꢂ
B.; Monge, A.; Gutierrez-Puebla, E.; Echavarren, A. M. Organometallics 2001, 20,
2998; (c) Widenhoefer, R. A.; Annita Zhong, H.; Buchwald, S. L. J. Am. Chem. Soc.
1997, 119, 6787; (d) Lu, G.; Malinakova, H. C. J. Org. Chem. 2004, 69, 8266.
11. Sicher, J. Angew. Chem., Int. Ed. Engl. 1972, 11, 200.
12. Catellani, M.; Chiusoli, G. P.; Ricotti, S. J. Organomet. Chem. 1985, 296, C11.
13. Dyker, G. J. Org. Chem. 1993, 58, 234.
14. (a) Li, C.-S.; Cheng, C.-H.; Cheng, S.-S.; Shaw, J.-S. J. Chem. Soc., Chem.
Commun. 1990, 1774; (b) Li, C.-S.; Jou, D.-C.; Cheng, C.-H. Organometallics
1993, 12, 3945.
15. Motti, E.; Ippomei, G.; Deledda, S.; Catellani, M. Synthesis 2003, 2671.
16. As previously reported (ref. 2) the o-trifluoromethyliodobenzene can be used in
combination with o-bromophenol because of its poor reactivity with type III
palladacycles (Scheme 3).
References and notes
1. (a) Kuhl, N.; Hopkinson, M. N.; Wencel-Delord, J.; Glorius, F. Angew. Chem.,
Int. Ed. 2012, 51, 10236; (b) Truong, T.; Daugulis, O. Angew. Chem., Int. Ed.
2012, 51, 11677; (c) Neufeldt, S. R.; Sanford, M. S. Acc. Chem. Res. 2012, 45,
936; (d) Baudoin, O. Chem. Soc. Rev. 2011, 40, 4902; (e) Ackermann, L. Chem.
Rev. 2011, 111, 1315; (f) Li, H.; Li, B.-J.; Shi, Z.-J. Catal. Sci. Technol. 2011, 1, 191;
(g) Jazzar, R.; Hitce, J.; Renaudat, A.; Sofack-Kreutzer, J.; Baudoin, O. Chem.
dEur. J. 2010, 16, 2654; (h) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem.
Rev. 2010, 110, 624; (i) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215; (j)
Sun, C.-L.; Li, B.-J.; Shi, Z.-J. Chem. Commun. 2010, 46, 677; (k) De Ornellas, S.;
Storr, T. E.; Williams, T. J.; Baumann, C. G.; Fairlamb, I. J. S. Curr. Org. Synth.
2011, 8, 79; (l) Lessi, M.; Masini, T.; Nucara, L.; Bellina, F.; Rossi, R. Adv. Synth.
Catal. 2011, 353, 501; (m) Zhao, L.; Bruneau, C.; Doucet, H. ChemCatChem
2013, 5, 255.
2. (a) Catellani, M.; Motti, E.; Della Ca’, N. Acc. Chem. Res. 2008, 41, 1512; (b)
Chiusoli, G. P.; Catellani, M.; Costa, M.; Motti, E.; Della Ca’, N.; Maestri, G. Coord.
Chem. Rev. 2010, 254, 456; (c) Martins, A.; Mariampillai, B.; Lautens, M. Top.
Curr. Chem. 2010, 292, 1; (d) Faccini, F.; Motti, E.; Catellani, M. J. Am. Chem. Soc.
2004, 126, 78; (e) Motti, E.; Della Ca’, N.; Deledda, S.; Fava, E.; Panciroli, F.;
Catellani, M. Chem. Commun. 2010, 46, 4291.
17. (a) Hartwig, J. Nature 2008, 455, 314; (b) Hartwig, J. In Organopalladium
Chemistry for Organic Synthesis; Negishi, E.-I., Ed.; Wiley: New York, NY, 2002;
pp 1097e1106; (c) Terao, Y.; Wakui, H.; Satoh, T.; Miura, M.; Nomura, M. J. Am.
Chem. Soc. 2001, 123, 10407; (d) Terao, Y.; Wakui, H.; Nomoto, M.; Satoh, T.;
Miura, M.; Nomura, M. J. Org. Chem. 2003, 68, 5236; (e) Hartwig, J. F. Angew.
Chem., Int. Ed. 1998, 37, 2046; (f) Kuwabe, S.-I.; Torraca, K. E.; Buchwald, S. L. J.
Am. Chem. Soc. 2001, 123, 12202; (g) Palucki, M.; Wolfe, J. P.; Buchwald, S. L. J.
Am. Chem. Soc. 1996, 118, 10333.
ꢂ
18. (a) Baudoin, O.; Herrbach, A.; Gueritte, F. Angew. Chem., Int. Ed. 2003, 42, 5736;
(b) Hitce, J.; Retailleau, P.; Baudoin, O. Chem.dEur. J. 2007, 13, 792; (c) Hitce, J.;
Baudoin, O. Adv. Synth. Catal. 2007, 349, 2054; (d) Motti, E.; Catellani, M. Adv.
Synth. Catal. 2008, 350, 565.
19. Lesslie, M. S.; Mayer, U. J. H. J. Chem. Soc. 1961, 611.
20. Della Ca’, N.; Motti, E.; Mega, A.; Catellani, M. Adv. Synth. Catal. 2010, 352, 1451.
21. (a) Sathiyapriya, R.; Karunakaran, R. J. Asian J. Chem. 2006, 18, 1321; (b) Miura,
T.; Murata, H.; Kiyota, K.; Kusama, H.; Iwasawa, N. J. Mol. Catal. A: Chem. 2004,
213, 59.
22. Yamamoto, T.; Toyota, K.; Morita, N. Tetrahedron Lett. 2010, 51, 1364.
23. Wang, C.; Piel, I.; Glorius, F. J. Am. Chem. Soc. 2009, 131, 4194.
3. (a) Motti, E.; Faccini, F.; Ferrari, I.; Catellani, M.; Ferraccioli, R. Org. Lett. 2006, 8,
3967; (b) Motti, E.; Della Ca’, N.; Ferraccioli, R.; Catellani, M. Synthesis 2008, 995.
4. (a) Fitton, P.; Rick, E. A. J. Organomet. Chem. 1971, 28, 287; (b) Roy, A. H.;
Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 13944; (c) Amatore, C.; Azzabi, M.;
Jutand, A. J. Am. Chem. Soc. 1991, 113, 8375.