Regioselective palladium-catalyzed ring-opening reactions of C 1-substituted oxabenzonorbornadienes

Article abstract of DOI:10.1139/cjc-2014-0217

The effect of ethyl and methoxycarbonyl substitution on the C₁ position of oxabenzonorbornadienes undergoing palladium-catalyzed nucleophilic ring opening was investigated with a variety of aryl iodide nucleophiles. Electron-withdrawing groups in the C₁ position or on the aryl iodide afforded lower yields and led to aromatization of products. The presence of an electron-donating group in either position provided high yields in all cases. Despite variances in electronic nature, all trials produced a single regioisomeric product resulting from addition of the aryl group to the olefin carbon farthest from the C₁ substituent. Based on these findings, a mechanism has also been proposed.

Full text of DOI:10.1139/cjc-2014-0217

888
ARTICLE
Regioselective palladium-catalyzed ring-opening reactions of
C1-substituted oxabenzonorbornadienes
Mohammed Abdul Raheem, Michael Edmunds, and William Tam
Abstract: The effect of ethyl and methoxycarbonyl substitution on the C1 position of oxabenzonorbornadienes undergoing
palladium-catalyzed nucleophilic ring opening was investigated with a variety of aryl iodide nucleophiles. Electron-withdrawing
groups in the C1 position or on the aryl iodide afforded lower yields and led to aromatization of products. The presence of an
electron-donating group in either position provided high yields in all cases. Despite variances in electronic nature, all trials
produced a single regioisomeric product resulting from addition of the aryl group to the olefin carbon farthest from the C1
substituent. Based on these findings, a mechanism has also been proposed.
Key words: palladium, ring-opening reaction, oxabicyclic alkenes, oxabenzonorbornadiene, catalysis.
Résumé : L’effet de la substitution éthyle et méthoxycarbonyle en position C1 des oxabenzonorbornadiènes sur l’ouverture
nucléophile du cycle catalysée par le palladium a été étudié en utilisant divers iodures d’aryle comme nucléophiles. Les groupements
électroattracteurs en position C1 ou sur l’iodure d’aryle ont produit des rendements faibles et entraîné la formation de produits
d’aromatisation. La présence d’un groupement électrodonneur, sans égard a` la position, a produit des rendements élevés dans
tous les cas. Malgré la diversité de la nature électronique des substituants, tous les essais ont produit un seul régioisomère issu
de l’addition d’un groupement aryle au carbone oléfinique le plus distant du substituant C1. À la lumière de ces résultats, un
mécanisme réactionnel a également été proposé. [Traduit par la Rédaction]
Mots-clés : palladium, réaction d’ouverture de cycle, alcènes oxabicycliques, oxabenzonorbornadiène, catalyse.
catalysis, it was found that the electronic nature of the C1 substitu-
Introduction
ent could determine which regioisomer formed (4 and 5).5 With
The palladium-catalyzed ring-opening reaction of oxabicyclic
an electron-donating C1-methyl substituent (R = Me), ruthenium-
alkenes with aryl iodides is an incredibly powerful tool for organic
catalyzed isomerization of C1-methyl-substituted oxabenzonor-
bornadiene led to the formation of one regiosiomer, 4. On the
other hand, with an electron-withdrawing methyl ester substitu-
ent (R = COOMe), ruthenium-catalyzed isomerization led to the
formation of the opposite regiosiomer, 5. Based on these findings,
it is possible that the electronic effect of the C1 substituent can
play a significant role in the regioselectivity of palladium-catalyzed
ring openings as well.
synthesis.1 In one step, ring opening allows for the creation of
complex dihydronaphthalene skeletons through simultaneous
formation of multiple stereocenters and carbon−carbon bonds.2
While this reaction has received much attention in the literature,
almost all focus has been directed toward opening symmetrical
oxabicyclic compounds.3 Our research group has a long-standing
interest in the reactivities of C1-substituted oxabenzonorborna-
dienes4,5 and was interested in observing the effect that it had on
the reaction’s outcome.
Imposing substitution on the C1 carbon of the oxabicycle has a
twofold effect: (i) the compound is rendered unsymmetrical, re-
sulting in the possible formation of two different regioisomers
when undergoing ring-opening reactions and (ii) new steric and
electronic effects are imposed on the incoming palladium−aryl
complex, which may favour one regioisomer over the other. Inter-
estingly, both regioisomers have been observed under different
conditions when 1-methyloxabenzonorbornadiene was subjected
to ring-opening reaction with palladium catalysts. Cheng and co-
workers reported the single regioisomer (1) (Scheme 1) (nucleo-
philic attack on C3) when working with alkyl halides,6 while
Lautens and co-workers reported the opposite regioisomer (2) (nu-
cleophilic attack on C2) using dialkylzinc reagents.7 Similar ring
openings using aryl nucleophiles under nickel catalysis reported
the production of both regioisomers as well (3a and 3b).8 During
recent investigations undertaken by our group on the isomeriza-
tion of C1-substituted oxabenzonorbornadienes under ruthenium
Results and discussion
To understand the impact of C1 substitution, palladium-catalyzed
ring-opening reactions of two oxabenzonorbornadienes bearing
ethyl (6) and methoxycarbonyl (8) C1 substituents were carried
out. Both model oxabicyclic compounds were ring opened using
aryl iodides possessing an electron-donating or -withdrawing
functional group in either the ortho, meta, or para position with
respect to the iodo group. The outcome of these reactions was then
compared against an unsubstituted phenyl iodide standard.
Optimizations of oxabenzonorbornadiene 6 focused on the pal-
ladium catalyst, solvent, and Lewis acid additives and are summa-
rized in Table 1. Palladium catalysts were chosen based on their
oxidation state and phosphine ligands. Palladium species lacking
phosphine ligands failed to catalyze the reaction (entry 1); how-
ever, this was easily reversed through addition of Ph3P (entry 2).
The low oxidation state palladium(0) catalyst, Pd(PPh3)4 (entry 3),
Received 6 May 2014. Accepted 25 June 2014.
M.A. Raheem, M. Edmunds, and W. Tam. Guelph–Waterloo Centre for Graduate Work in Chemistry and Biochemistry, Department of Chemistry,
University of Guelph, Guelph, ON N1G 2W1, Canada.
Corresponding author: William Tam (e-mail: wtam@uoguelph.ca).
Can. J. Chem. 92: 888–895 (2014) dx.doi.org/10.1139/cjc-2014-0217
Published at www.nrcresearchpress.com/cjc on 2 July 2014.

Raheem et al.
889
Scheme 1. Reported regioisomers in similar ring openings of oxabicycles.
The same optimization conditions were applied to the electron-
deficient oxabenzonorbornadiene 8 (Table 2). The reaction of 8 with
aryl iodides did not produce the expected 1,2-dihydronaphthalenol
derivatives like 7. It appears that the presence of the electron-
withdrawing group on the C1 position of the oxabenzonorbornadiene
prompts dehydration of the initially formed 1,2-dihydronaphthalenol
derivatives 7 into the corresponding 2-arylated naphthol deriva-
tive Pd(OAc)2. Ph3P afforded the ring-opened aromatized product
in 54% yield (Tableentry 1). A moderate increase in yield was ob-
served for the palladium(0) catalyst Pd(PPh3) (74%) (entry 2). Like
the ring opening of 6, PdCl2(PPh3)2 also provided the highest yield
at 85% (entry 3).
The ring opening of 8 with 4-iodoanisole in the presence of
PdCl2(PPh3)2 gave the best yields in polar aprotic solvents. The
reaction in THF afforded the ring-opened product in 85% yield
(Table 2, entry 3) and 80% in DMF (entry 10). The ring-opening
reaction in acetonitrile gave 68% yield (entry 7). The results were
reasonable in nonpolar solvents like toluene (71%) (entry 8) and
DCE (75%) (entry 9). However, the reaction in hexanes did not
proceed as well, providing a yield of only 9% (entry 4). The reaction
in polar protic solvent (ethanol) gave a lower yield of 41% due to
transesterification with ethanol to form the ethyl ester derivative
of naphthalene in 16% yield (entry 5). Avoiding this complication
through the use of methanol provided a modest yield of 75% (entry 6).
Comparative screening of a variety of Lewis acids against zinc
chloride (85%) (Table 2, entry 3) revealed no dramatic impact on
the yield of 9a. The lowest yield was provided by iron chloride at
59% (entry 11). Zinc iodide, zirconium chloride, and aluminum
chloride all produced moderate yields of the ring-opened product
at 70%, 74%, and 78%, respectively (entries 12–14). The best result
was achieved using copper chloride, affording the ring-opened
product in 86% yield (entry 15).
OH
R'
R=Me
R'I
1
R'2Zn
R=Me
R'
2
OH
Pd-Cat
OH
O
Ph
Ni-Cat
R=Me
3
1
2
Ph
R
3a
3b
OH
Ru-Cat
O
R=Me
4
5
R=COOMe
O
MeOOC
The results for the reaction of oxabenzonorbornadiene 6 with
various aryl iodides are summarized in Table 3. From the data, it
is clear that the presence of an electron-donating group such as
methoxy or methyl is favourable for ring opening. High yields of
7 were afforded with p- (95%) (entry 1) and o-iodoanisoles (91%)
(entry 3) with m-iodo anisole providing the lowest (80%) (entry 2)
and similarly high yields of 7 with p- (93%) (entry 4), m- (95%) (entry
5), and o-iodoanisoles (88%) (entry 6). In each case, the steric effect
of the substituent was overwhelmed by the electronics. Further-
more, although the yields dropped to 80% for m-iodo anisole and
88% for o-iodo toluene, they are still higher than the unsubstituted
aryl iodide (75%) (entry 7).
provided a yield similar to that obtained by the palladium(II) cat-
alyst, PdCl2(PPh3)2 (entry 4).
Solvent screening was carried out with nonpolar, polar protic,
and polar aprotic solvents (Table 1, entries 4–10). Nonpolar sol-
vents such as hexanes, toluene, and dichloroethane provided poor
yields at 19%, 54%, and 55%, respectively (entries 5–7). The polar
protic ethanol afforded the ring-opened product in excellent yield,
88% (entry 9). Moderate to good yields were obtained with the
polar aprotic solvents THF (entry 4), acetonitrile (entry 8), and
DMF (entry 10) at 72%, 63%, and 95%, respectively.
The reaction of oxabenzonorbornadiene 6 with iodonitrobenzenes
did not produce the expected 1,2-dihydronaphthalenol derivatives. It
appears that the presence of the strong electron-withdrawing group
on the aryl ring prompts dehydration into the corresponding
2-arylated naphthol derivative (10). The best yield of 10 was obtained
with p-iodonitrobenzene (61%) (Table 3, entry 8) but dropped substan-
tially with m-iodonitrobenzene (30%) (entry 9). o-Iodonitrobenzene
failed to afford 10 (entry 10).
The results for the reaction of oxabenzonorbornadiene 8 with
various aryl iodides are summarized in Table 4. Again, it is appar-
ent that the presence of an electron-donating group on the aro-
matic ring produces a favourable effect on the ring-opening
reaction. p-Iodoanisole gave the highest yield (85%) (entry 1) fol-
lowed closely by the m- (80%) (entry 2) and o-iodoanisoles (77%)
(entry 3). p- and o-Iodotoluenes afforded moderate yields of 9 at
73% (entry 4) and 71% (entry 6), respectively. Interestingly, ring
opening with m-iodotoluene gave the lowest yield at 68% (entry 5),
matching that of the unsubstituted species (68%) (entry 7).
The reaction of iodonitrobenzenes with 8 was extremely slug-
gish and afforded low yields of the corresponding naphthalene
derivatives. Among the nitro series, the best yield was obtained
with p-iodonitrobenzene (17%) (Table 4, entry 8) followed by the
meta derivative (14%) (entry 9). The reaction of o-iodonitrobenzene
Choice of Lewis acid provided a wide range of yields (Table 1,
entries 10–15). The reaction with zirconium chloride did not af-
ford ring-opening product but only resulted in isomerization and
aromatization of the starting oxabenzonorbornadiene 6 into the
corresponding naphthalene derivative (entry 11). Aluminum
(entry 12) and iron chloride (entry 13) were both able to give the
ring-opening product product but only in moderate yields (58%
and 66%, respectively). The reaction with copper chloride (entry
14) gave a moderate yield; however, the products appear to be a
mixture of cis and trans isomers. Although the formation of these
isomeric products was not expected, it is not surprising consider-
ing the literature precedent of copper-catalyzed ring openings
affording the trans product.9 Zinc iodide afforded a moderately
high yield of 78% (entry 15); however, this was still considerably
lower than that of zinc chloride, 95% (entry 10).
A control reaction using the same conditions as entry 10 but in
the absence of Et3N was also performed (Table 1, entry 16). While
previously affording the ring-opened product in 95% yield, the
reaction in the absence of Et3N proved to be much less fruitful.
The reaction was sluggish, with 14% recovery of 6 after 20 h, and
afforded a mere 58% of the ring-opened product. It is apparent
that the presence of the tertiary amine is crucial to the efficient
production of the ring-opened product.
Published by NRC Research Press

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Can. J. Chem. Vol. 92, 2014
Table 1. Optimization of catalyst, solvent, and Lewis acid additive for compound 6.
Entry
Catalyst
Solvent
Lewis acid
Base
Yield (%)a
0b
60
74
72
19
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2, Ph3P
Pd(PPh3)4
THF
THF
THF
THF
Hexanes
Toluene
DCE
CH3CN
Ethanol
DMF
DMF
DMF
DMF
DMF
DMF
DMF
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZrCl4
AlCl3
FeCl3
CuCl2
ZnI2
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
54
55
63
88
95
9
10
11
12
13
14
15
16
0c
58
66
67d
78
ZnCl2
58e,f
aIsolated yield after column chromatography.
bNo reaction; all starting material recovered.
cCompound 6 was isomerized and aromatized to the corresponding naphthalene product.
dProduct appears to be a mixture of cis and trans isomers.
eReaction stopped after 20 h with 14% recovery of compound 6.
f Yield based on 1H NMR using toluene as internal standard.
Table 2. Optimization of catalyst, solvent, and Lewis acid additive for compound 8.
Entry
Catalyst
Solvent
Lewis acid
Yield (%)a
1
2
3
4
5
6
7
8
Pd(OAc)2, Ph3P
Pd(PPh3)4
THF
THF
THF
Hexanes
Ethanol
Methanol
CH3CN
Toluene
DCE
DMF
THF
THF
THF
THF
THF
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
FeCl3
ZnI2
54
74
85
9
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
41b
75
68
71
9
75
80
59
70
74
78
86
10
11
12
13
14
15
ZrCl4
AlCl3
CuCl2
aIsolated yield after column chromatography.
b16% of ethyl ester formed due to transesterification with ethanol.
failed to progress (entry 10), possibly as a result of both electronic
and steric disfavour.
noted for the sterically encumbered t-Bu-substituted species (11b)
at 54% yield (entry 3). With substitution of a cyclobutyl group onto
the C1 position, the ring-opened product was obtained in 65% yield
(entry 4). A small yield of 19% was provided by the bulky biphenyl-
substituted species (11d) (entry5) and a moderate yield of 43%
was afforded by the hydroxymethyl-substituted species. The
electron-withdrawing methylamide species (11f) (entry 7) pro-
vided the aromatized product in 12% yield. Higher yields of the
aromatized product were afforded through both the methylketone
and trimethylsilane groups at 27% and 62%, respectively (entries
8–10).
In broadening the scope of this reaction, the reaction condi-
tions optimized for oxabenzonorbornadiene 6 were applied to
eight other C1-substituted oxabenzonorbornadiene species vary-
ing widely in steric and electronic nature. All species containing
electron-donating substituents provided the unaromatized ring-
opened product (Table 5, entries 1–6), while those containing
electron-withdrawing substituents resulted in aromatization
(entries 7–10). The ring opening of the methyl-substituted species
(11a) afforded 12a in 85% yield (entry 1). A steep drop in yield was
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Raheem et al.
891
Table 3. Effect of ring-opening 6 with variously substituted aryl iodides.
Entry
R1
R2
R3
Product
Yield (%)a
1
OMe
H
H
Me
H
H
H
NO2
H
H
OMe
H
H
Me
H
H
H
NO2
H
H
H
OMe
H
H
Me
H
H
H
NO2
7a
7b
7c
7d
7e
7f
95
80
91
93
95
88
75
61
30
0
2
3
4
5
6
7
8
9
10
7g
10a
10b
10c
H
aIsolated yield after column chromatography.
Table 4. Effect of ring opening 8 with variously substituted aryl iodides.
of the ␤-oxygen results in the ring-opened intermediate 21. Reduc-
tion of the palladium species to 16 with zinc metal restarts the
catalytic cycle while also affording ring-opened intermediate 22.
Intermediate 22 can then undergo one of three pathways based on
its substituents. If 22 lacks electron-withdrawing groups, then it
can either accumulate until the reaction is quenched or undergo
solvolysis to afford the final ring-opened product 23 (Path A). If
22 contains an electron-withdrawing group on either the newly
added aromatic ring or the oxabenzonorbornadiene structure,
then dehydration promoted by resonance and the increased Lewis
acidity of the oxygen atom will produce the corresponding arom-
atized product 24 or 25 (Paths B and C). The role of Et3N in the
reaction mechanism is currently unknown, but as stated previ-
ously, its presence is paramount to the reaction’s success.
In conclusion, we have investigated the effect of two C1 substitu-
ents (ethyl and methoxycarbonyl groups) on oxabenzonorborna-
dienes in the palladium-catalyzed ring-opening reaction using a
variety of aryl iodides. From the results obtained, it appears that
the electronic nature of the substituent dictates the product of
the arylative ring opening. The presence of electron-withdrawing
groups on either the aromatic ring or the C1 position of the oxa-
benzonorbornadiene produced 2-aryl naphthalenes. Reactions
involving electron-withdrawing substituents were much more
susceptible to steric interactions at the reaction site and produced
lower yields overall. In the presence of electron-donating sub-
stituents, the reaction proceeded at relatively high yields regardless
of substituent location. Despite the disparity between electron-
donating and -withdrawing species, both were highly regioselec-
tive, producing a single product as a result of addition of the aryl
group to the olefin carbon away from the C1 substituent.
Entry
R1
R2
R3
Product
Yield (%)a
1
OMe
H
H
Me
H
H
H
NO2
H
H
OMe
H
H
Me
H
H
H
NO2
H
H
H
OMe
H
H
Me
H
H
H
NO2
9a
9b
9c
9d
9e
9f
9g
9h
9i
85
80
77
71
68
73
68
17
14
0
2
3
4
5
6
7
8
9
10
H
9j
aIsolated yield after column chromatography.
The tendency for the ring opening-reaction to form the aroma-
tized product (9) when in the presence of electron-withdrawing
substituents was intriguing to us. A similar ring-opening reaction
using aryl boronic acids under rhodium catalysis afforded the
nonaromatized product (14) (Scheme 2). When subjected to the
palladium-catalyzed ring-opening conditions, 14 was stable at
room temperature but quickly aromatized at 60 °C. No aromati-
zation of 14 was detected in the absence of Et3N at either temper-
ature. These results lead us to believe that the sole cause of the
aromatization is due to base-catalyzed dehydration with Et3N.
Based on our findings, a mechanism is presented. The ring-
opening reaction mechanism is initiated by the reduction of
palladium(II) (15) (Scheme 3) to palladium(0) (16) by zinc metal
(Scheme 3). Following this reduction, oxidative addition of the
aryl halide 17 produces the aryl−palladium complex 18. Insertion
of 19 into the Pd−Ph generates intermediate 20 in what is thought
to be the rate-determining step.6 It is possible that chelation with
the olefin or oxygen atom of the oxabicycle promotes the high exo
selection observed in this reaction. As reported by Chen and
Duan, the likely role of ZnCl2 is to assist in the removal of iodide
on the Pd(PPh3)2ArI complex and thus enhancing coordination
and insertion of 19 into the R−Pd bond.6 Following this, cleavage
Experimental
All reactions were performed in septum-sealed, flame-dried
flasks under nitrogen. Dried and degassed solvents were obtained
from an LC-SPS solvent purification system supplied with dry-
packed columns containing 3 Å molecular sieves. Commercial
reagents were purchased from Sigma-Aldrich and used without
further purification. Standard column chromatography was per-
formed on 230–400 mesh silica gel using flash column chroma-
tography techniques. Analytical thin-layer chromatography was
performed on Merck precoated silica gel 60 F254 plates. Infrared
spectra were obtained as thin films on KBr disks using a Bomem
MB-100 FTIR or Nicolet-380 FTIR spectrophotometer. 1H and
13C NMR (JMOD) spectra were recorded on Bruker Avance 300 or
Published by NRC Research Press

892
Can. J. Chem. Vol. 92, 2014
Table 5. Effect of C1 substitution on the palladium-catalyzed ring-opening reaction.
Entry
Oxabenzonorbornadiene
R
Product
Yield (%)a
1
11a
6
Me
Et
t-Bu
Cyclobutyl
Biphenyl
CH2OH
CONH2
COCH3
CO2Me
SiMe3
12a
7a
85
95
54
65
19
43
12
27
80b
62
2
3
4
5
6
7
8
9
10
11b
11c
11d
11e
11f
11g
8
12b
12c
12d
12e
13a
13b
9a
11h
13c
aIsolated yield after column chromatography.
bTHF used as solvent.
Scheme 2. Two methods of ring opening 8: palladium-catalyzed ring opening with phenyl iodide to afford the aromatized 9g and rhodium-
catalyzed ring opening with phenyl boronic acid to afford the nonaromatized 14.
400 MHz spectrometers with the solvent resonance as the internal
(1S*,2R*)-1,2-dihydro-4-ethyl-2-(4-methoxyphenyl)-1-naphthalenol
(7a) (Table 3, entry 1)
1
standard (deuterochloroform; H: ␦ 7.24 ppm, 13C: ␦ 77.0 ppm).
Yield 95% (119 mg, 0.45 mmol); off-white solid; mp 63–65 °C; Rf =
0.30 (EtOAc–hexanes, 1:5). IR (␯, cm−1): 3444, 2962, 2931, 1641, 1473,
1267, 1132. 1H NMR (400 MHz, CDCl3) ␦: 1.23 (t, J = 7.3 Hz, 3H), 1.45
(d, J = 8.6 Hz, 1H), 2.57 (dq, J = 7.3, 1.4 Hz, 2H), 3.73–3.78 (m, 4H),
4.85–4.89 (m, 1H), 5.91 (d, J = 4.6 Hz, 1H), 6.81 (d, J = 8.7 Hz, 2H), 7.11
(d, J = 8.7 Hz, 2H), 7.22–7.26 (m, 1H), 7.29–7.34 (m, 1H), 7.35–7.37 (m,
2H). 13C NMR (100 MHz, CDCl3) ␦: 12.9, 25.1, 46.0, 55.2, 71.4, 114.0,
122.8, 124.7, 126.4, 127.6, 127.9, 129.6, 130.3, 133.6, 137.1, 138.3,
158.8. HRMS (ESI) calcd. for C19H20O2Na (M+Na+): 303.1360; found:
303.1364.
HRMS was performed at the Mass Spectrometry & Proteomics
Services Unit of Queen’s University, Kingston, Ontario. The sam-
ples were ionized by electron impact (EI) or positive electrospray
ionization (ESI) and ion detection was performed by time of flight.
General procedure for palladium-catalyzed ring-opening
reaction of C1-substituted oxabenzonorbornadienes with
aryl iodides
PdCl2(PPh3)2 (0.016 g, 0.05 mmol), zinc powder (0.315 g, 5 mmol),
C1-substituted oxabenzonorbornadiene derivative (0.50 mmol),
and zinc chloride (0.025 mmol) were weighed out in dry flask
equipped with a magnetic stirring bar. After the flask was sealed
with a rubber septum, the system was evacuated and purged with
nitrogen gas three times followed by addition of solvent (3.0 mL).
The flask was charged with triethylamine (4.0 mmol) and aryl
halide (0.55 mmol) via a syringe through the rubber septum into
the flask. The mixture was heated with stirring at 60–65 °C until
the bicyclic alkene derivative was consumed as indicated by thin-
layer chromatography analysis of the solution.
The reaction mixture was then cooled and stirred under air for
15–20 min at room temperature. The reaction mixture was diluted
with dichloromethane (10–15 mL) and filtered through a pad of
Celite™. The obtained filtrate was concentrated on a rotary evap-
orator to obtain a brown oily residue. The crude residue was
purified by flash chromatography, eluting with mixtures of EtOAc−
hexanes to provide the product.
(1S*,2R*)-1,2-dihydro-4-ethyl-2-(3-methoxyphenyl)-1-naphthalenol
(7b) (Table 3, entry 2)
Yield 80% (112 mg, 0.5 mmol); light-brown oil; Rf = 0.27 (EtOAc–
hexanes, 1:5). IR (␯, cm−1): 3559, 3054, 2986, 1599, 1486, 1422, 1264,
1155, 1050. 1H NMR (400 MHz, CDCl3) ␦: 1.22 (t, J = 7.4 Hz, 3H), 1.49
(d, J = 8.4 Hz, 1H), 2.54–2.58 (m, 2H), 3.71 (s, 3H), 3.79 (dd, J = 5.6,
4.4 Hz, 1H), 4.88 (dd, J = 6.1, 8.2 Hz, 1H), 5.91 (d, J = 4.3 Hz, 1H),
6.73–6.85 (m, 3H), 7.20 (t, J = 7.9 Hz, 1H), 7.23–7.27 (m, 1H), 7.31 (dt,
J = 7.6, 1.3 Hz, 1H), 7.37 (t, J = 6.2 Hz, 2H). 13C NMR (100 MHz, CDCl3)
␦: 12.9, 25.1, 46.9, 55.0, 71.4, 112.5, 114.8, 121.5, 122.8, 124.2, 126.5,
127.6, 128.0, 129.4, 133.5, 136.9, 138.5, 139.8, 159.6. HRMS (EI) calcd.
for C19H20O2 (M+): 280.1463; found: 280.1465.
(1S*,2R*)-1,2-dihydro-4-ethyl-2-(2-methoxyphenyl)-1-naphthalenol
(7c) (Table 3, entry 3)
Yield 91% (127 mg, 0.5 mmol); off-white solid; mp 70–72 °C; Rf =
0.24 (EtOAc–hexanes, 1:5). IR (␯, cm−1): 3565, 3054, 2986, 1600,
Published by NRC Research Press

Raheem et al.
893
Scheme 3. Proposed mechanism for the palladium-catalyzed ring
opening of C1-substituted oxabenzonorbornadienes with aryl iodides.
(1S*,2R*)-1,2-dihydro-4-ethyl-2-(3-methlyphenyl)-1-naphthalenol
(7e) (Table 3, entry 5)
Yield 95% (125 mg, 0.5 mmol); light-brown oil; Rf = 0.35 (EtOAc–
hexanes, 1:5). IR (␯, cm−1): 3560, 3054, 2986, 1605, 1422, 1264, 1094,
896. 1H NMR (400 MHz, CDCl3) ␦: 1.28 (t, J = 7.4 Hz, 3H), 1.62 (d, J =
8.1 Hz, 1H), 2.35 (s, 3H), 2.62 (dq, J = 1.5, 7.4 Hz, 2H), 3.80–3.82 (m,
1H), 4.87 (dd, J = 6.0, 7.8 Hz, 1H), 5.96 (d, J = 4.1 Hz, 1H), 7.05 (d, J =
7.4 Hz, 1H), 7.09 (d, J = 7.3 Hz, 2H), 7.20 (t, J = 8.0 Hz, 1H), 7.28 (dt, J =
7.3, 1.3 Hz, 1H), 7.33–7.45 (m, 3H). 13C NMR (100 MHz, CDCl3) ␦: 12.9,
21.4, 25.1, 46.9, 71.4, 122.9, 124.3, 126.1, 126.7, 127.5, 127.9, 128.0,
128.4, 130.0, 133.5, 136.9, 138.0, 138.30, 138.32. HRMS (EI) calcd. for
C19H20O (M+): 264.1514; found: 264.1517.
ZnI
O
Cl
Cl Pd P
P
15
Ar
22
Zn
ZnCl2
I
Ar
17
R
P Pd P
16
Zn
IP2Pd
Ar
O
R
I
P Pd Ar
O
P
18
21
(1S*,2R*)-1,2-dihydro-4-ethyl-2-(2-methlyphenyl)-1-naphthalenol
(7f) (Table 3, entry 6)
R
19
Yield 88% (116 mg, 0.5 mmol); off-white solid; mp 95–96 °C; Rf =
0.40 (EtOAc–hexanes, 1:5). IR (␯, cm−1): 3562, 3054, 2986, 1602,
1488, 1422, 1265, 896, 739. 1H NMR (400 MHz, CDCl3) ␦: 1.17 (t, J =
7.4 Hz, 3H), 1.44 (d, J = 7.2 Hz, 1H), 2.34 (s, 3H), 2.52 (q, J = 7.4 Hz, 2H),
4.05–4.15 (m, 1H), 4.70 (t, J = 6.0 Hz, 1H), 5.79 (d, J = 2.2 Hz, 1H),
7.07–7.12 (m, 2H), 7.13–7.16 (m, 1H), 7.17–7.21 (m, 2H), 7.26–7.30 (m,
2H), 7.34 (d, J = 7.7 Hz, 1H). 13C NMR (100 MHz, CDCl3) ␦: 12.9, 19.8,
25.1, 42.7, 70.0, 123.0, 125.0, 126.2, 127.1, 127.5, 127.6, 128.4, 129.2,
O
O
R
Ar
Cl2ZnI
Ar
P
P Pd
I
P
Pd
P
R
O
Ar
P
P Pd
I
ZnCl2
130.6, 133.4, 136.3, 136.6, 137.3, 138.1. HRMS (EI) calcd. for C19H20
O
(M+): 264.1514; found: 264.1518.
R
20
(1S*,2R*)-1,2-dihydro-4-ethyl-2-phenyl-1-naphthalenol (7g)
(Table 3, entry 7)
Path A
No EWG
Path B
Ar=EWG
Path C
R=EWG
Yield 75% (94 mg, 0.5 mmol); light-brown oil; Rf = 0.35 (EtOAc–
hexanes, 1:5). IR (␯, cm−1): 3564, 3054, 2986, 1602, 1452, 1422, 1265,
896, 739. 1H NMR (400 MHz, CDCl3) ␦: 1.17 (t, J = 7.4 Hz, 3H), 1.41 (d,
J = 8.4 Hz, 1H), 2.52 (dq, J = 1.3, 7.4 Hz, 2H), 3.75 (dd, J = 5.8, 4.4 Hz,
1H), 4.81 (dd, J = 8.3, 5.9 Hz, 1H), 5.87 (d, J = 4.4 Hz, 1H), 7.15–7.33 (m,
9H). 13C NMR (100 Mhz, CDCl3): 12.9, 25.1, 47.0, 71.5, 122.9, 124.3,
126.6, 127.3, 127.6, 128.1, 128.5, 129.3, 133.6, 136.9, 138.2, 138.5.
HRMS (EI) calcd. for C18H18O (M+): 250.1358; found: 250.1354.
ZnI
O
ZnI
O
ZnI
O
Ar
Ar
EWG
Ar
Et
R
EWG
3-(4-Methoxyphenyl)-1-naphthalene carboxylic acid methyl ester
(9a) (Table 4, entry 1)
H2O
Et3N
Et3N
Yield 85% (105 mg, 0.45 mmol); white solid; mp 76–77 °C; Rf =
0.38 (EtOAc–hexanes, 1:5). IR (␯, cm−1): 3054, 2987, 1716, 1610, 1517,
1437, 1422, 1265, 1181, 739. 1H NMR (400 MHz, CDCl3) ␦: 3.85 (s, 3H),
4.02 (s, 3H), 7.02 (d, J = 8.8 Hz, 2H), 7.51–7.54 (m, 1H), 7.59 (dt, J = 8.4,
1.3 Hz, 1H), 7.66 (d, J = 8.7 Hz, 2H), 7.89 (d, J = 8.0 Hz, 1H), 8.13(d, J =
1.1 Hz, 1H), 8.44(d; J = 1.9 Hz, 1H); 8.91(d, J = 8.5 Hz, 1H). 13C NMR
(100 MHz, CDCl3) ␦: 52.1, 55.3, 114.3, 125.6, 126.5, 127.4, 127.5, 128.3,
128.6, 129.6, 129.9, 130.0, 132.3, 134.3, 136.8, 159.4, 167.9. HRMS
(ESI) calcd. for C19H16O3 (M+H+): 293.1177; found: 293.1176.
OH
Et
EWG
Ar
23
24
25
EWG
R
1491, 1463, 1439, 1422, 1264, 739. 1H NMR (400 MHz, CDCl3) ␦: 1.16
(t, J = 7.4 Hz, 3H), 2.05 (d, J = 5.3 Hz, 1H), 2.48–2.54 (m, 2H), 3.76 (s,
3H), 4.29–4.31 (m, 1H), 4.80 (t, J = 5.3 Hz, 1H), 5.77 (d, J = 3.6 Hz, 1H),
6.79–6.85 (m, 2H), 7.10–7.20 (m, 3H), 7.22–7.26 (m, 1H), 7.31 (d, J =
7.9 Hz, 2H). 13C NMR (100 MHz, CDCl3) ␦: 12.9, 25.1, 39.6, 55.4, 70.4,
110.4, 120.7, 122.8, 124.2, 127.2, 127.3, 127.4, 128.0, 128.1, 130.0, 133.2,
136.6, 138.3, 157.2. HRMS (EI) calcd. for C19H20O2 (M+): 280.1463;
found: 280.1467.
3-(3-Methoxyphenyl)-1-naphthalene carboxylic acid methyl ester
(9b) (Table 4, entry 2)
Yield 80% (117 mg, 0.5 mmol); off-white solid; mp 55–56 °C; Rf =
0.43 (EtOAc–hexanes, 1:5). IR (␯, cm−1): 3054, 2987, 1716, 1599, 1422,
1
1264, 1207. H NMR (400 MHz, CDCl3) ␦: 3.89 (s, 3H), 4.02 (s, 3H),
6.95 (ddd, J = 10.6, 0.8, 0.7 Hz, 1H), 7.24–7.26 (m, 1H), 7.31 (dd, J = 7.6,
0.9 Hz, 1H), 7.41 (t, J = 7.9 Hz, 1H), 7.52–7.56 (m, 1H), 7.59–7.63 (m,
1H), 7.92 (d, J = 7.9 Hz, 1H), 8.19 (d, J = 1.6 Hz, 1H), 8.46 (d, J = 2.0 Hz,
1H), 8.91 (d, J = 8.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) ␦: 52.2, 55.3,
113.0, 113.1, 119.8, 125.7, 126.6, 127.6, 127.7, 128.8, 129.8, 130.0, 130.5,
130.8, 134.2, 137.1, 141.4, 160.1, 167.9. HRMS (ESI) calcd. for
C19H16O3Na (M+Na+): 315.0997; found: 315.0992.
(1S*,2R*)-1,2-dihydro-4-ethyl-2-(4-methlyphenyl)-1-naphthalenol
(7d) (Table 3, entry 4)
Yield 93% (123 mg, 0.5 mmol); light-brown oil; Rf = 0.35 (EtOAc–
hexanes, 1:5). IR (␯, cm−1): 3560, 3054, 2986, 1603, 1514, 1422, 1266,
896, 735. 1H NMR (400 MHz, CDCl3) ␦: 1.38 (t, J = 7.4 Hz, 3H), 1.71 (d,
J = 8.5 Hz, 1H), 2.45 (s, 3H), 2.71–2.76 (m, 2H), 3.92 (dd, J = 5.6, 4.6 Hz,
1H), 5.01 (dd, J = 7.8, 6.5 Hz, 1H), 6.07 (d, J = 4.3 Hz, 1H), 7.20–7.30 (m,
4H), 7.34–7.42 (m, 1H), 7.44–7.58 (m, 3H). 13C NMR (100 MHz, CDCl3)
␦: 12.9, 21.0, 25.1, 46.5, 71.4, 122.8, 124.5, 124.6, 126.5, 127.5, 127.9, 129.1,
133.6, 134.9, 136.8, 137.0, 138.3. HRMS (ESI) calcd. for C19H20ONa
(M+Na+): 287.1411; found: 287.1420.
3-(2-Methoxyphenyl)-1-naphthalene carboxylic acid methyl ester
(9c) (Table 4, entry 3)
Yield 77% (112 mg, 0.5 mmol); light-brown oil; Rf = 0.38 (EtOAc–
hexanes, 1:5). IR (␯, cm−1): 3054, 2987, 1714, 1495, 1437, 1422, 1264,
1027, 743. 1H NMR (300 MHz, CDCl3) ␦: 3.83 (s, 3H), 4.01 (s, 3H), 7.03
(d, J = 9.9 Hz, 1H), 7.09 (dt, J = 0.7, 7.5 Hz, 1H), 7.34–7.46 (m, 2H),
7.51–7.56 (m, 1H), 7.60 (dt, J = 8.5, 1.4 Hz, 1H), 7.91(d, J = 7.8 Hz, 1H),
Published by NRC Research Press

894
Can. J. Chem. Vol. 92, 2014
8.16 (s, 1H), 8.43 (d, J = 1.7 Hz, 1H), 8.95 (d, J = 8.5 Hz, 1H). 13C NMR
(75 MHz, CDCl3) ␦: 52.1, 55.6, 111.3, 121.0, 125.6, 126.2, 126.5, 127.5,
128.7, 129.1, 129.5, 130.2, 130.9, 132.5, 133.4, 133.9, 134.9, 156.6,
168.1. HRMS (ESI) calcd. for C19H16O3Na (M+Na+): 315.0997; found:
315.0993.
3-(3-Nitrophenyl)-1-naphthalene carboxylic acid methyl ester (9i)
(Table 4, entry 9)
Yield 14% (22 mg, 0.5 mmol); light-yellow oil; Rf = 0.38 (EtOAc–
hexanes, 1:5). IR (␯, cm−1): 3054, 2987, 1716, 1436, 1422, 1265, 896,
1
739. H NMR (400 MHz, CDCl3) ␦: 4.04 (s, 3H), 7.55–7.63 (m, 2H),
7.67 (t, J = 7.8 Hz, 1H), 7.86–7.89 (m, 1H), 7.96–8.01 (m, 2H), 8.33 (d,
1.7 Hz, 1H), 8.35(t, J = 1.7 Hz, 1H), 8.55(d, J = 1.9 Hz, 1H), 8.91 (d,
8.7 Hz, 1H). 13C NMR (100 MHz, CDCl3): 52.3, 122.0, 125.8, 126.8,
127.9, 128.0, 128.9, 129.7, 129.8, 129.9, 130.7, 130.1, 134.3, 136.4, 141.1,
153.2, 167.9. HRMS (ESI) calcd. for C18H13NO4Na (M+Na+): 330.0743;
found: 330.0750.
3-(4-Methylphenyl)-1-naphthalene carboxylic acid methyl ester
(9d) (Table 4, entry 4)
Yield 71% (98 mg, 0.5 mmol); light-brown oil; Rf = 0.60 (EtOAc–
hexanes, 1:5). IR (␯, cm−1): 3054, 2987, 1716, 1602, 1518, 1436, 1265,
1
1211, 1152, 1137. H NMR (400 MHz, CDCl3) ␦: 2.43 (s, 3H), 4.04 (s,
3H), 7.31 (d, J = 7.9 Hz, 2H), 7.54 (dt, J = 6.9, 1.1 Hz, 1H), 7.58–7.59 (m,
1H), 7.60 (d, J = 8.5, 1.5 Hz, 1H), 7.64 (d, J = 8.1 Hz, 1H), 7.91 (d, J =
8.5 Hz, 1H), 8.18 (d, J = 1.7 Hz, 1H), 8.48 (d, J = 2.0 Hz, 1H), 8.93 (d, J =
8.7 Hz, 1H). 13C NMR (100 MHz, CDCl3) ␦: 21.1, 52.1, 125.6, 126.5,
127.0, 127.5, 127.5, 128.7, 129.6, 129.8, 130.2, 130.4, 134.2, 136.9,
137.1, 137.5, 167.9. HRMS (ESI) calcd. for C19H16O2 (M+): 276.1150;
found: 276.1146.
1-Ethyl-3-(4-nitrophenyl)-naphthalene (10a) (Table 3, entry 8)
Yield 61% (85 mg, 0.5 mmol); light-brown oil; Rf = 0.15 (EtOAc–
hexanes, 1:5). IR (␯, cm−1): 3471, 3386, 2970, 1674, 1621, 1519, 1265,
1184. 1H NMR (400 MHz, CDCl3) ␦: 1.46 (t, J = 7.6 Hz, 3H), 3.19 (q, J =
7.6 Hz, 2H), 6.81 (d, J = 8.5 Hz, 2H), 7.47–7.53 (m, 2H), 7.59 (d, J =
8.5 Hz, 2H), 7.62 (d, J = 1.6 Hz, 1H), 7.87 (d, J = 1.2 Hz, 1H), 7.90 (dd,
J = 6.1, 3.4 Hz, 1H), 8.07 (dd, J = 6.1, 3.4 Hz, 1H). 13C NMR (100 MHz,
CDCl3) ␦: 15.1, 26.0, 115.4, 122.9, 123.5, 124.4, 125.2, 125.7, 128.2,
128.8, 130.5, 131.5, 134.2, 138.1, 140.6, 145.8. HRMS (ESI) calcd. for
C18H15NO2 (M+H+): 278.1183; found: 278.1185.
3-(3-Methylphenyl)-1-naphthalene carboxylic acid methyl ester (9e)
(Table 4, entry 5)
Yield 68% (94 mg, 0.5 mmol); light-brown oil; Rf = 0.50 (EtOAc–
hexanes, 1:5). IR (␯, cm−1): 3054, 2987, 1716, 1436, 1422, 1265, 1198,
1021, 739. 1H NMR (400 MHz, CDCl3) ␦: 2.47 (s, 3H), 4.04 (s, 3H), 7.22
(d, J = 7.8 Hz, 1H), 7.39 (t, J = 7.6 Hz, 1H), 7.50–7.59 (m, 3H), 7.60–7.63
(m, 1H), 7.92 (d, J = 8.0 Hz, 1H), 8.19 (d, J = 1.5 Hz, 1H), 8.48 (d, J =
1.9 Hz, 1H), 8.93 (d, J = 8.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) ␦: 21.5,
52.2, 124.4, 125.7, 126.5, 127.5, 127.6, 128.0, 128.5, 128.8, 128.8, 129.9,
130.4, 130.7, 134.2, 137.3, 138.5, 139.8, 167.9. HRMS (ESI) calcd. for
C19H16O2 (M+): 276.1150; found: 276.1147.
1-Ethyl-3-(3-nitrophenyl)-naphthalene (10b) (Table 3, entry 9)
Yield 30% (42 mg, 0.5 mmol); light-brown oil; Rf = 0.24 (EtOAc–
hexanes, 1:5). IR (␯, cm−1): 3466, 3384, 3053, 2970, 1620, 1600, 1496,
1421, 1265. 1H NMR (400 MHz, CDCl3) ␦: 1.42 (t, J = 7.6 Hz, 3H), 3.16
(q, J = 7.6 Hz, 2H), 6.70 (dd, J = 7.9, 1.5 Hz, 1H), 7.04 (t, J = 1.9 Hz, 1H),
7.12 (d, J = 7.7 Hz, 1H), 7.27 (d, J = 7.8 Hz, 1H), 7.44–7.53 (m, 2H), 7.58
(s, 1H), 7.83–7.92 (m, 2H), 8.01–8.09 (m, 1H). 13C NMR (100 MHz,
CDCl3) ␦: 15.1, 26.0, 114.1, 117.9, 123.6, 124.1, 124.7, 125.7, 125.8,
129.0, 129.7, 131.0, 134.1, 138.4, 140.7, 142.5, 146.8. HRMS (ESI) calcd.
for C18H15NO2 (M+H+): 278.1183; found: 278.1181.
3-(2-Methylphenyl)-1-naphthalene carboxylic acid methyl ester (9f)
(Table 4, entry 6)
(1S*,2R*)-1,2-dihydro-4-methyl-2-(4-methoxyphenyl)-1-naphthalenol
(12a) (Table 5, entry 1)
Yield 73% (101 mg, 0.5 mmol); light-brown oil; Rf = 0.50 (EtOAc–
hexanes, 1:5). IR (␯, cm−1): 3054, 2987, 1715, 1436, 1422, 1265, 1212,
1197, 896, 742. 1H NMR (400 MHz, CDCl3) ␦: 2.33 (s, 3H), 4.01 (s, 3H),
7.26–7.38 (m, 4H), 7.57 (dt, J = 6.9, 1.1 Hz, 1H), 7.63–7.67 (m, 1H), 7.91
(d, J = 8.1 Hz, 1H), 7.97 (d, J = 1.4 Hz, 1H), 8.24 (d, J = 1.9 Hz, 1H), 8.98
(d, J = 8.7 Hz, 1H). 13C NMR (100 MHz, CDCl3): 20.4, 52.1, 125.7, 125.9,
126.5, 126.8, 127.7, 127.7, 128.6, 129.9, 130.2, 130.4, 131.9, 132.9,
133.8, 135.5, 138.2, 140.6, 167.9. HRMS (ESI) calcd. for C19H16O2 (M+):
276.1150; found: 276.1145.
Yield 85% (113 mg, 0.5 mmol); off-white solid; mp 58–60 °C; Rf =
0.42 (EtOAc–hexanes, 1:4). IR (␯, cm−1): 3556, 3446, 3060, 2980,
1607, 1507, 1421, 1308, 1168, 1181. 1H NMR (300 MHz, CDCl3) ␦: 1.45
(s, 1H), 2.16 (t, J = 1.6 Hz, 3H), 3.70–3.80 (m, 4H), 4.88 (dd, J = 6.3,
8.4 Hz, 1H), 5.87–5.93 (m, 1H), 6.81 (d, J = 8.7 Hz, 2H), 7.11 (d, J =
8.5 Hz, 2H), 7.21–7.30 (m, 2H), 7.31–7.39 (m, 3H). 13C NMR (75 MHz,
CDCl3) ␦: 19.1, 46.3, 55.1, 71.4, 113.9, 123.1, 126.3, 126.7, 127.7, 127.9,
129.7, 130.2, 132.6, 134.2, 136.8, 158.8. HRMS (ESI) calcd. for
C18H18O2 (M+): 266.1307; found: 266.1312.
3-Phenyl-1-naphthalene carboxylic acid methyl ester (9g) (Table 4,
entry 7)
(1S*,2R*)-1,2-dihydro-4-t-butyl-2-(4-methoxyphenyl)-1-naphthalenol
(12b) (Table 5, entry 3)
Yield 68% (89 mg, 0.5 mmol); light-brown oil; Rf = 0.50 (EtOAc–
hexanes, 1:5). IR (␯, cm−1): 3054, 2987, 1716, 1436, 1265, 1197, 1152,
897. 1H NMR (400 MHz, CDCl3) ␦: 4.03 (s, 3H), 7.40 (t, J = 7.3 Hz, 1H),
7.43 (t, J = 1.1 Hz, 1H), 7.50 (t, J = 7.3 Hz, 1H), 7.45–7.58 (m, 3H),
7.60–7.64 (m, 1H), 7.72–7.75 (m, 2H), 7.92 (d, J = 8.1 Hz, 1H), 8.20 (d,
J = 1.6 Hz, 1H), 8.48 (d, J = 1.9 Hz, 1H), 8.93 (d, J = 8.7 Hz, 1H). 13C NMR
(100 MHz, CDCl3): 52.2, 125.7, 126.5, 127.3, 127.6, 127.7, 128.8, 128.9,
129.8, 130.4, 130.8, 134.2, 137.2, 139.9, 167.9. HRMS (EI) calcd. for
C18H14O2 (M+): 262.0994; found: 262.0998.
Yield 54% (83 mg, 0.5 mmol); light-brown solid; mp 111–112 °C;
Rf = 0.31 (EtOAc–hexanes, 1:5). IR (␯, cm−1): 3559, 3054, 2987, 1512,
1265, 1180, 1035. 1H NMR (400 MHz, CDCl3) ␦: 1.41 (s, 9H), 1.47 (d, J =
9.1 Hz, 1H), 3.70 (t, J = 5.4 Hz, 1H), 3.75 (s, 3H), 4.76 (dd, J = 8.2,
6.0 Hz, 1H), 6.09 (d, J = 4.9 Hz, 1H), 6.80 (d, J = 8.6 Hz, 2H), 7.08 (d, J =
8.6 Hz, 2H), 7.22 (dt, J = 1.0, 7.3 Hz, 1H), 7.29 (dt, J = 7.8, 1.3 Hz, 1H),
7.34 (d, J = 7.3 Hz, 1H), 7.72 (d, J = 7.8 Hz, 1H). 13C NMR (100 MHz,
CDCl3) ␦: 31.1, 35.2, 46.1, 55.2, 71.6, 114.0; 124.9; 126.2, 126.5, 126.9,
127.1, 129.7, 130.3, 133.1, 138.5, 145.4, 158.8. HRMS (EI) calcd. for
C21H24O2 (M+): 308.1776; found: 308.1172.
3-(4-Nitrophenyl)-1-naphthalene carboxylic acid methyl ester (9h)
(Table 4, entry 8)
(1S*,2R*)-1,2-dihydro-4-cyclobutyl-2-(4-methoxyphenyl)-1-naphthalenol
(12c) (Table 5, entry 4)
Yield 17% (26 mg, 0.5 mmol); yellow solid; mp 141–143 °C; Rf =
0.50 (EtOAc–hexanes, 1:4). IR (␯, cm−1): 3080, 1715, 1597, 1519, 1434,
1350, 1250, 1193. 1H NMR (300 MHz, CDCl3) ␦: 4.03 (s, 3H), 7.55–7.70
(m, 2H), 7.85 (d, J = 8.9 Hz, 2H), 7.95 (d, J = 8.6 Hz, 1H), 8.23 (d, J =
1.6 Hz, 1H), 8.32 (d, J = 8.9 Hz, 2H), 8.42(d, J = 2.0 Hz, 1H), 8.91 (d, J =
8.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) ␦: 52.4, 124.2, 125.8, 127.1,
127.9, 128.2, 128.3, 128.7, 129.0, 131.0, 131.6, 134.1, 134.7, 146.2, 147.3,
167.5. HRMS (ESI) calcd. for C18H13NO4 (M+H+): 308.0922; found:
308.0936.
Yield 65% (99 mg, 0.5 mmol); off-white solid, mp 115–117 °C; Rf =
0.30 (EtOAc–hexanes, 1:5). IR (␯, cm−1): 3554, 3054, 2967, 1609, 1511,
1463, 1265, 1250, 1036, 764. 1H NMR (400 MHz, CDCl3) ␦: 1.49 (d, J =
8.7 Hz, 1H), 1.70–1.80 (m, 1H), 1.89–2.07 (m, 3H), 2.17–2.30 (m, 2H),
3.40–3.52 (m, 1H), 3.65 (s, 3H), 3.69 (m, 1H), 4.78 (dd, J = 8.5, 6.3 Hz,
1H), 5.80 (dd, J = 4.6, 1.7 Hz, 1H), 6.71 (d, J = 8.7 Hz, 2H), 7.02 (d, J =
8.7 Hz, 2H), 7.10–7.23 (m, 3H), 7.26 (d, J = 7.3 Hz, 1H). 13C NMR
(100 MHz, CDCl3) ␦: 18.3, 28.0, 28.2, 37.3, 46.0, 55.1, 71.3, 113.9,
Published by NRC Research Press

Raheem et al.
895
123.3, 123.5, 126.2, 127.5, 127.8, 129.7, 130.3, 133.1, 137.1, 140.3, 158.8.
HRMS (ESI) calcd. for C21H23O2 (M+H+): 307.1692; found: 307.1698.
General procedure for rhodium-catalyzed ring opening of
C1-substituted oxabenzonorbornadiene with aryl boronic
acid
(1S*,2R*)-1,2-dihydro-4-biphenyl-2-(4-methoxyphenyl)-1-naphthalenol
(12d) (Table 5, entry 5)
Inside an inert atmospheric glove box system, [Rh(COD)Cl]2
(5 mol%), NaHCO3 (1 equiv.), and boronic acid (1.1 equiv.) were
weighed and added to a screw cap vial equipped with a stir bar.
To this mixture was charged the substituted oxabenzonorborna-
diene (0.24 mmol) and methanol (2 mL). The vial was then capped
and left to stir at room temperature. Upon reaction completion,
the vial was removed from the dry box, diluted with DCM, and
passed through a silica plug. The crude product was then sub-
jected to flash column chromatography, eluting with mixtures of
EtOAc−hexanes to provide the neat product.
Yield 19% (38 mg, 0.5 mmol); light-brown solid; mp 138–140 °C;
Rf = 0.37 (EtOAc–hexanes, 1:5). IR (␯, cm−1): 3550, 3052, 3030, 1608,
1509, 1485, 1263, 1178, 1035, 824, 763. 1H NMR (400 MHz, CDCl3) ␦:
1.49 (d, J = 8.7 Hz, 1H), 1.70–1.80 (m, 1H), 1.89–2.07 (m, 3H), 2.17–2.30
(m, 2H), 3.40–3.52 (m, 1H), 3.65 (s, 3H), 3.69 (m, 1H), 4.78 (dd, J = 8.5,
6.3 Hz, 1H), 5.80 (dd, J = 4.6, 1.7 Hz, 1H), 6.71 (d, J = 8.7 Hz, 2H), 7.02
(d, J = 8.7 Hz, 2H), 7.10–7.23 (m, 3H), 7.26 (d, J = 7.3 Hz, 1H). 13C NMR
(100 MHz, CDCl3) ␦: 53.9, 55.2, 77.2, 113.8, 114.1, 114.3, 126.3, 126.4,
127.0, 127.1, 127.2, 127.7, 127.9, 128.3, 128.4, 128.4, 128.5, 128.7, 128.8,
130.6, 131.1, 133.5, 139.3, 139.8, 140.8, 145.1, 159.1. HRMS (ESI) calcd.
for C29H25O2 (M+H+): 405.1849; found: 405.1856.
(3R,4S)*-4-hydroxy-3-phenyl-3,4-dihydro-1-naphthalene carboxylic
acid methyl (14)
Yield 77% (55.9 mg, 0.199 mmol); light-brown oil; Rf = 0.33
(EtOAc-Hexanes, 1:4). IR (␯, cm−1): 3465, 3060, 3029, 2951, 1717,
1493, 1452, 1436, 1286, 1265, 1198, 1171, 1075, 1034, 1010, 887, 785,
773, 755, 736, 702. 1H NMR (400 MHz, CDCl3) ␦: 1.58 (s, 1H), 3.77 (s,
3H), 3.81 (t, J = 4.7 Hz, 1H), 4.74 (t, J = 6.1 Hz, 1H), 7.11–7.30 (m, 9H),
7.87 (d, J = 7.7 Hz, 1H). 13C NMR (100 MHz, CDCl3) ␦: 47.5, 52.1, 71.1,
76.8, 77.1, 77.4, 126.6, 127.0, 127.7, 128.6, 128.7, 128.8, 129.3, 129.4,
130.6, 136.4, 136.9, 140.1, 166.5. HRMS (EI) calcd. for C18H16O3 (M+):
280.1099; found: 280.1108.
(1S*,2R*)-1,2-dihydro-4-hydroxymethyl-2-(4-methoxyphenyl)-1-
naphthalenol (12e) (Table 5, entry 6)
Yield 43% (61 mg, 0.5 mmol); off-white solid; mp 147–148 °C; Rf =
0.25 (EtOAc–hexanes, 1:1). IR (␯, cm−1): 3688, 3054, 2987, 1550, 1422,
1265, 738. 1H NMR (400 MHz, DMSO-d6) ␦: 3.64 (s, 1H), 3.66 (s, 3H),
4.42 (d, J = 5.3 Hz, 2H), 4.79 (t, J = 5.8 Hz, 1H), 4.97 (t, J = 5.3 Hz, 1H),
5.09 (d, J = 5.3 Hz, 1H), 6.09 (d, J = 4.8 Hz, 1H), 6.74 (d, J = 8.5 Hz, 2H),
7.02 (d, J = 8.5 Hz, 2H), 7.16–7.26 (m, 2H), 7.29 (d, J = 7.3 Hz, 1H), 7.34
(d, J = 6.9 Hz, 1H). 13C NMR (100 Mhz, DMSO-d6): 45.0, 54.9, 61.2,
69.9, 113.0, 122.5, 125.8, 126.8, 126.9, 127.1, 130.3, 130.8, 132.3, 136.1,
138.2, 157.9. HRMS (EI) calcd. for C18H18O3 (M+): 282.1256; found:
282.1259.
Supplementary material
Supplementary material is available with the article through
the journal Web site at http://nrcresearchpress.com/doi/suppl/10.
1139/cjc-2014-0217.
3-(4-Methoxyphenyl)-1-naphthalene carboxamide (13a) (Table 5,
entry 7)
Acknowledgement
This work was supported by the Natural Sciences and Engineer-
ing Research Council of Canada.
Yield 12% (17 mg, 0.5 mmol); light-brown oil; Rf = 0.57 (EtOAc–
hexanes, 1:1). IR (␯, cm−1): 3054, 2987, 1670, 1654, 1517, 1422, 1265,
896, 749. 1H NMR (400 MHz, CDCl3) ␦: 3.87 (s, 3H), 7.01 (d, J = 8.8 Hz,
2H), 7.58–7.64 (m, 4H), 7.94 (d, J = 7.4 Hz, 1H), 8.14 (d, J = 1.7 Hz, 1H),
8.19 (s,1H), 8.22 (d, J = 8.1 Hz, 1H). 13C NMR (100 MHz, CDCl3) ␦: 55.4,
114.1, 114.6, 117.9, 125.0, 127.7, 127.9, 128.2, 128.4, 128.8, 130.0, 131.1,
131.3, 132.0, 133.4, 137.8, 159.9, 162.2. HRMS (EI) calcd. for
C18H15NO2 (M+): 277.1103, found: 277.1112.
References
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Preparation of 3-(4-methoxy-henyl)-1-naphthalene methylketone
(13b, Table 5, entry 8)
Yield: 27% (37 mg, 0.5 mmol); Rf = 0.38 (EtOAc–hexanes, 1:5);
light brown oil; IR (␯, cm−1); 3054, 2987, 1715, 1679, 1610, 1422, 1265,
896, 739; 1H NMR (400 MHz, CDCl3) ␦: 2.78 (s, 3H), 3.87 (s, 3H), 7.04
(d, J = 8.7 Hz, 2H), 7.50–7.60 (m, 2H), 7.64 (d, J = 8.7 Hz, 2H), 7.89 (d,
J = 7.6 Hz, 1H), 8.11 (d, J = 4.4 Hz, 2H), 8.67 (d, J = 8.1 Hz, 1H); 13C NMR
(100 MHz, CDCl3): 30.1, 55.4, 114.5, 125.8, 126.8, 127.7, 128.1, 128.4,
128.6, 128.9, 129.7, 132.6, 134.4, 136.2, 136.8, 159.6, 202.0; HRMS
(ESI) calcd. for C19H17O2 (M+H+): 277.1223; found: 277.1226.
3-(4-Methoxyphenyl)-1-naphthalene trimethylsilane (13c) (Table 5,
entry 10)
Yield 62% (95 mg, 0.5 mmol); light-brown solid; mp 94–96 °C;
Rf = 0.52 (EtOAc–hexanes, 1:5). IR (␯, cm−1): 3054, 2959, 1609, 1515,
1464, 1265, 1250, 1033, 739. 1H NMR (400 MHz, CDCl3) ␦: 0.50 (s, 9H),
3.87 (s, 3H), 7.03 (dd, J = 6.8, 2.0 Hz, 2H), 7.49 (dd, J = 6.2, 3.4 Hz, 2H),
7.65 (dd, J = 6.8, 2.0 Hz, 2H), 7.86–7.92 (m, 2H), 7.98 (d, J = 1.4 Hz,
1H), 8.07–8.14 (m, 1H). 13C NMR (100 MHz, CDCl3) ␦: 0.3, 55.4, 114.2,
114.3, 125.4, 125.7, 126.9, 127.9, 128.1, 128.5, 129.3, 132.8, 133.7, 133.9,
135.7, 137.1, 138.7, 159.2. HRMS (EI) calcd. for C20H22OSi (M+):
306.1440; found: 306.1447.
(9) Bos, P.; Rudolph, A.; Pérez, M.; Fañanás-Mastral, M.; Harutyunyan, S. Chem.
Commun. 2012, 48, 1748. doi:10.1039/c2cc16855c.
Published by NRC Research Press

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