Unexpected regioselectivity observed in the bromination and epoxidation reactions of p-benzoquinone-fused norbornadiene: An experimental and computational study

Article abstract of DOI:10.1016/j.tet.2017.02.017

The bromination reaction of p-benzoquinone-fused norbornadiene was studied at various temperatures (?78,??50, 0, 25, and 77?°C). At room temperature, the double bonds of the p-benzoquinone units were mainly brominated. The double bond of the norbornene unit also underwent a bromination reaction in a yield of only 2%. However, the reaction at??78?°C resulted in the formation of products derived from the attack of bromine on the norbornene double bond with higher charge density. In contrast to the bromination reaction, the epoxidation reaction of the same compound with m-chloroperbenzoic acid and dimethyldioxirane exclusively resulted in the formation of products derived from the addition to the double bond of norbornadiene. The regioselectivity observed was investigated and the results were supported by theoretical calculations.

Full text of DOI:10.1016/j.tet.2017.02.017

Accepted Manuscript
Unexpected regioselectivity observed in the bromination and epoxidation reactions of
p-benzoquinone-fused norbornadiene: An experimental and computational study
Selcuk Essiz, Erdin Dalkilic, Ozlem Sari, Arif Dastan, Metin Balci
PII:
S0040-4020(17)30142-4
10.1016/j.tet.2017.02.017
TET 28458
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 28 November 2016
Revised Date: 26 January 2017
Accepted Date: 6 February 2017
Please cite this article as: Essiz S, Dalkilic E, Sari O, Dastan A, Balci M, Unexpected regioselectivity
observed in the bromination and epoxidation reactions of p-benzoquinone-fused norbornadiene: An
experimental and computational study, Tetrahedron (2017), doi: 10.1016/j.tet.2017.02.017.
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ACCEPTED MANUSCRIPT
Graphical Abstract
1

ACCEPTED MANUSCRIPT
Unexpected regioselectivity observed in the bromination and
epoxidation reactions of p-benzoquinone-fused norbornadi-
ene: An experimental and computational study
Selcuk Essiza,b, Erdin Dalkilica, Ozlem Saric,d, Arif Dastan*,a, Metin Balci*,c
aDepartment of Chemistry, Atatürk University, 25240, Erzurum, Turkey
bDepartment of Chemical Engineering, Hakkari University, TR-30000 Hakkari, Turkey
cDepartment of Chemistry, Middle East Technical University, 06800 Ankara, Turkey
dDepartment of Chemistry, Ahi Evran University, 40100 Kırşehir, Turkey
adastan@atauni.edu.tr, mbalci@metu.edu.tr
Abstract: The bromination reaction of p-benzoquinone-fused norbornadiene was studied at var-
ious temperatures (-78, -50, 0, 25, and 77 °C). At room temperature, the double bonds of the p-
benzoquinone units were mainly brominated. The double bond of the norbornene unit also un-
derwent a bromination reaction in a yield of only 2%. However, the reaction at -78 °C resulted in
the formation of products derived from the attack of bromine on the norbornene double bond
with higher charge density. In contrast to the bromination reaction, the epoxidation reaction of
the same compound with m-chloroperbenzoic acid and dimethyldioxirane exclusively resulted in
the formation of products derived from the addition to the double bond of norbornadiene. The
regioselectivity observed was investigated and the results were supported by theoretical calcula-
tions.
Keywords:
Bromination
Epoxidation
Norbornadiene
1,4-Benzoquinone
Electrophilic addition
2

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1.
Introduction
Bromination of alkenes is an important task in synthetic organic chemistry. Bromine can ste-
reospecifically add to alkenes and form trans-adducts which serve as valuable precursors in the
synthesis of a variety of organic and organometallic species. The mechanism of electrophilic ad-
dition of bromine to alkenes has been intensively studied.1 The mechanism is based on the for-
mation of a bromonium ion and the formation of a trans-addition product by anti-attack of bro-
mide or tribromide ion to a cyclic ion.1,2 On the other hand, the bromination of strained cyclic
systems such as norbornadiene (1) and benzonorbornadiene (5) is more complicated. Addition of
bromine to norbornadiene (1) at lower temperatures results in the formation of products 2-4 de-
rived from Wagner-Meerwein rearrangement and homoallylic conjugation (Scheme 1).3 The ex-
pected trans-addition product was not detected.
Scheme 1. Bromination of norbornadiene and benzonorbornadiene derivatives 1, 5, and 7.
3

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However, the electrophilic addition of bromine to benzonorbornadiene (5) at 10 °C exclu-
sively gave the rearranged product 6 in quantitative yield.4 In the course of studying the bro-
mination reaction of unsaturated bicyclic systems we noted that the reaction temperature has a
dramatic influence on product distribution. When the bromination reaction was carried out at
higher temperatures (77-150 °C) the formation of rearranged products was suppressed and 1,2-
addition products were formed in high yields.5 Kobayashi and Miki6 reacted norbornadiene-fused
pyrazine derivatives 7a with bromine to afford trans-adduct 8a as the major product accompa-
nied by an adduct 9a derived from Wagner-Meerwein type rearrangement and cis-adduct 10a in
a ratio of 20:5:1 (86%), respectively (Scheme 1). On the other hand, treatment of dicyanopyra-
zine derivative 7b with bromine resulted exclusively in the formation of a trans-adduct, 8b. Con-
trary to this finding, a pyrazine-fused norbornadiene with an N-oxide electron donating group
only gave a rearranged product having the same skeleton as 9. All this information shows that
the charge density on the ring fused to the norbornadiene unit has a dramatic effect on the distri-
bution of the products. As part of our ongoing research on bromination of hydrocarbons we were
interested in the bromination reaction of benzoquinone-fused norbornadiene 11 (Figure 1) to
investigate the effect of the p-benzoquinone unit on the mode of the reaction. Furthermore, this
compound 11 contains three different double bonds that can undergo bromine addition. In this
context, we investigated the regioselectiviy as well as the stereoselectivity of bromination and
epoxidation reactions. Furthermore, the effect of double bond pyramidalization on the outcome
of the bromination reaction is discussed.
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Fig. 1. Structure of benzoquinone-fused norbornadiene 11.
2. Results and discussion
The starting material, 1,4-methanonaphthalene-5,8(1H,4H)-dione (11), was synthesized as
described in the literature.7 Enedione 128 obtained from the Diels-Alder reaction of 1,4-
benzoquinone with cyclopenta-1,3-diene was aromatized over silica gel to afford the correspond-
ing annulated hydroquinone-fused norbornadiene 13. Subsequent oxidation of 13 with ceric am-
monium nitrate (CAN) gave p-benzoquinone-annulated norbornadiene 11 in high yield (Scheme
2).
Scheme 2. Synthesis of p-benzoquinone-annulated norbornadiene 11.
The addition of bromine to 11 was carried out in methylene chloride at various temperatures.
1
The analysis of the H NMR spectrum obtained from the reaction at room temperature revealed
the presence of two major products 14 and 15, besides several minor products, 16-19 (Scheme 3).
The two major products, 14 (47%) and 15 (45%), were separated by crystallization of the reaction
mixture from CH2Cl2/n-hexane. The residue was separated by silica gel column chromatography.
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O
O
11
Br2
CH2Cl2
O
O
O
O
O
O
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
+
+
+
+
+
O
O
O
O
O
O
17
18
19
14
15
16
Yields in %
Temperature
14
50
47
44
-
15
50
45
42
-
16
-
2
8
63
64
17
-
2
2
17
15
18
-
19
-
77 °Ca
25 °Ca
0 °Cb
-50 °Cb
-78 °Cb
1
1
13
14
1
1
-
-
-
-
a) Isolated yields, b) Yields were determined with 1H-NMR spectroscopy
Scheme 3. Bromination of 11 at various temperatures.
The structures of these compounds were determined on the basis of 1D and 2D (COSY,
HSQC, HMBC) spectral data. The dibromides 14 and 19 were characterized easily because of
the symmetrical structures, exhibiting six-line 13C NMR spectra. The presence of four double
1
bond proton resonances in the H NMR spectra of 14 and 19 clearly indicated the addition of
bromine atoms to the central double bond with cis-configuration. To distinguish between these
isomers (14 and 19), we analyzed the 1H NMR chemical shift of the bridge protons. It is well es-
tablished that the interactions related to the van der Waals effect cause a paramagnetic contribu-
tion to the shielding constants. As a consequence of this, the proton resonances are shifted to
downfield.9 The chemical shift difference between the endo methylene bridge protons in 14 and
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19 (∆δ = 1.39 ppm) is very large and considerably meaningful to determine the exact structures.
In 14 and 19, a γ-gauche effect was observed depending on the configuration of bromine atoms.
The exo-orientation of the bromine atoms in 14 causes a remarkable downfield shift of the endo-
bridge proton (2.59 ppm) because of the steric repulsion caused by bromine atoms (Figure 2).
However, in the case of 19 the endo-methylene proton resonance is shifted to upfield (1.10 ppm)
due to the presence of this proton in the shielding zone of the double bond as shown in Figure 2.
Fig. 2. The 1H NMR data of the methylene protons in 14, 17, 18, and 19 and JCH coupling constants in 17.
The existence of cyclopropane structures in 17 and 18 was determined by measuring the rel-
evant JCH coupling constants in the proton coupled 13C NMR spectra of 17 and 18. The deter-
mined coupling constants JCH (185.2 and 187.5 Hz) in the sp3-region were decisive for the identi-
fication of cyclopropane rings.10 The configuration of the bromine atoms in 18 was assigned as
described above. The downfield chemical shifts of the endo-methylene proton (2.50 ppm) as well
as the exo-methylene proton (2.56 ppm) in 18 were in agreement with the exo-configuration of
the bromine atoms. The 1H NMR spectra of the regioisomers 15 and 16 revealed sufficient infor-
13
mation for tentative assignments to be made. The 11-line C NMR spectra of 15 and 16 in par-
ticular confirm the presence of asymmetry in the molecule, in other words, the trans-addition of
the bromine atom to the corresponding double bonds.
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During the column chromatography of the reaction mixture, an additional product 20 was
isolated. We noted that this compound was formed on a silica gel column by HBr elimination
from the major product 15. Independently, treatment of pure dibromide 15 with silica gel yielded
monobromide 2011 in quantitative yield (Scheme 4).
Scheme 4. Formation of 20.
For the formation of stereoisomers 14 and 19, we propose the following reaction mecha-
nism. Formation of the products 14 and 19 is unexpected because the electrophilic addition of
molecular bromine to a double bond under ionic conditions generally gives trans-dibromides.
Electrophilic bromine can attack the central double bond from the endo- as well as from the exo-
face of the double bond. It is evident from the configurations of the bromine atoms in 14 that the
initial attack occurred from the exo-face of the double bond. The formed bromonium ion 21 can
rearrange to the non-classical carbocation 22 by an alkyl shift (Scheme 5). The bromide anion
present in the reaction media can attack the carbon atoms C-5 (path a) and C-4 (path b) to form
14 and 23, respectively. The product 14 with cis-configuration was formed as one of the major
products. However, the product 23 was not formed. We assume that the attack of the bromide ion
on the C-4 carbon atom is hindered by the neighboring bromine atom as well as by the exo-
positioned bridge proton. Compounds 17 and 18, comprising cyclopropane moieties, may also be
formed through the same intermediate 22 by attacking of the bromide anion on the C-2 carbon
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atom from the exo- and endo-faces (path c) where a double bond shift is involved. The formation
of 19 can be explained by the formation of the endo-bromonium ion 24 in the same way (Scheme
5).
Scheme 5. Mechanisms for formation of 14, 17, and 18.
The configuration of the bromine atoms in 14 shows that the exo-attack of bromine on the
central double bond is favored. This is due to the pyramidalization of the double bonds in 11. The
double bonds in norbornadiene are pyramidalized in the endo-direction.12 Norbornadiene and
related compounds exclusively undergo an exo-attack upon treatment with bromine. We calculat-
ed the pyramidalization angle of the double bonds in 1 and 11. We noted that there is no dra-
matic change in the degree of pyramidalization when going from 1 to 11 (Figure 3). The double
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bonds in 11 are endo-pyramidalized so that the attack of bromine mainly occurs from the exo-
face.
Fig. 3. Pyramidalization angles of optimized molecules at the M06-2X/6-31+G(d,p) level.
To determine the regioselectivity of bromine addition to 11 having three different double
bonds, the compound was submitted to a bromination reaction at lower temperatures. Unexpect-
edly, the reaction at -78 °C gave three products 16, 17, and 18 with yields of 64%, 15%, and
14%, respectively (Scheme 3). The major product 16 was formed by trans-addition of bromine to
the norbornene double bond. The formation of a rearranged product with a structure similar to
9a was not observed. We assume that the carbonyl groups retarded the formation of a non-
classical carbocation. The bromination reaction at -50 °C gave similar results (Scheme 3). How-
ever, when the reaction was carried out at 0 °C, the product distribution was completely
changed. We obtained products with similar distribution as observed during the reaction at room
temperature.
To check the regio- and stereoselectivity of bromine addition to 11, the bromination reac-
tion was carried out at 77 °C. The high temperature bromination gave two non-rearranged prod-
ucts 14 and 15 in a ratio of 1:1 in quantitative yield (Scheme 3). The mechanism of bromine addi-
tion at high temperatures is different than the mechanism at low temperatures. We demonstrated
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that at high temperatures bromine radicals are involved.5 Generally, the radicals have a low ten-
dency for rearrangements.
After completion of bromine addition to 11 we focused on the epoxidation reaction of 11 to
investigate again regio- and stereoselectivity. The reaction of 11 with m-chloroperbenzoic acid
1
(m-CPBA) was performed in methylene chloride at room temperature. The H NMR spectral
studies of the crude product showed the formation of two isomeric epoxides 25 and 26 in almost
quantitative yield in a ratio of 4.6:1, respectively (Scheme 6). Similarly, epoxidation of 11 with
dimethyldioxirane (DMDO) also resulted in the formation of the same isomeric mixture 25 and
26, in a ratio of 3:1. Contrary to the bromination reaction of 11, no trace of epoxidation products
derived from oxidation of the quinoid ring was observed.
Scheme 6. Epoxidation of 11 with m-CPBA and DMDO at room temperature.
Computational Methods: To support the unusual behavior of 11 against bromination and
epoxidation reactions we performed a series of density functional theory calculations. All calcu-
lations were performed using the Gaussian0913 program. The molecular geometries of all struc-
tures for the formation of non-classical carbocations were fully optimized with M06-2X14 hybrid
functional combined with the 6-31+G(d,p) basis set using the conductor-like polarizable continu-
um solvation model (CPCM)15 in DCM.
The epoxidation reaction of triene 11 with m-chloroperbenzoic acid (m-CPBA) was also in-
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vestigated with the exchange-correlation functional B3LYP16] at 6-31+G(d,p) theory level in the
gas phase. In order to include the solvent effect, single-point calculations were carried out at the
same level as the geometry optimizations using the CPCM solvation model with DCM since it
was used in the experimental study. All stationary points along the reaction paths were verified
by harmonic vibrational frequencies calculated using analytical second derivatives at 25 °C and 1
atm. Intrinsic reaction coordinate (IRC)17 analysis was performed to ensure that the transition
states led to the corresponding minima. Natural bond orbital (NBO)18 analyses were applied to
obtain the atomic charges.
The p-quinone-fused norbornadiene 11 has three different double bonds that can be attacked
to form a bromonium ion, from the endo- as well as the exo-faces. First we determined the rela-
tive energies of the adducts formed during the reaction of 11 with bromine at room temperature
to find whether the thermodynamically most stable compounds were formed as the major product
or not (Table 1).
Table 1
Calculated relative enthalpy energies of six possible products using M06-2X/6-31+G(d,p) level in
kcal/mol.
We found that the cyclopropane derivatives 18 and 17 were the thermodynamically most sta-
ble compounds followed by 16. The products 14, 15, and 19 derived from the addition of bromine
to the p-quinone unit are the less stable compounds. To explain the formation of less stable com-
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pounds during the bromination reaction at room temperature we first determined the relative
energies of bromonium ions derived from different attacks (Table 2).
Table 2
Relative enthalpies of the bromine-cation complexes (in kcal/mol) for 21, 24, and 27-30 using M06-2X/6-
31+G(d,p) level.
Bromine-
cation com-
plexes
Energy
differences
-3.5
-1.0
0.0
6.7
18.3
18.9
It was found that bromonium ion 21 derived from the exo-attack of bromine on the central
double bond and 27 and 28 derived from the exo- and endo-attack on the norbornene double bond
are the most stable ones. However, only the formation of 21 was in agreement with the products
formed by the bromination reaction of 11 at room temperature. Unfortunately, the product 16
derived from the most stable intermediates 27 and 28, was isolated in 2% yields. To address the
question of why the major products were not formed from the intermediates 27 and 28, we calcu-
lated the charge distribution in 11. Geometry optimization and frequency calculation of 11 were
performed with the M06-2X/6-31+G(d,p) method. We found that the greater negative charges are
located on the C2-C3 and C6-C7 double bond carbon atoms (Figure 4). Therefore, one would
expect that an electrophile, the bromonium ion, would attack the more negatively charged carbon
atoms in 11. The formation of the product 15 is in agreement with the charge distribution. How-
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ever, an addition product 16 derived from the attack on the norbornene double bond was formed
in a yield of only 2%.
Fig. 4. Geometry optimized structure of 11 and atomic charge distribution (NBO analysis)
carried out using the M06-2X method and a basis set 6-31+G(d,p). Distances are given in Å.
Furthermore, we calculated the highest occupied (HOMO) and lowest unoccupied (LUMO)
molecular orbitals of 11 shown in Figure 5. In the case of HOMO, the charge is mainly accumu-
lated on the norbornene double bond. In contrast, the LUMO is located over the benzoquinone
ring.
11 (HOMO)
11 (LUMO)
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Fig. 5. The calculated highest occupied (HOMO) and lowest unoccupied (LUMO) MOs of 11.
After calculation of the relative energies of the bromonium ion complexes 21 and 27, we
calculated the transition structures for formations of their non-classical carbocations 22 and 31
starting from the exo-bromonium ions (Figure 6). The formation of non-classical carbocations via
sigma bond participation was investigated using M06-2X/6-31+G(d,p) level in DCM. For the
formation of 22, an activation energy of 0.44 kcal/mol (with respect to the energy of 21) is re-
quired (Figure 7). On the other hand, 2.92 kcal/mol is required for the formation of 31 with re-
spect to the energy of 27 (Figure 7). Therefore, we assume that the lower activation barrier for the
formation of 22 is the driving force of this reaction and is also responsible for the regioselectivi-
ty. At low temperature reactions bromine exclusively attacks the norbornene double bond with
the higher charge density.
+
Br
Br
+
O
O
O
O
Br
Br
+
+
O
O
O
O
22
21
31
27
Fig. 6. The structures of intermediates 21, 22, 27, and 31.
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21
TS1
22
27
TS2
31
Fig. 7. Optimized geometries of bromonium cation complexes (21 and 27), transition states, and non-
classical carbocations at the M06-2X/6-31+G(d,p) level in DCM. Some critical distances (Å) are given.
Epoxidation reactions of 11 with m-CPBA and DMDO were also theoretically investigated.
In contrast to the bromination reaction, epoxidation of 11 took place exclusively on the nor-
bornadiene double bond C2-C3, forming the exo- and endo-products 25 and 26; 25 was the major
product. In both cases, exo-products were the major products (Scheme 6). Interestingly, epoxida-
tion took place only on the norbornadiene double bond. There are three double bonds in 11,
which can be attacked from both sides of the double bonds to give six possible epoxides; 25, 26,
and 32-35. First, we calculated the relative enthalpies of the six possible isomers at B3LYP/6-
31+G(d,p) level and found that the isomers 25 and 26 were the most thermodynamically stable
(Table 3). The formation of 25 as the major product can be explained by the endo-
pyramidalization of the double bond so that attack from the exo-face is preferred. Furthermore,
we investigated the activation barriers for the formation of all six possible isomers 25, 26, and
32-35 in the gas phase and dichloromethane. The values are tabulated in Table 3.
16

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Table 3
Relative energies of the possible epoxides 25, 26, and 32-35 derived from the reaction of m-CPBA (in
kcal/mol) with 11 at B3LYP/6-31+G(d,p) level.
Epoxides
Relative
-10.2
16.5
-6.8
-2.6
0.0
-0.4
+1.4
26.7
Energies
Activation
energies in
Gas Phase
Activation
energies in
CH2Cl2
18.8
22.9
23.1
23.5
14.0
15.9
22.7
22.1
22.5
26.5
The calculated energy barriers were generally about 1 kcal/mol lower in methylene chloride
compared to the gas phase (Table 3). The Gibbs free energy barriers for the formation of 32-35
were about 6 to 10 kcal/mol higher than those for the formation for 25 and 26. Therefore, epoxi-
dation of the norbornadiene double bond was both thermodynamically and kinetically more fa-
vorable (Figure 8). The optimized structures of TS3 and TS4 are shown in Figure 8 (for all sta-
tionary points, see the Supporting Information. These computational results are in quite good
agreement with the experimental findings.
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TS3
TS4
Fig. 8. Optimized geometries of transition states for the formation of 25 and 26 at the B3LYP/6-
31+G(d,p) level. Some critical distances (Å) are given.
3.
Conclusions
The electrophilic addition of bromine to 11 at room temperature led to the formation of two
major products 14 and 15. The cis-configuration of the bromides in 14 was explained by the for-
mation of a non-classical carbocation 22 by an alkyl shift. The exo-attack was attributed to the
double bond pyramidalization. Furthermore, we determined that the lower activation barrier for
the formation of 22 is the driving force of this reaction and is also responsible for the regioselec-
tivity although the charge density at the central double bond was lower compared to that of the
other double bonds. Reaction at lower temperatures (-50 and -78 °C) gave 16 as the major prod-
uct arising from the attack of bromine on the norbornene double bond with higher charge density.
On the other hand, epoxidation of 11 took place exclusively at the norbornadiene double bond
C2-C3, forming the exo- and endo-products 25 and 26, where 25 was the major product. The cal-
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culated activation barriers showed that the barrier for the formation of 25 and 26 was about 6-10
kcal/mol lower than that for the formation of products 32-35.
4.
Experimental Section
4.1. General Methods
Reactions were monitored using Thin Layer Chromatography (TLC) using aluminium-
backed Silica-Gel 60 F254 plates. Column chromatography was performed using Silica-Gel 60
(Merck). All chromatography was carried out using a combination of n-hexane and ethyl acetate
as an eluent. Preparative TLC was performed using Silica-Gel 60 HF254+366. Infrared spectra
were recorded on a Perkin Elmer FT-IR spectrometer with KBr pellets. NMR spectra were rec-
orded using a Bruker and Varian 400 MHz NMR instrument (1H NMR at 400 MHz, 13C NMR at
100 MHz) in CDCl3. All chemical shifts are reported in ppm and J values are quoted in Hz. Ele-
mental analyses were recorded on LECO 932 CHNS elemental analyzer. Mass spectra were per-
formed with ThermoFinnigan instrument (EI, 70 eV).
4.2. Synthesis of 1,4-dihydro-1,4-methanonaphthalene-5,8-dione (11)
A solution of freshly distilled cyclopentadiene (6.60 g, 0.10 mol) in dichloromethane (10
mL) was added to a solution of 1,4-benzoquinone (10.80 g, 0.10 mol) in dichloromethane (30
mL) at 0 °C dropwise. Then, the solution was stirred at room temperature for 2 h to give product
12 (17.0 g, 97%). The addition product 12 (10.0 g 57.4 mmol) was dissolved in dichloromethane
(50 mL) and silica gel (60-mesh, 50.0 g) was added. The resulting mixture was stirred at room
19

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temperature for 0.5 h to promote adsorption of 12 onto the silica gel surface. The resulting sus-
pension was placed onto a silica gel column (100 g, dimensions 80 cm x 3 cm) and then was al-
lowed to stand on the column overnight. The formed hydroquinone derivative 13 was obtained in
quantitative yield (10.0 g, 100%) by elution with ethyl acetate/n-hexane (1:3) solution. A solution
of ceric ammonium nitrate ((Ce(NH4)2(NO3)6, 78.70 g, 143.5 mmol) in water (100 mL) was added
to a solution of 13 (10.0 g, 57.4 mmol) in CH3CN (100 mL) at 0 °C and the resulting mixture was
stirred at room temperature for 1 h. After adding water (100 mL) the reaction mixture was ex-
tracted with ether (3 x 100 mL). The combined organic layers were washed with brine (50 mL),
dried over Na2SO4, and filtered. The solvent was evaporated under reduced pressure and the res-
idue was purified via column chromatography on silica gel (100 g) by eluting with EtOAc/n-
hexane (3:17). The product 11 was obtained as a yellow solid (9.0 g, 91%); m.p. 62-64 ºC (Lit.
m.p. 65-67 ºC[7]).
4.3. Bromination of 1,4-dihydro-1,4-methanonaphthalene-5,8-dione (11) at Room Tempera-
ture
To a magnetically stirred solution of 11 (1.72 g, 10.0 mmol) in 30 mL of dry methylene chlo-
ride was added a solution of bromine (1.68 g, 10.5 mmol) in methylene chloride (5 mL) at room
temperature over a period of 5 min. The resulting reaction mixture was stirred for 10 min. The
solvent was evaporated under reduced pressure and the residue was recrystallized from meth-
ylene chloride/n-hexane (2:1). Major products 14 and 15 were separated. The remaining part
was submitted to column chromatography (silica gel, 100 g) eluting with EtOAc/n-hexane (1:9).
The products were separated in the following order:
4.3.1.
rel-(1
R
,4S
)-6-Bromo-1,4-methanonaphthalene-5,8(1H,4H
)-dione (20)11
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1
(0.525 g, 21%); m.p. 95-96 °C Lit. m.p. 101-103 °C. H NMR (400 MHz, CDCl3): = 7.09
(s, 1H), 6.90-6.83 (m, 2H), 4.18-4.15 (m, 1H), 4.12-4.09 (m, 1H), 2.35 (dt, A-part of AB system, J
= 7.2 and 1.3 Hz, 1H), 2.30 (bd, B-part of AB system, J = 7.2 Hz, 1H). 13C NMR (100 MHz,
CDCl3): = 181.3, 175.8, 161.7, 160.3, 142.5, 142.4, 136.9, 136.8, 74.0, 49.3, 48.6. IR (KBr, cm-
1):
= 3048, 3003, 2975, 2943, 2873, 1700, 1569, 1453, 1360, 1304, 1256, 1218, 1074, 1005,
max
883. MS (EI, 70 eV): (MH)+ = 252.9/250.9 (35), 171.9 (100), 143.9 (25), 114.7 (20).
4.3.2. rel-(1 ,4 ,4a ,8a )-4a,8a-dibromo-1,4,4a,8a-tetrahydro-1,4-methanonaphthalene-
5,8-dione (14)
R
S
R
S
(0.30 g + 1.25 g from crystallization, 47%); m.p. 186-187 °C. 1H NMR (400 MHz, CDCl3):
= 6.83 (s, 2H), 6.15-6.14 (m, 2H), 3.73-3.71 (m, 2H), 2.59 (bd, A-part of AB system, J = 9.9 Hz,
1H), 2.10 (dt, B-part of AB system, J = 9.9 Hz and J = 1.7 Hz, 1H). 13C NMR (100 MHz, CDCl3):
= 188.6, 140.6, 137.7, 70.2, 55.2, 45.3. IR (KBr, cm-1):
= 3064, 2992, 2952, 1682, 1365,
max
1266, 1242, 1099, 987, 905, 857. MS (EI, 70 eV): (MH)+ = 334.9/332.9/331 (50%), 304.8 (75),
252.9/250.9 (60), 224.9/222.9 (60), 143.7 (100), 114.8 (55). Anal. Calcd. for C11H8Br2O2: C,
39.80; H, 2.43%. Found: C, 39.67; H, 2.41.
4.3.3.
rel-(1R
,4
S,4a
S,8aR
)-4a,8a-dibromo-1,4,4a,8a-tetrahydro-1,4-methanonaphthalene-
5,8-dione (19)
1
The dibromide 19 was isolated as a mixture with 14 (33.0 mg, 1%) in a ratio of (2:5). H
NMR (400 MHz, CDCl3): = 6.99 (s, 2H), 6.47-6.46 (m, 2H), 3.93-3.91 (m, 2H), 1.84 (dt, A-
part of AB system, J =11.0 and 1.8 Hz, 1H), 1.16 (bd, B-part of AB system, J = 11.0 Hz, 1H).
13C NMR (100 MHz, CDCl3): = 187.4, 140.8, 138.0, 70.3, 51.0, 44.7. IR (KBr, cm-1):
=
max
3064, 3048, 2986, 2953, 1689, 1603, 1449, 1365, 1265, 1098, 987. MS (EI, 70 eV): (MH)+ =
21

ACCEPTED MANUSCRIPT
334.2/332.6/331 (50), 304.9 (75), 253/250.9 (50), 224.9/222.9 (60), 143.8 (100), 115.8/114.7
(70). Anal. Calcd. for C11H8Br2O2: C, 39.80; H, 2.43%. Found: C, 39.76; H, 2.38.
4.3.4.
rel-(1a
S,2S,3S,3aS,7aR)-2,3a-dibromo-1a,2,3,3a-tetrahydro-1H-1,3-methanocyclo-
propa-[
c]indene-4,7-dione (18)
(34.0 mg, 1%), colorless wax. 1H NMR (400 MHz, CDCl3): = 6.82 (d, A-part of AB system,
J = 10.5 Hz, 1H), 6.73 (d, B-part of AB system, J = 10.5 Hz, 1H), 4.14 (bs, 1H), 2.97-2.95 (m,
1H), 2.89 (bd, J = 5.1 Hz, 1H), 2.56 (bd, A-part of AB system, J =12.0 Hz, 1H), 2.50 (bd, B-part
of AB system, J = 12.0 Hz, 1H), 2.30 (dt, J = 5.1 and 1.0 Hz, 1H). 13C NMR (100 MHz, CDCl3):
= 190.1, 188.7, 141.1, 139.4, 66.1, 46.3, 45.9, 41.2, 37.7, 31.6, 23.0. IR (KBr, cm-1): max = 3081,
2958, 2964, 1689, 1586, 1455, 1393, 1295, 1259, 1126, 1039, 982, 851. MS (EI, 70 eV): m/z
333/330.9 (35), 251/252.3 (100), 222.9 (25), 170.9 (70), 146.8 (25). Anal. Calcd. for C11H8Br2O2:
C, 39.80; H, 2.43%. Found: C, 39.86; H, 2.65.
4.3.5.
rel-(1a
S,2R,3S,3aS,7aR)-2,3a-dibromo-1a,2,3,3a-tetrahydro-1H-1,3-methanocyclo-
propa-[
c]indene-4,7-dione (17)
(60.0 mg 2%). Colorless wax. 1H NMR (400 MHz, CDCl3): = 6.77 (d, A-part of AB system,
J = 10.6 Hz, 1H), 6.69 (d, B-part of AB system, J =10.6 Hz, 1H), 4.86 (bs, 1H), 3.04 (d, J = 5.2
Hz, 1H), 2.92-2.91 (m, 1H), 2.26 (bd, A-part of AB system, J = 12.6 Hz, 1H), 2.15 (dd, J = 5.2 Hz
and 1.1 Hz, 1H), 1.92 (bd, B-part of AB system, J = 12.6 Hz, 1He). 13C-NMR (100 MHz, CDCl3):
= 190.1, 187.9, 140.7, 138.7, 68.2, 52.1, 46.1, 41.3, 32.6, 29.4, 28.8. IR (KBr, cm-1): max = 3048,
2958, 2924, 2846, 1701, 1587, 1459, 1400, 1256, 1123, 1088, 1016, 910, 851. MS (EI, 70 eV):
(MH)+ = 333/334.3 (20), 253.1/252.3/254.1 (50), 171/173 (60), 146.8 (100), 114.9 (20). Anal.
Calcd. for C11H8Br2O2: C, 39.80; H, 2.43%. Found: C, 39.70; H, 2.66.
22

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4.3.6.
rel-(1
R
,2R
,3
R
,4
S)-2,3-dibromo-1,2,3,4-tetrahydro-1,4-methanonaphthalene-5,8-
dione (16)
1
(70.0 mg, 2%). Colorless wax. H NMR (400 MHz, CDCl3): = 6.71 (bs, 2H), 4.58 (dd, J
=3.8 and 2.5 Hz, 1H), 3.87-3.83 (m, 2H), 3.72-3.69 (m, 1H), 2.38 (dt, A-part of AB system, J =
13
10.3 and 1.2 Hz, 1H), 2.16 (ddt, B-part of AB system J = 10.3, 2.5, and 1.7 Hz, 1H). C NMR
(100 MHz, CDCl3): = 183.3, 183.0, 151.4, 148.8, 136.4, 136.3, 53.8, 52.3, 50.2, 49.5, 46.2. IR
(KBr, cm-1):
= 3053, 2986, 2956, 2880, 1657, 1584, 1495, 1458, 1399, 1322, 1175, 1084,
max
1015, 960. MS (EI, 70 eV) (MH)+ = 334.9/332.9/330.8 (30), 252.8/253.9 (40), 224.9 (10), 170.9
(50), 146.8/145.8 (100), 114.8 (10). Anal. Calcd. for C11H8Br2O2: C, 39.88; H, 2.36; Found: C,
39.80; H, 2.43%.
4.3.7.
rel-(1R,4S,6S,7S)-6,7-dibromo-6,7-dihydro-1,4-methanonaphthalene-5,8(1H,4H)-
dione (15)
(0.80 g + 0.70 g from crystallization) 45%; m.p.139-140 °C. 1H NMR (400 MHz, CDCl3) =
6.92 (dd, A-part of AB system, J = 4.0 Hz and 3.1 Hz, 1H), 6.89 (dd, B-part of AB system, J = 4.0
Hz and 3.1 Hz, 1H), 4.79 (d, A-part of AB system, J =2.8 Hz, 1H), 4.77 (d, B- part of AB system,
J = 2.7 Hz, 1H), 4.14 (bs, 1H), 4.07 (bs, 1H), 2.38-2.36 (bs, 2H). 13C-NMR: = (100 MHz,
CDCl3) = 184.4, 183.8, 161.23, 161.16, 142.2 141.7, 73.3, 49.2, 49.1, 47.4, 46.6. IR (KBr, cm-
1): max = 2980, 2936, 2868, 1675, 1583, 1561, 1362, 1281, 1222, 1197, 1150. MS (EI, 70 eV): m/z
252.9/251.0 (M+-Br, 50), 171.8 (100), 143.8/142.7 (35), 114.7 (20). Anal. Calcd. for C11H8Br2O2:
C, 39.80; H, 2.43%. Found: C, 39.94; H, 2.49.
4.4. Bromination of 1,4-dihydro-l,4-methanonaphthalene-5,8-dione (11) at 0, -50 and -78 °C
To a magnetically stirred solution of 11 (0.344 g, 2.0 mmol) in 10 mL of dry methylene chlo-
23

ACCEPTED MANUSCRIPT
ride at 0, -50 or -78 °C was added a solution of bromine (336.0 mg, 2.1 mmol) in 2 mL of dry
methylene chloride over a period of 5 min. The resulting reaction mixture was allowed to warm
up to room temperature and the solvent was evaporated. The product ratio was determined by
1H-NMR analysis.
4.5. Bromination of 1,4-dihydro-1,4-methanonaphthalene-5,8-dione (11) at 77 °C
A hot (~60 °C) solution of bromine (0.335 g, 2.10 mmol) in carbon tetrachloride
(CAUTION: toxic!) (2 mL) was added to a magnetically stirred solution of 11 (345 mg, 2.0
mmol) in carbon tetrachloride (10 mL) at reflux in a 25 mL flask, over a period of 2 min. The
resulting reaction mixture was kept at reflux temperature for 5 min. After evaporation of the sol-
vent the residue was chromatographed on silica gel (30.0 g), eluting with EtOAc/n-hexane (1:9)
to give 20 (251.0 mg, 50%) as the first fraction. The compound 14 (332 mg, 50%) was isolated as
the second fraction.
4.6. Reaction of 1,4-dihydro-l,4-methanonaphthalene-5,8-dione (11) with
chloroperbenzoic acid ( -CPBA) at 0 °C
m-
m
To a magnetically stirred solution of 11 (0.345 g, 2.0 mmol) in methylene chloride (10 mL)
at was added m-CPBA (0.380 g, 2.20 mmol) portionwise at 0 °C. The reaction mixture was
stirred for 15 h at room temperature. After adding water (25 mL), the mixture was extracted with
methylene chloride (3 x 20 mL). The combined organic layers were washed with saturated brine
(2 x 10 mL), water, dried over Na2SO4, and filtered. The solvent was removed in vacuo. The resi-
due was purified via column chromatography on silica gel (30.0 g) by eluting with EtOAc/n-
hexane (3:17). The monoepoxides 25 and 26 were separated.
24

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4.6.1.
rel-(1aR,2R,7S,7aS)-1a,2,7,7a-tetrahydro-2,7-methanonaphtho[2,3-b]oxirene-3,6-
dione (25)
The epoxide 25 was isolated as the first fraction. Orange solid (0.310 g, 82%) decom. >120
°C. 1H NMR (400 MHz, CDCl3): = 6.65 (s, 2H), 3.59-3.58 (m, 2H), 3.58-3.57 (m, 2H), 1.97 (bd,
13
A-part of AB system, J = 9.2 Hz, 1H), 1.58 (bd, B-part of AB system, J =9.2 Hz, 1H). C NMR
(100 MHz, CDCl3): = 183.8, 157.4, 136.0, 57.6, 42.5, 39.9. IR (KBr, cm-1):
= 3048, 3008,
max
2971, 2353, 2336, 1650, 1572, 1499, 1446, 1379, 1315, 1278, 1231, 1194, 1136, 1077, 999. MS
(EI, 70 eV): (MH)+ = 188.9 (5), 170.9/172 (100) 158.9/159.9/160.9 (100), 142.8 (30),
130.8/132.8/133.9 (80), 114.8/117 (75), 102.8/103.7/104.7 (60), 77(10). Anal. Calcd. for
C11H8O3: C, 70.21; H, 4.29%. Found: C,70.53; H, 4.21.
4.6.2.
rel-(1aR,2S,7R,7aS)-1a,2,7,7a-tetrahydro-2,7-methanonaphtho[2,3-b]oxirene-3,6-
dione (26)
The epoxide 26 was isolated as the second fraction. Orange solid (66.0 mg 18%), decom.
1
>160 °C: H NMR (400 MHz, CDCl3): = 6.65 (s, 2H), 3.92 (d, J =3.0 Hz, 2H), 3.45-3.43 (m,
2H), 2.33 (dt, A-part of AB system, J = 8.9 and 1.6 Hz, 1H), 2.22 (bd, B-part of AB system, J =
8.9 Hz, 1H). 13C-NMR (100 MHz, CDCl3): = 184.3, 146.6, 136.2, 60.5, 52.7, 41.8. IR (KBr, cm-
1): max = 2952, 2913, 2857, 2347, 1656, 1575, 1455, 1357, 1264, 1055. MS (EI, 70 eV): (MH)+ =
188.7 (20), 170.9/172 (100), 158.9/160.2/161 (80), 142.9 (20), 130.9/133 (30), 114.7/117.1 (25),
102.9 (20), 76.7 (20). Anal. Calcd. for C11H8O3: C, 70.21; H, 4.29%. Found: C, 70.38; H, 4.42.
4.7. Preparation of dimethyldioxirane (DMDO)19
Sodium bicarbonate (29.0 g, 345.0 mmol) was dissolved in 225 mL of acetone-water
(4:5/225 mL) at 5 °C. Potassium peroxymonosulfate (60.0 g, 195.0 mmol) was added to the solu-
25

ACCEPTED MANUSCRIPT
tion in five portions at 3 min intervals. After 5 min the cooling bath was removed and a moderate
vacuum (80-100 torr) was applied while vigorously stirring. The DMDO/acetone distillate was
collected in the cooled (-78 °C) receiving flask. (The concentration of DMDO can be determined
by oxidation of methyl phenyl sulfide to its sulfoxide.)
4.8. Reaction of 1,4-dihydro-l,4-methanonaphthalene-5,8-dione (11) with DMDO
To a magnetically stirred solution of 11 (0.10 g, 0.58 mmol) in 10 mL of methylene chloride
was added a solution (excess amount) of DMDO/acetone (25 mL, 0.58 mmol) dropwise at -30 °C.
The cooling bath was removed and the reaction mixture was stirred for 30 min at room tempera-
ture. The solvent was removed under reduced pressure and the residue was purified via column
chromatography on silica gel (20.0 g) eluting with EtOAc/n-hexane (3:17). The products 25 and
26 were obtained in quantitative yield in a ratio 3:1, respectively.
Acknowledgments
Financial support from Atatürk University (Grant no. BAP 2010/33), the Turkish Academy
of Sciences (TUBA), and the Middle East Technical University (METU) is gratefully acknowl-
edged. We would also like to thank to Prof. Cavit Kazaz for NMR spectra.
Supplementary data
Supplementary data (1D and 2D NMR spectra) of the products and cartesian coordinates for
the optimized structures, transition states and NBO charges. This material (63 pages) can be
found in the online version, at http://dx.doi.org/........
References and notes
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29