Towards the cis-bromination of double bonds

Article abstract of DOI:10.1071/CH01016

The bromination of olefins yielding a trans-1,2-dibromo-product was studied. Reagents were proposed to brominate the double bonds of cis-olefins mildly and stereospecifically. Reagents delivering two bromine atoms to the same side of olefins through a cyclic six-membered transition state were studied.

Full text of DOI:10.1071/CH01016

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Aust. J. Chem. 2001, 54, 117–126
Towards the cis-Bromination of Double Bonds
A,B
A
A
C
Raymond M. Carman, Roger P. C. Derbyshire, Karl A. Hansford, Renu Kadirvelraj and
Ward T. RobinsonC
A
Department of Chemistry, The University of Queensland, Brisbane, Qld 4072.
Author to whom correspondence should be addressed (e-mail: carman@chemistry.uq.edu.au).
Chemistry Department, University of Canterbury, Christchurch, New Zealand.
B
C
Simple bromination of olefins almost invariably yields the trans-1,2-dibromo-product, and in many cases the
corresponding cis-product is an unknown compound. Approaches towards a reagent which will generally, mildly
and stereospecifically cis-brominate olefins are now discussed.
Manuscript received: 1 March 2001.
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Introduction
allowing dehydrobromination to then afford a range of
generally-novel vinyl bromides.
Electrophilic bromination of simple olefins almost
invariably[
1–4]
We now discuss attempts to find a reagent which will
mildly and generally cis-brominate olefinic double bonds.
While we have not yet succeeded in this aim, we describe
preliminary approaches, together with a number of novel
compounds.
yields trans-1,2-dibromides. The reaction
normally proceeds through a bridged bromonium ion which
is then attacked by bromide from the rear (Scheme 1). When
the olefin is within a cyclohexyl system, the major product
from this route is normally the trans-diaxial-dibromide.
Some exceptions leading to cis-1,2-dibromides are known,
but these examples involve ‘complicated’ olefins, either with
delocalized double bonds, or with serious hindrance at one
face, or with geometry such that other incorporated
functional groups can participate during the olefinic
bromination.
Discussion and Results
The discussion above indicates that a suitable cis-
+
•
brominating reagent cannot involve Br or Br . We have
therefore explored reagents which might deliver two
bromine atoms to the same side of the olefin through a cyclic
six-membered transition state (Scheme 3).
Radical addition of bromine to olefins, when it can be
[5]
made to occur, is normally also a trans process, again, with
evidence[
Scheme 2). Radical bromination of monobromo
compounds may also lead to 1,2-dibromo products, but again
6,7]
for bridging in the radical intermediate
There are two problems with Scheme 3, as drawn. Firstly,
it is degenerate as written and requires adjustment to drive it
to the right-hand side. Secondly, the starting agent is a cis-
dibromide; the very material we argue is in short supply. We
sought to overcome both these problems by employing the
cis-dibromosuccinic anhydride (3) (Scheme 4). This
compound was expected to be available by normal trans-
(
[
6,8]
(
Scheme 2), the observed product is normally
trans-
disubstituted.
For these reasons, cis-1,2-dibromo compounds are not
well known, and cis-dibromides derived from many readily-
available olefins have not been described. If a reagent were
available to readily cis-brominate olefins it would therefore
make immediately available a large number of novel
compounds. Furthermore, the cis-bromination of di- or tri-
substituted cyclic olefins will normally provide compounds
with a bromine and a hydrogen vicinal and antiperiplanar,
©
CSIRO 2001
10.1071/CH01016
0004-9425/01/020117

1
18
R. M. Carman et al.
dibromination of fumaric acid (1), followed by cyclization to
the succinic anhydride (3). The structure (3) was then
expected to provide a driving force through the cyclic
transition state, since it leads to the conjugated maleic
anhydride (4) as product. As an added bonus, we anticipated
that anhydride (4) would then be easily removed from the
brominated product in work-up.
Attempts to convert the meso-dibasic acid (2) into the
required, but unknown, anhydride (3) failed by the literature
methods[
9–13]
for anhydride formation. The primary product
was the unsaturated anhydride (5), sometimes formed
together with the corresponding diacid (6). The required
product (3) is apparently thermally unstable, readily
eliminating hydrogen bromide to alleviate the steric strain
associated with two cis-vicinal bromine atoms.
elimination or double bond migration into the adjacent
bridgehead carbons (C1 and C4) due to Bredt strain.
Compound (12) was first reported[ by Diels and Alder,
and is available from the cycloaddition reaction between
18]
cyclopentadiene and dibromomaleic anhydride (15). The
endo configuration has been demonstrated[
18,19]
by using the
standard method of bromolactonization, and this
stereochemistry is now confirmed by an X-ray
crystallographic analysis (Fig. 1). This structure provides the
expected torsion of ca. 0° between the two bromine atoms.
To overcome this problem we have examined compounds
structured without an α-hydrogen. The meso-dibasic acid (9)
[
14]
(
Scheme 5) is described in the literature, although it is not
available by simple bromination of the olefin (8) and data
reported for the compound are inconclusive. However,
vapour-phase bromination of solid compound (8) over 14
days afforded the dibromide (9) which could then be
converted to the thermally stable novel anhydride (10).
Attempts using compound (10) as a cis-brominating agent
are discussed below.
During the synthetic steps of Scheme 5 it is necessary to
isomerize about the double bond going from (7) to (8). This
can be achieved by the high temperature alkaline treatment
of compound (7), in which the cis-dicarboxylate dianion
Compound (12) is a stable compound but, with an
available double bond to undergo further bromination,
cannot in its own right be a satisfactory brominating agent.
Hydrogenation afforded compound (13), potentially more
useful, while bromination afforded the novel tetrabromide
(14). The X-ray structure of compound (14), provided in
Figure 2, shows the syn-exo disposition (see below) of the C5
and C6 bromines.
Compound (14) is stable to recrystallization from
benzene, but it decomposes quantitatively in more polar
solvents such as acetone to afford the novel dibromide (16a).
When this reaction was followed by NMR spectroscopy,
transient signals for a second, very similar, product could be
seen. This latter compound, which could not be isolated, is
presumed to be the anhydride (17). We have been unable to
find conditions to convert diacid (16a) into the anhydride
rearranges to the more stable trans-dianion. However, in our
hands, as in others,[
15–17]
this step is accompanied by the
formation of considerable amounts of the undesired
methylitaconic acid (11). While this compound can be
removed from the mixture through anhydride formation
(
when compound (8) does not react), its undesired formation
encouraged us to explore further into compounds in which
double bond migration could not occur. Thus, we have
examined the bicyclic anhydrides (12)–(14). These
compounds are substituted succinic anhydrides, with the C2
and C3 bromines cis, but with no hydrogens at C2 or C3 to
enable dehydrohalogenation, and with little likelihood of

Towards the cis-Bromination of Double Bonds
119
1
3
Table 1.
Compound
C NMR shifts (δ) in (D )acetone solution
6
C1,4
C2,3
C5,6
C7
C8,9
(
(
(
12)
13)
14)
58.4
54.3
49.7
51.5
52.5
52.0
54.4
66.1
69.3
65.6
147.4
143.8
49.9
138.2
25.6
63.7
57.5
55.8
53.0
52.4
51.9
39.9
36.6
43.1
43.8
38.4
30.4
167.0
167.4
166.1
165.3
163.6
171.6
171.8
17), and note that other workers[20,21] also report difficulties
(16a)
(
A
(
(
(
16b)
19)
25)
in achieving anhydride formation by ring closure of similar
compounds.
48.2
Compound (16a) was readily converted into the diester
16b) which provided appropriate spectral data. For
A
With 50.6, OMe; data in CDCl3.
(
comparison and complete identification purposes, the same
product (16b) was synthesized by an independent and
ostensibly simple route.
1
Table 2. H NMR shifts (δ) in (D )acetone solution
6
Compound
H1,4
H2,3
H5,6exo
H7a
H7b
(
(
12)
13)
3.68
3.09
–
–
6.51A
1.95
2.37
2.03
2.57
2.47
B
(
(
(
(
(
14)
3.43
3.66
3.48
3.13
2.98
–
–
4.64
4.56
4.23
4.52
4.66
2.83
2.36
2.40
2.47
2.26
2.72
2.18
2.05
2.05
1.48
16a)
16b)C
19)
–
3.85
3.44
25)
A
B
C
Vinyl protons.
With 1.44, H5,6endo
With 3.78, s, two OMe.
.
hand, at least five major products (all present in the same
TLC spot!) were obtained when diene diester (20b) was
brominated under similar conditions. These products were
identified as compounds (16b) (10%), (21) (10%), (22)
(
46%), (23) (13%), and (24) (20%). Compound (16b) was
identical with the material described above. The structures of
the other rearranged compounds are discussed below.
NMR spectral data for the symmetrical bromides (12),
(
13), (14), (16a,b), and (19) are collected in Tables 1–3, with
It has been claimed[22–25] that the addition of bromine in
structure (25) also included for comparison. The chemical
shift data is unexceptional. The relative chemical shifts of the
H5, H6 exo- and endo-protons in compound (13) were in
accord with similar compounds, with the exo occurring at
lower field (δ 1.95) than the endo system (δ 1.44). The
proton coupling constants (Table 3) provided uniform
results. The bridging methylene protons H7a and H7b
non-polar solvents, to the C5–C6 double bond of
compounds such as (18) occurs predominantly syn and exo,
due to steric and/or electronic blocking by the endo-
anhydride moiety. We now confirm by X-ray
crystallographic analysis that the major bromination product
from compound (18) is dibromide (19) (Fig. 3). On the other

1
20
R. M. Carman et al.
Table 3. 1H NMR coupling constants (Hz)
Table 5. Bond angles and selected torsion angles for compounds
(
12), (14) and (19)
Compound J1,7a(4,7a) J1,7b(4,7b) J1,5(4,6) J1,6(4,5)
J7a,7b J5,7a(6,7a) J5,7b(6,7b)
Atoms
Angle (degrees)
Compound
(14)
(
(
(
(
(
(
(
12)
13)
14)
1.6
1.5
1.5
1.6
1.4
1.5
1.5
1.8
1.5
1.5
1.9
1.8
1.5
1.5
0.4
—
0
0
0
2.5
–10.1
0
0
0
0
0
0
0
2.0
2.8
2.3
1.9
2.1
2.2
2.1
A
Compound
12)
Compound
(19)
1.5, 3.5 –11.0
0
0
0
0
(
–12.3
–10.0
–11.1
–10.7
–12.3
16a)
16b)
C(1)–C(2)–C(3)
C(1)–C(2)–C(8)
C(1)–C(2)–Br(2)
C(1)–C(6)–C(5)
C(1)–C(6)–Br(6)
C(1)–C(7)–C(4)
C(2)–C(1)–C(6)
C(2)–C(1)–C(7)
C(2)–C(3)–C(4)
C(2)–C(3)–C(9)
C(2)–C(3)–Br(3)
C(2)–C(8)–O(1)
C(2)–C(8)–O(2)
C(3)–C(2)–C(8)
C(3)–C(2)–Br(2)
C(3)–C(4)–C(5)
C(3)–C(4)–C(7)
C(3)–C(9)–O(1)
C(3)–C(9)–O(3)
C(4)–C(3)–C(9)
C(4)–C(3)–Br(3)
C(4)–C(5)–C(6)
C(4)–C(5)–Br(5)
C(5)–C(4)–C(7)
C(5)–C(6)–Br(6)
C(6)–C(1)–C(7)
C(6)–C(5)–Br(5)
C(8)–C(2)–Br(2)
C(8)–O(1)–C(9)
C(9)–C(3)–Br(3)
O(1)–C(8)–O(2)
O(1)–C(9)–O(3)
Br(2)–C(2)–C(3)–Br(3)
Br(5)–C(5)–C(6)–Br(6)
102.5(6)
113.2(6)
111.8(5)
108.1(7)
—
104.5(7)
113.9(7)
109.3(5)
103.8(6)
110.6(6)
94.9(7)
103.3(4)
116.1(4)
—
B
19)
0
0
C
25)
0.2
104.2(4)
110.8(4)
94.6(4)
108.4(4)
100.3(4)
104.0(4)
105.7(5)
—
109.7(5)
132.0(6)
104.8(5)
—
109.8(4)
99.9(4)
108.5(5)
131.8(6)
115.2(5)
—
102.5(4)
108.6(4)
101.2(4)
116.9(3)
101.9(4)
116.3(3)
—
A
B
C
With J5exo,5endo (J6exo,6endo) = 10 Hz.
With J1,2 (J3,4) = 3.6; and J1,3 (J2,4) = 2.2 Hz.
With J1,2 (J3,4) = 0.2; and J2,7a (J3,7a) = 1.5 Hz.
93.9(6)
106.4(6)
99.5(5)
102.4(5)
103.7(6)
117.6(5)
110.1(6)
129.8(7)
104.4(6)
117.3(5)
106.0(6)
99.6(6)
110.2(6)
129.6(7)
113.5(6)
111.5(5)
107.9(7)
—
100.2(6)
—
100.9(6)
—
107.5(5)
111.6(6)
108.1(5)
120.0(7)
120.2(7)
–0.4(7)
—
109.9(7)
99.6(7)
102.7(6)
105.9(7)
118.1(6)
108.3(7)
130.0(8)
104.0(7)
118.6(6)
108.3(7)
100.7(6)
109.1(7)
129.6(8)
114.0(7)
109.0(5)
102.1(6)
107.7(6)
101.8(7)
116.3(6)
101.9(6)
117.2(6)
106.6(6)
112.6(7)
107.5(5)
121.7(8)
121.3(8)
–0.3(9)
Table 4. Bond lengths for compounds (12), (14) and (19)
Atoms
Distance (Å)
Compound (12) Compound (14) Compound (19)
C(1)–C(2)
C(1)–C(6)
C(1)–C(7)
C(2)–C(3)
C(2)–C(8)
C(2)–Br(2)
C(3)–C(4)
C(3)–C(9)
C(3)–Br(3)
C(4)–C(5)
C(4)–C(7)
C(5)–C(6)
C(5)–Br(5)
C(6)–Br(6)
C(8)–O(1)
C(8)–O(2)
C(9)–O(1)
C(9)–O(3)
1.570(10)
1.516(10)
1.549(10)
1.581(10)
1.518(10)
1.957(7)
1.570(10)
1.535(11)
1.954(7)
1.542(10)
1.542(10)
1.311(11)
—
1.550(12)
1.518(11)
1.549(12)
1.528(12)
1.553(12)
1.939(8)
1.579(12)
1.511(12)
1.933(8)
1.559(11)
1.526(11)
1.535(11)
1.936(8)
1.554(7)
1.531(7)
1.533(7)
1.528(7)
1.484(8)
—
1.561(7)
1.501(8)
—
1.534(6)
1.545(7)
1.551(7)
1.953(5)
1.955(5)
1.406(7)
1.187(6)
1.400(6)
1.184(6)
—
1.937(8)
1.409(9)
1.202(9)
1.397(9)
1.195(9)
1.395(11)
1.172(10)
1.394(10)
1.174(10)
111.1(6)
—
118.3(6)
119.7(6)
—
4.2(8)
7.7(5)
coupled each other by J ≈ –11 Hz. The signal for H7a
normally provided a doublet of triplets, showing coupling to
the bridgehead protons. The signal for H7b normally showed
additional long-range W-coupling to the protons at H5 and
H6, and therefore appeared as a complex multiplet. The
signals for H5 and H6 appeared as a doublet in compounds
14), (16a,b), and (19), but were further complicated by
additional coupling in compounds (12), (13), and (25). The
endo C5, C6 protons in compounds (14), (16a,b), (19), and
25) make a torsion angle (H6–C6–C1–H1 = H5–C5–C4–
H4) of about ±90°, providing a near zero coupling between
neighbouring protons H1 and H6 (= H4 and H5). The
signals for H1, H4 in compounds (14) and (16a,b) then
appear as a triplet, coupled only to two H7. Compound (25)
also shows only a similar, small coupling between H1 and
H2 (= H4 and H3). H1 and H4 in compound (25) are then a
broadened triplet, both H2 + H3 and H5 + H6 are broadened
doublets, while H7a is a doublet of fine pentuplets and H7b
is a doublet of fine triplets of triplets.
Crystallographic bond lengths for compounds (12), (14),
and (19) are listed in Table 4, with bond angles in Table 5;
where a comparison of data between the three compounds
shows considerable consistency in both bond length and
bond angle.
A preliminary survey to examine the usefulness of
compounds (10), (13), and (14) as cis-brominating agents
has not yet led to success. Cyclohexene (26) was chosen as a
substrate since both cis- and trans-1,2-dibromocyclohexane,
(
(
(
27) and (28), respectively, are detectable and separable by
gas chromatography (GC). This substrate, with one of the
dibromides (10), (13) or (14), was heated in a wide range of
solvents, both in the presence and absence of light. No
evidence was detected for the formation of cis-1,2-
dibromocyclohexane (27). Control tests with authentic

Towards the cis-Bromination of Double Bonds
121
high-field chemical shifts for C1, C2 and C6. All evidence
suggested that they were C3 epimers, and the chemical shifts
of the two C7 protons were then used to distinguish them.
Compound (23) provided H7a and H7b with similar
chemical shifts (δ 2.40 and 2.57, respectively), consistent
with both these hydrogens experiencing a similar exo
bromine environment. In contrast, compound (24) provided
H7a and H7b at different chemical shifts (δ 2.20 and 1.67,
respectively), consistent with the more different environment
around C7 in structure (24). A similar trend was noted[ in
the iodinated series.
compound (27) showed that it was stable under our range of
conditions. Starting anhydrides (10) and (13) remained
essentially unchanged, although the fate of anhydride (14)
was more difficult to ascertain since it was less stable to GC
conditions. Extended and vigorous heating led to the
formation of a number of products as observed by GC
analysis. Some of these compounds were oxidation products
derived from cyclohexene, as confirmed when neat
cyclohexene alone was exposed to similar conditions. The
only identifiable bromination products were the trans-isomer
26]
Experimental
1H and 13C NMR spectra were recorded in (D )acetone solution unless
6
13
otherwise indicated, upon
a
Jeol GX 400 spectrometer.
C
multiplicities were assigned by the DEPT pulse sequence. GC analyses
were most effectively performed upon a capillary column (5%
phenylmethylpolysiloxane) with helium carrier gas and flame
ionization detection in a Varian 3300 instrument, using Delta software.
Preparative GC separations were achieved upon a Shimadzu GC9A
instrument (OV101 column) with nitrogen carrier gas. Mass spectra
were recorded upon a Hewlett Packard MSD 5970 spectrometer with a
gas chromatographic inlet (5% phenylmethylpolysiloxane column),
while HRMS data were obtained from a Kratos MS 25 RFA or a
Finnigan 2001 spectrometer. Infrared data were measured in KBr discs
for crystals, or as neat oils using a Perkin Elmer 1600 series FT-IR,
unless otherwise stated. Column chromatography was performed over
Kieselgel 60, 230–400 mesh. HPLC separations were run on Dynamax
silica columns with refractive index detection, whereby new
compounds were refined to > 99% (by NMR and GC) purity and
analysed by microanalysis and/or HRMS.
(
28) (trace amounts) and the allylic bromide (29). The
formation of compound (29) appeared to be independent of
reaction conditions (solvent, dark/light) and its mode of
formation is obscure but presumably involves the presence of
radicals and/or free bromine. Traces of debromoanhydrides
(
7) and (30) could on occasion be observed from their
respective dibromo starting materials (10) and (13).
The above results are disappointing in that they have
failed to provide a reagent that will generally cis-brominate
olefins. Additionally, these results suggest that further fine
tuning of Scheme 3 would be unlikely to provide useful cis-
dibromination results, and that a suitable reagent must
therefore be sought in a different area.
X-Ray crystallographic data were collected from single-crystal
samples mounted on a glass fibre. The diffractometer was a Siemens
P4, equipped with a Siemens SMART 1K charge-coupled device
The Compounds (21)–(24)
(CCD) area detector using the program SMART (v5.045 Bruker AXS
The compounds (21)–(24) were all separated from
compound (16b) by extensive chromatography. All were
colourless, viscous oils. Structural assignment was assisted
1998) and a graphite monochromated Mo-Kα radiation (λ = 0.71073
Å). Processing used Siemens XSCANS data collection, Siemens
SHELXTL data reduction, Siemens XSCANS cell refinement,
SHELXS-97 direct method structure solution, and SHELXL-97
[26]
by the work of McCulloch
who produced a range of
2
structure refinement by full-matrix least squares on F . Atomic
analogous diiodo compounds by the iodination of compound
coordinates, displacement parameters and observed and calculated
structure factors have been deposited and are available upon request
until 31 December 2006 from the Australian Journal of Chemistry—an
International Journal for Chemical Science, P.O. Box 1139,
Collingwood, Vic. 3066.
1
(
20b). Atomic connectivities were determined by using H,
1
3
1
1
1
C (both H coupled and decoupled), DEPT, H– H-COSY
1
13
and H– C-HSQC NMR techniques.
Compounds (16b), (21), and (22) all provided a near-zero
coupling between H4 and H5, indicating that the C5
bromine was exo in all these compounds. Compound (16b)
shows a plane of symmetry in NMR studies, while the
unsymmetrical (21) gave a 3.6 Hz coupling between H1 and
H6, suggesting that the C6 bromine was endo, and showing
that the two bromines in isomer (21) were trans.
Compound (22) provided a methylene group (C6)
showing the expected vicinal couplings. The coupling
between H6endo and H5 was large (8.1 Hz), suggesting a
torsion angle of ca. 0°. Long-range couplings were observed
from H7b to both H5 and H6endo, and the bromine attached
to C7 must therefore be anti to the ester groups as depicted
in structure (22).
The meso-Diacid (2)
Fumaric acid (1) (20 g) suspended in water (150 mL) containing a few
drops of phenophthalein indicator was stirred and titrated with sodium
hydroxide solution (20% w/v) until the pink end-point. Potassium
bromide (finely powdered, 81.9 g) was added portionwise until fully
dissolved, followed by a solution of bromine (36.8 g) in aqueous
potassium bromide (20% w/v, 100 mL) over 20 min. After 1 h, solid
sodium bisulphite (3 g) was added, and the mixture acidified with
hydrochloric acid (conc.). The product was filtered off and dried to give
a white powder (32.2 g, 68%). meso (2R,3S)-2,3-Dibromosuccinic acid
[28]
(
2) gave irregular blocks from water, m.p. 276–278°C (lit.
270–
1
13
273°C). H NMR δ 4.63, s. C NMR δ 44.1, C2,3; 169.1, C1,4. IR
2920, 2675, 2543, 1699, 1463, 1423, 1296, 1181, 1146, 913, 778, 656,
–
1
5
83, 541 cm .
Attempts to convert compound (2) into the unknown structure (3) by
The tricyclic compounds (23) and (24) lacked the double
bond present in the other compounds. A cyclopropyl ring
using acetyl chloride, acetic anhydride, dicyclohexylcarbodiimide, or
thionyl chloride in pyridine all failed to produce the dibromoanhydride
(3), but rather provided mixtures of compounds (5) and (6) which were
1
13
was apparent in both these products from the large H– C
[
27]
[29]
coupling (180 Hz)
between C1 and H1, and from the
identified by spectroscopic comparison with the literature.

1
22
R. M. Carman et al.
The Anhydride (7)
periodically weighed to determine bromine uptake, which appeared to
be complete after 14 days. During this time, the material in the beaker
was mixed daily, and the bromine replenished as required. Evaporation
of the excess bromine afforded compound (9) as an orange solid (0.93
g, 94%), > 99% pure by H and C NMR analysis. The corresponding
dimethyl ester (diazomethane) gave a single peak by GCMS analysis.
2
,2′-Dimethylmaleic anhydride (7) was prepared from maleic
[
30,31]
anhydride (4) and 2-aminopyridine by the literature
method, to
1
13
give pearly leaflets, > 99% pure by H and C NMR analysis, m.p. 92–
1
13
3°C (lit.[ 93–94°C). H NMR δ 2.06, s. C NMR δ 9.3, Me; 141.4,
30]
1
13
9
[
32]
C2,3; 167.2, C1,4. IR consistent with the literature. Mass spectrum:
m/z 127 (M+1, 1%), 126 (M, 17), 82 (M–CO , 45), 54 (88), 53 (36), 51
(
2R,3S)-2,3-Dibromo-2,3-dimethylsuccinic
dibromo-2,3-dimethylsuccinic acid) (9) gave colourless crystals
water), m.p. 203–204°C (Found: C, 23.6; H, 2.6. C H Br O requires
acid
(meso-2,3-
2
(18), 50 (20), 39 (100).
(
6
8
2
4
1
13
C, 23.7; H, 2.7%). H NMR δ 2.23, s, Me. C NMR δ 28.8, two Me;
5.7, C2,3; 169.5, C1,4. IR 2989, 2878, 2644, 2522, 1750, 1717, 1450,
1390, 1383, 1336, 1267, 1216, 1100, 1081, 1027, 899, 847, 712, 690,
The Diacid (8)
6
Anhydride (7) (5.0 g) dissolved in aqueous sodium hydroxide (3.2 g in
–
1
2
0 mL water) was heated to 185°C in a sealed bomb for 66 h. The
656, 621, 565, 464 cm . Mass spectrum: m/z (as the dimethyl ester)
303, 301, 299 (M–OMe, 1, 2, 1%), 275, 273, 271 (M–(OMe+CO), 1, 2,
1), 253, 251 (M–Br, 5, 5), 225 (10), 223 (10), 221, 219 (M–
(MeOH+Br), 35, 37), 209 (7), 207 (7), 193, 191 (M–(MeOH+CO+Br),
18, 19), 172 (M–2Br, 1), 163 (7), 161 (8), 141 (10), 140 (17), 135 (9),
133 (10), 113 (58), 59 (100), 53 (76), 43 (33), 41 (55), 39 (33).
solution was then cooled (ice) and acidified with six equal portions of
hydrochloric acid (10.5 M, 7.6 mL total). After each addition of acid,
the resultant precipitate was collected by filtration and the filtrates
retained. The six precipitated fractions were identical (m.p. 92–94°C)
and were combined to give unreacted anhydride (7) (1.52 g). Diacid (8)
was then precipitated from the remaining filtrate by acidification with
additional hydrochloric acid (10.5 M, 10.0 mL). The material was
collected by filtration and dried to give the diacid (8) as a colourless
powder (1.06 g). The material was pure by H and C NMR analysis
and the corresponding dimethyl ester (diazomethane) gave a single gas-
chromatographic peak. The mother liquors were then extracted with
ether, and the extracts dried (Na SO ). Evaporation afforded a fraction
The Anhydride (10)
Diacid (9) (0.15 g) in acetyl chloride (6 mL) was refluxed (2 h). A
drying tube (calcium chloride) was then connected to the flask and the
solvent allowed to evaporate over 48 h at room temperature. Residual
acetyl chloride was then removed under vacuum, and the product
sublimed (0.03 mmHg, 50°C, Kugelrohr) to give anhydride (10) (121
mg, 86%). meso (2R,3S)-2,3-Dibromo-2,3-dimethylsuccinic anhydride
1
13
2
4
(1.4 g) which was comprised of a mixture of anhydride (7), diacid (8)
and diacid (11) (ca. 1:5:6 by GCMS analysis of the corresponding
dimethyl esters). This material (1.4 g) was then taken up in hot benzene,
and the solvent decanted from the residual solids. This process was
repeated several times and the solvent removed to afford anhydride (7)
(
2
10) was a colourless powder, m.p. 118–121°C (sublimed) (Found: C,
1
5.1; H, 2.0. C H Br O requires C, 25.2; H, 2.1%). H NMR δ 2.11, s,
6 6 2 3
13
Me. C NMR δ 23.7, two Me; 63.8, C2,3; 167.2, C1,4. IR 1874, 1792,
1
7
448, 1392, 1378, 1244, 1220, 1185, 1100, 1086, 1070, 962, 896, 795,
62, 736, 670, 637, 532, 424 cm . Mass spectrum: m/z 216, 214, 212
(0.23 g). The remaining residue was then recrystallized (water) and the
–1
diacid (8), which separated as needles, was removed by filtration. The
resultant mother liquor was then evaporated to yield chiefly diacid (11),
contaminated with small amounts of diacid (8).
(
(
(
M–C O , 2, 3, 2%), 163, 161 (M–(Br+CO ), 66, 64), 135, 133 (M–
2
3
2
C O +Br), 12, 14), 126 (7), 54 (M–(C O +2Br), 40), 53 (M–
2
3
2
3
C O +HBr+Br), 100), 39 (57).
2
3
(E)-2,3-Dimethylbut-2-enedioic acid (dimethylfumaric acid) (8)
[
33]
gave colourless needles, m.p. 236–238°C (water) (lit.
241°C)
The Anhydride (12)
1
(
Found: C, 49.8; H, 5.6. Calc. for C H O : C, 50.0; H, 5.6%). H NMR
6 8 4
13
Dibromomaleic anhydride (15) was synthesized from maleic anhydride
δ 2.07, s. C NMR δ 17.6, two Me; 133.9, C2,3; 170.3, C1,4. IR 2989,
and powdered AlBr3 with bromine (140–160°C under an N2
2
6
878, 2678, 2567, 1700, 1411, 1378, 1317, 1289, 1200, 1100, 917, 872,
[37]
–1
atmosphere) by following the literature method.
gave needles (ether/hexane), m.p. 118.5–121°C (lit.
Compound (15)
44, 561 cm .
E)-Dimethyl 2,3-dimethylbut-2-enedioate (dimethyl dimethyl-
[
38]
118–119°C),
b.p.19 122°C (lit. b.p.19 117–127°C) (Found: C, 18.9; H, 0.0. Calc. for
(
[37]
[
17]
fumarate) had m.p. 39–40°C (lit. 41–42°C). Mass spectrum: m/z 142
1
3
C Br O : C, 18.8; H, 0.0%). C NMR δ 131.9, C2,3; 164.6, C1,4;
4
2
3
(6%), 141 (M–MeO, 41), 140 (M–MeOH, 100), 113 (35), 112 (26), 97
[29]
consistent with the literature.
IR 1765, 1595, 1280, 1233, 1177,
(7), 84 (17), 83 (24), 82 (14), 70 (9), 59 (56), 54 (30), 53 (46), 43 (55),
–
1
1
154, 971, 916, 827, 721, 684 cm ; also compatible with the
4
1 (50), 39 (35).
-Methyl-3-methylenesuccinic acid (methylitaconic acid) (11) had
[
38]
literature.
The anhydride was stored over P O . The material was
2 5
2
1
unstable to TLC analysis; development in methanol/chloroform
mixtures (2:1) gave two spots (alkaline permanganate) corresponding
to dibromomaleic anhydride (15) and dibromomaleic acid. Repeated
recrystallization of compound (15) from ether/hexane mixtures led to
hydrolysis.
The same material (15) could also be synthesized from
dibromomaleic acid with acetyl chloride and sulfuric acid (conc., 1
drop) after reflux.
H NMR [abstracted from mixtures containing compounds (7), (8), and
(
2
1
11)] δ 1.36, d, Me; 3.60, dq, H2; 5.79, dd, H5; 6.31, d, JMe,2 7.2 Hz, J2,5
.0 Hz, J5,5 2.0 Hz, H5′; consistent with the literature.[34,35] 13C NMR δ
6.6, Me; 41.7, C2; 125.8, C5; 141.6, C3; 167.7, 175.1, C1,4. Mass
spectrum: m/z (as dimethyl ester) 172 (M, 3%), 157 (56), 141 (21), 140
(20), 113 (70), 81 (66), 59 (100), 53 (67), 41 (24), 39 (39).
Compound (11) was also identified and separated through its
anhydride. The acid mixture (8) and (11) (0.21 g) was refluxed (2 h)
with acetyl chloride (5 mL). The excess acetyl chloride was evaporated
and the residue sublimed (0.03 mmHg, 70°C) to yield methylitaconic
anhydride [the anhydride of structure (11)] (114 mg, 62%). This
Freshly distilled cyclopentadiene (388 mg) and anhydride (15)
(1.0 g) in dry toluene (65 mL) were heated (4 h, 100°C). The solvent
was then evaporated. The residue was recrystallized (benzene) and then
sublimed (0.03 mmHg, Kugelrohr) to yield anhydride (12) (768 mg,
61%) which was stored over P O . (1R,2S,3R,4S)-2,3-
compound (2-methyl-3-methylenesuccinic anhydride) is a known
compound,[36] m.p. 63°C (Found: C, 56.8; H, 4.9. C H O requires C,
2
5
6
8
3
1
Dibromobicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride (meso 2-
exo,3-exo-dibromobicyclo[2.2.1]hept-5-ene-2-endo,3-endo-dicarboxy-
lic anhydride) (12) gave a colourless powder, m.p. 181–185°C
5
7.1; H, 4.8%). H NMR δ 1.50, d, Me; 3.86, qt, H2; 5.96, m, H5; 6.41,
m, JMe,3 7.5 Hz, J3,5 ≈ J3,5 2.8 Hz, J5,5 2.8 Hz, H5′. 13C NMR δ 15.0, Me;
4
1
6
0.0, C2; 124.7, C5; 138.6, C3; 165.6, 173.5, C1,4. IR 1843, 1778,
[
39]
(
sublimed), 188–189°C (benzene) (lit. 188–190°C) (Found: C, 33.6;
761, 1692, 1658, 1402, 1289, 1248, 1217, 1101, 1022, 964, 889, 814,
1
–1
H, 1.8. Calc. for C9H6Br2O3: C, 33.6; H, 1.9%). H NMR see Tables 2
and 3. C NMR see Table 1. IR 2990, 2944, 1847, 1784, 1321, 1261,
225, 1211, 1142, 986, 950, 936, 854, 797, 758, 741, 721, 692, 678, 499
cm . Mass spectrum: m/z 244 (9), 243, 241 (M–Br, 94, 86%), 215, 213
M–(Br+CO), 20, 20), 199, 197 (M–(Br+CO ), 22, 23), 171, 169 (M–
94, 612, 554 cm . Mass spectrum: m/z 126 (M, 14%), 83 (2), 82 (M–
13
CO , 39), 67 (4), 54 (83), 53 (40), 51 (21), 50 (24), 39 (100).
2
1
–
1
The Dibromide (9)
(
2
Diacid (8) (468 mg), in a pre-weighed beaker, was placed in a sealed
(Br+C O ), 17, 17), 149 (11), 147 (14), 118 (15), 90 (84), 89 (84), 66
2 3
dark-glass jar containing bromine (1–2 mL). The material was
(100), 63 (63), 51 (21), 50 (24), 44 (26), 39 (45), 38 (25).

Towards the cis-Bromination of Double Bonds
123
2
Crystallographic Data for Dibromoanhydride (12)
parameters 1724/0/146, goodness-of-fit on F 1.012; final R indices
I >2σ(I)] R = 0.0532, wR = 0.1312, R indices (all data) R = 0.0655,
[
1
2
1
C H Br O , M 321.96, m.p. 188–189°C, colourless needles from
9
6
2
3
–3
wR = 0.1374, largest difference peak and hole 1.793 and –1.620 e Å ,
2
benzene, crystal dimensions 0.84 by 0.78 by 0.04 mm, monoclinic, a
extinction coefficient 0.0106(9).
6
9
.555(4), b 21.577(8), c 7.393(5) Å, α 90°, β 112.79(4)°, γ 90°, V
3
–3
Data were collected at ca. 144 K. Of the 4309 reflections obtained,
1724 were unique (Rint 0.0676). Absorption correction: semi empirical.
Completeness to θ = 23.32: 98.5%. The structure is depicted in Fig. 2.
Bond lengths are listed in Table 4, with bond angles in Table 5.
64.0(9) Å , space group P2(1)/c, Z 4, F(000) 616, D 2.218 g cm ,
c
–
1
linear absorption coefficient 8.384 mm , θ-range for data collection
.13 to 24.99°, index ranges –7 ≤ h ≤ 0, –1 ≤ k ≤ 25, –7 ≤ l ≤ 8, data/
3
2
restraints/parameters 1693/0/127, goodness-of-fit on F 0.838; final R
indices [I >2σ(I)] R = 0.0480, wR = 0.1160, R indices (all data) R =
1
2
1
The Decomposition of Anhydride (14) (Diacid 16a)
0
.0652, wR = 0.1196, largest difference peak and hole 1.514 and –
2
–
3
Attempts to recrystallize anhydride (14) (400 mg) from acetone initially
provided pearly leaflets which re-dissolved on standing (overnight,
room temperature). Evaporation of the resultant discoloured solution
yielded an off-white gum, which was comprised of debrominated diacid
16a) and an unidentified compound (ca. 1:6 by H NMR analysis). On
further standing (2 days, benchtop), the NMR sample [(D )acetone]
containing this 1:6 mixture darkened considerably. Re-analysis ( H and
C NMR) indicated quantitative conversion into the diacid (16a). The
crude product was insoluble in chloroform and could not be sublimed.
0.957 e Å , extinction method: none.
Data were collected at ca. 293 K. Of the 1956 reflections obtained,
693 were unique (Rint 0.0302). Absorption correction: ψ. Check
1
reflections: 3 every 97. Completeness to θ = 24.99: 99.6%. The
structure is depicted in Fig. 1. Bond lengths are listed in Table 4, with
bond angles in Table 5.
1
(
6
1
1
3
The Anhydride (13)
Anhydride (12) (247 mg) in dry ethyl acetate (25 mL) was
hydrogenated (1 h, atmospheric pressure) with PtO2 (ca. 25 mg).
Filtration followed by sublimation of the crude material (0.03 mmHg,
The anhydride (14) (40 mg) in (D )acetone (ca. 1 mL) in an NMR
tube was allowed to stand in the light. Periodic analyses ( H NMR)
6
1
indicated a slow conversion of compound (14) into the unidentified
compound and the diacid (16a) (ca. 70:20:10, respectively, after three
days; 40:30:30 after six days; 10:30:60 after eight days). After 14 days
5
5°C) afforded anhydride (13) as a colourless solid (188 mg, 76%). The
material was stored over P O .
2
5
1
(1R,2R,3S,4S)-2,3-Dibromobicyclo[2.2.1]heptane-2,3-dicarboxylic
the mixture was comprised solely of diacid (16a) (100%; pure by H
1
3
anhydride (meso 2-exo,3-exo-dibromobicyclo[2.2.1]heptane-2-endo,3-
and C NMR analysis). The corresponding dimethyl ester (16b)
(methanol/sulfuric acid) gave a single peak by GCMS analysis. The
unidentified component could not be purified.
[
18]
endo-dicarboxylic anhydride) (13) had m.p. 186–192°C (subl.) (lit.
1
2
98–200°C) (Found: C, 33.7; H, 2.5. Calc. for C H Br O : C, 33.4; H,
.5%). H NMR see Tables 1 and 2. The 5exo,6exo system (δ 1.95) had a
9 8 2 3
1
(1R,4S,5S,6R)-5,6-Dibromobicyclo[2.2.1]hept-2-ene-2,3-dicarbox-
ylic acid (meso 5-exo,6-exo-dibromobicyclo[2.2.1]hept-2-ene-2,3-di-
carboxylic acid) (16a) gave irregular prisms, m.p. 266–267°C (water)
width between outside peaks of 22.3 Hz; H7 (δ 2.47) was a dddt with
b
1
4 resolved lines; H1 and H4 (δ 3.09) gave a ddt providing 8 lines with
13
1
width between outside peaks of 8 Hz. C NMR see Table 1. IR 2967,
(Found: C, 31.4; H, 2.2. C H Br O requires C, 31.8; H, 2.4%). H
9
8
2
4
1
3
2
9
3
889, 1877, 1856, 1795, 1453, 1385, 1286, 1217, 1149, 1125, 1029,
88, 940, 855, 838, 721, 697, 684, 506, 492 cm . Mass spectrum: m/z
26, 324, 322 (M, 0.2, 0.3, 0.1%), 245, 243 (M–Br, 1, 1), 226 (2), 224
NMR see Tables 2 and 3. C NMR see Table 1. IR 3456, 2989, 2911,
2644, 2489, 1699, 1627, 1580, 1450, 1354, 1299, 1258, 1142, 1101,
1026, 913, 882, 838, 817, 776, 764, 754, 622, 537, 474, 410 cm .
(1R,4S,5S,6R)-Dimethyl 5,6-dibromobicyclo[2.2.1]hept-2-ene-2,3-
dicarboxylate (meso dimethyl 5-exo,6-exo-dibromobicyclo[2.2.1]hept-
–
1
–
1
(
(
(
3), 222 (2), 201, 199 (M–(Br+CO ), 98, 100), 173, 171 (M–
2
Br+C O ), 31, 33), 164 (M–2Br, 1), 145 (15), 143 (15), 92 (21), 91
2
3
1
13
19), 79 (24), 63 (20).
2-ene-2,3-dicarboxylate) (16b), an oil, was identical ( H and C NMR,
MS, IR) with the material obtained from the bromination of compound
(20b) as described below.
The Anhydride (14)
The unidentified compound [possibly structure (17)] was too
Bromine in dichloromethane (10 mL, 0.086 M, 0.86 mmol) was added
dropwise to a stirred solution of anhydride (12) (276 mg, 0.86 mmol) in
dichloromethane (15 mL). The bromine had decolourized after 2 h. The
solvent was evaporated to afford anhydride (14) as an off-white solid
unstable to isolate. It had the following data [abstracted from mixtures
1
also containing compounds (14) and (16a)]. H NMR δ 2.69, dt, J –11.5,
1
4
.4 Hz, 1H; 2.81, dm, J –11.5, 2.2, 1.4 Hz, 1H; 3.19, t, J 1.4, 1.4 Hz, 2H;
13
.84, d, J 2.2 Hz, 2H. C NMR δ 34.5, 65.0, 71.9, 138.1, 169.0.
1
13
(400 mg, 97%) which was > 99% pure by H and C NMR analysis.
The material was stored in the dark over P O . (1R,2S,3R,4S,5R,6S)-
2
5
Dibromide (19)
2
,3,5,6-Tetrabromobicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride
meso 2-exo,3-exo,5-exo,6-exo-tetrabromobicyclo[2.2.1]heptane-2-
endo,3-endo-dicarboxylic anhydride) (14) gave colourless blocks, m.p.
05–207°C (dec.) (benzene) (Found: C, 22.3; H, 1.2. C H Br O
Bromination (CCl , under normal laboratory fluorescent lighting) of
anhydride (18) gave (1R,2S,3R,4S,5S,6R)-5,6-dibromobicyclo-
4
(
[2.2.1]heptane-2,3-dicarboxylic anhydride (meso 5-exo,6-exo-dibro-
2
9
6
4
3
1
mobicyclo[2.2.1]heptane-2-endo,3-endo-dicarboxylic anhydride) (19)
requires C, 22.4; H, 1.3%). H NMR (CDCl ) δ 2.60, dm, H7 ; 2.76, dt,
3
b
[40,41]
(90% yield) as needles from benzene, m.p. 206–209°C (lit.
206°C,
H7 ; 3.29, t, H1,4; 4.19, d, H5,6; with J
–12.0 Hz, J4,7a = J ≈ J4,7b
a
7a,7b
1,7a
1
209–210°C) (Found: C, 33.1; H, 2.4. Calc. for C9H8Br2O3: C, 33.4; H,
2.5%). NMR [(D )acetone]: see Tables 1–3. IR (Nujol mull) 1865,
1783, 1306, 1075, 944, 909 cm . Mass spectrum: m/z 326 (2%), 324
=
J1,7b 1.4 Hz, J5,7b = J6,7b 2.3 Hz, J = J1,6 0 Hz. H NMR
4,5
1
3
6
[(D )acetone] see Tables 2 and 3. C NMR (CDCl ) δ 35.2, C7; 47.9,
6
3
–1
13
C1,4; 62.5, C5,6; 64.6, C2,3; 164.4, C8,9. C [(D )acetone] see Table
6
(M, 5), 322 (2), 245 (M–Br, 36), 243 (36), 186 (13), 173 (25), 171 (25),
1
7
. IR 1878, 1794, 1461, 1383, 1289, 1229, 1203, 1180, 1144, 979, 934,
21, 693, 554, 488 cm . Mass spectrum: m/z 486, 484, 482, 480, 478
–
1
147 (12), 145 (11), 91 (82), 66 (C H , 100) 39 (48).
5
6
(
3
3
M, 1, 4, 7, 7, 1%), 405, 403, 401, 399 (M–Br, 5, 21, 17, 5), 361, 359,
Crystallographic Data for Dibromoanhydride (19)
C H Br O , M 323.97, m.p. 206–209°C (benzene), colourless needles,
57, 355 (M–(Br+CO ), 25, 80, 100, 29), 323, 321, 319 (M–(Br+HBr),
2
3, 56, 31), 250 (16), 173 (32), 171 (38), 145 (16), 143 (15), 89 (17).
9
8
2
3
crystal dimensions 0.85 by 0.20 by 0.13 mm, monoclinic, a 12.314(9),
3
b 6.730(5), c 12.966(9) Å, α 90°, β 115.80(3)°, γ 90°, V 967.4(12) Å ,
Crystallographic Data for Tetrabromoanhydride (14)
–3
space group P2(1)/c, Z 4, F(000) 624, D 2.224 g cm , linear
c
–
1
C H Br O , M 481.78, m.p. 203–204°C (benzene), colourless blocks,
absorption coefficient 8.355 mm , θ-range for data collection 3.16 to
25.00°, index ranges –14 ≤ h ≤ 3, 0 ≤ k ≤ 8, –14 ≤ l ≤ 14, data/restraints/
parameters 1677/0/117, goodness-of-fit on F 0.830; final R indices
9
6
4
3
crystal dimensions 0.20 by 0.50 by 0.60 mm, monoclinic, a 9.0388(6), b
.5409(6), c 14.0075(9) Å, α 90°, β 90.2040(10)°, γ 90°, V 1207.98(13)
2
9
3
–3
Å , space group P2(1)/c, Z 4, F(000) 896, D 2.649 g cm , linear
[I >2σ(I)] R = 0.0324, wR = 0.0634, R indices (all data) R = 0.0596,
c
1
2
1
–
1
–3
absorption coefficient 13.313 mm , θ-range for data collection 2.25 to
3.32°, index ranges –10 ≤ h ≤ 9, –7 ≤ k ≤ 10, –15 ≤ l ≤ 13, data/restraints/
wR = 0.0662, largest difference peak and hole 0.540 and –0.522 e Å ,
2
2
extinction coefficient 0.0106(9).

1
1
24
R. M. Carman et al.
Data were collected at 144(2) K. Of the 2117 reflections obtained,
677 were unique (Rint 0.040). Absorption correction: semi empirical.
J4,5 1.5 Hz, J4,6 1.4 Hz, J 1.3 Hz, J4,7b 1.5 Hz, J5,6 1.4 Hz, J5,7b 0.6
Hz, J7a,7b 12.1 Hz. C NMR (CDCl ) δ 26.4, C1; 31.8, C6; 32.1, C7;
4,7a
1
3
3
Completeness to θ = 25.00: 98.8%. Intensities of three standard
reflections, measured every 97 reflections throughout the data
collection, showed only negligible decay. Hydrogen atoms were fixed in
geometrically calculated positions and treated as riding. All non-
hydrogen atoms were refined with anisotropic atomic displacement
parameters. The structure is depicted in Fig. 3, with bond lengths listed
in Table 4 and bond angles in Table 5.
36.2, C2; 47.2, C5; 49.7, C4; 52.0 and 53.5, two OMe; 62.1, C3; 168.0
and 168.2, two CO; with JC1,H 1 183.1 Hz, JC4,H4 159.6 Hz, JC5,H 5 162.9
Hz, JC6,H 6 188.1 Hz, JC7,H7a ~ JC7,H7b 141.0 Hz, JC10,H10 148.3 Hz,
JC11,H11 147.6 Hz. IR (paraffin mull) 1745, 1724, 1440, 1329, 1301,
1280, 1255, 1235, 1200, 1170, 1137, 1132, 1114, 1061, 1054, 1029,
–1
1002, 988, 971, 886, 798, 783, 767, 739 cm . Mass spectrum: (Kratos)
8
1
m/z 369.9075, 367.9084, 365.9112; C H Br O requires 369.9064,
1
1
12
2
4
7
9
81
79
C H Br BrO
requires 367.9084, C H Br O
requires
365.9103. GCMS: m/z 339 (3%), 337 (M–31, 6), 335 (3), 311 (3), 309
7), 307 (3), 289 (90), 287 (100), 257 (39), 255 (31), 229 (16), 227 (18),
1
1
12
4
11 12
2
4
Bicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxylic acid (20a)
(
Hydrochloric acid (conc., 15 mL) was added to the monopotassium salt
of acetylene dicarboxylic acid (10 g) in water (90 mL). Freshly distilled
cyclopentadiene (23.15 g) was added and the mixture was stirred
vigorously for 4 h. The mixture containing a white precipitate was
extracted into chloroform and the solvent removed. The crude material
was dissolved in aqueous sodium hydroxide and the mixture washed
with chloroform. The aqueous layer was acidified (conc. hydrochloric
acid, pH 2) to give a white precipitate. The mixture was extracted into
dichloromethane, dried (magnesium sulfate), and evaporated to give the
207 (17), 149 (15), 148 (15), 91 (11), 90 (14), 89 (20), 59 (24).
(
1RS,2SR,3RS,4SR,5SR,6SR)-Dimethyl 3,5-dibromotricyclo[2.2.1.-
02
,6
]heptane-2,3-dicarboxylate (dimethyl 3-endo,5-exo-dibromotricy-
2
,6
clo[2.2.1.0 ]heptane-2-exo,3-exo-dicarboxylate) (24) (relative reten-
tion 1.25) (Found: C, 35.9; H, 3.4. C H Br O requires: C, 35.9; H,
11 12
2
4
1
3
.3%). H NMR (CDCl ) δ 1.67, ddt, H7b; 2.20, dt, H7a; 2.37, d of br
3
q, H1; 2.47, dt, H6; 2.58, br sextet, H4; 3.69 and 3.77, two s, OMe;
4
.82, dt, H5; with J1,4 1.3 Hz, J1,6 5.2 Hz, J1,7a 1.4 Hz, J1,7b 1.5 Hz, J4,5
[
42,43]
1.5 Hz, J 1.4 Hz, J4,7a ≈ J4,7b 1.5 Hz, J5,6 1.5 Hz, J5,7b 0.6 Hz, J7a,7b
title diacid (20a) (5.45 g, 46% yield), m.p. 165–167°C (lit.
1
163–
4,6
1
3
1
13
[42]
12.3 Hz. C NMR (CDCl ) δ 25.9, C1; 28.9, C7; 31.5, C6; 35.9, C2;
64°C, 170°C). H and C NMR were consistent with the literature,
with J1,5 = J4,6 1.6 Hz, J1,6 = J4,5 2.4 Hz, J1,7a = J4,7a 1.5 Hz, J1,7b = J4,7b
.6 Hz, J5,7a = J6,7a 0.3 Hz, J5,7b = J6,7b 0.4 Hz, J7a,7b 7.1Hz. IR
hexachlorobutadiene mull) 3300–2200, 2950, 2881, 2490, 1698, 1585,
3
49.2, C4; 52.2, C5; 52.0 and 53.4, two OMe; 62.9, C3; 167.3 and
1
68.1, two CO; with JC1,H 1 184.8 Hz, JC4,H4 160.6 Hz, JC5,H 5 166.9 Hz,
1
JC6,H 6 187.4 Hz, JC7,H7a and JC7,H7b 139.0 and 140.0 Hz, respectively,
JC10,H10 148.1 Hz, JC11,H11 147.5 Hz. IR (neat) 2954, 2852, 1742, 1736,
(
1
–
1
462, 1222, 706 cm .
1
439, 1435, 1373, 1301, 1282, 1258, 1239, 1209, 1162, 1131, 1114,
–
1
Dimethylbicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxylate (20b)
1058, 1036, 920, 765, 740 cm . Mass spectrum: (Kratos) m/z
8
1
3
69.9054, 367.9079, 365.9103; C H Br O requires 369.9064,
11 12 2 4
Compound (20a) (0.31 g) in methanol (60 mL) containing sulfuric acid
7
9
81
79
C H Br BrO
requires 367.9084, C H Br O
4
requires
1
1
12
4
11 12
2
(conc., 1 mL) was stirred (24 h), at which time analysis (GCMS)
3
3
65.9103. GCMS: m/z 370 (1%), 368 (M, 2), 366 (1), 339 (4), 337 (8),
35 (5), 311 (6), 309 (11), 307 (6), 290 (14), 289 (100), 287 (93), 257
showed that complete methylation of both acid groups had occured.
Methanol was removed. Dichloromethane (100 mL) was added and the
mixture was washed with saturated sodium bicarbonate solution (2 × 20
mL) and water. Drying (magnesium sulfate) and removal of the
dichloromethane gave the dimethyl ester (20b) as a colourless oil (0.35
g, 98% yield) (lit.[ pale yellow oil). This material was used without
(
(
47), 255 (46), 229 (16), 227 (18), 207 (64), 176 (22), 149 (26), 148
20), 105 (19), 91 (18), 90 (24), 89 (34), 77 (19), 63 (23), 59 (41).
(
1RS,4SR,5SR,6SR)-Dimethyl-5,6-dibromobicyclo[2.2.1]hept-2
ene-2,3-dicarboxylate
(dimethyl
5-exo,6-endo-dibromobicyclo-
22]
[
2.2.1]hept-2-ene-2,3-dicarboxylate) (21) (relative retention 1.59)
1
[44]
further purification. H NMR (CDCl ) consistent with the literature;
3
* 1
(Found: C, 37.8; H, 3.8. C H Br O requires C, 35.9; H, 3.3%).
H
1
1
12
2
4
with J1,5 = J4,6 1.7 Hz, J1,6 = J4,5 2.2 Hz, J1,7a = J4,7a 1.4 Hz, J = J4,7b
1,7b
NMR (CDCl ) δ 2.12, dddd, H7b; 2.18, dt, H7a; 3.41, d of br q, H4;
.5 Hz, J5,7a = J6,7a 0.3 Hz, J5,7b = J6,7b 0.4 Hz, J7a,7b 6.8Hz. 13C NMR
CDCl ) δ 51.7, two OMe; 53.2, C1,4; 72.7, C7; 142.1, C5,6; 152.2,
3
1
(
3
.64, ddt, H1; 3.71 and 3.83, two s, OMe; 4.06, dt, H5; 4.48, dd, H6;
3
with J1,4 1.8 Hz, J1,6 3.6 Hz, J1,7a 1.3, J1,7b 2.0 Hz, J4,5 0.6 Hz, J
4,7a
C2,3; 165.1, C8,9. IR (neat) 3629, 3552, 3420, 3126, 3071, 3000, 2950,
1
3
1
.4 Hz, J4,7b 1.6 Hz, J5,6 2.7 Hz, J5,7b 2.6 Hz, J7a,7b 10.2 Hz. C NMR
2
1
873, 2844, 1717, 1626, 1559, 1435, 1364, 1293, 1201, 1150, 1100,
055, 1019, 952, 918, 869, 832, 779, 758, 734, 714 cm . Mass
(
CDCl ) δ 45.7, C7; 52.2 and 52.3, two OMe; 52.2, C1; 52.8, C5; 54.2,
–
1
3
C6; 55.4, C4; 141.9 and 144.9, C2 and C3, respectively; 162.8 and
64.4, two CO; with JC1,H1 157.0 Hz, JC4,H4 157.2 Hz, JC5,H5 170.5 Hz,
spectrum: m/z 208 (M, 19%), 193 (16), 177 (38), 176 (43), 161 (20),
49 (61), 133 (11), 119 (32), 118 (36), 105 (26), 90 (59), 77 (45), 66
100), 59 (58), 51 (26), 39 (62).
1
1
(
JC6,H6 165.2 Hz, JC7,H7a and JC7,H7b 138.0 and 139.0 Hz, respectively,
JC10,H10 147.8 Hz, JC11,H11 147.6 Hz. IR (neat) 2952, 1722, 1630, 1450,
1
7
436, 1345, 1280, 1244, 1194, 1172, 1152, 1130, 1088, 1014, 976, 823,
Bromination of Dimethyl Ester (20b)
–
1
84, 749 cm . Mass spectrum: (Kratos) m/z 367.9094;
Bromine (0.11 g) in dichloromethane (5 mL) was added to a stirred
solution of diester (20b) (0.13 g) in dichloromethane (50 mL). The
reaction flask was sealed and left to stir for 8 h under standard
fluorescent lighting. Analysis (GC) showed at least five products, with
no starting material. The solvent was removed under reduced pressure
to give a viscous oil (0.21 g). Excess bromine was removed on a small
silica column (hexane/ethyl acetate, 4:1).
Flash column chromatography (hexane/ether, 83:17), followed by
normal-phase HPLC (hexane/ethyl acetate, 9:1) gave samples of the
five products, all as colourless, viscous oils. All the dibromides except
compound (16b) (meso) are assumed to be racemic. The products in
order of increasing polarity were the following.
79 81
C H Br BrO requires 367.9084. Mass spectrum: (Finnigan) m/z
3
1
1
12
4
79 81
68.9150; C H Br BrO (M+H) requires 368.9155. GCMS: m/z
11 13 4
370 (3%), 368 (M, 4), 366 (2), 339 (7), 337 (13), 335 (7), 311 (1), 309
(2), 307 (1), 289 (14), 287 (12), 257 (37), 255 (31), 183 (12), 182 (100),
1
5
51 (14), 150 (8), 149 (10), 148 (8), 119 (9), 105 (8), 89 (14), 79 (23),
9 (24).
(
1R,4S,5S,6R)-Dimethyl 5,6-dibromobicyclo[2.2.1]hept-2-ene-2,3-
dicarboxylate (meso dimethyl 5-exo,6-exo-dibromobicyclo-
2.2.1]hept-2-ene-2,3-dicarboxylate) (16b) (relative retention 1.84)
[
(
1
Found: C, 37.2; H, 3.6. C H Br O requires C, 35.9; H, 3.3%).* H
1
1
12
2
4
13
NMR (CDCl ) see Tables 2–3, with J
= J4,5endo 0 Hz. C NMR
3
1,6endo
(CDCl ) see Table 1, with J
= JC4,H4 157.1 Hz, JC5,H 5 = JC6,H6
3
C1,H 1
(
1RS,2SR,3SR,4SR,5SR,6SR)-Dimethyl-3,5-dibromotricyclo[2.2.-
1
=
66.5 Hz, JC7,H 7a and JC7,H7b 138.3 and 139.0 Hz, respectively, JC10,H10
.02 ]heptane-2,3-dicarboxylate (dimethyl 3-exo,5-exo-dibromotricy-
,6
1
JC11,H11 147.9 Hz. IR (paraffin mull) 1725, 1629, 1337, 1261, 1196,
2,6
clo[2.2.1.0 ]heptane-2-endo,3-endo-dicarboxylate) (23) (HPLC
–1
1156, 1134, 1091, 1026, 976, 886, 838, 784, 757 cm . Mass spectrum:
relative retention 1.00) (Found: C, 35.8; H, 3.3. C H Br O requires
81
1
1
12
2
4
(Kratos) m/z 369.9249, 367.9092, 365.9095; C H Br O requires
369.9064, C H Br BrO requires 367.9084, C H Br O
11 12 4 11 12 2 4
requires 365.9103. GCMS: m/z 370 (1%), 368 (M, 2), 366 (1), 339 (4),
1
11 12 2 4
C, 35.9; H, 3.3%). H NMR (CDCl ) δ 2.29, ddt, H1; 2.40, dt, H7a;
81 79
79
3
2.56, dt, H6; 2.57, dddd, H7b; 2.60, br sextet, H4; 3.69 and 3.79, two
s, OMe; 4.00, dt, H5; with J1,4 1.4 Hz, J1,6 5.1 Hz, J1,7a ~ J1,7b 1.3 Hz,
337 (10), 335 (5), 289 (7), 287 (7), 257 (21), 255 (17), 183 (12), 182
*
*
Despite giving correct NMR and HRMS data these samples consistently provided microanalyses high in both carbon and hydrogen.

Towards the cis-Bromination of Double Bonds
125
(
5
100), 151 (21), 150 (10), 149 (10), 119 (10), 93 (15), 89 (15), 79 (28),
9 (28).
1RS,4RS,5SR,7RS)-Dimethyl
For stability tests, the starting anhydrides (10), (13) and (14) and the
dibromides (27) and (28) were subjected to the same conditions as
outlined above. Analyses were performed using GC and/or GCMS
(Alltech EC-5 capillary column) using a temperature gradient of 80–5–
16–270, an injector temperature of 220°C and a detector temperature of
250°C. No product (27) was observed in any trial. The by-products
formed had the library mass spectra: 3-bromocyclohexene (m/z) 162,
160 (M, 1, 1%), 82 (8), 81 (M–Br, 100), 79 (31), 66 (5), 65 (5), 53 (18),
52 (7), 51 (10), 41 (14), 39 (19); 2-bromocyclohexanol (m/z) 180, 178
(M, 1, 1%), 137 (1), 135 (1), 134 (4), 132 (3), 122 (1), 121 (1), 99 (M–
Br, 27), 82 (7), 81 (100), 79 (11), 69 (5), 67 (3), 57 (64), 55 (15), 43
(17), 41 (30), 39 (24).
(
5,7-dibromobicyclo[2.2.1]hept-2-
ene-2,3-dicarboxylate (dimethyl 5-exo,7-anti-dibromobicyclo[2.2.1]-
hept-2-ene-2,3-dicarboxylate) (22) (relative retention 1.94) (Found: C,
3
1
5.3; H, 3.3. C H Br O requires: C, 35.9; H, 3.3%). H NMR
1
1
12
2
4
(CDCl ) δ 2.28, dddd, H6endo; 2.71, ddd, H6exo; 3.36, dddd, H1; 3.59,
3
dd, H4; 3.77 and 3.78, two s, OMe; 3.88, dd, H5; 4.15, br pentuplet,
H7b; with J1,4 1.8 Hz, J1,6endo 0.7 Hz, J1,6exo 3.6 Hz, J1,7b 1.5 Hz, J4,5
Hz, J4,7b 1.5 Hz, J5,6endo 8.1 Hz, J5,6exo 4.5 Hz, J5,7b 1.4 Hz, J6endo,6exo
3.5 Hz, J6endo,7b 1.3 Hz. 13C NMR (CDCl ) δ 33.6, C6; 41.6, C5; 51.9,
0
1
3
C1; 52.5 and 52.5, two OMe; 54.2, C7; 56.8, C4; 142.2 and 144.3, C2
and C3, respectively; 162.3 and 163.0, two CO; with JC1,H 1 155.1 Hz,
JC4,H 4 160.3 Hz, JC5,H 5 164.5 Hz, JC6,H 6 139.0 and 141.0 Hz,
respectively, JC7,H7b 167.2 Hz, JC10,H 10 148.1 Hz, JC11,H 11 147.9 Hz. IR
References
[
1] R. C. Fahey in ‘Topics in Stereochemistry’ (Eds E. L. Eliel, N. L.
Allinger) Vol. 3, p. 237 (Interscience: New York 1968).
(neat) 3000, 2953, 2848, 1733, 1731, 1622, 1435, 1337, 1287, 1223,
1
8
3
202, 1155, 1135, 1113, 1090, 1046, 1004, 965, 919, 888, 867, 839,
–
1
[2] P. B. D. de la Mare, ‘Electrophilic Halogenation’ Ch. 7, p. 124
(Cambridge University Press: 1976).
[3] G. H. Schmid, D. G. Garratt in ‘The Chemistry of Double
Bonded Functional Groups’ (Ed. S. Patai) Vol. 1, Part 2, Ch. 9
17, 796, 779, 764, 726 cm . Mass spectrum: (Kratos) m/z 369.9015,
81
67.9089,
365.9110;
C H Br O4
requires
369.9064,
requires 367.9084, C H Br O requires
11 12 2 4
1
1
12
2
8
1
79
79
C H Br BrO
1
1
12
4
3
(
2
65.9103. GCMS: m/z 368 (M, < 1%), 339 (16), 337 (33), 335 (15), 290
9), 289 (64), 287 (70), 262 (10), 260 (9), 258 (11), 257 (100), 255 (81),
29 (23), 227 (20), 207 (13), 201 (8), 176 (9), 175 (13), 173 (12), 172
(John Wiley & Sons: London 1977).
[
4] G. H. Schmid, D. G. Garratt in ‘The Chemistry of Double
Bonded Functional Groups. Supplement A’ (Ed. S. Patai) Vol. 2,
Part 1. Ch. 11 (John Wiley & Sons: Chichester 1989).
(8), 171 (11), 170 (8), 153 (8), 151 (9), 150 (9), 149 (30), 148 (30), 133
(9), 122 (12), 121 (11), 119 (32), 105 (27), 91 (33), 90 (29), 89 (44), 78
(21), 77 (35), 65 (23), 63 (42), 59 (69), 39 (37).
[
[
5] B. A. Bohm, P. I. Abell, Chem. Rev. 1962, 62, 599.
6] P. S. Skell, D. L. Tuleen, P. D. Readio, J. Am. Chem. Soc. 1963,
8
5, 2849.
Dibromoanhydride (25)
[
7] S. P. Maj, M. C. R. Symons, P. M. R. Trousson, J. Chem. Soc.,
Chem. Commun. 1984, 561.
Anhydride (19) (or its corresponding dibasic acid) was heated with a
small amount of water in a glass tube (230°C, Woods’ metal bath).
Water vapour and hydrogen bromide were evolved in the early part of
the reaction. Equilibrium appeared to be reached after 2 h between
anhydride (19) and anhydride (25) (1:4 by 1H NMR). The cooled
mixture was taken into ethyl acetate, washed with aqueous sodium
carbonate and water, then dried (magnesium sulfate) to afford a
crystalline mixture. Recrystallization (acetonitrile, 2×) gave
[8] P. S. Skell, P. D. Readio, J. Am. Chem. Soc. 1964, 86, 3334.
[9] W. Gerrard, A. M. Thrush, J. Chem. Soc. 1952, 741.
[10] W. Gerrard, A. M. Thrush, J. Chem. Soc. 1953, 2117.
[11] D. H. Rammler, Y. Lapidot, H. G. Khorana, J. Am. Chem. Soc.
1963, 85, 1997.
[12] C. W. Holzapfel, G. R. Pettit, J. Org. Chem. 1985, 50, 2323.
[13] R. C. Larock, ’Comprehensive Organic Transformations: A
Guide to Functional Group Preparations’ p. 965 (VCH: New
Yor k 1989).
[14] E. Hadjoudis, E. Kariv, G. M. Schmidt, J. Chem. Soc. Perkin
Trans. 2 1972, 9, 1056.
[15] R. E. Lutz, R. J. Taylor, J. Am. Chem. Soc. 1933, 55, 1585.
[16] M. Couper, C. J. Kibler, R. E. Lutz, J. Am. Chem. Soc. 1941, 63,
2.
(
1R,2S,3R,4S,5S,6R) 5,6-dibromobicyclo[2.2.1]hepta-2,5-diene-2,3-
dicarboxylic anhydride (25) (meso 5-exo,6-exo-dibromobicyclo-
2.2.1]hepta-2,5-diene-2-exo,3-exo-dicarboxylic anhydride) (yield
5%), m.p. 252–254°C (lit.[9,45] 248–249°C, 244–245°C). NMR see
[
4
–1
Tables 1–3. IR (Nujol) 1844, 1782, 1086, 951, 903, 606 cm . Mass
spectrum: m/z 326, 324, 322 (M, 3, 7, 3%), 245, 243 (M–Br, 41, 37),
173 (26), 171 (28), 91 (81), 66 (100), 39 (40).
When anhydride (19) was heated under strictly anhydrous
[17] L. M. Jackman, R. H. Wiley, J. Chem. Soc. 1960, 2886.
[18] O. Diels, K. Alder, E. Peterson, F. Querberitz, J. Liebigs Ann.
Chem. 1930, 478, 137.
conditions no rearrangement to anhydride (25) was observed. Both
starting material (19) and product (25) decomposed under prolonged
heating.
[19] K. Alder, F. Brochhagen, Chem. Ber. 1954, 87, 167.
[
[
20] J. R. Edman, H. E. Simmons, J. Org. Chem. 1968, 33, 3808.
21] R. V. Williams, C.-L. A. Sung, H. A. Kurtz, T. M. Harris,
Tetrahedron Lett. 1988, 29, 19.
Dibromides (27) and (28)
Dibromides (27) and (28) were synthesized by standard procedures,[46]
and separated and purified by preparative GC. Each compound (a
colourless oil) gave consistent spectral data and provided a single peak
by GCMS analysis, with trans-dibromide eluting first.
[22] H. Kwart, L. Kaplan, J. Am. Chem. Soc. 1954, 76, 4078.
[23] J. A. Berson, J. Am. Chem. Soc. 1954, 76, 5748.
[24] B. E. Smart, J. Org. Chem. 1973, 38, 2027.
[25] B. E. Smart, J. Org. Chem. 1973, 38, 2367.
[26] A. W. McCulloch, A. G. McInnes, D. G. Smith, J. A. Walter, Can.
J. Chem. 1976, 54, 2013.
syn-Bromination Trials
Cyclohexene was distilled and stored under argon prior to use. Syn-
bromination experiments were carried out by dissolving anhydride (10),
[27] F. W. Wehrli, T. Wirthlin, ‘Interpretation of Carbon-13 NMR
Spectra’ pp. 50–53 (Heyden & Son: London 1978).
[28] W. G. Young, D. Pressman, C. D. Coryell, J. Am. Chem. Soc.
1939, 61, 1640.
[29] J. Buckingham, S. M. Donaghy (Eds), ‘Dictionary of Organic
Compounds’, 5th Edn, p. 766 (Chapman and Hall: New York
1982).
[30] M. E. Baumann, H. Bosshard, Helv. Chim. Acta 1978, 61, 2751.
[31] M. E. Baumann, H. Bosshard, W. Breitenstein, G. Rihs, T.
Winkler, Helv. Chim. Acta 1984, 67, 1897.
[32] P. Markov, L. Dimitrova, C. Ivanov, J. Organomet. Chem. 1974,
81, 1.
(13) or (14) (1–2 mg, ca. 0.002–0.003 mmol) in either cyclohexene (1
mL), or mixtures (1:1) of cyclohexene (0.5 mL) and either benzene,
methanol, chloroform, acetone or 1,4-dioxan (0.5 mL). Trials were then
performed under a range of conditions:
a. The sample was refluxed under argon in diffuse light, and the
mixtures analysed at one, two and five hour intervals.
b. The sample was directly irradiated with a 100 W bulb overnight.
c. The sample was stored in the presence of sunlight, and analysed
after approx. one week.
d. The sample was placed both in the dark, and in diffuse light, and
left to stand for prolonged periods (weeks) at room temperature.
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