Asymmetric synthesis of chiral norbornenes from polybromocyclopentadienes

Article abstract of DOI:10.1023/A:1015386221273

Effect of the conditions on the enantiomeric purity, overall yield, and isomeric composition of chiral polybromonorbornene Diels-Alder adducts of polybromocyclopentadienes and (-)-menthyl acrylate was studied. Enantiomerically pure polybromonorbornenecarboxylic acids were obtained by resolution of the corresponding racemates through diastereoisomeric salts with l-ephedrine. The structure of the products was confirmed by the IR and ¹H NMR spectra.

Full text of DOI:10.1023/A:1015386221273

Russian Journal of Organic Chemistry, Vol. 38, No. 1, 2002, pp. 15 18. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 1, 2002,
pp. 25 28.
Original Russian Text Copyright
2002 by Mamedov.
Asymmetric Synthesis of Chiral Norbornenes
from Polybromocyclopentadienes
E. G. Mamedov
Institute of Petrochemical Processes, National Academy of Sciences of Azerbaijan,
ul. N. Rafieva 30, Baku, 370025 Azerbaijan
Received January 9, 2001
Abstract Effect of the conditions on the enantiomeric purity, overall yield, and isomeric composition of
chiral polybromonorbornene Diels Alder adducts of polybromocyclopentadienes and ( )-menthyl acrylate
was studied. Enantiomerically pure polybromonorbornenecarboxylic acids were obtained by resolution of the
corresponding racemates through diastereoisomeric salts with l-ephedrine. The structure of the products
was confirmed by the IR and 1H NMR spectra.
Synthesis and study of bromine-containing com-
pounds of the norbornene series attract a great interest,
for such compounds exhibit fungicide, insecticide,
herbicide, bactericide, and other important properties.
In most cases only one enantiomer possesses bio-
logical activity; therefore, preparation of optically
pure compounds is of specific significance. However,
only one brief communication on the synthesis of
chiral polybromonorbornenes has been reported [1].
160 C (reaction time 3 10 h) in various solvents. In
order to study asymmetric induction the chiral frag-
ment R in adducts IV and V was removed by alkaline
hydrolysis. In order to avoid possible racemization
during the hydrolysis, the chiral fragment was also
removed by reduction with LiAlH4 (Scheme 2).
*
Scheme 2.
The present article gives the results of studying
the synthesis of optically active polybrominated nor-
bornenes by [4+2]-cycloaddition of polybromocyclo-
pentadienes I and II to a chiral dienophile, ( )-men-
thyl acrylate (III) (Scheme 1). The reactions were
carried out in the temperature range from 100 to
Scheme 1.
VI, VIII, X = Br; VII, IX, X = OCH3.
The influence of temperature, reaction time, and
solvent nature on the enantiomeric purity, overall
yield, and isomeric composition of the adducts was
examined. Compounds VI IX obtained under various
conditions (after removal of the chiral fragment) were
optically active; they were characterized by negative
values of specific rotation. The results are summarized
*
R = ( )-l-menthyl; I, IV, X = Br; II, V, X = OCH3.
1070-4280/02/3801-0015$27.00 2002 MAIK Nauka/Interperiodica

16
MAMEDOV
Table 1. [4+2]-Cycloaddition of polybromocyclopentadienes I and II to ( )-menthyl acrylate (III); yields and enantio-
meric purities of adducts IV and V and their hydrolysis (VI, VII) and reduction products (VIII, IX)
Yield
of IV, V,
%
Major enantiomer, %
[ ]2D0 (CCl4)
Time,
h
Diene T, C
Solvent
VI
VII
VIII
IX
( )-VI ( )-VII ( )-VIII ( )-IX
I
I
I
I
I
I
II
II
II
II
II
100 C6H5Cl
120 C6H5Cl
10
10
10
10
10
5
6
6
6
6
45
57
79
80
44
25
49
59
83
84
48
14
14
10
9
14
14
15
15
14
12
15
16
16
11
10
16
16
16
16
15
13
16
16
15
13
12
16
16
16
16
14
14
16
17
16
14
12
17
17
17
17
16
16
17
2.33
2.31
1.67
1.56
2.31
2.32
2.50
2.48
2.30
1.99
2.50
2.39
2.36
1.65
1.56
2.38
2.40
2.35
2.34
2.21
1.94
2.35
2.35
2.22
2.09
1.71
2.30
2.29
2.37
2.34
2.14
2.05
2.33
2.19
2.09
1.72
1.54
2.20
2.95
2.05
2.18
2.14
2.08
2.20
140 C6H5Cl
160 ClC6H4CH3
100 C6H5CH3
100 C6H5Cl
100 C6H5Cl
120 C6H5Cl
140 C6H5Cl
160 ClC6H4CH3
100 C6H5Cl
3
in Table 1. One can see that the enantiomeric purity
of adducts VI IX changes insignificantly with rise
in temperature, whereas the overall yield appreciably
increases: At 140 C the yield of diene I attains 79%,
and the yield of II, 83%. Further raising the tempera-
ture no longer affects the overall yield of the Diels
Alder adducts. Under these conditions, no significant
effect of the solvent nature on the enantiomeric purity
and overall yield of the adducts was observed. In all
cases, the endo isomers were formed exclusively. The
structure of the products was confirmed by elemental
meric purity of the Diels Alder adducts. For this
puprose, racemic acids VI and VII were synthesized
[2, 3] and were resolved through diastereoisomeric
salts with ( )-l-ephedrine (Scheme 3).
Salts X and XI were precipitated from acetone.
Acids ( )-(S)-VI and ( )-(S)-VII were obtained by
repeated recrystallizations from chlorobenzene and
subsequent treatment with hydrochloric acid. After
removal of the solvent from the mother liquor, the
resudue was repeatedly recrystallized from ethanol.
Treatment of diastereoisomeric salts X and XI with
hydrochloric acid gave (+)-(R)-acids VI and VII.
Enantiomerically pure acids VI and VII had the
following parameters (5R)-VI, [ ]2D0 = 15.7 (c = 1.1,
1
analysis and IR (Table 2) and H NMR spectroscopy
(Table 3).
Enantiomerically pure samples of compounds
VI IX were necessary in order to estimate enantio-
CHCl3); (5S)-VI, [ ]D20
(5R)-VII, [ ]2D0 = 15.12 (c = 0.48, CHCl3); (5S)-VII,
[ ]2D0
14.82 (c = 1.3, CHCl3).
=
16.5 (c = 0.5, CHCl3);
Scheme 3.
=
Enantiomerically pure alcohols VIII and IX were
synthesized from enantiomerically pure acids VI and
VII. Initially, acids VI and VII were converted into
methyl esters XII and XIII, respectively, by the action
of diazomethane, and the esters were reduced with
LiAlH4. Enantiomerically pure alcohols VIII and IX
had the following specific rotations: (5R)-VIII,
[ ]2D0 = 14.12 (c = 0.64, CHCl3); (5S)-VIII, [ ]2D0
=
14.75 (c 0.67, CHCl3); (5R)-IX, [ ]2D0 = 13.35 (c =
0.35, CHCl3); (5S)-IX, [ ]D20
=
12.91 (c = 0.71,
CHCl3). The relative configurations of compounds
VI IX were established by comparing the signs of
their specific rotations and optical rotation dispersion
curves with those of known bromine-free norbornenes.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

ASYMMETRIC SYNTHESIS OF CHIRAL NORBORNENES
17
Table 2. Yields, melting points, Rf values, IR spectra, and elemental analyses of compounds IV IX
Found, %
Calculated, %
Comp. Yield,
IR spectrum,
mp,
C
Rf
Formula
1
no.
%
, cm
C
H
Br
C
H
Br
IV
80
146
0.93 1720 (C O), 28.91
1570 (C C),
2.75
62.84
C18H22Br6O2 28.82
C20H28Br4O4 36.83
2.93
63.97
49.05
78.41
62.22
80.25
63.97
375 (C Br)
V
84
95
94
91
92
125 126 0.94 1730 (C O), 35.79
1575 (C C),
4.11
0.66
1.85
1.09
2.45
48.10
78.62
63.10
81.10
63.80
4.29
0.65
1.94
1.00
2.40
400 (C Br)
VI
274 275 0.92 1735 (C O), 15.70
1580 (C C),
C8H4Br6O2
15.68
350 (C Br)
VII
VIII
IX
177 178 0.93 1730 (C O), 22.86
1580 (C C),
C10H10Br4O4 23.36
450 (C Br)
135 137 0.89 1725 (C O), 15.98
1570 (C C),
C8H6Br6O
16.06
400 (C Br)
118 119 0.90 1730 (C O), 24.16
1570 (C C),
C10H12Br4O3 24.02
430 (C Br)
It was assumed that laevorotatory acids VI and VII
and alcohols VIII and IX have 5S configuration,
whereas their dextrorotatory enantiomers have 5R
configuration.
ester III in 30 ml of chlorobenzene containing 0.05 g
of hydroquinone was heated for 10 h at 140 C. The
solvent was distilled off, the dark brown residue was
dissolved in ether, the solution was decolorized by
addition of charcoal and evaporated, and the residue
was recrystallized from diethyl ether hexane. Ester
IV, [ ]2D0 = 86 (c = 1.2, CHCl3). Other syntheses of
compound IV were performed in a similar way. The
results are summarized in Table 1.
EXPERIMENTAL
The IR spectra were recorded on a UR-20 spec-
1
trometer. The H NMR spectra were measured on
a Tesla BS-48 instrument (80 MHz) in CCl4 using
TMS as internal reference. The optical rotations were
measured on Perkin Elmer and Polamat A polarim-
eters. The purity of the products was checked by TLC
on plates with unfixed layer of silica gel; benzene
dichloroethane acetic acid (2 : 4 : 1) was used as
eluent; spots were developed with iodine vapor.
Hexabromocyclopentadiene (I) was synthesized by
the procedure described in [2], mp 85 86 C; 1,2,3,4-
tetrabromo-5,5-dimethoxycyclopentadiene (II) was
obtained as described in [3], mp 47 48 C; ( )-menthyl
( )-Menthyl 1,2,3,4-tetrabromo-7,7-dimethoxy-
bicyclo[2.2.1]hept-2-ene-5-carboxylate (V). A mix-
ture of 4.42 g (0.01 mol) of compound II, 2.12 g
(0.01 mol) of ester III, and 0.05 g of hydroquinone in
30 ml of chlorobenzene was heated for 6 h at 140 C
in a sealed ampule. The ampule was opened, and the
mixture was treated as described above for compound
IV to isolate ester V, [ ]D20
=
84.12 (c = 0.31,
CHCl3). Other syntheses of ester V were performed
in a similar way (Table 1).
1,2,3,4,7,7-Hexabromobicyclo[2.2.1]hept-2-ene-
5-carboxylic acid (VI). A mixture of 7.49 g
(0.01 mol) of adduct IV and 0.57 g of KOH in 30 ml
of ethanol was refluxed for 2 h. The solvent was
distilled off, and the residue was dissolved in 20 ml
of water and treated with dilute hydrochloric acid.
The product was recrystallized from ether hexane.
Yield of acid VI 5.81 g.
acrylate (III) was prepared by the procedure reported
20
in [4], [ ]
=
127 (c = 1.4, MeOH); published
77 .
546
data [4]: [ ]2D0
=
( )-Menthyl 1,2,3,4,7,7-hexabromobicyclo[2.2.1]-
hept-2-ene-5-carboxylate (IV). A mixture of 5.4 g
(0.01 mol) of compound I and 2.12 g (0.01 mol) of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

18
MAMEDOV
Table 3. 1H NMR spectra of compounds IV IX, , ppm, J, Hz
Comp. exo-5-H, endo-6-H, exo-6-H, COOH,
OCH3,
d
OCH2,
m
OH, s J5, endo-6 J5, exo-6
J6,6
no.
m
m
m
s
IV
V
VI
VII
VIII
IX
3.10
3.10
2.95
2.97
3.20
3.10
2.10
2.10
2.15
2.15
2.10
2.15
2.35
2.30
2.35
2.55
2.50
2.55
4.5
4.8
5.0
4.9
4.6
4.5
7.9
7.5
8.0
7.0
7.8
8.0
12.0
11.9
11.5
11.5
12.0
12.0
3.55
3.53
3.35
12.0
11.5
3.30
3.65
3.9
3.5
1,2,3,4-Tetrabromo-7,7-dimethoxybicyclo[2.2.1]-
hept-2-ene-5-carboxylic acid (VII) was synthesized
in a similar way.
16.5 g (0.1 mol) of ( )-l-ephedrine in 100 ml of
acetone was added on cooling to a solution of 18.3 g
(0.03 mol) of acid VI in 175 ml of acetone. The
mixture was left to stand for 24 h in a refrigerator,
and the precipitate was filtered off. Yield 19.54 g.
Recrystallization from chlorobenzene gave 18.4 g
of salt X. Compound XI was synthesized in a similar
way from acid VII. Enantiomerically pure laevo-
rotatory acid VI was obtained by fivefold recrystal-
lization of salt X, followed by treatment with dilute
hydrochloric acid. Likewise, enantiomerically pure
laevorotatory acid VII was obtained from salt XI.
The salt of dextrorotatory acid VI was isolated from
the mother liquors obtained after separation of laevo-
rotatory acid VI. The solvent was distilled off, and
the residue was recrystallized from ethanol. Sixfold
recrystallization from ethanol, followed by treatment
with dilute hydrochloric acid, gave enantomerically
pure dextrorotatory acid VI. Enantomerically pure
dextrorotatory acid VII was obtained in a similar way.
1,2,3,4,7,7-Hexabromo-5-hydroxymethylbicyclo-
[2.2.1]hept-2-ene (VIII). A solution of 7.49 g
(0.01 mol) of compound IV in 50 ml of dry diethyl
ether was added dropwise to a suspension of 4 g of
LiAlH4 in 20 ml of dry ether, and the mixture was
stirred for 4 h at 20 C. Excess LiAlH4 was decom-
posed with water and then with dilute hydrochloric
acid. The organic layer was separated, washed with
a 5% solution of NaHCO3 and with water to neutral
reaction, and dried over MgSO4. The solvent was
distilled off, and the residue was recrystallized from
acetone hexane. Yield of compound VIII 5.62 g.
Alcohol IX was synthesized in a similar way.
Methyl ( )-(5S)-1,2,3,4,7,7-hexabromobicyclo-
[2.2.1]hept-2-ene-5-carboxylate (XII). A solution of
diazomethane in ether was added at 10 C to a solu-
tion of 1.22 g (0.002 mol) of acid ( )-(5S)-VI,
obtained by resolution of the corresponding diastereo-
isomeric salt with l-ephedrine, in 20 ml of ether.
The mixture was stirred for 30 min at 20 C, and the
solvent was removed to obtain 1.2 g of compound XII
with mp 105 106 C (from hexane; published data [5]:
REFERENCES
1. Mamedov, E.G. and Efendieva, K.M., Abstracts of
Papers, II Bakinskaya mezhdunarodnaya neftekhimi-
cheskaya konferentsiya (IInd Baku Int. Petrochemical
Conf.), Baku, 1996, p. 98.
mp 104 105 C), [ ]2D0 = 17.2 (c = 0.35, CHCl3).
Compound XIII was synthesized in a similar way.
2. Kovacs, J. and Marvel, C.S., J. Pol. Sci., 1967, vol. 5,
mp 66 C (from hexane; published data [5]: mp 64
no. 6, pp. 1279 1286.
65 C), [ ]2D0
=
15.2 (c = 0.34, CHCl3).
3. Mustafaev, A.M., Imamaliev, A.B., and Gusei-
nov, M.M., Zh. Org. Khim., 1980, vol. 25, no. 9,
pp. 1908 1914.
Alcohols ( )-(5S)-VIII and ( )-(5S)-IX were syn-
thesized from esters XII and XIII, respectively, fol-
lowing the procedure given above for reduction of
adducts IV and V.
4. Berson, J.A. and Ben-Efraim, D.A., J. Am. Chem.
Soc., 1959, vol. 81, no. 15, pp. 4083 4087.
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isomeric salt with ( )-l-ephedrine. A solution of
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002