Asymmetric Diels-Alder reaction of 1,3-butadienes with (-)-dimenthyl fumarate in the presence of BBr3 and BBr3·OEt 2

Article abstract of DOI:10.1134/S1070428007020054

Asymmetric synthesis of substituted cyclohexenes was performed by [4+2]-cycloaddition of (-)-dimenthyl fumarate to 1,3-butadienes in the presence of BBr₃ and BBr₃·OEt₂. The latter are efficient catalysts for this reaction.

Full text of DOI:10.1134/S1070428007020054

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 2, pp. 184−187. © Pleiades Publishing, Ltd. 2007.
Original Russian Text © E.G. Mamedov, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 2, pp. 192−195.
Asymmetric Diels−Alder Reaction
of 1,3-Butadienes with (−)-Dimenthyl Fumarate in the Presence
of BBr3 and BBr3·OEt2
E. G. Mamedov
Institute of Petrochemical Processes, National Academy of Sciences of Azerbaidzhan, Baku, AZ1025 Azerbaidzhan
Received February 2, 2002
Abstract—Asymmetric synthesis of substituted cyclohexenes was performed by [4+2]-cycloaddition of (–)-di-
menthyl fumarate to 1,3-butadienes in the presence of ΒΒr3 and BBr3·OEt2. The latter are efficient catalysts for
this reaction. The effect of various factors on the chemical and optical yield of compounds synthesized was
studied. The lowering of the reaction temperature to –70°C favors increase in the enantiomeric purity of products
up to 81%. The overall yield of adducts grows with temperature and catalyst amount. The solvent character
insignificantly affects the overall and optical yield of compounds obtained.
DOI: 10.1134/S1070428007020054
Asymmetric Diels–Alder reaction in the presence of
catalysts is one among the promising methods for
preparation of various polyfunctional compounds
extensively used in the syntheses of natural substances
and their synthetic analogs, drugs, biologically active
substances, and specialty polymers proceeding from
available relatively simple reagents.
For instance, butadiene condensation with 8-phenyl-
menthyl acryate results in the fomation of the key product
for the synthesis of (–)-sarcomysin in an optically active
form and with enantiomeric purity of 86–91% [1].
CO2Ment
R
We report here on the results of the study of reaction
between 1,3-butadienes I and II with (–)-dimenthyl
fumarate (III) in the presence of ΒΒr3 and BBr3·OEt2,
efficient catalysts for this reaction.
R
MentO2C
I, II
III
The chiral auxiliary fragment (menthyl residue) was
removed by an alkaline hydrolysis. To avoid the probable
racemization at the alkaline hydrolysis the menthyl removal
was performed by reduction with LiAlH4.
CO2Ment
Catalyst
R
R
H
H
CO2Ment
CO2H
IV, V
The catalytic effect of BBr3 and BBr3·OEt2 may be
ascribed to complex formation with dienophile III.
OH _
R
The arising electron deficiency on the double bond of
(–)-dimenthyl fumarate (III) facilitates its reaction with
dienes I and II. This assumption is confirmed by the shift
H
H
R
CO2H
1S,2S-(+)-(VI, VII)
CH2OH
...
BBr3
O
LiAlH4
R
H
H
C OMent
BBr3
R
III
CH2OH
1S,2S-(+)-(VIII, IX)
MentO C
...
O BBr3
R = H (I, IV, VI, VIII), CH3 (II, V,VII, IX).
184

ASYMMETRIC DIELS−ALDER REACTION
185
Effect of conditions of asymmetric Diels–Alder reaction with butadienes in the presence of BBr3 and BBr3·OEt2 on the chemical
and optical yield of products IV–IX
a On removing the chiral fragment.
of the absorption band ν(C=O) in the IR spectrum from
1750 to 1600 cm–1 in going from dienophile III to its
complexes with BBr3 or BBr3·OEt2. These results are
consistent with the data of [2] where a similar shift from
1730 to 1630 cm–1 has been observed of the C=O group
absorption band in menthyl acrylate in the presence of
BBr3 indicating the complex formation between the
catalyst and dienophile.
catalyst virtually did not affect the optical yield of
compounds VI–IX, but their overall yield grew.
The data in the table also manifest that the overall
and optical yield of the reaction products is practically
insensitive to the solvent character.
In going from the noncatalyzed reaction of (–)-
dimenthyl fumarate with butadienes [3] to their reaction
in the presence of BBr3 and BBr3·OEt2 the configuration
of products VI–IX changes. In the noncatalyzed reaction
on removing the chiral agent compounds obtained have
the (1R,2R)-(–)-configuration, and in the presence of BBr3
and BBr3-·OEt2, (1S,2S)-(+)-configuration.
The reaction was carried out in a temperature range
from –70 to 20°C in the presence of various amounts of
catalysts in organic solvents for 3 h.
The effect was studied of temperature, amount and
type of the catalyst, and character of solvent on the
chenical and optical yield of the reaction products VI–
IX. The results obtained are compiled in a table.
The optical yield of compounds VI–IX was evaluated
from the comparison of their specific rotation measured
experimentally with the specific rotation of the enentio-
merically pure samples of the same compounds [4]. The
relative configuration of compounds VI–IX was establish-
ed from the correlation of the optical rotation sign with
that of identical in structure compounds with the known
configuration [4].
As seen from the table, in contrast to the noncatalyzed
reaction between butadiene and (–)-dimenthyl fumarate
where the changes in the temperature insignificantly
affect the enantiomeric purity of compounds obtained, in
the presence of BBr3 and BBr3·OEt2 the cooling to –70°C
favors the increase in the enantiomeric purity of products
VI–IX. It attains 81% in compound VIII, and in compound
IX, 78%. The overall yield of adducts IV and V decreases
with lowering temperature. The increased quantity of
The composition and structure of compounds
synthesized was confirmed by elemental analysis, IR and
1H NMR spectra.
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MAMEDOV et al.
186
Hence we investigated the possibility to use BBr3 and
of (–)-dimenthyl fumarate (III) in 20 ml of CH2Cl2 was
added dropwise 0.625 g (2.5 mmol) of BBr3 in 10 ml of
CH2Cl2. Then at –10°C was added 0.82 g (0.01 mol) of
2,3-dimethyl-1,3-butadiene in 10 ml of CH2Cl2, and the
mixture was stirred for 3 h at –10°C. Then it was treated
as above. On removing the solvent the residue was
recrystallized from ethanol. Yield 0.95 g (20%), mp 61–
63°C. IR spectrum, cm–1: 3030 (=C–H), 1730 (C=O).
1H NMR spectrum, δ, ppm: 0.73–0.85 d (CH3), 5.47 m
(HC=CH). Found, %: C 75.10; H 10.07. C30H50O4.
Calculated, %: C 75.94; H 10.51.
BBr3·OEt2 as catalysts for asymmetric Diels–Alder
reaction of (–)-dimenthyl fumarate with 1,3-butadienes.
These catalysts are efficient in this reaction, and their
application permitted after the removal of auxiliary chiral
fragment to obtain substituted (1S,2S)-(+)-cyclohexenes
in optical yields of 78–81%.
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
UR-20 from thin film or pellets with potassium bromide.
1H NMR spectra were registered on a spectrometer BS-
484 Tesla (80 MHz) from solutions in CCl4 with TMS
serving as internal reference. The optical rotation was
measured on a polarimeter Perkin Elmer-141 and
a spectropolarimeter Spektropol-1.
The other syntheses of compound V were performed
in a similar manner. The conditions and results are given
in the table.
(1S,2S)-(+)-trans-Cyclohex-4-ene-1,2-dicarb-
oxylic acid (VI). For 2 h 4.46 g of adduct IV was heated
at reflux in 15 ml of 5% KOH solution in methanol. On
removing methanol the residue was dissolved in 30 ml of
water. Menthol was extracted into ether. The water layer
was treated with dilute HCl, and the reaction product
was extracted into ether. The extract was washed with
water and dried with MgSO4. On removing ether we
obtained compound VI in 1.6 g (95%) yield, mp 172–
173°C (from acetone), [α]D20 +65.6° (C 0.2, CHCl3). IR
spectrum, cm–1: 3025 (=C–H), 1735 (C=O), 1050–1120
(C–O). 1H NMR spectrum, δ, ppm: 5.4 m (HC=CH),
11.5 s (COOH). Found, %: C 55.98; H 5.13. C8H10O4.
Calculated, %: C 56.47; H 5.88.
BBr3·OEt2. Under a nitrogen atmosphere 25 g
(0.07 mol) of BBr3 was slowly added to 11.1 g
(0.15 mol) of ethyl ether cooled to –10°C. Then the
mixture was maintained at 5°C for 30 min more. The
excess ethyl ether was remived. The residue was distilled
in a vacuum in a nitrogen flow. Yield 28.5 g (95%), bp
58°C (3 mm Hg).
(–)-Dimenthyl fumarate (III) was obtained from
fumaryl chloride and l-(–)-menthol [4]. [α]D20 –102° (C
1.6, CHCl3), mp 51–53°C (from acetone). IR spectrum,
cm–1: 1730 (C=O), 1330 (CH3), 1100–1150 (C–O).
Dimenthyl trans-cyclohex-4-ene-1,2-dicarboxy-
late (IV). To a solution of 3.92 g (0.01 mol) of (–)-
dimenthyl fumarate (III) in 20 ml of CH2Cl2 at –10°C
was added dropwise 0.625 g (2.5 mmol) of BBr3 in 10
ml of CH2Cl2. Then at –10°C was added 1.08 g (0.02
mol) of 1,3-butadiene in 10 ml of CH2Cl2, and the mixture
was stirred for 3 h at –10°C. Then it was treated first
with dilute HCl followed by 5% solution of NaHCO3,
washed with water, and dried with MgSO4. On removing
the solvent the residue was recrystallized from ethanol.
Yield 1.07 g (24%), mp 59–60°C, [α]D20 –74.2° (C 0.1,
CHCl3). IR spectrum, cm–1: 3030 (=C–H), 1730 (C=O),
(1S,2S)–(+)-trans-4,6-Dimethylcyclohex-4-ene-
1,2-dicarboxylic acid (VII) was obtained similarly from
4.74 g of adduct V. Yield 1.53 g (96%), mp 213–215°C
(from acetone), [α]D20 +64.2° (C 0.1, CHCl3). IR
spectrum, cm–1: 3030 (=C–H), 1740 (C=O). 1H NMR
spectrum, δ, ppm: 0.8–0.85 d (CH3), 5.8 m (HC=CH),
11.2 s (COOH). Found, %: C 60.12; H 6.95. C10H14O4.
Calculated, %: C 60.60; H 7.07.
(1S,2S)–(+)-trans-1,2-Dihydroxymethylcyclohex-
4-ene (VIII). To a dispersion of 4 g of LiAlH4 in 100 ml
of anhydrous ether was added dropwise a solution of
4.46 g (0.01 mol) of adduct IV in 30 ml of anhydrous
ether, and the reaction mixture was stirred for 2 h at
20°C. Excess LiAlH4 was quenched with water, then to
the reaction mixture was slowly added cooled dilute HCl.
The ether layer was separated, washed with 5% solution
of NaHCO3 and water till neutral reaction, and dried with
MgSO4. On removing ether we obtained compound VIII
in 1.13 g yield, bp 105–107°C (1 mm Hg), [α]D20 +30.1°
1
1050 (C–O). H NMR spectrum, δ, ppm: 0.71–0.86 d
(CH3), 5.5 m (HC=CH). Found, %: C 75.59; H 10.11.
C28H46O4. Calculated, %: C 75.33; H 10.31.
The other syntheses of compound IV were performed
in a similar manner. The conditions and results are given
in the table.
Dimenthyl trans-4,5-dimethylcyclohex-4-ene-
1,2-dicarboxylate (V). To a solution of 3.92 g (0.01 mol)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 2 2007

ASYMMETRIC DIELS−ALDER REACTION
187
(C 0.11, CHCl3). IR spectrum, cm-1: 3600 (OH), 3030
(=C–H), 1660 (C=C). HNMR spectrum, δ, ppm: 4.5 s
(HCO), 5.56 m (HC=CH). Found, %: C 70.12; H 10.11.
C10H18O2. Calculated, %: C 70.58; H 10.58.
1
(OH), 4.8 m (HCO), 5.62 (HC=CH). Found, %: C 67.39;
H 10.02. C8H14O2. Calculated, %: C 67.60; H 9.85.
REFERENCES
1. Boekman, R.K., Naegeli, P.C., andAiter, S.D., J. Org. Chem.,
1980, vol. 45, p. 752.
2. Mamedov, E.G., Zh. Org. Khim., 2001, vol. 37, p. 230.
3. Walborsky, H.M., Barash, L., and Davis, T.C., J. Org. Chem.,
1961, vol. 26, p. 4778.
(1S,2S)–(+)-trans-4,5-Dimethyl-1,2-dihydroxy-
methylcyclohex-4-ene (IX) was obtained in the same
way from 4.47 g of adduct V. Yield 1.38 g (87%), bp 125–
127°C (1 mm Hg), [α]D20 +28° (C 0.12, CHCl3). IR spec-
1
trum, cm–1: 3300–3600 (OH), 3036 (=C–H). H NMR
4. Walborsky, H.M., Barash, L., and Davis, T.C.., Tetrahedron,
1963, vol. 19, p. 233.
spectrum, δ, ppm: 0.75–0.85 d (CH3), 4.5 s (OH), 4.8 m
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 2 2007