Asymmetric radical synthesis of 2,5-diaryl-2,3-dihydrofurans - Application to the preparation of (+)-phyltetralin

Article abstract of DOI:10.1002/ejoc.200390198

The diastereoselective Mn^III-promoted radical addition of βoxo ester 1 onto N-cinnamoyloxazolidinone 2 affords, after removal of the chiral auxiliary, the enantiopure 2,5-diaryl2,3-dihydrofuran (-)-4. Its SnCl₄-induced rearrangement

Full text of DOI:10.1002/ejoc.200390198

FULL PAPER
Asymmetric Radical Synthesis of 2,5-Diaryl-2,3-dihydrofurans ؊ Application
to the Preparation of (؉)-Phyltetralin
[a]
[a]
[a]
´ ´
´
Frederic Garzino, Alain Meou, and Pierre Brun*
Keywords: Manganese / Asymmetric synthesis / Radical reactions / Total synthesis / Chiral auxiliaries
The diastereoselective MnIII-promoted radical addition of β-
oxo ester 1 onto N-cinnamoyloxazolidinone 2 affords, after
removal of the chiral auxiliary, the enantiopure 2,5-diaryl-
2,3-dihydrofuran (−)-4. Its SnCl4-induced rearrangement
leads to a 4-aryltetralone immediate precursor of the arylte-
tralin lignan (+)-phyltetralin (9).
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
Phyltetralin, an aryltetralin lignan, was first isolated from
the leaves of Phyllanthus niruri L. (Euphorbiaceae).[1Ϫ3] P.
niruri is one of the most widely used plants of the Phyl-
lanthus genus in world folk medicine owing to its extensive
distribution throughout many tropical and subtropical
areas. It has been claimed to possess beneficial therapeutic
effects against genitourinary infections, hepatitis B virus,
and in the treatment of asthma and bronchial infections
and it has a good reputation for its liver-protecting quali-
ties.[4]
It was not until 1977 that Stevenson unambiguously es-
tablished the structure and absolute configuration of phylte-
tralin by a semisynthesis starting from another, firmly
known, aryltetralin lignan: simple manipulations performed
on (Ϫ)-α-conidendrin led to the (Ϫ) enantiomer of the nat-
urally occurring (ϩ)-phyltetralin.[5] Two total syntheses of
(Ϯ)-phyltetralin appeared shortly thereafter.[6,7] The first
truly total synthesis of nonracemic phyltetralin was carried
out by Meyers in 1988. It featured, as the key step, the
conjugate addition of an aryllithium compound to a substi-
tuted naphthalene bearing a chiral oxazoline from which
(ϩ)-phyltetralin (68% ee) was obtained in five steps and
44% overall yield.[8] In addition, it should be noted that
(Ϫ)-phyltetralin was formed as a minor compound (10%)
by cyclization of the dibenzylbutane lignan (ϩ)-phyllan-
thin.[9] Finally, a few syntheses of closely related com-
pounds, namely α-conidendrin (dimethyl ether), α-retroden-
drin (dimethyl ether) and isolariciresinol (dimethyl ether)
have also been reported.[10Ϫ17]
We describe here a short total synthesis of (ϩ)-phyltetra-
lin (100% ee) which constitutes the first realization of a
strategy outlined by Fristad[18] in 1987 (but never validated
since then, probably for want of a dependable method of
obtaining the requisite enantiopure starting dihydrofurans)
to prepare aryltetralin lignans (Scheme 1). It features, as the
key step, the Lewis-acid-induced rearrangement of a 2,5-
diaryl-2,3-dihydrofuran into a 4-aryltetralone possessing
three contiguous stereogenic centers, followed by a few
straightforward transformations. If applied to a (2R,3R)-
2,5-diveratryl-2,3-dihydrofuran, this sequence could provide
an easy access to (ϩ)-phyltetralin.
[a]
Results and Discussion
`
´
Laboratoire de Synthese Organique Selective, GCOMM,
UMR-CNRS 6114,
´
Faculte des Sciences de Luminy,
We have previously reported that enantiopure func-
tionalized trans-2,3-disubstituted 2,3-dihydrofurans can be
prepared in good overall yield by the diastereoselective
163 Avenue de Luminy, 13288 Marseille Cedex 9, France
Fax: (internat.) ϩ 33-4/91829415
E-mail: brun@chimlum.univ-mrs.fr
1410
 2003 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/03/0408Ϫ1410 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2003, 1410Ϫ1414

Asymmetric Radical Synthesis of 2,5-Diaryl-2,3-dihydrofurans
FULL PAPER
Scheme 1. Retrosynthetic analysis of (ϩ)-phyltetralin
MnIII-mediated radical addition of acetoacetic esters to chi-
ral N-cinnamoyloxazolidinones,[19] separation of the major
diastereomer, and cleavage of the chiral auxiliary. Further-
more, when using diverse (S)-4-substituted oxazolidinones,
in each case the major dihydrofuran was shown to be
(2R,3R).[20] Provided that this approach could be extended
to the use of substituted benzoylacetic esters in terms of
both yield and diastereoselectivity, we would have ready ac-
cess to the required (2R,3R)-2,5-diveratryl-2,3-dihydrofuran
4 (Scheme 1).
A preliminary study conducted with benzoylacetate 1 and
N-cinnamoyloxazolidinone 2a demonstrated that this is in-
deed the case (Table 1 and Scheme 2). We then tested the
three other oxazolidinones already employed in our pre-
vious work involving acetoacetates, in order to identify the
chiral auxiliary able to ultimately furnish the maximum
yield in pure isolated 4.
Scheme 2. Synthesis of enantiopure (Ϫ)-4; reaction conditions: (i)
Mn(OAc)3·2H2O, AcOH, 70 °C, N2; (ii) LiBr, DBU, MeOH/THF,
0 °C, 3 h, 63%
Its absolute configuration was tentatively ascribed as
(2R,3R) as we surmised that replacing acetoacetates by ben-
zoylacetates in this reaction should not have altered its
stereochemical course.
Having the chiron (Ϫ)-4 in hand, the synthesis of (ϩ)-
phyltetralin was completed as shown in Scheme 3. The
SnCl4-induced rearrangement of (Ϫ)-4 leads to the trisub-
stituted aryltetralone 5, which exists in solution as an equi-
librium mixture of the 2,3-trans, 2,3-cis and, mostly, enol
forms.[24] 5 was then subjected to a reductive deoxygenation
giving the epimeric aryltetralin diesters 6/6Ј (2,3-trans/2,3-
cis, 70:30). Treatment with MeONa/MeOH allowed us to
raise this ratio to 94:6 in favor of the desired all-trans dia-
stereomer with the concomitant (but not detrimental) trans-
formation of the C-3 ester into the corresponding acid.[25]
At this stage, the two isomers 7/7Ј are inseparable. We there-
fore decided to treat the mixture with LiAlH4, hoping to
obtain a separation later.
Table 1. Addition of benzoylacetate 1 to 2aϪd
Substrate
R
Time [h] Unchanged 2 (%) 3 ϩ 3Ј (%) 3/3Ј
2a
2b
2c
2d
Bn
tBu
iPr
Ph2CH
3
11
10
13
7
73
73
70
72
65:35
84:16
79:21
90:10
3.5
2.5
3
As can be seen for each entry, the oxidative addition of
Although the resulting diols (isolariciresinol dimethyl
methyl 3,4-dimethoxybenzoylacetate (1)[21] to N-(3,4-di- ether 8 and its C-2 epimer β-conidendrol dimethyl ether 8Ј)
methoxycinnamoyl)oxazolidinones 2aϪd[22] affords the two could have been separated by crystallization,[14] we nonethe-
diastereomers 3 (major) and 3Ј (minor) in good combined less preferred to transform the primary alcohols into their
yield and with diastereoselectivities similar to those ob- methyl ethers because we found that pure (ϩ)-phyltetralin
served when using acetoacetates, with 2d giving the best dia- 9 could be easily isolated by silica-gel chromatography
stereomeric ratio. Accordingly, after condensing 1 onto 2d, alongside its minor epimer β-conidendrol tetramethyl ether
careful chromatography allowed us to obtain pure 3d, 9Ј. With hindsight, we see that the formation of the (ϩ)-
which was then submitted to mild methanolysis to remove enantiomer of phyltetralin validates our assumption that
the chiral auxiliary,[23] furnishing (in 38% overall yield from (Ϫ)-4 actually possessed the (2R,3R) configuration depicted
2d) enantiopure (Ϫ)-4.
in Scheme 2.
Eur. J. Org. Chem. 2003, 1410Ϫ1414
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´
F. Garzino, A. Meou, P. Brun
FULL PAPER
Scheme 3. Synthesis of (ϩ)-phyltetralin 9 from (Ϫ)-4; reaction conditions: (i) SnCl4, CH2Cl2, r.t., 12 h, 93%; (ii) H2, Pd/C, AcOH, 3 bar,
80 °C, 8 h, 73%; (iii) MeONa, MeOH, reflux, 24 h, 81%; (iv) LiAlH4, THF, reflux, 30 min; (v) NaH, CH3I, THF, r.t., 6 h, 74% over 2 steps
(238 mg, 1 mmol) and Mn(OAc)3·2H2O (590 mg, 2.2 mmol) in
AcOH (10 mL) were heated at 70 °C until complete discoloration.
Conclusion
After cooling, H2O (5 mL) was added and the mixture extracted
with Et2O (3 ϫ 10 mL). The combined organic layers were washed
We have demonstrated that enantiopure (ϩ)-phyltetralin
can be prepared in five steps and 40% overall yield from
with satd. aqueous NaHCO3 and dried with MgSO4. Evaporation
a chiral 2,5-diaryl-2,3-dihydrofuran readily obtained by
of the solvent afforded the crude product which was purified by
means of a short asymmetric radical synthesis. In conjunc-
flash chromatography.
tion with the development of more discriminative chiral
Dihydrofuran 3d: The above procedure was applied starting from
auxiliaries (which we are currently investigating) this pro-
2d (443 mg, 1 mmol). The crude product was purified by flash chro-
vides the basis of a general method to access a wide array
of enantiopure aryltetralin lignans (natural and nonnatural)
of predictable absolute configuration from easily available
starting materials.
matography (hexane/Et2O, from 9:1 to 1:1) to give first 3d (414 mg,
0.61 mmol, 61% yield) then a mixture of 3d and 3Јd (74 mg,
0.11 mmol, 11% yield). 3d: M.p. 154Ϫ155 °C. [α]2D0 ϭ Ϫ22.7 (c ϭ
1
1.0, CHCl3). H NMR (250 MHz, CDCl3): δ ϭ 3.65 (s, 3 H), 3.90
(s, 3 H), 3.93 (s, 6 H), 3.95 (s, 3 H), 4.42Ϫ4.45 (m, 2 H), 4.72 (d,
J ϭ 6.7 Hz, 1 H), 5.28 (d, J ϭ 6.6 Hz, 1 H), 5.48 (td, J ϭ 3.1,
7.2 Hz, 1 H), 5.77 (d, J ϭ 6.6 Hz, 1 H), 6.90 (m, 2 H), 6.93 (m, 2
H), 7.16Ϫ7.19 (m, 4 H), 7.25Ϫ7.33 (m, 6 H), 7.54Ϫ7.58 (m, 2 H)
ppm. 13C NMR (62 MHz, CDCl3): δ ϭ 51.22, 51.62, 53.68, 55.93,
55.96, 55.98, 56.00, 56.82, 65.47, 85.85, 101.70, 109.49, 110.09,
110.98, 112.82, 119.02, 121.48, 123.41, 127.17, 127.92, 128.46 (2 C),
128.69 (2 C), 129.03 (2 C), 129.25 (2 C), 131.20, 138.04, 139.31,
148.01, 149.13, 149.37, 151.36, 153.37, 164.69, 166.80, 173.11 ppm.
IR (CHCl3): ν˜ ϭ 3052, 2932, 1773, 1727, 1697, 1593, 1507, 1255,
1090 cmϪ1. C39H37NO10 (679.73): calcd. C 68.91, H 5.49, N 2.06,
O 23.54; found C 68.58, H 5.54, N 2.00, O 23.88.
Experimental Section
General Remarks: All NMR spectra were recorded with a Bruker
AC 250 spectrometer (1H: 250 MHz; 13C: 62 MHz). Chemical shifts
are reported in ppm. The following abbreviations are used in re-
porting spectra: s ϭ singlet, d ϭ doublet, t ϭ triplet, q ϭ quad-
ruplet, m ϭ multiplet, dd ϭ doublet of doublets, br. s ϭ broad
singlet. Infrared spectra were recorded with a PerkinϪElmer 297
spectrometer using thin-film deposition on NaCl plates, or in
CHCl3. Melting points were determined with an Electrothermal
IA 9100 apparatus and are uncorrected. Optical rotations were
measured with a PerkinϪElmer 241 polarimeter in a 1-dm cell.
Dihydrofuran 4: LiBr (159 mg, 1.83 mmol) and DBU (0.11 mL,
0.73 mmol) were added to a cooled (0 °C) solution of 3d (250 mg,
0.37 mmol) in MeOH (3 mL)/THF (1 mL). The stirring was con-
tinued at 0 °C until 3d had been totally consumed (4 h). H2O
(5 mL) and Et2O (5 mL) were then added. The aqueous layer was
extracted with Et2O (3 ϫ 10 mL). The combined organic extracts
were washed with 1  aqueous HCl (3 ϫ 5 mL) and H2O (3 ϫ
5 mL), and dried with MgSO4. Evaporation of the solvent afforded
the crude product which was purified by flash chromatography
(hexane/Et2O, from 9:1 to 1:1) to give 4 (105 mg, 0.23 mmol, 63%
yield). M.p. 113 °C. [α]2D3 ϭ Ϫ67.4 (c ϭ 1.0, CHCl3). 1H NMR
(250 MHz, CDCl3): δ ϭ 3.66 (s, 3 H), 3.78 (s, 3 H), 3.88 (s, 6 H),
3.93 (s, 6 H), 4.25 (d, J ϭ 6.6 Hz, 1 H), 5.69 (d, J ϭ 6.6 Hz, 1 H),
6.78Ϫ7.03 (m, 4 H), 7.62 (dd, J ϭ 8.6, 1.3 Hz, 1 H), 7.68 (d, J ϭ
1.3 Hz, 1 H) ppm. 13C NMR (62 MHz, CDCl3): δ ϭ 51.22, 52.55,
55.91, 55.98, 56.03, 58.17, 58.26, 84.74, 100.47, 108.73, 110.20,
Materials: All experiments were conducted under nitrogen unless
indicated otherwise and the reaction mixtures stirred magnetically.
Mn(OAc)3·2H2O was prepared from Mn(OAc)2·4H2O (Acros) ac-
cording to a literature procedure.[26] SnCl4 packaged under nitrogen
(Aldrich) was used as received. Dichloromethane was distilled from
P2O5, and THF from sodium benzophenone ketyl immediately
prior to use. Flash chromatography was performed with Merck sil-
ica gel 60 H. Thin layer chromatography (TLC) was carried out on
Merck silica-gel 60 F254 aluminum-backed plates. TLC visualiz-
ation was done with a 254-nm UV lamp and phosphomolybdic
acid staining solution.
General Procedure for the Oxidative Addition: N-Cinnamoyloxazol-
idinone
2 (1 mmol), methyl 3,4-dimethoxybenzoylacetate (1)
1412
Eur. J. Org. Chem. 2003, 1410Ϫ1414

Asymmetric Radical Synthesis of 2,5-Diaryl-2,3-dihydrofurans
FULL PAPER
111.39, 112.97, 118.03, 121.37, 123.39, 132.52, 148.10, 149.42,
49.01, 51.49, 51.86, 53.51, 55.85, 55.94, 55.99, 110.77, 110.96,
111.71, 112.12, 121.60, 125.91, 129.71, 135.26, 147.70, 147.85,
151.49, 164.82, 166.20, 173.32 ppm. IR (CHCl3): ν˜ ϭ 3051, 2985,
2952, 1730, 1600, 1507, 1261, 1090 cmϪ1. C24H26O9 (458.47): calcd. 148.10, 149.06, 174.74, 179.42 ppm. IR (neat): ν˜ ϭ 3410Ϫ3051
C 62.88, H 5.72, O 31.41; found C 62.73, H 5.88, O 31.39.
(broad), 1732, 1640, 1633, 1507, 1420, 1261 cmϪ1
.
Aryltetralone 5: SnCl4 (0.115 mL, 1 mmol) was added to a solution
of (Ϫ)-4 (46 mg, 0.10 mmol) in dry CH2Cl2 (2.5 mL) at room tem-
perature. After 4 had been totally consumed (12 h), the reaction
was quenched by slow addition of satd. aqueous NaHCO3, diluted
(؉)-Phyltetralin (9): A solution of 7/7Ј (35 mg, 0.08 mmol) in dry
THF (2 mL) was added dropwise to a suspension of LiAlH4
(61 mg, 1.62 mmol) in dry THF (3 mL). The reaction mixture was
refluxed for 30 min. After cooling, H2O (61 µL), 15% aqueous
with an equal volume of H2O, and extracted with Et2O (3 ϫ 5 mL). NaOH (61 µL), and H2O (122 µL) were successively added. The
The combined organic layers were washed with satd. aqueous resulting cloudy suspension was filtered through Celite which was
NaHCO3 (5 ϫ 5 mL) and H2O (2 ϫ 5 mL), and dried with MgSO4. then rinsed with CH2Cl2 (3 ϫ 10 mL). The filtrate was concen-
Evaporation of the solvent afforded the crude product which was trated to afford quantitatively the mixture 8/8Ј, which was used in
purified by flash chromatography (hexane/EtOAc, from 9:1 to 1:1) the next step without further purification. A suspension of oil-free
to give 5 (43 mg, 0.09 mmol, 93% yield). 5 (Enol Form): M.p.
133Ϫ134 °C. H NMR (250 MHz, CDCl3): δ ϭ 3.66 (s, 3 H), 3.74
NaH (4 mg, 0.08 mmol) in dry THF (5 mL) containing 8/8Ј (32 mg,
0.08 mmol) was stirred at room temperature for 1 h. CH3I (50 µL,
1
(s, 3 H), 3.81 (s, 3 H), 3.83 (s, 3 H), 3.86 (s, 3 H), 3.96 (s, 3 H), 0.08 mmol) was added. After stirring for another 3 h, CH3I (25 µL,
4.54 (s, 1 H), 6.43 (dd, J ϭ 7.2, 1.4 Hz, 1 H), 6.61 (br. s, 2 H), 6.68
0.04 mmol) and oil-free NaH (4 mg, 0.08 mmol) were further added
and the stirring continued for 2 h. The reaction mixture was cooled
(d, J ϭ 7.2 Hz, 1 H), 7.44 (s, 1 H), 12.77 (br. s, 1 H) ppm. 13C
NMR (62 MHz, CDCl3): δ ϭ 45.12, 46.51, 51.96, 52.43, 55.83 (2 to 5 °C and quenched with H2O (5 mL). The aqueous layer was
C), 56.01 (2 C), 107.18, 108.31, 110.82, 110.97, 111.44, 119.67, extracted with Et2O (3 ϫ 5 mL). The combined organic extracts
132.50, 134.96, 139.35, 148.49, 148.55, 148.81, 151.79, 166.41,
169.43, 173.69 ppm. IR (CHCl3): ν˜ ϭ 3550Ϫ3000 (broad), 3050,
2992, 1739, 1513, 1420, 1261 cmϪ1. C24H26O9 (458.47): calcd. C
62.88, H 5.72, O 31.41; found C 63.06, H 5.55, O 31.39.
were washed with H2O (3 ϫ 4 mL) and dried with MgSO4. Evapo-
ration of the solvent afforded the crude product which was purified
by flash chromatography (hexane/Et2O, from 9:1 to 1:1) to give
first phyltetralin 9 (25 mg, 0.06 mmol, 74% yield over two steps)
then β-conidendrol tetramethyl ether 9Ј (1 mg, 0.002 mmol). The
enantiomeric purity of 9 can be checked by HPLC using a Daicel
Amylose normal phase column CHIRALPAK AD (hexane/2-pro-
panol, 90:10, 1 mL/min). 9: M.p. 98 °C. [α]2D3 ϭ ϩ7.0 (c ϭ 0.8,
CHCl3).[28] 1H NMR (250 MHz, CDCl3): δ ϭ 1.75Ϫ1.89 (m, 1 H),
2.10Ϫ2.24 (m, 1 H), 2.84 (d, J ϭ 6.2 Hz, 2 H), 3.08 (dd, J ϭ 9.4,
3.3 Hz, 1 H), 3.26 (s, 3 H), 3.36 (s, 3 H), 3.37 (dd, J ϭ 9.4, 3.3 Hz,
1 H), 3.46 (m, 2 H), 3.58 (s, 3 H), 3.80 (s, 3 H), 3.84 (s, 3 H), 3.87
(s, 3 H), 3.99 (d, J ϭ 10.3 Hz, 1 H), 6.22 (s, 1 H), 6.61 (s, 1 H),
6.62 (d, J ϭ 1.7 Hz, 1 H), 6.70 (dd, J ϭ 8.0, 1.7 Hz, 1 H), 6.81 (d,
J ϭ 8.0 Hz, 1 H) ppm. 13C NMR (62 MHz, CDCl3): δ ϭ 33.20,
36.48, 45.02, 47.38, 55.95, 56.01, 56.05, 58.99, 59.06, 71.52, 75.48,
111.08, 111.25, 112.49, 113.05, 121.93, 129.02, 132.23, 138.18,
147.16, 147.30, 147.59, 149.04 ppm. IR (CHCl3): ν˜ ϭ 3045, 2972,
2932, 1513, 1480, 1420, 1260, 1130, 1102 cmϪ1. C24H32O6 (416.52):
calcd. C 69.21, H 7.74, O 23.05; found C 69.37, H 7.80, O 22.83.
Aryltetralin Diesters 6/6Ј: A solution of 5 (150 mg, 0.33 mmol) in
AcOH (7 mL) was introduced into a stainless steel reactor. 10% Pd
on charcoal (166 mg) was then added. The mixture was placed un-
der H2 (3 bar) and heated at 80 °C for 8 h. After cooling, Pd was
filtered through Celite and rinsed with Et2O (3 ϫ 10 mL). The fil-
trate was washed with satd. aqueous NaHCO3 (5 ϫ 5 mL) and
dried with MgSO4. Evaporation of the solvent afforded the crude
product which was purified by flash chromatography (hexane/
EtOAc, from 9:1 to 1:1) giving 6/6Ј (106 mg, 0.24 mmol, 73% yield)
as an inseparable mixture. Owing to peak overlaps between 6 and
6Ј we only cite the 1H signals unambiguously pertaining to 6 by
comparison with the 1H NMR spectrum of pure 6 already re-
ported.[27] The 13C NMR spectrum contains all the peaks per-
taining to 6 by comparison with the 13C NMR spectrum of pure 6
reported by Charlton[16] (these values are also consistent with those
described by Nishizawa,[27] provided that all the chemical shifts
cited therein are systematically incremented by ϩ 1.0 ppm, in order
to annul the discrepancy between them and those of Charlton). 1H
NMR (250 MHz, CDCl3): δ ϭ 3.47 (s, 3 H), 3.58 (s, 3 H), 3.69 (s,
3 H), 3.79 (s, 3 H), 3.87 (s, 3 H), 3.89 (s, 3 H), 4.18 (d, J ϭ 10.9 Hz,
1 H) ppm. 13C NMR (62 MHz, CDCl3): δ ϭ 31.83, 43.30, 48.83,
51.65, 51.72, 55.80, 55.87 (2 C), 55.94, 110.81, 110.99, 111.83,
112.21, 121.56, 126.12, 129.71, 135.48, 147.72, 147.81, 148.06,
149.03, 174.10, 174.58 ppm.
1
9Ј: M.p. 115 °C. H NMR (250 MHz, CDCl3): δ ϭ 2.16Ϫ2.42 (m,
2 H), 2.54 (dd, J ϭ 16.1, 9.5 Hz, 1 H), 2.88 (dd, J ϭ 16.1, 6.9 Hz,
1 H), 3.21Ϫ3.51 (m, 4 H), 3.27 (s, 3 H), 3.32 (s, 3 H), 3.69 (s, 3 H),
3.78 (s, 3 H), 3.82 (s, 3 H), 3.86 (s, 3 H), 4.09 (d, J ϭ 4.0 Hz, 1 H),
6.38 (s, 1 H), 6.43 (dd, J ϭ 7.9, 1.3 Hz, 1 H), 6.59 (d, J ϭ 1.3 Hz,
1 H), 6.61 (s, 1 H), 6.71 (d, J ϭ 7.9 Hz, 1 H) ppm. 13C NMR
(62 MHz, CDCl3): δ ϭ 30.02, 31.65, 43.71, 46.02, 55.92, 55.97,
56.06, 58.86, 58.99, 72.42, 75.14, 110.99, 111.44, 112.31, 113.64,
121.39, 128.11, 128.99, 139.36, 147.43, 147.61, 147.73, 148.90 ppm.
IR (CHCl3): ν˜ ϭ 3043, 2975, 2932, 1520, 1480, 1418, 1260, 1130,
Aryltetralin Monoesters 7/7Ј: The purified mixture 6/6Ј (44 mg,
0.10 mmol) and MeONa (38 mg, 0.70 mmol) were refluxed in
MeOH (1 mL) for 24 h. After cooling, MeOH was evaporated and
the solid residue taken up in H2O (5 mL). After extraction with
Et2O (3 ϫ 5 mL), the aqueous layer was acidified with 10% aque-
ous HCl and re-extracted with Et2O (3 ϫ 5 mL). The combined
organic layers were then dried with MgSO4. Evaporation of the
solvent afforded 7/7Ј (35 mg, 0.08 mmol, 81% yield) as an insepa-
rable mixture, which was used in the next step without further puri-
fication. 1H NMR (250 MHz, CDCl3): δ ϭ 2.91Ϫ3.34 (m, 4 H),
3.46 (s, 3 H), 3.59 (s, 3 H), 3.79 (s, 3 H), 3.86 (s, 3 H), 3.88 (s, 3
H), 4.13 (d, J ϭ 10.6 Hz, 1 H), 6.20 (s, 1 H), 6.57 (d, J ϭ 1.8 Hz,
1 H), 6.61 (s, 1 H), 6.67 (dd, J ϭ 8.0, 1.8 Hz, 1 H), 6.78 (d, J ϭ
8.0 Hz, 1 H) ppm. 13C NMR (62 MHz, CDCl3): δ ϭ 31.81, 43.23,
1110 cmϪ1
.
Acknowledgments
´ ´
Nicolas Vanthuyne (Chiral Screening Center of the ‘‘Federation de
´ ˆ
Recherche 1719’’, Faculty of Sciences, St Jerome, Marseille) and
´
´ ˆ
Dr. Gerard Gil (Faculty of Sciences, St Jerome, Marseille) are
greatly acknowledged for performing the chiral HPLC analyses.
[1]
L. R. Row, C. Srinivasulu, M. Smith, G. S. R. Subba Rao,
Tetrahedron Lett. 1964, 5, 1557Ϫ1567.
L. R. Row, C. Srinivasulu, M. Smith, G. S. R. Subba Rao,
[2]
Tetrahedron 1966, 22, 2899Ϫ2908.
Eur. J. Org. Chem. 2003, 1410Ϫ1414
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F. Garzino, A. Meou, P. Brun
FULL PAPER
[3]
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[O02602]
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Eur. J. Org. Chem. 2003, 1410Ϫ1414