A novel method for the stereoselective synthesis of tetralins and indanes

Article abstract of DOI:10.1055/s-2002-33514

Heavily-substituted 1-aryltetralins and 1-arylindanes were prepared in a highly stereoselective manner using a two-step sequence. Addition of t-butyl benzyl sulfoxides to unsaturated carbonyl compounds gave conjugate adducts with high diastereoselectivity

Full text of DOI:10.1055/s-2002-33514

LETTER
1404
A Novel Method for the Stereoselective Synthesis of Tetralins and Indanes
Stereoselective
e
S
ynthesis
o
l
f
Tetra
d
lins and Inda
a
ne
s
Appelbe, Mike Casey,* Claire M. Keaveney, Cornelius J. Kelly
Chemistry Department, The Centre for Synthesis and Chemical Biology, and The Conway Institute of Biomolecular and Biomedical
Research, University College Dublin, Dublin 4, Ireland
Fax +353(1)7162127; E-mail: mike.casey@ucd.ie
Received 26 June 2002
ed. Due to the lack of precedent for the cyclisation step,
Abstract: Heavily-substituted 1-aryltetralins and 1-arylindanes
we began by investigating the use of benzyl sulfoxides 1,7
were prepared in a highly stereoselective manner using a two-step
bearing a range of different spectator groups, in a model
sequence. Addition of t-butyl benzyl sulfoxides to unsaturated car-
bonyl compounds gave conjugate adducts with high diastereoselec-
two-step conjugate addition/Friedel–Crafts cyclisation se-
tivity. Treatment of the adducts with SnCl4 generated benzyl quence, using a chalcone 28 as the conjugate acceptor
carbocations which reacted intramolecularly with suitably-posi-
(Scheme 1).
tioned aromatic rings to give tetralins and indanes, again with high
The results for the conjugate addition step are shown in
diastereoselectivity.
Table 1.9 It is clear that tert-butyl is the best spectator
Key words: carbocations, diastereoselectivity, natural products,
group, giving high yields and essentially complete stereo-
lignans, sulfoxides
control. Two aryl spectator groups, p-tolyl and 2,4-
dimethoxyphenyl, also gave high stereoselectivity, but the
yields were very poor. 2-Pyridyl sulfoxides gave poor dia-
The biological activity of 1-aryltetralin lignans, e.g. podo-
stereoselectivity when LDA was used as the base, but
phyllotoxin, means that the development of methods for
gave high selectivity and moderate yields using LHMDS.2
the synthesis of these systems is of continuing interest.1
The relative stereochemistry of the tert-butyl conjugate
We now report a new two-step stereoselective route to
adducts was assigned by analogy with earlier results,2 but
these targets. The first step of the sequence involves dia-
that of the other adducts cannot be assigned at this stage.
stereoselective conjugate addition of benzyl sulfoxides to
The stereochemical outcome of the tert-butyl sulfoxide
activated alkenes. The second step creates the tetralin, or
reactions can be accounted for by the transition state mo-
indane, ring system by an intramolecular Friedel–Crafts
del 5 (Figure). The sulfoxide-stabilised carbanion is as-
type reaction, in which the sulfinyl function acts as a leav-
sumed to be nearly planar, with the lithium counterion
ing group.
coordinated to the sulfinyl oxygen.10 We propose a cyclic
The conjugate addition of sulfoxide-stabilised carbanions
to , -unsaturated carbonyl compounds is a highly stereo-
selective process, provided that the correct combination of
‘spectator group’ (R1 in Scheme 1) and base is used.2,3 We
recognised that if benzyl sulfoxides were used, there was
the potential for C–S bond cleavage in the conjugate ad-
ducts to give benzylic carbocations, which could lead to 1-
aryltetralin formation by intramolecular electrophilic at-
tack on suitably-positioned aromatic rings.4 The removal
of a sulfinyl group in order to generate benzylic carboca-
tions is unusual, though a few examples of the formation
C–C bonds5 and C–O bonds6 in this way have been report-
eight-membered transition state, in which the , -unsatur-
ated carbonyl compound is coordinated to the lithium
counterion. Consideration of possible transition state con-
formers indicates that a chair-boat type structure 5 is the
most favourable (Figure). In 5 the aryl group is sufficient-
ly far away to avoid serious steric interactions with the
tert-butyl, and the full p-orbital on the anionic carbon is
roughly parallel with the S=O bond. This model is specu-
lative, but it does account for key observations, such as the
fact that only , -unsaturated carbonyl compounds that
can adopt an s-cis conformation undergo conjugate addi-
tions with sulfoxides.2,3,11
O
S
O
O
R1
O
1. LiNR22, THF, -78 °C
O
O
SnCl4
O
Ph
O
MeNO2
2.
O
Ph
C6H4X
O
O
S
C6H4X
R1
X
Ph
2
1
3
4a X = H
4b X = OMe
Scheme 1
Synlett 2002, No. 9, Print: 02 09 2002.
Art Id.1437-2096,E;2002,0,09,1404,1408,ftx,en;D10802ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
Stereoselective Synthesis of Tetralins and Indanes
1405
H
Table 2 Cyclisation of Conjugate Adducts 3 to Give Tetralones 4
O
Ph
Adduct
3a
R
X
Temp
80 °C
50 °C
50 °C
50 °C
50 °C
Yield
17%
81%
50%
<50%
36%
Li
H
Ar
O
But
S
t-Bu
H
..
C6H4X
3b
t-Bu
OMe
OMe
OMe
OMe
5
Figure
Table 1 Conjugate Additions of Benzyl Sulfoxides 1 to Chalcone 2
3c
p-Tolyl
DMPa
2-Pyridyl
3d
3f
Sulfoxide 1, R1
adduct 3
X
Base
Yield
Diastereo-
selectivitya
a 2,4-Dimethoxyphenyl.
a
b
c
d
e
e
f
t-Bu
H
LDA
LDA
LDA
LDA
LDA
86%
78%
21%
23%d
57%
>10:1
>10:1
>10:1b
>10:1b
1.5:1b
>10:1b
1.5:1b
>10:1b
t-Bu
OMe
OMe
OMe
H
ture. Instead, mixtures of hydroxy ketone 8b (mixture of
diastereomers) and dihydrofuran 9b, together with a Pum-
merer-type product 10 were obtained (Scheme 3). Tetral-
one 4b was formed at higher temperatures, and as the
proportion of tetralone increased the amounts of hydroxy
ketone and dihydrofuran decreased. The product ratios
varied depending on the conditions and the diastereomer
ratio of the conjugate adduct 3f, but the isolated yield of
tetralone never exceeded 36%. It is clear that the tert-butyl
sulfoxides gave the best yields of tetralones, i.e. tert-butyl
is the best spectator group for both steps of the sequence.
p-Tolyl
DMPc
2-Pyridyl
2-Pyridyl
2-Pyridyl
2-Pyridyl
H
LHMDS 53%
LDA 81%
LHMDS 56%
OMe
OMe
f
a Diastereomer ratios were measured by high-field 1H NMR.
b Relative stereochemistry not assigned.
All of cyclisation results are consistent with the mecha-
nism presented in Scheme 2. Loss of the sulfinyl groups
gives the carbocations 6 which are in equilibrium with the
oxonium ions 7. When Ar2 is phenyl, equilibrium favours
the oxonium ion, tetralone formation is slow, and the ma-
jor products 8 (one diastereomer) and 9 are formed from
7, by hydrolysis and loss of a proton, respectively. When
Ar2 is 4-methoxyphenyl, a larger proportion of the car-
bocation 6 is present and formation of the tetralone 4 is
relatively efficient at 50 °C. At lower temperatures, tetral-
one formation is slow and the by-products 8b (two dia-
stereomers) and 9b are formed. Resubjection of these by-
products to the reaction conditions resulted in their con-
version into tetralone 4b.
c 2,4-Dimethoxyphenyl.
d Me3SiCl was added with the chalcone to yield a TMS enol ether
(29%), which was hydrolysed to give the conjugate adduct (79%).
Cyclisation of the conjugate adducts 3, bearing the vari-
ous spectator groups, to give the tetralones 4 was then
studied. Tetralones of this type have frequently been used
as intermediates for lignan synthesis.1 It was hoped that
treatment of the benzyl sulfoxides 2 with Lewis acids
would result in cleavage of the C–S bonds to generate
benzylic carbocations. Murphy and Wattanasin had
shown that carbocations of this type, obtained from cyclo-
propylketones, did cyclise to give tetralones.12 Following
this precedent, the sulfoxides were treated with SnCl4 in
nitromethane (Table 2).13 Use of 2 molar equivalents of
SnCl4 at 50 °C resulted in conversion of the tert-butyl 4-
methoxybenzyl sulfoxide 3b into the tetralone 4b in high
yield. The product was formed as the trans isomer
(J1,2 = 11 Hz) with complete diastereoselectivity. The cor-
responding p-tolyl sulfoxide gave a lower yield and the
2,4-dimethoxyphenyl analogue gave a mixture of prod-
ucts from which the tetralone was not isolated. In line with
Murphy’s results, the unsubstituted benzyl sulfoxide 3a,
gave a very poor yield of tetralone 4a, accompanied by an
inseparable mixture of hydroxy ketone 8a (ca. 20%, one
diastereoisomer) and dihydrofuran 9a (ca. 25%,
Scheme 2). Thus, the presence of an electron-donating
substituent capable of stabilising the benzylic carbocation
is an essential requirement in these cyclisations. The 2-py-
ridylsulfinyl group was easily cleaved from adduct 3f,
even at 0 °C, but no tetralone was formed at this tempera-
O
Ph
Ar1
SnCl4
3
+
O
Ar1
Ar2
+
Ph
Ar2
6
7
H2O
H2O
-H+
O
Ph
Ar1
HO
SnCl4
4
MeNO2
50 °C
Ar2
Ar1
Ph
O
Ar2
8
9
6a–9a Ar1 = Piperonyl, Ar2 = Ph
6b–9b Ar1 = Piperonyl, Ar2 = 4-MeOC6H4
Scheme 2
Synlett 2002, No. 9, 1404–1408 ISSN 0936-5214 © Thieme Stuttgart · New York

1406
Z. Appelbe et al.
LETTER
Ph
Table 3 Two-step Annulation Sequence
SnCl4
MeNO2
3f
4b + 8b + 9b +
Alkene
Sulfoxide Adduct
Yield
Cyclisation Yield
C6H4OMe
SPy
Ar
O
Product
13a
13a
13b
13b
16
10
11a
11a
11b
11b
14
1b
1d
1b
1d
1g
1b
1d
12a
12b
12c
12d
15
74%
62%
76%
55%
53%
72%
60%c
74%
Scheme 3
<50%a
72%
A number of variations on the two-step annulation proce-
dure were then studied (Scheme 4, Table 3). Both tert-bu-
tyl 4-methoxybenzyl sulfoxide 1a and the 2,4-
dimethoxyphenyl analogue 1d, were used, because very
little work had been carried out on the latter spectator
group. The additions to the unsaturated esters 11a,14
11b,15 14,16 and 1717 proceeded smoothly,9 with the tert-
butyl sulfoxide giving consistently higher yields than the
2,4-dimethoxyphenyl derivative. Both spectator groups
gave high diastereoselectivity (except for the addition of
1d to 17) and the relative configurations of the chiral cen-
tres and to the sulfoxide in the tert-butyl adducts were
assigned on the basis of our earlier work.2 In a significant
extension to the methodology, it was shown that the arene
nucleophile could also be introduced by alkylation of a
conjugate adduct. The enolate formed by conjugate addi-
tion to the alkoxy crotonate 14 was alkylated in situ to
give diastereomerically pure product 15 in 53% yield
(58% overall by a two-step conjugate addition, alkylation
procedure). The relative stereochemistry of the extra
chiral centre was assigned by analogy with earlier results,2
and by reference to the standard model for reactions of
<50%a
46%b
55%
17
18a
18b
19
17
19
<50%a
a Impure product.
b 2.0 Equiv of SnCl4 used.
c 1:1 Mixture of diastereoisomers.
enolates bearing adjacent chiral centres.18 The stereo-
chemistry of adduct 18a, in which an additional chiral
centre was created by diastereoselective protonation, was
assigned in the same way. These assignments were
strongly supported by the stereochemical assignments of
the cyclised products, as described below.
It was found that use of 1.2 molar equivalents of SnCl4
gave better results in the cyclisations of the esters 12, 15
and 18 (as compared with 2.0 equiv for the ketones 3).13
X
X
X
SnCl4
1
CO2Et
CO2Et
O
MeNO2
50 °C
S
C6H4OMe
CO2Et
C6H4OMe
13a X = H
R
11a X = H
12a X = H, R = t-Bu
11b X = OMe
13b X = OMe
12b X = H, R = 2,4-(MeO)2C6H3
12c X = OMe, R = t-Bu
12d X = OMe, R = 2,4-(MeO)2C6H3
1. ButSOCH2Ar
MeO2C
MeO
MeO
CO2Me
OBn
MeO
MeO
CO2Me
OBn
SnCl4
LDA, THF, -78 °C
MeNO2
50 °C
2. ArCH2Br
-78 to 20 °C
O
S
BnO
Ar
But
14
15
OMe
OMe
16
CO2Me
Ph
CO2Me
CO2Me
SnCl4
1
Ph
MeNO2
50 °C
C6H4OMe
Ph
O
S
C6H4OMe
R
17
18a R = t-Bu
18b R = 2,4-(MeO)2C6H3
19
Scheme 4
Synlett 2002, No. 9, 1404–1408 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Stereoselective Synthesis of Tetralins and Indanes
1407
Although the 2,4-dimethoxyphenyl sulfoxides 12b and
12d cyclised efficiently, purification of the products
proved very difficult because of persistent contamination
with the sulfur-containing by-products. For this reason,
the use of tert-butyl sulfoxides was again preferred. For-
mation of the tetralins 13a and 13b both proceeded in
good yield, showing that the presence of an activating
group in the arene is not necessary. The trans stereochem-
istry of the 1,2-disubstituted tetralins 13a and 13b was de-
duced from the 1H NMR (J1,2 = 8.5 and 8.2 Hz,
respectively). The trisubstituted tetralin 16 was obtained
in moderate yield, but the optimised conditions had not
been developed at that stage. In this case, J1,2 was found to
be 3.2 Hz, which indicated 1,2-cis-stereochemistry. How-
ever, the correlations found in a NOESY spectrum were
consistent only with the 1,2-trans, 2,3-cis stereochemis-
try. The NOESY data showed that the small J1,2 value
arose from a preference for a half-chair conformation in
which the 1-aryl and the 2-methoxycarbonyl groups were
pseudoaxial. Durst and co-workers noted a surprisingly
low coupling constant for a closely related trisubstituted
tetralin and interpreted their results in the same way.19 Te-
tralin 16 has the carbon skeleton and the oxygenation pat-
tern found in several lignans. Finally, indane 19 was
obtained by cyclisation of adduct 18a, showing that five-
membered rings can also be prepared using this method.
The coupling constants (J1,2 = 10.0 Hz, J2,3 = 10.3 Hz)
showed that the trans-trans product was formed.20 The
exclusive formation of 1,2-trans disubstituted products in
these cyclisations is not surprising, carbocations generat-
ed from other precursors react in the same way.1,11,12,21,22
References
(1) Ward, R. S. Nat. Prod. Rep. 1999, 16, 75; and earlier reviews
in the series.
(2) (a) Casey, M.; Manage, A. C.; Nezhat, L. Tetrahedron Lett.
1988, 29, 5821. (b) Casey, M.; Manage, A. C.; Gairns, R. S.
Tetrahedron Lett. 1989, 30, 6919. (c) Casey, M.; Gairns, R.
S.; Geraghty, G. M.; Kelly, C. J.; Murphy, P. J.; Walker, A.
J. Synlett 2000, 1721.
(3) Nakamura, S.; Watanabe, Y.; Toru, T. J. Org. Chem. 2000,
65, 1758; and references therein.
(4) Angle, S. R.; Arnaiz, D. O. J. Org. Chem. 1992, 57, 5937;
and references therein.
(5) Berkowitz, D. B.; Choi, S. J.; Bhuniya, D.; Shoemaker, R. K.
Org. Lett. 2000, 2, 1149.
(6) Casey, M.; Manage, A. C.; Murphy, P. J. Tetrahedron Lett.
1992, 33, 965.
(7) The t-butyl, p-tolyl and 2-pyridyl sulfoxides 1a,b,c,e,f were
prepared by reacting the thiols with the benzyl halides in
refluxing acetone in the presence of K2CO3, and oxidising
the resulting sulfides using NaIO4 in aq methanol. The 2,4-
dimethoxyphenyl p-methoxybenzyl sulfoxide 1d was
obtained from the reaction of p-methoxybenzylmagnesium
chloride with 2,4-dimethoxybenzenesulfinyl chloride,25 in
THF at 0 °C.
(8) Dauksas, V.; Gaidelis, P.; Petrauskas, O.; Udrenaite, S.;
Gasperaviciene, G.; Ragoutiene, N. Khim. Farm. Zh. 1987,
21, 569.
(9) Typical Procedure for Conjugate Addition: A solution of
the sulfoxide 1b (0.50 g, 2.22 mmol) in THF (12 mL) at
–78 °C was added dropwise via cannula to a solution of
LDA, formed from diisopropylamine (0.76 mL, 5.42 mmol)
and 2.5 M BuLi in hexanes (2.08 mL, 5.2 mmol) in THF (20
mL), at –78 °C. After 15 min, a solution of the ester 11a
(1.09 g, 5.34 mmol) in THF (4 mL) at –78 °C was added,
also via cannula. After a further 30 min, the reaction was
quenched with sat. aq NH4C1 (7 mL) and the mixture was
warmed to r.t. The suspension was poured into water (10
mL) and extracted with CH2Cl2 (3 30 mL). The combined
extracts were dried over MgSO4 and concentrated in vacuo.
The crude product was purified using flash column
chromatography on silica (1:1 petrol:ethyl acetate) to give
(RS)-ethyl 3-[(lSR, SRS)-tert-butylsulfinyl-(4-methoxy-
phenyl)methyl]-5-phenylpentanoate 12a, as an off white
solid (0.72 g, 1.68 mmol, 74%), mp 95–96 °C. IR (KBr):
2941, 1732, 1610, 1511, 1258, 1177, 1039 cm–1. 1H NMR
(CDCl3, 300 MHz): = 1.06 (s, 9 H, t-Bu), 1.23 (t, J = 7.2
Hz, 3 H, OEt), 1.60–1.80 (m, 2 H, H-4), 2.06 (dd, J = 10.8,
16.2 Hz, 1 H, H-2), 2.70–2.79 (m, 2 H, H-5), 2.94 (dd,
J = 3.5, 16.2 Hz, 1 H, H-2), 2.94–3.02 (m, partially
obscured, 1 H, H-3), 3.80 (s, 3 H, OMe), 4.04 (d, J = 3.5 Hz,
1 H, SCH), 4.09–4.13 (m, 2 H, OEt), 6.86 (d, J = 8.8 Hz, 2
H, H3 ,H5 ), 7.13–7.27 (m, 7 H, Ar-H). 13C NMR (CDCl3,
67.5 MHz): = 14.22 (OEt), 23.85 (C(CH3)3), 33.57 (C-5),
33.80, 35.56, 36.03 (C-3), 55.27 (OCH3), 55.70 (CMe3),
60.52 (OEt), 61.96 (SCH), 114.19 (C-3 ,C-5 ), 125.93 (CAr),
126.15 (CAr), 128.37 (CAr), 128.41 (CAr), 131.02 (C-2 , C-6 ),
141.87 (CAr), 159.31 (C-4 ), 172.35 (C=O). Anal. Calcd for
C25H34O4S: C, 69.77; H, 7.91; S, 7.44. Found: C, 69.85; H,
7.97; S, 7.80.
In conclusion, a novel annulation strategy has been devel-
oped and it has been applied to the preparation of a range
of tetralones, tetralins and indanes. While the method is
restricted to the preparation of 1-aryltetralins, this is the
substitution pattern required for lignan synthesis. The
method requires just two steps and is efficient and highly
diastereoselective. It takes advantage of the ‘chemical
chameleon’ properties of sulfoxides to (i) generate stabi-
lised carbanions, which give highly regioselective and
diastereoselective conjugate additions, and (ii) generate
carbocations which undergo stereoselective cyclisations.
It is the combination of these two reactions which is nov-
el, and which makes the present method so efficient and
versatile. While other functional groups could be used in
the same way,23 none seem as versatile as sulfoxides. Ra-
cemic sulfoxides were used throughout this study, but the
availability of an excellent method for the preparation of
enantiopure tert-butyl sulfoxides24 means that our strategy
could be used to obtain enantiopure products. Applica-
tions of this annulation method to the synthesis of lignans
are underway.
(10) (a) Ohno, A.; Higaki, M. Rev. Heteroatom. Chem. 1995, 13,
1. (b) Boche, G.; Lohrenz, J. C. W.; Cioslowski, J.; Koch,
W. In The Chemistry of Sulphur-Containing Functional
Groups; Patai, S.; Rappoport, Z., Eds.; Wiley: New York,
1993, 339.
Acknowledgement
We are grateful to University College Dublin, Enterprise Ireland,
and Westmeath County Council for financial support.
(11) Ziegler, F. E.; Schwartz, J. A. J. Org. Chem. 1978, 43, 985.
Synlett 2002, No. 9, 1404–1408 ISSN 0936-5214 © Thieme Stuttgart · New York

1408
Z. Appelbe et al.
LETTER
(1RS, 2SR, 3RS)-Methyl 3-(4-methoxyphenyl)-2-
(12) (a) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Perkin
Trans. 1 1982, 1029. (b) Murphy, W. S.; Wattansasin, S. J.
Chem. Soc., Perkin Trans 1 1982, 271. (c) Murphy, W. S.;
Wattanasin, S. J. Chem. Soc., Perkin Trans. 1 1981, 2920.
(13) Typical Procedure for Cyclisation: A solution of the
sulfoxide 12a (1.31 g, 3.04 mmol) in nitromethane (32 mL)
was cooled to 0 °C under N2. Tin tetrachloride (0.44 mL,
3.79 mmol) was added dropwise and the solution was heated
at 50 °C for 90 min. Aq NaOH (5%, 15 mL) was added, the
solution was extracted with CH2Cl2 (2 100 mL), and the
combined organic extracts were washed with water (2 80
mL). The organic layer was dried over MgSO4 and con-
centrated in vacuo. The crude product was purified using
flash column chromatography on silica (80:20 petrol:ethyl
acetate) to give (1RS, 2SR)-ethyl l-(4-methoxyphenyl)-
l,2,3,4-tetrahydro-2-naphthaleneacetate 13a, as a yellow
solid (705 mg, 2.18 mmol, 72%), mp 84–85 °C. IR (KBr):
2912, 1727, 1513, 1240, 1124, 1021, 809 cm–1. 1H NMR
(CDCl3, 300 MHz): = 1.22 (t, J = 7.0 Hz, 3 H, OEt), 1.57–
1.62 (m, 1 H, H-3), 2.02–2.08 (m, 1 H, H-3), 2.17 (dd,
J = 10.0, 16.7 Hz, 1 H, CHCO2Et), 2.36–2.43 (m, 2 H, H-2,
CHCO2Et), 2.90–2.99 (m, 2 H, H-4), 3.74 (d, J = 8.5 Hz,
1 H, H-1), 3.78 (s, 3 H, OCH3), 4.07 (q, J = 7.0 Hz, 2 H,
OEt), 6.74 (d, J = 7.6 Hz, 1 H, H-8), 6.82 (d, J = 8.8 Hz, 2 H,
H-3 , H-5 ), 6.96–7.04 (m, 3 H, H-5, H-2 , H-6 ), 7.06–7.11
(m, 2 H, H-6, H-7). 13C NMR (CDCl3, 75 MHz): = 14.25
(OEt), 27.06 (C-3), 28.51 (C-4), 38.94 (CH2CO2Et), 39.14
(C-2), 50.56 (C-1), 55.22 (OCH3), 60.21 (OEt), 113.76,
125.79, 125.83, 128.64, 130.33, 130.48, 136.58, 137.52,
139.17, 158.13, 172.99 (C=O). Anal. Calcd for C21H24O3: C,
77.78; H, 7.41. Found: C, 77.72; H, 7.53. MS (EI): m/z
(rel. intensity) = 324 (9) [M+], 236 (100), 201 (8), 121 (13),
29 (8).
phenylindan-1-carboxylate(19): IR (KBr): 2946, 1735,
1512, 1246, 1169, 1034, 744 cm–1. 1H NMR (CDCl3, 300
MHz): = 3.75 (s, 3 H, OMe), 3.76 (s, 3 H, OMe), 3.98
(apparent t, J = 10.3 Hz, 1 H, H-2), 4.35 (d, J = 10.0 Hz, 1 H,
H-3), 4.38 (d, J = 10.3 Hz, 1 H, H-1), 6.79 (d, J = 8.8 Hz, 2
H, Ar-H), 6.89 (dd, J = 1.2, 7.3 Hz, 1 H, H-7). 7.02 (d,
J = 8.8 Hz, 2 H, Ar-H), 7.20–7.30 (m, 7 H, Ar-H), 7.38 (1 H,
dd, J = 1.2, 7.0 Hz, Ar-H). 13C NMR (CDCl3, 75 MHz):
= 52.39 (C-2) 55.43 (OMe), 56.92 (OMe), 58.21, 59.78,
114.10, 124.06, 125.46, 127.14, 127.65, 128.2, 128.33,
128.73, 129.88, 134.61, 140.02, 141.21 146.05, 172.99.
(14) Kang, J.; Lim, G. J.; Yoon, S. K.; Kim, M. Y. J. Org. Chem.
1995, 60, 564.
(15) Unsaturated ester 11b was prepared by Wittig reaction of the
substituted cinnamaldehyde, obtained according to:
Browder, C. C.; Marmsaeter, F. P.; West, F. G. Org. Lett.
2001, 3, 3033.
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(1SR, 2RS, 3SR)-Methyl 7,8-dimethoxy-1-(3,4-
dimethoxyphenyl)-2-benzyloxymethyl-1,2,3,4-tetra-
hydronaphthalene-3-carboxylate(16): IR absorption: IR
(KBr): 3010, 2930, 1730, 1244, 1027 cm–1. 1H NMR
(CDCl3, 500 MHz): = 2.75 (1 H, m, H-2), 2.92 (ddd,
J = 3.0 5.5, 9.0 Hz, 1 H, H-3), 2.98–3.00 (m, 2 H, H2-4),
3.40–3.50 (m, 2 H, CH2OBn), 3.55 (s, 3 H, OCH3), 3.71 (s,
3 H, OCH3), 3.80 (s, 3 H, OCH3), 3.84 (s, 3 H, OCH3), 3.88
(s, 3 H, OCH3), 4.19 (d, J = 3.2 Hz, 1 H, H-1), 4.45 (d,
J = 12.1 Hz, 1 H, OCH2Ph), 4.47 (d, J = 12.1 Hz, 1 H,
OCH2Ph), 6.41 (dd, J = 2.1, 8.4 Hz, 1 H, Ar-H), 6.42 (1 H,
s, H-9), 6.61 (d, J = 2.1 Hz, 1 H, Ar-H), 6.64 (1 H, s, H-6),
6.73 (d, J = 8.4 Hz, 1 H, Ar-H). Anal. Calcd for C30H34O7: C,
71.2; H, 6.7. Found: C, 71.4; H, 6.4. MS (EI): m/z (rel.
intensity) = 506 (7) [M+], 385 (22), 325 (12), 91 (100).
(25) Bell, K. H. Aust. J. Chem. 1985, 38, 1209.
Synlett 2002, No. 9, 1404–1408 ISSN 0936-5214 © Thieme Stuttgart · New York