Asymmetric synthesis of 3(S),17-dihydroxytanshinone

Article abstract of DOI:10.1016/j.tet.2003.11.091

The first synthesis of 3(S),17-dihydroxytanshinone was achieved by ultrasound promoted Diels-Alder reaction of the protected 3-hydroxymethyl-4,5- benzofurandione with a vinylcyclohexene derivative. Bioassay showed that the synthetic 3(S),17-dihydroxytanshinone was active in vitro against HL-60 tumor cell line by MTT method.

Full text of DOI:10.1016/j.tet.2003.11.091

Tetrahedron 60 (2004) 1665–1669
Asymmetric synthesis of 3(S),17-dihydroxytanshinone
*
Jiangang Zhang, Wenhu Duan and Junchao Cai
Shanghai Institute of Materia Madica, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China
Received 16 July 2003; revised 28 October 2003; accepted 25 November 2003
Abstract—The first synthesis of 3(S),17-dihydroxytanshinone was achieved by ultrasound promoted Diels–Alder reaction of the protected
3-hydroxymethyl-4,5-benzofurandione with a vinylcyclohexene derivative. Bioassay showed that the synthetic 3(S),17-dihydroxytanshinone
was active in vitro against HL-60 tumor cell line by MTT method.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
Danshen diterpene quinones exhibit significant cytotoxicity
against various tumor cell lines.1 It is notable that the extract
of Dan Shen showed higher activities than the pure natural
products.2 This has led to more intensive search for minor
active metabolites.3 3,17-Dihydroxytanshinone 1 was
isolated from the roots of Salvia bians Royle ex Benth.
(Labiatae), a native of the Kumaon Himalayan glaciers.4 It
is one of the three known tanshinone diterpene natural
products bearing 17-hydroxyl group. However, the authors
did not report its absolute configuration and biological
activities. Lee and co-workers reported that the absolute
stereochemistry of 3-hydroxytanshinone 2, another natural
product isolated from the same plant as 1, was S.5 According
In this paper, we described an asymmetric synthesis of
compound 1.
2. Result and discussion
to biosynthesis, 3(S),17-dihydroxytanshinone is likely to be
the natural one. Its unusual structure and potential biological
properties combined to make the compound a challenging
synthetic target.
The retro-synthesis of compound 1 was shown in Scheme 1.
The Diels–Alder approach to tanshinone diterpenes was
widely employed. Indeed, Lee and co-workers5 reported the
Scheme 1.
Keywords: Natural product; Antitumor; Tanshinone diterpene; Dihydroxytashinone; Diels–Alder cycloaddition; Ultrasound; Total synthesis.
*
Corresponding author. Tel./fax: þ86-21-50806032; e-mail address: whduan@mail.shcnc.ac.cn
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.11.091

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J. Zhang et al. / Tetrahedron 60 (2004) 1665–1669
Scheme 2. Conditions: (a) Baker’s yeast, 25 8C, 18 h, 70%; (b) 1.2 equiv. TBSCl, 1.5 equiv. imidazole, DMF, 25 8C, overnight, 91%; (c) 5 equiv.
vinylmagnesium bromide, THF, 0 8C, 2 h; (d) 0.01 equiv. p-toluenesulfonic acid, 10 equiv. MgSO4, toluene, reflux, 30 min, 42% two steps.
syntheses of some tanshinone diterpene natural products by
ultrasound-promoted Diels–Alder cycloaddition. However,
there were few reports on the synthesis of tanshinone
diterpenes bearing 17-hydroxyl group.6
with a synthetic route (Scheme 3) reported by Robins et al. 8
Robin’s synthesis of 11 was completed in three steps: first,
hydrolysis of benzofuran-2,3-dicarboxylate 8 to give
benzofuran-2,3-dicarboxylic acid 9, and then selective
decarboxylation of 2-carboxyl group to benzofuran
3-carboxylic acid 10 and finally esterification of carboxylic
acid 10 to afford 11 (Scheme 3).
The diene 3 was synthesized from 2,2-dimethyl-1,
3-dicyclohexanone 5. The starting material 5 was reduced
by baker’s yeast (70% yield, and .95% ee). Then the
hydroxyl group was protected with t-butyldimethylsilyl
(TBS) according to the conventional procedure to give
ketone 6, the analytical data (including optical rotation) of 6
was identical with that of product in literature.7 The
stereochemistry at C3 of ketone 6 was then assigned to be
‘S’ as reported in literature. To avoid harsh conditions in
synthesis of diene 3 reported by Lee and co-workers in
which LDA-mediated triflation, palladium-catalyzed
coupling and use of highly toxic tri-n-butylstannane were
involved, we resorted to a tertiary alcohol dehydration
approach. Ketone 6 was treated with vinylmagnesium
bromide to give tertiary alcohol 7 in 70% yield. Elimination
of the hydroxyl group to form diene was problematic due to
acid-sensitive TBS group. After failure with reagents such
as MsCl–Et3N, pyridine–SOCl2, and p-toluenesulfonic
acid, diene 3 was prepared by refluxing 7 with excessive
dry magnesium sulfate in the presence of catalytic amount
of p-toluenesulfonic acid (Scheme 2). The analytical data
including optical rotation of diene 3 were identical with that
of product in literature.5 So, the diene 3 possessed S
configuration as reported in literature.
Although the author reported a moderate yield in mono-
decarboxylation step, we found that the monodecarboxyl-
ation was affected by several factors such as reaction
temperature, the quantity of copper, the activation of
copper, particle size of copper, and stirring condition, etc.
the reaction often encountered either sluggish mono-
decarboxylation or rapid decarboxylation of two carboxyl
groups. We managed to prepare monocarboxylate 11 in a
more efficient way (Scheme 4). The 2-carboxylate group of
dicarboxylate 8 was selectively hydrolyzed to carboxylic
acid 12 when 8 upon reaction with 1 equiv. of sodium
hydroxide in ethanol. Then, the 2-carboxyl group of 12
underwent decarboxylation in the presence of copper
powder in quinoline at 200 8C to give monocarboxylate 11
in 70% overall yield.9 3-Hydroxylmethyl-5-hydroxybenzo-
furan 13 was then prepared from 3-carboxylate 11 by
debenzylation with Pd-catalyzed hydrogenation, and sub-
sequent reduction with LiAlH4 according to our previous
work.6 Cycloaddition of freshly prepared o-quinone 4a from
13 with Fremy’s salt with diene 3 was attempted with
ultrasonic irradiation to achieve 14, no cycloaddition
product was formed and o-quinone 4a was decomposed.
This result was in accordance with our previous findings that
o-quinone 4a was very sensitive to temperature, acidic, and
With the diene 3 at hand, the next step is to synthesize
o-quinone 4, of which compound 11 is the key intermediate,
Scheme 3. Conditions: (a) NaOH, EtOH, reflux; (b) Cu powder quinoline, 2 h, 200 8C; (c) SOCl2, EtOH.

J. Zhang et al. / Tetrahedron 60 (2004) 1665–1669
1667
Scheme 4. Conditions:(a) 1 equiv. NaOH, EtOH, 2 h, rt; (b) Cu powder, quinoline, 2 h, 200 8C, 70% in two steps; (c) H2/10% Pd–C, EtOH, 16 h, rt; (d)
5 equiv. LiAlH4, THF, 10 h, 25 8C; (e) Fremy’s salt, KH2PO4 buffer; (f) 3 equiv. 3, ultrasonic, 6 h, 5 8C; (g) 1.5 equiv. DDQ, benzene, 10 h, reflux.
basic condition. It is unstable after standing in room
temperature for several hours. The instability of o-quinone
4a in fact caused a low overall yield in synthesis of
Przewaquinone A.6 Alternatively, the hydroxyl groups of 13
was protected as its TBS ether.(Scheme 5). The phenolic
silyl ether was then selectively cleaved to give 15 upon
reflux with potassium carbonate in ethanol (80% yield in
two steps).10 Oxidation of 15 to o-quinone 4b with Fremy’s
salt was also troublesome. There was no reaction in aqueous
methanol and aqueous acetone as the solvents. Finally, the
oxidation of 15 to 4b was achieved with modified phase
transfer reaction pioneered by Kende.11 Compound 16, the
precursor of 1, was obtained after 3 and 4b were subjected to
ultrasonic irradiation at 5 8C for 6 h followed by aromatiza-
tion with DDQ. Since the stereochemistry of 3 determined
the stereochemistry of 16, the absolute configuration of 16
was ‘S’ as in compound 3. Finally, removal of the TBS
protective groups with 15% hydrogen fluoride in aceto-
nitrile12 gave the target molecule, 3(S),17-dihydroxy-
tanshinone, [a]2D0 2108 (acetone, c¼0.4). The data of H
1
NMR, IR, MS, and melting point are identical with that of
the natural product.4
In vitro cytotoxic activity of compound 1 on tumor lines was
evaluated by MTT and SRB method, the synthetic 3(S),17-
dihydroxytanshinone was active against HL60 cell line, the
inhibition rate is 62% at 3 mM.
3. Conclusions
We successfully used ultrasound-promoted Diels–Alder
cycloaddition to develop a first, concise total synthesis of
optically active 3(S),17-dihydroxytanshinone (1). Chemical
Scheme 5. Condition: (a) 3 equiv. TBSCl, 5 equiv. Imidazole, DMF, 16 h, 25 8C; (b) 1.5 equiv. K2CO3, 5 equiv. H2O, EtOH, reflux, 80% in two steps;
(c) 5 equiv. Fremy’s salt, 10 equiv. TBABr, CH2Cl2, KH2PO4 buffer, 18 h, 0 8C; (d) 3 equiv. 3, ultrasonic, 6 h, 5 8C; (e) 1.5 equiv. DDQ, benzene, 10 h, reflux,
28% in three steps; (f) 15% HF, CH3CN, 3 h, 25 8C, 85%.

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J. Zhang et al. / Tetrahedron 60 (2004) 1665–1669
synthesis and biological investigations of the analogues of
this natural product are in progress.
NaOH (0.108 g, 2.7 mmol) in ethanol (14 mL) was added
dropwise. After stirring for 2 h, the solution was acidified
with HCl (2 M) to pH¼4. Ethanol (40 mL) was removed
under reduced pressure. The resultant residue was added
with water (10 mL), the precipitate formed was collected by
filtration, and washed with cold ethanol to give 12 (0.83 g,
2.4 mmol, 90% yield) as a white solid: mp 132–134 8C; IR
(KBr): 2984, 1749 cm21; 1 H NMR (CDCl3, 400 Hz, TMS):
d 1.52 (t, 3H, J¼7.1 Hz), 4.61 (q, 2H, J¼7.1 Hz), 5.16 (s,
2H), 7.24 (dd, 1H, J¼9.3, 2.6 Hz), 7.35–7.48 (m, 5H), 7.49
(d, 1H, J¼2.6 Hz), 7.59 (d, 1H, J¼9.3 Hz) ppm. EIMS
(m/z): 340 (Mþ). HRMS 340.0963, calcd for C19H16O6,
340.0947.
4. Experimental
4.1. General
All moisture sensitive reactions were carried out under
nitrogen atmosphere All reagents were purchased from
Shanghai Chemical Reagent Company and Acros, and were
used without further purification unless otherwise stated.
Melting points were uncorrected. Infrared spectra were
recorded on a Nicolet Magna 750 spectrometer and only
characteristic absorptions were reported. The 1H NMR
spectra were measured with a Bruker AM-400 (400 MHz)
spectrometer. 13C NMR spectra were measured with an
AM-400 (100 MHz) spectrometer. Coupling constants
(J values) were reported in Hertz. Chemical shifts were
expressed in ppm, using residual solvent as an internal
standard. Mass spectra (medium and high resolution) were
run on Varian MAT-711 and MAT-95 spectrometers. All
solvents were purified and dried prior to use according to
standard procedures.13 ‘Petroleum ether’ referred to
petroleum ether bp, 60–90 8C.
4.2.3. 5-Benzyloxy-benzofuran-3-carboxylic acid ethyl
ester (11). Compound 12 (1.00 g, 2.94 mmol), copper
powder (30 mg, 0.47 mmol) and quinoline (5 mL) were
added to a flask. After stirring at 200 8C for 1 h, the mixture
was cooled to room temperature. The solution was acidified
with conc. HCl (16 mL), and extracted with ether
(3£30 mL). The combined extract was washed, respect-
ively, with water (3£30 mL), saturated NaHCO3 solution
(30 mL) and brine (30 mL), and dried over Na2SO4. After
evaporation of the solvent in vacuo, the residue was purified
by flash chromatography on silica gel eluting with
petroleum ether/ethyl acetate (10:1) to give 11 (0.694 g,
2.36 mmol, 80% yield) as a white crystal: mp 64–66 8C; IR
4.2. Synthesis
1
(KBr): 1720 cm 21; H NMR (CDCl3, 400 MHz, TMS): d
1.39 (t, 3H, J¼7.1 Hz), 4.38 (q, 3H, J¼7.1 Hz), 5.12 (s, 2H),
7.02 (dd, 1H, J¼9.2, 2.7 Hz), 7.35–7.50 (m, 6H), 7.59 (d,
1H, J¼2.7 Hz), 8.20 (s, 1H) ppm. EIMS (m/z): 296 (Mþ).
Anal. Calcd for C18H16O4: C, 72.96%; H, 5.44%. Found: C,
73.20%; H, 5.47%.
4.2.1. (2)-(S)-3-(tert-Butyldimethylsilyloxy)-2,2-
dimethyl-1-vinylcyclohexene (3). A solution of 6 (2.00 g,
7.8 mmol) in anhydrous THF (50 mL) was cooled to 0 8C,
vinylmagnesium bromide (1.0 M in THF, 39 mL, 39 mmol)
was then added dropwise, and the reaction mixture was
stirred at 0 8C for 2 h. The reaction was quenched with
saturated NH4Cl (50 mL), and the aqueous layer was
extracted with ether (3£30 mL). The combined organic
layer was washed with saturated NaHCO3 solution (50 mL)
and brine (50 mL), dried over Na2SO4, and filtered. The
solvent was removed in vacuo, and the residue was purified
by flash chromatography on silica gel (petroleum ether/ethyl
acetate, 40:1) to give 7 (1.60 g), as a mixture of
diastereomers. Then 7 was dissolved in dry toluene
(80 mL). MgSO4 (10 g, 83 mmol) and p-toluenesulfonic
acid (9 mg, 0.4 mmol) were added. Then the mixture was
refluxed for 30 min, and cooled to room temperature.
MgSO4 was then filtered off, the filtrate was washed with
saturated NaHCO3 solution (30 mL) and brine (30 mL),
dried over MgSO4, and filtered. The solvent was removed in
vacuo and the residue was purified by flash chromatography
on silica gel eluting with petroleum ether to afford 3 as a
colorless oil (0.873 g, 42% from 6): [a]2D0 214.68 (lit.5
4.2.4. 3-Hydroxymethyl-benzofuran-5-ol (13). A mixture
of 11 (1.20 g, 4.05 mmol) and 10% palladium on carbon
(0.2 g) in ethanol (100 mL) was hydrogenated at room
temperature under hydrogen (1 atm) for 16 h. Then, the
catalyst was filtered-off, and the solvent was removed in
vacuo. The residue was dissolved in anhydrous THF
(40 mL) under N2, and added dropwise to a mixture of
LiAlH4 (0.77 g, 20.1 mmol) in THF (40 mL) at room
temperature. After stirred for 10 h, ethyl acetate (20 mL)
was added to consume the residual LiAlH4, then HCl (2 M,
40 mL) was added to the reaction mixture. The aqueous
layer was then separated and extracted with ether
(3£30 mL). The combined organic layer was washed with
saturated NaHCO3 solution (40 mL) and brine (40 mL),
dried over Na2SO4 and filtered. The solvent was evaporated
to dryness, and the residue was purified by flash chroma-
tography on silica gel eluting with petroleum ether/acetone
(1:1) to give 13 (0.553 g, 3.36 mmol, 83% yield) as a white
215.08); IR (KBr): 2956, 2856, 1471, 1362, 1256, 1092,
1007, 879, 737, 773 cm21
1
crystal: mp 135–136 8C; IR (KBr) 3409, 3201 cm21; H
1
;
H NMR (CDCl3, J¼400 Hz,
NMR (400 Hz, DMCO-d6, TMS): d 4.70 (s, 2H), 6.84 (dd,
1H, J¼8.8, 2.6 Hz), 7.11 (dd, 1H, J¼2.6 Hz), 7.30 (d, 1H,
J¼8.8 Hz), 7.67 (s, 1H) ppm. EIMS (m/z): 164 (Mþ). Anal.
calcd for C9H8O3: C, 65.85%; H, 4.91. Found: C, 66.01%;
H, 4.91%.
TMS): d 0.05 (s, 3H), 0.06 (s, 3H), 0.9 (s, 9H), 0.98 (s, 3H),
1.01 (s, 3H), 1.64–1.68 (m, 2H), 2.01–2.20 (m, 2H), 3.53
(dd, 1H, J¼6.3, 6.3 Hz), 4.93 (dd, 1H, J¼10.7, 1.9 Hz), 5.27
(dd, 1H, J¼17.0, 1.9 Hz), 5.69 (dd, 1H, J¼3.6, 3.6 Hz), 6.29
(dd, 1H, J¼17.0, 10.7 Hz) ppm. EIMS (m/z): 266 (Mþ).
HRMS 266.2060, calcd for C16H30SiO, 266.2066.
4.2.5. 3-(tert-Butyldimethylsilyloxymethyl)-benzofuran-
5-ol (15). To a solution of 13 (0.630 g, 3.84 mmol), and
imidazole (1.30 g, 19.4 mmol) in anhydrous DMF (10 mL)
was added a solution of TBSCl (1.74 g, 11.5 mmol) in
4.2.2. 5-Benzyloxy-benzofuran-2,3-dicarboxylic acid
3-ethyl ester (12). Compound 8 (1.00 g, 2.7 mmol) was
dissolved in ethanol (50 mL) at room temperature, and

J. Zhang et al. / Tetrahedron 60 (2004) 1665–1669
1669
anhydrous DMF (8 mL). The resulting solution was stirred
at room temperature for 24 h. NaHCO3 solution (5%,
50 mL) and ether (60 mL) was added, and the aqueous layer
was separated and extracted with additional ether
(3£30 mL). The combined ether layer was washed with
brine (30 mL), dried with Na2SO4, and filtered. The solvent
was removed in vacuo, the residue was purified by flash
chromatograph on silica gel eluting with petroleum ether/
ethyl acetate (80:1) to afford a colorless oil. This oil was
dissolved in ethanol (32 mL), to which water (0.33 mL,
18 mmol) and K2CO3 (0.560 g, 4.06 mmol) were added.
The resultant mixture was heated to reflux for 12 h. Then the
reaction mixture was cooled to room temperature, and
filtered. The filtrate was evaporated to dryness. The residue
was purified by flash chromatograph on silica gel eluting
with petroleum ether/ethyl acetate (20:1) to give 15
(0.854 g, 3.07 mmol, 80% yield) as a white crystal: mp
72–74 8C; IR (KBr) 3244, 2955, 2854, 1462, 1217, 1070,
924, 845 cm21; 1H NMR (CDCl3, 400 MHz, TMS): d 0.1 (s,
6H), 0.9 (s, 9H), 4.8 (s, 2H), 6.79 (dd, 1H, J¼8.8, 2.6 Hz),
6.89 (1H, d, J¼2.6 Hz), 7.30 (1H, d, J¼8.8 Hz), 7.49 (1H,
s) ppm. EIMS (m/z): 278 (Mþ); HRMS 278.1344, calcd for
C15H22SiO3, 278.1338.
40.6, 57.5, 74.8, 117.2, 120.7, 126.0, 127.3, 127.6, 133.8,
141.8, 143.6, 150.0, 162.1, 175.1, 183.3 ppm. EIMS (m/z):
554 (Mþ). HRMS 554.2892, calcd for C31H46Si2O5,
554.2884.
4.2.7. (2)-3(S),17-Dihydroxytanshinone 1. Silyl ether 16
(30 mg, 0.054 mmol) was dissolved in a solution of 40%
aqueous HF/CH3CN (20 mL, 1:4, v/v) and stirred at room
temperature for 3 h. Water (20 mL) was then added, and the
mixture was extracted with ethyl acetate (3£20 mL). The
combined organic layer was washed with saturated
NaHCO3 (20 mL) and brine (20 mL), dried over Na2SO4,
and filtered. The solvent was removed in vacuo. The residue
was purified by flash chromatography on silica gel eluting
with CH2Cl2/CH3OH (20:1) to give 1 (15 mg, 0.46 mmol,
85% yield) as red crystals: mp 208–210 8C (lit. 209–
210 8C);4 [a]2D0 210 (c 0.4, acetone); IR (KBr): 3553, 3045,
1673, 1658, 1383, 1365, 840 cm21 1H NMR (CDCl3,
;
400 MHz, TMS): d 1.32 (s, 3H), 1.35 (s, 3H), 2.15–2.29 (m,
2H), 3.32–3.45 (m, 2H), 3.96 (dd, 1H, J¼8.6, 2.8 Hz), 4.70
(s, 2H), 7.33 (s, 1H), 7.50 (d, 1H, J¼8.3 Hz), 7.63 (d, 1H,
1
J¼8.3 Hz); H NMR (DMSO-d6, 400 MHz, TMS): d 1.19
(s, 3H), 1.22 (s, 3H), 1.64–1.78 (m, 1H), 1.82–1.88 (m,
1H), 2.98–3.07 (m, 1H), 3.18–3.26 (m, 1H), 3.52 (dd, 1H,
J¼8.8, 2.6 Hz), 4.55 (s, 1H), 7.56 (d, 1H, J¼8.1 Hz), 7.73
(s, 1H), 7.76 (d, 1H, J¼8.1 Hz) ppm; 13C NMR (DMSO-d6,
100 MHz): d 25.3, 26.2, 26.5, 29.1, 54.6, 72.1, 118.3, 120.4,
126.0, 126.8, 126.9, 134.0, 142.4, 142.5, 149.7, 161.0,
174.7, 182.5 ppm. EIMS (m/z): 326 (Mþ). HRMS 326.1155,
calcd for C19H18O5, 326.1154.
4.2.6. Oxidize 15 to 3-(tert-butyldimethylsilyloxy
methyl)-benzofuran-4,5-dione and cycloaddition 3 with
4b to (1)-3(S),17-dihydroxytanshinone di-tert-butyl-
dimethylsilyl ether (16). A solution of 15 (50 mg,
0.18 mmol) and TBABr (579 mg, 1.8 mmol) in CH2Cl2
(20 mL) were cooled to 0 8C in an ice bath, and an ice-
cooled aqueous solution of Fremy’s salt (300 mg dissolved
in 20 mL of 0.1 M KH2PO4 buffer adjusted to pH 7) was
added dropwise. After the addition, the solution was stirred
at 0 8C for 18 h. The aqueous layer was separated and
extracted with CH2Cl2 (3£20 mL). The combined organic
phase was washed with water (2£20 mL) and brine
(3£20 mL), over Na2SO4. The solvent was removed under
reduced pressure to afford crude 4b as a red oil, which was
unstable at room temperature. Crude 4b was quickly used in
next step without purification. A mixture of crude 4b and 3
(144 mg, 0.54 mmol) in anhydrous methanol (0.2 mL) was
subjected to ultrasonic irradiation at 5 8C for 6 h. Methanol
was then removed in vacuo, and the residue was passed
through a silica gel plug, eluting initially with petroleum
ether to recover unreacted 3 (101 mg, 70% recovery), and
then with CH2Cl2 to give a mixture of aromatized and
dihydro-adducts. This mixture was fully aromatized by
refluxing in benzene (5 mL) with DDQ (62 mg, 0.27 mmol)
for 10 h. Then the solution was purified by flash chroma-
tography on silica gel eluting with petroleum ether/ethyl
acetate (8:1) to give 16 as a red crystal (34 mg, 0.06 mmol,
30% yield): mp 184–186 8C; [a]2D0 þ10 (c 0.4, CHCl3); IR
(KBr) 2955, 2856, 1697, 1677, 1471, 1387, 1082,
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1
849 cm21; H NMR (CDCl3, 400 MHz, TMS): d 0.06 (s,
3H), 0.10 (s, 3H), 0.12 (s, 6H), 0.88 (s, 9H), 0.94 (s, 9H),
1.26 (s, 3H), 1.29 (s, 3H), 1.80–1.85 (m, 1H), 1.86–2.00
(m, 1H), 3.18–3.24 (m, 1H), 3.31–3.40 (m, 1H), 3.70 (dd,
1H, J¼8.8, 2.9 Hz), 4.87 (d, 1H, J¼1.5 Hz), 7.41 (t, 1H,
J¼1.5 Hz), 7.59 (d, 1H, J¼8.2 Hz), 7.64 (d, 1H,
J¼8.2 Hz) ppm; 13C NMR (CDCl3, 100 MHz): d 25.3,
24.8, 24.0, 18.2, 18.4, 25.9, 25.96, 25.98, 26.8, 26.9, 29.3,
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