Total synthesis of (±)-lantalucratins A and B by CAN-mediated oxidative cyclization

Article abstract of DOI:10.1016/j.tet.2013.09.081

The first total synthesis of (±)-lantalucratins A and B is described. Introduction of an alkyl side chain at the 6-position was proceeded by directed ortho-lithiation and subsequent alkylation reaction to afford 6-alkyl-5,7,8-trimethoxy-1-naphthol as a sy

Full text of DOI:10.1016/j.tet.2013.09.081

Tetrahedron 69 (2013) 10470e10476
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Total synthesis of (ꢀ)-lantalucratins A and B by CAN-mediated
oxidative cyclization
Tokutaro Ogata, Yoshiko Sugiyama, Saki Ito, Kazuha Nakano, Eri Torii, Arisa Nishiuchi,
*
Tetsutaro Kimachi
School of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68 Koshien Kyu-bancho, Nishinomiya 663-8179, Hyogo, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 August 2013
Received in revised form 21 September 2013
Accepted 26 September 2013
Available online 3 October 2013
The first total synthesis of (ꢀ)-lantalucratins A and B is described. Introduction of an alkyl side chain at
the 6-position was proceeded by directed ortho-lithiation and subsequent alkylation reaction to afford
6
-alkyl-5,7,8-trimethoxy-1-naphthol as a synthetically important intermediate for (ꢀ)-lantalucratins A
and B in excellent yield with complete regioselectivity. The 1,2-naphthoquinone fused five-membered
cyclic ether framework was constructed directly from 3-hydroxyalkyl-naphthalenes by oxidative intra-
molecular cyclization reaction with diammonium cerium(IV) nitrate. (ꢀ)-Lantalucratins A and B were
obtained in 69% and 45% overall yields, respectively.
Keywords:
Total synthesis
Oxidative cyclization
Diammonium cerium(IV) nitrate
Naphthoquinone
Ó 2013 Elsevier Ltd. All rights reserved.
Natural product
Directed ortho-lithiation
1
. Introduction
1
2
1
0
1
1
4
12
10
R
O
2
Biologically active natural products containing the naph-
thoquinone skeleton have been widely found in extensive regions
around the world from many years ago. Recently, lantalucratins
and related compounds were isolated from rainforest plants such
as Lantana involucrata, and they were found to possess cytotoxic
O
R
3
8
9
3
2
9
9b
5
3
9b
3
a
11
4
8
7
3
a
7
OH
3
1
4
R2
4
6
5
R2
OCH
6
O
R1
O
R1
O
1
2
1
2
3
2
Lantalucratin A ( ): R =OCH
1
3
, R =H
2
D ( ): R =OCH
1
3
, R =H, R =H, R =H
E ( ): R =OCH , R =H, R =H, R =OH
3
F ( ): R =H, R =OCH , R =OH, R =OH
3
activity against various human tumor cell lines. Among the
2
3
4
B ( ): R =OH, R =H
naphthoquinone derivatives, lantalucratins AeC consist of 1,2-
naphthoquinone including the cyclic ether moiety as a central
backbone and having an oxygen function at the 6- or 7-position
1
2
1
2
3
4
C ( ): R =H, R =OH
1
2
Dehydroiso- -lapachone: R =H, R =H
Fig. 1. Biologically active naphthoquinone derivatives: lantalucratins AeF.
(Fig. 1). Other lantalucratins DeF have a 1,4-naphthoquinone
skeleton bearing a 3-(hydroxyalkyl) side chain with an oxygen
function at the aromatic ring. Although the structure of these
compounds has been determined by 2D NMR spectroscopic anal-
ysis and X-ray crystallographic analysis, as reported by Lee and co-
workers, their absolute configuration at the stereogenic C2 carbon
centers were not specified, and there has been no report of the
synthesis of these compounds. In our previous report, we demon-
strated the asymmetric synthesis of the natural product (R)-
During the study, we found that the 1,2-naphthoquinones
fused five-membered cyclic ether (dihydrofuranyl) moieties,
which could be directly constructed from 3-(hydroxyalkyl)-
1
,2,4-trimethoxynaphthalenes by exposure to diammonium
4
cerium(IV) nitrate (CAN) in high yields with good regiose-
lectivities. We expected that the CAN-mediated oxidative cycli-
zation method could be applied to the synthesis of
lantalucratins. Moreover, we considered that the convenient
synthesis of these compounds could be achieved if the oxygen
functional group could be appropriately introduced. Herein, we
describe the first, short step total synthesis of (ꢀ)-lantalucratins
A and B.
(
ꢁ)-dehydroiso-
b-lapachone that possesses the same structural
3
a
backbone as lantalucratins AeC except for the oxygen functions.
*
Corresponding
author.
E-mail
address:
tkimachi@mukogawa-u.ac.jp
(
T. Kimachi).
0
040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.09.081

T. Ogata et al. / Tetrahedron 69 (2013) 10470e10476
10471
2
2
. Results and discussion
bromide afforded the alkylated product 7a in excellent yield. The
regioselectivity of the directed ortho-lithiation reaction was abso-
lutely controlled; it might be explainable by the coordination
property difference with the lone pair at the oxygen atoms of 6.
First, the deprotonation of compound 5 proceeds at the hydroxyl
group, and the subsequent second deprotonation at the aromatic
ring occurs to generate a dianion intermediate 6. In the latter
process, the deprotonation reaction occurs at the C6 position in
preference to the C2 position, because the C6 position is sur-
rounded by two methoxy groups, and a stronger coordination effect
can be obtained than at the C2 position. In addition, the deproto-
.1. Retrosynthetic analysis of (± ±)lantalucratins A and B
Initially, we planned the synthetic route to the target com-
pounds 1a and 1b as shown in Scheme 1.
The fused five-membered cyclic ether moiety of the lantalucra-
tins (I) can be constructed by CAN-mediated oxidative intra-
molecular cyclization from 3-(hydroxyalkyl)-1,2,4-trimethoxyn
aphthalenes (II). This seems to be the most reliable and effective
method for creating the dihydrofuranyl-1,2-naphthoquinone skel-
etons. The hydroxyalkyl fragment connecting at the C3 position of
compound II is introduced by directed ortho-lithiation5 of naph-
thalenes (III) and subsequent alkylation reaction. Compounds (III),
regarded as the ‘reduced naphthoquinone equivalent’, are synthe-
sized by benzyne-mediated [4þ2] cycloaddition reaction starting
from 1,2,4-trimethoxybenzene (IV).
7
nation reaction hardly occurs at the C2 position, probably because
electrical repulsion exists between the hydroxyl anion and the
butyl anion of n-butyllithium when the deprotonation occurs at the
C2 position. Although there is a possibility that the deprotonation
reaction by alkyllithium reagent also occurs potentially at the C4
position, actually, the lithiation occurred selectively at the C6 po-
OCH
3
OCH
3
OCH
3
O
OH
OCH
OCH
OR OCH3
3
OCH
3
OCH3
3
O
OR OCH3
OR
O
I
II
III
IV
Scheme 1. Synthetic strategies toward lantalucratins A and B.
2
.2. Total synthesis of (± ±)lantalucratin A
sition probably due to the difference of the coordination effect.8
The synthetically important compound 7a was obtained briefly
within four steps at over 90% yield. We next tried to focus on the
synthesis of the natural product 1a. The successful approach is
summarized in Scheme 3. After methylation of the hydroxyl group
of 7a, an oxygen atom was introduced by alkene epoxidation with
3-chloroperoxybenzoic acid to afford 2-epoxyalkyl-1,3,4,5-
tetramethoxynaphthalene 8a in excellent yield. The epoxy-ring
Based on the retrosynthetic analysis described in Section 2.1, we
began to plan the synthesis of the racemate of the natural products
a and 1b. The 3-alkyl substituted -naphthol derivative 7a, which
1
a
is a synthetically important building block for 1a and 1b, was
synthesized and the results are summarized in Scheme 2.
3
a
opening reaction was carried out in the presence of cam-
phorsulfonic acid to yield the desired product 9a as a (ꢀ)-lanta-
lucratin A precursor. The target compound 1a was finally obtained
from 9a by exposure to CAN in water in 89% yield. Although the
OCH
3
OCH
3
OCH
3
Br
i)
ii)
iii)
O
9
8%
OCH
OCH
3
97% (2steps)
OCH
3
3
9
OCH
3
OCH
3
OCH
3
side product, which is a regioisomer of 1a, was formed in less
than 1% yield, the major product was easily separated by silica gel
column chromatography. In addition, all measured data of the
spectroscopic analysis of the product 1a were identical with those
of the compounds derived from natural products except for the
OCH
3
OCH3
OCH3
Li
iv) a
iv) b
98%
2
optical rotation value. The melting point of the synthesized
OCH
3
OCH3
OCH3
OCH3
OH OCH3
compound 1a was different from that of the compound derived
from natural product because of the difference between the ra-
cemic compound and chiral one. Thus, we succeeded in the total
synthesis of (ꢀ)-lantalucratin A in a total of eight steps with a 69%
overall yield.
OH OCH
3
O
Li
2 3 4
Reaction conditions: i) Br , CHCl , 0°C, 1 h ii) LDA, furan, THF, -78°C to rt iii) cat. HClO , THF,
rt, 1 h iv) a) -BuLi, THF, 0°C to rt b) prenyl bromide, -80°C to rt, 1 h
Scheme 2. Synthetic route to compound 7a.
2.3. Total synthesis of (± ±)lantalucratin B
One of the most efficient synthetic routes will be the direct
In accordance with the literature protocols,6 1-naphthol de-
conversion from 1a to 1b by deprotection of methyl ether when
synthesizing both target compounds. Hence, we decided to exam-
ine the O-demethylation of 1a (Scheme 4).
rivative
trimethoxybenzene 2 within three steps in quantitative yield. The
HClO -catalyzed epoxy-ring opening reaction was accomplished
with complete regioselectivity, in the same manner as well as the
5 was prepared from commercially available 1,2,4-
4
First, we attempted to select some typical Lewis acids, such as
boron tribromide or aluminum trichloride, for the O-demethylation
of 1a. Unfortunately, the desired molecule 1b was not obtained and
some of the side products were formed probably due to a haloge-
1
13
reported one confirmed by H and C NMR analysis. Directed or-
tho-lithiation of 5 was carried out with more than twice the excess
amount of n-butyllithium against the substrate to generate the
dianion intermediate 6, and subsequent treatment with prenyl
10
nation reaction occurring at the terminal alkene of 1a. We as-
sumed that the side reaction would be caused by the hydrogen

10472
T. Ogata et al. / Tetrahedron 69 (2013) 10470e10476
OCH
3
OCH
3
OCH
3
v)
5%
vi)
O
OCH
3
9
92%
OCH
3
OCH
3
OH OCH
3
3
CH O
OCH
3
CH
3
O
OCH
3
OCH3
O
vii)
viii)
89%
OH
OCH3
OCH3
9
5%
O
CH O
3
CH O
O
3
(
±)-Lantalucratin A
Reaction conditions: v) Me SO , KOH, TBAB, THF/H O, 0°C, 1 h vi) -CPBA, NaHCO , CH Cl rt, 0.5 h
2
4
2
3
2
2
vii) CSA, TBAB, CH Cl , rt, 2 h viii) CAN (2.5 equiv), CH CN/H O, 0°C, 1 h.
2
2
3
2
Scheme 3. Total synthesis of (ꢀ)-lantalucratin A (1a).
conditions.12 However, all attempts met with failure under those
conditions, and only the recovery of starting material 1a and/or
decomposition was observed. Thus, we concluded that is too dif-
ficult to convert 1b directly from 1a by O-demethylation reaction.
On consideration of the above results, we decided to retrace the
synthetic route to naphthol 7a, which has a free hydroxy group at
the C1 position. Fortunately, the epoxidation of 7a and the fol-
lowing ring opening reaction proceeded smoothly in the presence
of free hydroxyl group under conditions similar to those described
in Scheme 3, and the desired products were produced in high
yields. However, in contrast to the former reaction, the oxidative
CAN cyclization of 9b did not occur to furnish the desired product.
In order to achieve the total synthesis of (ꢀ)-lantalucratin B, pro-
tection of the hydroxyl group at the C1 position of 9b was needed
when the compounds are treated with CAN. The acetyl group,
which seems to be suitable protecting group for 9b because it can
be survived under acidic conditions and it can be removed easily
under basic conditions. The hydroxyl group of 7a was protected
with acetic anhydride and sodium acetate under thermal condi-
tions to afford the corresponding acetate 7c in excellent yield. As
expected, introduction of the oxygen functional group to the in-
ternal alkene moiety was successful using the same method
without cleavage of the acetyl ester as shown in Scheme 5. The
oxidative cyclization of 9c was carried out with a stoichiometric
O
O
O
O
CH
3
O
O
OH O
reagents: BBr
additives: 2-methyl-2-butene, DBU, HMPA, etc.
3
, AlCl
3
, PhSH, PhSLi, PhSNa
Scheme 4. Direct conversion of 1a into 1b by O-demethylation.
halides, which were generated from Lewis acids. In order to in-
terrupt the side reaction processes, a large excess of 2-methyl-2-
butene was added to the reaction mixture as an acid scavenger.
However, this was not effective and the same side products were
formed and identified by TLC analysis. These results indicated that
the terminal alkene moiety of compound 1a was extremely sensi-
tive to the acidic conditions, and therefore, it might be difficult to
remove the O-methyl group by utilizing typical Lewis acids. During
the study, we found a similar case reported in a recent publica-
11
tion. We also examined another method for the O-demethylation
of 1a by nucleophilic substitution of thiolates under basic
OCH3
OCH3
O
i)
2%
ii)
iii)
O
OH
9
82%
OCH3
OCH3
OH OCH
3
OH OCH
3
O
OH
O
:
(±)-Lantalucratin B
v)
+
OCH
3
OCH
3
O
iv)
4%
1) i) 99%
2) ii) 78%
OH
OCH3
OCH3
9
OCH3
OCH3
O
AcO
AcO
OH
O
Reaction conditions: i) -CPBA, CH
2
Cl
2
rt, 0.5 h ii) CSA, TBAB, CH
2
Cl
2
, rt, 2 h iii) CAN (2.5 equiv), CH
3
2
CN/H O,
0
°C, 1 h iv) Ac O, AcONa, 120°C, 0.5 h v) CAN (2.5 equiv), CH CN/H O, 0°C, 0.5 h, then 1%
2
3
2
Na
2
CO
3
aq, rt, 2 h, : 66%, : 8%.
Scheme 5. Total synthesis of (ꢀ)-lantalucratin B (1b).

T. Ogata et al. / Tetrahedron 69 (2013) 10470e10476
10473
amount of CAN. Thereafter, subsequent deprotection of the acetyl
group was done by treatment with 1 wt/v% Na CO aq solution,
with the formation of the target compound 1b. The regioisomer 10
4.3. 1,4)Dihydro)5,6,8)trimethoxy)1,4)epoxynaphthalene (4±
2
3
According to a literature procedure,6 a solution of 3 (2.47 g,
was also obtained as a minor product in 8% yield, and the precise
10 mmol) and furan (21.8 mL) in anhydrous THF (39 mL) was
1
13
ꢂ
structure of this molecule was confirmed by H and C NMR
analysis. The major product 1b could be easily separated and iso-
lated by flash column chromatography on silica gel. Moreover, all
measured data of the spectroscopic analysis of product 1b were
identical with compounds derived from natural products except for
cooled to ꢁ78 C under an argon atmosphere. To the solution was
added LDA in THF dropwise via cannula over 1 h after prepara-
tion in situ from diisopropylamine (1.7 g, 16.8 mmol) and 1.6 M
n-butyllithium solution in hexane (10 mL, 16 mmol) in anhydrous
ꢂ
THF (21.5 mL) and precooling to ꢁ78 C. The reaction mixture
2
ꢂ
the optical rotation value. The melting point of the synthesized
was stirred at ꢁ78 C for 4 h, and then stirring was continued at
compound 1b was very different from that of the compound de-
rived from natural product because of the difference between the
racemic compound and chiral one. Thus, we first established the
synthetic route of (ꢀ)-lantalucratin B in a total of eight steps for 45%
overall yield.
room temperature for 15 h. The reaction was quenched with
water and extracted with AcOEt (ꢃ2). The combined organic
4
extracts were washed with brine, dried over MgSO , filtered, and
concentrated to give the title compound in quantitative yield. It
1
was used for the next step without further purification. H NMR
(
CDCl
OCH ), 5.90e5.95 (2H, m), 6.12 (1H, s, AreH), 6.98e7.00 (1H, m),
.03e7.05 (1H, m).
3 3 3
) d: 3.81 (3H, s, OCH ), 3.82 (3H, s, OCH ), 3.85 (3H, s,
3
. Conclusion
3
7
Total synthesis of (ꢀ)-lantalucratins A and B was accomplished
in high yield. The alkyl side chain was successfully introduced by
directed ortho-lithiation alkylation methodology to afford the
synthetically important 1-naphthol derivative 7a in excellent yield
4.4. 5,7,8)Trimethoxynaphthalen)1)ol (5±
6
According to a literature procedure, to a solution of 4 (2.34 g,
with
naphthoquinone skeleton was constructed directly from 3-
hydroxyalkyl)-naphthalenes (9a, 9c) by CAN-mediated oxidative
intramolecular cyclization reaction. The asymmetric total synthesis
of these compounds is currently in progress.
complete
regioselectivity.
The
dihydrofuranyl-1,2-
10 mmol) in anhydrous THF (21 mL) was slowly added 70 wt/v%
HClO aq (0.22 mL, 0.92 mmol) under ice-water bath cooling, and
4
was stirred at room temperature for 75 min. The reaction mixture
was diluted with ether, and then was successively washed with
4
water and brine, dried over MgSO , filtered, and concentrated. The
(
residue was purified by flash column chromatography eluting with
AcOEt and hexane in 1:3 ratio gave 2.26 g (97%) of the title com-
pound as a yellow solid. A small portion of the solid was separated
and recrystallized from AcOEt and hexane to give greenish-yellow
4
4
. Experimental
.1. General
ꢂ
1
cubic crystals of mp 92.5e94.0 C. H NMR (CDCl
OCH ), 3.98 (3H, s, OCH ), 4.01 (3H, s, OCH ), 6.60 (1H, s, AreH),
6.88 (1H, dd, J¼1.1, 7.7, AreH), 7.21 (1H, dd, J¼7.7, 8.4, AreH), 7.64
3
) d: 3.96 (3H, s,
All materials not explicitly mentioned were purchased from
3
3
3
Wako Pure Chemical Products Co., Kanto Chemical Co., TCI Lab-
oratory Chemical Co., Nacalai Tesque Co., and Aldrich Chemical
Co. H NMR (400 MHz) and C NMR (100 MHz) were recorded on
a JEOL JNM-ECP400 spectrometer. Chemical shift values were
1
3
(1H, dd, J¼1.1, 8.4, AreH), 9.66 (1H, s, OH). C NMR (CDCl
3
) d: 55.8,
1
13
57.4, 62.1, 95.6, 111.3, 113.1, 118.1, 123.2, 124.8, 136.9, 147.1, 153.0,
153.3.
expressed in parts per million (ppm) relative to an internal ref-
1
erence of tetramethylsilane (0 ppm) in H NMR and CDCl
(
(
3
4.5. 5,7,8)Trimethoxy)6)(3)methylbut)2)enyl±naphthalen)1)ol
(7a±
77.0 ppm) in 13C NMR. Coupling constants are shown in hertz
Hz). Abbreviations are as follows: s, singlet; d, doublet; t, triplet;
m, multiplet; br, broad. IR spectra were recorded on a JASCO IR
Report-100. Mass spectra (MS) were obtained on JEOL JMS-700
instruments. Melting points were measured on a Yanaco micro
melting point apparatus and are uncorrected. Flash chromatog-
raphy was performed with silica gel (Wakosil C-200) obtained
from Wako Pure Chemical Products Co. Analytical thin layer
chromatography was performed on Merck Silica Gel 60 F254
aluminum sheets and the visualization was done using an UV
lamp.
Under an argon atmosphere, to a solution of 5 (7.02 g,
30 mmol) in anhydrous THF (75 mL) was added dropwise 1.6 M
ꢂ
n-butyllithium in hexane solution (42 mL, 66 mmol) at 0 C. The
reaction mixture was warmed to room temperature, and then
was stirred for 2 h until a white precipitate formed. The reaction
ꢂ
mixture was cooled back to ꢁ80 C, and prenyl bromide (11.7 g,
30 mmol) was slowly added with stirring for 10 min. The reaction
mixture was warmed to room temperature again, with stirring
4
for 30 min. The reaction was quenched with satd NH Cl aq under
ice bath cooling, and the entire mixture was extracted with
4
.2. 1)Bromo)2,4,5)trimethoxybenzene (3±
AcOEt (ꢃ3). The organic layer was separated and successively
4
washed with water and brine, dried over MgSO , filtered, and
According to a literature procedure,6 to a solution of 1,2,4-
concentrated in vacuo. The residue was purified by flash column
chromatography eluting with AcOEt and hexane in 1:6 ratio to
obtain 8.86 g (98%) of the title compound as an orange oil. IR
(neat): 3360, 2945, 2850, 1605, 1505, 1455, 1375, 1360, 1245,
3
trimethoxybenzene (1.68 g, 10 mmol) in 20 mL of CHCl was
added dropwise a solution of bromine (1.6 g, 10 mmol) in 10 mL of
CHCl
atmosphere. After stirring for 45 min at the same temperature, the
reaction mixture was treated with 1 wt/v% Na aq, and was
then extracted with CHCl
(ꢃ3). The organic layer was washed with
brine, dried over MgSO , filtered, and concentrated in vacuo. The
residue was purified by flash column chromatography eluting with
AcOEt and hexane in 1:10 ratio to give 2.41 g (98%) of the title
ꢂ
3
over 45 min at 0 C (in an ice-water bath) under an argon
ꢁ
1 1
1200, 1115, 1080, 1058, 1005, 960, 840, 820, 770 cm
(CDCl : 1.70 (3H, s, CH ), 1.83 (3H, s, CH
), 3.51 (2H, d, J¼6.8),
3.86 (3H, s, OCH ), 3.91 (3H, s, OCH ), 4.06 (3H, s, OCH ), 5.21
(1H, t, J¼6.8), 6.83 (1H, dd, J¼1.1, 7.7, AreH), 7.29 (1H, t, J¼7.7, 8.4,
. H NMR
2
S
2
O
3
3
)
d
3
3
3
3
3
3
4
13
AreH), 7.49 (1H, dd, J¼1.1, 8.4, AreH), 9.57 (1H, s, OH). C NMR
(CDCl : 17.9, 24.0, 25.7, 60.7, 61.6, 61.9, 110.1, 113.2, 116.9, 123.0,
126.3, 127.51, 127.55, 131.8, 143.9, 147.4, 150.6, 154.0. EIMS m/z:
3
) d
1
compound as a white solid. H NMR (CDCl
3
)
d
: 3.83 (3H, s, OCH
3
),
þ
þ
3
.86 (3H, s, OCH
3
), 3.88 (3H, s, OCH
3
), 6.57 (1H, s, AreH), 7.04 (1H, s,
22 4
302 (M ). HRMS-EI m/z: (M ) calcd for C18H O , 302.1518;
AreH).
found, 302.1515.

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T. Ogata et al. / Tetrahedron 69 (2013) 10470e10476
4
.6. 1,3,4,5)Tetramethoxy)2)(3)methylbut)2)enyl±naphtha)
elution with AcOEt and hexane in 1:3 ratio gave 316 mg (95%) of the
title compound as a pale yellow oil. IR (neat): 3500, 2945, 2850,
lene (7b±
ꢁ
1 1
1
598, 1500, 1450, 1400, 1360, 1260, 1200, 1120, 1020 cm . H NMR
(CDCl : 1.89 (3H, s, CH
), 2.95 (1H, dd, J¼9.2, 13.5), 3.10 (1H, br s),
3.19 (1H, dd, J¼2.9, 13.5), 3.88 (3H, s, OCH ), 3.90 (3H, s, OCH ), 4.01
(3H, s, OCH ), 4.02 (3H, s, OCH ), 4.86 (1H, s), 5.06 (1H, s), 6.84 (1H,
d, J¼7.3, AreH), 7.33 (1H, t, J¼7.3, 8.4, AreH), 7.62 (1H, d, J¼8.4,
To a solution of 7a (151 mg, 0.5 mmol) and tetra-n-buty-
lammonium bromide (21 mg, 0.065 mmol) in anhydrous THF
3
)
d
3
3
3
(
0.15 mL) was added KOH (90 mg, 1.6 mmol) in water (54
m
L) and
3
3
ꢂ
dimethylsulfate (80
m
L, 0.8 mmol) at 0 C (ice-water bath) under an
13
argon atmosphere, and the mixture was stirred for 1 h at the same
temperature. The complete consumption of the starting material
was confirmed by TLC analysis. To the reaction mixture was added
AreH). C NMR (CDCl
3
) d: 18.1, 31.9, 56.1, 61.2, 61.6, 61.9, 76.3,106.0,
110.2, 114.8, 120.6, 124.7, 125.2, 127.8, 145.2, 147.8, 149.5, 150.6,
þ
þ
24 5
156.3. EIMS m/z: 332 (M ). HRMS-EI m/z: (M ) calcd for C19H O ,
1
(
0 wt/v% NaOH aq and the entire mixture was extracted with AcOEt
ꢃ3), and the combined organic layer was washed successively
with water and brine. The organic extracts were dried over MgSO
332.1624; found, 332.1627.
4
,
4.9. 2)Isopropenyl)6)methoxy)2,3)dihydronaphtho[1,2)b]fu)
filtered, concentrated in vacuo, and subjected to flash column
ran)4,5)dione (lantalucratin A: 1a±
chromatography eluting with AcOEt and hexane in 1:30 ratio gave
150 mg (95%) of the title compound as a pale yellow oil. IR (neat):
To a solution of 9a (500 mg, 1.51 mmol) in acetonitrile (21.6 mL)
2
935, 2840, 1598, 1587, 1500, 1460, 1400, 1372, 1347, 1262, 1124,
was gently added cerium ammonium nitrate (2.06 g, 3.77 mmol) in
13 mL of water at 0 C. After stirring for 1 h at the same tempera-
ꢁ1 1
ꢂ
1
070, 1015, 760 cm . H NMR (CDCl
s, CH
), 3.52 (2H, d, J¼6.2), 3.86 (3H, s, OCH
.96 (3H, s, OCH ), 4.00 (3H, s, OCH
), 5.24 (1H, t, J¼6.2), 6.81 (1H, d,
J¼7.7, AreH), 7.30 (1H, t, J¼7.7, 8.4, AreH), 7.63 (1H, d, J¼8.4, AreH).
3
)
d
: 1.70 (3H, s, CH
3
), 1.83 (3H,
3
3
), 3.87 (3H, s, OCH
3
),
ture, the reaction mixture was diluted with water and CHCl
the entire mixture was extracted with CHCl
(ꢃ3). The combined
organic layer was washed with water, dried over MgSO , filtered,
concentrated in vacuo, and subjected to flash column chromatog-
raphy eluting with CHCl and methanol in 100:1 ratio gave 343 mg
3
, and
3
3
3
3
4
13
C NMR (CDCl
3
) d: 17.9, 24.2, 25.7, 56.1, 61.1, 61.5, 62.0, 105.6, 114.8,
120.2, 123.3, 124.8, 127.8, 127.9, 131.5, 145.1, 149.97, 150.02, 156.2.
3
þ
þ
EIMS m/z: 316 (M ). HRMS-EI m/z: (M ) calcd for C19
16.1675; found, 316.1678.
H O
24 4
,
(84%) of the title compound as a dark orange solid. A small portion
of the solid was separated and recrystallized from AcOEt and hex-
3
ꢂ
2
ane gave dark orange crystals of mp 156.4e158.9 C (lit.:
ꢂ
4
.7. 2,2)Dimethyl)3)(1,3,4,5)tetramethoxynaphthalen)2)
mp146e158 C). IR (KBr): 2980, 2955, 1687, 1650, 1630, 1580,
ꢁ1 1
ylmethyl±oxirane (8a±
1465, 1358, 1297, 1205, 1070, 1004, 902, 799 cm . H NMR (CDCl
: 1.80 (3H, s, CH
), 2.94 (1H, dd, J¼8.4, 16.0), 3.24e3.31 (1H, m),
3.99 (3H, s, OCH
), 5.01 (1H, s), 5.12 (1H, s), 5.44 (1H, dd, J¼8.4,
10.8), 7.18 (1H, d, J¼8.1, AreH), 7.33 (1H, d, J¼7.5, AreH), 7.59 (1H, t,
3
)
d
3
To a solution of 7b (1.40 g, 4.43 mmol) in CH
2
Cl
2
(13.3 mL) was
3
ꢂ
slowly added satd NaHCO
3
aq (13.3 mL), and was cooled to 0
C
13
(
ice-water bath) equipped with an argon gas balloon. 3-
J¼7.5, 8.1, AreH). C NMR (CDCl
(CH ), 89.4 (CH), 113.6 (CH ), 114.6 (C), 116.8 (CH), 117.2 (CH), 118.1
(C), 129.4 (C), 135.8 (CH), 142.1 (C), 161.9 (C), 169.2 (C), 175.4 (C),
3 3 2
) d: 16.8 (CH ), 31.2 (CH ), 56.4
Chloroperoxybenzoic acid (1.15 g, 6.6 mmol) was added portion-
wise for 4e5 times to the reaction mixture, and stirring of the so-
lution was continued for 30 min at room temperature until the
starting material was fully consumed, which was checked by TLC
3
2
þ
þ
180.0 (C). EIMS m/z: 270 (M ). HRMS-EI m/z: (M ) calcd for
, 270.0892; found, 270.0890.
16 14 4
C H O
analysis. The reaction mixture was added water and CHCl
ice-water bath cooling, and the entire mixture was extracted with
CHCl . The organic layer was successively washed with 1 wt/v%
Na aq, 0.5 N NaHCO aq, and water. The resulting organic
extracts were dried over MgSO , filtered, and was subjected to flash
3
under
4.10. 6)(3,3)Dimethyl)oxiranylmethyl±)5,7,8)
trimethoxynaphthalen)1)ol (8b±
3
2
S
2
O
3
3
4
To a solution of 7a (1.51 g, 5.0 mmol) in CH
added 3-chloroperoxybenzoic acid (1.29 g, 7.5 mmol) at 0 C. The
reaction mixture was allowed to reach room temperature and
2
Cl
2
(15 mL) was
ꢂ
column chromatography eluting with AcOEt and hexane in 1:10
ratio gave 1.35 g (92%) of the title compound as a pale yellow oil. IR
ꢂ
(
neat): 2940, 2848, 1718, 1600, 1580, 1500, 1460, 1400, 1370, 1348,
stirred for 0.5 min. The reaction was quenched with water at 0 C,
ꢁ1 1
1
261, 1125, 1100, 1070, 1012, 761 cm . H NMR (CDCl
3
)
d
: 1.31 (3H,
), 2.98e3.14 (3H, m), 3.88 (3H, s, OCH ), 3.89
), 4.01 (3H, s, OCH ), 4.02 (3H, s, OCH ), 6.84 (1H, d,
J¼7.7, AreH), 7.32 (1H, t, J¼7.7, 8.1, AreH), 7.63 (1H, d, J¼8.1, AreH).
and the entire mixture was extracted with CHCl
extracts were washed successively with 1 wt/v% Na
and then dried over Na SO , filtered, and concentrated in vacuo.
3
(ꢃ3). The organic
s, CH
(
3
), 1.46 (3H, s, CH
3
3
2 2 3
S O , brine,
3H, s, OCH
3
3
3
2
4
The residue was purified by flash column chromatography eluting
with AcOEt and hexane in 1:5 ratio gave 1.46 g (92%) of the title
1
3
C NMR (CDCl
3
)
d: 19.0, 24.8, 25.0, 56.2, 59.1, 61.2, 61.6, 62.2, 64.0,
1
05.9, 114.9, 120.7, 124.1, 125.0, 127.8, 145.0, 150.0, 150.7, 156.2. EIMS
compound as a pale yellow oil. IR (neat): 3360, 2945, 2850, 1608,
þ
þ
ꢁ1
m/z: 332 (M ). HRMS-EI m/z: (M ) calcd for C19
found, 332.1621.
24
H O
5
, 332.1624;
1506, 1459, 1375, 1361, 1245, 1120, 1058, 1006, 905, 760, 739 cm
.
1
H NMR (CDCl
3
)
d
: 1.31 (3H, s, CH
3
), 1.46 (3H, s, CH
3
), 2.98e3.10 (3H,
m), 3.90 (3H, s, OCH
3
), 3.96 (3H, s, OCH
3
3
), 4.06 (3H, s, OCH ), 6.86
4
.8. 3)Methyl)1)(1,3,4,5)tetramethoxynaphthalen)2)yl±but)3)
(1H, dd, J¼1.1, 7.7, AreH), 7.30 (1H, t, J¼7.7, 8.4, AreH), 7.50 (1H, dd,
13
en)2)ol (9a±
J¼1.1, 8.4, AreH), 9.55 (1H, s, OH). C NMR (CDCl : 19.0 (CH
3
)
d
3
3
),
),
2
4.77 (CH ), 24.81 (CH ), 59.1 (C), 60.8 (CH ), 61.6 (CH ), 62.2 (CH
3
2
3
3
To a solution of 8a (332 mg, 1.0 mmol) in CH
added 1 M camphorsulfonic acid solution in water (1.15 mL,
.15 mmol) under ice-water bath cooling. After stirring for 30 min
at room temperature, tetra-n-butylammonium bromide (16 mg,
.05 mmol) was added to the flask, and stirring was continued for
.5 h at the same temperature. The reaction was quenched with
satd NH Cl aq, and diluted with water. The entire mixture was
extracted with CHCl , and the combined organic layer was washed
with water, dried over MgSO , filtered, and concentrated in vacuo.
The residue was purified by flash column chromatography and
2
Cl
2
(9.2 mL) was
63.9 (CH), 110.5 (CH), 113.3 (CH), 117.4 (C), 123.9 (C), 126.4 (CH),
127.4 (C), 143.9 (C), 147.3 (C), 151.5 (C), 154.0 (C). EIMS m/z: 318
þ
þ
1
22 5
(M ). HRMS-EI m/z: (M ) calcd for C18H O , 318.1467; found,
318.1467.
0
1
4.11. 6)(2)Hydroxy)3)methylbut)3)enyl±)5,7,8)
trimethoxynaphthalen)1)ol (9b±
4
3
4
The reaction was conducted in the same manner for the prep-
aration of 9a. Flash column chromatography was carried out using

T. Ogata et al. / Tetrahedron 69 (2013) 10470e10476
10475
AcOEt and hexane in 2:3 ratio as an eluant to give 82% of the title
compound as a pale yellow oil. IR (neat): 3500, 3370, 3080, 2950,
(1H, dd, J¼3.2, 9.2), 4.85 (1H, s), 5.04 (1H, s), 7.07 (1H, d, J¼7.3,
13
AreH), 7.38 (1H, t, J¼7.3, 8.4, AreH), 7.92 (1H, d, J¼8.4, AreH).
NMR (CDCl : 19.0 (CH ), 20.8 (CH ), 24.8 (CH ), 24.9 (CH ), 59.1
(C), 60.9 (CH ), 61.2 (CH ), 62.4 (CH ), 63.9 (CH), 119.9 (C), 120.8
C
2
9
2
1
4
850,1610,1580,1510,1450,1370,1320,1250,1200,1120,1060, 950,
3
)
d
3
3
3
2
ꢁ
1 1
00, 870, 820, 770, 730 cm . H NMR (CDCl
.81 (1H, d, J¼4.1), 2.96 (1H, dd, J¼9.2, 13.6), 3.15 (1H, dd, J¼3.7,
3.6), 3.91 (3H, s, OCH ), 3.96 (3H, s, OCH ), 4.06 (3H, s, OCH ),
.31e4.35 (1H, m), 4.86 (1H, s), 5.04 (1H, s), 6.86 (1H, dd, J¼1.1, 7.7,
3
)
d: 1.88 (3H, s, CH
3
),
3
3
3
(CH), 121.9 (C), 124.46 (C), 124.52 (CH), 127.6 (C), 143.2 (C), 145.9 (C),
þ
3
3
3
150.2 (C), 151.1 (C), 170.0 (C). EIMS m/z: 360 (M ). HRMS-EI m/z:
þ
(M ) calcd for C20
H O
24 6
, 360.1573; found, 360.1576.
AreH), 7.31 (1H, t, J¼7.7, 8.4, AreH), 7.49 (1H, dd, J¼1.1, 8.4, AreH).
1
3
C NMR (CDCl
1.8 (CH ), 76.1 (CH), 110.4 (CH
24.4 (C), 126.6 (CH), 127.3 (C), 144.0 (C), 147.0 (C), 147.6 (C), 151.3
3
)
d: 18.0 (CH
3
), 31.6 (CH
2 3 3
), 60.8 (CH ), 61.6 (CH ),
4.15. CAN)mediated oxidative intramolecular cyclization of 9c
6
1
3
2
), 110.5 (CH), 113.2 (CH), 117.3 (C),
To a solution of 9c (108 mg, 0.3 mmol) in acetonitrile (4.3 mL)
þ þ
(
C), 154.0 (C). EIMS m/z: 318 (M ). HRMS-EI m/z: (M ) calcd for
was gently added diammonium cerium(IV) nitrate (411 mg,
C
H
18 22
O
5
, 318.1467; found, 318.1469.
ꢂ
0
.75 mmol) in 2.6 mL of water at 0 C. After stirring for 0.5 h at the
same temperature, the reaction mixture was basified with 1 wt/v%
4
.12. 5,7,8)Trimethoxy)6)(3)methylbut)2)enyl±)naphthalen)1)
Na
2
CO
3
aq, and was allowed to reach room temperature with stir-
yl acetate (7c±
ꢂ
ring continuing for 2 h. The reaction mixture was cooled to 0 C and
acidified with 1 M HCl. The acidic solution was extracted with
A solution of 7a (2.02 g, 6.70 mmol) and sodium acetate (6.9 g,
3.1 mmol) in acetic anhydride (23.1 mL) was heated at 120 C and
stirred for 0.5 h. To the reaction mixture was added pH 7.4 phos-
phate buffer until a white suspension was formed in the reaction
CHCl
washed with water and brine, dried over MgSO
concentrated in vacuo. The crude red solid was purified by flash
column chromatography eluting with CHCl and AcOEt in 30:1 ratio
3
(ꢃ3) and the combined organic layer was successively
ꢂ
8
4
, filtered, and
3
mixture. The entire mixture was extracted with CHCl
3
(ꢃ2) and the
gave 51 mg (66%) of 1b as a red solid and 6 mg (8%) of 10 as
organic layer was dried over Na SO , filtered, and concentrated in
2
4
ꢂ
a reddish-orange solid of mp 120.6e122.9 C. A small portion of the
vacuo. The residue was purified by flash column chromatography
eluting with AcOEt and hexane in 1:3 ratio to give 2.16 g (94%) of
the title compound as a pale yellow solid. A small portion of the
solid was separated and recrystallization from hexane gave color-
1
b was separated and recrystallized from AcOEt and hexane gave
ꢂ
2
ꢂ
red crystals of mp 153.2e153.6 C (lit.: mp 179e181 C).
4
4
.15.1. 6-Hydroxy-2-isopropenyl-2,3-dihydronaphtho[1,2-b]furan-
,5-dione (lantalucratin B: 1b). IR (KBr): 3470, 2965, 1765, 1650,
ꢂ
less needles of mp 82.1e85.0 C. IR (KBr): 2940, 2875, 1700, 1600,
ꢁ1
1
7
500, 1441, 1401, 1345, 1305, 1235, 1121, 1090, 1062, 1012, 920, 898,
1
619, 1590, 1500, 1459, 1412, 1365, 1250, 1213, 1185, 935, 768 cm .
ꢁ
1 1
1
81 cm . H NMR (CDCl
3
)
d
: 1.70 (3H, s, CH
), 3.51 (2H, d, J¼7.0), 3.86 (3H, s, OCH
), 3.91 (3H, s, OCH
), 5.18e5.23 (1H, m), 7.04 (1H, dd, J¼1.1, 7.7,
3
), 1.82 (3H, s, CH
3
), 2.38
H NMR (CDCl
1H, dd, J¼10.6, 15.6), 5.03 (1H, s), 5.13 (1H, s), 5.46 (1H, dd, J¼7.7,
0.6), 7.14 (1H, d, J¼8.8, AreH), 7.24 (1H, d, J¼7.3, AreH), 7.54 (1H, t,
3
)
d
: 1.80 (3H, s, CH
3
), 2.95 (1H, dd, J¼7.7, 15.6), 3.28
(
3H, s, CH
3
3
), 3.87 (3H, s,
(
1
OCH
3
3
13
AreH), 7.35 (1H, t, J¼7.7, 8.5, AreH), 7.92 (1H, dd, J¼1.1, 8.5, AreH).
J¼7.3, 8.8, AreH), 11.93 (1H, s, OH). C NMR (CDCl
3 3
) d: 16.8 (CH ),
13
C NMR (CDCl
3
)
d: 17.9 (CH
3
), 20.9 (CH
3 2 3
), 24.1 (CH ), 25.7 (CH ),
31.0 (CH
2
), 89.8 (CH), 113.4 (C), 113.9 (CH
2
), 115.2 (C), 117.5 (CH),
6
0.9 (CH ), 61.2 (CH
3
3
), 62.2 (CH
3
), 119.5 (CH), 120.7 (CH), 121.4 (C),
123.4 (CH), 127.2 (C), 137.6 (CH), 141.9 (C), 164.5 (C), 169.1 (C), 174.8
þ
þ
1
23.0 (CH), 124.3 (CH), 127.8 (C), 128.1 (C), 131.7 (C), 143.3 (C), 145.9
(C), 185.2 (C). EIMS m/z: 256 (M ). HRMS-EI m/z: (M ) calcd for
þ
(
(
C),150.3 (C),150.4 (C),170.0 (C). EIMS m/z: 344 (M ). HRMS-EI m/z:
M ) calcd for C20
C
15 12 4
H O , 256.0736; found, 256.0736.
þ
H O
24 5
, 344.1624; found, 344.1624.
4
.15.2. 6-Hydroxy-2-isopropenyl-2,3-dihydronaphtho[1,2-b]furan-
4
.13. 6)(3,3)Dimethyl)oxiranylmethyl±)5,7,8)
4,5-dione (10). IR (KBr): 3450, 2940, 2828, 1732, 1650, 1620, 1580,
ꢁ1 1
trimethoxynaphthalen)1)yl acetate (8c±
1
460, 1412, 1383, 1320, 1275, 1253, 1187, 909, 742 cm . H NMR
CDCl : 1.81 (3H, s, CH
), 3.02 (1H, dd, J¼8.8, 17.6), 3.34 (1H, dd,
J¼10.6, 17.6), 5.01 (1H, s), 5.14 (1H, s), 5.42 (1H, t, J¼8.8, 10.6), 7.20
1H, dd, J¼1.8, 7.7, AreH), 7.57e7.63 (2H, m, AreH), 11.65 (1H, s,
(
3
)
d
3
The reaction was conducted in the same manner as the prepa-
ration of 8b. Flash column chromatography was carried out using
AcOEt and hexane in 1:3 ratio as an eluant to give 99% of the title
(
13
OH). C NMR (CDCl
3
)
d
: 17.0 (CH
), 114.7 (C), 119.1 (CH), 124.1 (CH), 124.9 (C), 133.3 (C), 136.9
CH),141.6 (C),159.9 (C),162.1 (C),181.3 (C),182.5 (C). EIMS m/z: 256
3 2
), 32.0 (CH ), 88.8 (CH), 114.1
ꢂ
compound as a white solid of mp 69.3e71.4 C. IR (KBr): 3090,
(
(
(
CH
2
2
8
2
950, 2850, 1765, 1700, 1600, 1455, 1370, 1230, 1125, 1060, 1008,
98, 780 cm . H NMR (CDCl
ꢁ
1 1
þ
þ
3
)
d
: 1.31 (3H, s, CH
3
), 1.46 (3H, s, CH
), 3.91 (3H, s,
), 7.07 (1H, d, J¼7.3, AreH), 7.37 (1H, dd,
3
),
M ). HRMS-EI m/z: (M ) calcd for C15
56.0736.
12 4
H O , 256.0736; found,
.39 (3H, s, CH
3
), 2.97e3.12 (3H, m), 3.86 (3H, s, OCH
3
2
OCH
3
), 3.97 (3H, s, OCH
3
13
J¼7.3, 8.4, AreH), 7.93 (1H, d, J¼8.4, AreH). C NMR (CDCl
3
)
d
: 19.0
), 61.2
), 63.9 (CH), 119.9 (CH), 120.8 (CH), 121.9 (C), 124.46
References and notes
(
(
(
CH
CH
3
), 20.8 (CH
), 62.4 (CH
3 3 2 3
), 24.8 (CH ), 24.9 (CH ), 59.1 (C), 60.9 (CH
3
3
1. Recent reviews: (a) Sunassee, S. N.; Davies-Coleman, M. T. Nat. Prod. Rep. 2012,
9, 513e535; (b) Kumagai, Y.; Shinkai, Y.; Miura, T.; Cho, A. K. Annu. Rev.
2
C), 124.52 (CH), 127.6 (C), 143.2 (C), 145.9 (C), 150.2 (C), 151.1 (C),
þ
þ
Pharmacol. Toxicol. 2012, 52, 221e247; (c) Babula, P.; Adam, V.; Havel, L.; Kizek,
R. Curr. Pharm. Anal. 2009, 5, 47e68; (d) Ventura Pinto, A.; Lisboa de Castro, S.
Molecules 2009, 14, 4570e4590; (e) Verma, R. P. Anticancer Agents Med. Chem.
170.0 (C). EIMS m/z: 360 (M ). HRMS-EI m/z: (M ) calcd for
C
H O
20 24 6
, 360.1573; found, 360.1576.
2006, 6, 489e499; (f) Suttie, J. W. Annu. Rev. Nutr. 1995, 15, 399e417.
2
. Hayashi, K.; Chang, F.-R.; Nakanishi, Y.; Bastow, K. F.; Gragg, G.; McPhail, A. T.;
Nozaki, H.; Lee, K.-H. J. Nat. Prod. 2004, 67, 990e993.
4
.14. 6)(2)Hydroxy)3)methylbut)3)enyl±)5,7,8)
trimethoxynaphthalen)1)yl acetate (9c±
3. (a) Kimachi, T.; Torii, E.; Kobayashi, Y.; Doe, M.; Ju-ichi, M. Chem. Pharm. Bull.
011, 59, 753e756; (b) Kimachi, T.; Torii, E.; Ishimoto, R.; Sakue, A.; Ju-ichi, M.
2
Tetrahedron: Asymmetry 2009, 20, 1683e1689.
The reaction was conducted in the same manner as the prepa-
ration of 9b. The product was obtained in 78% yield of a colorless oil.
IR (neat): 3451, 2860, 2820,1763,1653,1600,1458,1400,1360,1220,
4
. Recent review on the application of diammonium celium(IV) nitrate in organic
synthesis: Sridharan, V.; Menendez, J. C. Chem. Rev. 2010, 110, 3805e3849.
ꢀ
5. Snieckus, V. Chem. Rev. 1990, 90, 879e933.
6. Clive, D. L. J.; khodabocus, A.; Vernon, P. G.; Angoh, A. G.; Bordeleau, L.; Mid-
dleton, D. S.; lowe, C.; Kellner, D. J. Chem. Soc., Perkin Trans. 1 1991, 1433e1444.
. An example of directed ortho-lithiation of phenols with sec-butyllithium:
Katritzky, A. R.; Xu, Y.-J.; Jain, R. J. Org. Chem. 2002, 67, 8234e8236.
ꢁ1 1
1
122, 1062, 972, 910, 780, 738 cm . H NMR (CDCl
CH ), 2.38 (3H, s, CH
), 2.96 (1H, dd, J¼9.2, 13.5), 3.16 (1H, dd, J¼3.2,
3.5), 3.86 (3H, s, OCH ), 3.91 (3H, s, OCH ), 3.97 (3H, s, OCH ), 4.32
3
) d: 1.88 (3H, s,
3
3
7
1
3
3
3

10476
T. Ogata et al. / Tetrahedron 69 (2013) 10470e10476
8. Lithiation reaction hardly occurred at the peri-position of the 1-methox-
a saturated bond by an addition reaction judging from 1H NMR spectroscopic
ynaphthalene compared to those of ortho-position. See: (a) Betz, J.; Bauer, W. J.
Am. Chem. Soc. 2002, 124, 8699e8706; (b) Kirby, A. J.; Percy, J. M. Tetrahedron
analysis.
11. Singh, M.; Argade, N. P. Synthesis 2012, 44, 3797e3804.
12. (a) Chakraborti, A. K.; Sharma, L.; Nayak, M. K. J. Org. Chem. 2002, 67,
6406e6414; (b) Tanaka, T.; Mikamiyama, H.; Maeda, K.; Iwata, C. J. Org. Chem.
1998, 63, 9782e9793.
1
988, 44, 6911e6919.
9
1
. Compound similar to 10, judged by TLC and 1H NMR spectroscopic analysis
0. The exact structure of the side product is not yet established, but it is clear that
the double bond at the terminal alkene moiety of 1a was changed into