Diethylaminosulfur Trifluoride (DAST)-Mediated Intramolecular Benzannulation of o-Allylchalcones: Synthesis of 3-Fluorotetralins

Article abstract of DOI:10.1055/s-0037-1612419

A concise route for the synthesis of 3-fluorotetralines is described, including: (i) NaBH ₄ -mediated reduction of oxygenated o -allylchalcones and (ii) sequential DAST-mediated intramolecular annulation of the resulting alkenols. A plausible m

Full text of DOI:10.1055/s-0037-1612419

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–K
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M.-Y. Chang et al.
Paper
Synthesis
Diethylaminosulfur Trifluoride (DAST)-Mediated Intramolecular
Benzannulation of o-Allylchalcones: Synthesis of 3-Fluorotetralins
Meng-Yang Chang*a,b
Han-Yu Chena
Yu-Lin Tsaia
0
0
0
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0
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2-1
9
8
3-8
5
7
0
o
F
1) NaBH4, MeOH–THF
2) DAST, CH2Cl2
Ar
Ar
O
a Department of Medicinal and Applied Chemistry, Kaohsiung
Medical University, Kaohsiung 807, Taiwan
b Department of Medical Research, Kaohsiung Medical University
Hospital, Kaohsiung 807, Taiwan
R
R
Regio- and Stereocontrolled Synthesis
18 examples
65–82% yields
mychang@kmu.edu.tw
Received: 01.02.2019
Accepted after revision: 01.03.2019
Published online: 01.04.2019
Yeh's work
OTBS
Ma's work
O
O
O
O
F
Ts
Ts
BF3•OEt2
(ref 14)
NFSI
OR
N
N
F
OR
DOI: 10.1055/s-0037-1612419; Art ID: ss-2019-h0068-op
(ref 18)
Ar
NH
Bn
N
Ar
Bn
Abstract A concise route for the synthesis of 3-fluorotetralines is de-
scribed, including: (i) NaBH4-mediated reduction of oxygenated o-allyl-
chalcones and (ii) sequential DAST-mediated intramolecular annulation
of the resulting alkenols. A plausible mechanism is proposed and dis-
cussed. This protocol provides highly effective regio- and stereocon-
trolled allyl-enone cross-coupling to construct two stereocenters and
one E-configured styryl group.
Ph
Ph
Wang's work
You's work
Ar
F
F
1) NIS
1) AgNO3
2) Selectfluor
(ref 20)
Ar
2) TBAF, Ag (I)
(ref 16)
N
NH
Bn
NH
N
R
R
Bn
Cheng's work
Selectfluor
this work
Me
Me
F
3
F
1) NaBH4
2) DAST
Key words DAST, intramolecular benzannulation, o-allylchalcones,
cross-coupling reaction, 3-fluorotetralines
O
O
Ar
Ar
(ref 17)
Ph
N
H
N
Ph
O
R
R
Organofluorine heterocycles, cycloalkanes, or benzo-
cycles are main core structures in pharmaceuticals, function-
alized materials, and synthetic intermediates, especially in
agrochemicals.1–9 Hence, different organic fluorinating re-
agents (e.g., F2, Et3N·3HF, Selectfluor, aminosulfuranes, and
BF3·OEt2) have been utilized to introduce the fluorine atom
into diversified linear structures.10 Recently, mono-fluori-
nated heterocycles, such as 3-fluoropyrrolidines,11 4-fluo-
rotetrahydropyrans,12 and 3- or 4-fluoropiperidines,13 are
of particular interest since they have potential synthetic ap-
plications in the organic field. Among them, there are few
reports on the synthesis of mono-fluorinated bicycles by
different fluorinating reagent-promoted intramolecular
tandem cyclization/fluorination processes, as shown in
Scheme 1.14–21 These elegant synthetic routes have exhibit-
ed some advantages, including easy operation, high site-
specific selectivity, and optimal reaction conditions.
Scheme 1 Synthetic routes of monofluorinated bicycles
tion of 4-alkenamine followed by aminocyclization of ami-
no group with in situ formed iodonium ion.16 Cheng et al.
explored the possibility of Selectfluor-mediated efficient
installation of the primary fluoro group on a benzo[d]ox-
azine skeleton via fluorocyclization of o-styryl ben-
zamides.17 By the addition of N-fluorobenzenesulfonimide
(NFSI), Ma et al. developed a stereoselective synthesis of
fluorinated dihydroquinolinones via one-pot intermolecu-
lar Knoevenagel condensation of o-amino -keto esters
with aryl aldehydes followed by the -fluorination of the
resulting azaflavones.18 With the use of Selectfluor and cat-
alytic amounts of Ag(I), You et al. described that one-pot in-
tramolecular cyclization/fluorination of 2-alkynylanilines
afforded a variety of structurally diverse fluorinated indole
derivatives.20
For the involvement of boron trifluoride etherate, Yeh et
al. demonstrated that transition-metal-free carbofluorina-
tion of TBS-protected cyclic enynols provided bicyclic octa-
hydroisoquinolines.14 Wang et al. investigated the synthesis
of fluorinated azaheterobicycles via NIS-mediated iodina-
Despite the above-mentioned cyclization/fluorination
affording diversified azabicycles using various fluorine
sources, a direct intramolecular regio- and stereospecific
fluorocyclization employing diethylaminosulfur trifluoride
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

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M.-Y. Chang et al.
Paper
Synthesis
(DAST) to generate benzofused carbocycles via formation of
one carbon–fluorine bond and one carbon–carbon bond
has yet to be developed. Among the existing popular syn-
thetic applications toward DAST,3,4 the focus is still on the
conversion of alcohols into fluorides; aldehydes and ke-
tones to difluorides; and carboxylic acids to acyl fluorides.
In fact, to the best of our knowledge, so far no examples of
the synthesis of 3-fluorotetralins and their related deriva-
tives via DAST-mediated intramolecular cyclizative carbo-
fluorination of oxygenated o-allylchalcones have been
found, and only two sets of data are available on the synthe-
sis of fluorotetralins.10c,21a As a result of recent findings,
new methods for the construction of 3-fluorotetralins still
represent a continuing need in the organic synthetic field.
Continuing our research on the synthetic application of
o-allylchalcones 1 for the formation of benzofused hetero-
cycles and carbocycles,22 we present the synthesis of 3-flu-
orotetralins 4 via a one-pot two-steps process, including (i)
NaBH4-mediated reduction of oxygenated o-allylchalcones
1 and (ii) fluorine source-mediated intramolecular annula-
tion of the corresponding alkenols 2. The starting substrates
1 were prepared from aldol condensation of 2-allylbenzal-
dehydes 3 with different acetophenones in a range of 70–
86% yields under NaOH/MeOH condition for 20–30 hours
(Scheme 2). Oxygenated 2-allylbenzaldehydes 3 were syn-
thesized easily from commercially available isovanillin and
3-hydroxybenzaldehyde via a three-step synthetic route
(O-allylation, Claisen rearrangement, O-alkylation) accord-
ing to our previous reports.23–31
Table 1 Reaction Conditionsa,b
OMe
OMe
OMe
3
F
MeO
MeO
MeO
[F] source
conditions
NaBH4
4
MeOH–THF
O
OH
Ph
Ph
Ph
1a
2a
4a
Entry
Reagent
DAST
Solvent
Time (h)
Temp (°C) Yield (%)c
1
2
CH2Cl2
CH2Cl2
THF
5
5
5
5
5
5
5
5
5
5
8
3
5
5
5
5
25
25
25
25
25
25
25
25
25
25
25
25
40
0
82
25
BF3·OEt2
TBAF
d
3
–
4
NFSI
MeCN
MeCN
CH2Cl2
acetone
(CH2Cl)2
MeCN
THF
40
34
28
5
Selectfluor
Et3N·3HF
AgF
6
e
7
–
8
DAST
73
22
12
68
74
47
28
53
74
9
DAST
10
11
12
13
14
15
16
DAST
DAST
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DAST
DAST
DAST
DASTf
DAST
25
25
g
CH2Cl2
a The reactions were run on a 1.0 mmol scale with 1a, NaBH4 (1 equiv),
MeOH (5 mL), THF (5 mL), 25 °C, 30 min.
b The reactions were run on a resulting crude alcohol 2a, fluorine source
(1.6 equiv), solvent (10 mL).
O
OH
OR"
OR"
c Isolated yield over the two steps.
d No reaction.
R'
R'
R'
1) K2CO3, allylBr
Me
R
e Complex products.
2) decalin, reflux
3) K2CO3, R"–X
NaOH, MeOH
(70–86%)
CHO
CHO
f DAST: 1.0 equiv.
O
g CH2Cl2 used: 20 mL.
R' = MeO or H
3
1
R
Scheme 2 Synthetic route to the starting materials 1
reaction conditions. No desired 4a was observed for the
TBAF/THF combination, and only 2a was recovered in an
82% yield (entry 3). For the AgF/acetone combination, how-
ever, a complex unknown mixture was detected (entry 7).
According to the experimental results, DAST was the pre-
ferred choice as the fluorine source to screen the reaction
conditions. Then, different solvents such as 1,2,dichlo-
roethane [(CH2Cl)2], MeCN, and THF were examined. By the
use of (CH2Cl)2, a good yield of 4a was maintained (entry 8).
In particular, MeCN and THF gave much lower yields of 4a
(22% and 12%), respectively (entries 9, 10). We found that
CH2Cl2 still performed better for the formation of 4a. Next,
changing the times to 8 hours or 3 hours showed that iso-
lated yield of 4a were decreased to 68% or 74%, respectively
(entries 11, 12). Furthermore, after adjusting the tempera-
tures to reflux (40 °C) or ice bath (0 °C), poorer yields (47%
and 28%) were observed (entries 13, 14). Under ice-bath
conditions, the yield of 4a was still low even when the reac-
tion time was increased to 10 or 20 hours. By decreasing
The initial study commenced with the treatment of
model material 1a [Ar = 3,4-(MeO)2C6H2, R = Ph, 1.0 mmol)
with 1 equivalent of NaBH4 in a mixture of MeOH (5 mL)
and THF (5 mL) at 25 °C for 30 minutes. Subsequently, treat-
ment of the resulting secondary alcohol 2a (in a quantita-
tive yield) with 1.6 equivalents of DAST in CH2Cl2 (10 mL) at
25 °C for 5 hours provided styryl-containing fluorotetralin
4a in 82% yield for the two-step route (Table 1, entry 1). En-
tries 2–7 show that six combinations of fluorine reagents
(BF3·OEt2, TBAF, NFSI, Selectfluor, Et3N·3HF, AgF) and sol-
vents (CH2Cl2, THF, MeCN, acetone) were studied at 25 °C
for 5 hours. However, none of them produced higher yields
of 4a than DAST/CH2Cl2 under the above-mentioned condi-
tions.
Among the combinations, BF3·OEt2/CH2Cl2, NSFI/MeCN,
Selectfluor/MeCN, and Et3N·3HF/CH2Cl2 produced 4a in
lower yields (25%, 40%, 34%, 28%, Table 1, entries 2, 4–6)
along with unknown products under the 25 °C for 5 hours
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

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M.-Y. Chang et al.
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Synthesis
the amount of DAST to 1 equivalent, the yield of 4a was also
diminished (entry 15). Attempts to enhance the yield by di-
luting the reaction system failed (entry 16). On the basis of
our observations, we concluded that DAST/CH2Cl2 was an
optimal fluorinated combination to promote the generation
of 4a with two stereocenters and one (E)-styryl moiety via
the domino cyclization/fluorination process under the
25 °C for 5 hours reaction conditions.
equatorial addition to generate isomer 4a′. For the NFSI or
Selectfluor-mediated intramolecular fluorocyclizations of
2a (Table 1, entries 4, 5), the possible intermediates B and C
provide with similar configuration of A to obtain 4a by the
removal of PhSO2H (for entry 4) or HF, F2, and ammonium
salts (for entry 5).
To study the scope and limitations of this approach,
substituted oxygenated o-allylchalcones 1 were reacted
further to afford diversified 3-fluorotetralins 4 via a NaBH4-
mediated reduction and a DAST-promoted intramolecular
fluorocyclization, as shown in Table 2. With optimal condi-
tions established (Table 1, entry 1) and a plausible reaction
On the basis of experimental results, a plausible mecha-
nism for the formation of 4a is illustrated in Scheme 3. Ini-
tially, NaBH4-mediated 1,2-hydride reduction of enone 1a
formed allylic alcohol 2a. Then, by the involvement of DAST
(for Table 1, entry 1), the resulting 2a was chelated with di-
fluoroaminosulfur moiety to provide A along with the re-
moval of HF via a chair-like transition state. For the interac-
tion of the sulfur atom with the terminal allyl chain, Fuchi-
gami et al. had reported similar phenomenon for preparing
fluorinated thiacyclohexanes via the reaction of substituted
aldehydes and homoallylic thios.13b By the assistance of
para-methoxy group, OSF(NEt2) group should be easily re-
leased. For the relative configuration of A, the ring junction
of two chair-like conformations with six-membered ring is
preferred to orientate as a trans-form due to the higher sta-
bility and lower steric hindrance revealed. Furthermore, by
the participation of a nitrogen lone-pair, the in situ formed
intramolecular 1,3-syn migration of the axial-fluoro group
(yellow) produced single (for cyclohexyl) and double (for
styryl) carbon–carbon bond formations via regio- and ste-
reocontrolled fluoroannulation procedure. Finally, removal
of OSF(NEt2) provides 4a. For another 1,3-migration, how-
ever, the fluoro group (green, equatorial position) could be
affected by the cis-orientated diethylaminosulfur bulkier
moiety such that the formed steric hindrance inhibits the
Table 2 Synthesis of 3-Fluorotetralins 4a–ra,b
OMe
3
F
MeO
4
1) NaBH4, MeOH–THF
2) DAST, CH2Cl2
Ar
Ar
O
O
R
R
1
4
5a
Entry
1 Ar, R
1a, 3,4-(MeO)2C6H2, Ph
4 Yield (%)c
1
2
4a, 82
4b, 77
4c, 73
4d, 75
4e, 80
4f, 74
4g, 70
4h, 67
4i, 73
4j, 65
4k, 68
4l, 72
4m, 70
4n, 73
4o, 65
4p, 76
4q, 74
4r, 70
4s, –d
4t, –d
1b, 3,4-(MeO)2C6H2, 4-MeC6H4
1c, 3,4-(MeO)2C6H2, 2-naphthyl
1d, 3,4-(MeO)2C6H2, 4-PhC6H4
1e, 3,4-(MeO)2C6H2, 4-ClC6H4
1f, 3,4-(MeO)2C6H2, 3-FC6H4
1g, 3,4-(MeO)2C6H2, 3,4-Cl2C6H3
3
4
5
6
7
8
1h, 3,4-(MeO)2C6H2, 3,4,5-(MeO)3C6H2
1i, 3-i-PrOC6H3, 2-naphthyl
9
10
11
12
13
14
15
16
17
18
19
20
21
22
1j, 3-i-PrO,4-MeOC6H2, 2-naphthyl
1k, 3-n-BuO,4-MeOC6H2, 2-naphthyl
1l, 3-c-C5H9O,4-MeOC6H2, 2-naphthyl
1m, 3-BnO,4-MeOC6H2, 2-naphthyl
1n, 3,4-(MeO)2C6H2, 3,4-CH2O2C6H3
1o, 3,4-(MeO)2C6H2, 3-MeOC6H4
1p, 3,4-(MeO)2C6H2, 4-MeOC6H4
1q, 3,4-(MeO)2C6H2, 4-CF3C6H4
1r, 3,4-(MeO)2C6H2, 2-thienyl
1s, 3,4-(MeO)2C6H2, 4-NO2C6H4
1t, 3,4-(MeO)2C6H2, (CH2)2CHMe2
1u, 3,4-(MeO)2C6H2, 9-anthracenyl
1v, Ph, Ph
OMe
OMe
OMe
(Table 1, entry 1)
Et2N•SF3
F
MeO
MeO
MeO
NaBH4
MeOH–THF
CH2Cl2
OH
O
nitrogen lone-pair
promoted 1,3-
syn-migration of
axial fluoro group
1a
2a
4a
Ph
Ph
F
Ph
HF
OMe
F
OMe
OMe
MeO
MeO
3
MeO
F
F
S
1
NEt2
F
S
O
Ph
NEt2
A
4a'
O
Ph
Ph
OMe
F
(Table 1, entry 4)
MeO
2a
+
NFSI
O
4a
N
S
4u, –e
4v, –f
Ph
O
O
O
PhSO2H
N
Ph
S
O
B
Cl
BF4
2a
Ph
O
a The reactions were run on a 1.0 mmol scale with 1a, NaBH4 (1 equiv),
MeOH (5 mL), THF (5 mL), 25 °C, 30 min.
b The reactions were run on the resulting crude 2a, DAST (1.6 equiv), CH2-
Cl2 (10 mL), 25 °C, 5 h.
N
OMe
F
B
N
MeO
(Table 1, entry 5)
4a
+
F
c Isolated yields over two steps.
Selectfluor
O
B
Ph
HF + F2
d Complex products.
O
C
F
e 5a (96%) was isolated.
f 2v (35%) was isolated.
Scheme 3 Plausible mechanism
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

D
M.-Y. Chang et al.
Paper
Synthesis
mechanism proposed (Scheme 3), we found that the two-
step route could allow a direct synthesis of fluoro-contain-
ing tetralins 4a–r in moderate to good yields (65–82%).
Among Table 2, entries 1–21, for the electronic nature of an
Ar substituent of 1, electron-donating oxygenated groups
were appropriate; for the R substituent of 1, aromatic
groups were well tolerated. Therefore, efficient formation of
4a–r showed that the substituents (1, Ar, R) did not affect
the distribution of the provided yields (entries 1–18). 3-Flu-
orotetralins 4a–r were generated as the trans-isomers,
while no other diastereomers were observed. The stereo-
chemical structure of 4g was determined by single-crystal
X-ray crystallography.32 The crystal structure of 4g be-
longed to a monoclinic crystal system and P 21/n space
group. Single-crystal X-ray diffraction analysis was em-
ployed to prove the relative trans-configuration.
the dehydrofluorination of the resulting 4h followed by
aromaticity. Polymethoxy styrylnaphthalene 4h-1 was the
surrogate of combretastatin A-4 (CA-4). Combretastatin is a
naturally occurring well known tubulin polymerization in-
hibitor.33
Me
Me
OMe
OMe
MeO
F
MeO
1) NaBH4, MeOH–THF, rt, 30 min
2) DAST, CH2Cl2, rt, 5 h
O
1w
Ph
4w (ND)
Ph
OMe
OMe
MeO
MeO
1) NaBH4, MeOH–THF, rt, 30 min
2) DAST, CH2Cl2, rt, 60 h
O
However, when R was a 4-nitrophenyl group, complex
products resulted due to the presence of the stronger elec-
tron-withdrawing group (Table 2, entry 19). On the other
hand, entry 20 showed that when R was an aliphatic iso-
amyl [(CH2)2CHMe2] group, the results were similar to entry
19. The complex mixture should include different in situ
formed dehydrated olefinic isomers. Especially, when 1u
with a 9-anthracenyl group was treated by the two-step
method, only 5a with a keto group was isolated in a high
yield (96%). The structure of 5a was determined by single-
crystal X-ray crystallography.32 The possible reason could
be that the bulkier anthracenyl group forced the hydride
(from NaBH4) and it could not advance 1,2-reduction to
generate a secondary alcohol group such that 5a with a car-
bonyl group was formed by the 1,4-reduction process.
Then, the bulky anthracenyl group could also affect the
conversion of the carbonyl group of 5a to a geminal difluoro
group such that no fluorinated products were observed by
the following DAST-mediated reaction. Also, a simple aryl
substituent without the oxygenated group (Ar = Ph) on 1v
could not afford fluorotetralin skeleton 4v by this two-step
route, and only the secondary alcohol 2v was formed in a
35% yield. For the resulting phenomenon, we envisioned
that the role of the electron-donating oxygenated group
could enrich the -electron density of the reaction system
to trigger tandem fluorocyclization. Although substrate 1
was limited to the oxygenated aryl group, it still provided a
novel and efficient transformation from o-allylchalcones to
fluorotetralins.
MeO
OMe
MeO
OMe
OMe
OMe
1h
4h-1 (76%)
Scheme 4 Reaction of 1w and 1h with NaBH4/DAST (ND: Not detected)
In summary, we have developed a concise two-step
route for the effective regio- and stereocontrolled synthesis
of 3-fluorotetralines with two stereocenters and one E-con-
figured styryl group via the NaBH4-mediated reduction of
oxygenated o-allylchalcones and sequential DAST-mediated
intramolecular annulation of the resulting alkenols in mod-
erate to good yields under mild reaction conditions. The
process provides a cascade pathway of carbon–carbon and
carbon–fluorine bond formations. Related plausible mecha-
nisms have been proposed. The structures of the key prod-
ucts were confirmed by X-ray crystallography. Further in-
vestigations regarding the synthetic applications of o-allyl-
chalcones will be conducted and published in due course.
All reagents and solvents were obtained from commercial sources
and used without further purification. Reactions were routinely car-
ried out under an atmosphere of dry N2 with magnetic stirring. Prod-
ucts in organic solvents were dried with anhyd MgSO4 before concen-
tration in vacuo. Melting points were determined with a SMP3 melt-
ing apparatus. 1H and 13C NMR spectra were recorded on a Varian
INOVA-400 spectrometer operating at 400 and at 100 MHz, respec-
tively. Chemical shifts () are reported in parts per million (ppm) and
the coupling constants (J) are given in hertz (Hz). High-resolution
mass spectra (HRMS) were measured with a mass spectrometer Fin-
nigan/Thermo Quest MAT 95XL. X-ray crystal structures were ob-
tained with an Enraf-Nonius FR-590 diffractometer (CAD4, Kappa
CCD).
On the other hand, as an extension of the two-step
route, 1w with a butenyl side chain was examined, and no
desired fluorotetralin 4w was isolated among the complex
products due to the methyl group with bulkier steric hin-
drance inhibiting the installation of the fluoride ion
(Scheme 4). Next, the conversion from oxygenated fluorote-
tralin to naphthalene was investigated. When the reaction
time was increased to 60 hours, 1h with five methoxy
groups could transform into 4h-1 in a 76% yield. By extend-
ing the reaction time, the methoxy group could promote
o-Allylchalcones 1a–w; General Procedure
NaOH (100 mg, 2.5 mmol) was added to a solution of the respective
methyl ketone (1.2 mmol) in MeOH (10 mL) at 25 °C. A solution of o-
allylbenzaldehyde 3 (1.0 mmol) in MeOH (10 mL) was added to the
reaction mixture at 25 °C. The mixture was stirred at 25 °C for 20–30
h (monitored by TLC). The solvent was concentrated under reduced
pressure. The residue was diluted with H2O (10 mL) and the mixture
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

E
M.-Y. Chang et al.
Paper
Synthesis
was extracted with EtOAc (3 × 20 mL). The combined organic layers
were washed with brine, dried, filtered, and evaporated to afford
crude product. Purification on silica gel (hexanes–EtOAc 20:1 → 6:1)
afforded the respective compound 1a–w. Compounds 1a–w are
known compounds and the analytical data are consistent with the lit-
erature data.23–31
1H NMR (400 MHz, CDCl3):  = 8.01 (d, J = 15.2 Hz, 1 H), 7.93 (d, J = 8.8
Hz, 2 H), 7.52 (d, J = 8.8 Hz, 1 H), 7.44 (d, J = 8.8 Hz, 2 H), 7.29 (d, J =
15.6 Hz, 1 H), 6.85 (d, J = 8.4 Hz, 1 H), 6.01–5.91 (m, 1 H), 5.04 (dq, J =
1.6, 10.4 Hz, 1 H), 4.91 (dq, J = 1.6, 16.8 Hz, 1 H), 3.90 (s, 3 H), 3.81 (s, 3
H), 3.61 (dt, J = 1.6, 5.6 Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 189.2, 154.6, 147.3, 143.0, 138.8,
136.7, 136.6, 134.3, 129.8 (2 ×), 128.8 (2 ×), 127.2, 122.9, 121.1, 115.8,
110.4, 60.9, 55.7, 30.0.
3-(2-Allyl-3,4-dimethoxyphenyl)-1-phenylpropenone (1a)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H20ClO3: 343.1101; found:
Yield: 265 mg (86%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 8.02 (d, J = 15.6 Hz, 1 H), 8.00–7.98 (m,
2 H), 7.57–7.45 (m, 4 H), 7.35 (d, J = 15.6 Hz, 1 H), 6.85 (d, J = 8.4 Hz, 1
H), 6.01–5.91 (m, 1 H), 5.03 (dq, J = 1.6, 10.4 Hz, 1 H), 4.92 (dq, J = 1.6,
17.2 Hz, 1 H), 3.89 (s, 3 H), 3.81 (s, 3 H), 3.61 (dt, J = 1.6, 5.6 Hz, 2 H).
343.1108.
3-(2-Allyl-3,4-dimethoxyphenyl)-1-(3-fluorophenyl)propenone
(1f)
13C{1H} NMR (100 MHz, CDCl3):  = 190.5, 154.4, 147.2, 142.5, 138.3,
136.5, 134.1, 132.4, 128.4 (2 ×), 128.3 (2 ×), 127.3, 122.8, 121.7, 115.7,
110.4, 60.8, 55.6, 29.6.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H21O3: 309.1491; found:
309.1498.
Yield: 261 mg (80%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 7.97 (d, J = 15.2 Hz, 1 H), 7.71 (d, J = 8.0
Hz, 1 H), 7.61 (ddt, J = 2.4, 4.0, 9.6 Hz, 1 H), 7.46 (d, J = 8.4 Hz, 1 H),
7.36 (dt, J = 5.6, 8.0 Hz, 1 H), 7.25 (d, J = 15.2 Hz, 1 H), 7.16 (dt, J = 2.4,
8.4 Hz, 1 H), 6.77 (d, J = 8.8 Hz, 1 H), 5.94–5.84 (m, 1 H), 4.97 (dq, J =
1.6, 10.0 Hz, 1 H), 4.86 (dq, J = 1.6, 17.2 Hz, 1 H), 3.80 (s, 3 H), 3.74 (s, 3
H), 3.54 (d, J = 5.6 Hz, 2 H).
3-(2-Allyl-3,4-dimethoxyphenyl)-1-p-tolylpropenone (1b)
13C{1H} NMR (100 MHz, CDCl3):  = 188.6 (d, J = 1.6 Hz), 162.4 (d, J =
246.4 Hz), 154.4, 147.0, 142.8, 140.2 (d, J = 6.1 Hz), 136.4, 134.0, 129.9
(d, J = 7.6 Hz), 126.8, 123.8 (d, J = 3.0 Hz), 122.7, 120.6, 119.1 (d, J =
22.0 Hz), 115.5, 114.8 (d, J = 22.0 Hz), 110.2, 60.5, 55.3, 29.7.
The analytical data of the known compound 1b are consistent with
those in the literature;34 yield; 271 mg (84%); colorless gum.
3-(2-Allyl-3,4-dimethoxyphenyl)-1-naphthalen-2-ylpropenone
(1c)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H20FO3: 327.1397; found:
327.1392.
Yield: 287 mg (80%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 8.51 (s, 1 H), 8.09 (d, J = 15.2 Hz, 1 H),
8.09 (d, J = 1.6, 8.8 Hz, 1 H), 7.98 (d, J = 8.0 Hz, 1 H), 7.93 (d, J = 8.8 Hz,
1 H), 7.89 (d, J = 7.6 Hz, 1 H), 7.62–7.54 (m, 3 H), 7.51 (d, J = 15.2 Hz, 1
H), 6.88 (d, J = 8.8 Hz, 1 H), 6.05–5.95 (m, 1 H), 5.06 (dq, J = 1.6, 10.0
Hz, 1 H), 4.94 (dq, J = 1.6, 16.8 Hz, 1 H), 3.92 (s, 3 H), 3.83 (s, 3 H), 3.64
(d, J = 6.0 Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 190.4, 154.5, 147.3, 142.5, 136.6,
135.7, 135.3, 134.2, 132.5, 129.8, 129.4, 128.4, 128.2, 127.7, 127.5,
126.6, 124.5, 123.0, 121.9, 115.8, 110.5, 60.9, 55.7, 30.0.
3-(2-Allyl-3,4-dimethoxyphenyl)-1-(3,4-dichlorophenyl)prope-
none (1g)
Yield: 316 mg (84%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 8.06 (d, J = 2.0 Hz, 1 H), 8.01 (d, J = 15.6
Hz, 1 H), 7.81 (dd, J = 2.0, 8.4 Hz, 1 H), 7.56 (d, J = 8.34 Hz, 1 H), 7.54 (d,
J = 8.8 Hz, 1 H), 7.25 (d, J = 15.6 Hz, 1 H), 6.87 (d, J = 8.4 Hz, 1 H), 6.02–
5.93 (m, 1 H), 5.06 (dq, J = 1.6, 10.0 Hz, 1 H), 4.90 (dq, J = 1.6, 17.2 Hz,
1 H), 3.92 (s, 3 H), 3.82 (s, 3 H), 3.62 (dt, J = 1.6, 5.6 Hz, 2 H);
13C{1H} NMR (100 MHz, CDCl3):  = 188.1, 154.9, 147.4, 143.8, 138.0,
137.0, 136.6, 134.5, 133.1, 130.6, 130.5, 127.5, 127.0, 123.1, 120.6,
115.9, 110.5, 61.0, 55.7, 30.0.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C24H23O3: 359.1647; found:
359.1654.
3-(2-Allyl-3,4-dimethoxyphenyl)-1-biphenyl-4-ylpropenone (1d)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H19Cl2O3: 377.0711, found:
377.0715.
Yield: 280 mg (73%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 8.11–8.06 (m, 3 H), 7.73–7.70 (m, 2 H),
7.66–7.63 (m, 2 H), 7.56 (d, J = 8.8 Hz, 1 H), 7.49–7.44 (m, 3 H), 7.41–
7.37 (m, 1 H), 6.87 (d, J = 8.4 Hz, 1 H), 6.05–5.95 (m, 1 H), 5.07 (dq, J =
1.6, 10.0 Hz, 1 H), 4.96 (dq, J = 1.6, 17.2 Hz, 1 H), 3.90 (s, 3 H), 3.83 (s, 3
H), 3.65 (dt, J = 1.6, 5.6 Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 189.8, 154.4, 147.2, 145.1, 142.3,
139.8, 137.0, 136.5, 134.2, 129.0 (2 ×), 128.8 (2 ×), 128.0, 127.4, 127.1
(2 ×), 127.0 (2 ×), 122.9, 121.5, 115.7, 110.4, 60.8, 55.6, 30.0.
3-(2-Allyl-3,4-dimethoxyphenyl)-1-(3,4,5-trimethoxyphenyl)pro-
penone (1h)
Yield: 334 mg (84%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 7.99 (d, J = 15.6 Hz, 1 H), 7.50 (d, J = 8.8
Hz, 1 H), 7.28 (d, J = 15.6 Hz, 1 H), 7.24 (s, 2 H), 6.86 (d, J = 8.8 Hz, 1 H),
6.01–5.91 (m, 1 H), 5.02 (dq, J = 2.0, 10.0 Hz, 1 H), 4.91 (dq, J = 2.0,
17.2 Hz, 1 H), 3.92 (s, 6 H), 3.91 (s, 3 H), 3.90 (s, 3 H), 3.80 (s, 3 H), 3.61
(dt, J = 2.0, 5.6 Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 189.3, 154.5, 153.0, 147.3, 142.6
(2 ×), 142.2, 136.6, 134.2, 133.7, 127.5, 123.1, 121.6, 115.9, 110.4,
105.9 (2 ×), 60.9, 56.3 (3 ×), 55.7, 30.2.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H25O3: 385.1804; found:
385.1812.
3-(2-Allyl-3,4-dimethoxyphenyl)-1-(4-chlorophenyl)propenone
(1e)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H27O6: 399.1808; found:
399.1811.
Yield: 260 mg (76%); colorless gum.
3-(2-Allyl-3-isopropoxyphenyl)-1-naphthalen-2-ylpropenone (1i)
Yield: 303 mg (85%); colorless gum.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

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M.-Y. Chang et al.
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Synthesis
1H NMR (400 MHz, CDCl3):  = 8.54 (s, 1 H), 8.20 (d, J = 15.6 Hz, 1 H),
8.11 (dd, J = 1.6, 8.4 Hz, 1 H), 7.99 (d, J = 8.0 Hz, 1 H), 7.94 (d, J = 8.8 Hz,
1 H), 7.90 (d, J = 8.0 Hz, 1 H), 7.63–7.55 (m, 3 H), 7.38 (d, J = 7.6 Hz, 1
H), 7.25 (t, J = 7.6 Hz, 1 H), 6.96 (d, J = 8.4 Hz, 1 H), 6.00-5.91 (m, 1 H),
5.02 (dq, J = 1.6, 10.0 Hz, 1 H), 4.98 (dq, J = 1.6, 16.8 Hz, 1 H), 4.60–
4.54 (m, 1 H), 3.62 (d, J = 6.0 Hz, 2 H), 1.36 (t, J = 6.0 Hz, 6 H).
13C{1H} NMR (100 MHz, CDCl3):  = 190.4, 156.0, 142.9, 136.4, 135.54,
135.48, 135.4, 132.5, 130.0, 129.7, 129.5, 128.5, 128.3, 127.8, 127.1,
126.7, 124.5, 124.0, 118.7, 115.2, 114.7, 70.3, 30.0, 22.1 (2 ×).
3-(2-Allyl-3-benzyloxy-4-methoxyphenyl)-1-naphthalen-2-ylpro-
penone (1m)
Yield: 347 mg (80%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 8.54 (s, 1 H), 8.12–8.09 (m, 2 H), 7.99
(d, J = 8.0 Hz, 1 H), 7.94 (d, J = 8.8 Hz, 1 H), 7.90 (d, J = 8.0 Hz, 1 H), 7.64
(d, J = 8.8 Hz, 1 H), 7.61–7.55 (m, 3 H), 7.51 (d, J = 8.4 Hz, 2 H), 7.43–
7.33 (m, 3 H), 6.93 (d, J = 8.4 Hz, 1 H), 6.03–5.93 (m, 1 H), 5.07 (dq, J =
1.6, 10.0 Hz, 1 H), 5.02 (s, 2 H), 4.94 (dq, J = 1.6, 17.2 Hz, 1 H), 3.94 (s, 3
H), 3.66 (d, J = 5.6 Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 190.3, 154.5, 146.1, 142.5, 137.5,
136.6, 135.6, 135.3, 134.5, 132.4, 129.8, 129.4, 128.4, 128.3 (2 ×),
128.2, 128.0 (2 ×), 127.9, 127.7, 127.5, 126.6, 124.5, 123.1, 121.7,
115.9, 110.4, 74.8, 55.7, 30.2.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C25H25O2: 357.1855; found:
357.1861.
3-(2-Allyl-3-isopropoxy-4-methoxyphenyl)-1-naphthalen-2-yl-
propenone (1j)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C30H27O3: 435.1960; found:
Yield: 294 mg (76%); colorless gum.
435.1968.
1H NMR (400 MHz, CDCl3):  = 8.52 (d, J = 0.8 Hz, 1 H), 8.12–8.08 (m, 2
H), 7.98 (d, J = 8.0 Hz, 1 H), 7.93 (d, J = 8.8 Hz, 1 H), 7.89 (d, J = 8.0 Hz,
1 H), 7.62–7.53 (m, 3 H), 7.50 (d, J = 15.2 Hz, 1 H), 6.87 (d, J = 8.8 Hz, 1
H), 6.00–5.90 (m, 1 H), 5.04 (dq, J = 1.6, 10.0 Hz, 1 H), 4.94 (dq, J = 1.6,
17.2 Hz, 1 H), 4.56–4.49 (m, 1 H), 3.89 (s, 3 H), 3.68 (dt, J = 1.6, 6.0 Hz,
2 H), 1.29 (d, J = 6.0 Hz, 6 H).
13C{1H} NMR (100 MHz, CDCl3):  = 190.5, 154.6, 145.0, 143.1, 136.5,
135.7, 135.3, 134.7, 132.5, 129.8, 129.4, 128.4, 128.1, 127.7, 127.6,
126.6, 124.6, 122.4, 121.6, 115.9, 110.2, 74.8, 55.6, 30.5, 22.6 (2 ×).
3-(2-Allyl-3,4-dimethoxyphenyl)-1-benzo[1,3]dioxol-5-ylprope-
none (1n)
Yield: 268 mg (76%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 7.98 (d, J = 15.6 Hz, 1 H), 7.60 (dd, J =
1.6, 8.4 Hz, 1 H), 7.48 (d, J = 8.4 Hz, 1 H), 7.47 (d, J = 8.4 Hz, 1 H), 7.29
(d, J = 15.6 Hz, 1 H), 6.84 (dt, J = 0.8, 8.8 Hz, 1 H), 6.83 (d, J = 8.8 Hz, 1
H), 6.01 (s, 2 H), 6.00–5.91 (m, 1 H), 5.02 (dq, J = 1.6, 10.0 Hz, 1 H),
4.91 (dq, J = 1.6, 17.2 Hz, 1 H), 3.88 (s, 3 H), 3.79 (s, 3 H), 3.60 (d, J = 6.0
Hz, 2 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H27O3: 387.1960; found:
13C{1H} NMR (100 MHz, CDCl3):  = 188.1, 154.3, 151.4, 148.1, 147.2,
141.8, 136.5, 134.0, 133.0, 127.4, 124.4, 122.7, 121.2, 115.7, 110.3,
108.3, 107.7, 101.7, 60.8, 55.6, 29.9.
387.1968.
3-(2-Allyl-3-butoxy-4-methoxyphenyl)-1-naphthalen-2-ylprope-
none (1k)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H21O5: 353.1389; found:
Yield: 296 mg (74%); colorless gum.
353.1382.
1H NMR (400 MHz, CDCl3):  = 8.50 (s, 1 H), 8.12–8.07 (m, 2 H), 7.92
(d, J = 7.6 Hz, 1 H), 7.86 (d, J = 8.8 Hz, 1 H), 7.81 (d, J = 7.6 Hz, 1 H),
7.58–7.47 (m, 4 H), 6.80 (d, J = 8.8 Hz, 1 H), 6.03–5.93 (m, 1 H), 5.05
(dq, J = 1.6, 10.0 Hz, 1 H), 4.95 (dq, J = 1.6, 16.8 Hz, 1 H), 3.92 (t, J = 6.4
Hz, 2 H), 3.82 (s, 3 H), 3.63 (d, J = 5.6 Hz, 2 H), 1.80–1.73 (m, 2 H),
1.56–1.47 (m, 2 H), 0.98 (t, J = 7.2 Hz, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 189.9, 154.4, 146.4, 142.4, 136.5,
135.4, 135.1, 134.1, 132.3, 129.6, 129.2, 128.2, 127.9, 127.5, 127.2,
126.4, 124.3, 122.6, 121.3, 115.5, 110.2, 72.8, 55.4, 32.1, 29.9, 18.9,
13.7.
3-(2-Allyl-3,4-dimethoxyphenyl)-1-(3-methoxyphenyl)prope-
none (1o)
Yield: 277 mg (82%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 8.00 (d, J = 15.2 Hz, 1 H), 7.55 (d, J = 7.6
Hz, 1 H), 7.51 (d, J = 2.4 Hz, 1 H), 7.49 (d, J = 8.8 Hz, 1 H), 7.36 (d, J = 8.0
Hz, 1 H), 7.32 (d, J = 15.6 Hz, 1 H), 7.07 (dd, J = 2.8, 8.0 Hz, 1 H), 6.82 (d,
J = 8.8 Hz, 1 H), 5.99–5.89 (m, 1 H), 5.01 (dq, J = 1.6, 10.0 Hz, 1 H), 4.91
(dq, J = 1.6, 17.2 Hz, 1 H), 3.86 (s, 3 H), 3.82 (s, 3 H), 3.78 (s, 3 H), 3.59
(d, J = 5.6 Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 190.0, 159.6, 154.3, 147.1, 142.4,
139.6, 136.4, 134.0, 129.3, 127.2, 122.8, 121.5, 120.8, 118.8, 115.6,
112.7, 110.3, 60.7, 55.5, 55.2, 29.9.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C27H29O3: 401.2117; found:
401.2123.
3-(2-Allyl-3-cyclopentyloxy-4-methoxyphenyl)-1-naphthalen-2-
ylpropenone (1l)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H23O4: 339.1596; found:
339.1590.
Yield: 342 mg ( 83%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 8.52 (s, 1 H), 8.12–8.08 (m, 2 H), 7.98
(d, J = 8.0 Hz, 1 H), 7.93 (d, J = 8.8 Hz, 1 H), 7.89 (d, J = 8.0 Hz, 1 H),
7.61–7.53 (m, 3 H), 7.50 (d, J = 15.6 Hz, 1 H), 6.87 (d, J = 8.4 Hz, 1 H),
6.00–5.91 (m, 1 H), 5.04 (dq, J = 1.6, 10.0 Hz, 1 H), 4.93 (dq, J = 1.6,
17.2 Hz, 1 H), 4.88–4.84 (m, 1 H), 3.89 (s, 3 H), 3.64 (dd, J = 1.6, 6.0 Hz,
2 H), 1.93–1.79 (m, 4 H), 1.77–1.71 (m, 2 H), 1.63–1.58 (m, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 190.5, 154.4, 145.4, 143.1, 136.5,
135.7, 135.3, 134.5, 132.5, 129.8, 129.4, 128.4, 128.1, 127.7, 127.6,
126.6, 124.6, 122.3, 121.6, 115.8, 110.4, 84.6, 55.6, 32.8 (2 ×), 30.3,
23.6 (2 ×).
3-(2-Allyl-3,4-dimethoxyphenyl)-1-(4-methoxyphenyl)prope-
none (1p)
Yield: 260 mg (77%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 8.03–7.98 (m, 3 H), 7.52 (d, J = 8.4 Hz, 1
H), 7.37 (d, J = 15.2 Hz, 1 H), 6.97 (d, J = 9.2 Hz, 2 H), 6.86 (d, J = 8.4 Hz,
1 H), 6.02–5.93 (m, 1 H), 5.04 (dq, J = 1.6, 10.4 Hz, 1 H), 4.93 (dq, J =
1.6, 16.8 Hz, 1 H), 3.91 (s, 3 H), 3.88 (s, 3 H), 3.82 (s, 3 H), 3.63 (dt, J =
1.6, 5.6 Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 188.8, 163.2, 154.3, 147.3, 141.7,
136.6, 134.1, 131.2, 130.7 (2 ×), 127.7, 122.9, 121.7, 115.8, 113.7 (2 ×),
110.4, 60.9, 55.7, 55.4, 30.1.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C28H29O3: 413.2117; found:
413.2122.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

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M.-Y. Chang et al.
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Synthesis
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H23O4: 339.1596; found:
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H27O3: 303.1960; found:
339.1605.
303.1953.
3-(2-Allyl-3,4-dimethoxyphenyl)-1-(4-trifluoromethylphe-
nyl)propenone (1q)
3-(2-Allyl-3,4-dimethoxyphenyl)-1-anthracen-9-ylpropenone (1u)
Yield: 318 mg (78%); colorless gum.
Yield: 278 mg (74%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 8.53 (s, 1 H), 8.06–8.04 (m, 2 H), 7.91–
7.89 (m, 2 H), 7.50–7.43 (m, 5 H), 7.39 (d, J = 16.0 Hz, 1 H), 7.11 (d, J =
15.6 Hz, 1 H), 6.82 (d, J = 8.4 Hz, 1 H), 5.37–5.28 (m, 1 H), 4.36 (dq, J =
1.6, 10.0 Hz, 1 H), 3.91 (dq, J = 1.6, 17.2 Hz, 1 H), 3.87 (s, 3 H), 3.69 (s, 3
H), 3.04 (dd, J = 1.6, 5.6 Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 200.6, 154.8, 147.1, 146.6 (2 ×),
135.7, 134.7, 134.3, 131.1 (2 ×), 128.5 (2 ×), 128.44, 128.40, 128.1,
126.7, 126.4 (2 ×), 125.5 (2 ×), 125.4 (2 ×), 123.2, 115.3, 110.5, 60.8,
55.7, 30.0.
1H NMR (400 MHz, CDCl3):  = 8.07 (d, J = 8.4 Hz, 2 H), 8.03 (d, J = 15.6
Hz, 1 H), 7.75 (d, J = 8.0 Hz, 2 H), 7.55 (d, J = 8.4 Hz, 1 H), 7.31 (d, J =
15.6 Hz, 1 H), 6.88 (d, J = 8.8 Hz, 1 H), 6.02–5.92 (m, 1 H), 5.04 (dq, J =
2.0, 10.0 Hz, 1 H), 4.89 (dq, J = 2.0, 17.2 Hz, 1 H), 3.92 (s, 3 H), 3.82 (s, 3
H), 3.62 (dt, J = 2.0, 5.6 Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 189.8, 154.9, 147.4, 143.9, 141.3,
136.6, 134.5, 129.0 (q, J = 32.8 Hz), 128.7 (2 ×), 127.1, 125.5 (q, J = 3.8
Hz, 2 ×), 123.1, 121.2, 120.2 (q, J = 269.3 Hz), 115.9, 110.5, 60.9, 55.7,
30.0.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C28H25O3: 409.1804; found:
409.1810.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H20F3O3: 377.1365; found:
377.1369.
3-(2-Allylphenyl)-1-phenylpropenone (1v)
3-(2-Allyl-3,4-dimethoxyphenyl)-1-thiophen-2-ylpropenone (1r)
The analytical data of the known compound 1v are consistent with
Yield: 232 mg (74%); colorless gum.
those in the literature;34 yield: 174 mg (70%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 8.05 (d, J = 15.2 Hz, 1 H), 7.83 (dd, J =
0.4, 4.0 Hz, 1 H), 7.65 (dd, J = 0.4, 4.8 Hz, 1 H), 7.51 (d, J = 8.8 Hz, 1 H),
7.25 (d, J = 15.6 Hz, 1 H), 7.16 (ddd, J = 0.4, 4.0, 4.8 Hz, 1 H), 6.86 (d, J =
8.8 Hz, 1 H), 6.02–5.92 (m, 1 H), 5.04 (dq, J = 2.0, 10.0 Hz, 1 H), 4.94
(dq, J = 2.0, 17.2 Hz, 1 H), 3.90 (s, 3 H), 3.81 (s, 3 H), 3.63 (dt, J = 2.0, 5.6
Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 182.0, 154.5, 147.3, 145.6, 141.7,
136.5, 134.3, 133.5, 131.5, 128.1, 127.3, 123.0, 121.2, 115.8, 110.4,
60.9, 55.7, 30.0.
3-[3,4-Dimethoxy-2-(1-methylallyl)phenyl]-1-phenylpropenone
(1w)
Yield: 261 mg (81%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 8.23 (d, J = 15.6 Hz, 1 H), 8.00–7.97 (m,
2 H), 7.58–7.54 (m, 1 H), 7.50–7.45 (m, 3 H), 7.25 (d, J = 15.6 Hz, 1 H),
6.84 (d, J = 8.8 Hz, 1 H), 6.15 (ddd, J = 2.4, 10.8, 17.6 Hz, 1 H), 5.10–
5.01 (m, 2 H), 4.28–4.24 (m, 1 H), 3.90 (s, 3 H), 3.80 (s, 3 H), 1.43 (d, J =
7.2 Hz, 3 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H19O3S: 315.1055; found:
315.1064.
13C{1H} NMR (100 MHz, CDCl3):  = 190.6, 154.5, 147.2, 144.1, 142.2,
139.5, 138.3, 132.4, 128.44 (2 ×), 128.37 (2 ×), 127.4, 123.6, 121.7,
113.6, 110.3, 60.9, 55.7, 34.9, 19.5.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H23O3: 323.1647: found:
323.1651.
3-(2-Allyl-3,4-dimethoxyphenyl)-1-(4-nitrophenyl)propenone
(1s)
Yield: 247 mg (70%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 7.98 (d, J = 15.2 Hz, 1 H), 7.91 (d, J = 8.8
Hz, 2 H), 7.50 (d, J = 8.4 Hz, 1 H), 7.35 (d, J = 15.2 Hz, 1 H), 6.85 (d, J =
8.4 Hz, 1 H), 6.72 (d, J = 8.8 Hz, 2 H), 6.02–5.92 (m, 1 H), 5.03 (dq, J =
2.0, 10.0 Hz, 1 H), 4.93 (dq, J = 2.0, 17.2 Hz, 1 H), 3.91 (s, 3 H), 3.81 (s, 3
H), 3.62 (dt, J = 2.0, 5.6 Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 188.3, 154.2, 150.3, 147.3, 143.1,
141.0, 136.6, 134.1, 131.0 (2 ×), 128.0, 122.8, 121.9, 115.8, 114.2 (2 ×),
110.4, 60.9, 55.7, 30.1.
3-Fluorotetralins 4a–r and 5a; General Procedure
NaBH4 (38 mg, 1.0 mmol) was added to a solution of the respective
compound 1a–r and 1u (1.0 mmol) in a mixture of MeOH (5 mL) and
THF (5 mL) at 25 °C. The reaction mixture was stirred at 25 °C for 30
min and concentrated. The residue was diluted with H2O (10 mL) and
the mixture was extracted with CH2Cl2 (3 × 20 mL). The combined or-
ganic layers were washed with brine, dried, filtered, and evaporated
to afford the corresponding crude product (nearly quantitative yield)
under reduced pressure. Without further purification, DAST (260 mg,
1.6 mmol) was added to the resulting alcohol in CH2Cl2 (10 mL) and
the mixture was stirred at 25 °C for 5 h. The mixture was diluted with
H2O (10 mL) and extracted with CH2Cl2 (3 × 20 mL). The combined or-
ganic layers were washed with brine, dried, filtered, and evaporated
to afford the crude product under reduced pressure. Purification on
silica gel (hexanes–EtOAc 100:1 → 20:1) afforded the respective com-
pound 4a–r and 5a.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H20NO5: 354.1342; found:
354.1348.
1-(2-Allyl-3,4-dimethoxyphenyl)-6-methylhept-1-en-3-one (1t)
Yield: 230 mg (76%); colorless gum.
1H NMR (400 MHz, CDCl3):  = 7.77 (d, J = 16.0 Hz, 1 H), 7.40 (d, J = 8.8
Hz, 1 H), 6.83 (d, J = 8.4 Hz, 1 H), 6.57 (d, J = 16.0 Hz, 1 H), 6.01–5.91
(m, 1 H), 5.05 (dq, J = 1.6, 10.0 Hz, 1 H), 4.92 (dq, J = 1.6, 16.8 Hz, 1 H),
3.90 (s, 3 H), 3.80 (s, 3 H), 3.60 (dt, J = 1.6, 5.6 Hz, 2 H), 2.64–2.60 (m, 2
H), 1.64–1.53 (m, 3 H), 0.92 (d, J = 6.4 Hz, 6 H).
3-Fluoro-5,6-dimethoxy-1-styryl-1,2,3,4-tetrahydronaphthalene
(4a)
13C{1H} NMR (100 MHz, CDCl3):  = 201.0, 154.3, 147.3, 140.0, 136.6,
133.7, 127.1, 126.0, 122.7, 115.8, 110.5, 60.9, 55.7, 38.6, 33.5, 30.1,
27.8, 22.4 (2 ×).
Yield: 256 mg (82%); colorless solid; mp 95–97 °C (hexanes–EtOAc).
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M.-Y. Chang et al.
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Synthesis
1H NMR (400 MHz, CDCl3):  = 7.42–7.38 (m, 2 H), 7.35–7.30 (m, 2 H),
7.26–7.21 (m, 1 H), 6.97 (d, J = 8.4 Hz, 1 H), 6.78 (d, J = 8.4 Hz, 1 H),
6.49 (d, J = 8.0 Hz, 1 H), 6.21 (ddd, J = 0.8, 8.8, 15.6 Hz, 1 H), 5.30–5.13
(m, 1 H), 3.85 (s, 3 H), 3.84 (s, 3 H), 3.15 (t, J = 4.0 Hz, 1 H), 3.08 (dq, J =
4.0, 16.0 Hz, 1 H), 2.35–2.27 (m, 1 H), 1.98–1.83 (m, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 151.0, 146.8, 140.7, 140.1, 136.2,
133.5, 130.9, 130.3, 128.8 (2 ×), 127.3 (3 ×), 127.2, 126.9 (2 ×), 126.6 (2 ×),
124.1, 110.6, 87.2 (d, J = 166.7 Hz), 60.0, 55.8, 38.5 (d, J = 6.0 Hz), 34.9
(d, J = 19.7 Hz), 29.9 (d, J = 22.8 Hz).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H26FO2: 389.1917; found:
13C{1H} NMR (100 MHz, CDCl3):  = 150.9, 146.9, 137.2, 133.3, 131.3,
130.3, 128.6 (2 ×), 127.3, 127.2, 126.2 (2 ×), 124.1, 110.6, 87.2 (d, J =
166.8 Hz), 60.0, 55.8, 38.5 (d, J = 6.8 Hz), 34.9 (d, J = 20.5 Hz), 29.9 (d,
J = 22.7 Hz).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H22FO2: 313.1604; found:
313.1605.
389.1921.
1-[2-(4-Chlorophenyl)vinyl]-3-fluoro-5,6-dimethoxy-1,2,3,4-tet-
rahydronaphthalene (4e)
Yield: 277 mg (80%); colorless solid; mp 127–129 °C (hexanes–
EtOAc).
1H NMR (400 MHz, CDCl3):  = 7.29–7.20 (m, 4 H), 6.98 (d, J = 8.4 Hz, 1
H), 6.75 (d, J = 8.8 Hz, 1 H), 6.41 (d, J = 16.0 Hz, 1 H), 6.14 (ddd, J = 0.8,
8.8, 15.6 Hz, 1 H), 5.25–5.08 (m, 1 H), 3.81–3.75 (m, 1 H), 3.81 (s, 3 H),
3.80 (s, 3 H), 3.10 (t, J = 4.0 Hz, 1 H), 3.04 (dq, J = 4.8, 18.4 Hz, 1 H),
2.30–2.22 (m, 1 H), 1.93–1.78 (m, 1 H).
3-Fluoro-5,6-dimethoxy-1-(2-p-tolylvinyl)-1,2,3,4-tetrahy-
dronaphthalene (4b)
Yield: 251 mg (77%); colorless solid; mp 107–109 °C (hexanes–
EtOAc).
1H NMR (400 MHz, CDCl3):  = 7.28 (d, J = 8.0 Hz, 2 H), 7.13 (d, J = 8.0
Hz, 2 H), 6.89 (d, J = 8.4 Hz, 1 H), 6.76 (d, J = 8.4 Hz, 1 H), 6.45 (d, J =
16.0 Hz, 1 H), 6.15 (dd, J = 8.4, 15.6 Hz, 1 H), 5.29–5.13 (m, 1 H), 3.85
(s, 3 H), 3.84 (s, 3 H), 3.84–3.77 (m, 1 H), 3.14 (t, J = 4.0 Hz, 1 H), 3.07
(dq, J = 4.4, 18.4 Hz, 1 H), 2.34 (s, 3 H), 2.33–2.26 (m, 1 H), 1.96–1.82
(m, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 151.0, 146.8, 135.7, 134.0, 132.9,
130.1, 130.0, 128.8 (2 ×), 127.4 (2 ×), 127.1 (d, J = 3.1 Hz), 124.0, 110.6,
87.1 (d, J = 167.5 Hz), 60.0, 55.8, 38.5 (d, J = 6.8 Hz), 34.8 (d, J = 19.7
Hz), 29.9 (d, J = 22.7 Hz).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H21ClFO2: 347.1214; found:
347.1215.
13C{1H} NMR (100 MHz, CDCl3):  = 150.9, 146.7, 137.1, 134.4, 132.3,
131.1, 130.5, 129.2 (2 ×), 127.0 (d, J = 3.1 Hz), 126.1 (2 ×), 124.1, 110.5,
87.2 (d, J = 166.8 Hz), 60.0, 55.8, 38.5 (d, J = 6.8 Hz), 35.0 (d, J = 19.7
Hz), 29.9 (d, J = 23.5 Hz), 21.1.
3-Fluoro-1-[2-(4-fluorophenyl)vinyl]-5,6-dimethoxy-1,2,3,4-tet-
rahydronaphthalene (4f)
Yield: 244 mg (74%); colorless solid; mp 100–102 °C (hexanes–
EtOAc).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H24FO2: 327.1760; found:
327.1762.
1H NMR (400 MHz, CDCl3):  = 7.30–7.23 (m, 1 H), 7.15–7.07 (m, 2 H),
6.94–6.90 (m, 2 H), 6.78 (d, J = 8.4 Hz, 1 H), 6.45 (d, J = 15.6 Hz, 1 H),
6.21 (dd, J = 8.8, 15.6 Hz, 1 H), 5.29–5.12 (m, 1 H), 3.84–3.79 (m, 1 H),
3.85 (s, 3 H), 3.84 (s, 3 H), 3.14 (t, J = 4.0 Hz, 1 H), 3.05 (dq, J = 4.0, 17.6
Hz, 1 H), 2.34–2.26 (m, 1 H), 1.97–1.82 (m, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 163.1 (d, J = 243.3 Hz), 151.0,
139.6 (d, J = 7.6 Hz), 134.7, 130.3 (d, J = 2.3 Hz), 130.0, 129.9, 127.2 (d,
J = 21.2 Hz), 124.0, 122.7, 122.1 (d, J = 2.3 Hz),114.1 (d, J = 21.3 Hz),
112.6 (d, J = 21.2 Hz), 110.6, 87.1 (d, J = 167.5 Hz), 60.0, 55.8, 38.4 (d,
J = 6.8 Hz), 34.8 (d, J = 19.7 Hz), 29.9 (d, J = 23.5 Hz).
2-[2-(3-Fluoro-5,6-dimethoxy-1,2,3,4-tetrahydronaphthalen-1-
yl)vinyl]naphthalene (4c)
Yield: 264 mg (73%); colorless solid; mp 151–153 °C (hexanes–
EtOAc).
1H NMR (400 MHz, CDCl3):  = 7.81–7.75 (m, 3 H), 7.73 (s, 1 H), 7.61
(dd, J = 1.6, 8.8 Hz, 1 H), 7.48–7.41 (m, 2 H), 7.00 (d, J = 8.4 Hz, 1 H),
6.79 (d, J = 8.8 Hz, 1 H), 6.65 (d, J = 15.6 Hz, 1 H), 6.33 (dd, J = 8.8, 15.6
Hz, 1 H), 5.32–5.16 (m, 1 H), 3.92–3.84 (m, 1 H), 3.85 (s, 6 H), 3.16 (d,
J = 4.4 Hz, 1 H), 3.10 (dq, J = 4.0, 18.0 Hz, 1 H), 2.39–2.31 (m, 1 H),
2.02–1.88 (m, 1 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H21F2O2: 331.1510; found:
331.1510.
13C{1H} NMR (100 MHz, CDCl3):  = 151.0, 146.8, 134.6, 133.8, 133.6,
132.9, 131.4, 130.3, 128.2, 127.9, 127.6, 127.1 (d, J = 3.0 Hz), 126.3,
125.9, 125.7, 124.2, 123.5, 110.6, 87.2 (d, J = 166.7 Hz), 60.0, 55.8, 38.6
(d, J = 6.8 Hz), 35.0 (d, J = 20.5 Hz), 30.0 (d, J = 22.8 Hz).
1-[2-(3,4-Dichlorophenyl)vinyl]-3-fluoro-5,6-dimethoxy-1,2,3,4-
tetrahydronaphthalene (4g)
Yield: 266 mg (70%); colorless solid; mp 104–106 °C (hexanes–
EtOAc).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C24H24FO2: 363.1760; found:
363.1762.
1H NMR (400 MHz, CDCl3):  = 7.46 (d, J = 2.0 Hz, 1 H), 7.37 (d, J = 8.0
Hz, 1 H), 7.19 (dd, J = 2.0, 8.4 Hz, 1 H), 6.91 (d, J = 8.8 Hz, 1 H), 6.79 (d,
J = 8.8 Hz, 1 H), 6.38 (d, J = 15.6 Hz, 1 H), 6.20 (ddd, J = 1.2, 8.8, 15.6 Hz,
1 H), 5.28–5.12 (m, 1 H), 3.85 (s, 3 H), 3.84 (s, 3 H), 3.85–3.79 (m, 1 H),
3.14 (dt, J = 4.0, 18.0 Hz, 1 H), 3.08 (dq, J = 4.0, 18.0 Hz, 1 H), 2.33–2.25
(m, 1 H), 1.97–1.82 (m, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 151.0, 146.8, 137.3, 135.5, 132.6,
130.8, 130.4, 129.6, 129.0, 127.8, 127.0 (d, J = 3.0 Hz), 125.4, 123.9,
110.6, 86.9 (d, J = 167.5 Hz), 60.0, 55.7, 38.4 (d, J = 6.8 Hz), 34.7 (d, J =
20.4 Hz), 29.8 (d, J = 22.7 Hz).
1-(2-Biphenyl-4-ylvinyl)-3-fluoro-5,6-dimethoxy-1,2,3,4-tetrahy-
dronaphthalene (4d)
Yield: 291 mg (75%); colorless solid; mp 95–97 °C (hexanes–EtOAc).
1H NMR (400 MHz, CDCl3):  = 7.62–7.56 (m, 4 H), 7.48–7.42 (m, 4 H),
7.37–7.32 (m, 1 H), 6.98 (d, J = 8.4 Hz, 1 H), 6.79 (d, J = 8.4 Hz, 1 H),
6.53 (d, J = 15.6 Hz, 1 H), 6.25 (ddd, J = 0.8, 8.8, 15.6 Hz, 1 H), 5.31–
5.15 (m, 1 H), 3.88–3.83 (m, 1 H), 3.86 (s, 3 H), 3.85 (s, 3 H), 3.16 (t, J =
4.0 Hz, 1 H), 3.09 (dq, J = 4.0, 18.0 Hz, 1 H), 2.37–2.39 (m, 1 H), 1.99–
1.85 (m, 1 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H20Cl2FO2: 381.0824;
found: 381.0823.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

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M.-Y. Chang et al.
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X-ray Crystal Data32
2-[2-(5-Butoxy-3-fluoro-6-methoxy-1,2,3,4-tetrahydronaphtha-
len-1-yl)vinyl]naphthalene (4k)
A single crystal of compound 4g was grown by slow diffusion of
EtOAc into a solution of compound 4g in CH2Cl2 to yield a colorless
prism. The compound crystallized in the monoclinic crystal system,
space group P 21/n, a = 4.6282(3) Å, b = 9.9780(6) Å, c = 38.685(3) Å,
V = 1783.5(2) Å3, Z = 4, dcalcd = 1.420 g/cm3, F(000) = 792, 2θ range
1.054–26.433°, R indices (all data): R1 = 0.0841, wR2 = 0.1957.
Yield: 275 mg (68%); colorless solid; mp 138–140 °C (hexanes–
EtOAc).
1H NMR (400 MHz, CDCl3):  = 7.81–7.77 (m, 3 H), 7.73 (s, 1 H), 7.61
(dd, J = 1.6, 8.8 Hz, 1 H), 7.49–7.41 (m, 2 H), 6.98 (d, J = 8.8 Hz, 1 H),
6.79 (d, J = 8.4 Hz, 1 H), 6.64 (d, J = 15.6 Hz, 1 H), 6.35 (dd, J = 8.4, 15.6
Hz, 1 H), 5.32–5.15 (m, 1 H), 4.04–3.85 (m, 3 H), 3.84 (s, 3 H), 3.17 (d,
J = 4.4 Hz, 1 H), 3.10 (dq, J = 2.0, 18.0 Hz, 1 H), 2.38–2.30 (m, 1 H),
2.03–1.89 (m, 1 H), 1.85–1.76 (m, 2 H), 1.59–1.49 (m, 2 H), 1.01 (t, J =
7.6 Hz, 3 H).
3-Fluoro-5,6-dimethoxy-1-[2-(3,4,5-trimethoxyphenyl)vinyl]-
1,2,3,4-tetrahydronaphthalene (4h)
Yield: 269 mg (67%); colorless gum.
13C{1H} NMR (100 MHz, CDCl3):  = 151.0, 146.2, 134.7, 133.9, 133.6,
132.8, 131.3, 130.2, 128.1, 127.9, 127.6, 127.2 (d, J = 3.1 Hz), 126.2,
125.9, 125.7, 123.9, 123.5, 110.7, 87.3 (d, J = 166.7 Hz), 72.3, 55.8, 38.7
(d, J = 6.8 Hz), 35.0 (d, J = 19.7 Hz), 32.5, 30.2 (d, J = 22.7 Hz), 19.3,
14.0.
1H NMR (400 MHz, CDCl3):  = 6.97 (d, J = 8.8 Hz, 1 H), 6.79 (d, J = 8.4
Hz, 1 H), 6.61 (s, 2 H), 6.41 (d, J = 15.6 Hz, 1 H), 6.12 (dd, J = 8.8, 15.6
Hz, 1 H), 5.30–5.13 (m, 1 H), 3.87 (s, 6 H), 3.85 (s, 3 H), 3.844 (s, 3 H),
3.840 (s, 3 H), 3.86–3.80 (m, 1 H), 3.14 (dt, J = 4.0, 18.0 Hz, 1 H), 3.08
(dq, J = 4.0, 18.0 Hz, 1 H), 2.35–2.27 (m, 1 H), 1.98–1.84 (m, 1 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C27H30FO2: 405.2230; found:
405.2234.
13C{1H} NMR (100 MHz, CDCl3):  = 153.4 (2 ×), 151.0, 146.8, 137.7,
132.9, 132.8, 131.2, 130.2, 124.4, 124.1, 110.6, 103.2 (2 ×), 87.1 (d, J =
167.5 Hz), 60.9, 60.0, 56.1 (2 ×), 55.8, 38.4 (d, J = 6.8 Hz), 35.0 (d, J =
20.5 Hz), 29.9 (d, J = 23.5 Hz).
2-[2-(5-Cyclopentyloxy-3-fluoro-6-methoxy-1,2,3,4-tetrahy-
dronaphthalen-1-yl)vinyl]naphthalene (4l)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H28FO5: 403.1921; found:
403.1922.
Yield: 300 mg (72%); colorless solid; mp 125–127 °C (hexanes–
EtOAc).
1H NMR (400 MHz, CDCl3):  = 7.81–7.77 (m, 3 H), 7.72 (s, 1 H), 7.60
(dd, J = 1.6, 8.8 Hz, 1 H), 7.48–7.41 (m, 2 H), 6.95 (d, J = 8.4 Hz, 1 H),
6.78 (d, J = 8.4 Hz, 1 H), 6.62 (d, J = 15.6 Hz, 1 H), 6.35 (dd, J = 8.4, 15.6
Hz, 1 H), 5.29–5.12 (m, 1 H), 4.95–4.91 (m, 1H), 4.00–3.85 (m, 1 H),
3.83 (s, 3 H), 3.12 (d, J = 4.4 Hz, 1 H), 3.07 (dq, J = 2.0, 18.0 Hz, 1 H),
2.36–2.28 (m, 1 H), 2.03–1.97 (m, 1 H), 1.95–1.61 (m, 8 H).
13C{1H} NMR (100 MHz, CDCl3):  = 150.8, 145.0, 134.7, 134.09, 133.6,
132.8, 131.2, 130.3, 128.1, 127.9, 127.6, 127.6 (d, J = 3.8 Hz), 126.2,
125.9, 125.7, 123.6, 123.4, 110.8, 87.4 (d, J = 166.8 Hz), 83.9, 55.8, 38.9
(d, J = 6.8 Hz), 35.0 (d, J = 19.7 Hz), 32.2, 32.9, 30.6 (d, J = 22.8 Hz),
23.74, 23.73.
2-[2-(3-Fluoro-5-isopropoxy-1,2,3,4-tetrahydronaphthalen-1-
yl)vinyl]naphthalene (4i)
Rotamer ratio = 1:1; yield: 263 mg (73%); colorless solid; mp 109–
110 °C (hexanes–EtOAc).
1H NMR (400 MHz, CDCl3):  = 7.84–7.70 (m, 4 H), 7.61 (dt, J = 2.0, 8.8
Hz, 1 H), 7.48–7.40 (m, 2 H), 7.16–7.09 (m, 1 H), 6.76–6.34 (m, 3 H),
6.05–6.00 (m, 1 H), 5.33–5.13 (m, 1 H), 4.62–4.49 (m, 2 H), 3.97–3.64
(m, 1 H), 3.08–3.01 (m, 1 H), 2.60–2.30 (m, 1 H), 2.09–1.94 (m, 1 H),
1.38 (d, J = 6.4 Hz, 3 H), 1.37 (d, J = 7.2 Hz, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 155.9, 138.7, 134.7, 133.7, 133.0,
131.4, 130.3, 127.9, 127.6, 126.4, 125.8, 125.5, 123.5, 122.1, 120.5,
119.9, 112.4, 110.0, 87.4 (d, J = 166.8 Hz), 42.0, 39.4 (d, J = 6.8 Hz),
34.9 (d, J = 19.7 Hz), 30.0 (d, J = 22.8 Hz), 29.7 (d, J = 6.1 Hz), 22.2 (d, J =
26.0 Hz).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C28H30FO2: 417.2230; found:
417.2231.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C25H26FO: 361.1968; found:
361.1965.
2-[2-(5-Benzyloxy-3-fluoro-6-methoxy-1,2,3,4-tetrahydronaph-
thalen-1-yl)vinyl]naphthalene (4m)
Yield: 307 mg (70%); colorless solid; mp 161–163 °C (hexanes–
EtOAc).
2-[2-(3-Fluoro-5-isopropoxy-6-methoxy-1,2,3,4-tetrahydronaph-
thalen-1-yl)vinyl]naphthalene (4j)
1H NMR (400 MHz, CDCl3):  = 7.82–7.78 (m, 3 H), 7.74 (s, 1 H), 7.61
(dd, J = 1.6, 8.4 Hz, 1 H), 7.51–7.33 (m, 7 H), 7.02 (d, J = 8.4 Hz, 1 H),
6.84 (d, J = 8.4 Hz, 1 H), 6.64 (d, J = 16.0 Hz, 1 H), 6.34 (dd, J = 8.4, 15.6
Hz, 1 H), 5.25–5.09 (m, 1 H), 5.08 (d, J = 10.8 Hz, 1 H), 5.02 (d, J = 11.2
Hz, 1 H), 3.92–3.84 (m, 1 H), 3.89 (s, 3 H), 3.10 (dt, J = 4.0, 18.4 Hz, 1
H), 3.03 (dq, J = 3.6, 18.4 Hz, 1 H), 2.36–2.28 (m, 1 H), 1.99–1.85 (m, 1
H).
13C{1H} NMR (100 MHz, CDCl3):  = 151.0, 145.7, 137.9, 134.6, 133.8,
133.6, 132.8, 131.4, 130.3, 128.4 (2 ×), 128.2, 128.1, 127.92, 127.87,
127.6, 127.43, 127.39, 126.2, 125.9, 125.7, 124.2, 123.5, 110.7, 87.2 (d,
J = 166.8 Hz), 74.1, 55.9, 38.7 (d, J = 6.8 Hz), 34.9 (d, J = 19.7 Hz), 30.3
(d, J = 22.7 Hz).
Yield: 254 mg (65%); colorless solid; mp 141–143 °C (hexanes–
EtOAc).
1H NMR (400 MHz, CDCl3):  = 7.82–7.75 (m, 3 H), 7.73 (s, 1 H), 7.64
(dd, J = 1.6, 8.8 Hz, 1 H), 7.49–7.42 (m, 2 H), 6.97 (d, J = 8.4 Hz, 1 H),
6.79 (d, J = 8.4 Hz, 1 H), 6.63 (d, J = 16.0 Hz, 1 H), 6.36 (dd, J = 8.8, 16.0
Hz, 1 H), 5.30–5.13 (m, 1 H), 4.62–4.55 (m, 1 H), 3.93–3.87 (m, 1 H),
3.83 (s, 3 H), 3.17 (d, J = 4.4 Hz, 1 H), 3.11 (dq, J = 2.0, 18.0 Hz, 1 H),
2.38–2.31 (m, 1 H), 2.04–1.90 (m, 1 H), 1.34 (d, J = 6.0 Hz, 3 H), 1.31 (t,
J = 6.0 Hz, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 151.0, 144.8, 134.7, 134.0, 133.6,
132.8, 131.2, 130.2, 128.1, 127.9, 127.7 (d, J = 3.8 Hz), 127.6, 126.2,
125.9, 125.7, 123.6, 123.5, 110.6, 87.4 (d, J = 167.6 Hz), 74.3, 55.7, 38.9
(d, J = 6.0 Hz), 35.1 (d, J = 19.7 Hz), 30.8 (d, J = 22.8 Hz), 22.8, 22.7.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C30H28FO2: 439.2073; found:
439.2074.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H28FO2: 391.2073; found:
391.2074.
5-[2-(3-Fluoro-5,6-dimethoxy-1,2,3,4-tetrahydronaphthalen-1-
yl)vinyl]benzo[1,3]dioxole (4n)
Yield: 260 mg (73%); colorless solid; mp 97–99 °C (hexanes–EtOAc).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

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M.-Y. Chang et al.
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1H NMR (400 MHz, CDCl3):  = 6.96–6.93 (m, 2 H), 6.82–6.75 (m, 3 H),
6.39 (d, J = 15.6 Hz, 1 H), 6.02 (dd, J = 8.4, 15.6 Hz, 1 H), 5.95 (s, 2 H),
5.28–5.12 (m, 1 H), 3.85 (s, 3 H), 3.83 (s, 3 H), 3.85–3.75 (m, 1 H), 3.13
(dt, J = 4.0, 18.0 Hz, 1 H), 3.07 (dq, J = 4.0, 18.0 Hz, 1 H), 2.33–2.25 (m,
1 H), 1.95–1.81 (m, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 150.9, 148.0, 147.0, 146.7, 131.7,
131.6, 130.9, 130.4, 127.1, 124.1, 120.7, 110.5, 108.3, 105.6, 101.0,
87.2 (d, J = 166.7 Hz), 60.0, 55.8, 38.4 (d, J = 6.8 Hz), 35.0 (d, J = 19.7
Hz), 29.9 (d, J = 22.7 Hz).
2-[2-(3-Fluoro-5,6-dimethoxy-1,2,3,4-tetrahydronaphthalen-1-
yl)vinyl]thiophene (4r)
Yield: 223 mg (70%); colorless solid; mp 94–96 °C (hexanes–EtOAc).
1H NMR (400 MHz, CDCl3):  = 7.13 (d, J = 8.4 Hz, 1 H), 7.01–6.94 (m, 3
H), 6.79 (d, J = 8.4 Hz, 1 H), 6.59 (d, J = 15.6 Hz, 1 H), 6.05 (dd, J = 8.8,
15.2 Hz, 1 H), 5.28–5.12 (m, 1 H), 3.87–3.80 (m, 1 H), 3.852 (s, 3 H),
3.846 (s, 3 H), 3.13 (d, J = 4.0 Hz, 1 H), 3.07 (dq, J = 4.4, 18.4 Hz, 1 H),
2.33–2.25 (m, 1 H), 1.97–1.82 (m, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 151.0, 146.7, 142.3, 133.1, 131.0,
130.0, 127.3, 125.1, 124.5, 124.1, 123.7, 110.6, 87.1 (d, J = 166.8 Hz),
60.0, 55.8, 38.4 (d, J = 6.8 Hz), 34.8 (d, J = 19.7 Hz), 29.9 (d, J = 22.8 Hz).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H22FO4: 357.1502; found:
357.1503.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H20FO2S: 319.1168; found:
319.1164.
3-Fluoro-5,6-dimethoxy-1-[2-(3-methoxyphenyl)vinyl]-1,2,3,4-
tetrahydronaphthalene (4o)
Yield : 222 mg (65%); colorless gum.
3-(2-Allyl-3,4-dimethoxyphenyl)-1-anthracen-9-ylpropan-1-one
(5a)
1H NMR (400 MHz, CDCl3):  = 7.24 (t, J = 8.0 Hz, 1 H), 6.99 (d, J = 9.2
Hz, 1 H), 6.96 (d, J = 9.6 Hz, 1 H), 6.93 (t, J = 1.6 Hz, 1 H), 6.81–6.77 (m,
2 H), 6.46 (d, J = 15.6 Hz, 1 H), 6.20 (dd, J = 8.8, 15.6 Hz, 1 H), 5.30–5.13
(m, 1 H), 3.85 (s, 3 H), 3.84 (s, 3 H), 3.82 (s, 3 H), 3.85–3.81 (m, 1 H),
3.14 (dt, J = 4.0, 18.0 Hz, 1 H), 3.07 (dq, J = 4.0, 18.0 Hz, 1 H), 2.35–2.27
(m, 1 H), 1.97–1.83 (m, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 159.8, 150.9, 146.8, 138.6, 133.6,
131.2, 130.2, 129.5, 127.0 (d, J = 3.1 Hz), 124.1, 118.9, 113.0, 111.4,
110.6, 87.1 (d, J = 167.6 Hz), 60.0, 55.8, 55.2, 38.4 (d, J = 6.1 Hz), 34.9
(d, J = 20.5 Hz), 29.9 (d, J = 22.8 Hz).
Yield: 394 mg (96%); colorless solid; mp 98–100 °C (hexanes–EtOAc).
1H NMR (400 MHz, CDCl3):  = 8.45 (s, 1 H), 8.02–7.98 (m, 2 H), 7.76–
7.72 (m, 2 H), 7.49–7.45 (m, 4 H), 6.99 (d, J = 8.4 Hz, 1 H), 6.76 (d, J =
8.4 Hz, 1 H), 6.02–5.92 (m, 1 H), 4.98 (dq, J = 1.6, 10.0 Hz, 1 H), 4.89
(dq, J = 1.6, 17.2 Hz, 1 H), 3.84 (s, 3 H), 3.83 (s, 3 H), 3.52 (dt, J = 1.6, 5.6
Hz, 2 H), 3.36–3.32 (m, 2 H), 3.24–3.20 (m, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 209.5, 151.1, 147.3, 137.0 (2 ×),
136.3, 132.1, 131.7, 130.9 (2 ×), 128.7 (2 ×), 128.1, 126.8, 126.6 (2 ×),
125.3 (2 ×), 124.5, 124.2 (2 ×), 114.9, 110.4, 60.7, 55.5, 47.6, 30.5, 26.2.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H24FO3: 343.1710; found:
343.1711.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C28H27O3: 411.1960; found:
411.1962.
3-Fluoro-5,6-dimethoxy-1-[2-(4-methoxyphenyl)vinyl]-1,2,3,4-
tetrahydronaphthalene (4p)
X-ray Crystal Data32
Single-crystal of compound 5a was grown by slow diffusion of EtOAc
into a solution of compound 5a in CH2Cl2 to yield a colorless prism.
The compound crystallized in the triclinic crystal system, space group
P –1, a = 9.9598(15) Å, b = 10.2975(16) Å, c = 11.5688(19) Å, V =
1092.8(3) Å3, Z = 2, dcalcd = 1.247 g/cm3, F(000) = 436, 2θ range 1.797–
26.535°, R indices (all data): R1 = 0.0664, wR2 = 0.1337.
Yield: 260 mg (76%); colorless solid; mp 98–100 °C (hexanes–EtOAc).
1H NMR (400 MHz, CDCl3):  = 7.32 (d, J = 8.8 Hz, 2 H), 6.97 (d, J = 9.2
Hz, 1 H), 6.86 (d, J = 8.8 Hz, 2 H), 6.43 (d, J = 16.0 Hz, 1 H), 6.05 (ddd,
J = 0.8, 8.8, 16.0 Hz, 1 H), 5.29–5.13 (m, 1 H), 3.86–3.81 (m, 1 H), 3.85
(s, 3 H), 3.84 (s, 3 H), 3.81 (s, 3 H), 3.14 (t, J = 3.6 Hz, 1 H), 3.07 (dq, J =
4.8, 18.4 Hz, 1 H), 2.33–2.26 (m, 1 H), 1.96–1.82 (m, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 159.0, 150.9, 146.7, 131.1, 130.7,
130.6, 130.0, 127.3 (2 ×), 127.0 (d, J = 3.0 Hz), 124.1, 114.0 (2 ×), 110.5,
87.2 (d, J = 176.8 Hz), 60.0, 55.8, 55.3, 38.5 (d, J = 6.1 Hz), 35.0 (d, J =
19.7 Hz), 29.9 (d, J = 22.7 Hz).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H24FO3: 343.1710; found:
343.1712.
1,2-Dimethoxy-5-[2-(3,4,5-trimethoxyphenyl)vinyl]naphthalene
(4h-1)
NaBH4 (38 mg, 1.0 mmol) was added to a solution of compound 1h
(398 mg, 1.0 mmol) in a mixture of MeOH (5 mL) and THF (5 mL) at
25 °C. The reaction mixture was stirred at 25 °C for 30 min and con-
centrated. The residue was diluted with H2O (10 mL) and the mixture
was extracted with CH2Cl2 (3 × 20 mL). The combined organic layers
were washed with brine, dried, filtered, and evaporated to afford the
crude product (quantitative yield) under reduced pressure. Without
further purification, DAST (260 mg, 1.6 mmol) was added to the re-
sulting alcohol in CH2Cl2 (10 mL). The mixture was stirred at 25 °C for
60 h, diluted with H2O (10 mL), extracted with CH2Cl2 (3 × 20 mL). The
combined organic layers were washed with brine, dried, filtered, and
evaporated to afford the crude product under reduced pressure. Puri-
fication on silica gel (hexanes–EtOAc 100:1 → 20:1) afforded com-
pound 4h-1; yield: 289 mg (76%); colorless solid; mp 195–197 °C
(hexanes–EtOAc).
3-Fluoro-5,6-dimethoxy-1-[2-(4-trifluoromethylphenyl)vinyl]-
1,2,3,4-tetrahydronaphthalene (4q)
Yield: 281 mg (74%); colorless solid; mp 112–114 °C (hexanes–
EtOAc).
1H NMR (400 MHz, CDCl3):  = 7.57 (d, J = 8.0 Hz, 2 H), 7.48 (d, J = 8.0
Hz, 2 H), 6.93 (d, J = 8.4 Hz, 1 H), 6.79 (d, J = 8.4 Hz, 1 H), 6.52 (d, J =
15.6 Hz, 1 H), 6.31 (dd, J = 8.8, 16.0 Hz, 1 H), 5.28–5.15 (m, 1 H), 3.85–
3.84 (m, 1 H), 3.85 (s, 3 H), 3.84 (s, 3 H), 3.14 (t, J = 3.6 Hz, 1 H), 3.06
(dq, J = 3.6, 18.4 Hz, 1 H), 2.35–2.29 (m, 1 H), 1.98–1.84 (m, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 151.1, 146.9, 140.7, 140.6, 136.1,
130.1, 129.7, 127.08, 127.05, 126.3 (2 ×), 125.5 (d, J = 3.8 Hz, 2 ×),
124.0, 110.6, 87.0 (d, J = 167.5 Hz), 60.0, 55.8, 38.5 (d, J = 6.8 Hz), 34.7
(d, J = 20.5 Hz), 29.9 (d, J = 22.7 Hz).
1H NMR (400 MHz, CDCl3):  = 8.11 (d, J = 8.4 Hz, 1 H), 7.97 (d, J = 9.2
Hz, 1 H), 7.71 (d, J = 16.0 Hz, 1 H), 7.59 (d, J = 7.2 Hz, 1 H), 7.48 (t, J =
8.4 Hz, 1 H), 7.34 (d, J = 9.6 Hz, 1 H), 7.06 (d, J = 15.6 Hz, 1 H), 6.82 (s, 2
H), 4.02 (s, 3 H), 4.01 (s, 3 H), 3.95 (s, 6 H), 3.89 (s, 3 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H21F4O2: 381.1478; found:
381.1482.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

K
M.-Y. Chang et al.
Paper
Synthesis
13C{1H} NMR (100 MHz, CDCl3):  = 153.5 (2 ×), 148.3, 143.2, 138.2,
134.9, 133.4, 131.8, 129.6, 127.6, 126.1, 125.5, 122.0, 121.3, 120.2,
115.0, 103.8 (2 ×), 61.2, 61.0, 56.8, 56.2 (2 ×).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H28FO5: 381.1702; found:
381.1705.
(12) Selected examples for the synthesis of 4-fluorotetrahydropy-
rans, see: (a) Al-Mutairi, E. H.; Crosby, S. R.; Darzi, J.; Harding, J.
R.; Hughes, R. A.; King, C. D.; Simpson, T. J.; Smith, R. W.; Willis,
C. L. Chem. Commun. 2001, 835. (b) Kataoka, K.; Ode, Y.;
Matsumoto, M.; Nokami, J. Tetrahedron 2006, 62, 2471. (c) Luo,
H.-Q.; Hu, X.-H.; Loh, T.-P. Tetrahedron Lett. 2010, 51, 1041.
(13) Selected examples for the synthesis of 3- or 4-fluoropiperidines,
see: (a) Vardelle, E.; Martin-Mingot, A.; Jouannetaud, M.;
Bachmann, C.; Marrot, J.; Thibaudeau, S. J. Org. Chem. 2009, 74,
6025. (b) Kishi, Y.; Nagura, H.; Inagi, S.; Fuchigami, T. Chem.
Commun. 2008, 3876. (c) Okoromoba, O. E.; Hammond, G. B.;
Xu, B. Org. Lett. 2015, 17, 3975.
Funding Information
The authors would like to thank the Ministry of Science and Technol-
ogy, Taiwan for its financial support (MOST 106-2628-M-037-001-
MY3).
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J. Org. Chem. 2013, 78, 5521.
(15) Nonn, M.; Kiss, L.; Haukka, M.; Fustero, S.; Fülöp, F. Org. Lett.
2015, 17, 1074.
Supporting Information
(16) Huang, H. T.; Lacy, T. C.; Blachut, B.; Ortiz, G. X. Jr.; Wang, Q. Org.
Lett. 2013, 15, 1818.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1612419.
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(17) Yan, T.; Zhou, B.; Xue, X. S.; Cheng, J. P. J. Org. Chem. 2016, 81,
9006.
(18) Li, F.; Nie, J.; Wu, J. W.; Zheng, Y.; Ma, J. A. J. Org. Chem. 2012, 77,
2398.
(19) Probst, N.; Martin, A.; Désiré, J.; Mingot, A.; Marrot, J.; Blériot,
Y.; Thibaudeau, S. Org. Lett. 2017, 19, 1040.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K