Thermolytic Synthesis of Naphthalenes via Intramolecular Cyclocondensation of o -Phenylallylbenzaldehydes

Article abstract of DOI:10.1055/s-0037-1610175

The development of intramolecular carbonyl-ene type cyclocondensation of oxygenated o -phenylallylbenzaldehydes in refluxing decalin is reported. The facile and easy-to-operate thermolytic rearrangement procedure generates substituted naphthalenes in good to excellent yields.Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0037-1610175

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–L
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M.-Y. Chang, N.-C. Hsueh
Paper
Synthesis
Thermolytic Synthesis of Naphthalenes via Intramolecular
Cyclocondensation of o-Phenylallylbenzaldehydes
Meng-Yang Chang*a,b
Nai-Chen Hsueha
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Intramolecular carbonyl-ene cyclocondensation/Claisen rearrangement
MeO
HO
MeO
O
MeO
O
Ph
decalin
reflux
a Department of Medicinal and Applied Chemistry, Kaohsiung
Medical University, Kaohsiung 807, Taiwan
mychang@kmu.edu.tw
b Department of Medical Research, Kaohsiung Medical University
Hospital, Kaohsiung 807, Taiwan
+
Ph
Ph
O
Ph
Ph
Ph
Received: 28.02.2018
Accepted after revision: 04.05.2018
Published online: 13.06.2018
access for the construction of a naphthalene skeleton via
carbonyl-ene type cyclocondensation of oxygenated o-
phenylallylbenzaldehydes.
DOI: 10.1055/s-0037-1610175; Art ID: ss-2018-h0132-op
Abstract The development of intramolecular carbonyl-ene type cyclo-
condensation of oxygenated o-phenylallylbenzaldehydes in refluxing
decalin is reported. The facile and easy-to-operate thermolytic rear-
rangement procedure generates substituted naphthalenes in good to
excellent yields.
intramolecular
cyclocondensation
Ar
Ar
O
metal complexes (ref. 2)
Organobases (ref. 3)
Thermolysis (this work)
Lewis acids (ref. 4)
Key words carbonyl-ene type, cyclocondensation, o-carbonyl allyl-
benzenes, substituted naphthalenes
Photolytic irradiation (ref. 5)
Scheme 1 Methods for intramolecular cyclocondensation of o-carbonyl
allylbenzenes
Intramolecular cyclocondensation reactions for the con-
struction of diversified molecules from simple building
blocks have been indentified as attractive synthetic proto-
cols because they provide a facile and easy-operational syn-
thetic route and combine rapid and efficient transforma-
tions in one-single reaction vessel.1 Among these method-
ologies, various promoters mediating the synthesis of
substituted naphthalenes via cyclocondensation of o-car-
bonyl allylbenzenes and their derivatives have been well
developed (Scheme 1)2–5 including: (1) metal complex
(Au+/Ag+, Rh+)-catalyzed one-pot benzannulations,2 (2)
Lewis acid (metal triflates) promoted Friedel–Crafts type
ring closures,3 (3) base-mediated anionic annulations,4 and
(4) photo-initiated intramolecular cyclizations.5 However, a
new method for the simple preparation of diverse naphtha-
lenes via base-free, acid-free, and transition-metal-free
promoted intramolecular annulation of o-carbonyl allyl-
benzenes is still a continuing need in the organic synthetic
field. The naphthalene ring system6 is a key core structure
for bioactive molecules,7 natural products,8 and functional-
ized materials.9 In the comparison of the above-mentioned
routes, herein, we report a most convenient thermolytic
Continuing our research interests on synthetic applica-
tions of o-allylbenzaldehydes,10 herein, we have explored a
thermolytic carbonyl-ene type cyclocondensation of oxy-
genated o-phenylallylbenzaldehydes, as shown in Scheme
2. The two-step synthetic route toward naphthalenes 4 in-
cludes: (i) Suzuki cross-coupling of 2 [prepared by bromina-
tion of isovanillin (1) followed by O-alkylation with differ-
ent alkyl halides]10f with phenylallylboronic pinacol ester11
[prepared by addition of phenylallylmagnesium bromide to
bis(pinacolato)diboron] in boiling EtOH, and (ii) intramolec-
ular carbonyl-ene type cyclocondensation of 3 in refluxing
decalin.
Initially, 2a (R = Me) was chosen as the model substrate
to examine the reaction. Pd(OAc)2-catalyzed Suzuki cross-
coupling of 2a with freshly prepared phenylallylboronic
pinacol ester afforded 3a in 67% yield in the presence of
PPh3 and Na2CO3 in boiling EtOH. However, when phenyl-
allylboronic acid was used instead of the phenylallylboronic
pinacol ester, the isolated yield of 1a was only 50%. The
potential reason was the limited solubility of phenylallyl-
boronic acid than boronic pinacol ester in boiling EtOH,
which led to the isolation of 1a in lower yield. Then,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

B
M.-Y. Chang, N.-C. Hsueh
Paper
Synthesis
Pd(OAc)2, EtOH
Na2CO3, PPh3
MeO
NBS, MeCN, then
MeO
RO
Br
K2CO3, RX, MeCN
Me
O
B
HO
Ph
Me
Me
O
O
O
RX = MeI, iPrBr, nBuBr
cC5H5Br, PhCH2Br
2a–e
1
Me
carbonyl-ene reaction
H
MeO
MeO
RO
MeO
decalin
reflux
O
RO
Ph
Ph
RO
Ph
O
H2O
A
3a, R = Me (67%)
3b, R = iPr (60%)
3c, R = nBu (54%)
4a, R = Me (96%)
4b, R = iPr (98%)
4c, R = nBu (98%)
3d, R = cC5H5 (50%)
3e, R = CH2Ph (62%)
4d, R = cC5H9 (94%)
4e, R = CH2Ph (94%)
Scheme 2 Synthesis of naphthalenes 4a–e
thermolysis-induced intramolecular cyclocondensation of
3a produced 4a in a quantitative yield (96%) in refluxing
decalin (bp ~190 °C) for 20 hours (monitored by TLC). In
particular, heat-initiated spontaneous annulation of oxy-
genated o-phenylallylbenzaldehydes is a new route for the
preparation of substituted naphthalenes. In other words,
the overall procedure involved the initial carbonyl-ene
reaction of A followed by spontaneous dehydrative aromati-
zation of the resulting homoallylic alcohol. By changing the
reaction solvents from decalin to xylene (bp ~140 °C) and
cumene (bp ~150 °C), 4a was isolated in 50% and 58% yield,
respectively, along with the recovery of starting material 3a
(38% and 25%); by increasing the time (20 → 50 h), the
yields for 4a were increased to 89% and 95%. The results
meant that the reaction solvents with low boiling points
needed longer reaction times to generate 4a. Dimethylani-
line (DMA, bp ~195 °C) was used as the reaction solvent,
however, the yield of 4a (77%) was lower than for decalin
after 20 hours. After increasing the time (20 → 30 h), an in-
soluble black precipitate was generated as the major com-
ponent and only 32% of the desired 4a was observed.
Although the substrate scopes and reaction solvents were
limited, the present synthetic method, ‘refluxing decalin’,
was a simple, open-vessel, easy-operational tool. To investi-
gate one-pot thermolytic annulation, 3b–e (R = i-Pr, n-Bu,
c-C5H9, PhCH2) were easily transformed into 4b–e in excel-
lent yields (94–98%) on the basis of the above-mentioned
reaction conditions. The structure of 4c was determined by
single-crystal X-ray crystallography (Figure 1).12
rangement products 4f,g were formed as the major compo-
nents (84% and 86%) and displaced the expected products
4f-1 (10%) and 4g-1 (trace). According to the resulting prod-
ucts, we found that the spontaneous thermolysis-induced
conversions from 3f,g into 4f,g proceeded with carbonyl-
ene cyclocondensation and a Claisen rearrangement. We
perceived that the phenyl group with a rich π-electron den-
sity should be the main driving force to promote the occur-
rence of double rearrangements.
After replacement of the bromoalkane to dibromo-
alkane, di- and monoalkylation of 1 afforded starting sub-
strates 2h and 2i, as shown in Scheme 4. Then, with Suzuki
cross-coupling of 2h,i and 3.0 or 1.5 equivalents of phenyl-
allylboronic pinacol ester, lower yields of 3h,i (47% and 40%)
were produced. For the poorer yield of 3i (40%), a possible
reason might be that 3i exhibited two bromo groups (one
aryl and one alkyl bromide), and consequently regio-
controlled cross-coupling could not be performed easily.
Under refluxing decalin, 3h,i were transformed into 4h,i in
90% and 80% yield, respectively. High-temperature condi-
tions might cause trace β-elimination of primary bromide
slightly decreasing the yield of 4i.
After testing R = alkyl group, R = allyl was studied next.
As shown in Scheme 3, 2f (R = styryl) and 2g (R = phenyl-
allyl) were chosen as the model substrates to examine the
one-pot synthesis of a naphthalene skeleton. By Suzuki
cross-coupling of 2f,g and a phenylallylboronic pinacol
ester, 3f,g with p-phenylallyl substituents were produced in
modest (62% and 61%) yields. Furthermore, when 3f,g were
treated in refluxing decalin, interestingly, Claisen rear-
Figure 1 X-ray crystal structure of 4c
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

C
M.-Y. Chang, N.-C. Hsueh
Paper
Synthesis
Pd(OAc)2, EtOH
Na2CO3, PPh3
MeO
NBS, MeCN, then
K2CO3, MeCN
MeO
Br
Me
O
B
HO
RO
Ph
O
Me
Me
O
O
Ph
1
2f,g
Me
Br
Ph
Br
or
styryl bromide
phenylallyl bromide
MeO
MeO
+
O
Ph
HO
Ph
for 3f
MeO
RO
4f-1 (10%)
4f (84%)
Ph
Ph
decalin
reflux
Ph
O
MeO
O
MeO
HO
3f, R = styryl (62%)
3g, R = phenylallyl (61%)
+
for 3g
Ph
Ph
Ph
Ph
4g-1 (trace)
4g (86%)
Scheme 3 Synthesis of naphthalenes 4f, 4g, 4f-1, and 4g-1
MeO
Br
2h
O
O
(for 2.0 equiv of 1)
O
O
MeO
Br
Br
Pd(OAc)2, EtOH
Na2CO3, PPh3
MeO
NBS, MeCN, then
K2CO3, MeCN
+
Me
Me
Me
O
B
HO
MeO
O
Ph
O
Br
Br
O
( )6
1
Me
1,6-dibromohexane
Br
O
MeO
2i
Ph
(for 1.0 equiv of 1)
O
O
O
O
Ph
MeO
MeO
MeO
3h (47%)
decalin
reflux
O
O
Ph
Ph
O
Ph
+
+
Br
MeO
O
MeO
4h (90%)
4i (80%)
Ph
Br
O
3i (40%)
Scheme 4 Synthesis of naphthalenes 4h and 4i
For comparison, aliphatic allylic bromides (R = allyl, crotyl,
prenyl) were examined (Scheme 5). Next, from the Suzuki
cross-coupling of 2j–l with phenylallylboronic pinacol
ester, 3j–l were isolated in moderate yields (62%, 60%, and
56%). Under refluxing decalin conditions, however, different
results were observed. For the allyl derivative 3j, 80% of 4j
and 12% of 4j-1 were isolated. For the products distribution
of 4j and 4j-1, the migration behavior of 3j was similar to
that of 3f. For the crotyl derivative 3k, only 4k (86%) was
isolated via the combined carbonyl-ene/Claisen rearrange-
ment. The phenomenon resembled the formation of 3g. In
particular, when R was a prenyl group (for 3l), only 4l-1 was
isolated in 78% yield, and no double rearrangement product
was detected. We envisioned that the germinal dimethyl
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

D
M.-Y. Chang, N.-C. Hsueh
Paper
Synthesis
Pd(OAc)2, EtOH
Na2CO3, PPh3
MeO
MeO
Br
NBS, MeCN, then
K2CO3, MeCN
Me
O
B
HO
RO
Br
Ph
Me
Me
O
O
O
Br
Me
1
2j–l
Me
allyl bromide
Br
crotyl bromide
or
Me
MeO
MeO
prenyl bromide
Me
+
O
Ph
HO
Ph
for 3j
MeO
RO
4j–1 (12%)
4j (80%)
decalin
Ph
reflux
MeO
HO
MeO
O
O
for 3k,l
3j, R = allyl (62%)
3k, R = crotyl (60%)
3l, R = prenyl (56%)
Ph
Ph
Me
Me
Me
4k (86%)
4l–1 (78%)
Scheme 5 Synthesis of naphthalenes 4j, 4k, 4j-1, and 4l-1
group of 3l possessed a bulkier steric hindrance such that
the spontaneous Claisen rearrangement could not proceed
easily.
Furthermore, a bromostyryl bromide was examined. By
the same synthetic protocol, 2m was chosen as the starting
material to examine the formation of the naphthalene skel-
eton, as shown in Scheme 6. For Suzuki cross-coupling of
2m and phenylallylboronic pinacol ester, only a 34% yield of
3m was observed. The reason should be similar to the be-
havior of 2i. For the thermolytic reaction of 3m, unexpect-
edly, 4m was isolated as the major product (75%) via a
three-step pathway. The by-product 4m-1 was formed in
10% yield. For the formation of 4m, the one-pot synthetic
route included intramolecular carbonyl-ene annulation,
Claisen rearrangement, and SN2′ displacement. The struc-
ture of 4m was determined by single-crystal X-ray crystallo-
graphy (Figure 2).12
Figure 2 X-ray crystal structure of 4m
As an extension for thermolysis-induced annulation, o-
phenylallylbenzaldehyde 3f was changed to o-phenylallyl
benzoketones 3n,o via a two-step approach, as shown in
Scheme 7. By Grignard addition of 3f with Ar′MgBr (Ar′ =
Ph, 4-FC6H4, 1.0 M in THF) in THF at room temperature fol-
lowed by PCC-mediated oxidation of the resulting second-
ary alcohols in CH2Cl2 at room temperature, 3n and 3o were
generated in 52% and 53% yield, respectively. In refluxing
Pd(OAc)2, EtOH
Na2CO3, PPh3
MeO
MeO
O
Br
NBS, MeCN, then
K2CO3, MeCN
Me
O
B
HO
Ph
Br
Me
Me
O
Ph
Br
O
O
Me
1
2m
Ph
Br
MeO
O
MeO
MeO
decalin
reflux
MeO
O
MeO
O
Ph
+
Ph
O
Ph
O
Ph
Br
Br
O
decalin
reflux
Ar'MgBr, THF
O
Ph
3f
Ar'
Ar'
then PCC, CH2Cl2
Ph
4m (75%)
Ph
Ph
(yield over two steps)
3m (34%)
4m-1 (10%)
Ph
Ph
Scheme 6 Synthesis of naphthalenes 4m and 4m-1
3n, Ar' = Ph (52%)
3o, Ar' = 4-FC6H4 (53%)
4n-1, Ar' = Ph (84%)
4o-1, Ar' = 4-FC6H4 (83%)
Scheme 7 Synthesis of naphthalenes 4n-1 and 4o-1
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

E
M.-Y. Chang, N.-C. Hsueh
Paper
Synthesis
Pd(OAc)2, EtOH
Na2CO3, PPh3
Br
4
5
4
5
4
5
decalin
reflux
X
X
X
Me
O
B
Y
Y
Y
O
O
Me
Me
O
Y = Ph, Me
Me
2n, X = 4-F
2o, X = 5-F
2p, X = H
Y = Ph
Y = Ph
3p, X = 4-F (52%)
3q, X = 5-F (49%)
3r , X = H (65%)
Y = Me
4p, X = 4-F (ND)
4q, X = 5-F (ND)
4r, X = H (ND)
Y = Me
2s, X = 4,5-(MeO)2
3s, X = 4,5-(MeO)2 (33%)
4s, X = 4,5-(MeO)2 (ND)
Scheme 8 Synthetic route toward naphthalenes 4p–s; ND: not detected
MeO
O
MeO
HO
MeO
decalin
reflux
BF3•OEt2
Ph
Ph
Ph
O
CH2Cl2
O
Me
Ph
5a (90%)
Ph
Ph
4f
3f
Scheme 9 Synthesis of naphtho[2,1-b]furan 5a
decalin conditions, only carbonyl-ene products 4n-1 (84%)
and 4o-1 (83%) were produced. These results imply that the
Ar′ group with a bulky steric hindrance could inhibit the
Claisen rearrangement of 4n-1 and 4o-1 thus preventing
the migration of the styryl group. No migrated products
could be detected even after increasing the reaction time
(20 → 40 h).
Based on our developed methodology, a synthetic appli-
cation on the preparation of naphtho[2,1-b]furan was stud-
ied next (Scheme 9). Treatment of 4f with 1.0 equivalent of
BF3·OEt2 in CH2Cl2 at room temperature for 2 hours provid-
ed 5a in a 90% yield via an intramolecular ring-closure pro-
cess.
In summary, we have developed a thermolysis-induced
synthetic route for substituted naphthalenes in good yields
via an intramolecular carbonyl-ene annulation of oxygenat-
ed o-phenylallylbenzaldehydes in refluxing decalin. The
substrate scopes have been discussed. In addition, we have
also described a synthesis of naphtho[2,1-b]furan skeleton.
Further investigation regarding synthetic applications of o-
carbonyl allylbenzenes will be conducted and published in
due course.
To investigate the substrate scope and limitation of the
thermolytic synthesis, the starting materials were changed
from oxygenated o-bromobenzaldehydes to the commer-
cially available fluorine-containing o-bromobenzaldehydes
2n–o (X = 4-F, 5-F) and the simple o-bromobenzaldehyde
(2p; X = H), as shown in Scheme 8. By Suzuki cross-coupling
of 2n–p with phenylallylboronic pinacol ester (Y = Ph), 3p–r
were obtained in 52%, 49%, and 65% yield, respectively.
Then, when 3p–r were treated under refluxing decalin con-
ditions, unexpectedly, no desired 4p–r was provided and
only starting materials were recovered as major products.
On the other hand, by examining another type of allylic
side arm, the aromatic phenylallylboronic pinacol ester (Y =
Ph) was changed to the aliphatic crotylboronic pinacol ester
(Y = Me). Suzuki coupling of 2a with crotylboronic pinacol
ester produced 3s in 33% yield. However, 4s was not ob-
tained under thermolytic conditions. From these experi-
mental results, we found that two key substituents on the
skeleton of o-allylic benzaldehydes 3 could affect the reac-
tion pathway, including (1) oxygenated group on the benz-
aldehyde ring, and (2) aromatic group on the side arm. In
other words, the electron-withdrawing fluoro group and
the methyl group on the side arm provided less electron
density than the electron-donating oxygenated group and
the phenyl group such that the relative reactivity on the in-
tramolecular cyclocondensation of 3 was decreased to gen-
erate 4 under the catalyst-free thermolytic conditions.
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 air 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 100 MHz, respectively.
Chemical shifts (δ) are reported in parts per million (ppm) and the
coupling constants (J) are given in hertz. High-resolution mass spec-
tra (HRMS) were recorded on a Finnigan/Thermo Quest MAT 95XL
mass spectrometer. X-ray crystal structures were obtained with an
Enraf-Nonius FR-590 diffractometer (CAD4, Kappa CCD).
o-Phenylallylbenzaldehydes 3a–m; General Procedure
NBS (180 mg, 1.0 mmol) was added to a stirred solution of isovanillin
(1; 152 mg, 1.0 mmol) in MeCN (10 mL) at r.t. and stirred for 10 min.
The mixture was then stirred at reflux for 8 h. The reaction was mon-
itored by TLC until 1 was consumed. Then, K2CO3 (276 mg, 2.0 mmol)
was added to a stirred solution of the resulting product in MeCN (10
mL) at r.t. and stirred for 10 min. The corresponding alkyl halide (RX,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

F
M.-Y. Chang, N.-C. Hsueh
Paper
Synthesis
for 3a–g and 3i–m, 1.2 mmol; 1,6-dibromohexane for 3h, 134 mg,
0.55 mmol) was added at r.t. and the mixture was stirred at reflux for
8 h. The mixture was cooled to r.t., concentrated, and extracted with
EtOAc (3 × 15 mL). The combined organic layers were washed with
brine, dried, filtered, and evaporated under reduced pressure to afford
the crude product 2. Without further purification, freshly prepared
phenylallylboronic pinacol ester (365 mg, 1.5 mmol), Pd(OAc)2 (45
mg, 20 mol %), PPh3 (130 mg, 0.5 mmol), and Na2CO3 (110 mg, 1.0
mmol) were added sequentially to a solution of the bromide 2 in
EtOH (15 mL) at r.t. The reaction mixture was stirred at reflux for 8 h
(the reaction was monitored by TLC). The mixture was cooled to r.t.,
concentrated, and extracted with EtOAc (3 × 15 mL). The combined
organic layers were washed with brine, dried, filtered, and evaporated
under reduced pressure to afford the crude product. Purification on
silica gel (hexanes/EtOAc 8:1 to 4:1) afforded the desired 3a–m.
IR (CHCl3): 2950, 2832, 2746, 1680, 1589 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.21 (s, 1 H), 7.40 (s, 1 H), 7.34–7.26
(m, 4 H), 7.22–7.17 (m, 1 H), 6.76 (s, 1 H), 6.43–6.34 (m, 2 H), 4.87–
4.82 (m, 1 H), 3.91 (s, 3 H), 3.93–3.90 (m, 2 H), 2.02–1.77 (m, 6 H),
1.66–1.60 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 190.0, 154.8, 146.5, 137.2, 137.1,
131.3, 128.9, 128.4 (2 ×), 127.2, 126.7, 126.1 (2 ×), 114.9, 113.3, 80.5,
56.0, 34.9, 32.7 (2 ×), 24.0 (2 ×).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C22H25O3: 337.1804; found:
337.1802.
5-Benzyloxy-4-methoxy-2-(3-phenylallyl)benzaldehyde (3e)
Yield: 222 mg (62%); colorless solid; mp 108–110 °C (hexanes/EtOAc).
IR (CHCl3): 2956, 2835, 2746, 1687, 1584 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.19 (s, 1 H), 7.49–7.47 (m, 3 H),
7.41–7.20 (m, 8 H), 6.80 (s, 1 H), 6.41–6.37 (m, 2 H), 5.19 (s, 2 H), 3.95
(s, 3 H), 3.92 (d, J = 4.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 189.9, 154.4, 146.9, 137.9, 137.0,
136.4, 131.4, 128.7, 128.5 (2 ×), 128.4 (2 ×), 128.0, 127.4 (2 ×), 127.2,
126.7, 126.1 (2 ×), 114.0, 113.3, 70.9, 56.0, 34.9.
4,5-Dimethoxy-2-(3-phenylallyl)benzaldehyde (3a)
Yield: 189 mg (67%); colorless gum.
IR (CHCl3): 2951, 2832, 2744, 1682, 1588 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.24 (s, 1 H), 7.41 (s, 1 H), 7.38–7.24
(m, 4 H), 7.22–7.18 (m, 1 H), 6.77 (s, 1 H), 6.43–6.33 (m, 2 H), 4.04–
3.87 (m, 2 H), 3.95 (s, 3 H), 3.94 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.9, 154.0, 148.0, 137.7, 137.0,
131.5, 128.8, 128.6 (2 ×), 127.4, 126.9, 126.1 (2 ×), 113.0, 111.3, 56.13,
56.06, 34.9.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C24H23O3: 359.1647; found:
359.1648.
4-Methoxy-2-(3-phenylallyl)-5-(2-phenylallyloxy)benzaldehyde
(3f)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H19O3: 283.1334; found:
283.1334.
Yield: 238 mg (62%); colorless gum
IR (CHCl3): 2962, 2836, 2742, 1686, 1591 cm–1
.
4-Methoxy-5-isopropoxy-2-(3-phenylallyl)benzaldehyde (3b)
1H NMR (400 MHz, CDCl3): δ = 10.21 (s, 1 H), 7.54–7.51 (m, 2 H), 7.50
(s, 1 H), 7.41–7.28 (m, 7 H), 7.25–7.20 (m, 1 H), 6.81 (s, 1 H), 6.42–
6.40 (m, 2 H), 5.64 (d, J = 1.2 Hz, 1 H), 5.53 (d, J = 1.2 Hz, 1 H), 5.03 (s, 2
H), 3.92 (dt, J = 4.4, 6.4 Hz, 2 H), 3.92 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 189.9, 154.5, 146.7, 142.5, 138.1,
138.0, 136.9, 131.3, 128.7, 128.40 (2 ×), 128.35 (2 ×), 127.9, 127.2,
126.7, 126.02 (2 ×), 125.96 (2 ×), 114.9, 114.5, 113.5, 70.7, 56.0, 34.9.
Yield: 186 mg (60%); colorless gum.
IR (CHCl3): 2950, 2831, 2744, 1682, 1587 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.20 (s, 1 H), 7.42 (s, 1 H), 7.33–7.26
(m, 4 H), 7.21–7.18 (m, 1 H), 6.77 (s, 1 H), 6.39–6.38 (m, 2 H), 4.66–
4.59 (m, 1 H), 3.93–3.90 (m, 2 H), 3.92 (s, 3 H), 1.43–1.38 (m, 6 H).
13C NMR (100 MHz, CDCl3): δ = 190.0, 155.1, 146.1, 137.5, 137.0,
131.3, 128.9, 128.4 (2 ×), 127.2, 126.8, 126.1 (2 ×), 115.7, 113.5, 71.4,
56.0, 34.9, 21.9, 21.8.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H25O3: 385.1804; found:
385.1805.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H23O3: 311.1647; found:
311.1648.
4-Methoxy-2-(3-phenylallyl)-5-(3-phenylallyloxy)benzaldehyde
(3g)
5-Butoxy-4-methoxy-2-(3-phenylallyl)benzaldehyde (3c)
Yield: 234 mg (61%); colorless solid; mp 93–95 °C (hexanes/EtOAc).
IR (CHCl3): 2963, 2836, 2743, 1686, 1590 cm–1
.
Yield: 175 mg (54%); colorless gum.
IR (CHCl3): 2954, 2832, 2744, 1683, 1588 cm–1
1H NMR (400 MHz, CDCl3): δ = 10.23 (s, 1 H), 7.49 (s, 1 H), 7.43–7.40
(m, 2 H), 7.35–7.19 (m, 8 H), 6.80 (s, 1 H), 6.77 (d, J = 16.0 Hz, 1 H),
6.50–6.38 (m, 3 H), 4.82 (dd, J = 1.2, 6.0 Hz, 2 H), 3.96 (s, 3 H), 3.92 (d,
J = 4.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 189.9, 154.3, 146.8, 137.8, 137.0,
136.2, 133.9, 131.4, 128.8, 128.50 (2 ×), 128.47 (2 ×), 127.9, 127.3,
126.8, 126.6 (2 ×), 126.1 (2 ×), 123.7, 113.4, 113.2, 69.7, 56.1, 34.9.
.
1H NMR (400 MHz, CDCl3): δ = 10.21 (s, 1 H), 7.41 (s, 1 H), 7.32–7.24
(m, 4 H), 7.19–7.15 (m, 1 H), 6.76 (s, 1 H), 6.42–6.32 (m, 2 H), 4.05 (t,
J = 6.8 Hz, 2 H), 3.90 (s, 3 H), 3.88 (d, J = 4.4 Hz, 2 H), 1.86–1.80 (m, 2
H), 1.55–1.47 (m, 2 H), 0.98 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 189.7, 154.1, 147.3, 137.2, 136.9,
131.1, 128.8, 128.3 (2 ×), 127.1, 126.6, 125.9 (2 ×), 113.1, 112.7, 68.6,
55.9, 34.7, 30.9, 19.0, 13.6.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H25O3: 385.1804; found:
385.1806.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H25O3: 325.1804; found:
325.1803.
5-{6-[4-Methoxy-2-(3-phenylallyl)benzaldehydyl]hexyloxy}-4-
methoxy-2-(3-phenylallyl)benzaldehyde (3h)
5-Cyclopentoxy-4-methoxy-2-(3-phenylallyl)benzaldehyde (3d)
Yield: 145 mg (47%); colorless solid; mp 88–90 °C (hexanes/EtOAc).
Yield: 168 mg (50%); colorless gum.
IR (CHCl3): 2951, 2832, 2744, 1682, 1588 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

G
M.-Y. Chang, N.-C. Hsueh
Paper
Synthesis
1H NMR (400 MHz, CDCl3): δ = 10.21 (s, 2 H), 7.41 (s, 2 H), 7.34–7.25
(m, 8 H), 7.21–7.17 (m, 2 H), 6.77 (s, 2 H), 6.39–6.33 (m, 4 H), 4.08 (t,
J = 6.8 Hz, 4 H), 3.92 (s, 6 H), 3.90 (d, J = 4.4 Hz, 4 H), 1.92–1.88 (m, 4
H), 1.59–1.56 (m, 4 H).
1H NMR (400 MHz, CDCl3): δ = 10.21 (d, J = 1.6 Hz, 1 H), 7.42 (s, 1 H),
7.32–7.16 (m, 5 H), 6.76 (s, 1 H), 6.42–6.32 (m, 2 H), 5.55–5.51 (m, 1
H), 4.62 (d, J = 6.4 Hz, 2 H), 3.92–3.88 (m, 2 H), 3.91 (s, 3 H), 1.78 (s, 3
H), 1.76 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 189.9 (2 ×), 154.2 (2 ×), 147.2 (2 ×),
137.4 (2 ×), 136.9 (2 ×), 131.2 (2 ×), 128.8 (2 ×), 128.2 (4 ×), 127.1 (2 ×),
126.6 (2 ×), 126.0 (4 ×), 113.1 (2 ×), 112.7 (2 ×), 68.8 (2 ×), 55.9 (2 ×),
34.7 (2 ×), 28.8 (2 ×), 25.6 (2 ×).
13C NMR (100 MHz, CDCl3): δ = 190.0, 154.3, 147.2, 138.4, 137.5,
137.1, 131.4, 129.0, 128.5 (2 ×), 127.3, 126.8, 126.1 (2 ×), 119.3,
113.14, 113.07, 65.8, 56.1, 34.9, 25.9, 18.3.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C22H25O3: 337.1804; found:
337.1802.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C40H43O6: 619.3060; found:
619.3062.
5-(3-Bromo-2-phenylallyloxy)-4-methoxy-2-(3-phenylallyl)benz-
aldehyde (3m)
5-(6-Bromohexyloxy)-4-methoxy-2-(3-phenylallyl)benzaldehyde
(3i)
Yield: 157 mg (34%); colorless gum.
Yield: 172 mg (40%); colorless solid; mp 57–59 °C (hexanes/EtOAc).
IR (CHCl3): 2963, 2838, 2743, 1687, 1590 cm–1
.
IR (CHCl3): 2953, 2835, 2744, 1682, 1589 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.20 (s, 1 H), 7.53 (s, 1 H), 7.44–7.42
(m, 2 H), 7.36–7.28 (m, 7 H), 7.24–7.22 (m, 1 H), 6.76 (s, 1 H), 6.71 (s,
1 H), 6.41–6.39 (m, 2 H), 5.22 (s, 2 H), 3.93–3.92 (m, 2 H), 3.81 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 189.8, 154.6, 146.3, 140.9, 138.3,
137.7, 136.9, 131.2, 128.6, 128.32 (2 ×), 128.30 (2 ×), 128.1, 127.1,
126.5 (2 ×), 125.9 (2 ×), 116.0, 113.5, 110.0, 106.7, 68.6, 55.8, 34.9.
1H NMR (400 MHz, CDCl3): δ = 10.21 (s, 1 H), 7.40 (s, 1 H), 7.33–7.24
(m, 4 H), 7.21–7.16 (m, 1 H), 6.77 (s, 1 H), 6.42–6.32 (m, 2 H), 4.06 (t,
J = 6.8 Hz, 2 H), 3.92 (s, 3 H), 3.90 (d, J = 4.8 Hz, 2 H), 3.41 (t, J = 6.4 Hz,
2 H), 1.90–1.85 (m, 4 H), 1.52–1.49 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 189.8, 154.2, 147.2, 137.4, 136.9,
131.2, 128.8, 128.4 (2 ×), 127.2, 126.7, 126.0 (2 ×), 113.1, 112.7, 68.7,
56.0, 34.8, 33.6, 32.5, 28.7, 27.7, 25.0.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H24BrO3: 463.0909; found:
463.0911.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H28BrO3: 431.1222; found:
431.1223.
o-Phenylallyl Benzoketones 3n,o; General Procedure
PhMgBr or 4-FC6H4MgBr (1.0 M in THF, 1 mL, 1.0 mmol) was added to
a stirred solution of 3f (190 mg, 0.5 mmol) in THF (10 mL) at r.t. and
the reaction mixture was stirred at r.t. for 8 h. The reaction was mon-
itored by TLC until 3f was consumed. The mixture was concentrated,
extracted with EtOAc (3 × 15 mL), and the combined organic layers
were washed with aq 2 N HCl (10 mL) and brine, dried, filtered, and
evaporated under reduced pressure to afford the crude product. With-
out further purification, PCC (220 mg, 1.0 mmol) and Celite (300 mg)
were added to a solution of the above crude product in CH2Cl2. The
mixture was stirred at r.t. for 8 h and the reaction was monitored by
TLC until the reactants were consumed. The mixture was cooled to
r.t., filtered through a pad of silica gel and the filtrates were concen-
trated under reduced pressure to afford the crude product. Purifica-
tion on silica gel (hexanes/EtOAc 8:1 to 4:1) afforded the desired 3n,o.
5-Allyloxy-4-methoxy-2-(3-phenylallyl)benzaldehyde (3j)
Yield: 191 mg (62%); colorless gum.
IR (CHCl3): 2956, 2834, 2743, 1686, 1590 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.17 (s, 1 H), 7.38 (s, 1 H), 7.29–7.20
(m, 4 H), 7.16–7.12 (m, 1 H), 6.75 (s, 1 H), 6.37–6.33 (m, 2 H), 6.10–
6.00 (m, 1 H), 5.41 (dq, J = 1.6, 17.2 Hz, 1 H), 5.27 (dq, J = 1.6, 10.4 Hz,
1 H), 4.59 (dt, J = 1.6, 5.6 Hz, 2 H), 3.87 (s, 3 H), 3.85 (d, J = 4.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 189.4, 153.9, 146.4, 137.4, 136.7,
132.4, 131.0, 128.5, 128.1 (2 ×), 126.9, 126.4, 125.7 (2 ×), 117.9, 113.2,
112.9, 69.3, 55.6, 34.5.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H21O3: 309.1491; found:
309.1493.
[4-Methoxy-2-(3-phenylallyl)-5-(2-phenylallyloxy)phenyl]phenyl-
methanone (3n)
5-But-2-enyloxy-4-methoxy-2-(3-phenylallyl)benzaldehyde (3k)
Yield: 193 mg (60%); colorless gum.
Yield: 120 mg (52%); colorless gum.
IR (CHCl3): 2958, 2834, 2743, 1686, 1591 cm–1
.
IR (CHCl3): 2963, 1715, 1556 cm–1
.
1H NMR (400 MHz, CDCl3): δ (major product) = 10.21 (s, 1 H), 7.41 (s,
1 H), 7.33–7.25 (m, 4 H), 7.21–7.17 (m, 1 H), 6.77 (s, 1 H), 6.38–6.33
(m, 2 H), 5.92–5.86 (m, 1 H), 5.81–5.74 (m, 1 H), 4.57 (dt, J = 2.0, 6.8
Hz, 2 H), 3.92 (s, 3 H), 3.90 (d, J = 4.4 Hz, 2 H), 1.75 (dd, J = 1.2, 6.4 Hz,
3 H).
1H NMR (400 MHz, CDCl3): δ = 7.81–7.78 (m, 2 H), 7.58–7.51 (m, 2 H),
7.47–7.39 (m, 4 H), 7.36–7.23 (m, 7 H), 6.98 (s, 1 H), 6.90 (s, 1 H),
6.38–6.27 (m, 2 H), 5.55 (d, J = 0.8 Hz, 1 H), 5.42 (d, J = 0.8 Hz, 1 H),
4.91 (s, 2 H), 3.91 (s, 3 H), 3.62 (d, J = 5.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 197.4, 151.7, 145.2, 142.8, 138.3,
138.2, 137.4, 134.4, 132.7, 131.1, 130.6 (2 ×), 130.2, 129.1, 128.34 (4
×), 128.27 (2 ×), 128.1, 127.9, 127.0, 126.0 (2 ×), 116.4, 114.9, 113.8,
71.2, 56.0, 36.5, 23.8.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C32H29O3: 461.2117; found:
461.2118.
13C NMR (100 MHz, CDCl3): δ (major product) = 189.9, 154.2, 146.9,
137.5, 137.0, 131.28, 131.25, 128.8, 128.4 (2 ×), 127.2, 126.7, 126.0 (2
×), 125.4, 113.1, 113.0, 69.5, 56.0, 34.8, 17.7.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H23O3: 323.1647; found
323.1647.
4-Methoxy-5-(3-methylbut-2-enyloxy)-2-(3-phenylallyl)benzalde-
hyde (3l)
(4-Fluorophenyl)-[4-methoxy-2-(3-phenylallyl)-5-(2-phenylally-
loxy)phenyl]methanone (3o)
Yield: 188 mg (56%); colorless solid; mp 70–72 °C (hexanes/EtOAc).
Yield: 127 mg (53%); colorless gum.
IR (CHCl3): 2956, 2833, 2746, 1687, 1590 cm–1
.
IR (CHCl3): 2970, 1722, 1561 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

H
M.-Y. Chang, N.-C. Hsueh
Paper
Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.82–7.78 (m, 2 H), 7.43–7.40 (m, 2 H),
7.35–7.26 (m, 7 H), 7.22–7.17 (m, 1 H), 7.12–7.06 (m, 2 H), 6.93 (s, 1
H), 6.90 (s, 1 H), 6.36–6.25 (m, 2 H), 5.56 (d, J = 0.8 Hz, 1 H), 5.42 (d, J =
0.8 Hz, 1 H), 4.92 (s, 2 H), 3.92 (s, 3 H), 3.61 (d, J = 5.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 192.5, 142.4, 137.2, 134.0, 133.8,
132.1, 131.5, 131.1, 128.6, 128.5 (2 ×), 127.2, 127.0 (2 ×), 126.1, 35.8.
HRMS (ESI-TOF) m/z [M + H]+ calcd for C16H15O: 223.1123; found:
223.1122.
13C NMR (100 MHz, CDCl3): δ = 195.9, 165.5 (d, J = 253.2 Hz), 151.8,
145.3, 142.8, 138.2, 137.3, 134.6 (d, J = 3.0 Hz), 134.3, 132.6 (d, J = 9.1
Hz, 2 ×), 131.2, 129.9, 129.0, 128.4 (4 ×), 127.9, 127.1, 126.02 (2 ×),
126.01 (2 ×), 116.2, 115.4 (d, J = 22.0 Hz, 2 ×), 114.9, 113.9, 71.2, 56.0,
36.5.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C32H28FO3: 479.2023; found:
479.2025.
2-But-2-enyl-4,5-dimethoxybenzaldehyde (3s)
Freshly prepared crotylboronic pinacol ester (365 mg, 1.5 mmol),
Pd(OAc)2 (45 mg, 20 mol%), PPh3 (130 mg, 0.5 mmol), and Na2CO3
(110 mg, 1.0 mmol) were added sequentially to a solution of the com-
mercially available 2s (245 mg, 1.0 mmol) in EtOH (15 mL) at r.t. The
reaction mixture was stirred at reflux for 8 h (the reaction was moni-
tored by TLC). The mixture was cooled to r.t., concentrated, and ex-
tracted with EtOAc (3 × 15 mL). The combined organic layers were
washed with brine, dried, filtered, and evaporated under reduced
pressure to afford the crude product. Purification on silica gel (hex-
anes/EtOAc 8:1 to 4:1) furnished 3s; yield: 73 mg (33%); colorless oil.
o-Phenylallylbenzaldehydes 3p–r; General Procedure
Freshly prepared phenylallylboronic pinacol ester (365 mg, 1.5
mmol), Pd(OAc)2 (45 mg, 20 mol%), PPh3 (130 mg, 0.5 mmol), and
Na2CO3 (110 mg, 1.0 mmol) were added sequentially to a solution of
the commercially available respective 2n–o (203 mg, 1.0 mmol) or 2p
(185 mg, 1.0 mmol) in EtOH (15 mL) at r.t. The reaction mixture was
stirred at reflux for 8 h (the reaction was monitored by TLC). The mix-
ture was cooled to r.t., concentrated, and extracted with EtOAc (3 × 15
mL). The combined organic layers were washed with brine, dried, fil-
tered, and evaporated under reduced pressure to afford the crude
product. Purification on silica gel (hexanes/EtOAc 8:1 to 4:1) afforded
the desired 3p–r.
IR (CHCl3): 2960, 2828, 2739, 1691, 1588 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.18 (s, 1 H), 7.38 (s, 1 H), 6.69 (s, 1
H), 5.65–5.57 (m, 1 H), 5.45–5.38 (m, 1 H), 3.94 (s, 3 H), 3.91 (s, 3 H),
3.66 (dt, J = 1.6, 5.2 Hz, 2 H), 1.65 (dd, J = 1.6, 6.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 190.0, 153.9, 147.7, 138.8, 129.9,
127.0, 126.7, 112.7, 110.5, 56.04, 55.98, 34.5, 17.8.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H17O3: 221.1178; found:
221.1180.
4-Fluoro-2-(3-phenylallyl)benzaldehyde (3p)
Naphthalenes 4; General Procedure
Yield: 125 mg (52%); colorless oil.
Decalin (1 mL) was added to the corresponding 3 (0.5 mmol) at r.t.
The reaction mixture was stirred at reflux for 20 h. The mixture was
cooled to r.t. and the solvent was concentrated. Purification on silica
gel (hexanes/EtOAc 15:1 to 5:1) afforded the desired 4.
IR (CHCl3): 2956, 2822, 2741, 1678, 1581 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.23 (s, 1 H), 7.89 (dd, J = 6.0, 8.4 Hz, 1
H), 7.36–7.28 (m, 4 H), 7.24–7.20 (m, 1 H), 7.12–7.06 (m, 2 H), 6.44 (d,
J = 16.0 Hz, 1 H), 6.36 (dt, J = 6.0, 16.0 Hz, 1 H), 3.99 (d, J = 5.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 190.7, 165.9 (d, J = 255.5 Hz), 146.0 (d,
J = 9.1 Hz), 136.9, 135.0 (d, J = 9.8 Hz), 132.3, 130.4, 128.5 (2 ×),
127.43, 127.38, 128.1 (2 ×), 117.9 (d, J = 22.0 Hz), 114.1 (d, J = 21.9
Hz), 35.6.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H14FO: 241.1029; found:
241.1030.
2,3-Dimethoxy-6-phenylnaphthalene (4a)
Yield: 127 mg (96%); colorless solid; mp 131–133 °C (hexanes/EtOAc).
IR (CHCl3): 2956, 1542, 1302, 1218 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 1.6 Hz, 1 H), 7.76 (d, J = 8.4
Hz, 1 H), 7.72–7.70 (m, 2 H), 7.62 (dd, J = 2.0, 8.4 Hz, 1 H), 7.50–7.46
(m, 2 H), 7.38–7.35 (m, 1 H), 7.19 (s, 1 H), 7.15 (s, 1 H), 4.03 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 149.8, 149.6, 141.4, 137.0, 129.4,
128.8 (2 ×), 128.4, 127.2 (2 ×), 127.0, 126.8, 124.4, 123.8, 106.6, 106.1,
55.9 (2 ×).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H17O2: 265.1229; found:
265.1231.
5-Fluoro-2-(3-phenylallyl)benzaldehyde (3q)
Yield: 118 mg (49%); colorless oil.
IR (CHCl3): 2956, 2826, 2741, 1680, 1582 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.22 (s, 1 H), 7.90–7.86 (m, 1 H),
7.38–7.29 (m, 4 H), 7.25–7.22 (m, 1 H), 7.11–7.06 (m, 2 H), 6.45 (d, J =
16.0 Hz, 1 H), 6.38 (dt, J = 6.0, 16.0 Hz, 1 H), 3.98 (d, J = 6.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 190.5, 165.7 (d, J = 255.5 Hz), 145.9 (d,
J = 9.1 Hz), 136.8, 134.8 (d, J = 9.8 Hz), 132.1, 130.3 (d, J = 2.3 Hz),
128.4 (2 ×), 128.3 (2 ×), 127.3, 126.0, 117.7 (d, J = 22.0 Hz), 113.9 (d, J =
22.0 Hz), 35.4.
3-Isopropoxy-2-methoxy-6-phenylnaphthalene (4b)
Yield: 143 mg (98%); colorless gum.
IR (CHCl3): 2956, 1546, 1302, 1220 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 1.6 Hz, 1 H), 7.76 (d, J = 8.4
Hz, 1 H), 7.73–7.71 (m, 2 H), 7.61 (dd, J = 2.0, 8.4 Hz, 1 H), 7.50–7.46
(m, 2 H), 7.39–7.35 (m, 1 H), 7.23 (s, 1 H), 7.17 (s, 1 H), 4.78–4.72 (m,
1 H), 4.00 (s, 3 H), 1.49 (d, J = 6.0 Hz, 6 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H14FO: 241.1029; found:
241.1028.
13C NMR (100 MHz, CDCl3): δ = 150.6, 148.0, 141.4, 136.8, 129.4,
128.7 (2 ×), 128.4, 127.2 (2 ×), 127.0, 126.7, 124.3, 123.7, 109.9, 106.4,
70.9, 55.9, 21.9 (2 ×).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H21O2: 293.1542; found:
293.1543.
2-(3-Phenylallyl)benzaldehyde (3r)
Yield: 144 mg (65%); colorless oil.
IR (CHCl3): 2960, 2820, 2741, 1678, 1584 cm–1
1H NMR (400 MHz, CDCl3): δ = 10.30 (s, 1 H), 7.87 (dd, J = 1.6, 7.6 Hz, 1
H), 7.55 (dt, J = 1.6, 7.6 Hz, 1 H), 7.44–7.18 (m, 7 H), 6.42–6.39 (m, 2
H), 3.99 (dt, J = 2.4, 4.8 Hz, 2 H).
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

I
M.-Y. Chang, N.-C. Hsueh
Paper
Synthesis
3-Butoxy-2-methoxy-6-phenylnaphthalene (4c)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H23O2: 367.1698; found:
367.1699.
Yield: 150 mg (98%); colorless solid; mp 115–117 °C (hexanes/EtOAc).
IR (CHCl3): 2957, 1542, 1305, 1218 cm–1
.
2-Methoxy-6-phenyl-3-(2-phenylallyloxy)naphthalene (4f-1)
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 1.2 Hz, 1 H), 7.78–7.74 (m, 3
H), 7.63 (dd, J = 1.2, 8.4 Hz, 1 H), 7.52–7.49 (m, 2 H), 7.41–7.37 (m, 1
H), 7.22 (s, 1 H), 7.17 (s, 1 H), 4.19 (t, J = 6.8 Hz, 2 H), 4.02 (s, 3 H),
2.00–1.93 (m, 2 H), 1.65–1.55 (m, 2 H), 1.07 (d, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 149.9, 149.3, 141.4, 136.8, 129.4,
128.7 (2 ×), 128.3, 127.2 (2 ×), 126.9, 126.7, 124.2, 123.6, 107.6, 106.2,
68.4, 55.8, 31.0, 19.2, 13.9.
Yield: 18 mg (10%); colorless solid; mp 139–141 °C (hexanes/EtOAc).
IR (CHCl3): 2966, 1536, 1324, 1231 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.87 (d, J = 1.6 Hz, 1 H), 7.77 (d, J = 8.4
Hz, 1 H), 7.71–7.69 (m, 2 H), 7.62 (dd, J = 1.6, 8.4 Hz, 1 H), 7.56–7.53
(m, 2 H), 7.49–7.45 (m, 2 H), 7.42–7.32 (m, 4 H), 7.25 (s, 1 H), 7.17 (s,
1 H), 5.64 (d, J = 0.8 Hz, 1 H), 5.56 (d, J = 1.2 Hz, 1 H), 5.12 (s, 2 H), 4.00
(s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 150.1, 148.8, 142.4, 141.4, 138.5,
136.9, 129.3, 128.8 (2 ×), 128.7, 128.5 (2 ×), 128.0, 127.2 (2 ×), 127.0,
126.8, 126.1 (2 ×), 124.4, 124.0, 114.6, 109.1, 106.5, 70.5, 55.9.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H23O2: 307.1698; found:
307.1698.
X-Ray Crystallographic Data12
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H23O2: 367.1698; found:
367.1698.
Single crystal was grown by slow diffusion of EtOAc into a solution of
compound 4c in CH2Cl2 to yield a colorless prism. The compound
crystallized in the triclinic crystal system, space group P-1, a =
7.5311(6) Å, b = 9.3406(7) Å, c = 12.0799(9) Å, V = 823.02(11) Å3, Z = 2,
dcalcd = 1.236 g/cm3, F(000) = 328, 2θ range 2.243–26.771°, R indices
(all data): R1 = 0.0405, wR2 = 0.1010.
3-Methoxy-7-phenyl-1-(1-phenylallyl)naphthalen-2-ol (4g)
Yield: 157 mg (86%); colorless gum.
IR (CHCl3): 3452, 2960, 1534, 1319, 1231 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 1.6 Hz, 1 H), 7.76 (d, J = 8.4
Hz, 1 H), 7.55 (dd, J = 1.6, 8.4 Hz, 1 H), 7.46–7.20 (m, 10 H), 7.13 (s, 1
H), 6.78–6.69 (m, 1 H), 6.25 (s, 1 H), 5.89 (d, J = 8.0 Hz, 1 H), 5.31 (dt,
J = 1.6, 7.6 Hz, 1 H), 5.28 (d, J = 0.8 Hz, 1 H), 4.05 (s, 3 H).
3-Cyclopentyloxy-2-methoxy-6-phenylnaphthalene (4d)
Yield: 149 mg (94%); colorless solid; mp 118–120 °C (hexanes/EtOAc).
IR (CHCl3): 2953, 1544, 1302, 1219 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.89 (d, J = 1.2 Hz, 1 H), 7.75 (d, J = 8.4
Hz, 1 H), 7.73–7.70 (m, 2 H), 7.60 (dd, J = 2.0, 8.4 Hz, 1 H), 7.50–7.46
(m, 2 H), 7.38–7.34 (m, 1 H), 7.18 (s, 1 H), 7.15 (s, 1 H), 4.97–4.92 (m,
1 H), 3.99 (s, 3 H), 2.13–1.84 (m, 6 H), 1.72–1.62 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 150.5, 148.5, 141.5, 136.8, 129.5,
128.7 (2 ×), 128.2, 127.2 (2 ×), 126.9, 126.7, 124.3, 123.6, 109.4, 106.3,
80.2, 55.9, 32.8 (2 ×), 24.3 (2 ×).
13C NMR (100 MHz, CDCl3): δ = 147.0, 144.1, 143.2, 141.6, 138.4 (2 ×),
136.4, 128.7 (2 ×), 128.2 (2 ×), 128.0, 127.9, 127.6 (2 ×), 127.2 (2 ×),
126.8, 125.9, 123.0 (2 ×), 121.0, 117.2, 104.8, 55.9, 45.8.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H23O2: 367.1698; found:
367.1698.
3-[6-(2-Methoxy-6-phenylnaphthalene)hexyloxy]-2-methoxy-6-
phenylnaphthalene (4h)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C22H23O2: 319.1698; found:
319.1695.
Yield: 262 mg (90%); colorless solid; mp 197–199 °C (hexanes/EtOAc).
IR (CHCl3): 2968, 1536, 1318, 1215 cm–1
.
3-Benzyloxy-2-methoxy-6-phenylnaphthalene (4e)
1H NMR (400 MHz, CDCl3): δ = 7.88 (d, J = 2.0 Hz, 2 H), 7.75 (d, J = 8.4
Hz, 2 H), 7.71–7.68 (m, 4 H), 7.59 (dd, J = 2.0, 8.4 Hz, 2 H), 7.48–7.44
(m, 4 H), 7.37–7.33 (m, 2 H), 7.19 (s, 2 H), 7.14 (s, 2 H), 4.19 (t, J = 6.8
Hz, 4 H), 3.99 (s, 6 H), 2.05–1.99 (m, 4 H), 1.67–1.63 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 150.0 (2 ×), 149.3 (2 ×), 141.4 (2 ×),
136.9 (2 ×), 129.5 (2 ×), 128.8 (4 ×), 128.3 (2 ×), 127.2 (4 ×), 127.0 (2 ×),
126.8 (2 ×), 124.3 (2 ×), 123.7 (2 ×), 107.8 (2 ×), 106.3 (2 ×), 68.7 (2 ×),
55.9 (2 ×), 29.0 (2 ×), 25.9 (2 ×).
Yield: 160 mg (94%); colorless solid; mp 147–149 °C (hexanes/EtOAc).
IR (CHCl3): 2961, 1543, 1302, 1222 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.85 (d, J = 1.6 Hz, 1 H), 7.76 (d, J = 8.4
Hz, 1 H), 7.70–7.68 (m, 2 H), 7.61 (dd, J = 1.6, 8.4 Hz, 1 H), 7.53–7.31
(m, 8 H), 7.23 (s, 1 H), 7.18 (s, 1 H), 5.31 (s, 2 H), 4.03 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 150.0, 148.9, 141.3, 136.9, 136.7,
129.3, 128.7 (2 ×), 128.6 (2 ×), 128.5, 127.9, 127.3 (2 ×), 127.2 (2 ×),
127.0, 126.7, 124.4, 123.9, 108.8, 106.4, 70.7, 55.9.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C40H39O4: 583.2848; found:
HRMS (ESI-TOF): m/z [M + H]+ calcd for C24H21O2: 341.1542; found:
583.2846.
341.1544.
3-(6-Bromohexyloxy)-2-methoxy-6-phenylnaphthalene (4i)
3-Methoxy-7-phenyl-1-(2-phenylallyl)naphthalen-2-ol (4f)
Yield: 165 mg (80% ); colorless gum.
IR (CHCl3): 2960, 1546, 1310, 1217 cm–1
.
Yield: 154 mg (84%); colorless gum.
IR (CHCl3): 3431, 2963, 1530, 1312, 1225 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.88 (d, J = 1.6 Hz, 1 H), 7.75 (d, J = 8.4
Hz, 1 H), 7.71–7.69 (m, 2 H), 7.60 (dd, J = 2.0, 8.4 Hz, 1 H), 7.49–7.45
(m, 2 H), 7.38–7.34 (m, 1 H), 7.18 (s, 1 H), 7.15 (s, 1 H), 4.16 (t, J = 6.8
Hz, 2 H), 4.00 (s, 3 H), 3.44 (t, J = 6.8 Hz, 2 H), 1.98–1.91 (m, 4 H),
1.62–1.55 (m, 4 H).
1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 1.6 Hz, 1 H), 7.78 (d, J = 8.8
Hz, 1 H), 7.68–7.59 (m, 5 H), 7.46–7.39 (m, 4 H), 7.36–7.32 (m, 2 H),
7.12 (s, 1 H), 6.16 (s, 1 H), 5.37 (d, J = 1.2 Hz, 1 H), 4.69 (d, J = 1.6 Hz, 1
H), 4.30 (t, J = 1.6 Hz, 2 H), 4.06 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 150.0, 149.3, 141.4, 136.9, 129.5,
128.8 (2 ×), 128.4, 127.2 (2 ×), 127.0, 126.8, 124.3, 123.8, 107.8, 106.3,
66.6, 55.9, 33.8, 32.7, 28.8, 28.0, 25.3.
13C NMR (100 MHz, CDCl3): δ = 147.0, 145.9, 143.9, 142.1, 141.7,
136.9, 129.2, 128.7 (2 ×), 128.3 (2 ×), 128.2, 127.6, 127.5, 127.3 (2 ×),
126.9, 126.1 (2 ×), 123.3, 121.8, 117.7, 113.1, 107.3, 55.9, 30.4.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

J
M.-Y. Chang, N.-C. Hsueh
Paper
Synthesis
HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H26BrO2: 413.1116; found:
HRMS (ESI-TOF): m/z [M + H]+ calcd for C22H23O2: 319.1698; found:
413.1117.
319.1700.
1-Allyl-3-methoxy-7-phenylnaphthalen-2-ol (4j)
5-Methoxy-2,9-diphenyl-3H-benzo[f]chromene (4m)
Yield: 116 mg (80%); colorless gum.
Yield: 137 mg (75%); colorless solid; mp 153–155 °C (hexanes/EtOAc).
IR (CHCl3): 3410, 2968, 1523, 1310, 1233 cm–1
.
IR (CHCl3): 2960, 1541, 1331, 1227 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 2.0 Hz, 1 H), 7.75 (d, J = 8.4
Hz, 1 H), 7.71–7.69 (m, 2 H), 7.59 (dd, J = 2.0, 8.4 Hz, 1 H), 7.51–7.46
(m, 2 H), 7.39–7.34 (m, 1 H), 7.09 (s, 1 H), 6.15–6.05 (m, 1 H), 6.10 (br
s, 1 H), 5.12–5.05 (m, 2 H), 4.04 (s, 3 H), 3.91 (d, J = 6.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 147.0, 143.5, 141.9, 137.0, 136.2,
128.83, 128.77 (2 ×), 128.2, 127.7, 127.4 (2 ×), 127.0, 123.3, 121.5,
117.8, 115.3, 104.1, 55.9, 29.2.
1H NMR (400 MHz, CDCl3): δ = 8.17 (d, J = 1.6 Hz, 1 H), 7.78 (d, J = 8.4
Hz, 1 H), 7.75–7.72 (m, 2 H), 7.64 (dd, J = 1.6, 8.4 Hz, 1 H), 7.58–7.35
(m, 9 H), 7.15 (s, 1 H), 5.33 (d, J = 0.8 Hz, 2 H), 4.05 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 148.3, 143.3, 141.6, 137.4 (2 ×), 137.0,
130.7, 128.83 (2 ×), 128.78 (2 ×), 128.1, 127.8, 127.4 (2 ×), 127.2,
125.6, 125.1 (2 ×), 124.2, 119.5, 117.4, 116.3, 107.0, 67.5, 55.9.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H21O2: 365.1542; found:
365.1545.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H19O2: 291.1385; found:
291.1386.
X-ray Crystallographic Data12
3-Allyloxy-2-methoxy-6-phenylnaphthalene (4j-1)
Single crystal was grown by slow diffusion of EtOAc into a solution of
compound 4m in CH2Cl2 to yield a colorless prism. The compound
crystallized in the monoclinic crystal system, space group P 21, a =
11.1511(15) Å, b = 6.2381(8) Å, c = 13.3264(18) Å, V = 920.3(2) Å3, Z =
2, dcalcd = 1.315 g/cm3, F(000) = 384, 2θ range 1.539–26.634°, R indices
(all data): R1 = 0.0625, wR2 = 0.0956.
Yield: 17 mg (12%); colorless solid; mp 117–119 °C (hexanes/EtOAc).
IR (CHCl3): 2952, 1537, 1322, 1218 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 1.6 Hz, 1 H), 7.77 (d, J = 8.8
Hz, 1 H), 7.74–7.71 (m, 2 H), 7.63 (dd, J = 1.6, 8.4 Hz, 1 H), 7.51–7.47
(m, 2 H), 7.40–7.36 (m, 1 H), 7.21 (s, 1 H), 7.17 (s, 1 H), 6.25–6.15 (m,
1 H), 5.52 (dq, J = 1.6, 17.2 Hz, 1 H), 5.38 (dq, J = 1.6, 10.4 Hz, 1 H), 4.77
(dt, J = 1.6, 5.2 Hz, 2 H), 4.02 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 149.8, 148.7, 141.3, 136.9, 132.9,
129.3, 128.7 (2 ×), 128.4, 127.2 (2 ×), 127.0, 126.7, 124.3, 123.8, 118.3,
108.2, 106.2, 69.6, 55.8.
3-(3-Bromo-2-phenylallyloxy)-2-methoxy-6-phenylnaphthalene
(4m-1)
Yield: 22 mg (10%); colorless solid; mp 111–113 °C (hexanes/EtOAc).
IR (CHCl3): 2958, 1521, 1312, 1216 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 1.6 Hz, 1 H), 7.76–7.72 (m, 3
H), 7.63 (dd, J = 1.6, 8.4 Hz, 1 H), 7.52–7.32 (m, 9 H), 7.11 (s, 1 H), 6.73
(s, 1 H), 5.33 (s, 2 H), 3.89 (s, 3 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H19O2: 291.1385; found:
291.1386.
13C NMR (100 MHz, CDCl3): δ = 150.1, 148.5, 141.5, 141.3, 137.8,
136.9, 129.2, 128.83, 128.76 (2 ×), 128.4 (2 ×), 128.2, 127.2 (2 ×),
127.0, 126.9 (2 ×), 126.7, 124.5, 124.0, 109.8, 109.6, 106.6, 68.4, 55.9.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H22BrO2: 445.0803; found
445.0804.
3-Methoxy-1-(1-methylallyl)-7-phenylnaphthalen-2-ol (4k)
Yield: 131 mg (86%); colorless gum.
IR (CHCl3): 3411, 2970, 1525, 1310, 1235 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.27 (d, J = 1.6 Hz, 1 H), 7.76 (d, J = 8.4
Hz, 1 H), 7.71–7.67 (m, 2 H), 7.57 (dd, J = 1.6, 8.4 Hz, 1 H), 7.50–7.46
(m, 2 H), 7.38–7.34 (m, 1 H), 7.07 (s, 1 H), 6.46–6.37 (m, 1 H), 6.20 (br
s, 1 H), 5.21 (dq, J = 2.0, 17.2 Hz, 1 H), 5.16 (dq, J = 2.0, 10.4 Hz, 1 H),
4.59–4.55 (m, 1 H), 4.04 (s, 3 H), 1.62 (d, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 147.1, 143.4, 142.8, 141.9, 136.5,
128.8 (2 ×), 128.6, 128.2, 128.0, 127.3 (3 ×), 126.9, 123.0, 122.2, 113.1,
104.3, 55.9, 34.6, 18.0.
6-Methoxy-1,2-diphenyl-7-(2-phenylallyloxy)naphthalene (4n-1)
Yield: 186 mg (84%); colorless gum.
IR (CHCl3): 2953, 1539, 1328, 1226 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.78 (d, J = 8.4 Hz, 1 H), 7.46 (d, J = 8.4
Hz, 1 H), 7.33–7.30 (m, 5 H), 7.26–7.15 (m, 11 H), 7.11 (s, 1 H), 5.44 (s,
1 H), 5.27 (s, 1 H), 4.88 (s, 2 H), 4.02 (s, 3 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H21O2: 305.1542; found
13C NMR (100 MHz, CDCl3): δ = 149.8, 148.2, 142.7, 142.2, 139.3,
138.4, 136.7, 136.4, 131.2 (2 ×), 130.1 (2 ×), 128.9, 128.3 (2 ×), 128.2,
127.9 (2 ×), 127.8, 127.5 (2 ×), 126.8, 126.6, 126.3 (2 ×), 125.9, 125.8,
114.8, 108.5, 106.6, 70.5, 55.9.
305.1543.
2-Methoxy-3-(3-methylbut-2-enyloxy)-6-phenylnaphthalene (4l-
1)
Yield: 124 mg (78%); colorless solid; mp 119–121 °C (hexanes/EtOAc).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C32H27O2: 443.2011; found:
443.2012.
IR (CHCl3): 2956, 1538, 1329, 1219 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 1.6 Hz, 1 H), 7.77 (d, J = 8.4
Hz, 1 H), 7.75–7.71 (m, 2 H), 7.62 (dd, J = 1.6, 8.4 Hz, 1 H), 7.51–7.47
(m, 2 H), 7.40–7.36 (m, 1 H), 7.22 (s, 1 H), 7.16 (s, 1 H), 5.66–5.62 (m,
1 H), 4.75 (d, J = 6.8 Hz, 2 H), 4.02 (s, 3 H), 1.83 (s, 3 H), 1.82 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 149.9, 149.0, 141.4, 137.9, 136.8,
129.4, 128.7 (2 ×), 128.3, 127.2 (2 ×), 126.9, 126.7, 124.3, 123.7, 119.6,
107.9, 106.1, 65.6, 55.8, 25.8, 18.3.
1-(4-Fluorophenyl)-6-methoxy-2-phenyl-7-(2-phenylally-
loxy)naphthalene (4o-1)
Yield: 191 mg (83%); colorless gum.
IR (CHCl3): 2955, 1539, 1327, 1224 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

K
M.-Y. Chang, N.-C. Hsueh
Paper
Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 8.4 Hz, 1 H), 7.45 (d, J = 8.4
Hz, 1 H), 7.35–7.31 (m, 5 H), 7.23–7.11 (m, 8 H), 7.04 (s, 1 H), 6.96–
6.92 (m, 2 H), 5.46 (d, J = 0.4 Hz, 1 H), 5.29 (d, J = 1.2 Hz, 1 H), 4.91 (s, 2
H), 4.03 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 161.6 (d, J = 244.0 Hz), 149.8, 148.3,
142.6, 142.0, 138.3, 137.0, 135.2, 132.7 (d, J = 7.6 Hz, 2 ×), 130.0 (2 ×),
128.9, 128.4, 128.2, 127.9, 127.7, 127.6 (2 ×), 127.5, 126.7, 126.1 (2 ×),
126.0 (2 ×), 114.9 (d, J = 21.3 Hz, 2 ×), 114.6, 108.3, 106.6, 70.4, 55.9.
Scott, D. E.; Scherer, A.; Hampel, F.; Hamilton, R. J.; Gray, M. R.;
Tykwinski, R. R.; Stryker, J. M. Org. Lett. 2015, 17, 5930. For pyr-
azoquinolines, see: (i) Kawakami, T.; Uehata, K.; Suzuki, H. Org.
Lett. 2000, 2, 413. For pyrazoles, see: (j) Götzinger, A. C.;
Thebeling, F. A.; Hoppe, C.; Muller, T. J. J. J. Org. Chem. 2016, 81,
10328. For guanidines, see: (k) Overman, L. E.; Wolfe, J. P. J. Org.
Chem. 2001, 66, 3167. For cycloalkenes, see: (l) Miyahara, Y.; Ito,
Y. N. J. Org. Chem. 2014, 79, 6801. For β-lactones, see:
(m) Nelson, S. G.; Spencer, K. L. J. Org. Chem. 2000, 65, 1227. For
triazines, see: (n) Le Falher, L.; Ayad, O. B.; Ziyaret, O.;
Mamontov, A.; Botuha, C.; Thorimbert, S.; Slowinski, F. J. Org.
Chem. 2014, 79, 6579. For pyrroles, see: (o) Bergner, I.; Wiebe,
C.; Meyer, N.; Opatz, T. J. Org. Chem. 2009, 74, 8243. For dihydro-
pyranols, see: (p) Garcia, J. L.; Fernandez-Ibanez, R. M. A.;
Maestro, M. C. J. Org. Chem. 2006, 71, 7683. For furans, see:
(q) Mross, G.; Holtz, F.; Langer, P. J. Org. Chem. 2006, 71, 8045.
For chromenes, see: (r) Kumar, A.; Thadkapally, S.; Menon, R. S.
J. Org. Chem. 2015, 80, 11048.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C32H26FO2: 461.1917; found:
461.1918.
4-Methoxy-2-methyl-2,8-diphenyl-1,2-dihydronaphtho[2,1-b]fu-
ran (5a)
BF3·OEt2 (30 mg, 0.2 mmol) was added to a solution of 4f (73 mg, 0.2
mmol) in CH2Cl2 (10 mL) at r.t. and the reaction mixture was stirred at
r.t. for 2 h. The residue was diluted with sat. aq NaHCO3 (2 mL) and
extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were
washed with brine, dried, filtered, and evaporated under reduced
pressure to afford the crude product. Purification on silica gel (hex-
anes/EtOAc 10:1 to 4:1) afforded 5a; yield: 66 mg (90%); colorless
gum.
(2) Metal-mediated cyclocondensation of o-carbonyl allylben-
zenes; for Au(I)/Ag(I), see: (a) Jagdale, A. R.; Park, J. H.; Youn, S.
W. J. Org. Chem. 2011, 76, 7204. For Rh(I), see: (b) Johnson, K.
F.; Schmidt, A. C.; Stanley, L. M. Org. Lett. 2015, 17, 4654.
(3) Lewis acid mediated cyclocondensation of o-carbonyl allylben-
zenes; for Bi(OTf)3, see: (a) Chan, C.-K.; Wang, H.-S.; Tsai, Y.-L.;
Chang, M.-Y. RSC Adv. 2017, 7, 29321. For Cu(OTf)2, see: (b) Qin,
Y.; Luo, S.; Cheng, J.-P. Org. Lett. 2014, 16, 5032. For In(OTf)3,
see: (c) Kuninobu, Y.; Tatsuzaki, T.; Matsuki, T.; Takai, K. J. Org.
Chem. 2011, 76, 7005.
(4) Base-mediated cyclocondensation of o-carbonyl allylbenzenes;
for DBU, see: (a) Chang, M.-Y.; Wu, M.-H. Tetrahedron 2013, 69,
129. (b) Janssen-Muller, D.; Schedler, M.; Fleige, M.; Daniliuc, C.
G.; Glorius, F. Angew. Chem. Int. Ed. 2015, 54, 12492. For
KHMDS, see: (c) Makra, F.; Rohloff, J. C.; Muehldorf, A. V.; Link, J.
O. Tetrahedron Lett. 1995, 36, 6815. For NaOMe, see: (d) Hattori,
T.; Takeda, A.; Suzuki, K.; Koike, N.; Koshiishi, E.; Miyano, S. J. Chem.
Soc., Perkin Trans. 1 1998, 3661. For MeLi, see: (e) Fu, J.-m.;
Snieckus, V. Can. J. Chem. 2000, 78, 905.
IR (CHCl3): 2958, 1546, 1340, 1230 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.85 (d, J = 8.4 Hz, 1 H), 7.77–7.75 (m, 3
H), 7.65–7.62 (m, 3 H), 7.54–7.51 (m, 2 H), 7.44–7.40 (m, 3 H), 7.34–
7.30 (m, 1 H), 7.18 (s, 1 H), 4.10 (s, 3 H), 3.84 (d, J = 15.2 Hz, 1 H), 3.77
(d, J = 15.2 Hz, 1 H), 2.00 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 147.7, 146.5, 146.1, 141.4, 137.0,
129.5, 128.7 (2 ×), 128.3 (2 ×), 127.8, 127.2 (2 ×), 127.1, 127.0, 126.3,
124.4 (2 ×), 123.1, 120.4, 119.4, 106.2, 91.0, 55.7, 44.2, 29.3.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H23O2: 367.1698; found:
367.1699.
Funding Information
(5) Light-mediated cyclocondensation of o-carbonyl allylbenzenes,
see: (a) de Koning, C. B.; Manzini, S. S.; Michael, J. P.; Mmutlane,
E. M.; Tshabidi, T. R.; van Otterlo, W. A. L. Tetrahedron 2005, 61,
555. (b) de Koning, C. B.; Michael, J. P.; Rousseau, A. L. J. Chem.
Soc., Perkin Trans. 1 2000, 787. (c) de Koning, C. B.; Michael, J. P.;
Rousseau, A. L. Tetrahedron Lett. 1997, 38, 893.
(6) For reviews on naphthalenes, see: (a) de Koning, C. B.; Rousseau,
A. L.; van Otterlo, W. A. L. Tetrahedron 2003, 59, 7. (b) Kotha, S.;
Somnath-Halder, S. M. Tetrahedron 2008, 64, 10775. (c) Kobaisi,
M. A.; Bhosale, S. V.; Latham, K.; Raynor, A. M.; Bhosale, S. V.
Chem. Rev. 2016, 116, 11685. (d) Suraru, S. L.; Würthner, F.
Angew. Chem. Int. Ed. 2014, 53, 7428.
The authors would like to thank the Ministry of Science and Technol-
ogy of the Republic of China for the financial support (MOST 106-
2628-M-037-001-MY3).
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610175. Scanned photocopies of
NMR (CDCl3) spectral data for all compounds and X-ray analysis data
of 4c and 4m are provided.
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(7) For bioactive molecules with the core naphthalene skeleton,
see: (a) Ukita, T.; Nakamura, Y.; Kubo, A.; Yamomoto, Y.;
Takahashi, M.; Kotera, J.; Ikeo, T. J. Med. Chem. 1999, 42, 1293.
(b) Yeo, H.; Li, Y.; Fu, L.; Zhu, J.-L.; Gullen, E. A.; Dutschman, G.
E.; Lee, Y.; Chung, R.; Huang, E.-S.; Austin, D. J.; Cheng, Y.-C.
J. Med. Chem. 2005, 48, 534. (c) Shen, W.; Zou, X.; Chen, M.; Liu,
P.; Shen, Y.; Huang, S.; Guo, H.; Zhang, L. Eur. J. Pharmacol. 2011,
667, 330. (d) Aszno, J.; Chiba, K.; Tada, M.; Yoshii, T. Phytochem-
istry 1996, 42, 713.
(8) For natural products with the core naphthalene skeleton, see:
(a) Ward, R. S. Nat. Prod. Rep. 1999, 16, 75. (b) Apers, S.;
Vlietinck, A.; Pieters, L. Phytochem. Rev. 2003, 2, 201.
(c) Abdissa, N.; Pan, F.; Gruhonjic, A.; Grafenstein, J.; Fitzpatrick,
References
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obtained free of charge from The Cambridge Crystallographic
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L