Synthesis of benzofused cyclobutaoxepanones: Via intramolecular annulation of o -cinnamyl chalcones

Article abstract of DOI:10.1039/d1ob00058f

Intramolecular stereoselective annulation of o-cinnamyloxy chalcones provides two kinds of tricyclic benzofused cyclobutaoxepanones via the synthesized routes of DABCO/NBS (1,4-diazabicyclo[2.2.2]octane/N-bromosuccinimide)-mediated Baylis-Hillman type cyc

Full text of DOI:10.1039/d1ob00058f

Organic &
Biomolecular Chemistry
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Synthesis of benzofused cyclobutaoxepanones via
intramolecular annulation of o-cinnamyl
chalcones†
Cite this: Org. Biomol. Chem., 2021,
9, 2254
1
a,b
a
Meng-Yang Chang
*
and Min-Chen Tsai
Intramolecular stereoselective annulation of o-cinnamyloxy chalcones provides two kinds of tricyclic
benzofused cyclobutaoxepanones via the synthesized routes of DABCO/NBS (1,4-diazabicyclo[2.2.2]
octane/N-bromosuccinimide)-mediated Baylis–Hillman type cyclization or low-pressure mercury (LP Hg)
lamp-promoted photocontrolled [2 + 2] cycloaddition. Diversified reaction conditions have been investi-
gated for one-pot facile, high-yield transformation.
Received 12th January 2021,
Accepted 12th February 2021
DOI: 10.1039/d1ob00058f
rsc.li/obc
expensive, open-vessel, and high-yield route in the preparation
of functionalized cyclobutyl-conjugated molecules is still
Introduction
In organic fields, synthetic efforts toward the high ring- highly desired. Herein, we present the organoamine-mediated
1
–4
strain,
focused on photoinitiated [2 + 2] cycloaddition (a + c sides),
intramolecular S 2 cyclization of homoallylic mesylates (b molecular (2 + 2) stepwise annulation of o-cinnamyloxy chal-
rigid skeleton of cyclobutanes have largely been one-pot synthesis of tricyclic benzofused cyclobutaoxepanones
5
via the DABCO/NBS-mediated Baylis–Hillman type intra-
N
6
7
side), ring-expansion of cyclopropyl derivatives (d side), and cone under refluxing CCl conditions (Scheme 2).
4
direct Suzuki–Miyaura coupling of BF
3
K-containing cyclobu-
In fact, to the best of our knowledge, no cyclobutyl-fused
8
tanes with haloarenes, Lewis acid-mediated cycloaddition of ring on a core structure of benzoxepanone has been reported.
9
allenes and allenoates (a + c sides), metal-catalyzed [2 + 2] Benzoxepanone moiety plays a key role in naturally occurring
1
0
17
18
annulation of electron-deficient allenes (a + c sides), and products and bioactive molecules. Therefore, a number of
other elegant synthetic routes (Scheme 1).
The cyclobutane unit can be found as a basic structural been reported via various prepared protocols.
element in a wide range of naturally occurring compounds in
1
1
attempts to synthesize the skeletons of benzoxepanones have
1
9
bacteria, fungi, plants, and marine invertebrates. The mole-
cules containing four-membered ring(s) represent potential
Results and discussion
1
2
13
biological properties, such as ivabradine, iobucavir, scep-
1
4
15
16
trin, hippolachnin A, and piperarborenine B. Compared
with these previous synthetic routes, most showed photo-trig-
gered [2 + 2] cycloaddition and metal-promoted [2 + 2] annula-
tion in the formation of cyclobutane derivatives. However,
there are few studies on non-photo and metal-free synthetic
works. In spite of these prominent advancements, some pro-
blems exist, such as complicated catalytic conditions, lack of
broad substrate generality, and prefunctionalized fragments.
As a result of the recent findings, an easily controlled, in-
Continuing our synthetic research on synthetic applications on
substituted o-hydroxy-2-acetophenones for the generation of
diversified benzannulated molecules (e.g., benzofuran-3-ones,
chroman-4-ones, aurones, flavones), a convenient route for
preparing benzofused cyclobutaoxepanones was explored next.
2
0
a
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University,
Kaohsiung 807, Taiwan. E-mail: mychang@kmu.edu.tw
b
Department of Medical Research, Kaohsiung Medical University Hospital,
Kaohsiung 807, Taiwan
†
Electronic supplementary information (ESI) available: Scanned photocopies of
NMR spectral data for all compounds and X-ray analysis data of 6a, 6d, 7a and
m were supported. CCDC 1943157–1943160. For ESI and crystallographic data
in CIF or other electronic format see DOI: 10.1039/d1ob00058f
7
Scheme 1 Synthetic routes of cyclobutane core.
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to 15 and 20 h, similar results were observed (entries 2 and 3).
Next, elevating the temperature to reflux (77 °C) and control-
ling the time at 10, 15, and 20 h, the yields of 6a were
increased to 75%, 90% and 88%, respectively (entries 4–6).
From the results, we found that temperature is an important
factor that affects the formation of 6a. Then, by controlling the
temperature and time as 77 °C and 15 h, the equivalents of
DABCO and NBS were screened. In entry 7, we found that cata-
lytic amounts (0.3 equiv.) of DABCO could provide 6a in a 25%
yield along with 55% of unknown products. By use of the stoi-
chiometric amounts (1.1 equiv.) of DABCO, 6a was isolated in
an 85% yield (entry 8). From the phenomenon, we understood
that 0.6 equivalents of DABCO was an appropriate amount for
intramolecular annulation reaction.
Scheme 2 Our synthetic route of benzofused cyclobutaoxepanones.
The required starting materials, o-cinnamyloxy chalcones 5,
were easily prepared from two-step synthetic routes, including
the (1) O-allylation of substituted o-hydroxyacetophenones 2
2 3
with cinnamyl chloride (3a) in the presence of K CO , (2) fol-
lowed by Claisen–Schmidt condensation of the resulting o-ally-
loxy acetophenones 4 with diversified arylaldehydes under the
alkali-mediated conditions (Scheme 3).
On the other hand, the equivalent of NBS was checked.
Entry 9 showed that no better yield (77%) was detected when
decreasing the amounts of NBS (0.3 equiv.). Although 0.3 equi-
valent of NBS could promote the stepwise (2 + 2) annulation
completely, the isolated yield of 6a was lower than 0.6 equiva-
lents of NBS. In particular, the stoichiometric amounts (1.1
equiv.) of NBS initiated a multi-bromination of electron-rich
arenes such that low yields (48%) of 6a were isolated along
with a major complex mixture (40%, entry 10). To obtain
better yields, we wanted to change DABCO to other di-nitrogen
atom-containing organoamines. When using DBU (0.6 equiv.),
the desired 6a could not be generated due to NBS reacting
with the amidine moiety of DBU (entry 11), and only 5a was
recovered. By changing the base to DMAP (an aromatic amine),
however, 6a was produced in a 65% yield (entry 12). 2,2′-
Bipyridine (BPY) also provided similar yields (60%) compared
with DMAP (entry 13). Furthermore, three solvents with temp-
eratures near boiling points (82–85 °C) were tested. Entries
The study commenced with the treatment of model sub-
strates 5a (Ar = Ph, R = Ph, R′ = 3,4-(MeO) C H , 1.0 mmol)
2
6
3
and the combination of DABCO (0.6 equiv.) and NBS (0.6
equiv.) in CCl (10 mL) at 25 °C for 10 h (Table 1, entry 1). By
the reaction conditions it can be seen that only trace amounts
∼3%) of 6a were detected. After elongating the time from 10
4
(
Scheme 3 Synthesis of 5.
a
Table 1 Reaction conditions
1
4–16 show that MeCN, (CH
2
Cl)
2
and glyme didn’t obtain
(90%). From the
better yields (36% 81% and 70%) than CCl
4
above observations, we conclude that DABCO/NBS/CCl is an
4
optimal combination for synthesizing 6a via a stepwise Baylis–
Hillman type (2 + 2) annulation. The stereochemistry of 6a was
determined as a monoclinic crystal system and P2 /c space
1
2
1
group by single-crystal X-ray analysis.
To study the scope and limitations of this route, substituted
o-cinnamyloxy acetophenones 5a–5u were reacted with a com-
bination of DABCO (0.6 equiv.) and NBS (0.6 equiv.) to afford
diversified tricyclic benzofused cyclobutaoxepanones 6a–6u
under refluxing CCl4 (77 °C/15 h) conditions, as shown in
Table 2. With optimal conditions established (Table 1, entry
5), we found that this route allowed direct stepwise (2 + 2)
annulation in good to excellent yields (86%–98%). Among
entries 1–21, efficient formation of 6a–6u showed that two aryl
substituents (5, Ar and R′) did not affect the yields. After
careful purification on a column chromatography, we found
that skeleton 6 was isolated as the sole isomer, while no other
diastereomers were observed on the basis of the analysis of
NMR spectrum. Furthermore, the molecular structure of 6d
with the relative configuration of a cyclobutane ring was deter-
b
Entry
Base/NBS (equiv.)
Temp. (°C)
Time (h)
6a , %
1
2
3
4
5
6
7
8
9
DABCO (0.6)/NBS (0.6)
DABCO (0.6)/NBS (0.6)
DABCO (0.6)/NBS (0.6)
DABCO (0.6)/NBS (0.6)
DABCO (0.6)/NBS (0.6)
DABCO (0.6)/NBS (0.6)
DABCO (0.3)/NBS (0.6)
DABCO (1.1)/NBS (0.6)
DABCO (0.6)/NBS (0.3)
DABCO (0.6)/NBS (1.1)
DBU (0.6)/NBS (0.6)
DMAP (0.6)/NBS (0.6)
BPY (0.6)/NBS (0.6)
DABCO (0.6)/NBS (0.6)
DABCO (0.6)/NBS (0.6)
DABCO (0.6)/NBS (0.6)
25
25
25
77
77
77
77
77
77
77
77
77
77
82
84
85
10
15
20
10
15
20
15
15
15
15
15
15
15
15
15
15
Trace
Trace
Trace
75
90
88
25
c
85
77
c
10
11
12
13
14
15
16
48
d
—
65
60
36
81
70
e
f
g
a
b
The reactions were run on a 1.0 mmol scale with 5a, CCl
4
(10 mL).
2
1
c
mined by single-crystal X-ray analysis. For the electronic
nature of the aryl substituent (Ar) of 5, not only haloaryl
Isolated yields. Unknown mixture was isolated (for entry 7, 55%;
d
e
f
g
entry 10, 40%). 5a (65%) was recovered. MeCN. (CH
2 2
Cl) .
Glyme.
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a
Table 2 Synthesis of 6a–6u
pathway, the olefinic group of the styryl moiety on intermedi-
ate II could trap the bromo atom to release the tertiary amino
group again from the endo-face. Following, α-carbanion attacks
the in situ generated bromonium ion on intermediate III to
give intermediate IV with a core of benzofused oxepanone. For
synthetic applications on DABCO-Br complex (ammonium
bromide salt), Xie et al. have reported similar phenomenon for
highly asymmetric bromocyclization of tryptophol. Finally,
by the intramolecular nitrogen atom-promoted debromination,
sequential removal of DABCO skeleton furnishes the trans-
formation from intermediate IV to skeleton 6. The resulting tri-
cyclic structural framework of skeleton 6 possessed four con-
tiguous cis–trans–cis–trans stereocenters on the cyclobutane
ring.
b
Entry
5a–5u, Ar=, R′=
6a–6u , %
22
1
2
3
4
5
6
7
8
9
5a, Ph, 3,4-(MeO)
2
C
6
H
3
6a, 90
6b, 94
6c, 93
6d, 98
6e, 94
6f, 90
6g, 90
6h, 94
6i, 90
6j, 90
6k, 90
6l, 89
6m, 88
6n, 86
6o, 89
6p, 92
6q, 94
6r, 93
6s, 95
6t, 87
6u, 87
5b, 4-BrC
5c, 4-ClC
6
H
3
, 3,4-(MeO)
, 3,4-(MeO)
2 6 3
, 3,4-(MeO) C H
2 6 3
C H
C H
2 6 3
6
H
3
6
5d, 4-FC H
3
5e, 4-MeC
5f, 5-MeOC
6
H
3
, 3,4-(MeO)
, 3,4-(MeO)
2
C
6
H
3
6
H
3
2
C
6
H
3
5g, Ph, 3,4-CH
5h, Ph, 3,4,5-(MeO)
5i, Ph, 3-MeOC
5j, Ph, 4-MeOC
5k, Ph, 2,3,4-(MeO)
5l, Ph, 2-HOC
5m, Ph, 2,4-(MeO)
5n, Ph, 4-NO
5o, Ph, 4-PhC
5p, Ph, 3,4-Cl C H
2 6 3
5q, Ph, 2-naphthyl
5r, Ph, 2-furyl
5s, Ph, 2-thienyl
2
O
2
C
6
H
3
3
C
6
H
2
6
H
H
4
10
11
12
13
14
15
16
17
18
19
20
21
6
4
Based on the results, photo-initiated intramolecular [2 + 2]
cycloaddition of 5 with two olefinic arms was examined next,
as shown in Scheme 5. First, treatment of model substrate 5a
(0.3 mmol) with the radiation of a low-pressure mercury lamp
3 6
C H
2
6
H
4
2 6 3
C H
C H
2 6 4
6 4
H
(
LP Hg, λ = 254 nm, hard UV) provided sole 7a in an 85% yield
in the presence of iodine (10 mol%) for 15 h at 25 °C. Based
2
1
on single-crystal X-ray diagram of 7a, the exact structure of
a could be determined. In particular, four contiguous stereo-
7
6 4
5t, Ph, 2-FC H
centers of the cyclobutane ring on 7a possessed a cis–cis–cis–
trans configuration. The reason for this is that the olefinic iso-
merization from (E)-5a to (Z)-A was initiated first. Then, the
concerted [2 + 2] cycloaddition of A to 7a was accomplished.
Compared with the combination of DABCO/NBS, the alterna-
tive photolytic route provides complementary results in the
construction of cyclobutane with four stereogenic centers.
5u, Ph, 4-pyridyl
a
The reactions were run on a 1.0 mmol scale with 5a–5u, DABCO
(10 mL), reflux
(
(
70 mg, 0.6 mmol), NBS (107 mg, 0.6 mmol), CCl
4
b
77 °C), 15 h. Isolated yields.
(
bromo, chloro) groups but also electron-neutral (methyl), elec-
Furthermore, controlling the R′ = 3,4-(MeO)
with different Ar group (4-FC , 4-MeC
2
C
6
H
3
group, 5d–5f
tron-withdrawing (fluoro), and electron-donating (methoxy)
groups were appropriate. For the R′ substituent, electron-
releasing mono-, di-, tri oxygenated groups, the electron-with-
drawing nitro group, dichloro, bicyclic 2-naphthyl, and hetero-
cyclic groups (2-furyl, 2-thienyl, 2-pyridyl) were well tolerated.
On the basis of our experimental results, a plausible mecha-
nism for the stereoselective formation of skeleton 6 is illus-
trated in Scheme 4. Initially, the bromo-exchange reaction
between DABCO and NBS provides a bromo ammonium succi-
nimide complex. Upon a pseudo-axial intermolecular Michael
addition, the tertiary amino group on the in situ formed inter-
mediate I attacks in the β-position of skeleton 5 to lead to
intermediate II. On the basis of the Baylis–Hillman-type
6
H
3
6
H
3
and 5-MeOC H )
6 3
produced 7d–7f in 84%, 80%, and 75% yields, respectively. On
the other way, by adjusting the Ar substituent as the Ph group,
five R′ groups (e.g. 3,4,5-(MeO)
3
C
6
H
2
,
4-MeOC
6 4
H , 2,4-
(
MeO) C H , 4-PhC H and 2-naphthyl) provided 7h, 7j, 7m,
2
6
3
6
4
7o, and 7q in a range of 76%–85% yields.
To investigate the substrate scope, 5v–5y with a styryloxy
group were examined. According to the above synthetic route
of 5a–5u with a cinnamyoxy group, the starting materials 5v–5y
(
2 6 3 2 6 4
R′ = 3,4-(MeO) C H , 4-NO C H , 2-naphthyl, 2-thienyl) were
easily prepared from a two-step route (O-styrylation and
Scheme 4 Plausible mechanism.
Scheme 5 Photo-triggered [2 + 2] cycloaddition of 5.
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Claisen–Schmidt condensation). However, attempts to afford
6
v–6y failed since the steric hindrance of the Ph group inhib-
ited intramolecular annulation between the carbanion and
bromonium ion on intermediate III under the DABCO/NBS-
mediated condition, and major bromo-containing products
were separated among the product mixture (Scheme 6, eqn
(1)). In particular, the photolytic reaction of 5v–5y could not
Scheme 7 Synthesis of 6ad.
produce 7v–7y. Only starting materials were recovered.
Compared with the Ph group of the cinnamyloxy arm, we
believed that the Ph group of the styryloxy arm could stabilize
an in situ formed tertiary radical such that the reactivity was
low. The steric hindrance of the Ph group could play another
important role in affecting the formation of the cyclobutane
ring.
Then, by changing the cinnamyloxy to a crotyloxy group,
DABCO/NBS-mediated reactions of 5z-5ab were checked. When
the reaction of 5z-5ab was treated with a combination of
DABCO/NBS, however, a bromo-containing mixture displaced
Scheme 8 Synthesis of 7ae.
the desired 6z-6ab (Scheme 6, eqn (2)). Compared with the cin- to 5ad with the o-cinnamylamino group, 6ad was isolated in a
namyl group, we thought that the olefinic moiety of the crotyl 90% yield (Scheme 7). To date, no reports have documented
group could exhibit higher reactivity to react with NBS for the the synthesis of the novel tricyclic cyclobutyl-fused benzoazepi-
formation of a brominium ion of intermediate III such that none skeleton. On the other hand, two groups (2- and 4-posi-
the intramolecular ring-closure would become complex. For tions) on the chalcone skeleton were exchanged to extend the
photo-triggered annulation of 5z-5ab, still no reactions were photolytic applications. The starting material, 5ae, was pre-
observed. The results were similar to those for 5v–5y. From the pared from Claisen–Schmidt condensation of o-cinnamyloxy
results, we understand that homolytic bond cleavage of the benzaldehyde with acetone, as shown in Scheme 8.
crotyl group (an aliphatic substituent) was not easier to initiate Interestingly, after photolytic radiation of 5ae, only 50% of 8
than the cinnamyl group (an aromatic substituent) since the was obtained via the olefinic (E)- and (Z)-isomerization along
methyl group could not stabilize the formed radical species with the recovery of 23% of 5ae. The expected 7ae with the tri-
such that [2 + 2] cycloaddition was blocked. As shown in cyclic cyclobutyl-fused chromane skeleton was not detected.
Scheme 6 and eqn (3), 5ac with a prenyloxy arm was checked.
In summary, we have developed a DABCO/NBS-controlled
Under DABCO/NBS conditions especially, 6ac could be synthesis of tricyclic benzofused cyclobutaoxepanones via
obtained in a 45% yield along with a 30% yield of an unknown intramolecular stereoselective Baylis–Hillman type annulation
bromo-containing mixture. Although the isolated yield of 6ac of o-cinnamyloxy chalcones under refluxing CCl reaction con-
4
was low, a geminal dimethyl-conjugated cyclobutane ring was ditions in good to excellent yields. Also, a low-pressure
formed. But, even using radiation of 5ac with an LP Hg lamp, mercury lamp-promoted photocontrolled intramolecular [2 +
7
ac was still not detected.
2] cycloaddition of o-cinnamyloxy chalcones has been investi-
Based on the above-mentioned DABCO/NBS conditions, by gated. The process provides a one-pot pathway of two carbon–
changing the mode substrate 5a with the o-cinnamyoxy group carbon bond formations. The uses of various organoamines
and solvents are investigated for facile and efficient transform-
ation. Related plausible mechanisms have been proposed. The
structures of the key products were confirmed by X-ray crystal-
lography. Further investigations regarding the synthetic appli-
cations of o-cinnamyloxy chalcones will be conducted and
published in due course.
Experimental
General
All reagents and solvents were obtained from commercial
sources and used without further purification. Reactions were
routinely carried out under an atmosphere of dry nitrogen
with magnetic stirring. The heating mantle is used to provide
a stable heat source. Products in organic solvents were dried
Scheme 6 Reactions of 5v-5ac.
with anhydrous magnesium sulfate before concentration in
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1
3
3
vacuo. Melting points were determined with a SMP3 melting 3H); C NMR (100 MHz, CDCl ): δ 198.0, 156.3, 135.8, 133.8,
1
13
apparatus. H and C NMR spectra were recorded on a Varian 132.9, 129.9, 129.4, 128.5 (2×), 128.1, 126.5 (2×), 125.9, 122.9,
INOVA-400 spectrometer operating at 400 and at 100 MHz, 114.3, 69.5, 31.8.
respectively. Chemical shifts (δ) are reported in parts per
1-[5-Fluoro-2-(3-phenylallyloxy)phenyl]ethanone (4d). Yield =
million (ppm) and the coupling constants (J) are given in 90% (243 mg); colorless solid; mp = 77–79 °C (recrystallized
+
hertz. High resolution mass spectra (HRMS) were measured from hexanes and EtOAc); HRMS (ESI, M + 1) calcd for
1
with a mass spectrometer Finnigan/Thermo Quest MAT 95XL.
C
17
H
16FNO
2
271.1134, found 271.1128, err (ppm): 2.21;
H
X-ray crystal structures were obtained with an Enraf-Nonius NMR (400 MHz, CDCl ): δ 7.48 (dd, J = 3.2, 8.8 Hz, 1H),
3
FR-590 diffractometer (CAD4, Kappa CCD).
7.44–7.27 (m, 5H), 7.18–7.13 (m, 1H), 6.97 (dd, J = 4.4, 9.2 Hz,
For the starting substituted o-hydroxyacetophenones 2a–2h, 1H), 6.75 (d, J = 16.0 Hz, 1H), 6.42 (dt, J = 6.0, 16.0 Hz, 1H),
1
3
allylic halides 3a–3d and arylaldehydes, these reagents were 4.78 (dd, J = 1.2, 6.0 Hz, 2H), 2.67 (s, 3H); C NMR (100 MHz,
obtained from commercial sources and used without further CDCl ): δ 156.8 (d, J = 238.8 Hz), 154.2, 136.0, 134.1, 133.8,
128.7 (2×), 128.2, 126.61 (2×), 126.59 (d, J = 3.0 Hz), 123.3,
20.0 (d, J = 23.5 Hz), 116.5 (d, J = 23.5 Hz), 114.4 (d, J = 6.9
3
purification.
1
A representative synthetic procedure of skeleton 4 is as follows
Hz), 70.0, 31.9.
K
2
CO
3
(300 mg, 2.2 mmol) was added to a solution of o-hydro-
1-[5-Methyl-2-(3-phenylallyloxy)phenyl]ethanone (4e). Yield =
xyacetophenones 2a–2f, o-N-phenylsulfonyl aminoacetophe- 93% (247 mg); colorless solid; mp = 59–60 °C (recrystallized
+
none 2g or o-hydroxybenzaldehyde 2h (1.0 mmol) in MeCN from hexanes and EtOAc); HRMS (ESI, M + 1) calcd for
1
(10 mL) at 25 °C. The reaction mixture was stirred at 25 °C for
C
18
H
19
O
2
267.1385, found 267.1380, err (ppm): 1.87; H NMR
1
0 min. Halides (1.1 mmol, for cinnamyl chloride 3a, 170 mg; (400 MHz, CDCl ): δ 7.55 (d, J = 2.4 Hz, 1H), 7.43–7.41 (m, 2H),
3
for styryl bromide 3b, 220 mg; for crotyl bromide 3c, 100 mg; 7.37–7.33 (m, 2H), 7.30–7.24 (m, 2H), 6.91 (d, J = 8.4 Hz, 1H),
for prenyl chloride 3d, 115 mg) in MeCN (10 mL) was added to 6.74 (d, J = 16.0 Hz, 1H), 6.43 (dt, J = 6.0, 16.0 Hz, 1H), 4.78
1
3
the reaction mixture at 25 °C. The reaction mixture was stirred (dd, J = 1.2, 6.0 Hz, 2H), 2.67 (s, 3H), 2.31 (s, 3H); C NMR
at reflux for 20 h. The reaction mixture was cooled to 25 °C (100 MHz, CDCl ): δ 200.2, 156.0, 136.2, 134.1, 133.4, 130.6,
and the solvent was concentrated. The residue was diluted 130.2, 128.6 (2×), 128.4, 128.1, 126.6 (2×), 123.9, 113.0, 69.4,
3
with water (10 mL) and the mixture was extracted with CH Cl
32.0, 20.2.
2
2
(3 × 20 mL). The combined organic layers were washed with
1-[4-Methoxy-2-(3-phenylallyloxy)phenyl]ethanone (4f). Yield
brine, dried, filtered and evaporated to afford crude product = 96% (271 mg); colorless solid; mp = 79–81 °C (recrystallized
+
under reduced pressure. Purification on silica gel (hexanes/ from hexanes and EtOAc); HRMS (ESI, M + 1) calcd for
1
EtOAc = 20/1–10/1) afforded skeleton 4.
C
18
H
19
O
3
283.1334, found 283.1329, err (ppm): 1.77; H NMR
1
-[2-(3-Phenylallyloxy)phenyl]ethanone (4a). Yield = 95% (400 MHz, CDCl
3
): δ 7.86 (d, J = 8.8 Hz, 1H), 7.44–7.41 (m, 2H),
7.42–7.33 (m, 2H), 7.31–7.26 (m, 1H), 6.76 (d, J = 16.0 Hz, 1H),
NMR 6.54 (dd, J = 2.0, 8.4 Hz, 1H), 6.51 (d, J = 2.4 Hz, 1H), 6.43 (dt, J
+
(
2
239 mg); colorless oil; HRMS (ESI, M + 1) calcd for C H O
53.1229, found 253.1238, err (ppm): −3.67;
1
7
17
2
1
H
(
(
400 MHz, CDCl
3
): δ 7.76 (dd, J = 2.0, 7.6 Hz, 1H), 7.48–7.42 = 6.0, 16.0 Hz, 1H), 4.78 (dd, J = 1.2, 6.0 Hz, 2H), 3.85 (s, 3H),
1
3
m, 3H), 7.37–7.33 (m, 2H), 7.31–7.27 (m, 1H), 7.04–7.00 (m, 2.63 (s, 3H); C NMR (100 MHz, CDCl ): δ 197.7, 164.3, 160.0,
3
2
4
H), 6.76 (d, J = 16.0 Hz, 1H), 6.44 (dt, J = 5.6, 16.0 Hz, 1H), 136.1, 133.7, 132.7, 128.6 (2×), 128.1, 126.6 (2×), 123.4, 121.4,
1
3
.81 (dd, J = 1.6, 6.0 Hz, 2H), 2.67 (s, 3H); C NMR (100 MHz, 105.3, 99.4, 69.3, 55.5, 32.1.
1-[2-(2-Phenylallyloxy)phenyl]ethanone (4g). Yield = 93%
CDCl ): δ 199.9, 157.9, 136.1, 133.6, 133.5, 130.4, 128.70,
1
3
+
28.65 (2×), 128.1, 126.6 (2×), 123.6, 120.8, 112.9, 69.3, 32.0.
-[5-Bromo-2-(3-phenylallyloxy)phenyl]ethanone (4b). Yield = 253.1229, found 253.1238, err (ppm): −3.56;
4% (310 mg); colorless solid; mp = 85–87 °C (recrystallized (400 MHz, CDCl ): δ 7.74 (dd, J = 1.6, 7.6 Hz, 1H), 7.49–7.44
17 2
(234 mg); colorless oil; HRMS (ESI, M + 1) calcd for C17H O
1
1
H NMR
9
3
+
from hexanes and EtOAc); HRMS (ESI, M + 1) calcd for (m, 3H), 7.39–7.32 (m, 3H), 7.04–6.99 (m, 2H), 5.62 (s, 1H),
C
1
13
17
H
16BrO
2
331.0334, found 331.0339, err (ppm): −1.51;
H
5.47 (d, J = 0.8 Hz, 1H), 5.02 (s, 2H), 2.38 (s, 3H); C NMR
NMR (400 MHz, CDCl ): δ 7.86 (d, J = 2.4 Hz, 1H), 7.52 (dd, J = (100 MHz, CDCl ): δ 199.9, 157.8, 142.9, 138.1, 133.5, 130.5,
3
3
2
7
1
2
1
.8, 8.8 Hz, 1H), 7.42 (d, J = 8.8 Hz, 2H), 7.37–7.33 (m, 2H), 128.5 (3×), 128.2, 126.1 (2×), 120.9, 115.7, 112.6, 70.5, 31.7.
.31–7.27 (m, 1H), 6.90 (d, J = 8.8 Hz, 1H), 6.75 (d, J = 16.0 Hz, 1-(2-But-2-enyloxyphenyl)ethanone (4h). Two isomers (E/Z =
H), 6.40 (dt, J = 6.0, 16.0 Hz, 1H), 4.78 (dd, J = 1.2, 6.0 Hz, 5/1); yield = 89% (169 mg); colorless oil; HRMS (ESI, M + 1)
+
1
3
H), 2.65 (s, 3H); C NMR (100 MHz, CDCl
35.93, 135.87, 134.0, 132.9, 130.0, 128.6 (2×), 128.2, 126.7 −4.19; for major E-isomer: H NMR (400 MHz, CDCl
(dd, J = 2.0, 8.0 Hz, 1H), 7.24 (dt, J = 2.0, 8.4 Hz, 1H), 6.81–6.75
-[5-Chloro-2-(3-phenylallyloxy)phenyl]ethanone (4c). Yield = (m, 2H), 5.73–5.66 (m, 1H), 5.60–5.53 (m, 1H), 4.35 (dd, J = 1.2,
3 15 2
): δ 198.2, 156.9, calcd for C12H O 191.1072, found 191.1080, err (ppm):
1
3
): δ 7.59
(2×), 123.0, 114.8, 113.3, 69.6, 31.9.
1
+
13
9
0% (257 mg); colorless oil; HRMS (ESI, M + 1) calcd for 5.6 Hz, 2H), 2.46 (s, 3H), 1.59 (dd, J = 1.2, 6.4 Hz, 3H);
C
1
C H ClO 287.0839, found 287.0846, err (ppm): −2.44;
H
NMR (100 MHz, CDCl ): δ 198.8, 157.6, 133.0, 130.0, 129.7,
3
1
7
16
2
NMR (400 MHz, CDCl
(
(
3
): δ 7.74 (d, J = 2.8 Hz, 1H), 7.44–7.27 128.4, 125.0, 119.9, 112.3, 68.6, 31.4, 17.2.
m, 6H), 6.93 (d, J = 8.8 Hz, 1H), 6.74 (d, J = 16.0 Hz, 1H), 6.40 1-[2-(3-Methylbut-2-enyloxy)phenyl]ethanone (4i). Yield =
dt, J = 6.0, 16.0 Hz, 1H), 4.75 (dd, J = 1.2, 6.0 Hz, 2H), 2.65 (s, 85% (173 mg); colorless oil; HRMS (ESI, M + 1) calcd for
+
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205.1229, found 205.1238, err (ppm): −4.39;
Paper
1
C
13
H
17
O
2
H
Hz, 1H), 7.60 (d, J = 15.6 Hz, 1H), 7.50 (dd, J = 2.4, 8.8 Hz, 1H),
NMR (400 MHz, CDCl ): δ 7.73 (dd, J = 1.6, 8.0 Hz, 1H), 7.35 (d, J = 15.6 Hz, 1H), 7.26–7.17 (m, 5H), 7.11 (dd, J = 1.6,
3
7
.45–7.41 (m, 1H), 6.99–6.94 (m, 2H), 5.52–5.48 (m, 1H), 4.61 8.4 Hz, 1H), 7.02 (d, J = 1.2 Hz, 1H), 6.87 (d, J = 8.8 Hz, 1H),
(
3
1
d, J = 6.8 Hz, 2H), 2.62 (s, 3H), 1.80 (d, J = 1.2 Hz, 3H), 1.75 (s, 6.69 (d, J = 16.0 Hz, 1H), 6.63 (d, J = 8.0 Hz, 1H), 6.33 (dt, J =
13
H); C NMR (100 MHz, CDCl ): δ 200.1, 158.3, 138.3, 133.5, 5.6, 16.0 Hz, 1H), 4.70 (d, J = 4.8 Hz, 2H), 3.82 (s, 3H), 3.71 (s,
3
1
3
30.3, 128.6, 120.4, 119.2, 112.7, 65.3, 32.0, 25.7, 18.2.
3
3H); C NMR (100 MHz, CDCl ): δ 190.5, 156.1, 151.1, 149.0,
N-(2-Acetylphenyl)-N-(3-phenylallyl)benzenesulfonamide (4j). 143.8, 135.8, 135.1, 133.2, 133.0, 131.0, 128.4 (2×), 127.9, 127.6,
+
Yield = 60% (235 mg); colorless oil; HRMS (ESI, M + 1) calcd 126.4 (2×), 124.5, 122.9, 122.6, 114.7, 113.4, 111.0, 110.3, 69.3,
for C23 S 392.1320, found 392.1326, err (ppm): −1.53; 55.8, 55.5.
H NMR (400 MHz, CDCl ): δ 7.64–7.57 (m, 4H), 7.48–7.44 (m, 1-[5-Chloro-2-(3-phenylallyloxy)phenyl]-3-(3,4-dimethoxyphe-
H
22NO
3
1
3
2
=
2
1
H), 7.38–7.19 (m, 7H), 6.76 (dd, J = 1.2, 7.6 Hz, 1H), 6.40 (d, J nyl)propenone (5c). Yield = 86% (373 mg); colorless solid; mp
16.0 Hz, 1H), 6.23 (dt, J = 6.8, 16.0 Hz, 1H), 4.60 (br s, 2H), = 128–130 °C (recrystallized from hexanes and EtOAc); HRMS
1
3
+
.63 (s, 3H); C NMR (100 MHz, CDCl
3
): δ 200.4, 141.5, 138.1, (ESI, M + 1) calcd for C26
H
24ClO
4
435.1363, found 435.1370,
1
36.2, 136.0, 134.6, 132.8, 131.1, 129.0, 128.9, 128.8 (2×), 128.4 err (ppm): −1.61; H NMR (400 MHz, CDCl ): δ 7.65 (d, J = 2.8
3
(2×), 128.3, 127.9, 127.7 (2×), 126.3 (2×), 123.3, 54.2, 30.1.
Hz, 1H), 7.61 (d, J = 15.6 Hz, 1H), 7.41 (dd, J = 2.8, 8.8 Hz, 1H),
2
-(3-Phenylallyloxy)benzaldehyde (4k). Yield = 68% (162 mg); 7.35 (d, J = 16.0 Hz, 1H), 7.28–7.22 (m, 5H), 7.15 (dd, J = 2.0,
+
colorless oil; HRMS (ESI, M + 1) calcd for C H O 239.1072, 8.4 Hz, 1H), 7.05 (d, J = 2.0 Hz, 1H), 6.98 (d, J = 8.8 Hz, 1H),
found 239.1080, err (ppm): −3.34; H NMR (400 MHz, CDCl
1
6
15 2
1
3
): 6.72 (d, J = 16.4 Hz, 1H), 6.69 (d, J = 8.4 Hz, 1H), 6.37 (dt, J =
δ 10.6 (s, 1H), 7.80 (dd, J = 2.0, 8.0 Hz, 1H), 7.55 (dd, J = 1.6, 5.2, 16.0 Hz, 1H), 4.76 (dd, J = 1.6, 6.0 Hz, 2H), 3.86 (s, 3H),
1
3
8
.4 Hz, 1H), 7.45–7.43 (m, 2H), 7.38–7.34 (m, 2H), 7.31–7.27 3.75 (s, 3H); C NMR (100 MHz, CDCl ): δ 190.9, 155.7, 151.3,
3
(
2
m, 1H), 7.06–7.2 (m, 2H), 6.77 (d, J = 16.4 Hz, 1H), 6.42 (dt, J = 149.1, 144.0, 136.0, 133.3, 132.3, 130.9, 130.2, 128.6 (2×), 128.1,
.0, 16.0 Hz, 1H), 4.79 (dd, J = 1.6, 5.6 Hz, 2H); C NMR 127.8, 126.5 (2×), 126.4, 124.7, 123.1, 122.8, 114.5, 111.1, 110.3,
1
3
(100 MHz, CDCl ): δ 189.5, 160.8, 135.9, 135.7, 133.3, 128.5 69.6, 55.9, 55.7.
3
(
2×), 128.2, 128.0, 126.4 (2×), 124.9, 123.2, 120.7, 112.7, 68.9.
3-(3,4-Dimethoxyphenyl)-1-[5-fluoro-2-(3-phenylallyloxy)phenyl]
propenone (5d). Yield = 83% (347 mg); colorless solid; mp =
23–125 °C (recrystallized from hexanes and EtOAc); HRMS
A representative synthetic procedure of skeleton 5 is as follows
Sodium hydroxide (NaOH, 100 mg, 2.5 mmol) was added to a (ESI, M + 1) calcd for C26
1
+
H
24FO
4
419.1659, found 419.1653,
1
solution of 4 (1.0 mmol) in MeOH (10 mL) at 25 °C. A solution err (ppm): 1.43; H NMR (400 MHz, CDCl ): δ 7.63 (d, J = 15.6
3
of substituted arylaldehydes (1.0 mmol) in THF (5 mL) was Hz, 1H), 7.42 (dd, J = 3.2, 8.8 Hz, 1H), 7.41 (d, J = 15.6 Hz, 1H),
added to the reaction mixture at 25 °C. The reaction mixture 7.28–7.22 (m, 5H), 7.18 (dd, J = 3.2, 8.4 Hz, 1H), 7.16 (dd, J =
was stirred at 25 °C for 20 h (monitored by TLC). The solvent 2.4, 8.4 Hz, 1H), 7.05 (d, J = 2.0 Hz, 1H), 7.00 (dd, J = 4.0, 8.8
was concentrated under reduced pressure. The residue was Hz, 1H), 6.72 (d, J = 16.0 Hz, 1H), 6.68 (d, J = 8.4 Hz, 1H), 6.38
diluted with water (10 mL) and the mixture was extracted with (dt, J = 5.6, 16.0 Hz, 1H), 4.75 (dd, J = 1.6, 5.6 Hz, 2H), 3.86 (s,
1
3
3
EtOAc (3 × 20 mL). The combined organic layers were washed 3H), 3.75 (s, 3H); C NMR (100 MHz, CDCl ): δ 190.9, 157.1
with brine, dried, filtered and evaporated to afford crude (d, J = 239.6 Hz), 153.4 (d, J = 1.6 Hz), 151.2, 149.1, 143.9,
product. Purification on silica gel (hexanes/EtOAc = 20/1–6/1) 136.0, 133.2, 130.8 (d, J = 6.1 Hz), 128.5 (2×), 128.0, 127.8,
afforded skeleton 5.
126.5 (2×), 124.7, 123.4, 122.8, 119.1 (d, J = 23.5 Hz), 117.0 (d, J
3
-(3,4-Dimethoxyphenyl)-1-[2-(3-phenylallyloxy)phenyl]pro- = 23.5 Hz), 114.7 (d, J = 7.6 Hz), 111.1, 110.3, 70.1, 55.9, 55.7.
penone (5a). Yield = 80% (320 mg); colorless solid; mp =
3-(3,4-Dimethoxyphenyl)-1-[5-methyl-2-(3-phenylallyloxy)phenyl]
1
31–133 °C (recrystallized from hexanes and EtOAc); HRMS propenone (5e). Yield = 73% (302 mg); colorless solid; mp =
+
(ESI, M + 1) calcd for C H O 401.1753, found 401.1763, err 114–116 °C (recrystallized from hexanes and EtOAc); HRMS
2
6
25 4
1
+
(
ppm): −2.49; H NMR (400 MHz, CDCl
3
): δ 7.70 (dd, J = 2.0, (ESI, M + 1) calcd for C27
H
27
O
4
415.1909, found 415.1915, err
): δ 7.63 (d, J = 16.0
1
7
.6 Hz, 1H), 7.63 (d, J = 15.6 Hz, 1H), 7.46–7.41 (m, 1H), 7.43 (ppm): −1.45; H NMR (400 MHz, CDCl
3
(
d, J = 15.6 Hz, 1H), 7.26–7.17 (m, 5H), 7.13 (dd, J = 2.0, 8.4 Hz, Hz, 1H), 7.50 (d, J = 2.4 Hz, 1H), 7.43 (d, J = 16.0 Hz, 1H),
H), 7.05 (dt, J = 1.2, 7.6 Hz, 1H), 7.04 (s, 1H), 6.99 (d, J = 8.0 7.27–7.18 (m, 6H), 7.15 (dd, J = 1.6, 8.4 Hz, 1H), 7.06 (d, J = 1.6
Hz, 1H), 6.72 (d, J = 16.0 Hz, 1H), 6.64 (d, J = 8.4 Hz, 1H), 6.37 Hz, 1H), 6.93 (d, J = 8.4 Hz, 1H), 6.72 (d, J = 16.4 Hz, 1H), 6.67
1
(
dt, J = 5.6, 16.4 Hz, 1H), 4.74 (dd, J = 1.6, 5.6 Hz, 2H), 3.82 (s, (d, J = 8.4 Hz, 1H), 6.38 (dt, J = 5.2, 16.0 Hz, 1H), 4.74 (dd, J =
1
3
13
3
1
1
1
H), 3.71 (s, 3H); C NMR (100 MHz, CDCl
50.9, 148.9, 142.8, 135.9, 132.7, 132.7, 130.5, 129.4, 128.3 (2×), NMR (100 MHz, CDCl
27.8, 127.7, 126.3 (2×), 125.2, 123.4, 122.4, 120.9, 112.8, 110.9, 136.1, 133.3, 132.7, 130.9, 130.5, 129.4, 128.4 (2×), 128.0, 127.8,
3
): δ 192.1, 157.0, 1.6, 5.6 Hz, 2H), 3.85 (s, 3H), 3.73 (s, 3H), 2.33 (s, 3H);
C
3
): δ 192.4, 155.1, 150.9, 149.0, 142.8,
10.1, 68.9, 55.7, 55.5.
126.4 (2×), 125.4, 123.7, 122.5, 113.1, 111.0, 110.2, 69.3, 55.8,
1-[5-Bromo-2-(3-phenylallyloxy)phenyl]-3-(3,4-dimethoxyphenyl) 55.6, 20.3.
propenone (5b). Yield = 84% (402 mg); colorless solid; mp =
3-(3,4-Dimethoxyphenyl)-1-[4-methoxy-2-(3-phenylallyloxy)
1
46–148 °C (recrystallized from hexanes and EtOAc); HRMS phenyl]propenone (5f). Yield = 84% (361 mg); colorless solid;
+
4
(ESI, M + 1) calcd for C26H24BrO 479.0858, found 479.0866, mp = 132–133 °C (recrystallized from hexanes and EtOAc);
1
+
err (ppm): −1.67; H NMR (400 MHz, CDCl ): δ 7.77 (d, J = 2.4 HRMS (ESI, M + 1) calcd for C H O 431.1859, found
3
27 27 5
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Paper
31.1851, err (ppm): 1.86; H NMR (400 MHz, CDCl
Organic & Biomolecular Chemistry
1
4
3
): δ 7.83 (2×), 127.83, 127.75 (2×), 126.5, 125.1, 123.6, 121.0, 114.2 (2×),
(
d, J = 8.8 Hz, 1H), 7.66 (d, J = 15.6 Hz, 1H), 7.57 (d, J = 15.6 112.9, 69.1, 55.2.
Hz, 1H), 7.26–7.20 (m, 5H), 7.13 (dd, J = 2.0, 8.4 Hz, 1H), 7.03 1-[2-(3-Phenylallyloxy)phenyl]-3-(2,3,4-trimethoxyphenyl)pro-
d, J = 1.6 Hz, 1H), 6.75 (d, J = 15.6 Hz, 1H), 6.58 (d, J = 8.8 Hz, penone (5k). Yield = 79% (340 mg); colorless solid; mp =
(
1
=
3
1
1
1
H), 6.57 (d, J = 8.4 Hz, 1H), 6.51 (d, J = 2.4 Hz, 1H), 6.40 (dt, J 89–91 °C (recrystallized from hexanes and EtOAc); HRMS (ESI,
+
5.2, 15.6 Hz, 1H), 4.73 (dd, J = 1.2, 5.6 Hz, 2H), 3.84 (s, 3H),
M
+ 1) calcd for C27
H
27
O
5
431.1859, found 431.1864, err
1
3
1
.80 (s, 3H), 3.68 (s, 3H); C NMR (100 MHz, CDCl
3
): δ 189.9, (ppm): −1.16; H NMR (400 MHz, CDCl ): δ 7.94 (d, J = 16.0
3
64.0, 159.3, 150.6, 148.9, 141.7, 136.0, 133.1, 133.0, 128.4 (2×), Hz, 1H), 7.73 (dd, J = 1.6, 7.6 Hz, 1H), 7.54 (d, J = 16.0 Hz, 1H),
28.2, 127.9, 126.4 (2×), 125.5, 123.2, 122.4, 122.0, 111.0, 110.4, 7.44 (dt, J = 1.6, 7.6 Hz, 1H), 7.29 (d, J = 8.8 Hz, 1H), 7.26–7.20
05.6, 99.5, 69.1, 55.8, 55.5, 55.4.
(m, 5H), 7.04 (dt, J = 0.8, 7.6 Hz, 1H), 7.01 (d, J = 8.4 Hz, 1H),
3-Benzo[1,3]dioxol-5-yl-1-[2-(3-phenylallyloxy)phenyl]propenone 6.73 (d, J = 16.0 Hz, 1H), 6.40 (dt, J = 5.2, 15.6 Hz, 1H), 6.33 (d,
(
5g). Yield = 87% (334 mg); colorless solid; mp = 99–101 °C J = 8.8 Hz, 1H), 4.75 (dd, J = 1.2, 5.6 Hz, 2H), 3.87 (s, 3H), 3.82
+
13
3
(recrystallized from hexanes and EtOAc); HRMS (ESI, M + 1) (s, 3H), 3.77 (s, 3H); C NMR (100 MHz, CDCl ): δ 192.3,
calcd for C H O 385.1440, found 385.1432, err (ppm): 2.08; 157.2, 155.3, 153.5, 142.1, 137.5, 136.1, 132.9, 132.8, 130.6,
2
5
21 4
1
H NMR (400 MHz, CDCl
3
): δ 7.72 (dd, J = 2.0, 7.6 Hz, 1H), 129.6, 128.4 (2×), 127.7, 126.4 (2×), 126.2, 123.6, 122.9, 122.0,
.61 (d, J = 15.6 Hz, 1H), 7.44 (dt, J = 2.0, 8.0 Hz, 1H), 7.39 (d, J 120.9, 112.8, 107.5, 69.0, 61.4, 60.7, 55.8.
15.6 Hz, 1H), 7.26–7.18 (m, 5H), 7.06–6.98 (m, 4H), 6.69 (d, J 3-(2-Hydroxyphenyl)-1-[2-(3-phenylallyloxy)phenyl]propenone
16.0 Hz, 1H), 6.67 (d, J = 7.6 Hz, 1H), 6.34 (dt, J = 5.6, 16.4 (5l). Yield = 74% (263 mg); colorless solid; mp = 150–152 °C
7
=
=
13
+
Hz, 1H), 6.85 (s, 2H), 4.71 (dd, J = 1.2, 5.2 Hz, 2H); C NMR (recrystallized from hexanes and EtOAc); HRMS (ESI, M + 1)
(
100 MHz, CDCl ): δ 191.9, 157.1, 149.3, 148.1, 142.2, 136.0, calcd for C H O 357.1491, found 357.1498, err (ppm):
3 24 21 3
1
1
32.8, 132.6, 130.5, 129.4, 129.3, 128.2 (2×), 127.6, 126.3 (2×), −1.96; H NMR (400 MHz, CDCl
25.3, 124.6, 123.3, 120.9, 112.8, 108.3, 106.5, 104.2, 68.8. 7.71 (dd, J = 1.6, 8.0 Hz, 1H), 7.68 (d, J = 16.0 Hz, 1H),
-[2-(3-Phenylallyloxy)phenyl]-3-(3,4,5-trimethoxyphenyl)pro- 7.51–7.45 (m, 2H), 7.31–7.20 (m, 5H), 7.18 (dt, J = 1.6, 8.4 Hz,
penone (5h). Yield = 80% (344 mg); colorless solid; mp = 1H), 7.08–7.01 (m, 2H), 6.83 (d, J = 8.0 Hz, 1H), 6.74 (d, J = 16.0
3
): δ 8.02 (d, J = 16.0 Hz, 1H),
1
1
9
M
2–94 °C (recrystallized from hexanes and EtOAc); HRMS (ESI, Hz, 1H), 6.73 (d, J = 8.4 Hz, 1H), 6.46 (br s, 1H), 6.40 (dt, J =
+
13
+ 1) calcd for C H O 431.1859, found 431.1863, err 1.6, 16.0 Hz, 1H), 4.80 (dd, J = 1.6, 5.6 Hz, 2H); C NMR
27 27 5
1
(
ppm): −0.93; H NMR (400 MHz, CDCl
3
): δ 7.68 (dd, J = 2.0, (100 MHz, CDCl
.6 Hz, 1H), 7.59 (d, J = 15.6 Hz, 1H), 7.47 (dt, J = 2.0, 8.0 Hz, 133.1, 133.0, 131.4, 130.8, 129.6, 129.2, 128.6 (2×), 127.9, 126.5
H), 7.42 (d, J = 15.6 Hz, 1H), 7.26–7.18 (m, 5H), 7.09–7.04 (m, (2×), 123.7, 122.4, 121.1, 120.9, 116.5, 113.1, 69.3.
H), 6.80 (s, 2H), 6.73 (d, J = 16.4 Hz, 1H), 6.37 (dt, J = 5.6, 16.4 3-(2,4-Dimethoxyphenyl)-1-[2-(3-phenylallyloxy)phenyl]prope-
3
): δ 194.0, 157.4, 155.4, 138.6 (2×), 136.2,
7
1
2
+
Hz, 1H), 4.80 (dd, J = 1.6, 5.6 Hz, 2H), 3.85 (s, 3H), 3.74 (s, 6H); none (5m). Yield = 82% (328 mg); colorless oil; HRMS (ESI, M +
1
3
C NMR (100 MHz, CDCl ): δ 192.5, 157.1, 153.3 (2×), 143.0, 1) calcd for C H O 401.1753, found 401.1760, err (ppm):
3
26 25 4
1
1
1
5
40.1, 136.0, 132.9, 132.5, 130.6, 130.5, 129.7, 128.5 (2×), 127.9, −1.74; H NMR (400 MHz, CDCl
26.6, 126.3 (2×), 123.5, 121.1, 112.9, 105.5 (2×), 69.0, 60.9, 7.71 (dd, J = 2.0, 7.6 Hz, 1H), 7.53 (d, J = 16.0 Hz, 1H), 7.49 (d, J =
5.9 (2×). 8.4 Hz, 1H), 7.44 (dt, J = 2.0, 7.6 Hz, 1H), 7.26–7.22 (m, 5H), 7.05
-(3-Methoxyphenyl)-1-[2-(3-phenylallyloxy)phenyl]propenone (dt, J = 0.8, 7.6 Hz, 1H), 7.01 (d, J = 8.4 Hz, 1H), 6.74 (dt, J = 1.2,
3
): δ 8.00 (d, J = 16.0 Hz, 1H),
3
+
(5i). Yield = 84% (311 mg); colorless oil; HRMS (ESI, M + 1) 16.0 Hz, 1H), 6.42–6.36 (m, 2H), 6.26 (dd, J = 2.0, 8.4 Hz, 1H),
13
calcd for C H O 371.1647, found 371.1654, err (ppm): 4.76 (dd, J = 1.2, 5.6 Hz, 2H), 3.77 (s, 3H), 3.76 (s, 3H); C NMR
2
5
23 3
1
−
1.89; H NMR (400 MHz, CDCl
H), 7.69 (d, J = 15.6 Hz, 1H), 7.57 (d, J = 15.6 Hz, 1H), 7.48 (dt, 132.6, 132.5, 130.5, 130.1, 130.0, 128.4 (2×), 127.7, 126.4 (2×),
J = 2.0, 8.0 Hz, 1H), 7.28–7.02 (m, 10H), 6.89 (dt, J = 2.0, 8.4 125.3, 123.7, 120.9, 117.1, 112.9, 105.1, 98.3, 69.0, 55.29, 55.27.
Hz, 1H), 6.73 (d, J = 16.0 Hz, 1H), 6.38 (dt, J = 5.6, 16.4 Hz, 3-(4-Nitrophenyl)-1-[2-(3-phenylallyloxy)phenyl]propenone (5n).
H), 4.76 (dd, J = 1.6, 5.6 Hz, 2H), 3.70 (s, 3H); C NMR Yield = 78% (300 mg); colorless solid; mp = 173–175 °C (recrys-
3 3
): δ 7.75 (dd, J = 1.6, 7.6 Hz, (100 MHz, CDCl ): δ 192.9, 162.7, 160.0, 157.1, 138.3, 136.2,
1
1
3
1
+
(100 MHz, CDCl ): δ 197.1, 159.7, 157.2, 142.4, 136.3, 136.0, tallized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd
3
1
1
(
33.0, 132.8, 130.6, 129.7, 129.2, 128.3 (2×), 127.7, 127.4, 126.3 for C24
2×), 123.3, 120.9, 120.7, 115.9, 113.2, 112.8, 68.9, 54.9. NMR (400 MHz, CDCl
-(4-Methoxyphenyl)-1-[2-(3-phenylallyloxy)phenyl]propenone 2.0, 8.0 Hz, 1H), 7.73 (d, J = 16.0 Hz, 1H), 7.65 (d, J = 16.0 Hz,
H
20NO
4
386.1392, found 386.1399, err (ppm): −1.81; H
3
): δ 7.92 (d, J = 8.8 Hz, 2H), 7.81 (dd, J =
3
(
5j). Yield = 85% (315 mg); colorless solid; mp = 115–117 °C 1H), 7.61 (d, J = 8.8 Hz, 2H), 7.53 (dt, J = 1.6, 8.0 Hz, 1H),
+
(recrystallized from hexanes and EtOAc); HRMS (ESI, M + 1) 7.30–7.25 (m, 5H), 7.10 (dt, J = 1.2, 8.4 Hz, 1H), 7.06 (d, J = 8.0
calcd for C H O 371.1647, found 371.1642, err (ppm): 1.35; Hz, 1H), 6.76 (dt, J = 1.2, 16.0 Hz, 1H), 6.43 (dt, J = 5.6, 16.0
2
5
23 3
1
13
H NMR (400 MHz, CDCl
3
): δ 7.73 (dd, J = 2.0, 7.6 Hz, 1H), Hz, 1H), 4.81 (dd, J = 1.6, 6.0 Hz, 2H); C NMR (100 MHz,
.66 (d, J = 16.0 Hz, 1H), 7.52–7.44 (m, 4H), 7.29–7.22 (m, 5H), CDCl ): δ 191.0, 157.9, 148.1, 141.4, 138.5, 135.8, 134.2, 134.0,
.07 (dt, J = 0.8, 7.6 Hz, 1H), 7.03 (d, J = 8.4 Hz, 1H), 6.77–6.72 131.2, 131.1, 128.7 (2×), 128.6 (2×), 128.5 (2×), 126.4 (2×), 124.0
7
7
3
(
2
m, 3H), 6.41 (dt, J = 5.6, 16.0 Hz, 1H), 4.78 (dd, J = 1.6, 5.6 Hz, (2×), 123.1, 121.3, 112.9, 69.3.
1
3
H), 3.76 (s, 3H); C NMR (100 MHz, CDCl
3
): δ 192.2, 161.3,
3-Biphenyl-4-yl-1-[2-(3-phenylallyloxy)phenyl]propenone (5o).
1
57.3, 142.6, 136.1, 133.1, 132.8, 130.7, 130.0 (2×), 129.6, 128.5 Yield = 80% (333 mg); colorless solid; mp = 138–140 °C (recrys-
2260 | Org. Biomol. Chem., 2021, 19, 2254–2268
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tallized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd 5.6 Hz, 2H); C NMR (100 MHz, CDCl
Paper
+
13
3
): δ 191.6, 157.3, 140.6,
1
for C H O 417.1855, found 417.1850, err (ppm): 1.19;
H
136.2, 135.0, 133.1, 133.0, 131.3, 130.7, 129.2, 128.4 (2×), 128.3,
): δ 7.80 (dd, J = 2.0, 7.6 Hz, 1H), 7.76 128.1, 127.8, 126.5 (2×), 126.3, 123.5, 121.0, 112.9, 69.1.
d, J = 15.6 Hz, 1H), 7.66 (d, J = 16.0 Hz, 1H), 7.64–7.46 (m, 3-(2-Fluorophenyl)-1-[2-(3-phenylallyloxy)phenyl]propenone (5t).
H), 7.41–7.37 (m, 1H), 7.28–7.22 (m, 5H), 7.10 (dt, J = 1.2, 8.4 Yield = 72% (258 mg); colorless solid; mp = 73–74 °C (recrystal-
3
0
25 2
NMR (400 MHz, CDCl
3
(
9
+
Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 6.78 (dt, J = 1.2, 16.0 Hz, 1H), lized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd for
1
3
1
6
.44 (dt, J = 5.6, 16.0 Hz, 1H), 4.80 (dd, J = 1.6, 5.6 Hz, 2H);
C
C
24
H
20FO
2
359.1447, found 359.1456, err (ppm): −2.51; H
NMR (100 MHz, CDCl ): δ 192.0, 157.5, 142.7, 142.0, 140.1, NMR (400 MHz, CDCl ): δ 7.90 (d, J = 16.0 Hz, 1H), 7.80 (dd, J
3
3
1
(
1
36.1, 134.1, 133.3, 133.2, 130.8, 129.3, 128.81 (3×), 128.77 = 1.6, 7.6 Hz, 1H), 7.72 (d, J = 16.0 Hz, 1H), 7.55 (dt, J = 1.6, 7.6
2×), 128.5 (2×), 127.9, 127.7, 127.4 (2×), 127.2, 126.9 (2×), Hz, 1H), 7.47 (dt, J = 2.0, 7.6 Hz, 1H), 7.28–7.22 (m, 6H), 7.07
26.5 (2×), 123.5, 121.1, 69.1. (dt, J = 0.8, 7.6 Hz, 1H), 7.05–7.02 (m, 1H), 7.01 (d, J = 8.4 Hz,
-(3,4-Dichlorophenyl)-1-[2-(3-phenylallyloxy)phenyl]propenone 1H), 6.91 (dt, J = 1.2, 7.6 Hz, 1H), 6.73 (dt, J = 1.2, 16.0 Hz, 1H),
3
1
3
(5p). Yield = 80% (326 mg); colorless solid; mp = 244–246 °C 6.39 (dt, J = 5.6, 16.0 Hz, 1H), 4.73 (dd, J = 1.2, 5.6 Hz, 2H);
C
+
(recrystallized from hexanes and EtOAc); HRMS (ESI, M + 1) NMR (100 MHz, CDCl ): δ 191.6, 161.3 (d, J = 252.5 Hz), 157.4,
3
calcd for C24
H
19Cl
2
O
2
409.0762, found 409.0768, err (ppm): 135.9, 134.4 (d, J = 3.0 Hz), 133.2, 133.0, 131.2 (d, J = 8.3 Hz),
1
−1.47; H NMR (400 MHz, CDCl ): δ 7.74 (dd, J = 2.0, 7.6 Hz, 130.6, 129.2 (d, J = 6.1 Hz), 128.79 (d, J = 2.3 Hz), 128.75, 128.3
3
1
H), 7.60 (d, J = 2.0 Hz, 1H), 7.51 (s, 1H), 7.52–7.48 (m, 2H), (2×), 127.7, 126.3 (2×), 124.2 (d, J = 3.0 Hz), 123.2, 122.9 (d, J =
7
.34 (dd, J = 1.6, 8.4 Hz, 1H), 7.33–7.23 (m, 5H), 7.21 (d, J = 8.4 11.4 Hz), 120.8, 115.8 (d, J = 22.0 Hz), 112.7, 68.9.
Hz, 1H), 7.08 (dt, J = 0.8, 7.6 Hz, 1H), 7.05 (d, J = 8.0 Hz, 1H),
1-[2-(3-Phenylallyloxy)phenyl]-3-pyridin-3-ylpropenone (5u).
6
.7 (d, J = 16.0 Hz, 1H), 6.39 (dt, J = 5.6, 16.0 Hz, 1H), 4.80 (dd, Yield = 73% (249 mg); colorless solid; mp = 106–108 °C (recrys-
1
3
+
J = 1.6, 5.6 Hz, 2H); C NMR (100 MHz, CDCl
3
): δ 191.6, 157.6, tallized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd
1
1
1
1
39.3, 135.9, 135.3, 133.8, 133.59, 133.56, 133.1, 130.9, 130.8, for C23
H
20NO
2
342.1494, found 342.1501, err (ppm): −2.04; H
29.9, 129.0, 128.9, 128.6 (2×), 128.1, 126.9, 126.5 (2×), 123.2, NMR (400 MHz, CDCl ): δ 8.73 (d, J = 2.0 Hz, 1H), 8.48 (d, J =
3
21.2, 113.0, 69.2.
1.6, 4.8 Hz, 1H), 7.79 (dt, J = 2.0, 8.0 Hz, 1H), 7.74 (dd, J = 2.0,
3-Naphthalen-2-yl-1-[2-(3-phenylallyloxy)phenyl]propenone (5q). 7.6 Hz, 1H), 7.62 (d, J = 0.8 Hz, 2H), 7.47 (dt, J = 2.0, 8.4 Hz,
Yield = 84% (328 mg); colorless solid; mp = 129–131 °C (recrys- 1H), 7.26–7.23 (m, 5H), 7.07–6.98 (m, 3H), 6.71 (d, J = 16.0 Hz,
+
tallized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd 1H), 6.37 (dt, J = 1.6, 16.0 Hz, 1H), 4.76 (dd, J = 1.2, 5.2 Hz,
1
13
for C28
H
23
O
2
391.1698, found 391.1706, err (ppm): −2.04; H 2H); C NMR (100 MHz, CDCl
3
): δ 191.3, 157.5, 150.6, 150.1,
NMR (400 MHz, CDCl ): δ 7.96 (s, 1H), 7.87 (d, J = 7.6 Hz, 1H), 138.1, 135.8, 133.7, 133.5, 133.3, 130.8, 130.7, 129.0, 128.8,
3
7
7
1
.79–7.67 (m, 5H), 7.60 (d, J = 8.4 Hz, 1H), 7.52–7.44 (m, 3H), 128.5 (2×), 127.9, 126.3 (2×), 123.5, 123.2, 121.1, 112.9, 69.1.
.21–7.05 (m, 7H), 6.75 (d, J = 16.0 Hz, 1H), 6.41 (dt, J = 5.6, 3-(3,4-Dimethoxyphenyl)-1-[2-(2-phenylallyloxy)phenyl]pro-
6.0 Hz, 1H), 4.81 (dd, J = 1.6, 5.6 Hz, 2H); C NMR (100 MHz, penone (5v). Yield = 84% (336 mg); colorless oil; HRMS (ESI,
1
3
+
CDCl
3
): δ 192.3, 157.4, 142.7, 136.1, 134.2, 133.3, 133.2, 133.1,
32.7, 130.8, 130.3, 129.4, 128.7, 128.5, 128.4 (2×), 127.9, 127.7, (ppm): −1.25; H NMR (400 MHz, CDCl
27.5, 127.0, 126.53, 126.47 (2×), 123.7, 123.5, 121.1, 113.0, Hz, 1H), 6.54 (d, J = 16.0 Hz, 1H), 7.44–7.36 (m, 3H), 7.27 (d, J
M
+ 1) calcd for C26
H
25
O
4
401.1753, found 401.1758, err
1
1
1
6
3
): δ 7.64 (d, J = 1.6, 7.6
9.2.
-Furan-2-yl-1-[2-(3-phenylallyloxy)phenyl]propenone
= 15.6 Hz, 1H), 7.26–7.21 (m, 3H), 7.04–6.99 (m, 4H), 6.78 (d, J
3
(5r). = 8.8 Hz, 1H), 5.51 (s, 1H), 5.47 (d, J = 1.2 Hz, 1H), 4.92 (s, 2H),
13
Yield = 78% (257 mg); colorless solid; mp = 84–86 °C (recrystal- 3.85 (s, 3H), 3.79 (s, 3H); C NMR (100 MHz, CDCl ): δ 192.2,
lized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd for 156.7, 150.8, 148.8, 142.9, 142.3, 137.8, 132.5, 130.2, 129.6,
C
3
+
1
22
H
19
O
3
331.1334, found 331.1342, err (ppm): −2.42;
H
128.2 (2×), 127.8, 127.7, 125.6 (2×), 124.8, 122.7, 120.9, 114.4,
NMR (400 MHz, CDCl ): δ 7.75 (dd, J = 2.0, 7.6 Hz, 1H), 7.51 112.8, 110.8, 109.9, 70.0, 55.6, 55.5.
3
(
6
d, J = 1.2 Hz, 2H), 7.45 (dt, J = 1.6, 8.4 Hz, 1H), 7.30–7.22 (m,
H), 7.05 (dt, J = 0.8, 8.4 Hz, 1H), 7.01 (d, J = 8.0 Hz, 1H), 6.77 Yield = 82% (316 mg); colorless oil; HRMS (ESI, M + 1) calcd
3-(4-Nitrophenyl)-1-[2-(2-phenylallyloxy)phenyl]propenone (5w).
+
1
(dt, J = 1.6, 16.0 Hz, 1H), 6.64 (dd, J = 2.8, 3.6 Hz, 1H), for C H NO 386.1392, found 386.1388, err (ppm): 1.04; H
24 20 4
1
3
6
.43–6.37 (m, 2H), 4.76 (d, J = 5.2 Hz, 2H); C NMR (100 MHz, NMR (400 MHz, CDCl
): δ 191.6, 157.3, 151.5, 144.5, 136.2, 132.9, 132.5, 130.5, 2.0, 8.0 Hz, 1H), 7.58–7.39 (m, 7H), 7.33–7.28 (m, 3H), 7.12 (d,
29.2, 128.7, 128.3 (2×), 127.6, 126.3 (2×), 124.7, 123.5, 120.9, J = 7.6 Hz, 1H), 7.09 (dt, J = 1.2, 8.0 Hz, 1H), 5.64 (s, 1H), 5.47
3
): δ 8.12 (d, J = 8.8 Hz, 2H), 7.76 (dd, J =
CDCl
1
1
3
1
3
15.4, 112.9, 112.3, 68.9.
(d, J = 0.8 Hz, 1H), 5.02 (d, J = 0.4 Hz, 2H); C NMR (100 MHz,
): δ 191.1, 157.6, 148.1, 142.2, 141.4, 138.8, 138.0, 137.5,
1
-[2-(3-Phenylallyloxy)phenyl]-3-thiophen-2-ylpropenone (5s). CDCl
3
Yield = 73% (253 mg); colorless solid; mp = 125–127 °C (recrys- 133.9, 131.2, 130.5, 128.7 (2×), 128.6 (2×), 128.3, 125.7 (2×),
+
tallized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd 123.9 (2×), 121.4, 115.9, 112.8, 70.6.
1
for C22
H
19
O
2
S 347.1106, found 347.1110, err (ppm): −1.15; H
3-Naphthalen-1-yl-1-[2-(2-phenylallyloxy)phenyl]propenone (5x).
NMR (400 MHz, CDCl ): δ 7.83 (d, J = 15.6 Hz, 1H), 7.74 (dd, J Yield = 84% (328 mg); colorless solid; mp = 123–125 °C (recrys-
3
+
=
2.0, 8.0 Hz, 1H), 7.48 (dt, J = 2.0, 8.4 Hz, 1H), 7.41 (d, J = 15.6 tallized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd
Hz, 1H), 7.29–7.24 (m, 7H), 7.09–6.99 (m, 3H), 6.75 (dt, J = 1.6, for C28
1
H
23
O
2
391.1698, found 391.1694, err (ppm): 1.02;
H
1
6.0 Hz, 1H), 6.42 (dd, J = 5.6, 16.0 Hz, 1H), 4.79 (dd, J = 1.6, NMR (400 MHz, CDCl ): δ 8.53 (d, J = 15.6 Hz, 1H), 8.23 (dd, J
3
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+
=
1
25 4
1.6, 7.6 Hz, 1H), 7.90–7.88 (m, 2H), 7.82 (dd, J = 1.6, 7.6 Hz, (ESI, M + 1) calcd for C22H O 353.1753, found 353.1761, err
1
H), 7.62 (d, J = 7.6 Hz, 1H), 7.59–7.49 (m, 4H), 7.44–7.41 (m, (ppm): −2.27; H NMR (400 MHz, CDCl ): δ 7.64 (dd, J = 1.6,
3
3
H), 7.27–7.21 (m, 3H), 7.13 (t, J = 7.6 Hz, 1H), 7.11 (d, J = 8.4 7.6 Hz, 1H), 7.55 (d, J = 15.6 Hz, 1H), 7.42 (dt, J = 1.6, 7.6 Hz,
1
3
Hz, 1H), 5.58 (s, 1H), 5.51 (d, J = 0.8 Hz, 1H), 5.02 (s, 2H);
C
1H), 7.34 (d, J = 16.0 Hz, 1H), 7.14 (ddd, J = 0.4, 2.0, 8.4 Hz,
NMR (100 MHz, CDCl ): δ 192.1, 157.2, 142.3, 139.2, 137.7, 1H), 7.09 (d, J = 2.0 Hz, 1H), 7.02 (dt, J = 1.2, 7.6 Hz, 1H), 6.98
3
1
1
1
33.5, 133.0, 132.2, 131.6, 130.7, 130.2, 129.6, 129.2, 128.5, (dd, J = 0.8, 8.4 Hz, 1H), 6.85 (d, J = 8.4 Hz, 1H), 5.48–5.44 (m,
28.3 (2×), 127.9, 126.6, 126.0, 125.7 (2×), 125.3, 124.9, 123.4, 1H), 4.59 (d, J = 6.4 Hz, 2H), 3.898 (s, 3H), 3.896 (s, 3H), 1.71
1
3
21.1, 115.2, 112.8, 70.4.
(d, J = 0.8 Hz, 3H), 1.69 (d, J = 0.8 Hz, 3H); C NMR (100 MHz,
): δ 192.6, 157.4, 151.0, 149.0, 142.9, 138.0, 132.6, 130.4,
1
-[2-(2-Phenylallyloxy)phenyl]-3-thiophen-2-ylpropenone (5y). CDCl
3
+
Yield = 80% (277 mg); colorless oil; HRMS (ESI, M + 1) calcd 129.7, 128.2, 125.3, 122.7, 120.7, 119.3, 113.1, 111.0, 110.1,
for C H O S 347.1106, found 347.1115, err (ppm): −2.59; H 65.6, 55.9, 55.8, 25.6, 18.2.
1
2
2
19 2
NMR (400 MHz, CDCl
3
): δ 7.76 (d, J = 15.2 Hz, 1H), 7.71 (dd, J
N-{2-[3-(3,4-Dimethoxyphenyl)acryloyl]phenyl}-N-(3-phenylallyl)
=
2.0, 8.0 Hz, 1H), 7.50–7.43 (m, 3H), 7.35–7.26 (m, 5H), 7.19 benzenesulfonamide (5ad). Yield = 83% (447 mg); colorless oil;
+
(
(
1
1
1
dd, J = 0.4, 3.2 Hz, 1H), 7.09–7.02 (m, 3H), 5.60 (s, 1H), 5.53 HRMS (ESI, M + 1) calcd for C H NO S 540.1845, found
32 30 5
1
3
1
d, J = 1.2 Hz, 1H), 4.99 (s, 2H); C NMR (100 MHz, CDCl
3
): δ 540.1854, err (ppm): −1.67; H NMR (400 MHz, CDCl
91.6, 157.0, 142.2, 140.3, 137.8, 135.1, 132.8, 131.1, 130.4, 7.78–7.75 (m, 2H), 7.60–7.58 (m, 1H), 7.52–7.36 (m, 6H),
29.3, 128.4, 128.3 (2×), 128.0, 127.9, 125.8, 125.7 (2×), 121.0, 7.27–7.11 (m, 8H), 7.03–7.00 (m, 1H), 6.82 (d, J = 8.4 Hz, 1H),
14.8, 112.9, 70.1. 6.33 (d, J = 16.0 Hz, 1H), 6.19 (dt, J = 7.2, 16.0 Hz, 1H), 4.41
-(2-But-2-enyloxyphenyl)-3-(3,4-dimethoxyphenyl)propenone (dd, J = 0.8, 6.4 Hz, 2H), 3.912 (s, 3H), 3.905 (s, 3H); C NMR
5z). Two isomers (E/Z = 5/1); yield = 75% (254 mg); colorless (100 MHz, CDCl ): δ 193.3, 151.4, 149.2, 145.4, 141.5, 139.5,
3
): δ
1
3
1
(
3
+
oil; HRMS (ESI, M + 1) calcd for C21
39.1603, err (ppm): −2.06; for major E-isomer: H NMR (2×), 128.3, 128.0 (2×), 127.8, 127.7, 126.5 (2×), 124.1, 123.7,
400 MHz, CDCl ): δ 7.62 (dd, J = 1.6, 7.6 Hz, 1H), 7.56 (d, J = 123.4, 111.0, 110.1, 55.93, 55.91, 55.2.
23 4
H O 339.1596, found 137.0, 136.2, 134.5, 132.8, 130.8, 130.2, 129.6, 128.9 (2×), 128.4
1
3
(
3
1
5.6 Hz, 1H), 7.41 (dt, J = 0.8, 7.6 Hz, 1H), 7.32 (d, J = 15.6 Hz,
4-[2-(3-Phenylallyloxy)phenyl]but-3-en-2-one (5ae). Sodium
1
H), 7.14 (dd, J = 2.8, 7.6 Hz, 1H), 7.09 (d, J = 2.0 Hz, 1H), 7.00 hydroxide (NaOH, 100 mg, 2.5 mmol) was added to a solution
(dt, J = 0.8, 7.6 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 6.85 (d, J = 8.0 of 4k (240 mg, 1.0 mmol) in a co-solvent of acetone (10 mL)
Hz, 1H), 5.85–5.78 (m, 1H), 5.70–5.63 (m, 1H), 4.53 (dt, J = 1.2, and MeOH (10 mL) at 25 °C. The reaction mixture was stirred
1
3
5
.6 Hz, 2H), 3.89 (s, 6H), 1.64 (dd, J = 1.6, 6.4 Hz, 3H);
C
at 25 °C for 20 h (monitored by TLC). The solvent was concen-
NMR (100 MHz, CDCl ): δ 192.5, 157.2, 151.0, 149.0, 142.9, trated under reduced pressure. The residue was diluted with
3
1
1
32.6, 130.3, 129.9, 128.1, 125.4, 125.3, 125.1, 122.8, 120.7, water (10 mL) and the mixture was extracted with EtOAc (3 ×
13.0, 111.0, 109.9, 69.1, 55.8, 55.7, 17.7. 20 mL). The combined organic layers were washed with brine,
-(2-But-2-enyloxyphenyl)-3-naphthalen-1-ylpropenone (5aa). dried, filtered and evaporated to afford crude product.
1
Two isomers (E/Z = 5/1); yield = 76% (249 mg); colorless solid; Purification on silica gel (hexanes/EtOAc = 20/1–6/1) afforded
mp = 77–79 °C (recrystallized from hexanes and EtOAc); HRMS compound 5ae. Yield = 84% (234 mg); colorless solid; mp =
+
(
(
8
4
7
ESI, M + 1) calcd for C H O 329.1542, found 329.1551, err 85–87 °C (recrystallized from hexanes and EtOAc); HRMS (ESI,
23
21 2
1
+
ppm): −2.73; for major E-isomer: H NMR (400 MHz, CDCl
.57 (d, J = 16.0 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 7.87–7.82 (m, (ppm): −2.15; H NMR (400 MHz, CDCl
H), 7.64 (d, J = 15.6 Hz, 1H), 7.56–7.43 (m, 4H), 7.07 (dt, J = 0.8, Hz, 1H), 7.58 (dd, J = 1.6, 7.6 Hz, 1H), 7.44–7.41 (m, 2H),
.6 Hz, 1H), 6.95 (d, J = 8.0 Hz, 1H), 5.87–5.79 (m, 1H), 5.75–5.65 7.38–7.33 (m, 3H), 7.30–7.26 (m, 1H), 7.01–6.97 (m, 2H), 6.79
3
): δ
M
+ 1) calcd for C19
H
19
O
2
279.1385, found 279.1391, err
): δ 7.98 (d, J = 16.4
1
3
(
m, 1H), 4.50 (dt, J = 1.2, 5.6 Hz, 2H), 1.64 (dd, J = 1.2, 6.4 Hz, (d, J = 16.4 Hz, 1H), 6.76 (d, J = 16.4 Hz, 1H), 6.44 (dt, J = 5.6,
13
13
3
1
1
H); C NMR (100 MHz, CDCl ): δ 191.8, 157.4, 138.5, 133.4, 16.0 Hz, 1H), 4.79 (dd, J = 1.2, 5.6 Hz, 2H), 2.40 (s, 3H);
C
3
3
33.0, 132.9, 132.2, 131.5, 130.5, 130.2, 130.11, 130.08, 129.5, NMR (100 MHz, CDCl ): δ 198.9, 157.2, 138.6, 136.1, 133.1,
28.4, 126.4, 125.8, 125.2, 124.7, 123.2, 120.6, 112.7, 68.9, 17.5.
131.7, 128.6 (2×), 128.2, 128.0, 127.7, 126.5 (2×), 123.8, 123.6,
1
-(2-But-2-enyloxyphenyl)-3-thiophen-2-ylpropenone (5ab). 121.0, 112.6, 69.0, 27.1.
Two isomers (E/Z = 4/1); yield = 79% (224 mg); colorless oil;
+
A representative synthetic procedure of skeleton 6 is as follows
17 2
HRMS (ESI, M + 1) calcd for C17H O S 285.0949, found
1
2
85.0940, err (ppm): 3.16; for major E-isomer: H NMR NBS (107 mg, 0.6 mmol) was added to a solution of 5
(
400 MHz, CDCl ): δ 7.77 (d, J = 15.6 Hz, 1H), 7.69–7.67 (m, (1.0 mmol) in CCl (10 mL) at 25 °C. Then, DABCO (70 mg,
3
4
1
6
4
H), 7.41–7.32 (m, 3H), 7.24–7.33 (m, 1H), 7.01–6.95 (m, 2H), 0.6 mmol) was added to the reaction mixture at 25 °C. The
.93 (d, J = 8.0 Hz, 1H), 5.88–5.79 (m, 1H), 5.70–5.66 (m, 1H), reaction mixture was stirred under an air atmosphere (open-
13
.50 (d, J = 5.6 Hz, 2H), 1.67 (dd, J = 1.2, 6.4 Hz, 3H); C NMR vessel condition) at reflux (77 °C) for 15 h. The reaction
): δ 191.3, 157.3, 140.5, 134.6, 132.9, 131.1, mixture was cooled to 25 °C and the solvent was concentrated.
30.40, 130.37, 130.2, 128.1, 127.9, 126.1, 125.2, 120.5, 112.7, The residue was diluted with 2 N HCl(aq) (10 mL) and the
9.0, 17.6. mixture was extracted with CH Cl (3 × 10 mL). The combined
-(3,4-Dimethoxyphenyl)-1-[2-(3-methylbut-2-enyloxy)phenyl] organic layers were washed with brine, dried, filtered, and
propenone (5ac). Yield = 80% (282 mg); colorless oil; HRMS evaporated to afford crude product under reduced pressure.
(100 MHz, CDCl
3
1
6
2
2
3
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1
Purification on silica gel (hexanes/EtOAc = 15/1–5/1) afforded
skeleton 6.
C
26
H
24FO
4
419.1659, found 419.1653, err (ppm): 1.43; H NMR
(400 MHz, CDCl ): δ 7.45 (dd, J = 3.2, 9.2 Hz, 1H), 7.17–7.05
3
2
-(3,4-Dimethoxyphenyl)-1-phenyl-2,2a,9,9a-tetrahydro-1H-8- (m, 5H), 7.05–6.98 (m, 2H), 6.63 (d, J = 8.4 Hz, 1H), 6.59 (dd, J
oxabenzo[a]cyclobuta[d]cyclohepten-3-one (6a). Yield = 90% = 1.6, 8.4 Hz, 1H), 6.29 (d, J = 2.0 Hz, 1H), 4.51–4.45 (m, 2H),
72 mg); colorless solid; mp = 125–127 °C (recrystallized from 4.30 (dd, J = 4.4, 12.4 Hz, 1H), 4.00 (ddd, J = 1.2, 6.4, 10.8 Hz,
(
+
hexanes and EtOAc); HRMS (ESI, M + 1) calcd for C26
4
H
25
O
4
1H), 3.94 (dd, J = 6.4, 10.0 Hz, 1H), 3.76 (s, 3H), 3.69–3.61 (m,
1
13
01.1753, found 401.1758, err (ppm): −1.25;
3
H NMR 1H), 3.57 (s, 3H); C NMR (100 MHz, CDCl ): δ 199.4, 157.5
(
400 MHz, CDCl ): δ 7.36 (dd, J = 1.6, 7.6 Hz, 1H), 7.43 (dt, J = (d, J = 240.3 Hz), 156.8 (d, J = 1.4 Hz), 148.3, 147.3, 139.2,
3
1
7
.6, 8.0 Hz, 1H), 7.17–7.13 (m, 2H), 7.10–7.05 (m, 3H), 131.5, 128.1 (2×), 127.8 (2×), 126.9 (d, J = 6.0 Hz), 126.4, 121.6
.01–6.98 (m, 2H), 6.63 (d, J = 8.0 Hz, 1H), 6.60 (dd, J = 1.6, 8.4 (d, J = 7.6 Hz), 120.8 (d, J = 24.3 Hz), 119.6, 116.1 (d, J = 24.3
Hz, 1H), 6.30 (d, J = 1.6 Hz, 1H), 4.53–4.51 (m, 1H), 4.49 (d, J = Hz), 111.7, 110.5, 75.2, 55.7, 55.5, 53.5, 45.1, 43.5, 43.0. Single-
.6 Hz, 1H), 4.32 (dd, J = 8.8, 12.4 Hz, 1H), 3.99 (dd, J = 1.2, 6.0 crystal X-Ray diagram: crystal of compound 6d was grown by
Hz, 1H), 3.94 (dd, J = 7.6, 10.0 Hz, 1H), 3.76 (s, 3H), 3.73–3.65 slow diffusion of EtOAc into a solution of compound 6d in
3
1
3
(
m, 1H), 3.58 (s, 3H); C NMR (100 MHz, CDCl ): δ 200.8, CH Cl to yield colorless prisms. The compound crystallizes in
3 2 2
1
60.4, 148.3, 147.2, 139.3, 133.5, 131.7, 130.9, 128.1 (2×), 127.8 the monoclinic crystal system, space group C2/c, a = 27.5645
3
(2×), 126.3, 126.2, 121.9, 119.8, 119.6, 111.7, 110.5, 74.8, 55.7, (11) Å, b = 7.0521(3) Å, c = 22.8442(10) Å, V = 4038.4(3) Å , Z =
5.5, 53.6, 45.0, 43.4, 43.1. Single-crystal X-Ray diagram: crystal 8, dcalcd = 1.376 g cm− , F(000) = 1760, 2θ range 1.625–26.487°,
of compound 6a was grown by slow diffusion of EtOAc into a R indices (all data) R1 = 0.0412, wR2 = 0.0881.
solution of compound 6a in CH Cl to yield colorless prisms. 2-(3,4-Dimethoxyphenyl)-5-methyl-1-phenyl-2,2a,9,9a-tetra-
The compound crystallizes in the monoclinic crystal system, hydro-1H-8-oxabenzo[a]cyclobuta[d]cyclohepten-3-one (6e).
3
5
2
2
space group P2
1
/c, a = 17.962(3) Å, b = 10.2398(15) Å, c = Yield = 94% (78 mg); colorless solid; mp = 108–110 °C (recrys-
3
−3
+
1
1.0654(16) Å, V = 2030.8(5) Å , Z = 4, dcalcd = 1.310 g cm
,
tallized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd
1
F(000) = 848, 2θ range 2.273–26.665°, R indices (all data) R1 = for C H O 415.1909, found 415.1916, err (ppm): −1.69; H
2
7
27 4
0
.0878, wR2 = 0.2262.
-Bromo-2-(3,4-dimethoxyphenyl)-1-phenyl-2,2a,9,9a-tetrahy- 2.4, 8.4 Hz, 1H), 7.18–7.04 (m, 3H), 7.01–6.98 (m, 3H), 6.63 (d,
dro-1H-8-oxabenzo[a]cyclobuta[d]cyclohepten-3-one (6b). Yield J = 8.4 Hz, 1H), 6.58 (dd, J = 2.0, 8.4 Hz, 1H), 6.30 (d, J = 1.6
94% (90 mg); colorless solid; mp = 145–147 °C (recrystallized Hz, 1H), 4.50 (dd, J = 6.4, 10.0 Hz, 1H), 4.45 (dd, J = 4.0, 12.4
3
NMR (400 MHz, CDCl ): δ 7.55 (d, J = 2.0 Hz, 1H), 7.24 (dd, J =
5
=
+
from hexanes and EtOAc); HRMS (ESI, M + 1) calcd for Hz, 1H), 4.30 (dd, J = 8.8, 12.4 Hz, 1H), 4.01–3.91 (m, 2H), 3.76
1
13
C H BrO 479.0858, found 479.0863, err (ppm): −1.04;
H
(s, 3H), 3.67–3.62 (m, 1H), 3.58 (s, 3H), 2.32 (s, 3H); C NMR
): δ 7.85 (d, J = 2.8 Hz, 1H), 7.50 (dd, J = (100 MHz, CDCl ): δ 200.9, 158.5, 148.3, 147.2, 139.5, 134.5,
.4, 8.8 Hz, 1H), 7.17–7.06 (m, 3H), 6.99–6.97 (m, 3H), 6.63 (d, 131.9, 131.4, 130.7, 128.1 (3×), 127.9 (2×), 126.3, 119.8, 119.6,
J = 8.4 Hz, 1H), 6.58 (dd, J = 2.0, 8.4 Hz, 1H), 6.28 (d, J = 1.6 111.7, 110.5, 74.8, 55.7, 55.6, 53.7, 45.1, 43.5, 43.2, 20.3.
Hz, 1H), 4.52–4.46 (m, 2H), 4.29 (dd, J = 8.8, 12.4 Hz, 1H), 2-(3,4-Dimethoxyphenyl)-6-methoxy-1-phenyl-2,2a,9,9a-tetra-
2
6
24
4
NMR (400 MHz, CDCl
3
3
2
3
.99–3.87 (m, 2H), 3.76 (s, 3H), 3.71–3.62 (m, 1H), 3.57 (s, 3H); hydro-1H-8-oxabenzo[a]cyclobuta[d]cyclohepten-3-one
(6f).
1
3
C NMR (100 MHz, CDCl ): δ 199.4, 159.5, 148.3, 147.3, 139.1, Yield = 90% (77 mg); colorless solid; mp = 136–138 °C (recrys-
3
+
1
1
4
36.2, 133.2, 131.4, 128.2 (2×), 127.8 (2×), 127.7, 126.5, 121.9, tallized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd
1
19.6, 114.4, 111.7, 110.6, 75.1, 55.7, 55.6, 53.6, 45.0, 43.4, for C27
2.9.
-Chloro-2-(3,4-dimethoxyphenyl)-1-phenyl-2,2a,9,9a-tetrahy- (m, 2H), 7.09–7.06 (m, 1H), 7.01–6.99 (m, 2H), 6.64 (d, J = 9.2
dro-1H-8-oxabenzo[a]cyclobuta[d]cyclohepten-3-one (6c). Yield Hz, 1H), 6.63 (d, J = 8.8 Hz, 1H), 6.61 (br s, 1H), 6.60–6.57 (m,
93% (81 mg); colorless solid; mp = 154–156 °C (recrystallized 1H), 6.29 (d, J = 1.6 Hz, 1H), 4.49–4.44 (m, 2H), 4.35 (dd, J =
H
27
O
5
431.1859, found 431.1865, err (ppm): −1.39; H
NMR (400 MHz, CDCl ): δ 7.78 (d, J = 8.8 Hz, 1H), 7.16–7.13
3
5
=
+
from hexanes and EtOAc); HRMS (ESI, M + 1) calcd for 8.0, 12.4 Hz, 1H), 3.99–3.91 (m, 2H), 3.84 (s, 3H), 3.75 (s, 3H),
C
1
13
26
H
24ClO
4
435.1363, found 435.1370, err (ppm): −1.61;
H
3
3.61–3.52 (m, 1H), 3.57 (s, 3H); C NMR (100 MHz, CDCl ): δ
NMR (400 MHz, CDCl ): δ 7.71 (d, J = 2.8 Hz, 1H), 7.37 (dd, J = 199.2, 164.0, 162.7, 148.2, 147.1, 139.5, 132.8, 131.9, 128.1 (2×),
3
2
6
.4, 8.8 Hz, 1H), 7.17–7.07 (m, 3H), 7.04 (d, J = 8.8 Hz, 1H), 127.9 (2×), 126.3, 119.59, 119.56, 111.6, 110.5, 109.7, 103.6,
.99–6.97 (m, 2H), 6.63 (d, J = 8.4 Hz, 1H), 6.58 (dd, J = 1.6, 8.0 75.1, 55.7, 55.5 (2×), 53.4, 45.2, 43.9, 42.7.
Hz, 1H), 6.28 (d, J = 2.0 Hz, 1H), 4.52–4.47 (m, 2H), 4.30 (dd, J
2-Benzo[1,3]dioxol-5-yl-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-
=
8.8, 12.4 Hz, 1H), 3.99–3.87 (m, 2H), 3.76 (s, 3H), 3.71–3.63 oxabenzo[a]cyclobuta[d]cyclohepten-3-one (6g). Yield = 90%
1
3
(m, 1H), 3.57 (s, 3H); C NMR (100 MHz, CDCl
3
): δ 199.5, (69 mg); colorless solid; mp = 133–135 °C (recrystallized from
+
1
59.0, 148.3, 147.3, 139.1, 133.3, 131.5, 130.1, 128.2 (2×), 127.8 hexanes and EtOAc); HRMS (ESI, M + 1) calcd for C H O
2
5
21
4
1
(3×), 127.2, 126.4, 121.6, 119.6, 111.7, 110.6, 75.1, 55.7, 55.6, 385.1440, found 385.1446, err (ppm): −1.56;
H
NMR
5
3.6, 45.0, 43.4, 42.9.
-(3,4-Dimethoxyphenyl)-5-fluoro-1-phenyl-2,2a,9,9a-tetrahy-
dro-1H-8-oxabenzo[a]cyclobuta[d]cyclohepten-3-one (6d). Yield 7.01–6.99 (m, 2H), 6.55 (d, J = 8.0 Hz, 1H), 6.47 (dd, J = 1.2, 8.0
98% (82 mg); colorless solid; mp = 146–148 °C (recrystallized Hz, 1H), 6.44 (d, J = 1.6 Hz, 1H), 5.80 (d, J = 1.6 Hz, 1H), 5.79
(400 MHz, CDCl
2.0, 8.4 Hz, 1H), 7.19–7.15 (m, 2H), 7.11–7.04 (m, 3H),
3
): δ 7.75 (dd, J = 1.6, 7.6 Hz, 1H), 7.43 (dt, J =
2
=
+
from hexanes and EtOAc); HRMS (ESI, M + 1) calcd for (d, J = 1.6 Hz, 1H), 4.52–4.48 (m, 2H), 4.30 (dd, J = 8.8, 12.0 Hz,
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3
1
H), 3.97–3.88 (m, 2H), 3.72–3.64 (m, 1H); C NMR (100 MHz, 152.2, 151.5, 141.6, 139.7, 133.4, 130.9, 127.8 (2×), 127.6 (2×),
CDCl ): δ 200.6, 160.4, 147.3, 145.7, 139.1, 133.5, 133.1, 130.9, 126.2, 126.0, 124.9, 121.7, 121.6, 119.8, 106.1, 74.7, 60.3, 60.2,
3
1
1
28.1 (2×), 127.8 (2×), 126.3, 126.2, 121.9, 121.0, 119.8, 108.4, 55.7, 52.2, 45.0, 43.4, 39.0.
07.7, 100.7, 74.8, 53.7, 45.0, 43.6, 43.1. 2-(2-Hydroxyphenyl)-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-oxa-
-Phenyl-2-(3,4,5-trimethoxyphenyl)-2,2a,9,9a-tetrahydro-1H- benzo[a]cyclobuta[d]cyclohepten-3-one (6l). Yield 89%
-oxabenzo[a]cyclobuta[d]cyclohepten-3-one (6h). Yield = 94% (63 mg); colorless solid; mp = 164–166 °C (recrystallized from
1
=
8
+
21 3
(81 mg); colorless solid; mp = 134–136 °C (recrystallized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd for C24H O
+
1
hexanes and EtOAc); HRMS (ESI, M + 1) calcd for C H O
357.1491, found 357.1498, err (ppm): −1.96;
H NMR
2
7
27
5
1
4
31.1859, found 431.1865, err (ppm): −1.39;
H
NMR (400 MHz, CDCl ): δ 9.35 (s, 1H), 8.13 (dd, J = 2.0, 8.4 Hz, 1H),
3
(
400 MHz, CDCl
3
): δ 7.77 (dd, J = 2.0, 8.0 Hz, 1H), 7.43 (dt, J = 7.60 (dt, J = 2.0, 8.0 Hz, 1H), 7.31–7.16 (m, 9H), 7.01 (dd, J =
1
7
8
1
1
.6, 8.0 Hz, 1H), 7.19–7.15 (m, 2H), 7.11–7.05 (m, 3H), 0.8, 8.0 Hz, 1H), 6.89 (dt, J = 0.8, 8.4 Hz, 1H), 4.40 (d, J = 8.8
.02–7.00 (m, 2H), 6.12 (s, 2H), 4.52–4.48 (m, 2H), 4.32 (dd, J = Hz, 2H), 3.98 (t, J = 9.6 Hz, 1H), 3.81 (t, J = 9.6 Hz, 1H), 3.42
1
3
.8, 12.4 Hz, 1H), 3.99–3.93 (m, 2H), 3.70 (s, 3H), 3.70–3.67 (m, (dd, J = 9.2, 11.2 Hz, 1H), 2.69 (dt, J = 8.8, 11.2 Hz, 1H);
C
1
3
H), 3.62 (s, 6H); C NMR (100 MHz, CDCl ): δ 200.6, 160.4, NMR (100 MHz, CDCl ): δ 202.8, 159.7, 155.1, 140.9, 136.5,
3
3
52.6 (2×), 139.2, 134.9, 133.6, 130.9 (2×), 128.1 (2×), 127.8 130.0, 128.74, 128.70 (2×), 128.6, 127.1, 126.6 (2×), 126.5,
(2×), 126.4, 126.1, 121.9, 119.9, 105.3 (2×), 74.7, 60.7, 55.9 (2×), 126.2, 125.0, 124.7, 119.9, 117.6, 73.6, 53.5, 45.7, 43.2, 40.3.
5
3.7, 44.9, 43.9, 42.9.
2-(2,4-Dimethoxyphenyl)-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-
2
-(3-Methoxyphenyl)-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-oxa- oxabenzo[a]cyclobuta[d]cyclohepten-3-one (6m). Yield = 88%
benzo[a]cyclobuta[d]cyclohepten-3-one (6i). Yield
=
90% (70 mg); colorless solid; mp = 150–152 °C (recrystallized from
+
(
67 mg); colorless solid; mp = 113–115 °C (recrystallized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd for C H O
2
6
25
4
+
1
hexanes and EtOAc); HRMS (ESI, M + 1) calcd for C25
H
23
O
3
401.1753, found 401.1761, err (ppm): −1.99;
NMR (400 MHz, CDCl
400 MHz, CDCl ): δ 7.76 (dd, J = 1.6, 8.0 Hz, 1H), 7.43 (dt, J = 1.6, 8.0 Hz, 1H), 7.11–7.07 (m, 4H), 7.05–6.98 (m, 4H), 6.31
H
NMR
1
3
71.1647, found 371.1652, err (ppm): −1.35;
H
3
): δ 7.76 (dd, J = 2.0, 8.0 Hz, 1H), 7.42 (dt, J =
(
3
1
=
1
6
1
1
1
5
.6, 8.4 Hz, 1H), 7.17–6.99 (m, 8H), 6.61–6.56 (m, 2H), 6.48 (t, J (dd, J = 2.4, 8.0 Hz, 1H), 6.08 (d, J = 2.4 Hz, 1H), 4.60 (dd, J =
2.0 Hz, 1H), 4.57 (dd, J = 6.0, 10.0 Hz, 1H), 4.51 (dd, J = 4.0, 7.6, 10.0 Hz, 1H), 4.42–4.40 (m, 2H), 4.19–4.14 (m, 1H), 3.91
2.4 Hz, 1H), 4.31 (dd, J = 9.2, 12.4 Hz, 1H), 4.03 (ddd, J = 0.8, (dd, J = 6.0, 10.0 Hz, 1H), 3.69 (s, 3H), 3.51–3.46 (m, 1H), 3.45
1
3
.0, 10.4 Hz, 1H), 3.96 (dd, J = 7.6, 10.4 Hz, 1H), 3.75–3.65 (m, (s, 3H); C NMR (100 MHz, CDCl
3
): δ 201.4, 160.4, 159.4,
1
3
H), 3.60 (s, 3H); C NMR (100 MHz, CDCl
3
): δ 200.7, 160.4, 157.8, 140.4, 133.5, 131.1, 127.8 (2×), 127.6, 127.5 (2×), 126.3,
59.2, 140.8, 139.2, 133.5, 130.9, 128.9, 128.0 (2×), 127.8 (2×), 126.0, 121.8, 120.02, 119.97, 103.1, 98.0, 74.7, 55.2, 54.6, 52.0,
26.31, 126.27, 121.9, 120.3, 119.8, 113.7, 111.8, 74.8, 55.0, 45.2, 43.8, 39.8.
3.3, 45.0, 43.7, 43.3.
2-(4-Nitrophenyl)-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-oxabenzo
2
-(4-Methoxyphenyl)-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-oxa- [a]cyclobuta[d]cyclohepten-3-one (6n). Yield = 86% (66 mg);
benzo[a]cyclobuta[d]cyclohepten-3-one (6j). Yield
=
90% colorless solid; mp = 176–178 °C (recrystallized from hexanes
+
(
67 mg); colorless solid; mp = 125–127 °C (recrystallized from and EtOAc); HRMS (ESI, M + 1) calcd for C24
H
20NO
4
386.1392,
+
1
hexanes and EtOAc); HRMS (ESI, M + 1) calcd for C H O
found 386.1396, err (ppm): −1.03; H NMR (400 MHz, CDCl ):
2
5
23
3
3
1
3
71.1647, found 371.1653, err (ppm): −1.61;
H
NMR δ 7.94 (d, J = 8.8 Hz, 2H), 7.77 (dd, J = 2.0, 8.0 Hz, 1H), 7.45 (dt,
(
1
400 MHz, CDCl
3
): δ 7.75 (dd, J = 1.6, 8.0 Hz, 1H), 7.43 (dt, J = J = 1.6, 8.0 Hz, 1H), 7.17–7.06 (m, 7H), 6.98–6.96 (m, 2H), 4.67
.6, 8.4 Hz, 1H), 7.16–7.04 (m, 5H), 6.99–6.97 (m, 2H), 6.89 (d, (dd, J = 6.4, 10.0 Hz, 1H), 4.52 (dd, J = 4.0, 12.4 Hz, 1H), 4.34
J = 8.8 Hz, 2H), 6.63 (d, J = 8.8 Hz, 2H), 4.53 (dd, J = 7.6, 11.6 (dd, J = 9.2, 12.4 Hz, 1H), 4.08 (ddd, J = 1.2, 6.4, 10.4 Hz, 1H),
13
Hz, 1H), 4.51 (dd, J = 4.0, 7.6 Hz, 1H), 4.30 (dd, J = 9.2, 12.4 4.02 (dd, J = 6.8, 10.4 Hz, 1H), 3.75–3.68 (m, 1H); C NMR
Hz, 1H), 3.97 (ddd, J = 0.8, 6.0, 10.8 Hz, 1H), 3.92 (dd, J = 8.0, (100 MHz, CDCl ): δ 200.0, 160.5, 147.2, 146.2, 138.3, 133.9,
3
13
1
0.4 Hz, 1H), 3.75–3.68 (m, 1H), 3.68 (s, 3H); C NMR 130.9, 128.7 (2×), 128.4 (2×), 127.7 (2×), 126.9 (2×), 125.8,
(
100 MHz, CDCl ): δ 200.8, 160.4, 157.8, 139.3, 133.5, 131.3, 123.1, 122.1, 120.0, 74.6, 52.9, 45.1, 43.8, 43.0.
3
1
1
30.9, 128.9 (2×), 128.0 (2×), 127.8 (2×), 126.3, 126.2, 121.9,
19.8, 113.4 (2×), 74.9, 55.1, 53.7, 45.0, 43.2, 43.1.
2-Biphenyl-4-yl-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-oxabenzo
[a]cyclobuta[d]cyclohepten-3-one (6o). Yield = 89% (74 mg);
1
-Phenyl-2-(2,3,4-trimethoxyphenyl)-2,2a,9,9a-tetrahydro-1H- colorless solid; mp = 195–197 °C (recrystallized from hexanes
+
8
(
-oxabenzo[a]cyclobuta[d]cyclohepten-3-one (6k). Yield = 90% and EtOAc); HRMS (ESI, M + 1) calcd for C H O 417.1855,
30 25 2
1
77 mg); colorless solid; mp = 149–151 °C (recrystallized from found 417.1859, err (ppm): −0.96; H NMR (400 MHz, CDCl
3
):
δ 7.78 (dd, J = 2.0, 8.0 Hz, 1H), 7.50–7.26 (m, 8H), 7.17–7.01
NMR (m, 9H), 4.64 (dd, J = 6.0, 10.0 Hz, 1H), 4.54 (dd, J = 4.0, 12.4
): δ 7.75 (dd, J = 1.6, 8.0 Hz, 1H), 7.42 (dt, J = Hz, 1H), 4.34 (dd, J = 9.2, 12.4 Hz, 1H), 4.07 (ddd, J = 0.8, 6.0,
.6, 8.4 Hz, 1H), 7.12–7.00 (m, 7H), 6.78 (d, J = 8.4 Hz, 1H), 10.4 Hz, 1H), 4.00 (dd, J = 7.6, 10.0 Hz, 1H), 3.79–3.73 (m, 1H);
+
27 5
hexanes and EtOAc); HRMS (ESI, M + 1) calcd for C27H O
1
4
(
1
6
31.1859, found 431.1866, err (ppm): −1.62;
H
400 MHz, CDCl
3
1
3
.46 (d, J = 8.8 Hz, 1H), 4.73 (dd, J = 6.8, 10.0 Hz, 1H), 4.47 (dd,
C NMR (100 MHz, CDCl ): δ 200.7, 160.4, 140.7, 139.2, 138.7,
3
J = 3.6, 12.4 Hz, 1H), 4.35 (dd, J = 8.8, 12.4 Hz, 1H), 4.04 (ddd, J 138.3, 133.5, 130.9, 128.6 (2×), 128.4 (2×), 128.1 (2×), 127.8
=
3
0.8, 6.8, 10.0 Hz, 1H), 3.92–3.85 (m, 2H), 3.74 (s, 3H), 3.64 (s, (2×), 127.0, 126.8 (2×), 126.5 (2×), 126.33, 126.25, 121.9, 119.8,
1
3
H), 3.58 (s, 3H); C NMR (100 MHz, CDCl ): δ 200.9, 160.3, 74.8, 53.4, 45.0, 43.5, 43.3.
3
2264 | Org. Biomol. Chem., 2021, 19, 2254–2268
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-(3,4-Dichlorophenyl)-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-
Paper
2
δ 7.77 (dd, J = 1.6, 7.6 Hz, 1H), 7.45 (dt, J = 1.6, 8.4 Hz, 1H),
oxabenzo[a]cyclobuta[d]cyclohepten-3-one (6p). Yield = 92% 7.17–6.92 (m, 10H), 6.73 (dt, J = 1.2, 8.0 Hz, 1H), 4.78 (dd, J =
75 mg); colorless solid; mp = 114–116 °C (recrystallized from 7.2, 10.0 Hz, 1H), 4.49 (dd, J = 3.6, 12.4 Hz, 1H), 4.39 (dd, J = 4.8,
(
+
hexanes and EtOAc); HRMS (ESI, M + 1) calcd for C24
4
(
1
H
H
19Cl
2
O
2
12.4 Hz, 1H), 4.16 (ddd, J = 0.8, 7.2, 10.4 Hz, 1H), 3.99 (dd, J =
1
13
09.0762, found 409.0768, err (ppm): −1.47;
400 MHz, CDCl ): δ 7.75 (dd, J = 2.0, 8.0 Hz, 1H), 7.44 (dt, J = CDCl
.6, 8.0 Hz, 1H), 7.20–7.05 (m, 7H), 6.99–6.96 (m, 2H), 6.75 131.0, 128.2 (d, J = 4.5 Hz), 128.0 (d, J = 8.4 Hz), 127.9 (2×), 127.6
NMR 6.4, 10.0 Hz, 1H), 3.70–3.65 (m, 1H); C NMR (100 MHz,
3
3
): δ 200.5, 160.5 (d, J = 244.1 Hz), 160.4, 139.1, 133.6,
(
1
dd, J = 2.0, 8.0 Hz, 1H), 4.54–4.49 (m, 2H), 4.31 (dd, J = 9.2, (2×), 126.4, 126.3 (d, J = 15.1 Hz), 126.1, 123.6 (d, J = 3.1 Hz),
13
2.4 Hz, 1H), 3.97–3.93 (m, 2H), 3.74–3.66 (m, 1H); C NMR 121.9, 120.0, 114.8 (d, J = 22.0 Hz), 74.6, 51.6, 44.9, 43.2, 38.8.
): δ 200.1, 160.4, 139.6, 138.4, 133.7, 131.9, 1-Phenyl-2-pyridin-3-yl-2,2a,9,9a-tetrahydro-1H-8-oxabenzo[a]
30.9, 130.0, 129.83, 129.78, 128.4 (2×), 127.7 (2×), 127.4, cyclobuta[d]cyclohepten-3-one (6u). Yield = 87% (59 mg); color-
26.8, 126.0, 122.0, 119.9, 74.7, 53.1, 44.8, 43.0, 42.9. less solid; mp = 151–153 °C (recrystallized from hexanes and
-Naphthalen-2-yl-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-oxabenzo EtOAc); HRMS (ESI, M + 1) calcd for C23
(100 MHz, CDCl
3
1
1
+
2
2
H20NO 342.1494,
1
[a]cyclobuta[d]cyclohepten-3-one (6q). Yield = 94% (73 mg); found 342.1487, err (ppm): 2.05; H NMR (400 MHz, CDCl ): δ
3
colorless solid; mp = 139–141 °C (recrystallized from hexanes 8.27 (d, J = 2.4 Hz, 1H), 8.26 (dd, J = 1.6, 8.8 Hz, 1H), 7.74 (dd,
+
and EtOAc); HRMS (ESI, M + 1) calcd for C28
H
23
O
2
391.1698, J = 2.0, 8.0 Hz, 1H), 7.44 (dt, J = 2.0, 8.4 Hz, 1H), 7.24 (dt, J =
1
found 391.1690, err (ppm): 2.05; H NMR (400 MHz, CDCl ): δ 2.0, 8.0 Hz, 1H), 7.16–7.04 (m, 5H), 7.00–6.95 (m, 3H), 4.60
3
7
=
.80 (dd, J = 2.0, 8.0 Hz, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.67 (d, J (dd, J = 6.0, 10.0 Hz, 1H), 4.54 (dd, J = 4.0, 12.0 Hz, 1H), 4.30
8.0 Hz, 1H), 7.56 (br s, 1H), 7.51 (d, J = 8.4 Hz, 1H), 7.48–7.35 (dd, J = 10.0, 12.0 Hz, 1H), 4.01–3.96 (m, 2H), 3.82–3.74 (m,
1
3
(m, 3H), 7.14–7.07 (m, 4H), 7.03–6.97 (m, 4H), 4.77 (dd, J = 6.0, 1H); C NMR (100 MHz, CDCl ): δ 200.1, 160.4, 149.6, 147.5,
3
1
1
7
0.0 Hz, 1H), 4.55 (dd, J = 4.0, 12.4 Hz, 1H), 4.37 (dd, J = 9.2, 138.2, 135.2, 134.6, 133.7, 130.8, 128.3 (2×), 127.7 (2×), 126.6,
2.4 Hz, 1H), 4.19 (ddd, J = 0.8, 6.0, 10.4 Hz, 1H), 4.06 (dd, J = 126.0, 122.7, 121.9, 119.9, 74.7, 52.6, 44.7, 42.8, 41.4.
1
3
.2, 10.0 Hz, 1H), 3.83–3.75 (m, 1H); C NMR (100 MHz,
2-(3,4-Dimethoxyphenyl)-1,1-dimethyl-2,2a,9,9a-tetrahydro-1H-
CDCl
3
): δ 200.7, 160.5, 139.2, 136.8, 133.5, 133.1, 131.9, 130.9, 8-oxabenzo[a]cyclobuta[d]cyclohepten-3-one (6ac). Yield = 45%
+
1
1
25 4
28.1 (2×), 127.8 (2×), 127.6, 127.4 (2×), 126.7, 126.31, 126.27, (32 mg); colorless oil; HRMS (ESI, M + 1) calcd for C22H O
26.0, 125.7, 125.3, 121.9, 119.9, 74.8, 53.3, 45.0, 43.9, 43.5.
1
353.1753, found 353.1761, err (ppm): −2.27; H NMR (400 MHz,
): δ 7.76 (dd, J = 2.0, 8.0 Hz, 1H), 7.40 (dt, J = 1.6, 8.4 Hz,
2
-Furan-2-yl-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-oxabenzo[a] CDCl
3
cyclobuta[d]cyclohepten-3-one (6r). Yield = 93% (61 mg); color- 1H),7.05 (d, J = 8.0 Hz, 1H), 7.02 (dt, J = 0.8, 8.0 Hz, 1H), 6.80 (d,
less solid; mp = 118–120 °C (recrystallized from hexanes and J = 8.0 Hz, 1H), 6.70 (dd, J = 2.0, 8.4 Hz, 1H), 6.63 (d, J = 2.0 Hz,
+
EtOAc); HRMS (ESI, M + 1) calcd for C22
H
19
O
3
331.1334, 1H), 4.54 (dd, J = 2.8, 12.8 Hz, 1H), 4.32 (dd, J = 2.8, 12.4 Hz,
): 1H), 3.97 (t, J = 10.0 Hz, 1H), 3.86 (s, 3H), 3.85 (dd, J = 9.6, 12.4
δ 7.71 (dd, J = 2.0, 8.0 Hz, 1H), 7.42 (dt, J = 1.6, 8.0 Hz, 1H), Hz, 1H), 3.84 (s, 3H), 2.61–2.56 (m, 1H), 1.35 (s, 3H), 0.87 (s,
1
found 331.1340, err (ppm): −1.81; H NMR (400 MHz, CDCl
3
1
3
7
1
1
4
3
.22–7.12 (m, 5H), 7.08–7.04 (m, 3H), 6.12 (dt, J = 1.6, 3.2 Hz, 3H); C NMR (100 MHz, CDCl ): δ 201.7, 160.2, 148.7, 147.6,
H), 5.95 (dd, J = 0.8, 2.8 Hz, 1H), 4.60 (dd, J = 4.0, 10.0 Hz, 133.7, 132.3, 131.2, 125.9, 121.8, 120.3, 119.0, 111.0, 110.7, 72.4,
H), 4.57 (dd, J = 4.0, 12.0 Hz, 1H), 4.12 (t, J = 12.0 Hz, 1H), 55.9, 55.8, 50.8, 50.6, 46.8, 40.0, 25.4, 24.5.
.06–3.98 (m, 1H), 3.91 (ddd, J = 0.8, 4.0, 10.4 Hz, 1H), 3.78 (t,
J = 8.8 Hz, 1H); C NMR (100 MHz, CDCl
8-Benzenesulfonyl-2-(3,4-dimethoxyphenyl)-1-phenyl-1,2,2a,8,9,
1
3
3
): δ 199.8, 160.5, 9a-hexahydro-8-azabenzo[a]cyclobuta[d]cyclohepten-3-one (6ad).
1
1
53.3, 141.5, 138.8, 133.3, 130.6, 128.0 (2×), 127.2 (2×), 126.5, Yield = 90% (97 mg); colorless solid; mp = 180–181 °C (recrystal-
+
26.4, 121.7, 119.7, 110.0, 107.3, 74.9, 52.1, 44.6, 43.2, 37.5.
-Phenyl-2-thiophen-2-yl-2,2a,9,9a-tetrahydro-1H-8-oxabenzo
a]cyclobuta[d]cyclohepten-3-one (6s). Yield = 95% (66 mg); NMR (400 MHz, CDCl ): δ 7.85 (dd, J = 1.6, 7.6 Hz, 1H), 7.84–7.79
lized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd for
1
1
32 5
C H30NO S 540.1845, found 540.1850, err (ppm): −0.93; H
[
3
colorless solid; mp = 142–144 °C (recrystallized from hexanes (m, 3H), 7.60–7.56 (m, 1H), 7.51–7.47 (m, 3H), 7.31 (dt, J = 1.2,
+
19 2
and EtOAc); HRMS (ESI, M + 1) calcd for C22H O S 347.1106, 8.0 Hz, 1H), 7.17–7.13 (m, 2H), 7.13–7.07 (m, 1H), 6.91 (d, J = 7.2
1
found 347.1110, err (ppm): −1.15; H NMR (400 MHz, CDCl ): Hz, 2H), 6.64 (d, J = 8.0 Hz, 1H), 6.40 (dd, J = 2.0, 8.4 Hz, 1H),
3
δ 7.75 (dd, J = 1.6, 7.6 Hz, 1H), 7.44 (dt, J = 2.0, 8.4 Hz, 1H), 6.26 (d, J = 2.0 Hz, 1H), 4.69 (dd, J = 5.2, 14.4 Hz, 1H), 4.49 (dd, J
7
1
4
3
1
1
.23–7.12 (m, 3H), 7.11–7.05 (m, 4H), 6.98 (dt, J = 1.2, 5.2 Hz, = 2.8, 9.2 Hz, 1H), 4.16–4.07 (m, 1H), 3.80 (s, 3H), 3.65 (t, J = 9.6
H), 6.77 (dd, J = 3.2, 5.2 Hz, 1H), 6.67 (dt, J = 1.2, 3.2 Hz, 1H), Hz, 1H), 3.56 (s, 3H), 3.42 (dd, J = 12.4, 14.8 Hz, 1H), 3.06 (dd, J =
13
.83–4.80 (m, 1H), 4.58–4.54 (m, 1H), 4.23–4.18 (m, 1H), 2.4, 10.4 Hz, 1H); C NMR (100 MHz, CDCl
3
): δ 199.7, 148.3,
): δ 199.7, 160.5, 147.4, 140.9, 140.7, 138.6, 133.1, 132.8, 132.5, 131.2, 131.0, 129.4
42.7, 138.4, 133.5, 130.7, 128.0 (2×), 127.6 (2×), 126.6, 126.4, (2×), 128.1 (2×), 127.4 (2×), 126.7 (2×), 126.3, 126.2, 125.6, 119.4,
1
3
.94–3.87 (m, 3H); C NMR (100 MHz, CDCl
3
26.3, 125.0, 123.9, 121.8, 119.8, 74.8, 55.2, 45.4, 42.6, 34.5.
-(2-Fluorophenyl)-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-oxabenzo
a]cyclobuta[d]cyclohepten-3-one (6t). Yield = 87% (62 mg); color-
less solid; mp = 148–150 °C (recrystallized from hexanes and
113.0, 110.4, 56.0, 55.73, 55.69, 51.5, 46.0, 42.6, 42.0.
2
A representative synthetic procedure of skeletons 7 and 8 is as
follows
[
+
EtOAc); HRMS (ESI, M + 1) calcd for C24
found 359.1452, err (ppm): −1.39; H NMR (400 MHz, CDCl ): (0.2 mmol) in degassed EtOAc (30 mL) at 25 °C. Then, 1,2-
H
20FO
2
359.1447, Iodine (8 mg, 0.03 mmol) was added to a solution of 5
1
3
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Paper
Organic & Biomolecular Chemistry
epoxybutane (20 mg, 0.3 mmol) was added to the reaction 4.36 (d, J = 8.0, 12.4 Hz, 1H), 4.22 (t, J = 9.6 Hz, 1H), 4.08 (t, J =
mixture at 25 °C. By use of a Pyrex glass filter, the reaction 9.6 Hz, 1H), 4.03 (t, J = 9.6 Hz, 1H), 3.83 (s, 3H), 3.71 (s, 3H),
1
3
mixture was irradiated under a nitrogen atmosphere with a 3.27–3.20 (m, 1H), 2.18 (s, 3H); C NMR (100 MHz, CDCl
LED lamp (λ > 2540 Å) at 25 °C for 15 h. The reaction mixture 201.2, 156.9, 148.5, 147.5, 142.5, 134.1, 131.7, 131.0, 130.8,
was washed with saturated Na S O (3 × 10 mL). The com- 128.7 (2×), 127.2, 126.7, 126.4 (2×), 119.4 (2×), 110.7, 110.5,
3
): δ
2
2 3(aq)
bined organic layers were washed with brine, dried, filtered, 72.2, 55.8, 55.6, 54.5, 46.5, 42.9, 42.2, 20.1.
and evaporated to afford crude product under reduced
2-(3,4-Dimethoxyphenyl)-6-methoxy-1-phenyl-2,2a,9,9a-tetra-
pressure. Purification on silica gel (hexanes/EtOAc = 20/1–8/1) hydro-1H-8-oxabenzo[a]cyclobuta[d]cyclohepten-3-one
(7f).
afforded skeletons 7 and 8.
Yield = 75% (65 mg); colorless solid; mp = 160–162 °C (recrys-
+
2
-(3,4-Dimethoxyphenyl)-1-phenyl-2,2a,9,9a-tetrahydro-1H-8- tallized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd
1
oxabenzo[a]cyclobuta[d]cyclohepten-3-one (7a). Yield = 85% for C H O 431.1859, found 431.1863, err (ppm): −0.93; H
2
7
27 5
(
68 mg); colorless solid; mp = 155–157 °C (recrystallized from NMR (400 MHz, CDCl
3
): δ 7.39 (d, J = 8.8 Hz, 1H), 7.35–7.31
(m, 2H), 7.27–7.22 (m, 3H), 6.70 (d, J = 8.4 Hz, 1H), 6.66 (dd, J
NMR = 1.6, 8.0 Hz, 1H), 6.60 (d, J = 1.6 Hz, 1H), 6.49 (d, J = 2.0 Hz,
): δ 7.35–7.31 (m, 4H), 7.27–7.22 (m, 3H), 7.01 1H), 6.46 (dd, J = 2.4, 8.8 Hz, 1H), 4.47–4.38 (m, 2H), 4.28–4.23
dd, J = 1.2, 7.6 Hz, 1H), 6.87 (dt, J = 0.8, 8.4 Hz, 1H), 6.71 (d, J (m, 1H), 4.09–4.01 (m, 2H), 3.814 (s, 3H), 3.808 (s, 3H), 3.71 (s,
+
25 4
hexanes and EtOAc); HRMS (ESI, M + 1) calcd for C26H O
4
(
(
=
1
1
9
1
1
1
4
7
1
01.1753, found 401.1759, err (ppm): −1.50;
H
400 MHz, CDCl
3
1
3
8.4 Hz, 1H), 6.67 (dd, J = 1.6, 8.4 Hz, 1H), 6.61 (d, J = 1.6 Hz, 3H), 3.22–3.15 (m, 1H); C NMR (100 MHz, CDCl ): δ 199.2,
3
H), 4.46 (dd, J = 3.2, 12.8 Hz, 1H), 4.39 (dd, J = 8.4, 12.8 Hz, 163.8, 161.0, 148.4, 147.5, 142.7, 133.4, 131.6, 128.6 (2×), 126.7,
H), 4.22 (t, J = 9.6 Hz, 1H), 4.10 (t, J = 9.6 Hz, 1H), 4.04 (t, J = 126.4 (2×), 121.1, 119.5, 110.7, 110.6, 109.4, 103.0, 72.2, 55.7,
.6 Hz, 1H), 3.82 (s, 3H), 3.72 (s, 3H), 3.26 (dt, J = 3.2, 9.6 Hz, 55.6, 55.5, 54.4, 46.9, 42.8, 41.6.
13
H); C NMR (100 MHz, CDCl
3
): δ 200.9, 158.9, 148.5, 147.4,
1-Phenyl-2-(3,4,5-trimethoxyphenyl)-2,2a,9,9a-tetrahydro-1H-
42.4, 133.1, 131.6, 131.2, 128.7 (2×), 127.5, 126.8, 126.4 (2×), 8-oxabenzo[a]cyclobuta[d]cyclohepten-3-one (7h). Yield = 80%
21.4, 119.5, 119.2, 110.7, 110.4, 72.2, 55.8, 55.6, 54.4, 46.3, (69 mg); colorless solid; mp = 170–172 °C (recrystallized from
2.9, 42.3. Single-crystal X-Ray diagram: crystal of compound hexanes and EtOAc); HRMS (ESI, M + 1) calcd for C27
a was grown by slow diffusion of EtOAc into a solution of 431.1859, found 431.1866, err (ppm): −1.62; H NMR (400 MHz,
+
H O
27 5
1
compound 7a in CH Cl to yield colorless prisms. The com- CDCl ): δ 7.37–7.23 (m, 7H), 7.01 (dd, J = 1.2, 8.4 Hz, 1H), 6.85
2
2
3
pound crystallizes in the monoclinic crystal system, space (dt, J = 1.2, 8.0 Hz, 1H), 6.27 (s, 2H), 4.47–4.39 (m, 2H), 4.29 (t, J
group P2 /c, a = 13.8730(7) Å, b = 22.7202(12) Å, c = 6.3384(3) = 10.0 Hz, 1H), 4.15 (t, J = 9.6 Hz, 1H), 4.06 (t, J = 10.0 Hz, 1H),
Å, V = 1974.10(17) Å , Z = 4, d
1
3
−3
13
= 1.347 g cm , F(000) = 848, 3.78 (s, 3H), 3.69 (s, 6H), 3.27–3.20 (m, 1H); C NMR (100 MHz,
calcd
2
0
θ range 1.485–26.410°, R indices (all data) R1 = 0.0849, wR2 = CDCl
.1787.
-(3,4-Dimethoxyphenyl)-5-fluoro-1-phenyl-2,2a,9,9a-tetrahy-
dro-1H-8-oxabenzo[a]cyclobuta[d]cyclohepten-3-one (7d). Yield
3
): δ 201.1, 158.6, 152.8 (2×), 142.5, 136.4, 134.8, 133.1,
131.3, 128.7 (2×), 127.5, 126.8, 126.3 (2×), 121.4, 119.4, 104.1
(2×), 71.8, 60.8, 55.9 (2×), 54.9, 46.7, 42.2, 41.8.
2
2-(4-Methoxyphenyl)-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-oxa-
=
84% (70 mg); colorless solid; mp = 157–159 °C (recrystallized benzo[a]cyclobuta[d]cyclohepten-3-one (7j). Yield
=
76%
+
from hexanes and EtOAc); HRMS (ESI, M + 1) calcd for (56 mg); colorless solid; mp = 152–154 °C (recrystallized from
C
NMR (400 MHz, CDCl
1
+
26
H
24FO
4
419.1659, found 419.1668, err (ppm): −2.14;
H
hexanes and EtOAc); HRMS (ESI, M + 1) calcd for C25
H
23
O
3
1
3
): δ 7.36–7.32 (m, 2H), 7.27–7.23 (m, 371.1647, found 371.1655, err (ppm): −2.16;
H NMR
3
1
H), 7.08–7.02 (m, 2H), 7.00–6.96 (m, 1H), 6.72 (d, J = 8.0 Hz, (400 MHz, CDCl ): δ 7.35–7.31 (m, 4H), 7.27–7.21 (m, 3H), 7.06
3
H), 6.66 (dd, J = 2.0, 8.0 Hz, 1H), 6.64 (d, J = 2.0 Hz, 1H), 4.44 (d, J = 8.4 Hz, 2H), 7.00 (dd, J = 0.8, 8.4 Hz, 1H), 6.88 (dt, J =
(dd, J = 3.2, 12.4 Hz, 1H), 4.36 (d, J = 8.0, 12.4 Hz, 1H), 4.21 (t, J 1.2, 8.0 Hz, 1H), 6.77 (d, J = 8.8 Hz, 2H), 4.50 (dd, J = 3.6, 12.8
=
3
9.6 Hz, 1H), 4.11 (t, J = 9.6 Hz, 1H), 4.05 (t, J = 9.6 Hz, 1H), Hz, 1H), 4.33 (dd, J = 9.6, 12.8 Hz, 1H), 4.14 (t, J = 10.0 Hz,
1
3
.83 (s, 3H), 3.75 (s, 3H), 3.30–3.22 (m, 1H); C NMR 1H), 4.07 (t, J = 9.2 Hz, 1H), 4.02 (t, J = 9.2 Hz, 1H), 3.77 (s,
13
3 3
(100 MHz, CDCl ): δ 199.5, 157.2 (d, J = 239.6 Hz), 155.3, 148.6, 3H), 3.29 (dt, J = 3.6, 9.6 Hz, 1H); C NMR (100 MHz, CDCl ):
1
1
1
4
47.6, 142.3, 131.4, 128.7 (2×), 128.2 (d, J = 6.1 Hz), 126.9, δ 200.9, 159.1, 158.0, 142.3, 133.0, 131.2, 131.0, 128.7 (2×),
26.4 (2×), 121.3 (d, J = 7.6 Hz), 120.6 (d, J = 23.5 Hz), 119.2, 128.2 (2×), 127.6, 126.8, 126.5 (2×), 121.4, 119.4, 113.4 (2×),
16.2 (d, J = 24.3 Hz), 110.8, 110.6, 72.7, 55.8, 55.7, 54.2, 46.5, 72.6, 55.2, 53.9, 45.9, 43.5, 42.9.
3.1, 42.3.
-(3,4-Dimethoxyphenyl)-5-methyl-1-phenyl-2,2a,9,9a-tetra-
hydro-1H-8-oxabenzo[a]cyclobuta[d]cyclohepten-3-one
2-(2,4-Dimethoxyphenyl)-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-
oxabenzo[a]cyclobuta[d]cyclohepten-3-one (7m). Yield = 80%
2
(7e). (64 mg); colorless solid; mp = 203–205 °C (recrystallized from
+
Yield = 80% (66 mg); colorless solid; mp = 154–156 °C (recrys- hexanes and EtOAc); HRMS (ESI, M + 1) calcd for C H O
tallized from hexanes and EtOAc); HRMS (ESI, M + 1) calcd 401.1753, found 401.1745, err (ppm): 1.99; H NMR (400 MHz,
for C27
2
6
25
4
+
1
1
H
27
O
4
415.1909, found 415.1918, err (ppm): −2.17; H CDCl
3
): δ 7.38–7.24 (m, 7H), 7.01–6.97 (m, 2H), 6.90 (dt, J =
NMR (400 MHz, CDCl ): δ 7.35–7.31 (m, 2H), 7.27–7.22 (m, 0.8, 8.0 Hz, 1H), 6.41 (d, J = 2.4 Hz, 1H), 6.37 (dd, J = 2.4, 8.4
3
3
H), 7.14 (dd, J = 2.8, 8.4 Hz, 1H), 7.09 (d, J = 2.8 Hz, 1H), 6.90 Hz, 1H), 4.54 (dd, J = 4.4, 12.8 Hz, 1H), 4.24 (dd, J = 10.4, 12.4
(
d, J = 8.4 Hz, 1H), 6.71 (d, J = 8.4 Hz, 1H), 6.66 (dd, J = 2.0, 8.4 Hz, 1H), 4.08–4.03 (m, 3H), 3.78 (s, 3H), 3.74 (s, 3H), 3.37–3.33
1
3
Hz, 1H), 6.60 (d, J = 2.0 Hz, 1H), 4.42 (dd, J = 3.2, 12.8 Hz, 1H), (m, 1H); C NMR (100 MHz, CDCl ): δ 200.7, 159.39, 159.35,
3
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58.1, 142.3, 132.5, 130.4, 128.6 (2×), 127.7, 126.9, 126.7, 126.6
Paper
1
Notes and references
(2×), 121.3, 120.7, 119.2, 103.4, 98.0, 73.4, 55.2, 55.1, 52.8, 44.4,
4
7
3.1, 41.6. Single-crystal X-Ray diagram: crystal of compound
m was grown by slow diffusion of EtOAc into a solution of
1 For reviews, see: (a) E. Lee-Ruff and G. Mladenova, Chem.
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Y. Q. Zou and T. Bach, Chem. Rev., 2016, 116, 9748–
9815.
compound 7m in CH Cl to yield colorless prisms. The com-
pound crystallizes in the triclinic crystal system, space group P ˉ1 ,
2
2
a = 9.4174(5) Å, b = 10.5047(5) Å, c = 11.7070(6) Å, V = 1015.58(9)
2 (a) Y.-Y. Fan, X.-H. Gao and J. M. Yue, Sci. China: Chem.,
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3
−3
Å , Z = 2, d
= 1.310 g cm , F(000) = 424, 2θ range
calcd
1
.866–26.432°, R indices (all data) R1 = 0.0443, wR2 = 0.0909.
-Biphenyl-4-yl-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-oxabenzo[a]
2
cyclobuta[d]cyclohepten-3-one (7o). Yield = 83% (69 mg); color-
3 (a) J. C. Namyslo and D. E. Kaufmann, Chem. Rev., 2003,
103, 1485–1583; (b) T. Seiser, T. Saget, D. N. Tran and
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14606.
6 H. Ito, T. Toyata and M. Sawamura, J. Am. Chem. Soc., 2010,
132, 5990–5992.
less solid; mp = 140–142 °C (recrystallized from hexanes and
+
EtOAc); HRMS (ESI, M + 1) calcd for C30
H
25
O
2
417.1855,
1
found 417.1848, err (ppm): 1.68; H NMR (400 MHz, CDCl ): δ
3
7
.58–7.56 (m, 2H), 7.48–7.21 (m, 14H), 7.02–6.99 (m, 1H), 6.86
(
(
(
2
1
dt, J = 0.8, 8.4 Hz, 1H), 4.53 (dd, J = 4.0, 12.8 Hz, 1H), 4.34
dd, J = 10.0, 12.8 Hz, 1H), 4.21 (t, J = 9.6 Hz, 1H), 4.19–4.09
1
3
m, 2H), 3.39–3.31 (m, 1H); C NMR (100 MHz, CDCl
3
): δ
00.8, 159.1, 142.1, 141.0, 139.0, 138.5, 133.0, 130.9, 128.7 (2×),
28.6 (2×), 127.5, 127.4 (2×), 127.0 (3×), 126.9, 126.7 (2×), 126.5
(
2×), 121.4, 119.4, 72.7, 53.8, 46.0, 43.4, 43.2.
-Naphthalen-2-yl-1-phenyl-2,2a,9,9a-tetrahydro-1H-8-oxabenzo
a]cyclobuta[d]cyclohepten-3-one (7q). Yield = 85% (66 mg);
colorless solid; mp = 153–155 °C (recrystallized from hexanes
7 C. Guerot, B. H. Tchitchanov, H. Knust and E. M. Carreira,
Org. Lett., 2011, 13, 780–783.
8 G. A. Molander and P. E. Gormisky, J. Org. Chem., 2008, 73,
7481–7485.
9 M. L. Conner and M. K. Brown, J. Org. Chem., 2016, 81,
8050–8060.
2
[
+
and EtOAc); HRMS (ESI, M + 1) calcd for C28
found 391.1705, err (ppm): −1.79; H NMR (400 MHz, CDCl ): δ
H O
23 2
391.1698,
1
3
7
=
.78 (dd, J = 3.6, 6.0 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.66 (dd, J 10 S. Saito, K. Hirayama, C. Kabuto and Y. Yamamoto, J. Am.
3.6, 6.0 Hz, 1H), 7.54 (br s, 1H), 7.42–7.38 (m, 2H), 7.36–7.23 Chem. Soc., 2000, 122, 10776–10780.
(m, 8H), 7.01 (dd, J = 0.8, 8.4 Hz, 1H), 6.78 (dt, J = 1.2, 8.4 Hz, 11 Recent examples on photo-controlled intramolecular annu-
1
1
8
H), 4.57 (dd, J = 3.6, 12.4 Hz, 1H), 4.36 (dd, J = 9.6, 12.8 Hz,
lation, see: (a) Y.-M. Wang, N. C. Bruno, A. L. Placeres,
S. Zhu and S. L. Buchwald, J. Am. Chem. Soc., 2015, 137,
10524–10527; (b) C. Andersen, V. Ferey, M. Daumas,
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21, 1384–1387; (d) L. D. Elliott and K. I. Booker-Milburn,
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H), 4.31 (t, J = 9.6 Hz, 1H), 4.23 (t, J = 8.8 Hz, 1H), 4.18 (t, J =
1
3
.8 Hz, 1H), 3.39 (dt, J = 3.6, 9.6 Hz, 1H); C NMR (100 MHz,
): δ 200.6, 159.2, 142.2, 137.0, 133.2, 133.0, 132.2, 130.9,
28.8 (2×), 127.7, 127.6, 127.5 (2×), 126.9, 126.5 (2×), 126.0,
25.8, 125.3, 125.1, 121.4, 119.4, 72.9, 53.8, 46.4, 43.4, 43.2.
-[2-(3-Phenylallyloxy)phenyl]but-3-en-2-one (8). Yield = 50%
CDCl
1
1
3
4
+
19 2
(28 mg); colorless oil; HRMS (ESI, M + 1) calcd for C19H O
1
2
79.1385, found 279.1391, err (ppm): −2.15;
H NMR
(400 MHz, CDCl ): δ 7.43–7.25 (m, 7H), 7.18 (d, J = 12.4 Hz,
3
1
5
H), 6.97–6.94 (m, 2H), 6.72 (d, J = 16.0 Hz, 1H), 6.41 (dt, J = 12 W. Ruzyllo, M. Tendera, I. Ford and K. M. Fox, Drugs, 2007,
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3
Hz, 2H), 2.13 (s, 3H); C NMR (100 MHz, CDCl
3
): δ 201.2, 13 J. Singh, G. S. Bisacchi, S. Ahmad, J. D. Godfrey Jr.,
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1
56.1, 136.3, 136.2, 133.1, 130.9, 130.5, 129.6, 128.6 (2×), 127.9,
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There are no conflicts of interest to declare.
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Acknowledgements
The authors would like to thank the Ministry of Science and 17 V. Dumontet, O. Thoison, O. R. Omobuwajo, M.-T. Martin,
Technology of the Republic of China (Taiwan) for its financial
support (MOST 109-2113-M-037-014-MY3).
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(
2
2
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2268 | Org. Biomol. Chem., 2021, 19, 2254–2268
This journal is © The Royal Society of Chemistry 2021