Electrophilic cyclization and intermolecular acetalation of 2-(4- hydroxybut-1-yn-1-yl)benzaldehydes: Synthesis of diiodinated diepoxydibenzo[c,k][1,9]dioxacyclohexadecines

Article abstract of DOI:10.1021/acs.joc.7b01646

An expedient strategy for the preparation of diiodinated diepoxydibenzo[c,k][1,9]dioxacyclohexadecines from readily available 2-(4-hydroxybut-1-yn-1-yl)- benzaldehydes through electrophile-triggered tandem cyclization/ intermolecular acetalation sequence

Full text of DOI:10.1021/acs.joc.7b01646

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Note
Electrophilic Cyclization and Intermolecular Acetalation
of 2-(4-hydroxybut-1-yn-1-yl)benzaldehydes: Synthesis of
Diiodinated Diepoxydibenzo[c,k][1,9]dioxacyclohexadecines
Jia Wang, Hai-Tao Zhu, Si Chen, Cheng Luan, Yu Xia,
Yi Shen, Ying-Xiu Li, Yingxi Hua, and Yong-Min Liang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01646 • Publication Date (Web): 01 Sep 2017
Downloaded from http://pubs.acs.org on September 1, 2017
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Electrophilic Cyclization and Intermolecular Acetalation of
2-(4-hydroxybut-1-yn-1-yl)benzaldehydes: Synthesis of
Diiodinated Diepoxydibenzo[c,k][1,9]dioxacyclohexadecines
Jia Wang,† Hai-Tao Zhu,‡ Si Chen,† Cheng Luan,† Yu Xia,† Yi Shen,† Ying-Xiu
Li,† Yingxi Hua,† and Yong-Min Liang*,†
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†State Key Laboratory of Applied Organic Chemistry, Lanzhou University,
Lanzhou 730000, People’s Republic of China
‡Shannxi Key Laboratory of Phytochemistry, Baoji University of Arts and
Sciences, Baoji 721013, People’s Republic of China
liangym@lzu.edu.cn
ABSTRACT
An
diepoxydibenzo[c,k][1,9]dioxacyclohexadecines
2-(4-hydroxybut-1-yn-1-yl)benzaldehydes through
expedient
strategy
for
the
preparation
of
diiodinated
available
from
readily
electrophile-triggered
tandem cyclization/intermolecular acetalation sequence has been presented.
The electrophilic macrocyclization can be performed under mild conditions and
up to gram quantities. Moreover, palladium-catalyzed coupling and reduction
reactions of the resulting iodides could efficiently afford oxa-macrocycles.
Macrocyclic polyethers acted as a special type of compounds have found
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versatile applications in material science,1 environmental science,2
bioscience,3 scientific energy,4 and pharmacology.5 Macrocyclic polyethers
have played important roles in phase-transfer catalysis6 and metal complex.7
Moreover, macrocyclic polyethers continue to emerge in diverse fields, not
only are common in antibiotic,8 antitumoral9 and protein,10 but also are
exploited in coordination chemistry11 and supramolecular chemistry.12 As
applications of macrocyclic polyethers and their derivatives across many fields,
the efficient strategies for the synthesis of macrocycles have been the focus of
considerable attention for organic chemists and medicinal chemists. Within the
quest for innovative strategies toward multifarious macrocyclic polyethers, a
variety of effective methods have been explored. Usually, the methods for
gaining access to macrocyclic polyethers involve Williamson’s reaction,13
ring-closing metathesis (RCM),14 Pd-catalyzed cross-coupling15 and activation
of C-H bonds.16 Although significant progress has been achieved for the
synthesis of macrocyclic polyethers, the need for alternative methods is indeed
desirable. Recently, electrophilic iodocyclization has emerged as a powerful
method to construct a variety of functionalized carbocycles17 and
heterocycles.18 The iodocyclizations are conducted under mild conditions,
metal-free and environmentally friendly. Although great achievements have
been made with respect to iodocyclization, few examples to prepare
macrocyclic polyethers based on sequential cascade iodocyclizations have
been reported until now.
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Scheme 1. Iodine-promoted Cascade Carbocyclization
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In recent years, methods involving iodonium-induced activation of alkyne
have provided the opportunity for preparing iodinated 1H-isochromene by
Barluenga19 and Larock20 (Scheme 1a). This reaction is generally believed that
the reactive species B activated by iodide cation was attacked by the oxygen
of the carbonyl group to give the intermediate C. Subsequently, the pyrilium
intermediate C is immediately trapped by the nucleophile to give the product D.
In 2013, Flynn’s group reported another analogous electrophilic cyclization to
form ring-fused indoles (Scheme 1b).21 The N-(2-alkynylphenyl)imines E
underwent similar iodocylization to an imminum ion G, which was trapped by a
nucleophile tethered to the alkynyl group to give H. Encouraged by these
achievements and continuing our interest in iodocyclization, we envisioned
that the substrates 1 containing a homopropargylic alcohol moiety could
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undergo a similar iodocyclization to form the important intermediate I, which
could go through the intramolecular cyclization to obtain the compound J
(Scheme 1c). To our surprise, the intermediate I underwent the intermolecular
acetalation rather than the intramolecular cyclization due to the ring strain
(Scheme 1c). Herein, we report an effective method for the synthesis of
diiodinated macrocyclic polyethers via cascade iodocyclization.
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Table 1. Optimization Studies for the Synthesis of 2aa
entry
1
solvent
DCE
electrophile (equiv)
I2 (1.0)
base (equiv)
NaOAc (1.0)
NaOAc (1.0)
NaOAc (1.0)
NaOAc (1.0)
NaOAc (1.5)
NaOAc (2.0)
NaOAc (2.5)
NaOAc (2.0)
NaOAc (2.0)
NaOAc (2.0)
NaOAc (2.0)
yieldb (%)
23
2
DCE
NIS (1.0)
IBr (1.0)
ICl (1.0)
trace
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3
DCE
4
DCE
48
5
DCE
ICl (1.0)
60
6
DCE
ICl (1.0)
70
7
DCE
ICl (1.0)
65
8
DCE
ICl (1.2)
ICl (1.5)
75
9
DCE
68
10
11
CH2Cl2
CH3CN
ICl (1.2)
45
ICl (1.2)
26
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THF
acetone
toluene
DCE
ICl (1.2)
ICl (1.2)
ICl (1.2)
ICl (1.2)
ICl (1.2)
ICl (1.2)
ICl (1.2)
ICl (1.2)
NaOAc (2.0)
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18
NaOAc (2.0)
NaOAc (2.0)
K2CO3 (2.0)
K3PO4 (2.0)
tBuOK (2.0)
NaOAc (2.0)
NaOAc (2.0)
trace
66
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DCE
70
DCE
trace
53c
61d
DCE
DCE
aAll reactions were run under the following conditions, unless otherwise indicated: 0.20
mmol of 1a and 1.2 equiv of electrophile in 4 mL of solvent were stirred at room
temperature for 1 h. bYields of isolated products. cThe reaction was run in 6 mL DCE. dThe
reaction was run in 2 mL DCE.
At the onset of our investigation, we examined the reaction of
2-(4-hydroxybut-1-yn-1-yl)benzaldehyde (1a) with 1.0 equiv of I2, 1.0 equiv
NaOAc in 1,2-dichloroethane (DCE) (4 mL) at room temperature. The
unexpected product 2a was isolated in 23% yield after 1 h (Table 1, entry 1).
After screening common electrophiles such as NIS, IBr and ICl, we found that
the electrophile ICl was better than others (entries 1-4). When we adjusted the
amount of NaOAc, the 2.0 equiv NaOAc was best for this reaction (entries 5-7).
By increasing the amount of ICl to 1.2 equiv, the product 2a was obtained in 75%
yield (entry 8). Further increasing the amount of ICl to 1.5 equiv, a lower yield
of 2a was received (entry 9). Subsequently, when different solvents involving
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CH2Cl2, CH3CN, THF, acetone and toluene were studied, no better results
were obtained (entries 10-14). After screening a series of bases such as
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t
NaOAc, K2CO3, K3PO4, and BuOK, we found that NaOAc was the best
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(entries 8 and 15-17). In addition, no satisfactory yields were obtained when
the reactions were carried out in diluted or concentrated conditions (entries
18-19). From the series of detailed investigations mentioned above, the
combination of 1.0 equiv of 1a, 1.2 equiv of ICl, and 2.0 equiv of NaOAc in
DCE at room temperature for 1 h was determined as the optimum reaction
conditions.
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Table 2. Synthesis of Diiodinated Macrocyclic Polyethers of 2a
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aAll reactions were run under the following conditions, unless otherwise indicated: 0.20
mmol of 1 and 1.2 equiv of ICl in 4 mL of DCE were stirred at room temperature for 1 h.
Yields are given for isolated products.
To investigate the generality and the scope of this reaction, various
2-(4-hydroxybut-1-yn-1-yl)benzaldehyde derivatives were subjected to the
above mentioned conditions, as summarized in Table 2. The substrate 1a with
primary alcohol was selected as standard substrate and gave the unfamiliar
product 2a in 75% yield. The structure of the representative product 2a was
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determined by X-ray crystallographic analysis. Subsequently, manifold
substituted secondary homopropargylic alcohol substrates were prepared to
investigate the scope of this reaction. In the case of Ph-substituted substrate
1b, the corresponding product 2b was obtained in 57% yield. The reactions of
substrates 1c-1i bearing electron-donating or electron-withdrawing
substituents resulted in the corresponding products 2c-2i in moderate to good
yields. The structure of 2h was identified by X-ray crystallographic analysis.
The substrate 1j with 2-naphthyl group was also tolerated and the desired
product 2j was obtained in 63% yield. Afterward, substrate 1k with piperonyl
group was attempted and afforded the product 2k in 55% yield. In contrast to
the products containing aryl-substituents, the yields of 2l and 2m which had
alkyl groups remarkably decreased because of the weak nucleophilicity of the
hydroxyl group and the severe decomposition of the substrates. In particular,
substrate 1n with cinnamyl group only led to 2n in 15% yield. However,
substrate 1o with a tertiary alcohol failed to afford the corresponding product
2o. This might be due to the huge steric hindrance impairing the nucleophilicity
of the hydroxyl group. The transformations also proceeded smoothly with
substrates 1p-1s with electron-donating or -withdrawing substituents on R2,
furnishing the products 2p-2s in moderate to good yields. Fortunately, the
substrate 1t could work smoothly and gave the desired product 2t in 61% yield.
Subsequently, the ketone substrate 1u was examined, however, the desired
product 2u was not observed. According to Barluenga’s19 and Larock’s20 work,
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the ketone substrate provided 5-exo-dig rather than 6-endo intermediate,
which was not compatible with this transformation. Thus, we failed to obtain
the product 2u. To further extend the application of this reaction, we designed
the substrates 1v and 1w, achieved the desired products 2v and 2w in 48%
and 81% yields, respectively. The structure of products 2v and 2w were also
determined by X-ray crystallographic analysis.
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Scheme 2. Scale-up Experiments
It's worth noting that the reaction can be scaled up to gram quantities
(Scheme 2). The desired product 2a was isolated in 57% yield on the gram
scale under the standard conditions, which provide possibilities for the
industrial applications.
Scheme 3. Palladium-catalyzed Coupling and Reduction Reactions
As shown in Scheme 3, macrocyclic polyether 2a can be further
demonstrated by conducting relevant postfunctionalization reactions. For
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example, the Suzuki coupling of 2a afforded the corresponding product 3a in
75% yield.22 Furthermore, the product 4a can be obtained in 78% yield by
Pd-catalyzed reduction.23
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CONCLUSION
In conclusion, a concise and mild protocol for the synthesis of diiodinated
macrocyclic polyethers has been established. This new strategy relates to the
incorporation of iodine and the diiodinated moiety is readily introduced into the
macrocycles. Moreover, the resulting diiodinated macrocycle is readily
elaborated to more products by palladium-catalyzed coupling and reduction
reactions, which may be essential intermediates for the synthesis of other
valuable compounds. The application of this methodology is currently
underway.
EXPERIMENTAL SECTION
General Remarks
1
Column chromatography was carried out on silica gel. H NMR spectra were
13
recorded on 400 MHz in CDCl3 and C NMR spectra were recorded on 100
MHz in CDCl3. IR spectra were recorded on a FT-IR spectrometer and only
major peaks are reported in cm-1. The substrates (1a-1i and 1u-1w) are known
compounds.24 The substrates (1j-1w) and all products were further
characterized by high resolution mass spectra (HRMS), the HRMS was
obtained on a Q-Exactive Hybrid Quadrupole-Orbitrap Mass Sepctrometer.
1
13
Copies of their H NMR and C NMR spectra are provided in the Supporting
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Information. Room temperature is 23-25°C. The ICl was 0.5 M in CH2Cl2. THF
was distilled over Na/benzophenone. DCE, CH2Cl2, CH3CN, acetone and
toluene were distilled over CaH2, and other solvents were used without further
purification.
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General Procedure for Synthesis of Homopropargylic Alcohols
Method A: To a soluton of corresponding aldehydes (R1-CHO, R1 = aryl-,
2-naphthyl-, piperonyl-, cinnamyl-) (20 mmol) was dissolved in THF (8 mL) and
added saturated aqueous NH4Cl (40 mL). Subsequently, the propargyl
bromide (2.0 equiv) was added into the mixture. Portions of activated zinc dust
(2.0 equiv) were added slowly at 0 oC. The resulting solution was stirred for 1 h
o
at 0 C. Then, the reaction mixture was stirred at room temperature for 24 h.
When the reaction was considered complete as determined by TLC analysis,
the mixture was extracted by ethyl acetate (3 × 40 mL). The combined organic
layer was dried over anhydrous Na2SO4, the Na2SO4 was removed by
decantation and the organic phase was concentrated under reduced pressure
and purified by silica gel flash column chromatography (petroleum ether/EtOAc
= 4/1) to provide corresponding homopropargylic alcohols in 60-85% yields.
Method B: A solution of Et2O (30 mL), hexane (18 mL) and n-BuLi (2.4
mol/L in THF, 4.2 equiv) was cooled to -78 oC, the TMEDA (1.1 equiv) was
added, followed by dropwise addition of propargyl bromide (2.0 equiv). The
o
resulting solution was stirred for 20 min at -78 C, then, a white precipitate
formed. A solution of cyclopropanecarbaldehyde (10 mmol) in Et2O (5 mL) was
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added dropwise over 5 min and the reaction mixture were allowed to warm to
room temperature over 2 h. When the reaction was considered complete as
determined by TLC analysis, the mixture was quenched with water (30 mL)
and extracted by ethyl acetate (3 × 40 mL). The combined organic layer was
dried over anhydrous Na2SO4, the Na2SO4 was removed by decantation and
the organic phase was concentrated under reduced pressure and purified by
silica gel flash column chromatography (petroleum ether/EtOAc = 4/1) to
provide homopropargylic alcohol of 1-cyclopropylbut-3-yn-1-ol in 30% yield.
The homopropargylic alcohol of 1,1-diphenylbut-3-yn-1-ol was synthesized
from benzophenone according to the method B.
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Other alcohols such as but-3-yn-1-ol, pent-4-yn-2-ol, pent-4-yn-1-ol and
hex-5-yn-1-ol were obtained through purchase.
General
Procedure
for
Synthesis
2-(4-hydroxybut-1-yn-1-yl)-
benzaldehyde Derivatives (1a-1w)
To a soluton of 2-iodobenzaldehyde derivatives (7.5 mmol) in Et3N (20 mL)
was added Pd(PPh3)2Cl2 (1 mol %) and CuI (2 mol %). The reaction vial was
flushed with Ar and the reaction mixture was stirred for 5 minutes. A solution of
corresponding homopropargylic alcohols (5 mmol) in Et3N (5 mL) were then
added dropwise through a syringe for 5 minutes. The resulting solution was
stirred at room temperature overnight. When the reaction was considered
complete as determined by TLC analysis, the mixture was quenched by
addition of saturated aqueous NH4Cl (20 mL) and extracted with ethyl acetate
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(3 x 30 mL). The combined organic layers were washed with water, brine, dried
over Na2SO4, the Na2SO4 was removed by decantation and the organic phase
was concentrated under reduced pressure. The crude material was purified by
flash column chromatography (petroleum ether/EtOAc = 4/1) to give the
substrates 1 (1a-1u) in 70-85% yields. The substrate 1v was synthesized from
pent-4-yn-1-ol according to general procedure as mentioned above. The
substrate 1w was synthesized from hex-5-yn-1-ol according to general
procedure as mentioned above. The reaction to the synthesis of substrate 1w
was run at 60 oC.
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General
Procedure
for
Synthesis
of
Diiodinated
Diepoxydibenzo[c,k][1,9]dioxacyclohexadecines
To a solution of 2-(4-hydroxybut-1-yn-1-yl)benzaldehyde derivatives 1 (0.20
mmol) and NaOAc (2.0 equiv) in DCE (4.0 mL) was added ICl (1.2 equiv)
dropwise at room temperature. When the reaction was considered complete
as determined by TLC analysis, the reaction mixture was quenched by addition
of saturated aqueous sodium thiosulfate (10 mL) and diluted with ethyl acetate
(3 x 10 mL), washed with water, saturated brine, dried over Na2SO4 and
evaporated under reduced pressure. The residue was purified by
chromatography on silica gel (petroleum ether/CH2Cl2 = 2/1) to afford 2.
Typical Procedure for 3a: To a solution of 2a (120.0 mg, 0.20 mmol) in
dioxane/H2O (2/0.5 mL) was added 4-methoxyphenylboronic acid (121.6 mg,
4.0 equiv), Pd(PPh3)4 (46.2 mg, 20 mol % ) and Na2CO3 (212 mg, 10.0 equiv).
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The reaction vial was flushed with Ar and the reaction mixture was stirred at
80 °C for 12 h. Afterwards, the reaction mixture was quenched with H2O (10
mL) and extracted with ethyl ether (3 x 10 mL). The combined organic layers
were washed with water, brine, dried over Na2SO4, the Na2SO4 was removed
by decantation and the organic phase was concentrated under reduced
pressure. The crude material was purified by flash column chromatography
(petroleum ether/EtOAc = 10/1) to give 3a (yield 75%) as a yellow solid.
Typical Procedure for 4a: To a solution of 2a (120.0 mg, 0.20 mmol) in DMF
(2 mL) was added Pd(PPh3)2Cl2 (5.6 mg, 4 mol %) and HCOONa (41 mg, 3.0
equiv). The reaction vial was flushed with Ar and the reaction mixture was
stirred at 90 °C for 12 h. The reaction mixture was quenched with H2O (10 mL)
and extracted with ethyl ether (3 x 10 mL). The combined organic layers were
washed with water, brine, dried over Na2SO4, the Na2SO4 was removed by
decantation and the organic phase was concentrated under reduced pressure.
The crude material was purified by flash column chromatography (petroleum
ether/EtOAc = 10/1) to give 4a (yield 78%) as a white solid.
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Characterization Data of 1a−1w
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2-(4-hydroxybut-1-yn-1-yl)benzaldehyde (1a). Yellow oil (0.72 g, 83%). H
NMR (400 MHz, CDCl3) δ ppm 10.44 (s, 1H), 7.85 (d, J = 7.6 Hz, 1H),
7.54-7.51 (m, 2H), 7.42-7.38 (m, 1H), 3.87 (q, J = 6.0 Hz, 2H), 2.98 (s, 1H),
2.76 (t, J = 6.0 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ ppm 192.1, 135.8, 133.7,
133.3, 128.1, 126.5, 94.4, 78.2, 60.8, 23.8.
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2-(4-hydroxy-4-phenylbut-1-yn-1-yl)benzaldehyde (1b). Pale yellow solid (1.0
g, 80%). mp: 56-58 °C. 1H NMR (400 MHz, CDCl3) δ ppm 10.24 (s, 1H), 7.83
(d, J = 7.6 Hz, 1H), 7.52-7.42 (m, 4H), 7.41-7.35 (m, 3H), 7.33-7.29 (m, 1H),
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4.99 (t, J = 6.0 Hz, 1H), 3.07 (s, 1H), 2.94 (d, J = 6.0 Hz, 2H). C NMR (100
MHz, CDCl3) δ ppm 192.0, 142.6, 136.0, 133.6, 133.3, 128.5, 128.2, 128.1,
128.0, 126.3, 125.7, 93.7, 79.0, 72.4, 30.5.
2-(4-hydroxy-4-(o-tolyl)but-1-yn-1-yl)benzaldehyde (1c). Pale yellow oil (1.06 g,
80%). 1H NMR (400 MHz, CDCl3) δ ppm 10.26 (s, 1H), 7.82 (d, J = 7.6 Hz, 1H),
7.56 (d, J = 6.8 Hz, 1H), 7.51-7.45 (m, 2H), 7.39-7.35 (m, 1H), 7.26-7.17 (m,
2H), 7.14 (d, J = 7.2 Hz, 1H), 5.24-5.20 (m, 1H), 3.12 (s, 1H), 2.90-2.88 (m,
2H), 2.35 (s, 3H). 13C NMR (100 MHz, CDCl3) δ ppm 192.0, 140.6, 135.9,
134.4, 133.6, 133.3, 130.3, 128.1, 128.1, 127.7, 126.4, 126.2, 125.1, 93.9,
78.7, 68.8, 29.2, 19.0.
2-(4-hydroxy-4-(m-tolyl)but-1-yn-1-yl)benzaldehyde (1d). Pale yellow oil (1.08
g, 82%). 1H NMR (400 MHz, CDCl3) δ ppm 10.23 (s, 1H), 7.81 (d, J = 7.6 Hz,
1H), 7.50-7.44 (m, 2H), 7.36 (t, J = 7.2 Hz, 1H), 7.27-7.19 (m, 3H), 7.11 (d, J =
6.8 Hz, 1H), 4.93 (t, J = 6.0 Hz, 1H), 3.17 (s, 1H), 2.92-2.90 (m, 2H), 2.34 (s,
3H). 13C NMR (100 MHz, CDCl3) δ ppm 192.0, 142.5, 138.0, 135.9, 133.6,
133.3, 128.7, 128.3, 128.1, 127.9, 126.5, 126.4, 122.7, 93.8, 78.8, 72.4, 30.4,
21.3.
2-(4-hydroxy-4-(p-tolyl)but-1-yn-1-yl)benzaldehyde (1e). Pale yellow oil (1.03 g,
78%). 1H NMR (400 MHz, CDCl3) δ ppm 10.24 (s, 1H), 7.82 (d, J = 7.6 Hz, 1H),
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7.51-7.45 (m, 2H), 7.39-7.35 (m, 1H), 7.31 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.0
Hz, 2H), 4.95 (t, J = 6.0 Hz, 1H), 3.01 (s, 1H), 2.93-2.91 (m, 2H), 2.34 (s, 3H).
13C NMR (100 MHz, CDCl3) δ ppm 192.0, 139.6, 137.7, 136.0, 133.6, 133.3,
129.1, 128.1, 127.9, 126.5, 125.7, 93.9, 78.8, 72.3, 30.4, 21.1.
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2-(4-hydroxy-4-(4-methoxyphenyl)but-1-yn-1-yl)benzaldehyde
(1f).
Pale
yellow oil (1.18 g, 84%). 1H NMR (400 MHz, CDCl3) δ ppm 10.24 (s, 1H), 7.82
(d, J = 7.6 Hz, 1H), 7.51-7.45 (m, 2H), 7.39 (d, J = 7.2 Hz, 1H), 7.34 (d, J = 8.0
Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 4.96-4.92 (m, 1H), 3.79 (s, 3H), 3.06 (s, 1H),
13
2.97-2.86 (m, 2H). C NMR (100 MHz, CDCl3) δ ppm 192.0, 159.2, 136.0,
134.8, 133.6, 133.3, 128.1, 127.9, 127.0, 126.5, 113.8, 93.9, 78.8, 72.1, 55.2,
30.4.
2-(4-(4-chlorophenyl)-4-hydroxybut-1-yn-1-yl)benzaldehyde (1g). Pale yellow
oil (1.21 g, 85%). 1H NMR (400 MHz, CDCl3) δ ppm 10.26 (s, 1H), 7.82 (d, J =
7.6 Hz, 1H), 7.53-7.49 (m, 1H), 7.45 (d, J = 6.8 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H),
7.37-7.31 (m, 4H), 4.97 (t, J = 6.4 Hz, 1H), 3.40 (s, 1H), 2.90 (d, J = 6.4 Hz,
2H). 13C NMR (100 MHz, CDCl3) δ ppm 192.0, 141.1, 135.9, 133.7, 133.5,
133.4, 128.6, 128.5, 128.3, 127.1, 125.9, 93.2, 79.4, 71.7, 30.6.
2-(4-(4-bromophenyl)-4-hydroxybut-1-yn-1-yl)benzaldehyde (1h). Yellow oil
(1.37 g, 83%). 1H NMR (400 MHz, CDCl3) δ ppm 10.27 (s, 1H), 7.83-7.81 (m,
1H), 7.53-7.45 (m, 4H), 7.41 (t, J = 7.6 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 4.96 (t,
13
J = 6.0 Hz, 1H), 3.37 (s, 1H), 2.90 (d, J = 6.0 Hz, 2H). C NMR (100 MHz,
CDCl3) δ ppm 191.9, 141.6, 135.9, 133.7, 133.4, 131.5, 128.7, 128.3, 127.5,
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2-(4-hydroxy-4-(4-(trifluoromethyl)phenyl)but-1-yn-1-yl)benzaldehyde
(1i).
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Pale yellow solid (1.14 g, 72%). mp: 76-78 °C. H NMR (400 MHz, CDCl3) δ
ppm 10.26 (s, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 8.4 Hz, 2H), 7.55 (d, J
= 8.4 Hz, 2H), 7.51-7.49 (m, 1H), 7.45 (d, J = 6.4 Hz, 1H), 7.41 (t, J = 7.6 Hz,
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1H), 5.06 (t, J = 6.0 Hz, 1H), 3.65 (s, 1H), 2.99-2.88 (m, 2H). C NMR (100
MHz, CDCl3) δ ppm 192.0, 146.6, 135.9, 133.7, 133.4, 130.0 (q, 1JC-F = 32 Hz),
2
129.0, 128.3, 126.1, 125.7, 125.3 (q, JC-F = 4 Hz), 122.7, 92.9, 79.7, 71.7,
30.6.
2-(4-hydroxy-4-(naphthalen-2-yl)but-1-yn-1-yl)benzaldehyde (1j). Pale yellow
oil (1.19 g, 79%). 1H NMR (400 MHz, CDCl3) δ ppm 10.27 (s, 1H), 7.85 (s, 1H),
7.82-7.76 (m, 4H), 7.52-7.49 (m, 1H), 7.46-7.40 (m, 4H), 7.35-7.30 (m, 1H),
5.13-5.10 (m, 1H), 3.35 (s, 1H), 2.98 (d, J = 6.4 Hz, 2H). 13C NMR (100 MHz,
CDCl3) δ ppm 191.9, 140.0, 135.9, 133.6, 133.3, 133.1, 133.0, 128.2, 128.2,
128.1, 127.9, 127.6, 126.2, 126.2, 126.0, 124.6, 123.6, 93.7, 79.1, 72.5, 30.5.
HRMS (ESI) m/z Calcd for C21H16O2Na: [M+Na]+ = 323.1043. Found:
323.1045.
2-(4-(benzo[d][1,3]dioxol-5-yl)-4-hydroxybut-1-yn-1-yl)benzaldehyde
(1k).
Yellow oil (1.10 g, 75%). 1H NMR (400 MHz, CDCl3) δ ppm 10.24 (s, 1H), 7.82
(d, J = 7.6 Hz, 1H), 7.52-7.45 (m, 2H), 7.38 (t, J = 7.6 Hz, 1H), 6.93 (s, 1H),
6.86 (d, J = 8.0 Hz, 1H), 6.77 (d, J = 8.0 Hz, 1H), 5.94 (s, 1H), 4.89 (t, J = 6.0
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Hz, 1H), 3.16 (s, 1H), 2.94-2.83 (m, 2H). C NMR (100 MHz, CDCl3) δ ppm
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192.0, 147.7, 147.2, 136.6, 135.9, 133.6, 133.3, 128.1, 128.0, 126.4, 119.2,
108.0, 106.2, 101.0, 93.7, 78.9, 72.3, 30.5. HRMS (ESI) m/z Calcd for
C18H14O4Na: [M+Na]+ = 317.0784. Found: 317.0782.
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2-(4-hydroxypent-1-yn-1-yl)benzaldehyde (1l). Yellow oil (0.76 g, 81%). H
NMR (400 MHz, CDCl3) δ ppm 10.45 (s, 1H), 7.55-7.52 (m, 2H), 7.43-7.39 (m,
1H), 4.16-4.08 (m, 1H), 2.87 (s, 1H), 2.73-2.61 (m, 2H), 1.36 (d, J = 6.0 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ ppm 191.9, 135.9, 133.7, 133.4, 128.2,
128.1, 126.5, 94.0, 78.8, 66.3, 30.0, 22.5. HRMS (ESI) m/z Calcd for C12H13O2:
[M+H]+ = 189.0910. Found: 189.0909.
2-(4-cyclopropyl-4-hydroxybut-1-yn-1-yl)benzaldehyde (1m). Yellow oil (0.75 g,
70%). 1H NMR (400 MHz, CDCl3) δ ppm 10.48 (s, 1H), 7.87 (d, J = 7.6 Hz, 1H),
7.53 (d, J = 4.4 Hz, 2H), 7.43-7.39 (m, 1H), 3.24-3.19 (m, 1H), 2.88-2.76 (m,
2H), 2.55 (s, 1H), 1.14-1.06 (m, 1H), 0.61-0.57 (m, 2H), 0.45-0.40 (m, 1H),
0.35-0.31 (m, 1H). 13C NMR (100 MHz, CDCl3) δ ppm 192.0, 136.0, 133.6,
133.3, 128.1, 127.9, 126.7, 94.3, 78.5, 74.7, 28.3, 17.0, 2.9, 2.6. HRMS (ESI)
m/z Calcd for C14H14O2Na: [M+Na]+ = 237.0886. Found: 237.0887.
2-(4-hydroxy-6-phenylhex-5-en-1-yn-1-yl)benzaldehyde (1n). Brown oil (1.04 g,
75%). 1H NMR (400 MHz, CDCl3) δ ppm 10.43 (s, 1H), 7.83 (d, J = 8.0 Hz, 1H),
7.50-7.47 (m, 2H), 7.39-7.35 (m, 3H), 7.30 (d, J = 7.6 Hz, 1H), 7.25-7.21 (m,
1H), 6.70 (d, J = 16.0 Hz, 1H), 6.33 (dd, J = 16, 6.4 Hz, 1H), 4.59 (q, J = 6.0 Hz,
1H), 3.06 (s, 1H), 2.88-2.78 (m, 2H). 13C NMR (100 MHz, CDCl3) δ ppm 191.9,
136.2, 135.9, 133.6, 133.4, 131.2, 130.2, 128.5, 128.2, 128.1, 127.8, 126.5,
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126.3, 93.4, 79.0, 70.9, 28.8. HRMS (ESI) m/z Calcd for C19H16O2Na: [M+Na]+
= 299.1043. Found: 299.1040.
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2-(4-hydroxy-4,4-diphenylbut-1-yn-1-yl)benzaldehyde (1o). Pale yellow solid
(1.17 g, 72%). mp: 110-112 °C . 1H NMR (400 MHz, CDCl3) δ ppm 9.92 (s, 1H),
7.75 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 7.6 Hz, 4H), 7.43 (t, J = 7.6 Hz, 1H),
7.38-7.32 (m, 6H), 7.26 (t, J = 7.2 Hz, 2H), 3.48 (s, 1H), 3.45 (s, 2H). 13C NMR
(100 MHz, CDCl3) δ ppm 191.7, 145.4, 136.1, 133.5, 133.4, 128.4, 128.2,
127.3, 126.0, 125.8, 93.3, 80.3, 77.7, 34.7. HRMS (ESI) m/z Calcd for
C23H18O2Na: [M+Na]+ = 349.1199. Found: 349.1197.
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2-(4-hydroxybut-1-yn-1-yl)-4-methylbenzaldehyde (1p). Pale yellow solid (0.73
g, 78%). mp: 22-24 °C. 1H NMR (400 MHz, CDCl3) δ ppm 10.37 (s, 1H), 7.76
(d, J = 8.0 Hz, 1H), 7.33 (s, 1H), 7.22 (d, J = 8.0 Hz, 1H), 3.87 (t, J = 6.4 Hz,
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2H), 2.75 (t, J = 6.4 Hz, 2H), 2.56 (s, 1H), 2.38 (s, 1H). C NMR (100 MHz,
CDCl3) δ ppm 191.6, 144.8, 133.9, 133.8, 129.2, 128.6, 126.3, 93.7, 78.6, 61.0,
24.0, 21.6. HRMS (ESI) m/z Calcd for C12H13O2: [M+H]+ = 189.0910. Found:
189.0908.
2-(4-hydroxybut-1-yn-1-yl)-5-methylbenzaldehyde (1q). Yellow solid (0.76 g,
81%). mp: 44-46 °C . 1H NMR (400 MHz, CDCl3) δ ppm 10.40 (s, 1H), 7.65 (s,
1H), 7.40 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H), 3.86 (t, J = 6.4 Hz, 2H),
2.87 (s, 1H), 2.75 (t, J = 6.4 Hz, 2H), 2.38 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ ppm 192.2, 138.4, 135.7, 134.6, 133.2, 128.4, 123.7, 93.3, 78.2, 60.9, 23.9,
21.1. HRMS (ESI) m/z Calcd for C12H13O2: [M+H]+ = 189.0910. Found:
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4-chloro-2-(4-hydroxybut-1-yn-1-yl)benzaldehyde (1r). Pale yellow oil (0.89 g,
85%). 1H NMR (400 MHz, CDCl3) δ ppm 10.38 (s, 1H), 7.79 (d, J = 8.4 Hz, 1H),
7.49 (s, 1H), 7.37 (d, J = 8.4 Hz, 1H), 3.88 (t, J = 6.4 Hz, 2H), 2.84 (s, 1H), 2.76
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(t, J = 6.4 Hz, 2H). C NMR (100 MHz, CDCl3) δ ppm 190.8, 140.1, 134.2,
133.1, 129.3, 129.6, 128.0, 95.9, 77.0, 60.7, 23.8. HRMS (ESI) m/z Calcd for
C11H10ClO2: [M+H]+ = 209.0364. Found: 209.0363.
5-chloro-2-(4-hydroxybut-1-yn-1-yl)benzaldehyde (1s). Pale yellow oil (0.82 g,
79%). 1H NMR (400 MHz, CDCl3) δ ppm 10.39 (s, 1H), 7.81 (s, 1H), 7.50-7.44
(m, 2H), 3.87 (t, J = 6.4 Hz, 2H), 2.76 (t, J = 6.4 Hz, 2H), 2.65 (s, 1H). 13C NMR
(100 MHz, CDCl3) δ ppm 190.7, 137.0, 134.6, 133.7, 127.7, 124.9, 95.5, 77.2,
60.8, 23.9. HRMS (ESI) m/z Calcd for C11H10ClO2: [M+H]+ = 209.0364. Found:
209.0363.
3-(4-hydroxybut-1-yn-1-yl)-2-naphthaldehyde (1t). Yellow solid (0.82 g, 73%).
mp: 64-66 °C . 1H NMR (400 MHz, CDCl3) δ ppm 10.45 (s, 1H), 8.26 (s, 1H),
7.91 (s, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.55 (t, J = 7.2
Hz, 1H), 7.48 (t, J = 7.2 Hz, 1H), 3.92 (t, J = 6.4 Hz, 2H), 3.30 (s, 1H), 2.79 (t, J
= 6.4 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ ppm 192.1, 135.2, 133.3, 132.3,
131.6, 131.4, 129.6, 129.3, 127.4, 127.3, 120.3, 93.1, 78.9, 60.9, 24.0. HRMS
(ESI) m/z Calcd for C15H13O2: [M+H]+ = 225.0910. Found: 225.0909.
1-(2-(4-hydroxybut-1-yn-1-yl)phenyl)ethanone (1u). Pale yellow oil (0.77 g,
82%). 1H NMR (400 MHz, CDCl3) δ ppm 7.75-7.73 (m, 1H), 7.52-7.50 (m, 1H),
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7.45-7.41 (m, 1H), 7.38-7.34 (m, 1H), 3.85 (t, J = 6.0 Hz, 2H), 3.23 (s, 1H),
2.70 (t, J = 6.0 Hz, 2H), 2.66 (s, 3H). 13C NMR (100 MHz, CDCl3) δ ppm 199.9,
139.8, 134.0, 131.5, 129.1, 127.7, 122.0, 92.8, 81.9, 60.9, 29.2, 24.2. HRMS
(ESI) m/z Calcd for C12H13O2: [M+H]+ = 189.0910. Found: 189.0909.
2-(5-hydroxypent-1-yn-1-yl)benzaldehyde (1v). Pale yellow oil (0.71 g, 76%).
1H NMR (400 MHz, CDCl3) δ ppm 10.50 (s, 1H), 7.86 (d, J = 7.6 Hz, 1H),
7.53-7.48 (m, 2H), 7.40-7.36 (m, 1H), 3.82 (t, J = 6.4 Hz, 2H), 2.62 (t, J = 7.2
Hz, 2H), 2.58 (s, 1H), 1.93-1.87 (m, 2H). 13C NMR (100 MHz, CDCl3) δ ppm
192.2, 135.8, 133.7, 133.2, 127.9, 127.4, 127.1, 97.1, 76.6, 61.2, 31.1, 16.0.
HRMS (ESI) m/z Calcd for C12H13O2: [M+H]+ = 189.0910. Found: 189.0909.
2-(6-hydroxyhex-1-yn-1-yl)benzaldehyde (1w). Pale yellow oil (0.71 g, 70%).
1H NMR (400 MHz, CDCl3) δ ppm 10.52 (s, 1H), 7.87 (d, J = 7.6 Hz, 1H),
7.54-7.49 (m, 2H), 7.40-7.36 (m, 1H), 3.72 (t, J = 6.0 Hz, 2H), 2.54 (t, J = 6.8
Hz, 2H), 2.10 (s, 1H), 1.79-1.72 (m, 4H). 13C NMR (100 MHz, CDCl3) δ ppm
192.2, 135.8, 133.7, 133.3, 127.9, 127.6, 127.0, 97.6, 76.0, 62.1, 31.8, 24.8,
19.3. HRMS (ESI) m/z Calcd for C13H15O2: [M+H]+ = 203.1067. Found:
203.1065.
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Characterization Data of Products
(9E,19E)-10,20-diiodo-5,9,15,19-diepoxy-5,7,8,15,17,18-hexahydrodibenzo[c,
k][1,9]dioxacyclohexadecine (2a). White solid (45.0 mg, 75%). mp: 154-156 °C.
1H NMR (400 MHz, CDCl3) δ ppm 7.39 (d, J = 8.0 Hz, 2H), 7.36-7.32 (m, 2H),
7.25-7.21 (m, 2H), 7.11 (d, J = 7.2 Hz, 2H), 5.93 (s, 2H), 4.55-4.49 (m, 2H),
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3.83-3.79 (m, 2H), 3.48-3.40 (m, 2H), 2.51-2.46 (m, 2H). 13C NMR (100 MHz,
CDCl3) δ ppm 150.7, 131.2, 129.4, 128.8, 127.4, 126.9, 125.2, 97.2, 75.8, 64.7,
37.1. IR (neat, cm-1): 2865, 1614, 1483, 1118, 1098, 1004, 969, 758. HRMS
(ESI) m/z Calcd for C22H19I2O4: [M+H]+ = 600.9367. Found: 600.9367.
(9E,19E)-10,20-diiodo-5,9,15,19-diepoxy-7,17-diphenyl-5,7,8,15,17,18-hexah
ydrodibenzo[c,k][1,9]dioxacyclohexadecine (2b). White solid (42.9 mg, 57%).
mp: 190-192 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.62 (d, J = 7.2 Hz, 4H),
7.52 (t, J = 7.2 Hz, 4H), 7.44-7.40 (m, 4H), 7.35 (t, J = 7.6 Hz, 2H), 7.24-7.20
(m, 2H), 6.89 (d, J = 7.2 Hz, 2H), 5.85 (s, 2H), 5.55 (dd, J = 11.2, 2.4 Hz, 2H),
3.54-3.47 (m, 2H), 2.59 (dd, J = 14.4, 2.4 Hz, 2H). 13C NMR (100 MHz, CDCl3)
δ ppm 150.0, 141.1, 131.4, 129.2, 128.9, 128.8, 128.4, 127.4, 127.3, 126.9,
124.7, 94.1, 76.2, 75.8, 46.0. IR (neat, cm-1): 2922, 1613, 1454, 1168, 1075,
988, 757, 697. HRMS (ESI) m/z Calcd for C34H27I2O4: [M+H]+ = 752.9993.
Found: 752.9990.
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(9E,19E)-10,20-diiodo-5,9,15,19-diepoxy-7,17-di-o-tolyl-5,7,8,15,17,18-hexah
ydrodibenzo[c,k][1,9]dioxacyclohexadecine (2c). White solid (49.9 mg, 64%).
mp: 246-248 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.68 (s, 2H), 7.44-7.34 (m,
6H), 7.32-7.21 (m, 6H), 6.95 (d, J = 7.2 Hz, 2H), 5.89-5.87 (m, 2H), 5.81 (s,
2H), 3.42-3.26 (m, 2H), 2.59 (s, 6H), 2.53 (dd, J = 14.8, 2.0 Hz, 2H). 13C NMR
(100 MHz, CDCl3) δ ppm 150.0, 139.2, 135.6, 131.4, 130.6, 129.3, 128.8,
128.0, 127.4, 126.9, 126.0, 124.7, 93.9, 76.1, 71.3, 44.7, 19.1. IR (neat, cm-1):
2920, 1616, 1485, 1079, 1038, 991, 757, 578. HRMS (ESI) m/z Calcd for
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C36H31I2O4: [M+H]+ = 781.0306. Found: 781.0307.
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(9E,19E)-10,20-diiodo-5,9,15,19-diepoxy-7,17-di-m-tolyl-5,7,8,15,17,18-hexah
ydrodibenzo[c,k][1,9]dioxacyclohexadecine (2d). White solid (49.1 mg, 63%).
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mp: 222-224 °C. H NMR (400 MHz, CDCl3) δ ppm 7.43-7.40 (m, 8H),
7.37-7.33 (m, 2H), 7.24-7.20 (m, 4H), 6.89 (d, J = 6.8 Hz, 2H), 5.85 (s, 2H),
5.52 (dd, J = 11.2, 2.4 Hz, 2H), 3.52-3.46 (m, 2H), 2.59 (dd, J = 14.4, 2.4 Hz,
2H), 2.48 (s, 6H). 13C NMR (100 MHz, CDCl3) δ ppm 150.1, 141.1, 138.6,
131.4, 129.2, 129.1, 128.8, 128.8, 128.0, 127.4, 126.8, 124.7, 124.2, 94.0,
76.1, 75.9, 45.9, 21.6. IR (neat, cm-1): 2919, 1613, 1484, 1080, 1040, 992, 756,
705. HRMS (ESI) m/z Calcd for C36H31I2O4: [M+H]+ = 781.0306. Found:
781.0303.
(9E,19E)-10,20-diiodo-5,9,15,19-diepoxy-7,17-di-p-tolyl-5,7,8,15,17,18-hexah
ydrodibenzo[c,k][1,9]dioxacyclohexadecine (2e). White solid (46.8 mg, 60%).
mp: 232-234 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.51 (d, J = 8.0 Hz, 4H),
7.41 (d, J = 7.6 Hz, 2H), 7.35 (d, J = 7.6 Hz, 2H), 7.32 (d, J = 7.6 Hz, 4H), 7.21
(t, J = 7.2 Hz, 2H), 6.88 (d, J = 7.6 Hz, 2H), 5.84 (s, 2H), 5.51 (dd, J = 11.6, 2.4
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Hz, 2H), 3.52-3.45 (m, 2H), 2.57 (dd, J = 14.4, 2.4 Hz, 2H), 2.44 (s, 6H). C
NMR (100 MHz, CDCl3) δ ppm 150.1, 138.2, 138.1, 131.4, 129.6, 129.2, 128.7,
127.4, 127.3, 126.8, 124.7, 94.0, 76.1, 75.7, 46.0, 21.3. IR (neat, cm-1): 2918,
1610, 1482, 1082, 1039, 991, 814, 753. HRMS (ESI) m/z Calcd for C36H31I2O4:
[M+H]+ = 781.0306. Found: 781.0301.
(9E,19E)-10,20-diiodo-5,9,15,19-diepoxy-7,17-bis(4-methoxyphenyl)-5,7,8,15,
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17,18-hexahydrodibenzo[c,k][1,9]dioxacyclohexadecine (2f). White solid (47.1
mg, 58%). mp: 204-206 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.54 (d, J = 8.4
Hz, 4H), 7.42 (d, J = 7.6 Hz, 2H), 7.35 (t, J = 7.6 Hz, 2H), 7.21 (t, J = 7.2 Hz,
2H), 7.04 (d, J = 8.4 Hz, 4H), 6.86 (d, J = 7.2 Hz, 2H), 5.83 (s, 2H), 5.49 (dd, J
= 11.2, 2.4 Hz, 2H), 3.89 (s, 6H), 3.52-3.46 (m, 2H), 2.57 (dd, J = 14.4, 2.4 Hz,
2H). 13C NMR (100 MHz, CDCl3) δ ppm 159.7, 150.2, 133.0, 131.4, 129.2,
128.7, 128.6, 127.5, 126.8, 124.7, 114.3, 93.9, 76.1, 75.4, 55.4, 46.0. IR (neat,
cm-1): 2925, 1614, 1249, 1175, 1034, 985, 830, 761. HRMS (ESI) m/z Calcd
for C36H31I2O6: [M+H]+ = 813.0205. Found: 813.0198.
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(9E,19E)-10,20-diiodo-5,9,15,19-diepoxy-7,17-bis(4-chlorophenyl)-10,20-diiod
o-5,7,8,15,17,18-hexahydrodibenzo[c,k][1,9]dioxacyclohexadecine (2g). White
solid (54.1 mg, 66%). mp: 212-214 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.55
(d, J = 8.4 Hz, 4H), 7.48 (d, J = 8.4 Hz, 4H), 7.42 (d, J = 7.6 Hz, 2H), 7.34 (t, J
= 7.2 Hz, 2H), 7.23 (t, J = 6.8 Hz, 2H), 6.86 (d, J = 7.2 Hz, 2H), 5.79 (s, 2H),
5.49 (dd, J = 11.6, 2.4 Hz, 2H), 3.49-3.42 (m, 2H), 2.55 (dd, J = 14.4, 2.4 Hz,
2H). 13C NMR (100 MHz, CDCl3) δ ppm 149.2, 139.6, 134.2, 131.2, 129.4,
129.2, 128.9, 128.6, 127.0, 124.7, 94.1, 76.4, 75.1, 45.8. IR (neat, cm-1): 2917,
1614, 1482, 1080, 1037, 994, 823, 755. HRMS (ESI) m/z Calcd for
C34H25Cl2I2O4: [M+H]+ = 820.9214. Found: 820.9208.
(9E,19E)-10,20-diiodo-5,9,15,19-diepoxy-7,17-bis(4-bromophenyl)-10,20-diiod
o-5,7,8,15,17,18-hexahydrodibenzo[c,k][1,9]dioxacyclohexadecine (2h). White
solid (58.1 mg, 64%). mp: 236-238 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.64
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(d, J = 8.0 Hz, 4H), 7.49 (d, J = 8.4 Hz, 4H), 7.42 (d, J = 6.8 Hz, 2H), 7.38-7.34
(m, 2H), 7.25-7.21 (m, 2H), 6.86 (d, J = 6.8 Hz, 2H), 5.80 (s, 2H), 5.48 (dd, J =
11.6, 2.4 Hz, 2H), 3.48-3.42 (m, 2H), 2.55 (dd, J = 14.4, 2.4 Hz, 2H). 13C NMR
(100 MHz, CDCl3) δ ppm 149.4, 140.1, 132.1, 131.2, 129.4, 129.0, 128.9,
127.0, 127.0, 124.7, 122.4, 94.1, 76.4, 75.1, 45.8. IR (neat, cm-1): 2918, 1615,
1480, 1078, 1037, 993, 819, 754. HRMS (ESI) m/z Calcd for C34H25Br2I2O4:
[M+H]+ = 908.8203. Found: 908.8208.
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(9E,19E)-10,20-diiodo-5,9,15,19-diepoxy-7,17-bis(4-(trifluoromethyl)phenyl)-5,
7,8,15,17,18-hexahydrodibenzo[c,k][1,9]dioxacyclohexadecine (2i). White
solid (49.7 mg, 56%). mp: 214-216 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.79
(d, J = 8.4 Hz, 4H), 7.75 (d, J = 8.4 Hz, 4H), 7.44 (d, J = 7.2 Hz, 2H), 7.38 (t, J
= 7.2 Hz, 2H), 7.28-7.24 (m, 2H), 6.90 (d, J = 7.2 Hz, 2H), 5.82 (s, 2H), 5.60
(dd, J = 11.6, 2.4 Hz, 2H), 3.51-3.45 (m, 2H), 2.59 (dd, J = 14.4, 2.4 Hz, 2H).
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13C NMR (100 MHz, CDCl3) δ ppm 149.1, 145.3, 131.2, 130.8 (q, JC-F = 33
2
Hz), 129.6, 129.0, 127.5, 127.2, 126.9, 126.0 (d, JC-F = 3 Hz), 125.4, 124.7,
94.3, 76.6, 75.2, 45.9. IR (neat, cm-1): 2924, 1617, 1326, 1125, 1167, 994, 840,
759. HRMS (ESI) m/z Calcd for C36H25F6I2O4: [M+H]+ = 888.9741. Found:
888.9741.
(9E,19E)-10,20-diiodo-5,9,15,19-diepoxy-7,17-di(naphthalen-2-yl)-5,7,8,15,17
,18-hexahydrodibenzo[c,k][1,9]dioxacyclohexadecine (2j). White solid (53.7
mg, 63%). mp: 232-234 °C. 1H NMR (400 MHz, CDCl3) δ ppm 8.12 (s, 2H),
8.04 (d, J = 8.8 Hz, 2H), 7.99 (d, J = 7.6 Hz, 2H), 7.95 (d, J = 7.2 Hz, 2H),
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7.79-7.76 (m, 2H), 7.62-7.55 (m, 4H), 7.45 (d, J = 7.2 Hz, 2H), 7.39-7.35 (m,
2H), 7.25-7.21 (m, 2H), 6.88 (d, J = 7.2 Hz, 2H), 5.91 (s, 2H), 5.78 (dd, J = 11.6,
2.8 Hz, 2H), 3.68-3.61 (m, 2H), 2.69 (dd, J = 14.8, 2.8 Hz, 2H). 13C NMR (100
MHz, CDCl3) δ ppm 150.0, 138.4, 133.5, 133.4, 131.5, 129.3, 129.1, 128.9,
128.0, 127.9, 127.4, 126.9, 126.9, 126.6, 126.4, 124.8, 124.6, 94.2, 76.3, 76.1,
45.8. IR (neat, cm-1): 2919, 1608, 1482, 1080, 1037, 989, 819, 753. HRMS
(ESI) m/z Calcd for C42H31I2O4: [M+H]+ = 853.0306. Found: 853.0300.
(9E,19E)-7,17-bis(benzo[d][1,3]dioxol-5-yl)-10,20-diiodo-5,9,15,19-diepoxy-5,
7,8,15,17,18-hexahydrodibenzo[c,k][1,9]dioxacyclohexadecine (2k). White
solid (45.9 mg, 55%). mp: 218-220 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.41
(d, J = 7.2 Hz, 2H), 7.37-7.33 (m, 2H), 7.24-7.20 (m, 2H), 7.10-7.07 (m, 4H),
6.91 (t, J = 8.0 Hz, 4H), 6.06-6.03 (m, 4H), 5.85 (s, 2H), 5.42 (dd, J = 11.6, 2.4
Hz, 2H), 3.49-3.42 (m, 2H), 2.55 (dd, J = 14.4, 2.4 Hz, 2H). 13C NMR (100 MHz,
CDCl3) δ ppm 149.9, 148.4, 147.7, 135.0, 131.4, 129.2, 128.8, 127.3, 126.9,
124.7, 121.0, 108.4, 107.2, 101.3, 93.9, 76.2, 75.6, 46.0. IR (neat, cm-1): 2921,
1613, 1484, 1247, 1039, 987, 797, 757. HRMS (ESI) m/z Calcd for C36H27I2O8:
[M+H]+ = 840.9790. Found: 840.9788.
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(9E,19E)-10,20-diiodo-5,9,15,19-diepoxy-7,17-dimethyl-5,7,8,15,17,18-hexah
ydrodibenzo[c,k][1,9]dioxacyclohexadecine (2l). White solid (22.6 mg, 36%).
mp: 158-160 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.41 (d, J = 7.6 Hz, 2H),
7.36-7.32 (m, 2H), 7.25-7.21 (m, 2H), 7.07 (d, J = 7.6 Hz, 2H), 6.11 (s, 2H),
4.65-4.58 (m, 2H), 3.21-3.14 (m, 2H), 2.39 (dd, J = 14.4, 2.0 Hz, 2H), 1.41 (d, J
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= 6.0 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ ppm 150.3, 131.6, 129.2, 128.6,
127.3, 126.7, 124.7, 93.1, 75.7, 68.0, 44.6, 18.6. IR (neat, cm-1): 2925, 1615,
1374, 1176, 1128, 1067, 1001, 758. HRMS (ESI) m/z Calcd for C24H23I2O4:
[M+H]+ = 628.9680. Found: 628.9675.
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(9E,19E)-7,17-dicyclopropyl-10,20-diiodo-5,9,15,19-diepoxy-5,7,8,15,17,18-h
exahydrodibenzo[c,k][1,9]dioxacyclohexadecine (2m). White solid (21.7 mg,
32%). mp: 176-178 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.40 (d, J = 7.2 Hz,
2H), 7.36-7.32 (m, 2H), 7.25-7.21 (m, 2H), 7.13 (d, J = 6.8 Hz, 2H), 6.56 (s,
2H), 3.65-3.60 (m, 2H), 3.31-3.25 (m, 2H), 2.53 (dd, J = 14.4, 2.4 Hz, 2H),
1.04-2.99 (m, 2H), 0.96-0.92 (m, 2H), 0.77-0.70 (m, 2H), 0.61-0.54 (m, 2H),
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0.23-0.17 (m, 2H). C NMR (100 MHz, CDCl3) δ ppm 150.4, 131.6, 129.1,
128.6, 127.6, 126.6, 124.8, 92.8, 77.3, 75.8, 43.0, 14.1, 6.6, -0.4. IR (neat,
cm-1): 2915, 1616, 1382, 1087, 1061, 1036, 992, 758. HRMS (ESI) m/z Calcd
for C28H27I2O4: [M+H]+ = 680.9993. Found: 680.9994.
(9E,19E)-10,20-diiodo-5,9,15,19-diepoxy-7,17-distyryl-5,7,8,15,17,18-hexahy
drodibenzo[c,k][1,9]dioxacyclohexadecine (2n). White solid (12.6 mg, 15%).
mp: 146-148 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.55 (d, J = 7.2 Hz, 4H),
7.44-7.40 (m, 6H), 7.38-7.34 (m, 4H), 7.24-7.22 (m, 2H), 7.05 (d, J = 6.8 Hz,
2H), 6.96 (d, J = 16 Hz, 2H), 6.29 (dd, J = 16, 8.4 Hz, 2H), 6.14 (s, 2H),
5.13-5.08 (m, 2H), 3.44-3.38 (m, 2H), 2.59 (dd, J = 14.4, 2.0 Hz, 2H). 13C NMR
(100 MHz, CDCl3) δ ppm 149.6, 136.0, 134.7, 131.5, 129.3, 128.8, 128.8,
128.3, 128.0, 127.3, 126.9, 126.7, 124.9, 93.6, 76.2, 74.4, 43.4. IR (neat, cm-1):
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2923, 1612, 1454, 1078, 1036, 989, 752, 695. HRMS (ESI) m/z Calcd for
C38H31I2O4: [M+H]+ = 805.0306. Found: 805.0305.
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(9E,19E)-10,20-diiodo-5,9,15,19-diepoxy-2,12-dimethyl-5,7,8,15,17,18-hexah
ydrodibenzo[c,k][1,9]dioxacyclohexadecine (2p). White solid (37.0 mg, 59%).
mp: 194-196 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.19 (s, 2H), 7.05-7.00 (m,
4H), 5.91 (s, 2H), 4.55-4.49 (m, 2H), 3.81-3.78 (m, 2H), 3.47-3.40 (m, 2H),
2.50-2.45 (m, 2H), 2.37 (s, 6H). 13C NMR (100 MHz, CDCl3) δ ppm 150.7,
139.2, 130.9, 129.3, 127.6, 125.2, 124.9, 97.2, 75.9, 64.7, 37.1, 21.6. IR (neat,
cm-1): 2892, 1615, 1450, 1098, 1040, 1010, 977, 812. HRMS (ESI) m/z Calcd
for C24H23I2O4: [M+H]+ = 628.9680. Found: 628.9686.
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(9E,19E)-10,20-diiodo-5,9,15,19-diepoxy-3,13-dimethyl-5,7,8,15,17,18-hexah
ydrodibenzo[c,k][1,9]dioxacyclohexadecine (2q). White solid (28.3 mg, 45%).
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mp: 168-170 °C. H NMR (400 MHz, CDCl3) δ ppm 7.28-7.25 (m, 2H),
7.16-7.13 (m, 2H), 6.94 (s, 2H), 5.89 (s, 2H), 4.55-4.49 (m, 2H), 3.82-3.78 (m,
13
2H), 3.46-3.38 (m, 2H), 2.50-2.45 (m, 2H), 2.36 (s, 6H). C NMR (100 MHz,
CDCl3) δ ppm 149.8, 136.7, 130.1, 128.7, 127.3, 125.7, 97.3, 75.8, 64.7, 37.0,
21.0. IR (neat, cm-1): 2863, 1616, 1495, 1103, 1036, 1010, 969, 820. HRMS
(ESI) m/z Calcd for C24H23I2O4: [M+H]+ = 628.9680. Found: 628.9680.
(9E,19E)-2,12-dichloro-10,20-diiodo-5,9,15,19-diepoxy-5,7,8,15,17,18-hexahy
drodibenzo[c,k][1,9]dioxacyclohexadecine (2r). White solid (38.1 mg, 57%).
mp: 206-208 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.42 (d, J = 1.6 Hz, 2H),
7.21-7.19 (m, 2H), 7.06 (d, J = 7.6 Hz, 2H), 5.91 (s, 2H), 4.51-4.45 (m, 2H),
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The Journal of Organic Chemistry
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3.83-3.79 (m, 2H), 3.46-3.38 (m, 2H), 2.52-2.47 (m, 2H). 13C NMR (100 MHz,
CDCl3) δ ppm 151.9, 135.4, 133.0, 128.9, 126.9, 126.7, 125.6, 96.7, 74.0, 64.7,
37.1. IR (neat, cm-1): 2918, 1609, 1474, 1100, 1033, 1009, 969, 814. HRMS
(ESI) m/z Calcd for C22H17Cl2I2O4: [M+H]+ = 668.8588. Found: 668.8599.
(9E,19E)-3,13-dichloro-10,20-diiodo-5,9,15,19-diepoxy-5,7,8,15,17,18-hexahy
drodibenzo[c,k][1,9]dioxacyclohexadecine (2s). White solid (36.1 mg, 54%).
mp: 218-220 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.34 (d, J = 8.4 Hz, 2H),
7.31-7.28 (m, 2H), 7.13-7.12 (m, 2H), 5.88 (s, 2H), 4.51-4.45 (m, 2H),
3.83-3.79 (m, 2H), 3.46-3.38 (m, 2H), 2.51-2.46 (m, 2H). 13C NMR (100 MHz,
CDCl3) δ ppm 151.0, 132.2, 130.4, 129.8, 129.4, 128.3, 125.1, 96.5, 74.5, 64.8,
36.9. IR (neat, cm-1): 2903, 1618, 1480, 1096, 1038, 1010, 967, 805. HRMS
(ESI) m/z Calcd for C22H17Cl2I2O4: [M+H]+ = 668.8588. Found: 668.8594.
(10E,22E)-11,23-diiodo-6,10,18,22-diepoxy-6,8,9,18,20,21-hexahydrodinapht
ho[2,3-c:2',3'-k][1,9]dioxacyclohexadecine (2t). White solid (42.7 mg, 61%).
mp: 204-206 °C. 1H NMR (400 MHz, CDCl3) δ ppm 7.85 (t, J = 8.4 Hz, 4H),
7.80 (s, 2H), 7.63 (s, 2H), 7.49-7.41 (m, 4H), 6.10 (s, 2H), 4.62-4.56 (m, 2H),
3.93-3.90 (m, 2H), 3.54-3.46 (m, 2H), 2.56-2.52 (m, 2H). 13C NMR (100 MHz,
CDCl3) δ ppm 151.2, 134.0, 132.3, 129.1, 128.2, 127.6, 127.4, 127.3, 126.6,
125.7, 124.5, 97.4, 76.6, 64.9, 37.4. IR (neat, cm-1): 2895, 1614, 1318, 1101,
1004, 966, 877, 746. HRMS (ESI) m/z Calcd for C30H23I2O4: [M+H]+ =
700.9680. Found: 700.9685.
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(10E,21E)-11,22-diiodo-5,10,16,21-diepoxy-5,7,8,9,16,18,19,20-octahydrodib
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