Generation of 1,3-Dimethylene-Substituted Isobenzofurans via Pd(II)-Catalyzed Selective Oxo-cyclization/SO2 Insertion Cascade of β-Alkynyl Ketones

Article abstract of DOI:10.1021/acs.joc.8b02934

A new palladium(II)-catalyzed cyclization-radical addition cascade enables the direct construction of 1,3-dimethylene-substituted isobenzofuran derivatives containing a vinyl aryl sulfone unit in good yields by treating with β-alkynyl ketones, aryl diazonium salts, and DABCO·(SO₂)₂. The oxidant-free multicomponent reaction features good substrate scope and functional group tolerance, which proceeds through a sequence of Heck coupling, oxo-cyclization, and SO₂ insertion.

Full text of DOI:10.1021/acs.joc.8b02934

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Article
Generation of 1,3-Dimethylene-Substituted Isobenzofurans via Pd(II)-Catalyzed
Selective oxo-Cyclization/SO2 Insertion Cascade of #-Alkynyl Ketones
Shuai Liu, Ke Chen, Wen-Juan Hao, Xing-Chao Tu, Shu-Jiang Tu, and Bo Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02934 • Publication Date (Web): 11 Jan 2019
Downloaded from http://pubs.acs.org on January 12, 2019
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The Journal of Organic Chemistry
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Generation of 1,3-Dimethylene-Substituted Isobenzofurans via Pd(II)-Catalyzed
Selective oxo-Cyclization/SO Insertion Cascade of β-Alkynyl Ketones
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a,1
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,a
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a
,a
Shuai Liu, Ke Chen, Wen-Juan Hao,* Xing-Chao Tu, Shu-Jiang Tu, and Bo Jiang*
a
School of Chemistry & Materials Science, Jiangsu Key Laboratory of Green Synthetic Chemistry for
1
Functional Materials, Jiangsu Normal University, Xuzhou 221116, P. R. China. These authors
contributed equally
E-mail: wjhao@jsnu.edu.cn(WJH); jiangchem@jsnu.edu.cn(BJ);
RECEIVED DATE
O
O
S
ArN BF
2
4
Me
Ar
Pd(OAc)2
R2
O
O
R2
+
MeCN, 60 oC, air
DABSO
R1
R1
Ar
ABSTRACT. A new palladium(II)-catalyzed cyclization-radical addition cascade enables the
direct construction of 1,3-dimethylene-substituted isobenzofuran derivatives containing vinyl aryl
sulfone unit in good yields by treating with β-alkynyl ketones, aryl diazonium salts and
DABCO•(SO ) (DABSO). The oxidant-free multicomponent reaction features good substrate scope
2
2
and functional group tolerance, which proceeds through a sequence of by Heck coupling, oxo-
cyclization and SO insertion
2
Introduction
Isobenzofuran is a privileged oxygen-containing bicyclic motif that widely presents in a myriad of
pharmaceuticals, chemicals and bioactive natural products as well as functional materials.1
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Furthermore, such molecules could behave as key intermediates for the preparation of natural
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products as well as pharmaceutically important products. Among the family of isobenzofurans, 1,3-
disubstituted derivatives have been found to display a broad spectrum of extraordinary biologically
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and pharmaceutically properties, such as anti-inflammatory, antihistaminic, anti-HIV activity,
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and act as farnesyl transferase inhibitor, Accordingly, substantial effort has been paid for
identifying powerful and reliable synthetic methodologies for the construction of isobenzofuran
framework, especially with 1,3-disubstituted patterns. Generally, strategies for assembling1,3-
7
disubstituted isobenzofurans include iodocyclization of 2-(1-alkynyl)benzylic alcohols, radical-
8
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triggered cycloetherification, nucleophilic epoxide ring-opening, rhodium-catalyzed triazole
1
0
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denitrogenation, oxo-Michael reaction of o-formyl chalcones, 5-exo-dig oxo-cyclization of β-
1
2
13
alkynyl ketones, transition metal-catalyzed cyclization reactions of o-bromobenzyl alcohols, and
so on. Despite these significant achievements, synthetic approaches for installing 1,3-disubstituted
isobenzofurans are still rather limited, thus requiring the development of new and efficient
strategies for their syntheses.
Over the years, radical cyclization cascades have been emerged as a powerful tool toward cyclic
molecule system in the organic community which have enabled previously inaccessible
transformations.14 Specifically, radical addition-cyclization cascades have been extensively
investigated.15 In sharp contrast, the studies on new reactivity modes of cyclization-radical
additions are quite less and pose a particular challenge in the field of radical transformations due to
1
6
the inherent difficulty of controlling radicals’ behavior. Recently, our group have established an
3
attractive cyclization-radical addition cascade in which silver-mediated C(sp )-H biphosphinylation
of β-alkynyl ketones was realized to access functionalized isochromenes through 6-endo-dig
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cyclization/phosphinyl radical addition (Scheme 1a).16a In view of this successful transformation and
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recent findings on SO insertion. We envisaged that under silver-catalyzed conditions, β-alkynyl
2
ketones 1 could procced through 6-endo-dig cyclization to generate methyleneisochromenes,
trapped by sulfonyl radical from aryldiazonium tetrafluoroborates 2 and DABCO•(SO ) (DABSO),
2
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0
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providing sulfonylated isochromenes 3. Unluckily, this transformation did not work. Interestingly,
changing the silver catalyst to palladium salt drove the reaction to furnish the unexpected sulfone-
containing isobenzofurans 4 through 5-exo-dig cyclization/S-centered radical addition sequence.
The current protocol represents the first palladium(II)-catalyzed oxo-cyclization/S-centered radical
addition cascade together with SO insertion for the stereoselective synthesis of 1,3-disubstituted
2
isobenzofurans in generally good yields without additional oxidants. Herein, we elaborate this
unprecedented and attractive multicomponent transformation of β-alkynyl ketones, which also
provides a useful method for constructing vinyl aryl sulfone scaffold.
Scheme 1. Profiles of Cyclization-Radical Additions
a) our previous work
Me
Ar Ar
Ar
O
Ar
O
P
P
O
R2
P(O)Ar2
[Ag]
O
R1
R2
R2
O
R1
R1
b) this work
O
S
O
ArN BF
2
4
Me
Ar
2
Pd(OAc)2
R2
O
O
R2
+
MeCN, 60 oC, air
DABSO
R1
R1
Ar
O
O
S
1
4
Ar
[Ag]
O
R1
R2
3
Results and Discussion
Initially, we commenced our investigation by mixing easily available β-alkynyl ketone 1a,
phenyldiazonium tetrafluoroborate (2a) and DABSO in 1:2.5:2 mole ratio at 50 °C with acetonitrile
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(
MeCN) as the solvent, catalyst, but the transformation did not proceed (Table 1, entry 1). AgTFA
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9
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was employed as the silver catalyst to improve the transformation by taking advantage of our
previous discovery, but a complex mixture was observed (entry 2). The use of Cu(TFA) did not
2
drive this transformation (entry 3). To our delight, the reaction worked well when Pd(TFA) was
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added into the above system, and the unexpected sulfone-containing isobenzofuran 4a was obtained
in 61% yield, in which the geometry of the exocyclic olefin attached by sulfonyl group is the Z-
configuration confirmed by the analogy of X-ray structure 4f. Inspired by these satisfactory results,
several others palladium salts such as PdCl Pd(dba) and Pd(OAc) that are often employed in the
2
,
2
2
catalytic transformations, were subsequently tested for this transformation (entries 5–7). The former
two led to relatively lower conversions as compared with Pd(TFA) (entries 5−6 vs 4) whereas the
2
latter one showed the best catalytic performance in this transformation, affording higher yield of 4a
(75%, entry 7). Lowering the Pd-catalyst loading resulted in the remarkably dropped yield of 4a
(65%, entry 8). As the next optimization step, we conducted the screening of a variety of reaction
media, such as 1,4-dioxane, tetrahydrofuran (THF), 1,2-dichloroethane (DCE), toluene, and N,N-
dimethylformamide (DMF), for this cyclization-radical addition cascade by using Pd(OAc) as the
2
catalyst. The experimental results indicate that all these attempts did not show any improvements
with respect to the obtainable yield of 3a (entries 9-13). The reaction efficiency was proven to
display an important temperature dependence. An increase of the temperature to 60 °C could
accelerate the conversion into 4a in the rising yield of 81% (entry 15), whereas the lower
o
conversion was observed as the reaction was conducted at either room temperature or 70 C (entries
14 and 16).
Table 1. Optimization of Reaction Conditionsa
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O
O
S
1
2
3
4
5
6
7
8
9
PhN BF4
2
Me
Ph
2a
cat.
O
O
+
solvent, t
DABSO
Ph
Ph
Ph
1
a
(
Z)-4a
o
b
entry cat (mol %)
solvent
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
temp ( C) yield (%)
1
1
1
1
1
1
1
1
1
1
2
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2
2
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0
NRc
1
2
3
4
5
6
7
8
9
10
-
50
50
50
50
50
50
50
50
50
50
50
50
50
25
60
70
AgTFA (10)
NDd
NR
61
Cu(TFA) (10)
2
Pd(TFA) (10)
2
PdCl (10)
54
2
Pd(dba) (10)
51
2
Pd(OAc) (10)
75
2
Pd(OAc) (5)
65
2
Pd(OAc) (10)
1,4-dioxane
THF
25
2
Pd(OAc) (10)
45
2
1
1
1
1
1
2
3
4
Pd(OAc) (10)
DCE
ND
NR
ND
51
2
Pd(OAc) (10)
toluene
DMF
2
Pd(OAc) (10)
2
Pd(OAc) (10)
MeCN
MeCN
MeCN
2
15
Pd(OAc) (10)
81
2
1
6
Pd(OAc) (10)
72
2
aReaction conditions: 1a (0.2 mmol), 2a (0.5 mmol), DABSO (0.4 mmol), catalyst, solvent (3.0 mL), under the air
b
c
d
conditions, 6 h. Isolated yield based on substrate 1a. No reaction (NR). No detected (ND).
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With the optimized conditions in hand, we sought to explore the scope and generality of this
palladium(II)-catalyzed cyclization-radical addition for accessing functionalized isobenzofuran
derivatives 4 (Scheme 2). Due to the products have two exocyclic alkene units, we first directed the
Z-selectivity of exocyclic alkene associated with sulfonyl group by introducing two same aryl
groups into the other exocyclic alkene unit. β-Alkynyl ketones 1 bearing aryl substituents at the
alkynyl moiety were subjected to the reaction of substrates 2 having same aryl groups under the
standard conditions, and the corresponding Z-products 4b-4f were generated with acceptable yields
and high stereoselectivity. Both electron-donating (e.g. methyl, tert-butyl and methoxy (p-
methoxyphenyl = PMP) and electron-withdrawing (e.g. chloride and bromide) groups were proven
to be compatible in the present cyclization-radical addition condition. Next, the different aryl
substituents residing in substrates 1 and 2 were evaluated to explore the stereoselectivity of
exocyclic alkene linked by two different aryl substituents. As expected, the reaction occurred
readily to deliver the corresponding products 4g-4m, 4p-4x and 4z in generally good yields but with
very poor stereoselectivity except for 4q. Electronic nature of substituents on both arylalkynyl (R1)
of substrates 1 and aryl (Ar) of substrates 2 moieties was also systematically investigated. Either
electronically rich, neutral, or poor groups would be accommodated, confirming the success of this
transformation, as the corresponding products 4 were generated in 35%-70% yields. Unluckily, β-
alkynyl ketone having a 1-naphthyl (1-Np, 1j) or tert-butyl (t-Bu, 1l) group on the alkynyl moiety
was not an appropriate candidate, as only a trace amount of products 4n and 4y were detected under
the standard conditions, respectively (Scheme 2). Notably, o-tolyl diazonium tetrafluoroborate has
been found to show the high stereoselectivity, albeit with a lower 38% yield (4q). The structures of
these isobenzofuran derivatives 4 were characterized by their NMR spectroscopy and HRMS. In the
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The Journal of Organic Chemistry
case of 4f, its structure was unequivocally confirmed by carrying out single crystal X-ray diffraction
(see Supporting Information).
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1
1
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Scheme 2. Substrate Scope for Synthesis of Products 4a
O
O
ArN BF4
Me
2
S
2
Ar
Pd(OAc)2
O
0
1
2
3
4
5
6
7
8
9
0
1
2
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0
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0
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0
1
2
3
4
5
6
7
8
9
0
R2
R2
O
+
MeCN, 60 o
C
.
DABCO (SO )
2
2
R1
R1
Ar
1
4
O
O
O
S
O
S
O
O
O
S
O
S
t
PMP
Ph
p-tolyl
C6H4 Bu-4
O
O
O
O
t
PMP
Ph
p-tolyl
C6H4 Bu-4
t
PMP
Ph
4
p-tolyl
b (60%)
4- BuC6H4
a (81%)
4
4c (48%)
4d (62%)
O
O
O
O
O
O
S
S
S
C H Br-4
Ph
C H Cl-4
6 4
6
4
O
O
O
Z/E selectivity
C H Br-4
R1
C H Cl-4
6 4
6
4
4
-BrC H4
Ph
4g-4n
g, R1 = p-tolyl (67%,a sr = 1.4b)
4
-ClC H4
6
6
4
f (52%)
4
e (62%)
4
O
4h, R1 = m-tolyl (67%, sr = 1.7)
4i, R1 = 4-EtC H4 (61%, sr = 2)
O
O
S
O
S
6
Ph
Ar
4
4
4
j, R1 = 4- BuC H (56%, sr = 2)
t
6
4
O
O
k, R1 = 4-FC H4 (58%, sr = 2)
l, R1 = 4-ClC H4 (53%, sr = 1.2)
6
Cl
6
C H Cl-4
6
4
Ar
p-4v
4m, R1 = 4-BrC H4 (64%, sr = 1)
Ph
6
Ph
4
4
o (55%, Z/E = 1.1)
4n, R1 = 1 -Np (trace)
O
4p, Ar = p-tolyl (70%, sr = 1)
4q, Ar = o-tolyl (38%, sr >20)
O
S
p-Tolyl 4r, Ar = 4-EtC H (61%, sr = 1.3)
6
4
t
O
4s, Ar = 4- BuC H (65%, sr = 3.3)
O
6
4
4t, Ar = 4-FC H (53%, sr = 1.3)
S
O
6
4
C H4tBu-4
6
R1
4u, Ar = 4-ClC H (52%, sr = 1.1)
6 4
p-Tolyl
4w-4y
4
v, Ar = 4-BrC H (59%, sr = 1.5)
O
6
4
4
4
4
w, R1 = m-tolyl (58%, sr = 5)
x, R1 = 4-ClC H (51%, sr = 1.7)
t
p-tolyl
6
4
4- BuC6H4
y, R1 = t-Bu (trace)
4
z (50%, sr = 14)
a
b
1
Isolated total yields based on substrates 1. The stereoisomeric ratio (sr) value determined by its H NMR analysis
To gain more mechanistic insight into this transformation, several control experiments were
performed. When 3.0 equivalents of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) were subjected
with the reaction of β-alkynyl ketone 1a with DABSO and p-tolyldiazonium tetrafluoroborate 2b
under the standard conditions, the generation of the desired product 4g was dramatically suppressed
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and only 10% yield of 4g was obtained (Scheme 3a), in which a TEMPO−p-tolyl adduct was
detected by LC−MS analysis. The presence of 3.0 equivalents of butylhydroxytoluene (BHT)
lowered the yield of 4g to 23%. These results indicate that the reaction might include a radical
process. Then, 1,1-diphenylethylene was added into the above reaction system, and the product 4g
and (2-tosylethene-1,1-diyl)dibenzene 5 were isolated in 28% and 42% yields, respectively,
suggesting that the transformation could involve the in-situ-generation of sulfonyl radicals from the
combination of DABSO and aryldiazonium tetrafluoroborates (Scheme 3b).
1
2
3
4
5
6
7
8
9
1
1
1
1
1
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5
6
7
8
9
0
Scheme 3. Control Experiments
O
S
O
Me
p-tolylN BF
2
4
p-tolyl
2b
O
stardard conditions
additives
O
(
a)
+
DABSO
Ph
Ph
p-tolyl
1a
4g
additives
i) TEMPO, 4g (10%), TEMPO-p-tolyl (detected by LCMS)
ii) BHT, 4g (23%)
O
S
O
stardard conditions
,1-diphenylethylene
1a
+ 2b
+
DABSO
4g (28%)
+
p-tolyl
(b)
1
Ph
5
Ph
(42%)
1
8
On the basis of these mechanistic studies and related literature, a plausible cyclization-radical
addition process was proposed as depicted in Scheme 4. Initially, the oxidative addition of the active
17
Pd(0) species, which is in situ generated from PdCl , to substrates 2 yields Pd(II) species, which
2
undergoes the addition to the carbon–carbon triple bond of 1 to give intermediate A with poor
stereoselectivity. Intermediate A loses a proton to afford intermediate B, followed by reductive
elimination to construct isobenzofuran intermediate C and regenerate the active Pd(0) species.
Subsequently, the addition of in-situ generated sulfonyl radical from DABSO and aryldiazonium
tetrafluoroborates into the alkene unit of C occurs, leading to radical intermediate D which is
converted into the final products 4 through SET and deprotonation process.
Scheme 4. Plausible Reaction Pathways
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The Journal of Organic Chemistry
O
S
O
R'
R'
R'
O
N
N
Ar
1
2
3
4
5
6
7
8
9
N
SO2 + Ar•
S
Ar
O
N
DABSO
R'
R'
R'
O
S
Ar
O
O
R
O
ArN BF
2 4
O
S
Pd(0)
Ar
C
Ar
N2
O
O
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
R
Pd(II)
ArPdBF4
Ar
D
N
Ar
R
R'
B
R'
R'
SET
H
1
DABCO
O
HBF4
O
O
S
Ar DABCO
PdBF4
H
Ar
A (Z/E)
R1
O
4
R
+H-DABCO
Ar
In conclusion, we have illustrated the first palladium(II)-catalyzed cyclization-radical addition
cascade of β-alkynyl ketones, enabling a multicomponent strategy to access 1,3-disubstituted
isobenzofurans under mild and neutral redox conditions. The current protocol allows the direct
formation of multiple chemical bonds including the C–S and C–O bonds in a single step through
Heck-type addition, oxo-cyclization, and SO insertion cascades. Importantly, the results broaden
2
the scope and concept of transition-metal-catalyzed multicomponent reactions, and the significance
of the isobenzofuran skeleton may make this radical strategy attractive for organic and medical
syntheses, thereby offering a new potential entry for the preparation of other heterocyclic
architectures. Further investigations on its mechanism and application are currently underway in
our laboratories.
Experimental Section
General Information.
All melting points are uncorrected. The NMR spectra were recorded in CDCl or DMSO-d on a 400
3
6
MHz instrument with TMS as internal standard. Chemical shifts (δ) were reported in ppm with respect
to TMS. Data are represented as follows: chemical shift, mutiplicity (s = singlet, d = doublet, t = triplet,
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m = multiplet), coupling constant (J, Hz) and integration. HRMS analyses were carried out using a
TOF-MS instrument with an ESI source. X-ray crystallographic analysis was performed with a SMART
CCD and a P4 diffractometer.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
General Procedure for the Preparation of β-Alkynyl Ketones 1a−l (Known Compounds).
PdCl (PPh ) (2 mol%) and CuI (5 mol%) were added to a solution of 2-bromobenzaldehyde or 2-
2
3 2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
iodoacetophenone (5.0 mmol), phenylacetylene (6 mmol), and Et N (5 mL). The mixture was heated at
3
o
6
0 C under N . The system was filtered by short silica, then the solvent was evaporated under reduced
2
pressure, and the residue was purified by flash chromatography with petroleum to afford the desired
1
9
products 1. Yields of the β-alkynyl ketones 1 are ranged from 78% to 90%
General Procedure for the Preparation of Aryldiazonium Salts 2a−k (Known Compounds).
Aniline 1 (10 mmol) was added to a mixture of 50% fluoroboric acid (3 mL) and distilled water (3
mL)
in ice bath. To this solution, an ice-cold solution of sodium nitrite (704 mg, 10.2 mmol) in distilled
water (3 mL) was added. After stirring for 30 mins, the precipitate was collected on a hirch funnel and
washed with small amount of ice-cold distilled water. The solid was dissolved in acetone and
precipitated with slow addition of ethyl ether. White crystalline solids were obtained after repeat this
2
0
trituration two to three times. Yields of the aryldiazonium salts 2 are ranged from 70% to 88%.
General Procedure for the Synthesis of 4
Example for the synthesis of 4a
A mixture of 1-(2-(phenylethynyl)phenyl)ethanone (1a, 0.2 mmol, 44.0 mg), phenyldiazonium
tetrafluoroborate (2a, 0.5 mmol, 96.2 mg), 1,4-diazabicyclo[2.2.2]octane-bis(sulfur dioxide) adduct
(DABSO) (3, 0.4 mmol, 96.2 mg), Pd(OAc) (10 mol %, 4.5 mg) and 3.0 mL acetonitrile (MeCN)
2
o
were added in a 10-mL reaction vial, which was sealed and heated at 60 C for 6 h until TLC
(petroleum ether: ethyl acetate= 5:1) revealed that conversion of the starting material 1a was
completed. Then the reaction mixture was concentrated by vacuum distillation and was purified by
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flash column chromatography (silica gel, mixtures of petroleum ether / acetic ester, 15:1, v/v) to
afford the desired pure products (4a, 70.6 mg, 81% yield) as yellow solid.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Amplification Reaction for the Synthesis of 4a
A mixture of 1a (1.0 mmol, 220.0 mg), 2a (2.5 mmol, 481 mg), DABSO (3, 2.0 mmol, 480 mg),
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Pd(OAc) (10 mol %, 22.5 mg) and 8.0 mL acetonitrile (MeCN) were added in a 25-mL reaction vial,
2
o
which was sealed and heated at 60 C for 6 h. Then the reaction mixture was concentrated by
vacuum distillation and was purified by flash column chromatography (silica gel, mixtures of
petroleum ether / acetic ester, 15:1, v/v) to afford the desired pure products (4a, 331.4 mg, 76%
yield) as yellow solid.
(Z)-1-(diphenylmethylene)-3-((phenylsulfonyl)methylene)-1,3-dihydroisobenzofuran (4a)
o
1
7
0.6 mg, 81% yield; yellow solid, mp 217-218 C; H NMR (400 MHz, CDCl ; δ, ppm) 8.07 (d, J = 7.6
3
Hz, 1H), 7.90-7.85 (m, 2H), 7.67-7.62 (m, 1H), 7.61-7.55 (m, 5H), 7.52-7.46 (m, 5H), 7.42 (d, J = 7.2
1
3
Hz, 1H), 7.39-7.32 (m, 3H), 7.01 (s, 1H), 6.08 (d, J = 8.0 Hz, 1H). C{1H} NMR (100 MHz, CDCl ; δ,
3
ppm) 159.4, 147.9, 143.4, 137.7, 137.3, 134.1, 133.7, 132.8, 131.7, 130.7, 130.4, 130.2, 130.0, 129.6,
-1
1
29.2, 128.7, 128.5, 127.0, 123.2, 122.1, 99.1. IR (KBr, ν, cm ). 3052, 1621, 1444, 1305, 1144, 1047,
-
760, 672. HR-MS (APCI) m/z calcd for C H O S [M-H] 435.1055, found 435.1061.
2
8
19
3
(Z)-1-(di-p-tolylmethylene)-3-(tosylmethylene)-1,3-dihydroisobenzofuran (4b)
o
1
5
7.4 mg, 60% yield; yellow solid, mp 231-232 C; H NMR (400 MHz, CDCl ; δ, ppm) 7.82 (d, J = 8.0
3
Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 7.6 Hz, 1H), 7.28 (d, J = 8.0 Hz, 5H), 7.19 (d, J = 8.0 Hz,
3H), 7.09 (d, J = 8.0 Hz, 2H), 6.33 (d, J = 8.0 Hz, 1H), 6.20 (s, 1H), 2.46 (s, 3H), 2.42 (s, 3H), 2.34 (s,
13
3
1
H). C{1H} NMR (100 MHz, CDCl ; δ, ppm) 159.6, 147.5, 143.4, 140.4, 138.3, 138.0, 135.2, 134.9,
3
34.6, 131.7, 131.5, 130.5, 130.0, 129.5, 129.3, 129.0, 128.9, 128.8, 127.3, 123.5, 123.0, 121.2, 97.8,
-1
21.6, 21.4(4), 21.4(6). IR (KBr, ν, cm ). 3087, 1618, 1458, 1310, 1141, 1044, 762, 669. HR-MS (APCI)
-
m/z calcd for C H O S [M-H] 477.1524, found 477.1526.
3
1
25
3
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(
Z)-1-(bis(4-(tert-butyl)phenyl)methylene)-3-(((4-(tert-butyl)phenyl)sulfonyl)methylene)-1,3-
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
dihydroisobenzofuran (4c)
58.0 mg, 48% yield; yellow solid, mp 236-237 C; H NMR (400 MHz, CDCl ; δ, ppm) 7.86-7.82 (m,
o
1
3
2
1
1
1
H), 7.68-7.64 (m, 2H), 7.54-7.47 (m, 5H), 7.30 (d, J = 7.2 Hz, 1H), 7.26-7.21 (m, 4H), 7.18-7.14 (m,
1
3
H), 6.22 (s, 2H), 1.40 (s, 9H), 1.39 (s, 9H), 1.26 (s, 9H). C{1H} NMR (100 MHz, CDCl ; δ, ppm)
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
59.6, 156.3, 151.6, 151.1, 147.6, 140.1, 135.1, 134.9, 134.5, 131.7, 131.6, 130.2, 130.2, 128.9, 127.2,
26.0, 125.7, 125.6, 125.1, 123.6, 122.9, 121.2, 97.9, 35.0, 34.8, 34.8, 31.4(3), 31.4(8), 31.1. IR (KBr, ν,
-1
-
cm ). 3047, 1621, 1438, 1306, 1141, 1044, 761, 671. HR-MS (APCI) m/z calcd for C H O S [M-H]
4
0
43
3
6
03.2933, found 603.2940.
(Z)-1-(bis(4-methoxyphenyl)methylene)-3-(((4-methoxyphenyl)sulfonyl)methylene)-1,3-
dihydroisobenzofuran (4d)
o
1
6
5.2 mg, 62% yield; yellow solid, mp 192-193 C; H NMR (400 MHz, CDCl ; δ, ppm) 7.92-7.88 (m,
3
2H), 7.70-7.67 (m, 2H), 7.50 (d, J = 7.6 Hz, 1H), 7.29 (s, 1H), 7.23-7.20 (m, 2H), 7.19-7.16 (m, 1H),
7
3
1
9
.01 (d, J = 8.4 Hz, 4H), 6.78-6.76 (m, 2H), 6.33 (d, J = 8.0 Hz, 1H), 6.20 (s, 1H), 3.90 (s, 3H), 3.87 (s,
1
3
H), 3.79 (s, 3H). C{1H} NMR (100 MHz, CDCl ; δ, ppm) 158.3, 155.0, 154.7, 154.7, 142.3, 130.5,
3
30.2, 127.3, 127.2, 126.9, 126.6, 126.0, 125.1, 124.6, 124.0, 118.6, 117.5, 116.4, 109.9, 109.1, 108.8,
-1
3.1, 50.8, 50.7, 50.6. IR (KBr, ν, cm ). 3062, 1616, 1445, 1307, 1139, 1047, 758, 689. HR-MS (APCI)
-
m/z calcd for C H O S [M-H] 525.1372, found 525.1369.
3
1
25
6
(Z)-1-(bis(4-chlorophenyl)methylene)-3-(((4-chlorophenyl)sulfonyl)methylene)-1,3-
dihydroisobenzofuran (4e)
o
1
6
6.9 mg, 62% yield; yellow solid, mp 233-234 C; H NMR (400 MHz, CDCl ; δ, ppm) 7.82-7.79 (m,
3
2
H), 7.60-7.54 (m, 3H), 7.51-7.45 (m, 4H), 7.40 (d, J = 7.2 Hz, 1H), 7.30-7.26 (m, 5H), 6.43 (d, J = 8.0
1
3
Hz, 1H), 6.24 (s, 1H). C{1H} NMR (100 MHz, CDCl ; δ, ppm) 159.6, 148.2, 141.4, 139.4, 135.9,
3
1
1
35.4, 135.0, 134.3, 134.1, 132.3, 132.1, 131.7, 131.6, 129.8(0), 129.8(6), 129.0, 128.6, 128.5, 123.5,
-1
21.6, 120.5, 98.2. IR (KBr, ν, cm ). 3083, 1618, 1455,1318, 1142, 1044, 763, 690. HR-MS (APCI)
-
m/z calcd for C H Cl O S [M-H] 536.9886, found 536.9887.
28 16
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The Journal of Organic Chemistry
(
Z)-1-(bis(4-bromophenyl)methylene)-3-(((4-bromophenyl)sulfonyl)methylene)-1,3-
dihydroisobenzofuran (4f)
70.1 mg, 52% yield; yellow solid, mp 243-244 C; H NMR (400 MHz, DMSO-d ; δ, ppm) 8.07 (d, J =
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
o
1
6
7
2
1
1
.6 Hz, 1H), 7.80-7.73 (m, 6H), 7.70-7.66 (m, 2H), 7.55-7.50 (m, 1H), 7.49-7.42 (m, 3H), 7.38-7.34 (m,
1
3
H), 7.05 (s, 1H), 6.29 (d, J = 8.0 Hz, 1H). C{1H} NMR (100 MHz, DMSO-d ; δ, ppm) 159. 5, 148. 3,
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
42.6, 136.7, 136.1, 133.7, 133.2, 133.1, 132.8, 132.2, 131.9, 131.7, 130.8, 128.9, 127.7, 123.4, 123.2,
-1
22.9, 121.9, 119.7, 98.9. IR (KBr, ν, cm ). 3089, 1618, 1472, 1307, 1141, 1044, 763, 689. HR-MS
-
(APCI) m/z calcd for C H Br O S [M-H] 670.8350, found 670.8355.
2
8
16
3
3
(3Z)-1-(phenyl(p-tolyl)methylene)-3-((phenylsulfonyl)methylene)-1,3-dihydroisobenzofuran (4g)
o
1
60.3 mg, 67% yield; yellow solid, mp 195-196 C; H NMR (400 MHz, CDCl ; δ, ppm) 8.05 (d, J = 7.6
3
Hz, 1H), 7.93-7.90 (m, 2H), 7.58-7.54 (m, 5H), 7.50-7.47 (m, 4H), 7.36-7.33 (m, 3H), 7.29 (d, J = 8.0
1
3
Hz, 2H), 6.98 (s, 1H), 6.03 (d, J = 8.0 Hz, 1H), 2.39 (s, 3H). C{1H} NMR (100 MHz, CDCl ; δ, ppm)
3
159.5, 147.5, 143.5, 138.1, 137.4, 134.8, 134.2, 133.7, 132.8, 131.5, 130.7, 130.6, 130.2, 130.0, 129.6,
-1
1
7
29.3, 128.6, 126.9, 123.2, 122.2, 98.7, 21.3. IR (KBr, ν, cm ). 3065, 1616, 1444, 1309, 1138, 1048,
-
59, 688. HR-MS (APCI) m/z calcd for C H O S [M-H] 449.1211, found 449.1217.
2
9
21
3
(3Z)-1-(phenyl(m-tolyl)methylene)-3-((phenylsulfonyl)methylene)-1,3-dihydroisobenzofuran (4h)
o
1
6
7
7
0.3 mg, 67% yield; yellow solid, mp 185-186 C; H NMR (400 MHz, DMSO-d ; δ, ppm) 8.05 (d, J =
6
.6 Hz, 1H), 7.87-7.84 (m, 2H), 7.72 (s, 1H), 7.58-7.55 (m, 3H), 7.49-7.46 (m, 4H), 7.39-7.35 (m, 4H),
1
3
.24 (s, 1H), 7.18 (s, 1H), 6.98 (s, 1H), 6.07 (d, J = 8.0 Hz, 1H), 2.40 (s, 3H). C{1H} NMR (100 MHz,
CDCl ; δ, ppm) 159.4, 147.8, 143.6, 137.8, 137.6, 137.3, 134.1, 133.7, 132.8, 131.6, 130.9, 130.7,
3
30.2, 130.0, 129.6, 129.2, 128.7, 128.5, 127.3, 126.9, 126.8, 123.2, 122.3, 99.0, 21.6. IR (KBr, ν, cm-1).
1
-
3
058, 1611, 1444, 1308, 1141, 1408, 763, 687. HR-MS (APCI) m/z calcd for C H O S [M-H]
2
9
21
3
449.1211, found 449.1209.
(
3Z)-1-((4-ethylphenyl)(phenyl)methylene)-3-((phenylsulfonyl)methylene)-1,3-dihydroisobenzofuran
4i)
(
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Page 14 of 24
o
1
5
6.6 mg, 61% yield; yellow solid, mp 181-182 C; H NMR (400 MHz, DMSO-d ; δ, ppm) 8.04 (s, 1H),
6
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
7
.93-7.89 (m, 2H), 7.57-7.55 (m, 3H), 7.52-7.48 (m, 5H), 7.38-7.31 (m, 6H), 6.98 (s, 1H), 6.04 (d, J =
1
3
8.0 Hz, 1H), 2.71-2.66 (m, 2H), 1.28 (t, J = 6.8 Hz, 2H). C{1H} NMR (100 MHz, DMSO-d ; δ, ppm)
6
1
1
1
59.5, 147.5, 144.4, 143.5, 137.4, 135.1, 134.2, 133.7, 132.8, 131.5, 130.7, 130.3, 130.0, 129.6, 129.3,
-1
28.6, 128.1, 127.0, 123.2, 122.2, 98.8, 28.4, 16.1. IR (KBr, ν, cm ). 3081, 1620, 1445, 1309, 1141,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
-
047, 759, 688. HR-MS (APCI) m/z calcd for C H O S [M-H] 463.1368, found 463.1372.
30 23
3
(
3Z)-1-((4-(tert-butyl)phenyl)(phenyl)methylene)-3-((phenylsulfonyl)methylene)-1,3-
dihydroisobenzofuran (4j)
5.1 mg, 56% yield; yellow solid, mp 194-195 C; H NMR (400 MHz, DMSO-d ; δ, ppm) 8.06 (d, J =
o
1
5
6
7.6 Hz, 1H), 7.89 (m, 2H), 7.57-7.54 (m, 5H), 7.50-7.45 (m, 5H), 7.36-7.32 (m, 3H), 7.27 (d, J = 8.0 Hz,
13
1
H), 7.00 (s, 1H), 6.04 (d, J = 8.0 Hz, 1H), 1.34 (s, 9H). C{1H} NMR (100 MHz, DMSO-d ; δ, ppm)
6
1
59.5, 151.2, 147. 6, 143.4, 137.3, 134.8, 134.2, 133.7, 132.8, 131.5, 130.7, 130.3, 130.1, 129.9, 129.5,
-1
129.2, 128.7, 127.0, 126.6, 125.4, 123.2, 123.1, 122.1, 98.9, 34.9, 31.5.IR (KBr, ν, cm ). 3079, 1617,
-
1
4
445, 1307, 1140, 1046, 760, 670. HR-MS (APCI) m/z calcd for C H O S [M-H] 491.1681, found
3
2
27
3
91.1685.
(
3Z)-1-((4-fluorophenyl)(phenyl)methylene)-3-((phenylsulfonyl)methylene)-1,3-
dihydroisobenzofuran (4k)
o
1
5
2.7 mg, 58% yield; yellow solid, mp 211-212 C; H NMR (400 MHz, DMSO-d ; δ, ppm) 8.06 (d, J =
6
8
.0 Hz, 1H), 7.92-7.88 (m, 2H), 7.60-7.54 (m, 6H), 7.50-7.46 (m, 3H), 7.44-7.40 (m, 3H), 7.35-7.32 (m,
1
3
1
2H), 7.03 (s, 1H), 6.05 (d, J = 8.0 Hz, 1H). C{1H} NMR (100 MHz, DMSO-d ; δ, ppm) 162.4 ( J =
6
CF
4
3
2
1
47.9 Hz), 148.1, 142.9, 137.3, 134.4, 133.4 ( J = 3.5 Hz), 132.8 ( J = 7.5 Hz), 132.4, 132.3, 132.0,
CF CF
31.7, 131.5, 130.4, 129.4, 129.3, 128.8, 128.3, 127.3, 123.6, 123.4, 121.8, 121.5, 115.1 (2JCF = 21.2
-1
Hz), 98.3. IR (KBr, ν, cm ). 3045, 1620, 1446, 1307, 1144, 1047, 760, 667. HR-MS (APCI) m/z calcd
-
for C H FO S [M-H] 453.0961, found 453.0962.
2
8
18
3
(3Z)-1-((4-chlorophenyl)(phenyl)methylene)-3-((phenylsulfonyl)methylene)-1,3-
dihydroisobenzofuran (4l)
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The Journal of Organic Chemistry
o
1
4
9.8 mg, 53% yield; yellow solid, mp 218-219 C; H NMR (400 MHz, DMSO-d ; δ, ppm) 8.06 (d, J =
6
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
7
.6 Hz, 1H), 7.92-7.88 (m, 2H), 7.60-7.53 (m, 9H), 7.51-7.46 (m, 5H), 7.03 (s, 1H), 6.06 (d, J = 8.0 Hz,
1
3
1H). C{1H} NMR (100 MHz, DMSO-d ; δ, ppm) 159.2, 148.3, 143.4, 136.8, 136.6, 133.9, 133.7,
6
1
1
33.0, 132.9, 132.7, 131.9, 131.8, 130.7, 130.3, 130.1, 129.7, 129.4, 128.7, 128.6, 126.9, 123.3, 123.1,
-1
20.6, 99.3. IR (KBr, ν, cm ). 3057, 1619, 1444, 1310, 1143, 1047, 761, 687. HR-MS (APCI) m/z calcd
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
-
for C H ClO S [M-H] 469.0665, found 469.0666.
28 18
3
(
3Z)-1-((4-bromophenyl)(phenyl)methylene)-3-((phenylsulfonyl)methylene)-1,3-
dihydroisobenzofuran (4m)
6.0 mg, 64% yield; yellow solid, mp 193-194 C; H NMR (400 MHz, DMSO-d ; δ, ppm) 8.06 (d, J =
o
1
6
6
8.0 Hz, 1H), 7.92-7.87 (m, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.59-7.53 (m, 8H), 7.38-7.33 (m, 4H), 7.01 (s,
13
1
1
H), 6.07 (d, J = 8.0 Hz, 1H). C{1H} NMR (100 MHz, DMSO-d ; δ, ppm) 159.3, 147.9, 143.4, 137.5,
6
36.8, 133.9, 133.8, 133.0, 132.9, 132.2, 131.6, 130.8, 130.3, 129.7, 129.6, 123.3, 123.2, 122.7, 120.9,
-1
99.4. IR (KBr, ν, cm ). 3063, 1616, 1444, 1307, 1142, 1046, 759, 689. HR-MS (APCI) m/z calcd for
-
C H BrO S [M-H] 513.0160, found 513.0162.
2
8
18
3
(3Z)-5-chloro-3-((4-chlorophenyl)(phenyl)methylene)-1-((phenylsulfonyl)methylene)-1,3-
dihydroisobenzofuran (4o)
o
1
5
2
1
5.4 mg, 55% yield; yellow solid, mp 214-215 C; H NMR (400 MHz, DMSO-d ; δ, ppm) 8.25 (d, J =
6
.0 Hz, 1H), 7.91-7.87 (m, 2H), 7.61-7.55 (m, 7H), 7.53-7.47 (m, 6H), 7.11 (s, 1H), 6.01 (d, J = 8.6 Hz,
1
3
H). C{1H} NMR (100 MHz, DMSO-d ; δ, ppm) 158.0, 147.4, 143.2, 137.4, 136.6, 136.4, 136.0,
6
135.2, 133.9, 133.6, 133.2, 131.9, 130.3, 130.2, 129.8, 128.7, 126.9, 124.7, 123.1, 121.1, 100.4. IR (KBr,
-1
ν, cm ). 3074, 1615,1445, 1308, 1144, 1044, 763, 668. HR-MS (APCI) m/z calcd for C H Cl O S [M-
2
8
17
2
3
-
H] 503.0275, found 503.0278.
(3Z)-1-(phenyl(p-tolyl)methylene)-3-(tosylmethylene)-1,3-dihydroisobenzofuran (4p)
o
1
6
7
8
5.0 mg, 70% yield; yellow solid, mp 191-192 C; H NMR (400 MHz, DMSO-d ; δ, ppm) 8.03 (d, J =
6
.6 Hz, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.38-7.33 (m, 6H), 7.31-7.23 (m, 7H), 6.95 (s, 1H), 6.21 (d, J =
1
3
.0 Hz, 1H), 2.43 (s, 3H), 2.34 (s, 3H). C{1H} NMR (100 MHz, DMSO-d ; δ, ppm) 159.5, 151.2,
6
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1
47.6, 143.4, 137.3, 134.8, 134.2, 133.7, 132.8, 131.5, 130.7, 130.3, 130.1, 129.9, 129.5, 129.2, 128.7,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
-1
27.0, 126.6, 125.4, 123.2, 123.1, 122.1, 98.9, 34.9, 31.5. IR (KBr, ν, cm ). 3051, 1618, 1443, 1310,
-
1141, 1045, 761, 668. HR-MS (APCI) m/z calcd for C H O S [M-H] 463.1368, found 463.1367.
3
0
23
3
(3Z)-1-(phenyl(o-tolyl)methylene)-3-((o-tolylsulfonyl)methylene)-1,3-dihydroisobenzofuran (4q)
o
1
3
8
7
5.3 mg, 38% yield; yellow solid, mp 186-187 C; H NMR (400 MHz, DMSO-d ; δ, ppm) 8.15 (d, J =
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
.0 Hz, 1H), 8.09-8.06 (m, 1H), 7.61-7.57 (m, 2H), 7.53-7.44 (m, 6H), 7.40 (m, 3H), 7.42-7.37 (m, 3H),
1
3
.12 (s, 1H), 5.82 (d, J = 8.0 Hz, 1H), 2.66 (s, 3H), 1.97 (s, 3H). C{1H} NMR (100 MHz, DMSO-d ; δ,
6
ppm) 159.5, 147.8, 141.2, 137.4, 137.3, 136.4, 136.3, 134.2, 133.7, 133.1, 133.0, 131.6, 131.4, 131.0,
30.4, 129.8, 129.5, 128.8, 128.5, 128.4, 127.6, 126.4, 123.3, 122.8, 120.5, 98.5, 20.3, 19.4. IR (KBr, ν,
1
-1
-
cm ). 3062, 1613, 1446, 1299, 1146, 1045, 762, 669. HR-MS (APCI) m/z calcd for C H O S [M-H]
3
0
23
3
4
63.1368, found 463.1371.
(
3Z)-1-((4-ethylphenyl)(phenyl)methylene)-3-(((4-ethylphenyl)sulfonyl)methylene)-1,3-
dihydroisobenzofuran (4r)
o
1
6
7
2
1
1
6
0.0 mg, 61% yield; yellow solid, mp 175-176 C; H NMR (400 MHz, DMSO-d ; δ, ppm) 8.03 (s, 1H),
6
.77 (d, J = 8.0 Hz, 2H), 7.61- 7.53 (m, 7H), 7.35-7.31 (m, 6H), 6.95 (s, 1H), 6.16 (d, J = 8.0 Hz, 1H),
1
3
.67-2.61 (m, 4H), 1.27 (m, 6H). C{1H} NMR (100 MHz, DMSO-d ; δ, ppm) 159.2, 150.1, 147.9,
6
44.8, 141.0, 137.9, 137.4, 135.1, 134.6, 134.12, 132.8, 131.7, 130.7, 130.3, 130.0, 129.3, 128.6, 127.1,
-1
23.1, 122.1, 99.3, 28.5, 28.4, 15.9, 15.6. IR (KBr, ν, cm ). 3062, 1611, 1455, 1308, 1145, 1043, 762,
-
88. HR-MS (APCI) m/z calcd for C H O S [M-H] 491.1681, found 491.1685.
32 27
3
(3Z)-1-((4-(tert-butyl)phenyl)(phenyl)methylene)-3-(((4-(tert-butyl)phenyl)sulfonyl)methylene)-1,3-
dihydroisobenzofuran (4s)
o
1
71.2 mg, 65% yield; yellow solid, mp 237-238 C; H NMR (400 MHz, CDCl ; δ, ppm) 7.81 (d, J = 8.4
3
Hz, 2H), 7.71-7.68 (m, 2H), 7.51-7.47 (m, 5H), 7.31- 7.26 (m, 4H), 7.25-7.23 (m, 2H), 7.19-7.16 (m,
1
3
1
H), 6.29 (d, J = 8.0 Hz, 1H), 6.23 (s, 1H), 1.40 (s, 9H), 1.27 (s, 9H). C{1H} NMR (100 MHz, CDCl ;
3
δ, ppm) 154.8, 151.6, 147.0, 142.9, 135.3, 132.9, 130.1, 129.7, 127.0, 125.9, 125.4, 124.5, 124.3, 123.7,
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-1
1
23.4, 122.4, 121.3, 120.8, 120.4, 118.8, 118.0, 116.5, 93.3, 26.6, 26.3. IR (KBr, ν, cm ). 3089, 1619,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
-
1
456, 1306, 1146, 1048, 762, 669. HR-MS (APCI) m/z calcd for C H O S [M-H] 547.2307, found
3
6
35
3
547.2312.
(
3Z)-1-((4-fluorophenyl)(phenyl)methylene)-3-(((4-fluorophenyl)sulfonyl)methylene)-1,3-
dihydroisobenzofuran (4t)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
o
1
5
8
3
2
0.0 mg, 53% yield; yellow solid, mp 203-204 C; H NMR (400 MHz, DMSO-d ; δ, ppm) 8.05 (d, J =
6
.0 Hz, 1H), 7.97-7.92 (m, 2H), 7.63-7.61 (m, 1H), 7.59-7.55 (m, 5H), 7.45-7.41 (m, 4H), 7.36-7.33 (m,
1
3
1
H), 7.02 (s, 1H), 6.07 (d, J = 8.0 Hz, 1H). C{1H} NMR (100 MHz, CDCl ; δ, ppm) 165.1 ( J
=
3
CF
2
8
7
52.9 Hz), 162.6 ( J = 248.2 Hz), 159.7, 148.0, 138.9 ( J = 3.0 Hz), 137.1, 134.3, 133.8 ( J = 3.3
CF
CF
CF
Hz), 132.4 (6JCF = 8.0 Hz), 132.05, 131.6, 130.4, 129.8 (5JCF = 9.4 Hz), 129.4, 128.3, 123.4, 122.0,
3
4
-1
1
1
21.4, 116.4 ( J = 21.4 Hz), 115.2 ( J = 21.2 Hz), 97.9. IR (KBr, ν, cm ). 3073, 1621, 1444, 1315,
CF CF
-
156, 1046, 762, 668. HR-MS (APCI) m/z calcd for C H F O S [M-H] 471.0866, found 471.0869.
2
8
17
2
3
(3Z)-1-((4-chlorophenyl)(phenyl)methylene)-3-(((4-chlorophenyl)sulfonyl)methylene)-1,3-
dihydroisobenzofuran (4u)
o
1
5
7
1
1
9
2.4 mg, 52% yield; yellow solid, mp 190-191 C; H NMR (400 MHz, DMSO-d ; δ, ppm) 8.06 (d, J =
6
.6 Hz, 1H), 7.90-7.87 (m, 2H), 7.65-7.56 (m, 9H), 7.45-7.39 (m, 4H), 7.04 (s, 1H), 6.08 (d, J = 8.0 Hz,
1
3
H). C{1H} NMR (100 MHz, DMSO-d ; δ, ppm) 159.6, 148.3, 148.0, 142.3, 138.6, 136.8, 136.6,
6
33.2, 133.1, 133.0, 132.7, 131.9, 130.7, 130.3, 130.1, 129.9, 129.7, 128.8, 128.7, 123.4, 123.3, 120.8,
-1
8.8. IR (KBr, ν, cm ). 3089, 1617, 1473, 1321, 1145, 1046, 762, 693. HR-MS (APCI) m/z calcd for
-
C H Cl O S [M-H] 503.0275, found 503.0280.
2
8
17
2
3
(
3Z)-1-((4-bromophenyl)(phenyl)methylene)-3-(((4-bromophenyl)sulfonyl)methylene)-1,3-
dihydroisobenzofuran (4v)
70.1 mg, 59% yield; yellow solid, mp 206-207 C; H NMR (400 MHz, DMSO-d ; δ, ppm) 8.07 (d, J =
o
1
6
8
1
1
.0 Hz, 1H), 7.82-7.72 (m, 7H), 7.59-7.56 (m, 2H), 7.53-7.49 (m, 6H), 7.02 (s, 1H), 6.32 (d, J = 8.0 Hz,
1
3
H). C{1H} NMR (100 MHz, DMSO-d ; δ, ppm) 159.7, 148.0, 142.7, 137.6, 136.8, 136.6, 133.8,
6
33.0, 132.8, 132.6, 132.1, 131.7, 130.7, 130.6, 130.3, 130.1, 129.0, 128.8, 127.6, 123.4, 122.7, 121.8,
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1
21.2, 98.7. IR (KBr, ν, cm ). 3089, 1618, 1472, 1307, 1141, 1044, 763, 689. HR-MS (APCI) m/z calcd
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
-
for C H Br O S [M-H] 592.9245, found 592.9248.
2
8
17
2
3
(3Z)-1-(m-tolyl(p-tolyl)methylene)-3-(tosylmethylene)-1,3-dihydroisobenzofuran (4w)
o
1
5
5.4 mg, 58% yield; yellow solid, mp 246-247 C; H NMR (400 MHz, CDCl ; δ, ppm) 7.83 (d, J = 8.0
3
Hz, 2H), 7.62 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.0 Hz, 1H), 7.33-7.27 (m, 5H), 7.22-7.15 (m, 2H), 7.13-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
7
.09 (m, 3H), 6.25 (d, J = 8.4 Hz, 1H), 6.21 (s, 1H), 2.43 (s, 3H), 2.38 (s, 3H), 2.35 (s, 3H). C{1H}
NMR (100 MHz, DMSO-d ; δ, ppm) 154.9, 142.7, 138.7, 135.7, 134.3, 133.3, 132.7, 130.2, 130.1,
6
1
1
27.0, 126.8, 126.4, 125.7, 124.6, 124.4, 124.3, 124.2, 124.1, 122.9, 122.5, 118.8, 118.3, 116.5, 93.1,
-1
6.8, 16.7, 16.6. IR (KBr, ν, cm ). 3083, 1619, 1455, 1320, 1141, 1048, 766, 687. HR-MS (APCI) m/z
-
calcd for C H O S [M-H] 477.1524, found 477.1529.
3
1
25
3
(
3Z)-1-((4-chlorophenyl)(p-tolyl)methylene)-3-(tosylmethylene)-1,3-dihydroisobenzofuran (4x)
o
1
5
0.8 mg, 51% yield; yellow solid, mp 233-234 C; H NMR (400 MHz, CDCl ; δ, ppm) 7.82 (d, J = 8.4
3
Hz, 2H), 7.64 (d, J = 8.8 Hz, 2H), 7.52 (d, J = 8.0 Hz, 2H), 7.44-7.41 (m, 2H), 7.31-7.28 (m, 4H), 7.19-
13
7
.13 (m, 4H), 6.32 (d, J = 8.0 Hz, 1H), 6.23 (s, 1H), 2.47 (s, 3H), 2.36 (s, 3H). C{1H} NMR (100
MHz, CDCl ; δ, ppm) 159.3, 148.1, 143.7, 140.3, 138.7, 136.4, 134.6, 134.0, 132.2, 131.8(3), 131.7(8),
3
1
2
30.5, 130.4, 130.1, 129.5, 129.4, 129.3, 129.0, 128.3, 127.3, 127.1, 123.7, 121.4, 121.3, 98.4, 21.6,
-1
1.4. IR (KBr, ν, cm ). 3088, 1619, 1473, 1311, 1141, 1043, 763, 668. HR-MS (APCI) m/z calcd for
-
C H ClO S [M-H] 497.0978, found 497.0979.
3
0
22
3
(
3Z)-1-((4-(tert-butyl)phenyl)(p-tolyl)methylene)-3-(((4-(tert-butyl)phenyl)sulfonyl)methylene)-1,3-
dihydroisobenzofuran (4z)
6.2 mg, 50% yield; yellow solid, mp 208-209 C; H NMR (400 MHz, CDCl ; δ, ppm) 7.85 (d, J = 8.4
o
1
5
3
Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H),7.54-7.45(m, 4H), 7.31-7.28 (m, 4H), 7.24-7.21 (m, 2H), 7.18-7.14 (m,
1
3
1H), 6.23 (d, J = 8.0 Hz, 1H), 6.20 (s, 1H), 2.43 (s, 3H), 1.40 (s, 9H), 1.27 (s, 9H). C{1H} NMR (100
MHz, CDCl ; δ, ppm) 159.6, 156.3, 151.2, 147.6, 140.1, 138.3, 135.1, 134.9, 134.6, 131.7, 130.4, 130.2,
3
1
29.9, 128.9, 127.2, 127.1, 126.0, 125.7, 125.6, 125.1, 123.6, 122.8, 121.2, 97.9, 34.8, 31.1, 21. 4. IR
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The Journal of Organic Chemistry
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(
KBr, ν, cm ). 2960, 1617, 1457, 1315, 1146, 1048, 762, 688. HR-MS (APCI) m/z calcd for C H O S
37 37 3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
-
[
M-H] 561.2463, found 561.2466.
ASSOCIATED CONTENT
Supporting Information
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3
4
5
6
7
8
9
0
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H and C NMR spectra for all pure products, and X-ray crystal data (CIF) for 4f. This material is
available free of charge via the Internet at http//pubs.acs.org.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We are grateful for financial support from the NSFC (Nos. 21602087 and 21871112), the Outstanding
Youth Fund of JSNU (YQ2015003), NSF of Jiangsu Province (BK20160212), and the Qing Lan Project
of Jiangsu Education Committee (2016006).
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