Ligand-Free Pd-Catalyzed Synthesis of 3-Allylbenzofurans by Merging Decarboxylative Allylation and Nucleophilic Cyclization

Article abstract of DOI:10.1021/acs.joc.0c00375

A new single Pd-catalyzed decarboxylative allylation-nucleophilic cyclization relay is reported by using α-alkynyl arylols and vinylethylene carbonates (or vinyl carbamates), and a wide range of 3-allyl benzofurans with generally good yields were stereoselectively synthesized under mild conditions, among which the complete stereoselectivity of some cases was also observed. Notably, the present catalysts can tolerate air conditions without any ligand, additive, or base, opening new avenues to build up oxa-heterocycle frameworks through catalytic difunctionalization of internal alkynes.

Full text of DOI:10.1021/acs.joc.0c00375

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Article
Ligand-Free Pd-Catalyzed Synthesis of 3-Allylbenzofurans by
Merging Decarboxylative Allylation and Nucleophilic Cyclization
Jie Zhang, Jia-Yin Wang, Min-Hua Huang, Wen-Juan Hao, Xing-Chao Tu, Shu-Jiang Tu, and Bo Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00375 • Publication Date (Web): 08 May 2020
Downloaded from pubs.acs.org on May 12, 2020
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Page 1 of 28
The Journal of Organic Chemistry
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Ligand-Free Pd-Catalyzed Synthesis of 3-Allylbenzofurans by Merging
Decarboxylative Allylation and Nucleophilic Cyclization
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Jie Zhang, Jia-Yin Wang, Min-Hua Huang, Wen-Juan Hao,* Xing-Chao Tu,* Shu-Jiang Tu, and Bo
Jiang*
School of Chemistry & Materials Science, Jiangsu Key Laboratory of Green Synthetic Chemistry for
Functional Materials, Jiangsu Normal University, Xuzhou 221116, P. R. China.
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E-mail: wjhao@jsnu.edu.cn(WJH); tuxingchao@jsnu.edu.cn(XCT), jiangchem@jsnu.edu.cn(BJ);
RECEIVED DATE
O
HO
R
Ar
Ar
Pd2(dba)3
MeCN, 60 o
air
O
O
Ar
+
C
Ar
OH
Ar
O
R
Ligand and additive-free
Single Pd-catalyzed relay
Wide substrate scope
O
N
O
R1
Ar
O
Pd2(dba)3, MeCN
60 oC, air
NHR1
R
ABSTRACT. A new single Pd-catalyzed decarboxylative allylation-nucleophilic cyclization relay is
reported by using α-alkynyl arylols and vinylethylene carbonates (or vinyl carbamates), and a wide
range of 3-allyl benzofurans with generally good yields were stereoselectively synthesized under the
mild conditions, among which the complete stereoselectivity of some cases was also observed. Notably,
the present catalysis can tolerate air conditions without any ligand, additive or base, opening new
avenues to build up oxa-heterocycle frameworks through catalytic difunctionalization of internal
alkynes.
Introduction
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Transition metal-catalyzed annulation-difunctionalization of alkynes linked to nucleophilic sites has
proven to be one of the most straightforward and atom-economical synthetic strategies to construct a
sequence of functionalized cyclic frameworks by incorporating two functional groups across the π
system of the alkyne unit.1 During these reaction processes, transition metal-catalysts with high-valence
states show a strong Lewis acidity and could activate alkynes by chelation to promote its intramolecular
cyclization, forming metal species I which capture electrophiles to give the targets (Scheme 1a).2 For
example, the group of Li reported an elegant Rh(III)-catalyzed annulation-difunctionalization of o-
alkynylanilines and olefins toward 3-allylindoles through a nucleophilic cyclization/oxidative allylation
cascade (Scheme 1b).3 Despite these great achievements gained in this field, the development of a new
catalysis for annulation-difunctionalization of alkynes remains a highly challenge because of the
difficult control in the multiple catalytic behaviors of transition metal catalysts in a one-pot
transformation.4
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It is well-known that decarboxylative allylation has been recognized as a powerful and versatile
synthetic tool for forging carbon−carbon and carbon−heteroatom bonds in complex molecule synthesis.5
During them, palladium-catalyzed alkylation via zwitterionic allylpalladium intermediates from
vinylethylene carbonates (VECs) is a reliable and valuable approach to construct functionalized allyl
molecules products.6 Zhang,7 Zhao,8 Kleij,9 Glorius10 and others11 have independently applied
palladium catalysis toward the construction of various functionalized molecules. Mechanistically, Pd(0)-
catalyst enabled decarboxylation of vinylethylene carbonates (VECs) to generate an electrophilic π-
allyl-palladium (II) intermediate A (Scheme 1c). Given the application of Lewis acidity of Pd(II)
catalysts in triple C≡C bond activation,12 π-allyl-palladium (II) intermediate may activate triple C≡C
bond of alkynes to accelerate nucleophilic cyclization, giving a Pd(II) complex B that may reductively
eliminate the product (Scheme 1c). The alternative alkyne cyclization−allylation sequence is less
feasible, which is based on the following factors: i) because of its coordinative saturation, Pd(0)-catalyst
is unfavorable for the formation of the cyclized intermediate C; ii) even if intermediate C is formed, it is
easily (irreversibly) protonolyzed. Herein, we successfully implemented this concept with a new Pd-
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The Journal of Organic Chemistry
catalyzed decarboxylative allylation and nucleophilic cyclization relay starting from α-alkynyl arylols
and vinylethylene carbonates (VECs) without any ligand or additive (Scheme 1d). The present approach
represents a precise single palladium-catalyzed relay process for the direct synthesis of a wide range of
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new 3-allylbenzofurans in a highly functional-group-compatible manner under ligand-free conditions.
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(a) Developed reaction mode of annulation-difunctionalization
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Nu
Nu
R
Nu
R
E
E
[M]
R
[M]
I
(b) Li's work
R2
R1
R
Cp*RhCl2]2
AgSbF6
R1
R2
+
NHSO2Ar
R
N
SO2Ar
(c) Integration of Allylation and Nucleophilic Cyclization (Rationale of Sequences)
NuH
O
PdII
[Pd0]
CO2
R
O
O
O
Ar
-H+
Ar
Ar
O
O
PdII
A
TM
O
O
R
Pd0
Ar
NuH
[Pd0]
-H+
Nu
B
R
R
R
Nu
C
(d) This work
O
HO
R
Ar
Ar
O
Pd2(dba)3
MeCN, 60 oC, air
O
Ar
+
Ar
OH
Ligand-free
O
1
2
3
Scheme 1. Profiles for Annulation-Difunctionalization of Alkynes
Results and Discussion
We commenced our studies with the optimization investigation on the coupling of phenyl vinylethylene
carbonate (1a) and 1-(phenylethynyl)naphthalen-2-ol (2a) as model substrates in the presence of
Pd2(dba)3·CHCl3 (10 mol%) as a catalyst. The reaction proceeded readily in 1,2-dichloroethane (DCE)
at 60 oC under air conditions (100 °C), and the desired product 3a was obtained in 68% yield (Table 1,
entry 1). The initial outcome impelled us to further investigate the reaction conditions. Several other
palladium catalysts often used in catalytic reactions, such as Pd(OAc)2, Pd(PPh3)4, (MeCN)2PdCl2,
PdCl2, Pd(PPh3)2Cl2, Pd(dppf)Cl2, and Pd2(dba)3 were then tested for this transformation (entries 2–8).
The results revealed that the former six did not exhibit any catalytic performances as their use in fact
completely suppressed the generation of 3a whereas the last one could accelerate this reaction more
efficiently, providing higher yield of 72% (entry 8), and thus it turned to be a better choice in this
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transformation. Taking Pd2(dba)3 as the catalyst, the effect of the solvents was then studied (entries 9-
13). The following screening of several other aprotic solvents, namely MeOH, DMSO, toluene, 1,4-
dioxane and MeCN, showed that MeCN resulted in a slightly higher yield as compared with DCE
(entries 1 vs 13), and the others all gave a yield of <63%. The lower conversion was observed when the
reaction temperature was adjusted to be either 40 or 80 °C (entries 14-15). After that, lowering the
Pd2(dba)3 loading could maintain the efficiency of this reaction (entries 16-17), and an employment of
2.5 mol% of Pd2(dba)3 produced product 3a in 74% yield. Fine-tuning the mol ratio of 1a and 2a in
1:1.2 favored the transformation to give 80% yield (entry 18).
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Table 1. Condition Optimization for Product 3aa
O
HO
Ph
O
conditions
O
Ph
+
Ph
OH
O
Ph
1a
2a
3a
entry
Pd-Cat. (mol %)
solvent
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
MeOH
t (oC) yield (%)b
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2
3
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9
Pd2(dba)3·CHCl3 (10)
Pd(OAc)2 (10)
60
60
60
60
60
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60
60
68
N.D.
N.D.
N.D.
N.D.
N.D.
N.D.
72
Pd(PPh3)4 (10)
(MeCN)2PdCl2 (10)
Pd(PPh3)2Cl2 (10)
Pd(dppf)Cl2 (10)
PdCl2 (10)
Pd2(dba)3 (10)
Pd2(dba)3 (10)
63
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The Journal of Organic Chemistry
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18 c
Pd2(dba)3 (10)
DMSO
toluene
60
60
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48
76
45
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76
74
80
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8
Pd2(dba)3 (10)
Pd2(dba)3 (10)
Pd2(dba)3 (10)
Pd2(dba)3 (10)
Pd2(dba)3 (10)
Pd2(dba)3 (5)
Pd2(dba)3 (2.5)
Pd2(dba)3 (2.5)
1,4-dioxane 60
9
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
60
40
80
60
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aReaction conditions: 1a (0.1 mmol), 2a (0.1 mmol), catalyst (x mol %), solvent (2.0 mL), under air
conditions. bIsolated yield based on substrate 1a. cThe mol ratio of 1a and 2a in 1:1.2. N.D. = not
detected
With the optimized reaction conditions in hand, we then evaluated the generality of this Pd-catalyzed
allylation-cyclization cascade toward synthesizing 3-allylbenzofurans by examining a range of α-
alkynylnaphth-2-ol and vinylethylene carbonate components. As depicted in Scheme 2, all tested
substrates did not hamper the reaction process, enabling the Pd-catalysis to access the desired products 3
in synthetically useful yields. Firstly, vinylethylene carbonates with diverse electronic properties and
different substituent patterns in the aryl ring were investigated by combining α-alkynylnaphth-2-ol 2a
under the standard conditions. Various substituents, such as methyl (1b), methoxy (p-methoxyphenyl =
PMP 1c and 1d), fluoro (1e), chloro (1f and 1g), and bromo (1h and 1i), were well-tolerated with this
catalytic conditions, delivering the corresponding products 3b−3i in 37%-63% yields and poor to high
stereoselectivities (2:1 to >19:1 Z/E ratio), among which 3-bromophenyl counterpart 1i could
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completely orient the (Z)-selectivity to construct the target product 3i in 60% yield. Next, the scope
regarding the α-alkynylnaphth-2-ols was detailly studied by independently installing different
substituents including aryl, heteroaryl and alkyl groups into the alkynyl unit. Satisfyingly, both electron-
donating (methyl 2b–2e, ethyl 2f, n-propyl 2g and tert-butyl 2h) and electron-withdrawing (fluoro 2i,
chloro 2j–2l and 2n, bromo 2m and nitro 2o) groups residing in various positions of the phenyl ring all
accessed the corresponding products 3j-3w with 40-82% yields and 1:1 to >19:1 Z/E ratio. Of these
groups, the sterically crowded o-chlorophenyl functionality (1l) seemed reluctant to undergo this
process, as product 3t was provided in an unsatisfactory yield of 40% and 2:1 Z/E ratio. In contrast, the
2-thienyl substrate 2p still displayed a good reactivity profile, offering product 3x in 70% yield, but with
poor stereoselectivity. Notably, substrate 2q with a methyl group linked to the alkynyl moiety was also
workable in this transformation, accessing product 3y with 75% yield and 3:1 Z/E ratio. Moreover, α-
alkynylnaphth-2-ols with either a C6 bromo (2s) or a C7 methoxy (2t) group were accommodated,
confirming the efficiency of the reaction, as products 3z and 3aa were furnished in 66% and 73% yields
with moderate stereoselectivities, respectively. Interestingly, o-arylalkynyl phenols 2u-2w with both
electron-poor and electron-rich groups at the arylalkynyl moiety (R2) can all tolerate this catalytic
system, rendering the corresponding products 3bb−3dd in 70−75% yields and 3:1 to >19:1 Z/E ratio.
To expand the utility of this methodology, we contributed our effort to test other alkylation reagents.
Fortunately, N-unprotected vinyl carbamates 4a and 4b were selected to react with 2a under the
standard conditions, providing the desired products 5a and 5b in 70% and 68% yields, respectively
(Scheme 3). Furthermore, N-tosyl vinyl carbamate 4c was appliable in this transformation as well, and
the expected product 5c was isolated in 76% yield (Scheme 3). The stereo-structure of product 5b was
assigned by X-ray diffraction analysis (CCDC 1983888).
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The Journal of Organic Chemistry
O
HO
R
R
Ar
1
2
3
Ar
O
Pd2(dba)3
O
Ar
+
MeCN, 60 o
C
Ar
OH
O
4
1
2
3
5
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7
8
HO
HO
Ph
Ph
Ar
O
R
O
9
3j-3x
3a-3i
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3j
, R = p-tolyl (82%, Z/E = 3:1)
3a,
Ar = Ph (80%, Z/E = 3:1)
3k
, R = m-tolyl (54%, Z/E = 15:1)
3b
3c
3d
3e
, Ar = p-tolyl (37%, Z/E = 6:1)
3l
, R = 3,4-Me2C6H3 (74%, Z/E = 7:1)
, Ar = 4-MeOC6H4 (40%, Z/E = 4:1)
, Ar = 3-MeOC6H4 (43%, Z/E = 2:1)
, Ar = 4-FC6H4 (45%, Z/E = 3:1)
, Ar = 4-ClC6H4 (48%, Z/E = 2:1)
3m
3n
, R = 3,5-Me2C6H3 (61%, Z/E = 2:1)
, R = 4-EtC6H4 (60%, Z/E = 5:1)
n
3o
3p
3q
, R = 4- PrC6H4 (63%, Z/E = 3:1)
3f
t
, R = 4- BuC6H4 (55%, Z/E > 19:1)
3g
3h
, Ar = 3-ClC6H4 (63%, Z/E = 5:1)
, Ar = 4-BrC6H4 (52%, Z/E = 10:1)
, Ar = 3-BrC6H4 (60%, Z/E > 19:1)
, R = 4-FC6H4 (70%, Z/E > 19:1)
, R = 4-ClC6H4 (75%, Z/E > 19:1)
3r
3s
3i
, R = 3-ClC6H4 (72%, Z/E > 19:1)
, R = 2-ClC6H4 (40%, Z/E = 2:1)
Br
3t
HO
3u
3v
, R = 4-BrC6H4 (80%, Z/E = 10:1)
, R = 4-F-3-ClC6H4 (80%, Z/E > 19:1)
Ph
3w
, R = 2-O2NC6H3 (72%, Z/E = 9:1)
, R = 2-thienyl (70%, Z/E = 3:1)
, R = Me (75%, Z/E = 3:1)
3x
3y
O
Ph
3z
(66%, Z/E = 3:1)
HO
OMe
HO
O
Ph
R
Ph
3bb-3dd
, R = p-tolyl (70%, Z/E > 19:1)
3bb
O
Ph
3cc
, R = 4-ClC6H4 (68%, Z/E = 13:1)
3aa
(73%, Z/E = 10:1)
3dd
, R = 4-PhC6H4 (75%, Z/E = 3:1)
Scheme 2. Substrate Scope for the Synthesis of Products 3
R2
Ph
O
Pd2(dba)3
+
MeCN, 60 oC, air
O
R2
N
O
R1
NHR1
OH
Ph
2a
5
4
, R1 = H, R2 = H (70%)
, R1 = H, R2 = Me (68%)
, R1 = Ts, R2 = H (76%)
5a
5b
5c
Scheme 3. Expansion of Substrate Scope
This catalytic system can be easily scaled up, as demonstrated by the synthetic utility in the
amplification reaction for the synthesis of 3a on a 3 mmol scale (63%, Scheme 4a). Next, treatment of
3a with pyridinium chlorochromate (PCC) at 0 °C in CH2Cl2 afforded aldehyde product 6a in 80% yield
(Scheme 4b). These results illustrate the synthetic potential of this protocol.
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(a) scale-up reaction
O
1
2
3
4
5
6
HO
Ph
Ph
O
O
Pd2(dba)3
MeCN, 60 o
Ph
+
C
Ph
OH
O
1a
(3 mmol)
2a
(3.6 mmol)
3a
(740 mg, 63%)
(b) late-stage transformation
7
8
9
O
HO
PCC (1.5 equiv)
DCM, 0.5 h
Ph
Ph
O
Ph
O
Ph
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59
60
3a
6a
(80%)
Scheme 4. Synthetic Potential of This Protocol
To ascertain the reaction process involving an allylation−cyclization sequence, several control
experiments were conducted. The [5 + 2] annulation of O-protected o-arylalkynyl phenol 2x with 1a did
not proceed and starting material 2x was recovered, indicating the free hydroxyl group in substrates 2
was key for this successful catalysis, which could accelerate nucleophilic cyclization when carbon-
carbon triple bond is activated by Pd(II) catalyst (Scheme 5a). Two palladium catalysts with different
valence states were used for the cyclization of o-arylalkynyl phenol 2u, and the outcomes revealed that
palladium catalyst with a higher valence state favored to activate the alkyne to realize the nucleophilic
cyclization (Scheme 5b). Without alkynyl moiety, phenol (9) gave allylic phenyl ether 10 (Scheme 5c).
Furthermore, benzofuran 8 proved to be inactive for this transformation (Scheme 5d). These results
showed that the reaction process should be the allylation−cyclization sequence.
Ph
O
p-tolyl
O
O
O
Pd2(dba)3
(a)
(b)
+
MeCN, 60 o
C
Ph
1a
OMe
p-tolyl
OMe
7
2x
(not detected)
p-tolyl
Pd-Cat., MeCN, 60 o
C
p-tolyl
O
8
Pd-Cat.:
OH
8
Pd2(dba)3, 46%
2u
PdCl2,
80%
HO
Pd2(dba)3
1a
(c)
+
OH
Ph
MeCN, 60 o
C
O
9
10
(20%)
HO
Pd2(dba)3
MeCN, 60 o
(d)
1a
+
C
O
O
8
Ph
p-tolyl
p-tolyl
3bb
(not detected)
Scheme 5. Preliminary Mechanistic Investigations
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The Journal of Organic Chemistry
O
1
2
3
4
O
O
1
HO
Ar
Ar
Pd(0)
5
R
CO2
O
6
3
7
8
9
Ar
PdII
O
OH
PdII
Ar
10
11
12
13
14
15
16
17
18
19
20
21
A
Ph
R
O
B
OH
Ar
O
PdII
2
R
OH
Scheme 6. Proposed Reaction Pathway
Based on the above experimental results and previous reports,4,7-10 a reasonable mechanism is depicted
in Scheme 6. Initially, vinylethylene carbonate 1 undergoes a decarboxylative process to afford the
zwitterionic Pd-π-allyl intermediate A, which activates the alkynyl unit of substrate 2 via chelation.
Subsequent nucleophilic cyclization and proton transfer occur to afford intermediate B, followed by
reductive elimination to give the desired product 3 and regenerate the Pd(0) catalyst for the next
catalytic cycle.
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In summary, we have established a new ligand-free single Pd-catalyzed relay consisted of
decarboxylative allylation and nucleophilic cyclization from α-alkynyl arylols and vinylethylene
carbonates, providing a general and facile method for the synthesis of a wide range of 3-
allylbenzofurans with generally good yields and stereoselectivity. In some cases, the complete
stereoselectivity was observed. Very interestingly, the present catalysis can tolerate air conditions
without any ligand, additive and base, featuring high atom economy, good functional group tolerance
and wide substrate scope and thus opening new avenues for catalytic difunctionalization of internal
alkynes. Further investigation and application of this alkylation–annulation reaction is underway in our
laboratory.
Experimental Section
General Information.
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All melting points are uncorrected. The NMR spectra were recorded in CDCl3 or DMSO-d6 on a 400
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,
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. The compounds 1,13 214 and 415 were prepared according to the reported
procedures.
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General Procedure for the Synthesis of 3
Example for the synthesis of 3a.
Under the air conditions, 1-(phenylethynyl)naphthalen-2-ol (1a, 0.36 mmol, 87.8 mg), vinyl cyclic
carbonate (2a, 0.3 mmol, 57.0 mg) and Pd2(dba)3 (2.5 mol %, 6.9 mg) were added in a 10-mL reaction
vial, Then, MeCN (3.0 mL) was added into this reaction system. The reaction vial was sealed and
o
heated at 60 C in an oil bath for 5 h until TLC (petroleum ether: ethyl acetate= 5:1) revealed that
conversion of the starting material 2a was completed. Then the reaction mixture was concentrated in
vacuum, and the resulting residue was purified by column chromatography on silica gel (eluent,
petroleum ether/ ethyl acetate = 10:1) to afford the desired product 3a as white solid.
Scale-up experiment of 3a
Under the air conditions, 1-(phenylethynyl)naphthalen-2-ol (1a, 3.6 mmol, 879.5 mg), vinyl cyclic
carbonate (2a, 3 mmol, 570.6 mg) and Pd2(dba)3 (2.5 mol %, 68.7 mg) were added in a 25-mL reaction
vial, Then, MeCN (10.0 mL) was added into this reaction system. The reaction vial was sealed and
heated at 60 oC in an oil bath until TLC (petroleum ether: ethyl acetate= 5:1) revealed that conversion of
the starting material 2a was completed. Then the reaction mixture was concentrated in vacuum, and the
resulting residue was purified by column chromatography on silica gel (eluent, petroleum ether/ ethyl
acetate = 10:1) to afford the desired product 3a as white solid with 63% yield.
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The Journal of Organic Chemistry
(Z)-2-Phenyl-4-(2-phenylnaphtho[2,1-b]furan-1-yl)but-2-en-1-ol (3a, major) Isolation by column
chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3a (93.6 mg, 80%) as a white solid,
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mp 129-130 C, Z/E= 3:1; H NMR (400 MHz, CDCl3; δ, ppm) 8.17-8.13 (m, 1H), 7.97-7.93 (m, 1H),
7.81-7.76 (m, 1H), 7.71 (d, J = 3.6 Hz, 1H), 7.68-7.64 (m, 3H), 7.52 (s, 1H), 7.50 (s, 2H), 7.48 (d, J =
2.4 Hz, 2H), 7.46 (s, 1H), 7.41-7.37 (m, 3H), 6.12 (t, J = 6.4 Hz, 1H), 4.43 (s, 2H), 4.03 (d, J = 6.4 Hz,
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2H). C{1H} NMR (100 MHz, CDCl3; δ, ppm) 152.1, 151.4, 141.9, 137.8, 130.9, 129.3, 129.0, 128.7,
128.6, 128.2, 128.0, 127.8, 127.4, 126.6, 126.3, 126.2, 125.9, 124.2, 123.6, 123.1, 116.7, 112.5, 67.8,
25.8. IR (KBr, ν, cm-1) 3445, 1622, 1490, 1435, 1393, 1062, 1023, 803. HRMS (ESI) m/z: [M + Na]+
Calcd for C28H22O2Na 413.1517; Found 413.1509.
(Z)-4-(2-Phenylnaphtho[2,1-b]furan-1-yl)-2-(p-tolyl)but-2-en-1-ol (3b, major) Isolation by column
chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3b (44.8 mg, 37%) as a white solid,
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mp 103-104 C, Z/E= 6:1; H NMR (400 MHz, CDCl3; δ, ppm) 7.64-7.61 (m, 2H), 7.59-7.44 (m, 3H),
7.44-7.36 (m, 2H), 7.35 (d, J = 2.4 Hz, 1H), 7.35-7.29 (m, 2H), 7.28 (d, J = 1.6 Hz, 2H), 7.26-7.20 (m,
3H), 5.93 (t, J = 7.2 Hz, 1H), 4.36 (d, J = 0.8 Hz, 2H), 3.70 (d, J = 7.2 Hz, 2H), 2.41 (s, 3H). C{1H}
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NMR (100 MHz, CDCl3; δ, ppm) 154.0, 151.1, 141.4, 137.5, 134.8, 131.0, 130.2, 129.4(8), 129.4(6),
128.9, 128.8, 128.6, 128.2, 127.3, 127.0, 126.4, 125.2, 124.5, 122.5, 119.7, 114.5, 111.5, 67.9, 24.1,
21.3. IR (KBr, ν, cm-1) 3325, 3508, 1494, 1441, 1262, 1085, 1010, 732. HRMS (ESI) m/z: [M + Na]+
Calcd for C29H24O2Na 427.1674; Found 427.1689.
(Z)-2-(4-methoxyphenyl)-4-(2-phenylnaphtho[2,1-b]furan-1-yl)but-2-en-1-ol (3c, major) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3c (50.4 mg, 40%) as a white
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solid, mp 110-111 C, Z/E= 4:1; H NMR (400 MHz, CDCl3; δ, ppm) 8.15 (d, J = 8.4 Hz, 1H), 7.96-
7.92 (m, 1H), 7.73-7.71 (m, 1H), 7.69-7.64 (m, 3H), 7.51-7.47 (m, 2H), 7.44-7.37 (m, 5H), 7.02 (d, J =
8.8 Hz, 2H), 6.06 (t, J = 6.4 Hz, 1H), 4.40 (s, 2H), 4.03 (d, J = 6.4 Hz, 2H), 3.86 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3; δ, ppm) 159.2, 152.0, 151.3, 141.4, 130.9, 130.1, 129.2 128.8, 128.7, 128.5, 128.1,
127.7, 127.4, 126.2, 125.8, 125.6, 124.1, 123.6, 123.1, 116.8, 114.1, 112.4, 67.9, 55.4, 25.8. IR (KBr, ν,
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cm-1) 3444, 1611, 1514, 1393, 1250, 1027, 803, 695. HRMS (ESI) m/z: [M + Na]+ Calcd for
C29H24O3Na 443.1623; Found 443.1631.
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(Z)-2-(3-methoxyphenyl)-4-(2-phenylnaphtho[2,1-b]furan-1-yl)but-2-en-1-ol (3d, major) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3d (54.2 mg, 43%) as a
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white solid, mp 136-137 C, Z/E= 2:1; H NMR (400 MHz, CDCl3; δ, ppm) 8.17 (d, J = 7.6 Hz, 1H),
7.98-7.94 (m, 1H), 7.80-7.70 (m, 3H), 7.69-7.64 (m, 3H), 7.51 (d, J = 8.0 Hz, 2H), 7.44-7.39 (m, 3H),
7.07-7.01 (m, 2H), 6.11 (t, J = 6.6 Hz, 1H), 4.42 (s, 2H), 4.04 (d, J = 6.4 Hz, 2H), 3.87 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3; δ, ppm) 159.8, 152.0, 151.3, 141.8, 139.2, 130.8, 129.7, 129.2, 128.9, 128.7,
128.1, 127.7, 127.4, 126.2, 125.8, 124.2, 123.6, 121.3, 119.0, 116.6, 114.9, 113.1, 112.4, 67.8, 55.4,
25.8. IR (KBr, ν, cm-1) 3445, 1606, 1577, 1491, 1395, 1285, 1203, 1002. HRMS (ESI) m/z: [M + Na]+
Calcd for C29H24O3Na 443.1623; Found 443.1607.
(Z)-2-(4-fluorophenyl)-4-(2-phenylnaphtho[2,1-b]furan-1-yl)but-2-en-1-ol (3e, major) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3e (55.1 mg, 45%) as a white
solid, mp 111-112 oC, Z/E= 3:1; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.15-8.11 (m, 1H), 7.98-7.94 (m,
1H), 7.79-7.75 (m, 1H), 7.74-7.71 (m, 1H), 7.68-7.61 (m, 3H), 7.54-7.46 (m, 3H), 7.42-7.39 (m, 3H),-
7.18-7.11 (m, 2H), 6.12 (t, J = 7.0 Hz, 1H), 4.38 (s, 2H), 4.00 (d, J = 6.8 Hz, 2H). 13C{1H} NMR (100
MHz, CDCl3; δ, ppm) 162.4(1JCF =245.8 Hz), 152.1, 151.4, 140.9, 130.9(0), 130.9(5), 130.6(3JCF =8.1
Hz), 129.3, 128.9, 128.7, 128.5, 128.2(4JCF =2.6 Hz), 127.8, 127.5,126.7, 126.3, 125.9, 124.2, 123.4,
116.4, 115.7(2JCF =21.4 Hz), 112.5, 67.9, 25.8. IR (KBr, ν, cm-1) 3390, 3050, 1601, 1508, 1393, 1222,
1157, 1008. HRMS (ESI) m/z: [M + Na]+ Calcd for C28H21FO2Na 431.1423; Found 431.1403.
(Z)-2-(4-chlorophenyl)-4-(2-phenylnaphtho[2,1-b]furan-1-yl)but-2-en-1-ol (3f, major) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3f (61.1 mg, 48%) as a white
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solid, mp 132-133 C, Z/E= 2:1; H NMR (400 MHz, CDCl3; δ, ppm) 7.78 (d, J = 7.2 Hz, 1H), 7.61-
7.58 (m, 2H), 7.51-7.47 (m, 2H), 7.45-7.42 (m, 1H), 7.41-7.36 (m, 5H), 7.34 (d, J = 8.8 Hz, 2H), 7.28
(d, J = 0.8 Hz, 2H), 5.99 (t, J = 7.0 Hz, 1H), 4.33 (s, 2H), 3.66 (d, J = 7.2 Hz, 2H). 13C{1H} NMR (100
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The Journal of Organic Chemistry
MHz, CDCl3; δ, ppm) 154.0, 151.1, 140.4, 138.8, 133.6, 130.9, 130.2, 130.0, 128.9(8), 128.9(6),
128.7(2), 128.7(7), 128.4, 127.9, 127.4, 127.1, 126.4, 124.6, 122.6, 119.6, 114.1, 111.3, 67.7, 24.1. IR
(KBr, ν, cm-1) 3343, 3058, 1489, 1441, 1263, 1092, 1009, 820. HRMS (ESI) m/z: [M + Na]+ Calcd for
C28H21ClO2Na 447.1128; Found 447.1113.
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(Z)-2-(3-chlorophenyl)-4-(2-phenylnaphtho[2,1-b]furan-1-yl)but-2-en-1-ol (3g, major) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3g (80.1 mg, 63%) as a
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white solid, mp 155-156 C, Z/E= 5:1; H NMR (400 MHz, CDCl3; δ, ppm) 8.37 (d, J = 8.0 Hz, 1H),
7.99 (d, J = 8.0Hz, 1H), 7.79-7.75 (m, 3H), 7.71 (d, J = 8.8 Hz, 1H), 7.60-7.56 (m, 1H), 7.53-7.48 (m,
3H), 7.43 (d, J = 7.2 Hz, 2H), 7.33-7.30 (m, 1H), 7.22 (d, J = 5.6 Hz, 2H), 6.23 (t, J = 6.4 Hz, 1H), 4.81
(s, 2H), 4.24 (d, J = 6.0 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 152.3, 151.9, 142.3, 139.3,
134.6, 132.0, 131.0, 130.9, 129.8, 129.4, 128.9, 128.8, 128.6, 128.5, 127. 8, 127.6, 127.5, 126.7, 126.6,
126.1, 124.8, 124.4, 123.3, 123.0, 116.1, 112.6, 60.0, 25.0. IR (KBr, ν, cm-1) 3441, 1591, 1491, 1395,
1263, 1096, 1006, 808. HRMS (ESI) m/z: [M + Na]+ Calcd for C28H21ClO2Na 447.1128; Found
447.1119.
(Z)-2-(4-bromophenyl)-4-(2-phenylnaphtho[2,1-b]furan-1-yl)but-2-en-1-ol (3h, major) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3h (73.0 mg, 52%) as a
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white solid, mp 127-128 C, Z/E= 10:1; H NMR (400 MHz, CDCl3; δ, ppm) 8.14-8.10 (m, 1H), 7.98-
7.94 (m, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.66 (d, J = 8.8 Hz, 1H), 7.64-7.61 (m, 2H), 7.59-7.56 (m, 2H),
7.52-7.47 (m, 2H), 7.43-7.38 (m, 3H), 7.31-7.27 (m, 2H), 6.13 (t, J = 7.0 Hz, 1H), 4.37 (s, 2H), 3.99 (d,
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J = 6.4 Hz, 2H). C{1H} NMR (100 MHz, CDCl3; δ, ppm) 152.1, 151.4, 140.8, 136.8, 131.8, 130.9,
130.8, 130.6, 129.3, 128.7, 128.5, 128.3, 127.5, 127.0, 126.3, 125.9, 124.2, 123.4, 123.0, 122.0, 116.3,
112.5, 67.7, 25.7. IR (KBr, ν, cm-1) 3422, 3053, 1488, 1393, 1070, 1011, 802, 730. HRMS (ESI) m/z:
[M + Na]+ Calcd for C28H21BrO2Na 491.0623; Found 491.0611.
(Z)-2-(3-bromophenyl)-4-(2-phenylnaphtho[2,1-b]furan-1-yl)but-2-en-1-ol (3i) Isolation by column
chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3i (95.5 mg, 68%) as a white solid,
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mp 167-168 oC, Z/E > 19:1; H NMR (400 MHz, CDCl3; δ, ppm) 8.36 (d, J = 8.4 Hz, 1H), 7.99 (d, J =
8.0 Hz, 1H), 7.79-7.75 (m, 3H), 7.71 (d, J = 8.8 Hz, 1H), 7.60-7.56 (m, 2H), 7.54-7.49 (m, 3H), 7.43 (d,
J = 7.2 Hz, 1H), 7.39-7.35 (m, 2H), 7.18-7.14 (m, 1H), 6.22 (t, J = 6.2 Hz, 1H), 4.80 (s, 2H), 4.24 (d, J
= 6.4 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 152.3, 152.0, 142.6, 139.3, 131.0(0),
131.0(9), 130.9, 130.5, 130.1, 129.6, 129.4, 128.9, 128.6(7), 128.6(4), 127.8, 126.6, 126.1, 125.1, 124.4,
123.2, 123.0, 122.8, 116.1, 112.6, 60.0, 25.3. IR (KBr, ν, cm-1) 3412, 1589, 1491, 1396, 1096, 1007,
807, 697. HRMS (ESI) m/z: [M + Na]+ Calcd for C28H21BrO2Na 491.0623; Found 491.0625.
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(Z)-2-phenyl-4-(2-(p-tolyl)naphtho[2,1-b]furan-1-yl)but-2-en-1-ol (3j, major) Isolation by column
chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3j (99.4 mg, 82%) as a white solid,
mp 123-124 oC, Z/E= 3:1; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.14 (d, J = 7.6 Hz, 1H), 7.97-7.93 (m,
1H), 7.70 (d, J = 2.8 Hz, 1H), 7.67 (s, 1H), 7.57 (d, J = 8.0 Hz, 2H), 7.51 (s, 1H), 7.49 (d, J = 2.4 Hz,
2H), 7.48-7.45 (m, 3H), 7.34-7.31 (m, 1H), 7.22 (d, J = 8.4 Hz, 2H), 6.10 (t, J = 6.6 Hz, 1H), 4.42 (s,
2H), 4.02 (d, J = 6.8 Hz, 2H), 2.43 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 151.9, 141.8,
138.1, 130.8, 129.6, 129.4, 129.2, 128.9, 128.7, 127.9, 127.6, 127.3, 126.6, 126.3, 126.1, 125.6, 124.1,
123.6, 123.1, 116.1, 112.4, 67.8, 25.8, 21.4. IR (KBr, ν, cm-1) 3424, 3022, 1505, 1441, 1392, 1266,
1085, 1005. HRMS (ESI) m/z: [M + Na]+ Calcd for C29H24O2Na 427.1674; Found 427.1665.
(Z)-2-phenyl-4-(2-(m-tolyl)naphtho[2,1-b]furan-1-yl)but-2-en-1-ol (3k, major) Isolation by column
chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3k (65.4 mg, 54%) as a white solid,
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mp 149-150 oC, Z/E= 15:1; H NMR (400 MHz, CDCl3; δ, ppm) 8.41 (d, J = 8.4 Hz, 1H), 7.99 (d, J =
8.0 Hz, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.62-7.56 (m, 3H), 7.52-7.49 (m, 1H),
7.47-7.45 (m, 2H), 7.43-7.38 (m, 1H), 7.34-7.26 (m, 3H), 7.24 (d, J = 7.2 Hz, 1H), 6.23 (t, J = 6.2 Hz,
1H), 4.86 (s, 2H), 4.24 (d, J = 6.4 Hz, 2H), 2.46 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3; δ, ppm)
152.1, 152.0, 140.3, 140.2, 138.6, 130.9, 130.8, 129.7, 129.3, 128.7, 128.6(4), 128.6(5), 128.3, 127.6,
126.6, 126.5, 125.8, 124.9, 124.3, 123.4, 123.1, 116.3, 112.5, 60.1, 25.2, 21.6. IR (KBr, ν, cm-1) 3416,
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3058, 1608, 1488, 1393, 1265, 1172, 1005. HRMS (ESI) m/z: [M + Na]+ Calcd for C29H24O2Na
427.1674; Found 427.1682.
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column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3l (92.8 mg, 74%) as a white
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solid, mp 143-144 oC, Z/E= 7:1; H NMR (400 MHz, CDCl3; δ, ppm) 8.40 (d, J = 8.4 Hz, 1H), 7.98 (d,
J = 8.0 Hz, 1H), 7.76 (d, J = 9.2 Hz, 1H), 7.72-7.69 (m, 1H), 7.59-7.54 (m, 2H), 7.52-7.48 (m, 2H),
7.48-7.43 (m, 3H), 7.33-7.27 (m, 3H), 7.25 (s, 1H), 6.22 (t, J = 4.8 Hz, 1H), 4.85 (s, 2H), 4.23 (d, J =
6.0 Hz, 2H), 2.36 (s, 3H), 2.34 (s, 3H). C{1H} NMR (100 MHz, CDCl3; δ, ppm) 152.3 152.1, 140.2,
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137.3, 137.2, 130.9, 130.1, 129.9, 129.3, 128.9, 128.7, 128.6, 128.5, 127.6, 126.6, 126.5, 125.6, 125.3,
124.2, 123.4, 115.8, 112.5, 60.1, 25.3, 20.0, 19.8. IR (KBr, ν, cm-1) 3426, 1624, 1500, 1436, 1389,
1086, 1086, 1009. HRMS (ESI) m/z: [M + Na]+ Calcd for C30H26O2Na 441.1830; Found 441.1847.
(Z)-4-(2-(3,5-dimethylphenyl)naphtho[2,1-b]furan-1-yl)-2-phenylbut-2-en-1-ol (3m, major) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3m (76.5 mg, 61%) as a
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white solid, mp 134-135 C, Z/E= 2:1; H NMR (400 MHz, CDCl3; δ, ppm) 8.15-8.11 (m, 1H), 8.01-
7.96 (m, 1H), 7.66, J = 8.8 Hz, 1H), 7.46 (d, J = 4.4 Hz, 5H), 7.41-7.37 (m, 2H), 7.32-7.28 (m, 3H),
7.02 (s, 1H), 6.08 (t, J = 6.4 Hz, 1H), 4.43 (d, J = 1.2 Hz, 2H), 4.04 (d, J = 6.4 Hz, 2H), 2.36 (s, 6H).
13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 152.0, 151.7, 141.7, 138.5, 138.3, 130.8, 130.3, 130.0, 129.2,
128.8, 128.7, 128.5, 127.8, 126.6, 126.2, 125.5, 125.3, 124.1, 123.6, 123.1, 116.4, 112.4, 67.8, 25.7,
21.5. IR (KBr, ν, cm-1) 3545, 3052, 1492, 1391, 1267, 1114, 1016, 836. HRMS (ESI) m/z: [M + Na]+
Calcd for C30H26O2Na 441.1830; Found 441.1852.
(Z)-4-(2-(4-ethylphenyl)naphtho[2,1-b]furan-1-yl)-2-phenylbut-2-en-1-ol (3n, major) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3n (75.2 mg, 60%) as a
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white solid, mp 161-162 C, Z/E= 5:1; H NMR (400 MHz, CDCl3; δ, ppm) 8.40 (d, J = 8.0 Hz, 1H),
7.99 (d, J = 7.6 Hz, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.73-7.69 (m, 3H), 7.58-7.54 (m, 1H), 7.51-7.44 (m,
4H), 7.37-7.28 (m, 4H), 6.23 (t, J = 6.2 Hz, 1H), 4.86 (s, 2H), 4.24 (d, J = 6.4 Hz, 2H), 2.76-2.70 (m,
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2H), 1.30 (t, J = 7.6 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 152.1, 152.1, 144.8, 140.3,
130.9, 129.8, 129.3, 128.6, 128.4, 127.7, 127.6, 126.6, 126.4, 125.7, 124.2, 123.4, 115.9, 112.5, 60.1,
28.8, 25.3, 15.5. IR (KBr, ν, cm-1) 3417, 2957, 1625, 1505, 1437, 1393, 1006, 797. HRMS (ESI) m/z:
[M + Na]+ Calcd for C30H26O2Na 441.1830; Found 441.1850.
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(Z)-2-phenyl-4-(2-(4-propylphenyl)naphtho[2,1-b]furan-1-yl)but-2-en-1-ol (3o, major) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3o (81.6 mg, 63%) as a
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white solid, mp 89-90 oC, Z/E= 3:1; H NMR (400 MHz, CDCl3; δ, ppm) 8.16-8.12 (m, 1H), 7.97-7.93
(m, 1H), 7.73-7.69 (m, 2H), 7.66 (d, J = 8.8 Hz, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.52-7.48 (m, 5H), 7.35-
7.32 (m, 1H), 7.23 (d, J = 8.4 Hz, 2H), 6.11 (t, J = 6.6 Hz, 1H), 4.43 (d, J = 0.8 Hz, 2H), 4.03 (d, J = 6.4
Hz, 2H), 2.70-2.61 (m, 2H), 1.76-1.64 (m, 2H), 1.04-0.98 (m, 3H). 13C{1H} NMR (100 MHz, CDCl3; δ,
ppm) 152.0, 151.6, 142.9, 141.8, 137.8, 130.8, 129.8, 129.2, 129.0(8), 129.0(5), 128.8, 128.7, 128.5,
128.3, 127.9, 127.6, 127.3, 126.6, 126.4, 126.1, 125.5, 124.1, 123.6, 123.2, 116.1, 112.4, 67.8, 37.9,
25.8, 24.5, 13.9. IR (KBr, ν, cm-1) 3427, 3052, 1623, 1505, 1436, 1392, 1267, 1087. HRMS (ESI) m/z:
[M + Na]+ Calcd for C31H28O2Na 455.1987; Found 455.1977.
(Z)-4-(2-(4-(tert-butyl)phenyl)naphtho[2,1-b]furan-1-yl)-2-phenylbut-2-en-1-ol (3p) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3p (73.6 mg, 55%) as a
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white solid, mp 88-89 C, Z/E > 19:1; H NMR (400 MHz, CDCl3; δ, ppm) 8.17-8.09 (m, 1H), 7.97-
7.91 (m, 1H), 7.71 (d, J = 9.2 Hz, 1H), 7.66 (d, J = 8.8 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.53-7.49 (m,
2H), 7.49-7.45 (m, 4H), 7.45-7.37 (m, 3H), 6.11 (t, J = 6.4 Hz, 1H), 4.43 (s, 2H), 4.03 (d, J = 6.4 Hz,
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2H), 1.38 (s, 9H). C{1H} NMR (100 MHz, CDCl3; δ, ppm) 152.0, 151.6, 151.2, 141.7, 137.8, 130.8,
129.2, 129.0, 128.6, 128.5, 128.0, 127.8, 127.2, 126.4, 126.1, 125.6, 125.5, 124.1, 123.5, 123.2, 116.1,
112.4, 67.8, 34.8, 31.3, 25.8. IR (KBr, ν, cm-1) 3428, 3053, 1623, 1441, 1392, 1173, 1012, 802. HRMS
(ESI) m/z: [M + Na]+ Calcd for C32H30O2Na 469.2143; Found 469.2120.
(Z)-4-(2-(4-fluorophenyl)naphtho[2,1-b]furan-1-yl)-2-phenylbut-2-en-1-ol (3q) Isolation by column
chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3q (85.7mg, 70%) as a white solid,
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mp 125-126 oC Z/E > 19:1; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.18 (d, J = 8.0 Hz, 1H), 7.97-7.93 (m,
1H), 7.73 (d, J = 8.8 Hz, 1H), 7.64 (d, J = 8.8 Hz, 1H), 7.61-7.56 (m, 2H), 7.55-7.47 (m, 4H), 7.46-7.38
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(m, 3H), 7.09-7.03 (m, 2H), 6.11 (t, J = 6.4 Hz, 1H), 4.43 (s, 2H), 3.98 (d, J = 6.8 Hz, 2H). C{1H}
NMR (100 MHz, CDCl3; δ, ppm) 162.5 (1JCF =247.1 Hz), 152.0, 150.4, 141.9, 137.7, 130.9, 129.2,
129.2(3JCF =8.2 Hz), 128.9, 128.7, 128.5, 128.0, 127.0(4JCF =3.3 Hz), 126.3, 125.9, 125.8, 124.2, 123.4,
122.9, 116.4, 115.7(2JCF =21.6 Hz), 112.4, 67.7, 25.7. IR (KBr, ν, cm-1) 3483, 3051, 1598, 1501, 1391,
1222, 1081, 993. HRMS (ESI) m/z: [M + Na]+ Calcd for C28H21FO2Na 431.1423; Found 431.1407.
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(Z)-4-(2-(4-chlorophenyl)naphtho[2,1-b]furan-1-yl)-2-phenylbut-2-en-1-ol (3r) Isolation by column
chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3r (95.4 mg, 75%) as a white solid,
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mp 88-89 C Z/E > 19:1; H NMR (400 MHz, CDCl3; δ, ppm) 7.48-7.41 (m, 4H), 7.40 (d, J = 7.6 Hz,
3H), 7.34 (d, J = 7.2 Hz, 1H), 7.32-7.26 (m, 3H), 7.25 (d, J = 6.8 Hz, 2H), 7.21-7.17 (m, 2H), 5.89 (t, J
= 7.0 Hz, 1H), 4.32 (s, 2H), 3.61 (d, J = 7.2 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 153.9,
149.9, 141.6, 137.7, 134.0, 130.0, 129.3, 128.8(0), 128.8(8), 128.7, 128.1, 127.8, 124.9, 124.8, 122.7,
119.7, 114.9, 111.1, 67.7, 24.0. IR (KBr, ν, cm-1) 3306, 1488,1453, 1094, 1008, 830, 756, 696. HRMS
(ESI) m/z: [M + Na]+ Calcd for C28H21ClO2Na 447.1128; Found 447.1131.
(Z)-4-(2-(3-chlorophenyl)naphtho[2,1-b]furan-1-yl)-2-phenylbut-2-en-1-ol (3s) Isolation by column
chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3s (91.5 mg, 72%) as a white solid,
mp 107-108 oC, Z/E > 19:1; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.46 (d, J = 8.4 Hz, 1H), 8.04 (d, J =
8.0 Hz, 1H), 7.84 (d, J = 9.2 Hz, 2H), 7.77-7.71 (m, 2H), 7.67-7.61 (m, 1H), 7.58-7.54 (m, 1H), 7.52-
7.47 (m, 3H), 7.39-7.31 (m, 4H), 6.24 (t, J = 6.6 Hz, 1H), 4.94 (s, 2H), 4.30 (d, J = 6.0 Hz, 2H).
13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 152.3, 150.2, 140.8, 140.1, 134.8, 132.6, 130.9, 130.1, 129.4,
129.1, 128.7, 128.3, 127.7, 127.4, 126.7, 126.6, 126.5, 125.6, 124.4, 123.3, 117.5, 112.4, 60.2, 25.2. IR
(KBr, ν, cm-1) 3419, 1600, 1478, 1393, 1237, 1108, 100, 803. HRMS (ESI) m/z: [M + Na]+ Calcd for
C28H21ClO2Na 447.1128; Found 447.1101.
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(Z)-4-(2-(2-chlorophenyl)naphtho[2,1-b]furan-1-yl)-2-phenylbut-2-en-1-ol (3t, major) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3t (50.9 mg, 40%) as a white
solid, mp 87-88 oC, Z/E= 2:1; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.15 (d, J = 8.0 Hz, 1H), 8.00-7.96
(m, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.70-7.66 (m, 2H), 7.54-7.50 (m, 2H), 7.49 (s, 1H), 7.47-7.44 (m,
4H), 7.40-7.36 (m, 1H), 7.32-7.29 (m, 2H), 6.08 (t, J = 6.4 Hz, 1H), 4.43 (s, 2H), 4.00 (d, J = 6.4 Hz,
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2H). C{1H} NMR (100 MHz, CDCl3; δ, ppm) 152.3, 149.7, 142.4, 137.7, 134.8, 132.6, 130.9, 129.9,
129.3, 128.9, 128.8, 128.5, 128.1, 128.0, 127.3, 126.6, 126.5, 126.4, 125.4, 124.4, 123.5, 123.0, 117.7,
112.4, 67.7, 25.7. IR (KBr, ν, cm-1) 3408, 3053, 1599, 1472, 1392, 1081, 999, 802. HRMS (ESI) m/z:
[M + H]+ Calcd for C28H22ClO2 425.1308; Found 425.1300.
(Z)-4-(2-(4-bromophenyl)naphtho[2,1-b]furan-1-yl)-2-phenylbut-2-en-1-ol (3u, major) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3u (120.7 mg, 86%) as a
white solid, mp 105-106 oC, Z/E= 10:1; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.96 (d, J = 8.0 Hz, 1H),
7.75-7.72 (m, 1H), 7.52 (d, J = 8.8 Hz, 1H), 7.43 (d, J = 4.0 Hz, 1H), 7.33-7.26 (m, 5H), 7.26-7.17 (m,
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5H), 7.04 (s, 1H), 5.88 (t, J = 6.4 Hz, 1H), 4.20 (s, 2H), 3.77 (d, J = 6.4 Hz, 2H). C{1H} NMR (100
MHz, CDCl3; δ, ppm) 152.1, 150.1, 142.1, 137.6, 131.8, 130.9, 129.7, 129.3, 128.9, 128.7(2), 128.7(7),
128. 5, 128.0, 126.4, 126.2, 125.4, 124.3, 123.4, 123.0, 122.2, 117.2, 112.4, 67.7, 25.7. IR (KBr, ν, cm-1)
3389, 1482, 1392, 1076, 1006, 837, 797, 712. HRMS (ESI) m/z: [M + Na]+ Calcd for C28H21BrO2Na
491.0623; Found 491.0625.
(Z)-4-(2-(3-chloro-4-fluorophenyl)naphtho[2,1-b]furan-1-yl)-2-phenylbut-2-en-1-ol (3v) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3v (106.1 mg, 80%) as a
white solid, mp 119-120 oC, Z/E > 19:1; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.17 (d, J = 8.0 Hz, 1H),
7.97-7.94 (m, 1H), 7.75-7.70 (m, 2H), 7.63 (d, J = 8.8 Hz, 1H), 7.54-7.46 (m, 4H), 7.45-7.38 (m, 4H),
7.11-7.06 (m, 1H), 6.07 (t, J = 6.4 Hz, 1H), 4.41 (d, J = 0.8 Hz, 2H), 3.96 (d, J = 6.4 Hz, 2H). 13C{1H}
NMR (100 MHz, CDCl3; δ, ppm) 157.8(1JCF =249.8 Hz), 152.2, 149.0(9), 149.0(7), 149.0(6),142.4,
137.6, 130.9, 129.5, 129.4, 128.8(3JCF =7.2 Hz), 128.5, 128.2(4JCF =4.1 Hz), 128.1, 127.1(3), 127.1(6),
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126.5, 126.4, 125.2, 124.4, 123.4, 122.8, 121.7, 121.5, 116.8 (2JCF =21.3 Hz) 112.4, 67.7, 25.6. IR (KBr,
ν, cm-1) 3424, 3060, 1494, 1392, 1262, 1087, 1011, 880. HRMS (ESI) m/z: [M + Na]+ Calcd for
C28H20ClFO2Na 465.1034; Found 465.1029.
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column chromatography (petroleum ether: ethyl acetate= 5/1 v/v) yielded 3w (94.1 mg, 72%) as an
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orange solid, mp 150-151 oC, Z/E= 9:1; H NMR (400 MHz, CDCl3; δ, ppm) 8.13 (d, J = 8.0 Hz, 1H),
7.99-7.96 (m, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.61-7.56 (m, 2H), 7.56-7.53 (m, 2H), 7.52-7.47 (m, 3H),
7.43-7.39 (m, 2H), 7.36-7.32 (m, 3H), 6.02 (t, J = 6.4 Hz, 1H), 4.35 (s, 2H), 3.86 (d, J = 6.8 Hz, 2H).
13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 153.0, 149.2, 147.0, 142.1, 137.8, 132.6, 132.3, 130.9, 129.7,
129.3, 128.7, 128.6, 128.5, 127.8, 126.6, 126.5, 125.1, 124.9, 124.4, 123.6, 122.2, 118.9, 112.6, 67.7(0),
67.7(9), 25.4. IR (KBr, ν, cm-1) 3450, 1619, 1528, 1393, 1026, 807, 702, 647. HRMS (ESI) m/z: [M +
Na]+ Calcd for C28H21NO4Na 458.1368; Found 458.1390.
(Z)-2-phenyl-4-(2-(thiophen-2-yl)naphtho[2,1-b]furan-1-yl)but-2-en-1-ol (3x, major) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3x (89.1 mg, 75%) as a
white solid, mp 88-89 oC, Z/E= 3:1; H NMR (400 MHz, CDCl3; δ, ppm) 8.03-7.99 (m, 1H), 7.94-7.90
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(m, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.62 (d, J = 8.8 Hz, 1H), 7.53-7.50 (m, 2H), 7.49 (d, J = 1.6 Hz, 1H),
7.47-7.46 (m, 1H), 7.45-7.40 (m, 3H), 7.39-7.35 (m, 1H), 7.33-7.30 (m, 1H), 7.11-7.07 (m, 1H), 5.99 (t,
J = 6.6 Hz, 1H), 4.40 (d, J = 1.2 Hz, 2H), 4.08 (d, J = 6.4 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3; δ,
ppm) 151.8, 146.7, 142.1, 137.8, 132.7, 130.8, 129.2, 129.0, 128.7, 128.3, 127.9, 127.7, 126.5, 126.2,
126.0, 125.8, 125.5, 125.4, 124.2, 123.5, 123.0, 116.3, 112.2, 67.7, 25.8. HRMS (ESI) m/z: [M + H]+
Calcd for C26H21O2S 397.1262; Found 397.1255.
(Z)-4-(2-methylnaphtho[2,1-b]furan-1-yl)-2-phenylbut-2-en-1-ol (3y, major) Isolation by column
chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3y (73.8 mg, 75%) as a white solid,
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1H), 7.56 (d, J = 9.2 Hz, 1H), 7.53-7.48 (m, 2H), 7.45-7.40 (m, 5H), 7.31-7.26 (m, 1H), 5.93 (t, J = 6.8
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Hz, 1H), 4.33 (s, 2H), 3.72 (d, J = 6.8 Hz, 2H), 2.35 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3; δ, ppm)
151.5, 150.4, 141.2, 138.1, 130.6, 130.1, 128.7, 128.0, 127.8, 126.5, 125.8, 124.3, 123.8, 123.5, 122.4,
115.0, 112.2, 67.8, 25.0, 11.9. IR (KBr, ν, cm-1) 3520, 1522, 1480, 1375, 1120, 1068, 953, 801. HRMS
(ESI) m/z: [M + Na]+ Calcd for C23H20O2Na 351.1361; Found 351.1373.
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(Z)-4-(7-bromo-2-phenylnaphtho[2,1-b]furan-1-yl)-2-phenylbut-2-en-1-ol (3z, major) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3z (92.7 mg, 66%) as a white
solid, mp 90-91 oC, Z/E= 3:1; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.15 (d, J = 1.6 Hz, 1H), 8.05 (d, J =
8.8 Hz, 1H), 7.69-7.65 (m, 4H), 7.62-7.60 (m, 1H), 7.59-7.57 (m, 1H), 7.52 (d, J = 1.2 Hz, 1H), 7.50 (s,
1H), 7.48 (d, J = 1.6 Hz, 1H), 7.43 (d, J = 2.8 Hz, 2H), 7.39-7.38 (m, 2H), 6.08 (t, J =6.6 Hz, 1H), 4.45
(d, J = 0.8 Hz, 2H), 4.01 (d, J = 6.4 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 152.5, 151.7,
142.0, 137.7, 131.7(9), 131.7(7), 130.7, 130.5, 128.9, 128.7, 128.4, 128.0, 127.8, 127.5, 125.9, 123.7,
123.2, 123.0, 118.8, 116.5, 116.4, 113.1, 67.7, 25.7. IR (KBr, ν, cm-1) 3423, 3053, 1564, 1499, 1391,
1296, 1168, 1068. HRMS (ESI) m/z: [M + Na]+ Calcd for C28H21BrO2Na 491.0623; Found 491.0627.
(Z)-4-(9-methoxy-2-phenylnaphtho[2,1-b]furan-1-yl)-2-phenylbut-2-en-1-ol (3aa, major) Isolation by
column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3aa (91.8 mg, 73%) as a
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white solid, mp 99-100 C, Z/E= 4:1; H NMR (400 MHz, CDCl3; δ, ppm) 7.88 (d, J = 9.2 Hz, 1H),
7.77-7.73 (m, 3H), 7.70 (d, J = 8.8 Hz, 1H), 7.60-7.57 (m, 1H), 7.53-7.49 (m, 2H), 7.47-7.40 (m, 4H),
7.32-7.27 (m, 2H), 7.16-7.13 (m, 1H), 6.23 (t, J = 5.8 Hz, 1H), 4.86 (s, 2H), 4.22 (d, J = 6.0 Hz, 2H),
3.86 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 158.3, 152.8, 151.5, 140.8, 140.1, 130.9, 130.7,
129.8, 129.7, 128.9, 128.8(0), 128.8(5), 128.7, 128.4, 127.8, 127. 7, 127.4, 126.5, 125.9, 125.8, 122.6,
116.3, 115.3, 110.2, 110.1, 103.9, 59.9, 55.6, 25.1. IR (KBr, ν, cm-1) 3435, 3026, 1588,1493, 1385,
1260, 1057, 807. HRMS (ESI) m/z: [M + Na]+ Calcd for C29H24O3Na 443.1623; Found 443.1615.
(Z)-2-phenyl-4-(2-(p-tolyl)benzofuran-3-yl)but-2-en-1-ol (3bb) Isolation by column chromatography
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(petroleum ether: ethyl acetate= 10/1 v/v) yielded 3bb (74.3 mg, 70%) as a white solid, mp 84-85 C,
Z/E > 19:1; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.51 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 4.4 Hz, 1H), 7.45
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(d, J = 3.6 Hz, 1H), 7.43 (s, 1H), 7.41 (s, 1H), 7.39-7.36 (m, 2H), 7.36 (s, 1H), 7.30-7.27 (m, 1H), 7.22
(d, J = 7.6 Hz, 1H), 7.18 (d, J = 8.0 Hz, 2H), 5.95 (t, J = 7.2 Hz 1H), 4.37 (s, 2H), 3.67 (d, J = 2.8 Hz,
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2H), 2.39 (s, 3H). C{1H} NMR (100 MHz, CDCl3; δ, ppm) 153.9, 151.3, 141.3, 138.2, 137.9, 130.2,
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129.3, 128.8, 128.6, 128.1, 127.7, 126.9, 125.7, 124.2, 122.4, 119.5, 113.7, 111.0, 67.8, 24.0, 21.4. IR
(KBr, ν, cm-1) 3306, 1571, 1507, 1402, 1262, 1100, 1010, 819. HRMS (ESI) m/z: [M + Na]+ Calcd for
C25H22O2Na 377.1517; Found 377.1510.
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(Z)-4-(2-(4-chlorophenyl)benzofuran-3-yl)-2-phenylbut-2-en-1-ol (3cc, major) Isolation by column
chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3cc (76.3 mg, 68%) as a white solid,
mp 89-90 oC, Z/E= 13:1; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.52 (s, 1H), 7.50 (s, 1H), 7.48-7.47 (m,
1H), 7.46 (d, J = 1.6 Hz, 2H), 7.44 (s, 1H), 7.41-7.38 (m, 1H), 7.36 (d, J = 1.6 Hz, 1H), 7.34 (s, 1H),
7.31 (d, J = 2.0 Hz, 2H), 7.29 (s, 1H), 7.23 (d, J = 7.6 Hz, 1H), 5.94 (t, J = 7.2 Hz, 1H), 4.38 (s, 2H), ,
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3.66 (d, J = 7.2 Hz, 2H). C{1H} NMR (100 MHz, CDCl3; δ, ppm) 153.9, 149.9, 141.6, 137.7, 134.0,
130.0, 129.3, 128.8(0), 128.8(7), 128.7, 128.1, 127.8, 124.9, 124.8, 122.7, 119.7, 114.8, 111.1, 67.7,
24.0. IR (KBr, ν, cm-1) 3445, 1543, 1488, 1400, 1259, 1093, 1008, 830. HRMS (ESI) m/z: [M + Na]+
Calcd for C24H19ClO2Na 397.0971; Found 397.0961.
(Z)-4-(2-([1,1'-biphenyl]-4-yl)benzofuran-3-yl)-2-phenylbut-2-en-1-ol (3dd, major) Isolation by column
chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 3dd (81.1 mg, 65%) as a white solid,
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mp 95-96 C, Z/E= 3:1; C{1H} NMR (100 MHz, CDCl3; δ, ppm) 7.75-7.67 (m, 3H), 7.64 (d, J = 1.6
Hz, 1H), 7.62 (s, 1H), 7.60 (s, 1H), 7.50-7.47 (m, 3H), 7.46-7.42 (m, 3H), 7.38 (d, J = 7.6 Hz, 4H),
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7.33-7.28 (m, 2H), 5.99 (t, J = 7.0 Hz, 1H), 4.39 (s, 2H), 3.73 (d, J = 7.2 Hz, 2H). C{1H} NMR (100
MHz, CDCl3; δ, ppm) 154.0, 150.8, 141.5, 140.8, 140.5, 137.9, 130.2, 129.8, 129. 3, 128.9, 128.7,
127.7, 127.6, 127.5, 127.3, 127.1, 125.4, 124.5, 122.5, 119.6, 114.6, 111.1, 67.8, 24.1. IR (KBr, ν, cm-1)
3431, 1599, 1487, 1403, 1261, 1097, 1008, 760. HRMS (ESI) m/z: [M + Na]+ Calcd for C30H24O2Na
439.1674; Found 439.1666;
General Procedure for the Synthesis of 5
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Example for the synthesis of 5a.
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Under the air conditions, 1-(phenylethynyl)naphthalen-2-ol (1a, 0.36 mmol, 87.8 mg), 4-vinyl-1,4-
dihydro-2H-benzo[d][1,3]oxazin-2-one (4a, 0.3 mmol, 52.6 mg) and Pd2(dba)3 (2.5 mol %, 6.9 mg)
were added in a 10-mL reaction vial, Then, MeCN (3.0 mL) was added into this reaction system. The
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reaction vial was sealed and heated at 60 C in an oil bath for 5 h until TLC (petroleum ether: ethyl
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acetate= 5:1) revealed that conversion of the starting material 4a was completed. Then the reaction
mixture was concentrated in vacuum, and the resulting residue was purified by column chromatography
on silica gel (eluent, petroleum ether/ ethyl acetate = 10:1) to afford the desired product 5a as white
solid.
(E)-2-(3-(2-phenylnaphtho[2,1-b]furan-1-yl)prop-1-en-1-yl)aniline (5a) Isolation by column
chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 5a (78.8 mg, 70%) as a white solid,
mp 96-97 oC, Z/E > 19:1; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.39 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 8.0
Hz, 1H), 7.83 (d, J = 7.2 Hz, 2H), 7.79-7.72 (m, 2H), 7.58-7.46 (m, 4H), 7.44-7.39 (m, 1H), 7.30 (d, J =
6.8 Hz, 1H), 7.06-7.01 (m, 1H), 6.77-6.71 (m, 1H), 6.61-6.52 (m, 3H), 4.17 (d, J = 2.8 Hz, 2H).
13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 152.2, 143.5, 130.9(3), 130.9(1), 129.3, 129.2, 128.8, 128.4,
128.3, 127.7, 127.5, 127.3, 126.4, 125.9, 124.2, 124.0, 123.5, 123.4, 118.9, 115.8, 114.7, 112.5, 29.5. IR
(KBr, ν, cm-1) 3434, 1613, 1489, 1393, 1266, 1070, 1024, 805. HRMS (ESI) m/z: [M + Na]+ Calcd for
C27H21NONa 398.1521; Found 398.1518.
(E)-5-methyl-2-(3-(2-phenylnaphtho[2,1-b]furan-1-yl)allyl)aniline
(5b)
Isolation
by
column
chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 5b (84.0 mg, 68%) as a white solid,
mp 101-102 oC, Z/E > 19:1; 1H NMR (400 MHz, DMSO; δ, ppm) 8.44 (d, J = 8.4 Hz, 1H), 8.07 (d, J =
7.6 Hz, 1H), 7.91-7.86 (m, 2H), 7.85-7.81 (m, 2H), 7.64-7.56 (m, 3H), 7.54-7.46 (m, 2H), 7.08 (d, J =
8.0 Hz, 1H), 6.70 (d, J = 15.6 Hz, 1H), 6.41-6.34 (m, 2H), 6.30 (d, J = 8.0 Hz, 1H), 4.78 (s, 2H), 4.11
(d, J = 4.0 Hz, 2H), 2.10 (s, 3H).13C{1H} NMR (100 MHz, DMSO; δ, ppm) 152.0, 151.7, 145.7, 137.6,
131.0, 130.8, 129.6, 129.6, 129.1, 128.3, 127.9, 127.6, 127.1, 126.8, 126.6, 126.0, 124.9, 124.0, 123.3,
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119.5, 118.1, 116.3, 116.1, 113.0, 29.3, 21.4. HRMS (ESI) m/z: [M + Na]+ Calcd for C28H23NO2Na
412.1677; Found 412.1689.
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(E)-4-methyl-N-(2-(3-(2-phenylnaphtho[2,1-b]furan-1-yl)prop-1-en-1-yl)phenyl)benzenesulfonamide
(5c) Isolation by column chromatography (petroleum ether: ethyl acetate= 10/1 v/v) yielded 5c (120.6
mg, 76%) as a white solid, mp 97-98 oC, Z/E > 19:1; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.19-8.10 (m,
2H), 7.94 (d, J = 8.8 Hz, 1H), 7.87 (d, J = 8.8 Hz, 1H), 7.66 (d, J = 7.6 Hz, 2H), 7.61-7.56 (m, 2H),
7.55-7.49 (m, 2H), 7.46-7.39 (m, 2H), 7.30 (d, J = 7.6 Hz, 1H), 7.25-7.20 (m, 1H), 7.19-7.13 (m, 1H),
6.70 (d, J = 8.0 Hz, 2H), 6.64 (d, J = 8.0 Hz, 2H), 6.43-6.35 (m, 1H), 5.62 (d, J = 16.0 Hz, 1H), 5.41 (s,
1H), 4.03-3.97 (m, 2H), 1.89 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 152.3 152.2, 143.5,
135.8, 133.1, 133.0, 132.5, 131.3, 130.7, 130.1, 129.2, 129.0, 128.6, 128.4, 128.0, 127.3, 127.2, 126.9,
126.7(3), 126.7(5), 126.2, 124.8, 123.3, 122.9, 113.7, 112.5, 29.4, 21.0. IR (KBr, ν, cm-1) 3311, 1485,
1385, 1183, 1090, 899, 818, 768. HRMS (ESI) m/z: [M + Na]+ Calcd for C34H27O3Sna 552.1609; Found
552.1589.
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General Procedure for the Synthesis of 6a
To a solution of (Z)-2-phenyl-4-(2-phenylnaphtho[2,1-b]furan-1-yl)but-2-en-1-ol (3a, 0.5 mmol,
195.0 mg) in DCM (5.0 mL) was added the solution of pyridinium chlorochromate (PCC, 1.5 mmol,
161.7 mg) in DCM (5.0 mL) at 0 °C. After stirring for 30 min, the reaction mixture was concentrated in
vacuum, and the resulting residue was purified by column chromatography on silica gel (eluent,
petroleum ether/ ethyl acetate = 10:1) to afford the desired product 6a as white solid.
(Z)-2-phenyl-4-(2-phenylnaphtho[2,1-b]furan-1-yl)but-2-enal (6a) Isolation by column chromatography
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(petroleum ether: ethyl acetate= 10/1 v/v) yielded 6a (116.4 mg, 95%) as a white solid, mp 92-93 C,
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Z/E > 19:1; H NMR (400 MHz, DMSO; δ, ppm) 9.67 (s, 1H), 8.11-8.06 (m, 2H), 7.90 (d, J = 9.2 Hz,
1H), 7.84 (d, J = 8.8 Hz, 1H), 7.63-7.59 (m, 2H), 7.58-7.52 (m, 4H), 7.49-7.45 (m, 3H), 7.44 (d, J = 1.6
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Hz, 3H), 7.23 (t, J = 6.8 Hz, 1H), 4.30 (d, J = 6.4 Hz, 2H). C{1H} NMR (100 MHz, DMSO; δ, ppm)
194.7, 153.0, 151.9, 151.7, 144.1, 132.5, 131.0, 130.4, 130.0, 129.8, 129.4, 129.2, 128.8, 128.7, 128.1,
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127.6, 127.1, 126.8, 125.0, 123.3, 122.5, 115.0, 112.9, 26.9. IR (KBr, ν, cm-1) 3650, 1683, 1492, 1394,
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ASSOCIATED CONTENT
Supporting Information
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1H and C NMR spectra for all pure products, and X-ray crystal data (CIF) for 5b. 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. 21871112 and 21971090) and the
Graduate Education Innovation Project of Jiangsu Province (No. SJKY19_2000).
REFERENCES
[1] For selected reviews, see: (a) Huang, M.-H.; Hao, W.-J.; Li, G.; Tu, S.-J.; Jiang, B. Recent Advances in Radical
Transformations of Internal Alkynes. Chem. Commun. 2018, 54, 10791−10811. (b) Huang, M.-H.; Hao, W.-J.; Jiang, B.
Recent Advances in Radical Enabled Bicyclization and Annulation /1, n-Bifunctionalization Reactions. Chem. Asian J.
2018, 13, 2958−2977. (c) Dorel, R.; Echavarren, A. M. Gold(I)-Catalyzed Activation of Alkynes for the Construction of
Molecular Complexity. Chem. Rev. 2015, 115, 9028−9072. (d) Chinchilla, R.; Najera, C. Chemicals from Alkynes with
Palladium Catalysts. Chem. Rev. 2014, 114, 1783−1826. (e) Gilmore, K.; Alabugin, I. V. Cyclizations of Alkynes:
Revisiting Baldwin’s Rules for Ring Closure. Chem. Rev. 2011, 111, 6513−6556. (f) Wille, U. Radical Cascades
Initiated by Intermolecular Radical Addition to Alkynes and Related Triple Bond Systems. Chem. Rev. 2013, 113,
813−853.
[2] (a) Li, Y.; Gryn'ova, G.; Saenz, Felipe; J. X.; Sivula, K.; Corminboeuf, C.; Waser, J. Heterotetracenes: Flexible
Synthesis and in Silico Assessment of the Hole-Transport Properties. Chem. Eur. J. 2017, 23, 8058−8065. (b) Zhang, T.-
S.; Wang, R.; Cai, P.-J.; Hao, W.-J.; Tu, S.-J.; Jiang, B. Silver-catalyzed Nitration/annulation of 2-alkynylanilines for
Tunable Synthesis of Nitrated Indoles and Indazole-2-oxides. Org. Chem. Front. 2019, 6, 2968−2973. (c) Liu, S.; Chen,
K.; Hao, W.-J.; Tu, X.-C.; Tu, S.-J.; Jiang, B. Generation of 1,3-dimethylene-substituted Isobenzofurans via Pd(II)-
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The Journal of Organic Chemistry
Catalyzed Selective oxo-cyclization/SO2 Insertion Ascade of β-alkynyl Ketones. J. Org. Chem. 2019, 84, 1964−1971.
(d) Hao, W.-J.; Wu, Y.-N.; Gao, Q.; Wang, S.-L.; Tu, S.-J.; Jiang, B. Dual Cobalt(II)/silver Catalysis: Synthesis of
Aryliminated Pyrrolo[2,3-b]indoles via Multicomponent Bicyclization Cascades. Tetrahedron Lett. 2016, 57,
4767−4769. (e) Cacchi, S.; Fabrizi, G.; Moro, L. Palladium-Catalyzed Cyclization of o-Alkynylphenols with Allyl
Carbonates. A Regioselective Synthesis of 2-Substituted-3-allylbenzo[b]furans. Synlett 1998, 741−745. (f) Swamy, N.
K.; Yazici, A.; Pyne, S. G. Copper-Mediated Cyclization-Halogenation and Cyclization-Cyanation Reactions of β-
Hydroxyalkynes and o-Alkynylphenols and Anilines. J. Org. Chem. 2010, 75, 3412−3419. (g) Xia, Z.; Khaled, O.;
Mouriès-Mansuy, V.; Ollivier, C.; Fensterbank, L. Dual Photoredox/Gold Catalysis Arylative Cyclization of o-
Alkynylphenols with Aryldiazonium Salts: A Flexible Synthesis of Benzofurans. J. Org. Chem. 2016, 81, 7182−7190,
and references cited therein.
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2
3
4
5
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9
10
11
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13
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40
41
42
43
44
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46
47
48
49
50
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53
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59
60
[3] Sun, J.; Wang, K.; Wang, P.; Zheng, G.; Li, X. Rhodium(III)-Catalyzed Oxidative Allylic C–H Indolylation via
Nucleophilic Cyclization. Org. Lett. 2019, 21, 4662−4666.
[4] (a) Watanabe, K.; Mino, T.; Ishikawa, E.; Masuda, C.; Yoshida, Y.; Sakamoto, M. Hydrazone–Pd-catalyzed Direct
Intermolecular Reaction of o-alkynylphenols with Allylic Acetates. Org. Biomol. Chem. 2018, 16, 575−584. (b) Tian,
M.; Bai, D.; Zheng, G.; Chang, J.; Li, X. Rh(III)-Catalyzed Asymmetric Synthesis of Axially Chiral Biindolyls by
Merging C−H Activation and Nucleophilic Cyclization, J. Am. Chem. Soc. 2019, 141, 9527−9532.
[5] Li, T.-R.; Wang, Y.-N.; Xiao, W.-J.; Lu, L.-Q. Transition-metal-catalyzed Cyclization Reactions using Vinyl and
Ehynyl Benzoxazinones as Dipole Precursors. Tetrahedron Lett. 2018, 59, 1521–1530.
[6] Guo, W.; Glmóz, J. E.; CristÒfol, À.; Xie, J.; Kleij, A. W. Catalytic Transformations of Functionalized Cyclic Organic
Carbonates. Angew. Chem. Int. Ed. 2018, 57, 13735–13747.
[7] (a) Khan, A.; Yang, L.; Xu, J.; Jin, L. Y.; Zhang, Y. J. Palladium-Catalyzed Asymmetric Decarboxylative Cycloaddition
of Vinylethylene Carbonates with Michael Acceptors: Construction of Vicinal Quaternary Stereocenters. Angew. Chem.
Int. Ed. 2014, 53, 11257–11260. (b) Khan, A.; Zheng, R.; Kan, Y.; Ye, J.; Xing, J.; Zhang, Y. J. Palladium-Catalyzed
Decarboxylative Cycloaddition of Vinylethylene Carbonates with Formaldehyde: Enantioselective Construction of
Tertiary Vinylglycols. Angew. Chem. Int. Ed. 2014, 53, 6439–6442. (c) Khan, A.; Xing, J.; Zhao, J.; Kan, Y.; Zhang,
W.; Zhang, Y. J. Palladium-Catalyzed Enantioselective Decarboxylative Cycloaddition of Vinylethylene Carbonates
with Isocyanates. Chem. Eur. J. 2015, 21, 120–124. (d) Yang, L.; Khan, A.; Zheng, R.; Jin, L. Y.; Zhang, Y. J. Pd-
Catalyzed Asymmetric Decarboxylative Cycloaddition of Vinylethylene Carbonates with Imines. Org. Lett. 2015, 17,
6230−6233. (e) Khan, A.; Zhang, Y. J. Palladium-Catalyzed Asymmetric Decarboxylative Cycloaddition of
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Vinylethylene Carbonates with Electrophiles: Construction of Quaternary Stereocenters. Synlett. 2015, 26, 853–860. (f)
Liu, K.; Khan, I.; Cheng, J.; Hsueh, Y. J.; Zhang, Y. J. Asymmetric Decarboxylative Cycloaddition of Vinylethylene
Carbonates with β‑Nitroolefins by Cooperative Catalysis of Palladium Complex and Squaramide. ACS Catal. 2018, 8,
11600−11604. (g) I.; Khan, Zhao, C.; Zhang, Y. J. Pd-Catalyzed Asymmetric Decarboxylative Cycloaddition of
Vinylethylene Carbonates with 3-cyanochromones. Chem. Commun. 2018, 54, 4708−4711.
1
2
3
4
5
6
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42
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[8] (a) Rong, Z.-Q.; Yang, L.-C.; Liu, S.; Yu, Z.; Wang, Y.-N.; Tan, Z. Y.; Huang, R.-Z.; Lan, Y.; Zhao, Y. Nine-Membered
Benzofuran-Fused Heterocycles: Enantioselective Synthesis by Pd-Catalysis and Rearrangement via Transannular Bond
Formation. J. Am. Chem. Soc. 2017, 139, 15304−15307. (b) Yang, L.-C.; Rong, Z.-Q.; Wang, Y.-N.; Tan, Z. Y.; Wang,
M.; Zhao, Y. Construction of Nine-Membered Heterocycles through Palladium-Catalyzed Formal [5 + 4] Cycloaddition.
Angew. Chem. Int. Ed. 2017, 56, 2927–2931. (c) Yang, L.-C.; Tan, Z. Y.; Rong, Z.-Q.; Liu, R.; Wang, Y.-N.; Zhao, Y.
Palladium-Titanium Relay Catalysis Enables Switch from Alkoxide-π-Allyl to Dienolate Reactivity for Spiro-
Heterocycle Synthesis. Angew. Chem. Int. Ed. 2018, 57, 7860–7864.
[9] (a) Guo, W.; Martínez-Rodríguez, L.; Martin, E.; Escudero-Adán, E. C.; Kleij, A. W. Highly Efficient Catalytic
Formation of (Z)-1,4-But-2-ene Diols Using Water as a Nucleophile. Angew. Chem. Int. Ed. 2016, 55, 11037–11040. (b)
Guo, W.; Martínez-Rodríguez, L.; Kuniyil, R.; Martin, E.; Escudero-Adán, E. C.; Maseras, F.; Kleij, A. W.
Stereoselective and Versatile Preparation of Tri- and Tetrasubstituted Allylic Amine Scaffolds under Mild Conditions. J.
Am. Chem. Soc. 2016, 138, 11970−11978. (c) Cai, A.; Guo, W.; Martínez-Rodríguez, L.; Kleij, A. W. Palladium-
Catalyzed Regio- and Enantioselective Synthesis of Allylic Amines Featuring Tetrasubstituted Tertiary Carbons. J. Am.
Chem. Soc. 2016, 138, 14194−14197. (d) Glmóz, J. E.; Guo, W.; Kleij, A. W. Palladium-Catalyzed Stereoselective
Formation of Substituted Allylic Thioethers and Sulfones. Org. Lett. 2016, 18, 6042−6045. (e) Guo, W.; Cai, A.; Xie, J.;
Kleij, A. W. Asymmetric Synthesis of α,α-Disubstituted Allylic Amines through Palladium-Catalyzed Allylic
Substitution. Angew. Chem. Int. Ed. 2017, 56, 11797–11801. (f) Xie, J.; Guo, W.; Cai, A.; Escudero-Adán, E. C.; Kleij,
A. W. Pd-Catalyzed Enantio- and Regioselective Formation of Allylic Aryl Ethers. Org. Lett. 2017, 19, 6388−6391. (g)
Miralles, N.; Gómez, J. E.; Kleij, A. W.; Fernández, E. Copper-Mediated SN2′ Allyl−Alkyl and Allyl−Boryl Couplings
of Vinyl Cyclic Carbonates. Org. Lett. 2017, 19, 6096−6099. (h) Guo, W.; Kuniyil, R.; Gómez, J. E.; Maseras, F.; Kleij,
A. W. A Domino Process toward Functionally Dense Quaternary Carbons through Pd-Catalyzed Decarboxylative
C(sp3)−C(sp3) Bond Formation. J. Am. Chem. Soc. 2018, 140, 3981−3987. (i) Cristòfol, À.; Escudero-Adán, E. C.; Kleij,
A.W. Palladium-Catalyzed (Z)‑Selective Allylation of Nitroalkanes: Access to Highly Functionalized Homoallylic
Scaffolds. J. Org. Chem. 2018, 83, 9978−9990.
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[10]Singha, S.; Patra, T.; Daniliuc, C. G.; Glorius F. Highly Enantioselective [5 + 2] Annulations through Cooperative
1
2
3
N‑Heterocyclic Carbene (NHC) Organocatalysis and Palladium Catalysis. J. Am. Chem. Soc. 2018, 140, 3551−3554.
4
5
6
7
8
9
[11](a) Yuan C.; Wu, Y.; Wang, D.; Zhang, Z.; Wang, C.; Zhou, L.; Zhang, C.; Song, B.; Guo, H. Formal [5 + 3]
Cycloaddition of Zwitterionic Allylpalladium Intermediates with Azomethine Imines for Construction of N,O-
containing Eight-Membered Heterocycles. Adv. Synth. Catal. 2018, 360, 652−658. (b) Das, P.; Gondo, S.; Nagender, P.;
Uno, H.; Tokunaga, E.; Shibata, N. Access to Denzo-fused Nine-membered Heterocyclic Alkenes with a
Trifluoromethyl Carbinol Moiety via a Double Decarboxylativeformal Ring-expansion Process under Palladium
Catalysis. Chem. Sci. 2018, 9, 3276−3281.
10
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14
15
16
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18
19
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21
22
23
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57
58
59
60
[12] (a) Kato, K.; Kusakabe, T.; Sekiyama, E.; Ishino, Y.; Motodate, S.; Kato, S.; Mochida, T. Cyclization-Carbonylation-
Cyclization Coupling Reactions of N-Propargylanilines and o-Alkynylphenols with Palladium(II)-Bisoxazoline
Catalysts. Synthesis 2012, 1825−1832. (b) Fischer, J.; Savage G. P.; Coster M. J. A Concise Route to
Dihydrobenzo[b]furans: Formal Total Synthesis of (+)-Lithospermic Acid. Org. Lett. 2011, 13, 3376−3379. (c) Hu, W.;
Li, M.; Jiang, G.; Wu, W.; Jiang H. Synthesis of 2,3-Difunctionalized Benzofuran Derivatives through Palladium-
Catalyzed Double Isocyanide Insertion Reaction. Org. Lett. 2018, 20, 3500−3503. (d) Nakamura, M.; Ilies, L.; Otsubo,
S.; Nakamura, E. 3-Zinciobenzofuran and 3-Zincioindole: Versatile Tools for the Construction of Conjugated Structures
Containing Multiple Benzoheterole Units. Angew. Chem. Int. Ed. 2006, 45, 944−947. (e) Hu, Y.; Nawoschik, K. J.;
Liao, Y.; Ma, J.; Fathi, R.; Yang, Z. Synthesis of Conformationally Restricted 2,3-Diarylbenzo[b]furan by the Pd-
Catalyzed Annulation of o-Alkynylphenols:ꢀ Exploring a Combinatorial Approach. J. Org. Chem. 2004, 69, 2235−2239.
(f) Watanabe, K.; Mino, T.; Ikematsu, T.; Hatta, C.; Yoshida Y.; Sakamoto, M.; Hydrazone–palladium Catalyzed
Annulation of 1-cinnamyloxy-2-ethynylbenzene Derivatives. Org. Chem. Front. 2016, 3, 979−984.
[13] Niu, B.; Wu, X.-Y.; Wei, Y.; Shi, M. Palladium-Catalyzed Diastereoselective Formal [5 + 3] Cycloaddition for the
Construction of Spirooxindoles Fused with an Eight-Membered Ring. Org. Lett. 2019, 21, 4859-4863.
[14](a) Li, D.; Tan, Y.; Peng, L.; Li, S.; Zhang, N.; Liu, Y.; Yan, H. Asymmetric Mannich Reaction and Construction of
Axially Chiral Sulfone-Containing Styrenes in One Pot from α‑Amido Sulfones Based on the Waste−Reuse Strategy.
Org. Lett. 2018, 20, 4959−4963. (b) Ji, C.-L.; Hao, W.-J.; Zhang, J.; Geng, F.-Z.; Xu, T.; Tu, S.-J.; Jiang, B. Catalytic
Three-Component Synthesis of Functionalized Naphtho[2,1-b]oxecines via a Double Bond Cleavage–Rearrangement
Cascade. Org. Lett. 2019, 21, 6494-6498.
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[15]Wang, C.; Ling, Y.; Wu, Y.; Wang, Q.; Shi, W.; Yuan, C.; Yuan, C.; Xiao, Y.; Guo, H. Enantioselective Construction of
Tetrahydroquinazoline Motifs via Palladium-Catalyzed [4 + 2] Cycloaddition of Vinyl Benzoxazinones with Sulfamate-
Derived Cyclic Imines. Org. Lett. 2018, 20, 2880-2883.
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