Silver/Scandium-Cocatalyzed Bicyclization of β-Alkynyl Ketones Leading to Benzo[c]xanthenes and Naphtho[1,2-b]benzofurans

Article abstract of DOI:10.1021/acs.joc.7b02134

The combination of AgTFA and Sc(OTf)₃ enables the bimetallic synergistic catalysis of β-alkynyl ketones and para-quinone methides (p-QMs), allowing direct synthesis of 17 examples of benzo[c]xanthenes with generally good yields through a benzannulation/1,6-addition/cyclization sequence. Exchanging p-QMs for quinone imine ketal resulted in 10 examples of tetracyclic naphtho[1,2-b]benzofurans via a similar benzannulation/1,4-addition/cyclization cascade. During these reaction processes, AgTFA and Sc(OTf)₃ could be perfectly compatible, together with the realization of C(sp³)-H functionalization adjacent to carbonyl group on the β-alkynyl ketone unit.

Full text of DOI:10.1021/acs.joc.7b02134

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Article
Silver/Scandium Co-Catalyzed Bicyclization of #-Alkynyl Ketones
Leading to Benzo[c]xanthenes and Naphtho[1,2-b]benzofurans
Ke Chen, Shuai Liu, Dan Wang, Wen-Juan Hao, Peng Zhou, Shu-Jiang Tu, and Bo Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02134 • Publication Date (Web): 13 Oct 2017
Downloaded from http://pubs.acs.org on October 13, 2017
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The Journal of Organic Chemistry
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Silver/Scandium CoꢀCatalyzed Bicyclization of βꢀAlkynyl Ketones Leading to
Benzo[c]xanthenes and Naphtho[1,2ꢀb]benzofurans
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Ke Chen,1 Shuai Liu,1 Dan Wang, WenꢀJuan Hao,* Peng Zhou, ShuꢀJiang 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.
1These authors contributed equally to this work
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Eꢀmail: wjhao@jsnu.edu.cn(WJH); laotu@jsnu.edu.cn(SJT); jiangchem@jsnu.edu.cn(BJ);
RECEIVED DATE
ABSTRACT. The combination of AgTFA and Sc(OTf)3 enables the bimetallic synergistic catalysis of
β
ꢀalkynyl ketones and paraꢀquinone methides (pꢀQMs), allowing direct synthesis of 17 examples of
benzo[c]xanthenes with generally good yields through a benzannulation /1,6ꢀaddition/cyclization
sequence. Exchanging pꢀQMs for quinone imine ketal (QIK) resulted in 10 examples of tetracyclic
naphtho[1,2ꢀb]benzofurans via a similar benzannulation /1,4ꢀaddition/cyclization cascade. During these
reaction processes, AgTFA and Sc(OTf)3 could be perfectly compatible, together with the realization of
C(sp3)ꢀH functionalization adjacent to carbonyl group on the βꢀalkynyl ketone unit.
Introduction
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In a valuable class of oxygenꢀcontaining molecular family, xanthenes are common constituents in a
broad array of natural products,1 synthetic bioactive substances2 and fluorescent dyes.3 Compounds
incorporating a xanthene core structure exhibit a wide range of biological and pharmacological activities
including antiviral,4 antibacterial,5 antiplasmodial,6 antimalarial,7 antifungal,8 antiꢀinflammatory,9
anticancer,10 and antihypertensive,11 and also act as trypanothione reductase inhibitior.12 With these
contributions in mind, many chemists have contributed their efforts to develop efficient incorporation of
xanthene unit into organic and medicinal targets. Most of the synthetic endeavors to assemble this
bioactive core include Pdꢀcatalyzed cyclization of polycyclic aryltriflate esters,13 Lewis acidꢀcatalyzed
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reaction of
β
ꢀnaphthol,14a phenol14b or 2ꢀaryloxybenzaldehydes,14c annulation of aryne precursor,15
ultravioletꢀcatalyzed tandem reaction of 2ꢀbenzylideneꢀ1ꢀtetralones,16 and Brønsted acidꢀpromoted
reaction of 2ꢀtetralone and salicylaldehydes.17 Despite the limited preparation of xanthenes, the
development of a new and versatile strategy for the direct formation of xanthene frameworks would be
highly favorable.
Meanwhile, bicyclization reaction has attracted a continuation of attention as an efficient and reliable
synthetic tool for the synthesis of polycyclic functional molecules of chemical and biomedical
importance.18 During this reaction process, the synergistic utilization of several reactive sites of starting
materials leads to direct construction of two new rings in a single step. Thus, such reaction features
bond forming/annulation efficiency and high levels of structural complexity. In recent years, widespread
application of bicyclization reaction has been conducted to access various carbocycles and
heterocycles.19 In addition, synergistic catalysis enables two different catalysts to precisely activate
nucleophiles and/or electrophiles, respectively, thereby facilitating their sequential coupling to build up
the target compounds.20 Obviously, merging bicyclization reaction with synergistic catalysis will
provide a new protocol to construct unusual functional molecules, which are difficult to obtain through
traditional methods. Very recently, we have established a AgTFA/1,1’ꢀbinaphthylꢀ2,2’ꢀdiyl hydrogen
phosphate (BiNPO4H) coꢀcatalyzed bicyclization reaction of βꢀalkynyl ketones with paraꢀquinone
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methides (pꢀQMs), generating functionalized 6,6ꢀbenzannulated spiroketals (Scheme 1a).21 To continue
our efforts in this project, we found that exchanging silver/Brønsted acid catalysis for silver/scandium
catalysis favored this bicyclization reaction to work in a completely different direction, allowing dual
metalꢀcatalyzed benzannulation/1,6ꢀaddition/cyclization cascades to access the unexpected
benzo[c]xanthenes 3 (Scheme 1b). Using quinone imine ketal (QIK) 4 as a replacement for pꢀQMs 2 to
expand its synthetic utility, a similar bicyclization reaction proceeded smoothly to deliver tetracyclic
naphtho[1,2ꢀb]benzofurans 5 with acceptable yields through synergistic silver/scandium catalysis
(Scheme 1c). Herein, we elaborated these attractive and useful transformations in which the
combination of dual metal catalysis with bicyclization cascades was well compatible and C(sp3)ꢀH
functionalization adjacent to carbonyl group on the βꢀalkynyl ketone unit was simultaneously achieved.
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Our previous work
O
tBu
tBu
tBu
OH
Me
O
[Ag]
BiNPO4H
(a)
OH
O
+
tBu
O
R1
R1
This work
tBu
OH
OH
tBu
tBu
R2
O
tBu
Ag
Sc
R3
(b)
(c)
R3
O
3
R1
2
R2
Ts
R1
O
R2
NH
O
1
Me
O
Ag
Sc
N
R1
5
Ts
4
Scheme 1. Profiling Applications of Catalytic Bicyclization
Results and Discussion
To exploit metalꢀcatalyzed bicyclization reaction, we began our investigations with the reaction of βꢀ
alkynyl ketone 1a with paraꢀquinone methide (pꢀQM) 2a. In our previous report, this reaction catalyzed
by AgTFA/BiNPO4H gave 6,6ꢀbenzannulated spiroketal (Scheme 1a).21 During this project, we adjusted
coꢀcatalytic system to explore this transformation. Delightedly, when the above coꢀcatalytic system was
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replaced by silver/scandium dual metal catalysts, this bicyclization reaction proceeded smoothly to offer
an unexpected benzo[c]xanthene 3a. Encouraged by the interesting results, we next screened the
reaction conditions for this protocol. Initially, 1a was subjected to the reaction with pꢀQM 2a in toluene
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o
using AgTFA (10 mol %)/Sc(OTf)3(10 mol %) as a coꢀcatalytic system at 80 C under air conditions
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(Table 1, entry 1), and benzo[c]xanthene 3a was obtained in 60% yield. Without Sc(OTf)3 or AgTFA,
the reaction scarcely worked to generate the desired product 3a (entries 2ꢀ3), indicating both of these
catalysts showed a synergistic catalytic performance in this reaction system. Increasing the loading of
Sc(OTf)3 to 20 mol% facilitated the transformation, providing 3a in 73% yield (entry 4). Further
increase of Sc(OTf)3 loading was not beneficial to this reaction (entry 5). The following screening of
several other silver salts such as Ag2CO3, AgOTf and AgNO3 showed that these silver catalysts did not
show any improvements in the yield of product 3a (entries 6ꢀ8). Raising the AgTFA loading resulted in
the slightly lower conversion into 3a (entry 9). A similar inferior outcome was observed when the
AgTFA loading was decreased to 5 mol % (entry 10). We next investigated the solvent effect by
employing different solvents including acetonitrile (CH3CN), tetrahydrofuran (THF), 1,4ꢀdioxane and
1,2ꢀdichloroethane (DCE), but < 63% yield was observed (entries 11ꢀ14). Moreover, the reaction could
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o
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run at either 60 C or 100 C, but provided the lower yield as compared with the reaction temperature
o
being 80 C (entries 15ꢀ16). Changing Lewis acid catalyst to Sn(OTf)2 gave a relatively inferior
.
outcome regarding the yield of 3a (61%, entry 17) whereas both Zn(OTf)2 and BF3 Et2O as Lewis acid
catalysts completely suppressed the reaction process (entries 18ꢀ19). Employment of
Pd(TFA)2/Sc(OTf)3 as a coꢀcatalytic system led to the lower conversion into 3a (entry 20). The reaction
did not work when Cu(OTf)2/Sc(OTf)3 was used as a coꢀcatalyst (entry 21).
Table 1. Optimization of Reaction Conditionsa
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entry
1
catalyst (mol %)
solvent
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
MeCN
THF
t (oC)
80
80
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80
yield (%)b
60
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AgTFA (10)/Sc(OTf)3 (10)
AgTFA (10)
2
trace
trace
73
3
Sc(OTf)3 (10)
4
AgTFA (10)/Sc(OTf)3 (20)
AgTFA (10)/Sc(OTf)3 (30)
Ag2CO3 (5)/Sc(OTf)3 (20)
AgOTf (10)/Sc(OTf)3 (20)
AgNO3 (10)/Sc(OTf)3(20)
AgTFA (15)/Sc(OTf)3 (20)
AgTFA (5)/Sc(OTf)3 (20)
AgTFA (10)/Sc(OTf)3 (20)
AgTFA (10)/Sc(OTf)3 (20)
AgTFA (10)/Sc(OTf)3 (20)
AgTFA (10)/Sc(OTf)3 (20)
AgTFA (10)/Sc(OTf)3 (20)
AgTFA (10)/Sc(OTf)3 (20)
AgTFA (10)/Sn(OTf)2 (20)
AgTFA (10)/Zn(OTf)2 (20)
5
40
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trace
30
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64
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20
59
22
trace
trace
63
1,4ꢀdioxane 80
DCE
80
60
toluene
toluene
toluene
toluene
28
100
80
49
61
80
trace
.
AgTFA (10)/BF3 Et2O (20)
toluene
toluene
80
80
N.D.c
59
Pd(TFA)2 (10)/Sc(OTf)3 (20)
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21
Cu(OTf)2 (10)/Sc(OTf)3 (20)
toluene
80
trace
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aReaction conditions: 1a (0.4 mmol), 2a (0.2 mmol), Ag, Pd and Cuꢀcatalyst (x mol %), coꢀcatalyst (y mol %), solvent
(3.0 mL), under air conditions. bIsolated yield based on substrate 2a. cNot detected (N.D.)
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With these optimal reaction conditions in hand (Table 1, entry 4), we next turned our attention to
explore the preparative scope of our silver/scandium catalysis toward benzo[c]xanthenes 3 by
examining βꢀalkynyl ketone and paraꢀquinone methide components (Scheme 2). As shown, a wide
variety of βꢀalkynyl ketones possessing a diverse set of substituents at different positions of arylalkynyl
(R2) moiety could be perfectly tolerated, accessing in all cases good yields of 3a-3i. Functional groups
like methyl (1b and 1c), ethyl (1d), tertꢀbutyl (1e), methoxy (pꢀmethoxyphenyl = PMP, 1f), fluoride
(1g), chloride (1h), and bromide (1i) would be accommodated with the coꢀcatalytic conditions. Among
them, an increase in the yield was obtained (3d, 83%) as the pꢀethylphenyl counterpart (1d) was
employed as a reaction partner whereas pꢀbromophenyl group resulted in a reduced yield (3i, 66%).
Notably, substrate 1j with a thienyl group and substrate 1k with an nꢀbutyl (nꢀBu) group on the alkynyl
moiety were also proven to be efficient components, as the corresponding products 3j and 3k were
generated in 68% and 66% yields, respectively. Substrate 1l having fluoro functionality at 4ꢀposition of
the internal arene ring still showed high reactivity, delivering product 3l in 83% yields. The reaction was
found to tolerate various pꢀQMs 2b-2f carrying electronꢀrich (Me, 2b and tꢀBu, 2c) and electronꢀ
deficient (F, 2d and Br, 2e) groups at 4ꢀposition of the phenol ring, leading to the formation of
benzo[c]xanthenes 3m-3p with yields ranging from 57% to 80%. Alternatively, pꢀQM 2f bearing a
methoxy group at 5ꢀposition of the phenol ring successfully participated in the current dual catalysis,
enabling 6ꢀendoꢀdig cyclization/1,6ꢀaddition/cyclization cascades to access benzo[c]xanthene 3q in 55%
yield.
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Scheme 2. Substrate Scope for Synthesis of Products 3a
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a Reaction conditions: All reactions were performed with 1 (0.4 mmol), 2 (0.2 mmol), AgTFA (10 mol %), Sc(OTf)3 (20
mol %), toluene (3.0 mL) at 80 oC under air conditions for 12 hours. bIsolated yields in brackets based on 2.
Scheme 3. Substrate Scope for Synthesis of Products 5a
a Reaction conditions: All reactions were performed with 1 (0.4 mmol), 4 (0.2 mmol), AgTFA (10 mol %), Sc(OTf)3 (20
mol %), toluene (3.0 mL) at 80 oC under air conditions for 12 hours. bIsolated yields in brackets based on 4.
On the other hand, oxygenꢀrich dibenzofurans are also a class of heterocycles prevalent in natural
products,22 pharmaceutically active agents,23 and materials science.24 For these reasons, much effort has
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been made toward identifying general methods for the synthesis of tetracyclic dibenzofuran
derivatives.25 However, the utilization of dual metalꢀcatalyzed bicyclization cascade of βꢀalkynyl
ketones with quinone imine ketals (QIKs) has not been documented yet. We thus considered to
investigate silver/scandium catalyzed bicyclization cascades of βꢀalkynyl ketones by using QIK 4 as a
cycloaddition partner to construct densely substituted dibenzofuran core. To our delight, the reaction
worked well under the aboveꢀdescribed reaction conditions. Various substituents including methyl,
ethyl, tꢀbutyl, methoxy, fluoro, chloro, and bromo at 4ꢀposition of arylalkynyl (R2) moiety did not
hamper the reaction process, furnishing the corresponding tetracyclic naphtho[1,2ꢀb]benzofurans 5a-5h
in 46%ꢀ62% yields (Scheme 3). Similar to the above conversion of nꢀbutyl (nꢀBu) counterpart 1k into
3k, substrate 1k was also smoothly transformed into naphtho[1,2ꢀb]benzofuran 5i in 52% yield. The
presence of fluoro substituent at 4ꢀposition of the internal arene ring (1l) was also suitable for this
silver/scandium catalysis under the standard conditions, confirming the success of the transformation
toward product 5j in 51% yield. The structures of products 3 and 5 have been determined by their NMR
and HRMS analysis. Furthermore, in the cases of 3a, its structure was based on Xꢀray diffraction
analysis (see the Supporting Information).26
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Scheme 4. Control Experiment
To gain a mechanistic insight into the formation of 3, treatment with 3ꢀphenylnaphthalenꢀ1ꢀol 6 with pꢀ
QM 2a under the optimized conditions (Table 1, entry 4) provided the desired product 3a in 86% yield
(Scheme 4), indicating that 3ꢀphenylnaphthalenꢀ1ꢀol may behave as an intermediate for the synthesis of
3. Without AgTFA, Sc(OTf)3ꢀcatalyzed reaction of 6 with 2a worked well, generating the corresponding
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product 3a in 85% yield, showing that AgTFA could not be involved in the catalysis for the formation
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of pyran ring.
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Scheme 5. Plausible Reaction Pathway
OH
OH
tBu
R2
tBu
tBu
R2
tBu
9
-H2O
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P.T.
[Sc]
(a)
O
O
OH
E
3
OH
OH
[Sc]
tBu
R2
tBu
O
tBu
R2
tBu
tBu
tBu
P.T.
cyclization
R2
HO
O
H
OH
HO
O
O
[Sc]
[Sc]
D
C
2, [Sc]
1,6-addition
R2
[Ag]
R2
[Ag]
R2
R2
P.T.
[Ag]
[Sc]
Me
[Sc]
[Ag]
HO
B
HO
A
HO
O
[Sc]
1
4, [Sc]
1,4-addition
Ts
N [Sc]
Ts
NH
Ts
R2
R2
R2
NH
-H2O
P.T.
(b)
[Sc]
O
OH
F
O
O
HO
R1
[Sc]
5
G
Combining the aforementioned results and the previous reports about silverꢀcatalyzed cyclization of βꢀ
alkynyl ketones,27 reasonable mechanisms for forming products 3 and 5 were proposed as shown in
Scheme 5. Firstly, Ag/Sc coꢀcatalyzed 6ꢀendoꢀdig cyclization of βꢀalkynyl ketones (1 to A) occurs,
giving intermediates A, followed by proton transfer (P.T.)ꢀtautomerization to afford 1ꢀnaphthols B
(detected by LCꢀMS, see Supporting Information). Next, Scꢀcatalyzed 1,6ꢀaddition of B into 2 yields
adduct intermediates C, which undergo proton transfer and intramolecular oxoꢀnucleophilic addition to
offer intermediates D. Finally, intermediates D would be transformed into the products 3 through
deprotonation and dehydration (Scheme 5a). The mechanism for forming products 5 was similar to the
above pathway, which includes 6ꢀendoꢀdig cyclization, 1,4ꢀ nucleophilic addition and oxoꢀcyclization as
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well as dehydration (Scheme 5b).
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In conclusion, we have accomplished a perfectly compatible silver/scandium catalysis, which
combined with bicyclization cascades to create two types of skeletally diverse oxoꢀheterocycles with
generally good yields under mild conditions. Starting from βꢀalkynyl ketones and pꢀQMs, tetracyclic
benzo[c]xanthenes were efficiently synthesized through coꢀcatalytic benzannulation/1,6ꢀ
addition/cyclization sequence. Similar to the former, synergistic silver/scandium catalysis enabled the
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direct transformation of βꢀalkynyl ketones and QIKs into naphtho[1,2ꢀb]benzofurans with moderate to
good yields. During these reaction processes, C(sp3)ꢀH functionalization adjacent to carbonyl group on
the βꢀalkynyl ketone unit was achieved. Further investigation on mechanistic insights and their
applications will be conducted in due course.
Experimental Section
General Information.
All melting points are uncorrected. The NMR spectra were recorded in CDCl3 or DMSOꢀd6 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
TOFꢀMS instrument with an ESI source. XꢀRay crystallographic analysis was performed with a
SMART CCD and a P4 diffractometer.
General Procedure for the Synthesis of 3
Example for the synthesis of 3a
1ꢀ(2ꢀ(Phenylethynyl)phenyl)ethanone (1a, 0.4 mmol, 88.0 mg), 2,6ꢀdiꢀtertꢀbutylꢀ4ꢀ(2ꢀhydroxy
benzylidene)cyclohexaꢀ2,5ꢀdienone (2a, 0.2 mmol, 62.0 mg), AgTFA (0.02 mmol, 4.4 mg), and
Sc(OTf)3 (0.04 mmol, 19.7 mg) were successively added in a 10ꢀmL reaction vial. Toluene (3.0 mL)
was then injected into the reaction system. The reaction vial was sealed and heated at 80 oC for 12 hours
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until TLC (petroleum ether: ethyl acetate= 12:1) revealed that conversion of the starting material 2a was
completed. Then the reaction mixture was concentrated by vacuum distillation and was purified by flash
column chromatography (silica gel, mixtures of petroleum ether / acetic ester, 100:1, v/v) to afford the
desired pure products 3a as white solid.
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2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ(6ꢀphenylꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)phenol (3a)
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White solid, 75.0 mg, 73%; mp 193ꢀ194 C; IR (KBr, ν, cmꢀ1) 3615 (OH). 1H NMR (400 MHz, CDCl3;
δ, ppm) 8.57 (d, J = 8.3 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.64ꢀ7.54 (m, 2H), 7.41 (s, 1H), 7.35 (d, J =
8.0 Hz, 4H), 7.27ꢀ7.18 (m, 2H), 7.06 (m, 3H), 6.52 (s, 2H), 5.30 (s, 1H), 4.91 (s, 1H), 1.23 (s, 18H). 13C
NMR (100 MHz, CDCl3; δ, ppm) 151.9, 150.9, 146.9, 140.9, 140.3, 137.3, 135.3, 132.8, 1295, 129.2,
127.8, 127.4, 127.3, 127.0, 126.4, 126.3, 125.7, 124.1, 123.8, 123.7, 123.6, 121.8, 118.4, 116.5, 42.6,
34.0, 30.1. HRMS (ESIꢀTOF) m/z: Calcd for C37H35O2, 511.2637 [MꢀH]ꢀ; found 511.2643.
2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ(6ꢀ(mꢀtolyl)ꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)phenol (3b)
Pale yellow solid, 80.0 mg, 76%; mp 153ꢀ154 C; IR (KBr, ν, cmꢀ1) 3603 (OH). H NMR (400 MHz,
CDCl3; δ, ppm) 8.57 (d, J = 8.0 Hz, 1H), 7.81 (d, J = 7.9 Hz, 1H), 7.64ꢀ7.53 (m, 2H), 7.42 (s, 1H), 7.35
(d, J = 8.1 Hz, 1H), 7.28ꢀ7.13 (m, 4H), 7.07ꢀ7.03 (m, 1H), 6.91 (d, J = 27.4 Hz, 2H), 6.54 (s, 2H), 5.36
o
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(s, 1H), 4.91 (s, 1H), 2.34 (s, 3H), 1.24 (s, 18H). C NMR (100 MHz, CDCl3; δ, ppm) 151.9, 150.9,
146.9, 140.9, 140.4, 137.3, 135.3, 132.8, 130.2, 129.2, 127.7, 127.4, 127.3, 126.4, 126.2, 125.7, 124.1,
123.7, 123.6, 123.5, 121.8, 118.2, 116.5, 42.5, 34.0, 30.1, 21.5. HRMS (ESIꢀTOF) m/z: Calcd for
C38H37O2, 525.2794 [MꢀH]ꢀ; found 525.2795
2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ(6ꢀ(pꢀtolyl)ꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)phenol (3c)
o
White solid, 82.0 mg, 78%; mp 213ꢀ214 C; IR (KBr, ν, cmꢀ1) 3615 (OH). 1H NMR (400 MHz, CDCl3;
δ, ppm) 8.56 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.63ꢀ7.53 (m, 2H), 7.40 (s, 1H), 7.35 (m,
1H), 7.25ꢀ7.15 (m, 4H), 7.06ꢀ6.96 (m, 3H), 6.51 (s, 2H), 5.32 (s, 1H), 4.90 (s, 1H), 2.44 (s, 3H), 1.23 (s,
18H). 13C NMR (100 MHz, CDCl3; δ, ppm) 151.9, 150.9, 146.8, 140.3, 138.0, 137.4, 136.4, 135.3,
132.8, 129.3, 129.2, 128.6, 127.4, 127.2, 126.4, 126.3, 125.6, 124.2, 123.7, 123.7, 123.5, 121.8, 118.5,
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116.5, 42.6, 34.0, 30.1, 21.2. HRMS (ESIꢀTOF) m/z: Calcd for C38H37O2, 525.2794 [MꢀH]ꢀ; found
525.2797.
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2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ(6ꢀ(4ꢀethylphenyl)ꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)phenol (3d)
Pale yellow solid, 90.0 mg, 83%; mp 233ꢀ234 C; IR (KBr, ν, cmꢀ1) 3614 (OH). H NMR (400 MHz,
CDCl3; δ, ppm) 8.57 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.63ꢀ7.53 (m, 2H), 7.41 (s, 1H), 7.37ꢀ
7.34 (m, 1H), 7.27ꢀ7.19 (m, 4H), 7.05 (m, 3H), 6.53 (s, 2H), 5.33 (s, 1H), 4.91 (s, 1H), 2.75 (m, 2H),
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1.35 (m, 3H), 1.23 (s, 18H). C NMR (100 MHz, CDCl3; δ, ppm) 151.9, 151.0, 146.9, 142.7, 140.3,
138.2, 137.3, 135.3, 132.8, 129.4, 129.2, 127.4, 127.3, 126.5, 126.4, 125.6, 124.1, 123.8, 123.6, 121.8,
118.7, 116.5, 42.6, 34.0, 30.1, 28.6, 15.4. HRMS (ESIꢀTOF) m/z: Calcd for C39H39O2, 539.2950 [MꢀH]ꢀ
; found 539.2942.
2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ(6ꢀ(4ꢀ(tertꢀbutyl)phenyl)ꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)phenol (3e)
o
White solid, 90.0 mg, 79%; mp 244ꢀ245 C; IR (KBr, ν, cmꢀ1) 3612 (OH). 1H NMR (400 MHz, CDCl3;
δ, ppm) 8.56 (d, J = 8.3 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.62ꢀ7.58 (m, 1H), 7.53 (m, 1H), 7.42 (m,
3H), 7.37 (d, J = 8.1 Hz, 1H), 7.24 (m, 2H), 7.07 (m, 3H), 6.56 (s, 2H), 5.34 (s, 1H), 4.91 (s, 1H), 1.43
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(s, 9H), 1.23 (s, 18H). C NMR (100 MHz, CDCl3; δ, ppm) 152.0, 151.4, 149.7, 147.1, 140.1, 137.9,
137.3, 135.3, 132.7, 129.2, 129.1, 127.4, 127.3, 126.8, 126.3, 125.6, 124.9, 124.0, 123.8, 123.6, 121.8,
118.9, 116.5, 42.6, 34.6, 34.1, 31.5, 30.2. HRMS (ESIꢀTOF) m/z: Calcd for C41H43O2, 567.3263 [MꢀH]ꢀ
; found 567.3264.
2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ(6ꢀ(4ꢀmethoxyphenyl)ꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)phenol (3f)
o
White solid, 80.0 mg, 74%; mp 216ꢀ217 C; IR (KBr, ν, cmꢀ1) 3614 (OH). 1H NMR (400 MHz, CDCl3;
δ, ppm) 8.56 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.63ꢀ7.53 (m, 2H), 7.40 (s, 1H), 7.35 (m, 1.0
Hz, 1H), 7.26ꢀ7.19 (m, 2H), 7.05 (m, 1H), 7.04ꢀ6.97 (m, 2H), 6.89 (d, J = 8.7 Hz, 2H), 6.55 (s, 2H),
5.31 (s, 1H), 4.91 (s, 1H), 3.89 (s, 3H), 1.24 (s, 18H). 13C NMR (100 MHz, CDCl3; δ, ppm) 151.9,
150.9, 146.9, 140.9, 140.3, 137.3, 135.3, 132.8, 129.5, 129.2, 127.8, 127.4, 127.3, 127.0, 126.4, 126.3,
125.7, 124.1, 123.8, 123.7, 123.6, 121.8, 118.4, 116.5, 42.6, 34.0, 30.1. HRMS (ESIꢀTOF) m/z: Calcd
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for C38H37O3, 541.2743 [MꢀH]ꢀ; found 541.2739.
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White solid, 85.0 mg, 80%; mp 191ꢀ192 C; IR (KBr, ν, cmꢀ1) 3613 (OH). 1H NMR (400 MHz, CDCl3;
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δ, ppm) 8.58 (d, J = 8.3 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.60 (m, 2H), 7.39 (s, 1H), 7.34 (d, J = 8.0
Hz, 1H), 7.30ꢀ7.17 (m, 3H), 7.07ꢀ6.99 (m, 4H), 6.53 (s, 2H), 5.24 (s, 1H), 4.94 (s, 1H), 1.25 (s, 18H).
13C NMR (100 MHz, CDCl3; δ, ppm) 162.0 (1JCF = 244.3 Hz), 152.0, 150.6, 146.8, 139.3, 137.3, 136.9,
136.9, 135.5, 132.8, 131.0 (3JCF = 7.9 Hz), 129.2, 127.4 (4JCF = 3.6 Hz), 126.6, 125.9, 125.9, 124.1,
123.8, 123.7, 123.6, 121.9, 118.1, 116.6, 114.6 (2JCF = 21.1 Hz), 42.7, 34.0, 30.1. HRMS (ESIꢀTOF)
m/z: Calcd for C37H34FO2, 529.2543 [MꢀH]ꢀ; found 529.2547.
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2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ(6ꢀ(4ꢀchlorophenyl)ꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)phenol (3h)
o
Pale yellow solid, 80.0 mg, 73%; mp 220ꢀ221 C; IR (KBr, ν, cmꢀ1) 3612 (OH). 1H NMR (400 MHz,
CDCl3; δ, ppm) 8.58 (d, J = 8.3 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.66ꢀ7.62 (m, 1H), 7.59ꢀ7.55 (m,
1H), 7.39ꢀ7.29 (m, 4H), 7.25 (m, 1H), 7.20ꢀ7.17 (m, 1H), 7.08ꢀ6.94 (m, 3H), 6.52 (s, 2H), 5.25 (s, 1H),
4.95 (s, 1H), 1.25 (s, 18H). 13C NMR (100 MHz, CDCl3; δ, ppm) 152.0, 150.5, 146.8, 139.4, 139.1,
137.2, 135.5, 133.0, 132.8, 130.7, 129.2, 127.9, 127.4, 127.4, 126.6, 126.0, 125.7, 124.2, 123.9, 123.6,
123.6, 121.9, 117.9, 116.6, 42.6, 34.0, 30.1. HRMS (ESIꢀTOF) m/z: Calcd for C37H34ClO2, 545.2247
[MꢀH]ꢀ; found 545.2252.
4ꢀ(6ꢀ(4ꢀBromophenyl)ꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)ꢀ2,6ꢀdiꢀtertꢀbutylphenol (3i)
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Pale yellow solid, 78.0 mg, 66%; mp 234ꢀ235 C; IR (KBr, ν, cmꢀ1) 3611 (OH). H NMR (400 MHz,
CDCl3; δ, ppm) 8.57 (d, J = 8.3 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.65ꢀ7.61 (m, 1H), 7.59ꢀ7.55 (m,
1H), 7.45 (d, J = 8.0 Hz, 2H), 7.37ꢀ7.32 (m, 2H), 7.24 (m, 1H), 7.19ꢀ7.16 (m, 1H), 7.04 (m, 1H), 6.92
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(s, 2H), 6.51 (s, 2H), 5.24 (s, 1H), 4.94 (s, 1H), 1.25 (s, 18H). C NMR (100 MHz, CDCl3; δ, ppm)
152.0, 150.9, 147.2, 141.7, 137.1, 135.5, 132.5, 132.2, 129.2, 127.5, 127.3, 127.1, 126.8, 126.6, 126.3,
126.2, 125.6, 125.5, 124.2, 124.0, 123.7, 121.9, 119.0, 116.5, 42.6, 34.1, 30.2. HRMS (ESIꢀTOF) m/z:
Calcd for C37H34BrO2, 589.1742 [MꢀH]ꢀ; found 589.1744.
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2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ(6ꢀ(thiophenꢀ2ꢀyl)ꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)phenol (3j)
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White solid, 70.0 mg, 68%; mp 179ꢀ180 C; IR (KBr, ν, cmꢀ1) 3611 (OH). 1H NMR (400 MHz, CDCl3;
δ, ppm) 8.54 (d, J = 8.4 Hz, 1H), 7.82 (d, J = 7.8 Hz, 1H), 7.65ꢀ7.60 (m, 1H), 7.59ꢀ7.54 (m, 1H), 7.41
(s, 1H), 7.40ꢀ7.32 (m, 3H), 7.32ꢀ7.29 (m, 1H), 7.06 (s, 1H), 6.96ꢀ6.91 (m, 1H), 6.87 (m, 1H), 6.50 (s,
2H), 5.25 (s, 1H), 4.95 (s, 1H), 1.24 (s, 18H). 13C NMR (100 MHz, CDCl3; δ, ppm) 152.0, 150.5, 146.8,
139.8, 139.1, 137.2, 135.5, 132.8, 131.1, 130.9, 129.2, 127.4, 127.4, 126.6, 126.0, 125.7, 124.2, 123.9,
123.6, 123.5, 121.9, 121.2, 117.8, 116.6, 42.6, 34.0, 30.1. HRMS (ESIꢀTOF) m/z: Calcd for C35H33O2S,
517.2201 [MꢀH]ꢀ; found 517.2193.
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o
White solid, 65.0 mg, 66%; mp 187ꢀ188 C; IR (KBr, ν, cmꢀ1) 3631 (OH). 1H NMR (400 MHz, CDCl3;
δ, ppm) 8.52ꢀ8.48 (m, 1H), 7.79ꢀ7.75 (m, 1H), 7.52 (m, 2H), 7.41ꢀ7.37 (m, 2H), 7.31 (m, 1H), 7.26ꢀ7.22
(m, 1H), 7.09 (m, 1H), 7.01 (s, 2H), 5.37 (s, 1H), 5.00 (s, 1H), 2.80 (m, 1H), 2.68ꢀ2.61 (m, 1H), 1.60 (s,
2H), 1.55ꢀ1.36 (m, 2H), 1.32 (s, 18H), 0.90 (m, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 152.2, 151.0,
147.2, 139.3, 137.0, 135.8, 133.2, 128.9, 127.3, 126.8, 126.6, 126.1, 124.9, 124.0, 123.4, 123.1, 122.0,
121.7, 118.8, 116.6, 42.6, 34.2, 33.0, 32.3, 30.2, 22.9, 14.0. HRMS (ESIꢀTOF) m/z: [Calcd for
C35H39O2, 491.2950 MꢀH]ꢀ; found 491.2954.
2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ(3ꢀfluoroꢀ6ꢀ(pꢀtolyl)ꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)phenol (3l)
o
White solid, 90.0 mg, 83%; mp 235ꢀ236 C; IR (KBr, ν, cmꢀ1) 3614 (OH). 1H NMR (400 MHz, CDCl3;
δ, ppm) 8.56 (m, 1H), 7.43ꢀ7.36 (m, 2H), 7.35ꢀ7.32 (m, 2H), 7.27ꢀ7.22 (m, 1H), 7.20ꢀ7.13 (m, 3H),
7.07ꢀ7.03 (m, 1H), 6.97 (s, 2H), 6.49 (s, 2H), 5.30 (s, 1H), 4.91 (s, 1H), 2.44 (s, 3H), 1.23 (s, 18H). 13C
NMR (100 MHz, CDCl3; δ, ppm) 161.3 (1JCF = 244.4 Hz), 151.9, 150.7, 147.0, 141.8, 137.7, 137.2,
136.6, 135.3, 133.8 (4JCF = 9.2 Hz), 129.2 (5JCF = 8.9 Hz), 128.6, 127.3, 126.2, 124.6, 124.5, 124.2,
123.7, 123.0, 122.9, 120.7, 117.9 (6JCF = 2.4 Hz), 116.5, 115.9, 115.6 (2JCF = 24.9 Hz), 110.6 (3JCF
=
20.4 Hz), 42.4, 34.0, 30.1, 21.2. HRMS (ESIꢀTOF) m/z: Calcd for C38H36FO2, 543.2699 [MꢀH]ꢀ; found
543.2696.
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2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ(9ꢀmethylꢀ6ꢀphenylꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)phenol (3m)
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Pale yellow solid, 60.0 mg, 57%; mp 260ꢀ261 C; IR (KBr, ν, cmꢀ1) 3626 (OH). H NMR (400 MHz,
CDCl3; δ, ppm) 8.57 (d, J = 8.3 Hz, 1H), 7.81 (d, J = 7.9 Hz, 1H), 7.63ꢀ7.59 (m, 1H), 7.57ꢀ7.52 (m,
1H), 7.41ꢀ7.34 (m, 4H), 7.25 (d, J = 8.2 Hz, 1H), 7.13ꢀ6.98 (m, 4H), 6.54 (s, 2H), 5.25 (s, 1H), 4.92 (s,
1H), 2.29 (s, 3H), 1.24 (s, 18H). 13C NMR (100 MHz, CDCl3; δ, ppm) 151.9, 148.9, 147.1, 140.9, 140.3,
137.4, 135.3, 132.9, 132.7, 129.5, 129.4, 128.0, 127.8, 127.38, 127.0, 126.4, 126.0, 125.7, 124.2, 123.9,
123.4, 121.9, 118.6, 116.3, 42.7, 34.1, 30.1, 20.8. HRMS (ESIꢀTOF) m/z: Calcd for C38H37O2 525.2794
[MꢀH]ꢀ; found 525.2789.
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2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ(9ꢀ(tertꢀbutyl)ꢀ6ꢀphenylꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)phenol (3n)
White solid, 73.0 mg, 64%; mp 285ꢀ286oC; IR (KBr, ν, cmꢀ1) 3631 (OH). H NMR (400 MHz, CDCl3;
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δ, ppm) 8.56 (d, J = 8.2 Hz, 1H), 7.82 (d, J = 7.8 Hz, 1H), 7.62ꢀ7.53 (m, 2H), 7.44 (s, 1H), 7.38ꢀ7.33
(m, 3H), 7.28 (s, 2H), 7.24 (s, 1H), 7.14 (s, 2H), 6.58 (s, 2H), 5.27 (s, 1H), 4.92 (s, 1H), 1.31 (s, 9H),
1.25 (s, 18H). 13C NMR (100 MHz, CDCl3; δ, ppm) 151.9, 149.1, 147.6, 146.2, 140.9, 140.2, 137.0,
135.3, 132.8, 129.5, 127.8, 127.4, 126.9, 126.4, 125.7, 125.6, 125.5, 124.4, 124.0, 123.9, 123.5, 121.8,
118.5, 116.0, 42.8, 34.3, 34.1, 31.5, 30.2. HRMS (ESIꢀTOF) m/z: Calcd for C41H43O2, 567.3263 [MꢀH]ꢀ
; found 567.3262.
2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ(9ꢀfluoroꢀ6ꢀphenylꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)phenol (3o)
White solid, 85.0 mg, 80%; mp 185ꢀ186 C; IR (KBr, ν, cmꢀ1) 3620 (OH). 1H NMR (400 MHz, CDCl3;
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δ, ppm) 8.55 (d, J = 8.3 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.65ꢀ7.54 (m, 3H), 7.37ꢀ7.33 (m, 2H), 7.26ꢀ
7.23 (m, 1H), 7.10ꢀ7.04 (m, 2H), 6.83 (m, 1H), 6.66 (s, 2H), 5.55 (s, 1H), 4.93 (s, 1H), 1.26 (s, 18H).
13C NMR (100 MHz, CDCl3; δ, ppm) 158.7 (1JCF = 239.3 Hz), 152.1, 146.9 (6JCF = 2.1 Hz), 146.8,
140.7, 140.16, 136.8, 135.5, 132.8, 129.4, 127.9, 127.6 (4JCF = 7.4 Hz), 127.5, 127.1, 126.6, 125.9,
124.1, 123.8, 123.7, 121.7, 117.6 (5JCF = 8.4 Hz), 117.4, 115.2 (2JCF = 23.1 Hz), 114.2 (3JCF = 23.6 Hz),
42.9, 34.1, 30.1. HRMS (ESIꢀTOF) m/z: Calcd for C37H34FO2, 529.2543 [MꢀH]ꢀ; found 529.2548.
4ꢀ(9ꢀBromoꢀ6ꢀphenylꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)ꢀ2,6ꢀdiꢀtertꢀbutylphenol (3p)
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White solid, 75.0 mg, 64%; mp 231ꢀ232 C; IR (KBr, ν, cmꢀ1) 3627 (OH). 1H NMR (400 MHz, CDCl3;
δ, ppm) 8.53 (d, J = 8.3 Hz, 1H), 7.82 (d, J = 7.9 Hz, 1H), 7.63 (m, 1H), 7.59ꢀ7.54 (m, 1H), 7.42 (s,
1H), 7.40ꢀ7.32 (m, 4H), 7.30 (d, J = 2.3 Hz, 1H), 7.24 (d, J = 8.6 Hz, 1H), 7.05 (d, J = 20.8 Hz, 2H),
6.50 (s, 2H), 5.24 (s, 1H), 4.96 (s, 1H), 1.24 (s, 18H). 13C NMR (100 MHz, CDCl3; δ, ppm) 152.2 150.1,
146.5, 140.6, 140.1, 136.7, 135.6, 132.8, 131.9, 130.3, 129.4, 128.5, 127.9, 127.5, 127.1, 126.6, 125.9,
124.1, 124.0, 123.7, 121.7, 118.4, 118.0, 115.7, 42.6, 34.1, 30.1. HRMS (ESIꢀTOF) m/z: Calcd for
C37H34BrO2, 589.1742 [MꢀH]ꢀ; Found 589.1736.
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2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ(10ꢀmethoxyꢀ6ꢀphenylꢀ7Hꢀbenzo[c]xanthenꢀ7ꢀyl)phenol (3q)
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Pale yellow solid, 60.0 mg, 55%; mp 192ꢀ193 C; IR (KBr, ν, cmꢀ1) 3614 (OH). H NMR (400 MHz,
CDCl3; δ, ppm) 8.56 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.64ꢀ7.60 (m, 1H), 7.57ꢀ7.53 (m,
1H), 7.40 (s, 1H), 7.34 (m, 3H), 7.07 (d, J = 8.5 Hz, 3H), 6.90 (d, J = 2.5 Hz, 1H), 6.63 (m, 1H), 6.49 (s,
2H), 5.25 (s, 1H), 4.90 (s, 1H), 3.86 (s, 3H), 1.23 (s, 18H). 13C NMR (100 MHz, CDCl3; δ, ppm) 159.0,
151.8, 151.4, 146.7, 141.0, 140.4, 137.6, 135.3, 132.7, 129.7, 129.4, 127.78, 127.4, 126.9, 126.4, 125.7,
124.1, 123.7, 123.7, 121.8, 118.6, 118.5, 110.4, 101.4, 55.5, 42.0, 34.0, 30.1. HRMS (ESIꢀTOF) m/z:
Calcd for C38H37O3, 541.2743 [MꢀH]ꢀ; found 541.2742.
General Procedure for the Synthesis of Products 5
Example for the synthesis of 5a.
1ꢀ(2ꢀ(Phenylethynyl)phenyl)ethanone (1a, 0.4 mmol, 88.0 mg), 4ꢀmethylꢀNꢀ(4ꢀoxocyclohexꢀ2,5ꢀdienꢀ1ꢀ
ylidene)benzenesulfonamide (4a, 0.2 mmol, 52.0 mg), AgTFA (0.02 mmol, 4.4 mg), and Sc(OTf)3 (0.04
mmol, 19.7 mg) were successively added in a 10ꢀmL reaction vial. Toluene (3.0 mL) was then injected
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into the reaction system. The reaction vial was sealed and heated at 80 C for 12 hours until TLC
(petroleum ether: ethyl acetate= 5:1) revealed that conversion of the starting material 4a was completed.
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 5a as pale yellow solid.
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4ꢀMethylꢀNꢀ(6ꢀphenylnaphtho[1,2ꢀb]benzofuranꢀ8ꢀyl)benzenesulfonamide (5a)
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Pale yellow solid, 48.0 mg, 52%; mp 150ꢀ151 C; IR (KBr, ν, cmꢀ1) 3235 (NH). H NMR (400 MHz,
CDCl3; δ, ppm) 8.46 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.69ꢀ7.65 (m, 2H), 7.64ꢀ7.60 (m,
2H), 7.54 (m, 7H), 7.23 (m, 1H), 7.19 (d, J = 8.1 Hz, 2H), 7.10 (d, J = 2.2 Hz, 1H), 6.44 (s, 1H), 2.39 (s,
3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 154.1, 153.1, 143.7, 139.4, 135.7, 135.3, 133.0, 131.1, 129.5,
128.9, 128.6, 128.3, 128.1, 127.4, 126.9, 126.5, 125.2, 123.7, 122.2, 120.9, 120.4, 117.1, 116.9, 112.2,
21.5. HRMS (ESIꢀTOF) m/z: Calcd for C29H20NO3S, 462.1164 [MꢀH]ꢀ; found 462.1162.
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4ꢀMethylꢀNꢀ(6ꢀ(pꢀtolyl)naphtho[1,2ꢀb]benzofuranꢀ8ꢀyl)benzenesulfonamide (5b)
White solid, 52.0 mg, 55%; mp 169ꢀ170 C; IR (KBr, ν, cmꢀ1) 3235 (NH). 1H NMR (400 MHz, CDCl3;
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δ, ppm) 8.45 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 7.9 Hz, 1H), 7.63 (m, 4H), 7.53 (d, J = 8.3 Hz, 2H), 7.46
(d, J = 8.0 Hz, 2H), 7.33 (d, J = 7.8 Hz, 2H), 7.25ꢀ7.18 (m, 3H), 7.15 (d, J = 2.1 Hz, 1H), 6.54 (s, 1H),
2.55 (s, 3H), 2.39 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 154.2, 153.1, 143.7, 137.8, 136.5,
135.7, 135.4, 133.1, 131.1, 129.5, 129.3, 128.8, 128.3, 127.4, 126.8, 126.4, 125.3, 123.6, 122.1, 120.9,
120.3, 117.2, 117.0, 112.2, 21.6, 21.4. HRMS (ESIꢀTOF) m/z: Calcd for C30H22NO3S, 476.1320 [MꢀH]ꢀ
; found 476.1325.
Nꢀ(6ꢀ(4ꢀEthylphenyl)naphtho[1,2ꢀb]benzofuranꢀ8ꢀyl)ꢀ4ꢀmethylbenzenesulfonamide (5c)
White solid, 45.0 mg, 46%; mp 207ꢀ208 C; IR (KBr, ν, cmꢀ1) 3239 (NH). 1H NMR (400 MHz, CDCl3;
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δ, ppm) 8.45 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H), 7.64 (m, 4H), 7.50 (m, 4H), 7.36 (d, J = 7.9
Hz, 2H), 7.24 (m, 1H), 7.19 (d, J = 8.1 Hz, 2H), 7.14 (s, 1H), 6.52 (s, 1H), 2.85 (m, 2H), 2.39 (s, 3H),
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1.41 (m, 3H). C NMR (101 MHz, CDCl3) δ 154.2, 153.1, 144.2, 143.7, 136.7, 135.7, 135.7, 133.1,
131.1, 129.5, 128.9, 128.3, 128.1, 127.4, 126.9, 126.4, 125.3, 123.6, 122.2, 122.1, 120.9, 120.3, 117.2,
117.0, 112.2, 28.7, 21.6, 15.6. HRMS (ESIꢀTOF) m/z: Calcd for C31H24NO3S, 490.1477 [MꢀH]ꢀ; found
490.1468.
Nꢀ(6ꢀ(4ꢀ(tertꢀButyl)phenyl)naphtho[1,2ꢀb]benzofuranꢀ8ꢀyl)ꢀ4ꢀmethylbenzenesulfonamide (5d)
White solid, 52.0 mg, 50%; mp 278ꢀ279 C; IR (KBr, ν, cmꢀ1) 3238 (NH). 1H NMR (400 MHz, CDCl3;
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δ, ppm) 8.45 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H), 7.68ꢀ7.59 (m, 4H), 7.55ꢀ7.46 (m, 6H), 7.25
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(m, 1H), 7.21ꢀ7.14 (m, 3H), 6.52 (s, 1H), 2.39 (s, 3H), 1.49 (s, 9H). C NMR (100 MHz, CDCl3; δ,
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ppm) 154.1, 153.1, 151.2, 143.6, 136.4, 135.6, 135.3, 133.1, 131.0, 129.5, 128.6, 128.3, 127.5, 126.8,
126.4, 125.5, 125.2, 123.7, 122.3, 120.9, 120.3, 117.2, 116.8, 112.2, 34.8, 31.5, 21.6. HRMS (ESIꢀTOF)
m/z: Calcd for C33H28NO3S, 518.1790 [MꢀH]ꢀ; found 518.1791.
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Nꢀ(6ꢀ(4ꢀMethoxyphenyl)naphtho[1,2ꢀb]benzofuranꢀ8ꢀyl)ꢀ4ꢀmethylbenzenesulfonamide (5e)
White solid, 61.0 mg, 62%; mp 167ꢀ168 oC; IR (KBr, ν, cmꢀ1) 3286 (NH). 1H NMR (400 MHz, CDCl3;
δ, ppm) 8.45 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 7.5 Hz, 1H), 7.67ꢀ7.60 (m, 4H), 7.53 (d, J = 8.3 Hz, 2H),
7.50ꢀ7.46 (m, 2H), 7.26ꢀ7.19 (m, 3H), 7.15 (d, J = 2.2 Hz, 1H), 7.06ꢀ7.03 (m, 2H), 6.45 (s, 1H), 3.98 (s,
3H), 2.40 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 159.6, 154.1, 153.1, 143.7, 135.8, 135.0, 133.1,
131.7, 131.1, 130.07, 129.5, 128.2, 127.4, 126.8, 126.3, 125.3, 123.4, 122.2, 120.9, 120.2, 117.3, 117.0,
114.0, 112.2, 55.5, 21.5. HRMS (ESIꢀTOF) m/z: Calcd for C30H22NO4S, 492.1270 [MꢀH]ꢀ; found
492.1274.
Nꢀ(6ꢀ(4ꢀFluorophenyl)naphtho[1,2ꢀb]benzofuranꢀ8ꢀyl)ꢀ4ꢀmethylbenzenesulfonamide (5f)
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White solid, 55.0 mg, 57%; mp 177ꢀ178 C; IR (KBr, ν, cmꢀ1) 3233 (NH). 1H NMR (400 MHz, CDCl3;
δ, ppm) 8.49ꢀ8.42 (m, 1H), 7.99 (d, J = 7.7 Hz, 1H), 7.69ꢀ7.60 (m, 4H), 7.53 ( m, 4H), 7.27ꢀ7.13 (m,
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5H), 7.08 (d, J = 2.2 Hz, 1H), 6.54 (s, 1H), 2.41 (s, 3H). C NMR (100 MHz, CDCl3; δ, ppm) 162.7
(1JCF = 245.9 Hz), 154.2, 153.1, 143.7, 135.9, 135.4 (4JCF = 3.4 Hz), 134.2, 133.0, 131.2, 130.6 (3JCF
8.0 Hz), 129.5, 128.3, 127.3, 127.0, 126.6, 125.1, 123.7, 122.5, 120.9, 120.4, 117.1, 116.9, 115.6 (2JCF
=
=
21.3 Hz), 112.3, 21.5. HRMS (ESIꢀTOF) m/z: Calcd for C29H19FNO3S, 480.1070 [MꢀH]ꢀ; found
480.1072.
Nꢀ(6ꢀ(4ꢀChlorophenyl)naphtho[1,2ꢀb]benzofuranꢀ8ꢀyl)ꢀ4ꢀmethylbenzenesulfonamide (5g)
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White solid, 50.0 mg, 50%; mp 203ꢀ204 C; IR (KBr, ν, cmꢀ1) 3286 (NH). 1H NMR (400 MHz, CDCl3;
δ, ppm) 8.45 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 7.9 Hz, 1H), 7.69ꢀ7.62 (m, 6H), 7.56 (d, J = 8.3 Hz, 2H),
7.46ꢀ7.42 (m, 2H), 7.28ꢀ7.25 (m, 1H), 7.23 (d, J = 8.1 Hz, 2H), 7.07 (d, J = 2.2 Hz, 1H), 6.62 (s, 1H),
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2.41 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 154.1, 153.2, 143.7, 137.8, 135.9, 134.1, 133.9,
132.9, 131.2, 130.2, 129.5, 128.8, 128.3, 127.4, 127.0, 126.8, 124.9, 123.7, 122.6, 121.0, 120.5, 116.8,
116.8, 112.3, 21.6. HRMS (ESIꢀTOF) m/z: Calcd for C29H19ClNO3S, 496.0774 [MꢀH]ꢀ; found
496.0775.
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White solid, 53.0 mg, 49%; mp 207ꢀ208 C; IR (KBr, ν, cmꢀ1) 3284 (NH). 1H NMR (400 MHz, CDCl3;
δ, ppm) 8.44 (d, J = 8.1 Hz, 1H), 7.98 (d, J = 8.1 Hz, 1H), 7.64 (m, 4H), 7.56 (d, J = 8.2 Hz, 2H), 7.52ꢀ
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7.46 (m, 4H), 7.27ꢀ7.20 (m, 3H), 7.09 (s, 1H), 6.74 (s, 1H), 2.41 (s, 3H). C NMR (100 MHz, CDCl3;
δ, ppm) 154.2, 153.2, 143.7, 138.3, 135.9, 133.9, 132.9, 131.8, 131.2, 130.6, 129.5, 128.3, 127.4, 127.1,
126.8, 124.9, 123.7, 122.7, 122.3, 121.0, 120.5, 116.8, 116.7, 112.4, 21.6. HRMS (ESIꢀTOF) m/z: Calcd
for C29H19BrNO3S, 540.0269 [MꢀH]ꢀ; found 540.0278.
Nꢀ(6ꢀButylnaphtho[1,2ꢀb]benzofuranꢀ8ꢀyl)ꢀ4ꢀmethylbenzenesulfonamide (5i)
Pale yellow solid, 46.0 mg, 52%; mp 194ꢀ195 C; IR (KBr, ν, cmꢀ1) 3240 (NH). H NMR (400 MHz,
CDCl3; δ, ppm) 8.40ꢀ8.37 (m, 1H), 7.93 (m, 1H), 7.75 (d, J = 2.1 Hz, 1H), 7.66 (d, J = 8.3 Hz, 2H), 7.59
(m, 3H), 7.52 (s, 1H), 7.22 (d, J = 8.1 Hz, 2H), 7.15 (m, 1H), 6.68 (s, 1H), 3.16ꢀ3.11 (m, 2H), 2.38 (s,
3H), 1.77 (m, 2H), 1.53 (m, 2H), 1.01 (m, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 154.1, 153.1,
143.8, 135.9, 135.8, 133.2, 131.4, 129.6, 127.7, 127.4, 126.6, 125.7, 125.7, 122.1, 122.0, 120.8, 119.9,
118.1, 117.4, 112.2, 33.7, 31.7, 22.6, 21.5, 14.0. HRMS (ESIꢀTOF) m/z: Calcd for C27H24NO3S,
442.1477 [MꢀH]ꢀ; found 442.1474.
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White solid, 50.0 mg, 51%; mp 212ꢀ213 C; IR (KBr, ν, cmꢀ1) 3235 (NH). 1H NMR (400 MHz, CDCl3;
δ, ppm) 8.43 (m, 1H), 7.58 (m, 3H), 7.53 (d, J = 8.3 Hz, 2H), 7.46ꢀ7.39 (m, 3H), 7.33 (d, J = 7.8 Hz,
2H), 7.24ꢀ7.18 (m, 3H), 7.14 (d, J = 2.2 Hz, 1H), 6.49 (s, 1H), 2.55 (s, 3H), 2.40 (s, 3H). 13C NMR (100
MHz, CDCl3; δ, ppm) 161.4 (1JCF = 245.6 Hz), 154.0, 153.1, 143.7, 138.1, 136.8, 136.1, 135.7, 134.1
(4JCF = 9.2 Hz), 131.3, 129.5, 129.4, 128.7, 127.4, 125.2, 123.5 (5JCF = 9.1 Hz) , 122.8, 122.7, 122.0,
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117.3, 116.8, 116.7 (6JCF = 2.1 Hz), 116.5 (2JCF = 25.2 Hz), 112.1, 111.8 (3JCF = 20.8 Hz), 21.6, 21.4.
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HRMS (ESIꢀTOF) m/z: Calcd for C30H21FNO3S, 494.1226 [MꢀH]ꢀ; found 494.1227.
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ASSOCIATED CONTENT
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Supporting Information
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1H and 13C NMR spectra for all pure products, and Xꢀray crystal data (CIF) for 3a. 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. 21232004, 21472071, and 21602087), PAPD
of Jiangsu Higher Education Institutions, the Outstanding Youth Fund of JSNU (YQ2015003), NSF of
Jiangsu Province (BK20151163 and BK20160212), and the Qing Lan Project and NSF of Jiangsu
Education Committee (15KJB150006).
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