Oxidative Catalytic Spiroketalization Leading to Diastereoselective Synthesis of Spiro[benzofuran-2,1′-isochromene]s

Article abstract of DOI:10.1002/adsc.201701149

A new one-pot, two-step silver-catalyzed spiroketalization of the in-situ generated quinone imine ketals (QIKs) with β-alkynyl ketones has been established, enabling multiple C?O and C?C bond-forming reactions to access densely functionalized spiro[benzof

Full text of DOI:10.1002/adsc.201701149

Title: Oxidative Catalytic Spiroketalization Leading to
Diastereoselective Spiro[benzofuran-2,1'-isochromene]s
Authors: Jiang-Kai Qiu, Wen-Juan Hao, Guigen Li, and Bo Jiang
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201701149
Link to VoR: http://dx.doi.org/10.1002/adsc.201701149

10.1002/adsc.201701149
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Oxidative Catalytic Spiroketalization Leading to
Diastereoselective Synthesis of Spiro[benzofuran-2,1'-
isochromene]s
Jiang-Kai Qiu,a,b Wen-Juan Hao,c Guigen Li*,a,b and Bo Jiang*,b,c
a
Institute of Chemistry & BioMedical Sciences, Nanjing University, Nanjing, 210023, China; E-mail:
guigen.li@ttu.edu; Tel./fax: +86 25 58139397
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409-1061, United States
School of Chemistry and Material Science, Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional
b
c
Materials, Jiangsu Normal University, Xuzhou, 211116, P. R. China; E-mail: jiangchem@jsnu.edu.cn (BJ); Tel./fax:
+86 516 83500065
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract.
A
new one-pot, two-step silver-catalyzed
highly diastereoselective spiro[chromane-2,1’-
isochromene] derivatives. The reaction features broad
substrate scope, mild oxidative catalytic conditions and
excellent diastereoselectivity.
spiroketalization of the in-situ generated quinone imine
ketals (QIKs) with β‑alkynyl ketones has been established,
enabling multiple C−O and C−C bond-forming reactions to
access densely functionalized spiro[benzofuran-2,1'-
isochromene] derivatives with generally good yields. The
use of β-alkynyl ketones bearing alkyl and aryl groups
located at the -position of the carbonyl group could lead to
Keywords: Spiroketalization; 1,4-Addition; Silver
Catalysis; Benzannulated 5,6-Spiroketals;
Diastereoselectivity
substrates under mild conditions, is still highly
desirable.
Introduction
Spiroketal is a privileged structural unit that exists
widely in a range of natural products that exhibit
interesting biological activity.[1] Among the family of
spiroketals, benzannulated 5,6-spiroketals behave as a
key pharmacophore in many bioactive natural
products, such as β-rubromycin,[2] heliquinomycin,[3]
griseorhodin A[4] (Figure 1). General strategies to
access this key motif are through oxidative
spiroketalization,[5] gold-catalyzed intramolecular
alkyne hydroalkoxylation,[6] Pd-catalyzed reductive
coupling,[7] copper(I)-catalyzed spiroketalization of
propargyl alcohols,[8] Sc(OTf)3-catalyzd epoxide-
Figure 1. Spirocyclic natural products
On the other hand, catalytic cyclization of β-alkynyl
ketones has proven to be a powerful tool for the
collection of biologically interesting cyclic structures
in a convergent manner.[14] Since the group of
Yamamoto
pioneered
AuCl3-catalyzed
opening
spiroketalizations,[9]
multi-step
benzannulation of β-alkynyl ketones with alkynes,[15]
catalytic cyclization cascades of β-alkynyl ketones
have been investigated extensively.[16] Recently, we
have developed a Ag/Brønsted acid co-catalyzed
bicyclization reaction of β-alkynyl ketones with para-
quinone methides (p-QMs), which provided a series of
functionalized benzannulated 6,6-spiroketals.[17]
During this project, we reasoned that catalytic
conversion of β-alkynyl ketones into electron-rich
methyleneisochromenes enables 1.4-addition and
spiroketalization of aryl acetylenes[10] or ketones,[11]
hetero-Diels-Alder reaction of o-quinone methide
precursors.[12] Very recently, Xu and co-workers
reported a gold/Lewis acid co-catalyzed bicyclization
of o-alkynyl benzyl alcohols toward benzannulated
5,6-spiroketals (Schemes 1a and 1b).[13] Despite these
advances, the development of a general and practical
protocol toward new functionalized benzannulated
5,6-spiroketals, starting from readily available
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701149
Advanced Synthesis & Catalysis
nucleophilic cyclization with quinone imine ketals
(QIKs), generated in situ from N-(4-hydroxyphenyl)
sulfonamides,[18] to access new functionalized
benzannulated 5,6-spiroketals. As anticipated, N-(4-
hydroxyphenyl) sulfonamides could be oxidized by
phenyliodine diacetate (PIDA) to QIKs, followed by
the interception of methyleneisochromenes from β-
alkynyl ketones through silver catalysis, giving access
to the desired spiro[benzofuran-2,1'-isochromene]
derivatives with excellent diastereoselectivity in an
atom-economic fashion. (Scheme 1c). Notably, the
one-pot, two-step spiroketalization reaction occurred
smoothly to give the desired products, avoiding the
transformation and provided 3a in 82% yield (entry 3).
In contrast, AgOAc and AgF completely suppressed
the reaction
Table 1 Optimization of the reaction conditions[a]
entry Oxidant
(equiv)
Cat. (mol %) solvent
Yield
(%)b
21
1
2
3
PIDA (2.0)
AgOTf (10)
toluene
pre-preparation of QIKs, which demanded
a
complicated process for their preparation.[18] The
current protocol represents a new and reliable silver
catalysis for forming diastereoselective benzannulated
5,6-spiroketals with a sulfonamide functionality
together with C(sp3)-H functionalization of β-alkynyl
ketones and C(sp2)-H functionalization of N-(4-
hydroxyphenyl) sulfonamides in a one-pot fashion. To
the best of our knowledge, this oxidative silver
catalysis toward benzannulated 5,6-spiroketals has
been virtually unexplored. Herein, we report this
attractive and useful transformation.
PIDA (2.0)
PIDA (2.0)
AgNO3 (10) toluene
47
82
CF3CO2Ag
toluene
(10)
4
5
6
PIDA (2.0)
PIDA (2.0)
AgOAc (10) toluene
ND
AgF (10)
toluene
toluene
trace
ND
Na2Cr2O7 (2.0) CF3CO2Ag
(10)
7
K2S2O8 (2.0)
Oxone (2.0)
TBHP(2.0)
mCPBA (2.0)
IBX (2.0)
CF3CO2Ag
(10)
CF3CO2Ag
(10)
CF3CO2Ag
(10)
CF3CO2Ag
(10)
CF3CO2Ag
(10)
CF3CO2Ag
(10)
CF3CO2Ag
(10)
CF3CO2Ag
(10)
CF3CO2Ag
(10)
CF3CO2Ag
(10)
CF3CO2Ag
(10)
CF3CO2Ag
(10)
CF3CO2Ag
(10)
CF3CO2Ag
(10)
CF3CO2Ag
(10)
toluene
toluene
toluene
toluene
toluene
toluene
1,4-dioxane
DCM
trace
trace
trace
trace
74
8
9
Scheme 1. Profiles of metal-catalyzed
spiroketalization
10
11
12
13
14
15
16
17
18
19
20
21
PIFA (2.0)
PIDA (2.0)
PIDA (2.0)
PIDA (2.0)
PIDA (2.0)
PIDA (2.0)
PIDA (2.0)
PIDA (2.0)
PIDA (2.0)
PIDA (2.0)
80
12c
77
CHCl3
DCE
65
56
DMF
trace
trace
76
EtOH
CH3CN
toluene
toluene
71c
64d
Results and Discussion
[a]Reaction conditions: (i) 1a (0.5 mmol), oxidant (1.0 mmol) and toluene
(2 mL) in the seal reaction tube under air conditions at room temperature
for 5 hours. (ii) 2a (0.2 mmol) in 1.0 mL of toluene was added by syringe
pump in 0.5 hour. Then, the reaction system was stirred at room
temperature for 7 hours.
We began our investigations by selecting N-(4-
hydroxyphenyl) sulfonamide 1a and β-alkynyl ketone
2a as model substrates. At the beginning, N-(4-
hydroxyphenyl) sulfonamide 1a was subjected with
2.0 equivalents of PIDA (PhI(OAc)2) in toluene at
room temperature for 5 hours. Without isolation, β-
alkynyl ketone 2a and AgOTf (10 mol %) were then
added into the above reaction system. The reaction
proceeded to access the desired product 3a, albeit with
a low 21% yield (Table 1, entry 1). Exchanging AgOTf
for AgNO3 resulted in a higher yield (47%, entry 2).
To our delight, the use of silver trifluoroacetate as
[b]Isolated yield is based on 2a.
[c]The reaction was carried out at 20 oC.
[d]The reaction was carried out at 40 oC
process (entries 4-5). Encouraged by these outcomes,
we considered to exploit different oxidants and
solvents to search for the optimal reaction conditions.
The screening of several other inorganic and organic
oxidants (2.0 equiv.) revealed that, compared with
Na2Cr2O7, K2S2O8, oxone, tert-butyl hydroperoxide
(TBHP, 70% in water), m-chloroperoxybenzoic acid
catalyst
could
significantly
facilitate
this
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701149
Advanced Synthesis & Catalysis
(mCPBA), 2-iodoxybenzoic acid (IBX), and
phenyliodine bis(trifluoroacetate) (PIFA) (entries
6−12), phenyliodine diacetate (PIDA) still gave the
best result in this spiroketalization (entry 3). Next, the
solvent effect of this transformation was investigated.
As shown in Table 1, toluene was proved to be an
effective medium for this silver catalysis (entry 3). The
other solvents, such as 1,4-dioxane, dichloromethane
(DCM),
trichloromethane
(CHCl3),
1,2-
dichloroethane (DCE), N,N-dimethylformamide
(DMF), ethanol (EtOH), and acetonitrile (CH3CN), all
gave unsatisfactory outcomes (entries 13-19). Lower
conversion of 3a was observed with the reaction
temperature being at either 20 oC or 40 oC (entries 20-
21).
Scheme 2. Substrate scope for synthesis of 3.
With the acceptable reaction conditions for this silver
catalysis in hand, we then set out to explore the scope
of these transformations by examining β-alkynyl
ketone and N-(4-hydroxyphenyl) sulfonamide
components. At first, β-alkynyl ketones with diverse
functionalities attached by arylalkynyl moiety (R2)
were explored in combination with N-(4-
hydroxyphenyl) sulfonamide 1a. Various substituents
with electronically rich and deficient property did not
hamper this Ag-catalyzed bicyclization process,
delivering the corresponding dibenzannulated 5,6-
spiroketals 3b−3j with 59%-81% yields. Functional
groups such as methyl (2b and 2c), ethyl (2d), t-butyl
(2e), methoxy (p-methoxyphenyl = PMP, 2f), fluoro
(2g), chloro (2h), bromo (2i), nitro (2j) were tolerated
well under the standard conditions. The scope of N-(4-
hydroxyphenyl)sulfonamides was then investigated by
utilizing β-alkynyl ketone 2a as a representative
reaction partner. As expected, the variant of aryl
groups directly bound to sulfonamide unit such as
phenyl (1b), 4-chlorophenyl (1c) and naphthalen-2-yl
(2-Np, 1d) all worked readily with these oxidative
catalytic conditions, affording the corresponding
products 3k-3m in 46%-60% yields. Next, we decided
to change the substituents located at α-position of the
carbonyl group on the β-alkynyl ketone unit to expand
its synthetic utility. As shown in Scheme 3, a large
variety of different substituents including alkyl
(methyl, ethyl, n-propyl, and i-propyl) and aryl groups
would be accommodated, confirming the success of
the reaction, as the corresponding products 4a–4aa as
sole diastereoisomers were generated in 37%–76%
yields. Among which, substrates 2 carrying the fluoro
Scheme 3. Substrate scope for synthesis of 4.
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701149
Advanced Synthesis & Catalysis
functionality at 4- or 5-position of the internal arene
ring were successfully engaged in the silver catalysis,
enabling
6-endo-dig
cyclization/1,4-addition-
cyclization cascades to access diastereoenriched
dibenzannulated 5,6-spiroketals 4f-4i in 37%-69%
yields. It is noteworthy that the present protocol
represents a reliable new and practical pathway for
flexible synthesis of a series of richly functionalized
dibenzannulated 5,6-spiroketals 4 with generally
excellent diastereoselectvity through Ag-catalyzed
bicyclization involving C(sp3)−H functionalization of
β-alkynyl ketones. The structures of these spiroketals
3 were fully characterized by their NMR spectroscopy
and HRMS. In the case of 4x, its stereoscopic structure
was unequivocally determined by conducting single
crystal X-ray diffraction (Figure 2).[19]
Scheme 5. Control experiments
To
understand
the
mechanism,
N-(4-
hydroxyphenyl)sulfonamide 1a was first oxidized by
phenyliodine diacetate (PIDA) to give QIK 6a in 92%
yield (Scheme 5a). Then, the preformed QIK 6a was
subjected with the reaction of β-alkynyl ketone 2a in
the presence of CF3CO2Ag, providing the
corresponding product 3a in 90% yield (Scheme 5b),
indicating that QIK could act as an intermediate for the
synthesis of 3 and4.
Figure 2. ORTEP drawing of 4x
To expand potential application of this method, the
two-step reaction of N-acetyl protected 4-aminophenol
1e with β-alkynyl ketone 2a was conducted under the
standard conditions. Regrettably, the reaction did not
give the desired product 5 as the starting material 1e
was recovered (Scheme 4).
Scheme 6. Proposed reaction mechanism
Based on the above observations and previous
literature survey,[14-16] we propose a tentative pathway
for this transformation as described in Scheme 6.
Initially, N-(4-hydroxyphenyl) sulfonamide 1a was
oxidized by phenyliodine diacetate (PIDA) to yield
QIK 6a and HOAc. Next, Ag-catalyzed 6-endo-dig
oxo-cyclization of β-alkynyl ketones 2[20] in the
presence of HOAc generates intermediate C through
continuous proton transfer (A to C). Ag-catalyzed 1,4-
conjugate addition of intermediate C into QIK 6a
gives adduct D, followed by twice proton transfer to
intermediate F, which undergoes oxo-nucleophilic
addition (oxo-cyclization) to generate final products 3.
Scheme 4. Two-step reaction of N-acetyl-protected 1e
Conclusion
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701149
Advanced Synthesis & Catalysis
In
summary,
starting
from
N-(4-
7.14 (d, J = 7.5 Hz, 1H), 6.71-6.68 (m, 1H), 6.64 (s, 1H),
6.58 (d, J = 8.4 Hz, 1H), 6.37 (s, 1H), 4.07 (d, J = 17.3 Hz,
1H), 3.71 (d, J = 17.3 Hz, 1H), 2.41 (s, 3H), 2.35 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 155.7, 149.8, 143.8, 138.1,
136.2, 134.0, 130.9, 129.9, 129.7, 129.6, 128.4, 127.5, 127.2,
126.7, 125.8, 125.2, 125.0, 124.3, 122.4, 121.8, 111.5, 110.2,
100.9, 41.4, 21.7, 21.6. HRMS (ESI) m/z: calcd for
[C29H23NO4SNa]+ requires: 518.1402 [M+Na]+; found:
518.1398.
hydroxyphenyl)sulfonamides and β-alkynyl ketones,
we have established one-pot, two-step Ag-catalyzed
spiroketalization cascades involving PIDA-mediated
in situ formation of QIKs, Ag-catalyzed 6-endo-dig
oxo-cyclization and 1,4-conjugate addition as well as
oxo-nucleophilic addition, in which a wide range of
structurally
diverse
spiro[benzofuran-2,1'-
isochromene] derivatives with generally good yields
were synthesized. β-Alkynyl ketones bearing alkyl and
aryl groups located at -position of the carbonyl group
could participate in this oxidative silver catalysis,
leading to highly diastereoselective spiro[chromane-
2,1’-isochromene] derivatives with generally good
yields. The present oxidative catalytic system provides
a general and practical pathway for constructing
dibenzannulated 5,6-spiroketals together with C(sp3)-
H functionalization of -alkynyl ketones and C(sp2)-H
4-methyl-N-(3'-(p-tolyl)-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)benzenesulfonamide (3c)
White solid, 78.2 mg, 79% yield; mp: 199-200 oC. 1H NMR
(400 MHz, CDCl3) δ 7.65-7.63 (m, 2H), 7.54-7.52 (m, 2H),
7.44-7.36 (m, 2H), 7.31-7.26 (m, 3H), 7.20 (d, J = 1.6 Hz,
1H), 7.15 (d, J = 8.1 Hz, 2H), 6.71-6.69 (m, 1H), 6.61 (s,
1H), 6.57 (d, J = 8.4 Hz, 1H), 6.42 (s, 1H), 4.07 (d, J = 17.2
Hz, 1H), 3.69 (d, J = 17.2 Hz, 1H), 2.41 (s, 3H), 2.36 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 155.7, 149.8, 143.8, 139.2,
136.2, 131.2, 131.0, 129.9, 129.7, 129.6, 129.2, 127.5, 127.1,
127.0, 126.7, 125.2, 125.1, 124.3, 121.7, 111.5, 110.2, 100.3,
functionalization
sulfonamides in
investigation of the bioactivity of these spiroketals is
underway.
of
N-(4-hydroxyphenyl)
a
one-pot fashion. Further
41.3,
21.7,
21.4.
HRMS
(ESI)
m/z:
calcd
for[C30H25NO4SNa]+ requires: 518.1402 [M+Na]+; found:
518.1396.
N-(3'-(4-ethylphenyl)-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)-4-methylbenzenesulfonamide (3d)
White solid, 68.3 mg, 67% yield; mp: 198-199 oC. 1H NMR
(400 MHz, CDCl3) δ 7.66-7.62 (m, 2H), 7.58-7.54 (m, 2H),
7.43-7.37 (m, 2H), 7.30 (s, 1H), 7.28-7.26 (m, 3H), 7.21 (d,
J = 2.0 Hz, 1H), 7.19-7.17 (m, 2H), 6.71-6.69 (m, 1H), 6.62
(s, 1H), 6.57 (d, J = 8.4 Hz, 1H), 6.43 (s, 1H), 4.07 (d, J =
17.2 Hz, 1H), 3.69 (d, J = 17.3 Hz, 1H), 2.65 (q, J = 7.6 Hz,
2H), 2.41 (s, 3H), 1.23 (t, J = 7.6 Hz, 3H). 13C NMR (100
MHz, CDCl3) δ 155.7, 149.8, 145.6, 143.8, 136.1, 131.5,
131.1, 129.9, 129.7, 129.5, 128.0, 127.5, 127.0, 126.7, 125.2,
125.1, 124.9, 124.3, 121.7, 111.5, 110.2, 100.3, 41.3, 28.8,
21.7, 15.6. HRMS (ESI) m/z: calcd for [C31H27NO4SNa]+
requires: 532.1558 [M+Na]+; found: 532.1553.
N-(3'-(4-(tert-butyl)phenyl)-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)-4-methylbenzenesulfonamide (3e)
White solid, 81.8 mg, 76% yield; mp: 201-202 oC. 1H NMR
(400 MHz, CDCl3) δ 7.66 (d, J = 8.1 Hz, 2H), 7.58 (d, J =
8.4 Hz, 2H), 7.43-7.37 (m, 4H), 7.30-7.22 (m, 4H), 6.73 (dd,
J = 8.3, 1.4 Hz, 1H), 6.66-6.62 (m, 2H), 6.57 (d, J = 8.4 Hz,
1H), 4.07 (d, J = 17.2 Hz, 1H), 3.68 (d, J = 17.2 Hz, 1H),
2.41 (s, 3H), 1.32 (s, 9H). 13C NMR (100 MHz, CDCl3) δ
155.6, 152.4, 149.8, 143.8, 136.2, 131.18 (d, J = 15.7 Hz),
129.9, 129.67 (d, J = 5.0 Hz), 127.5, 127.03 (d, J = 3.7 Hz),
126.7, 125.4, 124.97 (t, J = 15.8 Hz), 124.4, 121.6, 111.5,
110.2, 100.4, 41.2, 34.8, 31.3, 21.7. HRMS (ESI) m/z: calcd
for [C33H31NO4SH]+ requires: 538.2052 [M+H]+; found:
538.2051.
Experimental Section
Typical Procedure for the Preparation of 3a:
N-(4-Hydroxyphenyl)-4-methylbenzenesulfonamide (1a,
0.5 mmol, 131 g), iodobenzene diacetate (2.0 equiv, 322
mg) and toluene (2.0 mL) were added into a 10-mL Schlenk
tube. The mixture was stirred at room temperature for about
5 hours. After the reaction was complete, 10 mol% of silver
trifluoroacetate was added and the system was cooled to 0
oC. Then, 1-(2-(phenylethynyl)phenyl) ethan-1-one (2a, 0.2
mmol, 44 mg) was dissolved in 1.0 mL of toluene and added
to the above reaction system by syringe pump in 0.5 hour.
Then, the reaction system was stirred at room temperature
for about 7 hours under the starting material 2a completely
disappeared as monitored by TLC. The solution was then
extracted with EtOAc, the combined organic layers were
dried over anhydrous Na2SO4, filtered, and evaporated
under vacuum. The residue was purified by column
chromatography on silica gel to afford the desired product
3a.
4-methyl-N-(3'-phenyl-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)benzenesulfonamide (3a)
White solid, 79.0 mg, 82% yield; mp: 176-177 oC. 1H NMR
(400 MHz, CDCl3) δ 7.72-7.68 (m, 4H), 7.49-7.29 (m, 9H),
6.77 (d, J = 8.0 Hz, 1H), 6.70-6.68, 6.64-6.62 (m, 1H), 4.11
(d, J = 17.3 Hz, 1H), 3.74 (d, J = 17.2 Hz, 1H), 2.45(s, 3H).
13C NMR (100 MHz, CDCl3) δ 155.6, 149.7, 143.9, 136.2,
134.0, 130.9, 130.0, 129.7, 129.1, 128.5, 127.5, 127.3, 127.2,
126.7, 125.2(3), 125.2(0), 124.8, 124.4, 121.6, 111.5, 110.2,
101.0, 41.3, 21.7. HRMS (ESI) m/z: calcd for
[C29H23NO4S+Na]+ requires: 504.1245 [M+Na]+; found:
504.1240.
N-(3'-(4-methoxyphenyl)-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)-4-methylbenzenesulfonamide (3f)
White solid, 82.9 mg, 81% yield; mp: 186-187 oC. 1H NMR
(400 MHz, CDCl3) δ 7.68-7.62 (m, 2H), 7.60-7.54 (m, 2H),
7.42-7.35 (m, 2H), 7.29-7.26 (m, 3H), 7.21 (d, J = 2.0 Hz,
1H), 6.91-6.83 (m, 2H), 6.71 (dd, J = 8.5, 2.3 Hz, 1H), 6.58
(d, J = 8.4 Hz, 1H), 6.54-6.52 (m, 2H), 4.06 (d, J = 17.2 Hz,
1H), 3.81 (s, 3H), 3.68 (d, J = 17.3 Hz, 1H), 2.41 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 160.5, 155.6, 149.6, 143.9,
136.2, 131.2, 129.9, 129.7, 129.6, 127.5, 126.9, 126.8, 126.7,
126.6, 125.0, 124.9, 124.3, 121.7, 113.9, 111.5, 110.2, 99.4,
4-methyl-N-(3'-(m-tolyl)-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)benzenesulfonamide (3b)
White solid, 71.1 mg, 72% yield; mp: 209-210 oC. 1H NMR
(400 MHz, CDCl3) δ 7.65-7.62 (m, 2H), 7.46-7.36 (m, 4H),
7.31-7.29 (m, 2H), 7.27-7.24 (m, 2H), 7.22-7.20 (m, 1H),
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701149
Advanced Synthesis & Catalysis
55.4, 41.2, 21.7. HRMS (ESI) m/z: calcd for
[C30H25NO5SNa]+ requires: 534.1351 [M+Na]+; found:
534.1346.
Hz, 2H), 4.07 (d, J = 17.3 Hz, 1H), 3.69 (d, J = 17.3 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ 156.0, 149.6, 138.8, 135.0,
133.9, 133.0, 131.7, 130.3, 130.0, 129.7, 129.1, 128.9, 128.3,
128.2, 127.8, 127.5, 127.1, 126.1, 125.9, 125.4, 124.9, 124.7,
122.0, 112.6, 110.8, 100.3, 56.6. HRMS (ESI) m/z: calcd for
[C28H22NO4S]+ requires: 468.1270 [M+H]+; found:
468.1272.
N-(3'-(4-fluorophenyl)-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)-4-methylbenzenesulfonamide (3g)
White solid, 61.9 mg, 62% yield; mp: 176-177 oC. 1H NMR
(400 MHz, CDCl3) δ 7.66-7.58 (m, 4H), 7.44-7.37 (m, 2H),
7.33-7.27 (m, 3H), 7.22 (d, J = 2.0 Hz, 1H), 7.07-6.99 (m,
2H), 6.70 (dd, J = 8.4, 2.3 Hz, 1H), 6.58 (t, J = 4.2 Hz, 2H),
6.40 (s, 1H), 4.08 (d, J = 17.3 Hz, 1H), 3.69 (d, J = 17.3 Hz,
1H), 2.42 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 155.6,
148.8, 143.9, 136.2, 130.7, 130.2 (d, J = 3.1 Hz), 130.0,
129.7, 127.5, 127.2 (d, J = 16.0 Hz), 127.4 (d, J = 4.0 Hz),
4-chloro-N-(3'-phenyl-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)benzenesulfonamide (3l)
White solid, 46.3 mg, 46% yield; mp: 195-196 oC. 1H NMR
(400 MHz, CDCl3) δ 7.72-7.67 (m, 2H), 7.65-7.62 (m, 2H),
7.46-7.43 (m, 3H), 7.40-7.29 (m, 6H), 7.20 (m, 1H), 6.74
(dd, J = 8.4, 2.1 Hz, 1H), 6.66 (s, 1H), 6.61 (d, J = 8.4 Hz,
126.6, 125.2, 124.9, 124.4, 121.7, 115.6, 115.4, 111.5, 110.2, 1H), 6.54 (s, 1H), 4.09 (d, J = 17.3 Hz, 1H), 3.71 (d, J = 17.3
100.8 (d, J = 1.7 Hz), 41.3, 21.7. HRMS (ESI) m/z: calcd for
[C29H23FNO4S]+ requires: 500.1332 [M+H]+; found:
500.1344.
Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 155.9, 149.69,
139.69, 137.6, 134.0, 130.9, 130.1, 129.4, 129.2, 129.1,
128.9, 128.5, 127.3, 127.0, 126.9, 125.3, 125.2, 125.1, 124.4,
121.8, 111.6, 110.4, 101.1, 41.3. HRMS (ESI) m/z: calcd for
[C28H21ClNO4S]+ requires: 502.0880 [M+H]+; found:
502.0877.
N-(3'-(4-chlorophenyl)-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)-4-methylbenzenesulfonamide (3h)
White solid, 77.5 mg, 75% yield; mp: 190-191 oC. 1H NMR
(400 MHz, CDCl3) δ 7.64 (d, J = 8.0 Hz, 2H), 7.56 (d, J =
8.3 Hz, 2H), 7.45-7.37 (m, 2H), 7.34-7.27 (m, 5H), 7.23 (s,
1H), 6.70 (d, J = 8.0 Hz, 1H), 6.64 (s, 1H), 6.58 (d, J = 8.5
Hz, 1H), 6.41 (s, 1H), 4.08 (d, J = 17.2 Hz, 1H), 3.69 (d, J
= 17.3 Hz, 1H), 2.42 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ 155.5, 148.6, 143.9, 136.2, 134.9, 132.5, 130.6, 130.0,
129.7(1), 129.7(0) 128.7, 127.5, 127.4, 127.2, 126.6, 126.4,
125.3, 124.9, 124.4, 121.7, 111.5, 110.2, 101.4, 41.3, 21.7.
HRMS (ESI) m/z: calcd for [C29H22ClNO4SNa]+ requires:
538.0856 [M+Na]+; found: 538.0850.
N-(3'-(4-bromophenyl)-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)-4-methylbenzenesulfonamide (3i)
White solid, 78.2 mg, 70% yield; mp: 207-208 oC. 1H NMR
(400 MHz, DMSO-d6) δ 9.92 (s, 1H), 7.61-7.59 (m, 2H),
7.56-7.48 (m, 5H), 7.45-7.41 (m, 1H), 7.36-7.27 (m, 4H),
7.14-7.00 (m, 2H), 6.77 (dd, J = 8.5, 1.6 Hz, 1H), 6.55 (d, J
= 8.5 Hz, 1H), 4.20 (d, J = 17.6 Hz, 1H), 3.57 (d, J = 17.6
Hz, 1H), 2.31 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ
N-(3'-phenyl-3H-spiro[benzofuran-2,1'-isochromen]-5-
yl)naphthalene-2-sulfonamide (3m)
White solid, 54.9 mg, 53% yield; mp: 181-182 oC. 1H NMR
(400 MHz, CDCl3) δ 8.32 (d, J = 1.2 Hz, 1H), 7.94-7.87 (m,
3H), 7.74 (m, 1H), 7.66-7.60 (m, 3H), 7.60-7.55 (m, 1H),
7.42-7.38 (m, 1H), 7.35-7.32 (m, 4H), 7.30-7.26 (m, 2H),
7.21-7.17 (m, 1H), 6.73 (dd, J = 8.5, 2.3 Hz, 1H), 6.63 (s,
1H), 6.54 (m, 2H), 4.03 (d, J = 17.2 Hz, 1H), 3.66 (d, J =
17.3 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 155.8, 149.7,
136.0, 135.0, 134.0, 132.2, 130.8, 129.9, 129.4(1), 129.4(0),
129.1, 129.0, 128.9, 128.5, 128.0, 127.7, 127.2, 127.1, 126.7,
125.2, 125.1, 124.4, 122.6, 121.8, 111.5, 110.3, 101.0, 41.3.
HRMS (ESI) m/z: calcd for [C32H24NO4S]+ requires:
518.1426 [M+H]+; found: 518.1436.
4-methyl-N-(3-methyl-3'-phenyl-3H-spiro[benzofuran-
2,1'-isochromen]-5-yl)benzenesulfonamide (4a)
White solid, 66.5 mg, 67% yield; mp: 182-183 oC. 1H NMR
(400 MHz, CDCl3) δ 7.70-7.68 (m, 1H), 7.64-7.62 (m, 2H),
153.9, 147.9, 143.5, 137.3, 133.2, 132.1, 131.8, 130.8, 130.5, 7.46-7.43 (m, 1H), 7.39-7.36 (m, 3H), 7.30-7.27 (m, 4H),
130.1, 128.0, 127.3, 127.1, 127.0, 125.7, 125.3, 122.8, 122.4, 7.25 (d, J = 1.1 Hz, 1H), 7.22-7.18 (m, 5H), 6.98 (dd, J =
119.5, 111.4, 110.0, 102.4, 21.5. HRMS (ESI) m/z: calcd for
[C29H23BrNO4S]+ requires: 560.0531 [M+H]+; found:
560.0532.
8.4, 1.7 Hz, 1H), 6.91-6.89 (m, 1H), 6.74 (d, J = 8.4 Hz, 1H),
6.54 (s, 1H), 6.43 (s, 1H), 5.45 (s, 1H), 4.14 (q, J = 7.1 Hz,
1H), 2.43 (s, 3H), 1.44-1.10 (m, 2H). 13C NMR (100 MHz,
CDCl3) δ 155.9, 149.6, 143.8, 136.0, 135.1, 133.9, 131.7,
130.1, 130.0, 129.9, 129.7, 128.8, 128.3, 128.2, 127.8, 127.6,
127.1, 126.3, 125.8, 125.3, 124.9, 124.6, 122.0, 112.6, 110.7,
100.2, 60.5, 56.8, 21.7, 21.2, 14.3. HRMS (ESI) m/z: calcd
for [C30H25NO4SNa]+ requires: 518.1402 [M+Na]+; found:
518.1414.
4-methyl-N-(3'-(4-nitrophenyl)-3H-spiro[benzofuran-
2,1'-isochromen]-5-yl)benzenesulfonamide (3j)
White solid, 62.0 mg, 59% yield; mp: 187-188 oC. 1H NMR
(400 MHz, DMSO-d6) δ 9.95 (s, 1H), 7.70-7.53 (m, 5H),
7.48 (m, 1H), 7.43-7.28 (m, 7H), 7.19-6.98 (m, 2H), 6.82
(dd, J = 8.5, 2.0 Hz, 1H), 6.61 (d, J = 8.5 Hz, 1H), 4.25 (d,
J = 17.5 Hz, 1H), 3.62 (d, J = 17.6 Hz, 1H), 2.36 (s, 3H).
13C NMR (101 MHz, DMSO-d6) δ 154.0, 148.9, 143.5,
N-(3'-(4-ethylphenyl)-3-methyl-3H-spiro[benzofuran-
2,1'-isochromen]-5-yl)-4-methylbenzenesulfonamide
137.2, 133.9, 131.7, 131.0, 130.3, 130.0, 129.6, 129.0, 127.7, (4b)
127.2, 127.1(6), 127.1(4), 125.5, 125.2, 125.0, 122.4, 119.6,
111.3, 109.9, 101.6, 21.5. HRMS (ESI) m/z: calcd for
[C29H22N2O6SNa]+ requires: 549.1096 [M+Na]+; found:
549.1099.
White solid, 62.9 mg, 60% yield; mp: 195-196 oC. 1H NMR
(400 MHz, CDCl3) δ 7.62 (d, J = 8.1 Hz, 2H), 7.51-7.39 (m,
4H), 7.32-7.27 (m, 2H), 7.27-7.24 (m, 1H), 7.16 (d, J = 8.1
Hz, 2H), 7.08 (s, 1H), 6.71-6.69 (m, 1H), 6.64-6.52 (m, 2H),
6.35 (s, 1H), 4.25 (q, J = 6.9 Hz, 1H), 2.65 (q, J = 7.6 Hz,
2H), 2.40 (s, 3H), 1.45 (d, J = 7.0 Hz, 3H), 1.22 (t, J = 7.6
Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 155.1, 149.8, 145.5,
143.8, 136.0, 132.6, 132.0, 131.6, 130.0, 129.7, 129.6, 128.0,
127.5, 126.9, 125.8, 125.2, 125.1, 124.4, 120.8, 112.8, 110.3,
99.8, 44.3, 28.8, 21.7, 15.6, 12.1.HRMS (ESI) m/z: calcd for
N-(3'-phenyl-3H-spiro[benzofuran-2,1'-isochromen]-5-
yl)benzenesulfonamide (3k)
White solid, 56.1 mg, 60% yield; mp: 199-200 oC. 1H NMR
(400 MHz, CDCl3) δ 7.78-7.75 (m, 2H), 7.67-7.60 (m, 2H),
7.59-7.56 (m, 1H), 7.50-7.46 (m, 2H), 7.44-7.20 (m, 8H),
6.73 (dd, J = 8.4, 1.7 Hz, 1H), 6.66 (s, 1H), 6.58 (d, J = 8.5
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701149
Advanced Synthesis & Catalysis
[C32H30NO4S]+ requires: 524.1896 [M+H]+; found:
524.1895.
N-(6'-fluoro-3'-(4-methoxyphenyl)-3-methyl-3H-
spiro[benzofuran-2,1'-isochromen]-5-yl)-4-
N-(3'-(4-methoxyphenyl)-3-methyl-3H-
spiro[benzofuran-2,1'-isochromen]-5-yl)-4-
methylbenzenesulfonamide (4c)
methylbenzenesulfonamide (4g)
White solid, 75.0 mg, 69% yield; mp: 148-149 oC. 1H NMR
(400 MHz, CDCl3) δ 7.6-7.63 (m, 2H), 7.51-7.49 (m, 2H),
7.45-7.43 (m, 1H), 7.28-7.26 (m, 2H), 7.10 (s, 1H), 6.98-
6.96 (m, 2H), 6.87 (d, J = 8.6 Hz, 2H), 6.73 (d, J = 7.6 Hz,
1H), 6.60 (d, J = 8.4 Hz, 1H), 6.45 (d, J = 15.3 Hz, 2H), 4.21
(q, J = 6.9 Hz, 1H), 3.83 (s, 3H), 1.46 (d, J = 7.0 Hz, 3H).
13C NMR (100 MHz, CDCl3) δ 160.6, 154.8, 150.7, 143.8,
136.0, 132.2, 129.8, 129.5, 127.4, 126.7, 126.2, 125.0, 120.6,
113.9, 113.4, 112.6, 111.1, 110.2, 98.2, 65.9, 55.4, 44.6,
White solid, 67.3 mg, 64% yield; mp: 182-183 oC. 1H NMR
(400 MHz, DMSO-d6) δ 9.89 (s, 1H), 7.72 (d, J = 8.2 Hz,
1H), 7.68-7.60 (m, 3H), 7.48-7.44 (m, 3H), 7.38-7.25 (m,
3H), 7.33-7.22 (m, 2H), 7.06 (s, 1H), 6.94-6.92 (m, 2H),
6.81-6.79 (m, 2H), 6.60 (d, J = 8.4 Hz, 1H), 4.43 (q, J = 6.7
Hz, 1H), 3.77 (s, 3H), 2.36 (s, 3H), 1.33 (d, J = 6.9 Hz,
3H).13C NMR (100 MHz, DMSO-d6) δ 160.5, 153.4, 148.9,
143.5, 137.1, 132.6, 132.2, 131.7, 130.3, 130.0, 129.8, 127.3, 21.6, 12.0. HRMS (ESI) m/z: calcd for [C31H27FNO5S]+
127.1, 126.5, 126.4, 126.1, 125.6, 125.2, 126.5 122.8, 118.7,
114.5, 112.6, 111.0, 99.4, 55.7, 21.5, 12.2. HRMS (ESI)
m/z: calcd for [C31H27NO5SNa]+ requires: 548.1508
[M+Na]+; found: 548.1519.
requires: 544.1594 [M+H]+; found: 544.1596.
N-(7'-fluoro-3-methyl-3'-phenyl-3H-spiro[benzofuran-
2,1'-isochromen]-5-yl)-4-methylbenzenesulfonamide
(4h)
N-(3'-(3-fluorophenyl)-3-methyl-3H-spiro[benzofuran-
2,1'-isochromen]-5-yl)-4-methylbenzenesulfonamide
(4d)
White solid, 67.5 mg, 66% yield; mp: 230-231 oC. 1H NMR
(400 MHz, CDCl3) δ 7.64-7.53 (m, 4H), 7.33-7.30 (m, 3H),
7.18-6.98 (m, 4H), 6.73 (d, J = 7.5 Hz, 1H), 6.60-6.58 (m,
2H), 6.37 (s, 1H), 4.14 (d, J = 6.1 Hz, 1H), 2.40 (s, 3H), 1.46
(d, J = 6.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 164.9,
162.4, 154.7, 150.7, 143.8, 136.0, 134.2 (d, J = 9.3 Hz),
133.6, 132.1, 129.9, 129.5 (d, J = 19.3 Hz), 128.5, 127.4,
126.6 (d, J = 9.1 Hz), 125.2 (d, J = 7.4 Hz), 124.9, 120.6,
113.9, 113.7, 112.5, 111.4, 111.2, 110.2, 99.8 (d, J = 2.4 Hz),
44.7, 21.6, 12.0.HRMS (ESI) m/z: calcd for
[C30H24FNO4SNa]+ requires: 536.1308 [M+Na]+; found:
536.1302.
White solid,70.9 mg, 69% yield; mp: 141-142 oC. 1H NMR
(400 MHz, CDCl3) δ 7.62 (d, J = 8.2 Hz, 2H), 7.47 (d, J =
8.5 Hz, 3H), 7.43 (d, J = 7.3 Hz, 1H), 7.34-7.30 (m, 3H),
7.26-7.24 (m, 2H), 7.11 (s, 1H), 6.71-6.67 (m, 1H), 6.61 (s,
1H), 6.57 (d, J = 8.3 Hz, 1H), 6.37 (s, 1H), 4.26 (q, J = 6.8
Hz, 1H), 2.41 (s, 3H), 1.46 (d, J = 7.0 Hz, 3H). 13C NMR
(100 MHz, CDCl3) δ 164.2, 161.8, 154.8, 148.3 (d, J = 2.9
Hz), 143.9, 136.4 (d, J = 8.1 Hz), 135.9, 132.3, 131.4,
130.1(d, J = 4.6 Hz), 129.6, 127.5, 126.1, 125.5, 125.0,
124.5, 120.6 (d, J = 4.7 Hz), 115.9, 115.7, 112.7, 112.1,
111.8, 110.3, 101.5, 44.5, 21.6, 12.0. HRMS (ESI) m/z:
calcd for [C30H25FNO4S]+ requires: 514.1488 [M+H]+;
found: 514.1484.
N-(7'-fluoro-3'-(4-methoxyphenyl)-3-methyl-3H-
spiro[benzofuran-2,1'-isochromen]-5-yl)-4-
methylbenzenesulfonamide (4i)
White solid, 40.2 mg, 37% yield; mp: 181-182 oC. 1H NMR
(400 MHz, CDCl3) δ 7.66-7.62 (m, 2H), 7.54-7.50 (m, 2H),
7.29-7.26 (m, 4H), 7.21-7.07 (m, 3H), 6.88 (d, J = 8.7 Hz,
3H), 6.77-6.75 (m, 1H), 6.62 (d, J = 8.4 Hz, 1H), 6.51 (s,
1H), 6.42-6.38 (m, 1H), 4.15 (q, J = 6.7 Hz, 1H), 3.83 (s,
4H), 2.43 (s, 4H), 1.48 (d, J = 7.0 Hz, 3H). 13C NMR (100
MHz, CDCl3) δ 160.4, 154.8, 149.0 (d, J = 2.5 Hz), 143.9),
136.0, 132.2, 129.9, 129.6, 128.3 (d, J = 2.9 Hz), 127.5,
126.6 (dd, J = 16.9, 4.8 Hz), 125.2, 120.7, 117.3, 117.1,
113.9, 112.1 (d, J = 2.7 Hz), 111.7, 111.5, 110.3, 100.0, 98.1
(d, J = 1.1 Hz), 55.4, 44.7, 21.7, 12.2. HRMS (ESI) m/z:
N-(3'-(4-chlorophenyl)-3-methyl-3H-spiro[benzofuran-
2,1'-isochromen]-5-yl)-4-methylbenzenesulfonamide
(4e)
White solid, 65.5 mg, 62% yield; mp: 184-185 oC. 1H NMR
(400 MHz, CDCl3) δ 7.63-7.61 (m, 2H), 7.49-7.46 (m, 3H),
7.43 (d, J = 7.3 Hz, 1H), 7.34-7.30 (m, 3H), 7.27-7.24 (m,
2H), 7.11 (s, 1H), 6.70 (d, J = 8.3 Hz, 1H), 6.61-6.56 (m,
1H), 6.57 (d, J = 8.3 Hz, 1H), 6.37 (s, 1H), 4.26 (q, J = 6.8
Hz, 1H), 2.41 (s, 3H), 1.46 (d, J = 7.0 Hz, 3H). 13C NMR
(100 MHz, CDCl3) δ 154.9, 148.6, 143.9, 136.1, 134.9,
132.6, 132.4, 131.5, 130.1, 129.9, 129.6, 128.7, 127.5, 127.4, calcd for [C31H26FNO5SNa]+ requires: 566.1413 [M+Na]+;
126.3, 125.9, 125.4, 124.9, 124.5, 120.7, 112.8, 110.3, 100.9, found: 566.1409.
44.4, 21.7, 12.1. HRMS (ESI) m/z: calcd for
[C30H24ClNO4SNa]+ requires: 552.1012 [M+Na]+; found:
552.1006.
N-(6'-fluoro-3-methyl-3'-phenyl-3H-spiro[benzofuran-
2,1'-isochromen]-5-yl)-4-methylbenzenesulfonamide
(4f)
N-(3-methyl-3'-phenyl-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)benzenesulfonamide (4j)
White solid, 63.6 mg, 66% yield; mp: 187-188 oC. 1H NMR
(400 MHz, CDCl3) δ 7.76-7.65 (m, 2H), 7.61-7.53 (m, 2H),
7.51-7.40 (m, 4H), 7.38-7.28 (m, 5H), 7.09 (s, 1H), 6.76 (dd,
J = 8.3, 1.7 Hz, 1H), 6.70 (s, 1H), 6.64 (s, 1H), 6.61 (d, J =
8.4 Hz, 1H), 4.27 (q, J = 7.0 Hz, 1H), 1.48 (d, J = 7.0 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ 155.2, 149.6, 139.6,
137.4, 134.1, 132.7, 131.8, 130.1, 129.3, 129.1, 128.9, 128.5,
127.1, 125.8, 125.4, 125.06 (d, J = 5.6 Hz), 124.44 (s), 120.7,
112.9, 110.4, 100.6, 44.4, 12.1. HRMS (ESI) m/z: calcd for
White solid, 66.5 mg, 65% yield; mp: 204-205 oC. 1H NMR
(400 MHz, CDCl3) δ 7.64-7.53 (m, 4H), 7.33-7.30 (m, 3H),
7.18-6.98 (m, 4H), 6.73 (d, J = 7.5 Hz, 1H), 6.60-6.48 (m,
2H), 6.37 (s, 1H), 4.14 (d, J = 6.1 Hz, 1H), 2.40 (s, 3H), 1.46
(d, J = 6.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 153.3,
143.5, 137.0, 133.9, 132.5, 131.9, 130.0, 129.5, 129.1, 127.3, [C29H243NO4S]+ requires: 482.1426 [M+H]+; found:
124.7, 122.8, 118.6, 112.7, 112.4, 111.9 (d, J = 2.7 Hz),
110.1, 100.4, 43.3, 21.4, 12.0. HRMS (ESI) m/z: calcd for
[C30H24FNO4SNa]+ requires: 536.1308 [M+Na]+; found:
536.1298.
482.1424.
N-(3-methyl-3'-phenyl-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)naphthalene-2-sulfonamide (4k)
White solid, 47.8 mg, 45% yield; mp: 172-173 oC. 1H NMR
(400 MHz, CDCl3) δ 8.33 (d, J = 1.4 Hz, 1H), 7.93-7.88 (m,
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701149
Advanced Synthesis & Catalysis
3H), 7.75 (dd, J = 8.7, 1.9 Hz, 1H), 7.64-7.58 (m, 1H), 7.59-
7.54 (m, 3H), 7.44-7.40 (m, 2H), 7.32-7.27 (m, 5H), 7.10-
7.08 (m, 1H), 6.77-6.74 (m, 1H), 6.65-6.62 (m, 2H), 6.55 (d,
J = 8.4 Hz, 1H), 4.22 (q, J = 7.0 Hz, 1H), 1.40 (d, J = 7.1
Hz, 3H).13C NMR (100 MHz, CDCl3) δ 155.0, 149.6, 135.9,
4-chloro-N-(3'-phenyl-3-propyl-3H-spiro[benzofuran-
2,1'-isochromen]-5-yl)benzenesulfonamide (4p)
White solid, 77.3 mg, 71% yield; mp: 194-195 oC. 1H NMR
(400 MHz, CDCl3) δ 7.68-7.65 (m, 2H), 7.60-7.55 (m, 2H),
7.49 (d, J = 7.9 Hz, 1H), 7.46-7.40 (m, 3H), 7.37-7.28 (m,
135.0, 134.1, 132.5, 132.1, 131.7, 130.0, 129.6, 129.4, 129.3, 5H), 7.09 (s, 1H), 6.76-6.70 (m, 1H), 6.64 (s, 1H), 6.58 (d,
129.0, 128.5, 128.0, 127.7, 127.1, 125.9, 125.1, 125.0, 124.4, J = 8.4 Hz, 1H), 6.40 (s, 1H), 4.23 (dd, J = 8.2, 6.1 Hz, 1H),
122.6, 120.7, 112.7, 110.3, 100.5, 44.4, 12.1. HRMS (ESI)
m/z: calcd for [C33H26NO4S]+ requires: 532.1583 [M+H]+;
found: 532.1580.
2.05-1.90 (m, 2H), 1.33 (qd, J = 13.9, 7.2 Hz, 2H), 0.87 (t,
J = 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 155.3, 149.4,
139.6, 137.4, 134.2, 132.2, 131.1, 129.9, 129.3, 129.1, 128.9,
128.5, 127.0, 126.7, 125.38 (d, J = 11.9 Hz), 125.0, 124.7,
121.2, 112.3, 110.4, 100.5, 48.8, 30.6, 21.3, 14.5. HRMS
(ESI) m/z: calcd for [C31H27ClNO4S]+ requires: 544.1349
[M+H]+; found: 544.1344.
N-(3'-phenyl-3-propyl-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)naphthalene-2-sulfonamide (4q)
White solid, 80.3 mg, 72% yield; mp: 201-202 oC. 1H NMR
(400 MHz, DMSO-d6) δ 10.00 (s, 1H), 8.33 (s, 1H), 8.09-
8.07 (m, 2H), 7.99 (d, J = 8.1 Hz, 1H), 7.76 (dd, J = 8.7, 1.6
Hz, 1H), 7.65-7.59 (m, 3H), 7.47-7.45 (m, 2H), 7.40 (t, J =
7.4 Hz, 1H), 7.32-7.28 (m, 4H), 7.24-7.22 (m, 1H), 6.98 (s,
1H), 6.88 (s, 1H), 6.81 (dd, J = 8.4, 1.7 Hz, 1H), 6.51 (d, J
= 8.4 Hz, 1H), 4.30 (dd, J = 8.3, 5.9 Hz, 1H), 2.50-2.41 (m,
2H), 1.75-1.58 (m, 2H), 1.09 (ddt, J = 20.5, 13.0, 6.3 Hz,
2H), 0.67 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz, DMSO-
d6) δ 153.6, 148.6, 136.9, 134.8, 134.1, 132.1, 131.9, 131.5,
131.1, 130.3, 129.8, 129.7, 129.5, 129.4, 129.2, 128.6, 128.4,
128.2, 127.5, 127.0, 125.6, 124.8, 123.4, 122.8, 119.2, 112.1,
110.0, 100.9, 47.9, 30.5, 21.0, 14.7. HRMS (ESI) m/z: calcd
for [C35H30NO4S]+ requires: 560.1896 [M+H]+; found:
560.1893.
N-(3-ethyl-3'-phenyl-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)-4-methylbenzenesulfonamide (4l)
White solid, 70.1 mg, 69% yield; mp: 194-195 oC. 1H NMR
(400 MHz, CDCl3) δ 7.64-7.62 (m, 2H), 7.60-7.56 (m, 2H),
7.49 (d, J = 7.9 Hz, 1H), 7.44-7.42 (m, 1H), 7.36-7.29 (m,
5H), 7.25 (d, J = 8.0 Hz, 2H), 7.12 (s, 1H), 6.71 (dd, J =
8.4, 2.0 Hz, 1H), 6.64 (s, 1H), 6.56 (d, J = 8.4 Hz, 1H),
4.14 (t, J = 7.3 Hz, 1H), 2.40 (s, 3H), 2.09-2.01 (m, 2H),
0.92 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ
155.0, 149.4, 143.8, 136.0, 134.2, 131.8, 131.0, 129.9,
129.6, 129.0, 128.5, 127.5, 127.0, 125.4, 125.1, 125.0,
124.7, 121.0, 112.2, 110.2, 100.4, 50.5, 21.7, 21.5,
12.7.HRMS (ESI) m/z: calcd for [C31H28NO4S]+ requires:
510.1739 [M+H]+; found: 510.1740.
N-(3-ethyl-3'-phenyl-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)benzenesulfonamide (4m)
White solid, 69.4 mg, 70% yield; mp: 156-157 oC. 1H NMR
(400 MHz, CDCl3) δ 7.79-7.73 (m, 2H), 7.60-7.54 (m, 3H),
7.50-7.40 (m, 4H), 7.36-7.28 (m, 5H), 7.10 (dd, J = 2.0, 1.2
Hz, 1H), 6.76-6.73 (m, 1H), 6.64 (s, 1H), 6.60-6.51 (m, 2H),
4.14 (t, J = 7.4 Hz, 1H), 2.08-1.98 (m, 2H), 0.92 (s, 3H). 13
C
NMR (100 MHz, CDCl3) δ 155.0, 149.4, 138.9, 134.2,
N-(3-isopropyl-3'-phenyl-3H-spiro[benzofuran-2,1'-
133.0, 131.9, 131.0, 129.9, 129.4, 129.0, 128.5, 127.5, 127.0, isochromen]-5-yl)-4-methylbenzenesulfonamide (4r)
125.4, 125.2, 12.0, 124.7, 121.0, 112.2, 110.3, 100.4, 50.5,
21.5, 12.7. HRMS (ESI) m/z: calcd for [C30H26NO4S]+
requires: 496.1583 [M+H]+; found: 496.1582.
4-methyl-N-(3'-phenyl-3-propyl-3H-spiro[benzofuran-
2,1'-isochromen]-5-yl)benzenesulfonamide (4n)
White solid, 78.6 mg, 75% yield; mp: 202-203 oC. 1H NMR
(400 MHz, CDCl3) δ 7.67-7.59 (m, 4H), 7.42-7.33 (m, 5H),
7.29-7.27 (m, 1H), 7.26-7.24 (m, 2H), 7.16 (d, J = 1.1 Hz,
1H), 6.75 (dd, J = 8.4, 2.1 Hz, 1H), 6.65 (s, 1H), 6.55 (d, J
= 8.4 Hz, 1H), 6.28 (s, 1H), 4.02 (d, J = 5.5 Hz, 1H), 2.51
(dq, J = 13.7, 6.8 Hz, 1H), 2.40 (s, 3H), 1.08 (d, J = 6.7 Hz,
3H), 1.00 (d, J = 6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3)
δ 155.4, 149.5, 143.9, 136.0, 134.1, 130.5, 130.0, 129.8,
129.6, 129.1, 129.0, 128.5, 127.9, 127.6, 127.1, 125.5, 125.4,
125.1, 124.3, 122.2, 112.6, 110.3, 100.6, 55.0, 27.6, 22.3,
21.6, 20.3. HRMS (ESI) m/z: calcd for [C32H30NO4S]+
requires: 524.1896 [M+H]+; found: 524.1897.
White solid, 73.3 mg, 70% yield; mp: 161-162 oC. 1H NMR
(400 MHz, CDCl3) δ 7.64-7.62 (m, 2H), 7.60-7.56 (m, 2H),
7.49-7.47 (m, 1H), 7.44-7.40 (m, 1H), 7.36-7.28 (m, 5H),
7.28-7.25 (m, 2H), 7.10 (s, 1H), 6.71 (dd, J = 8.3, 1.8 Hz,
1H), 4.25-4.19 (m, 1H), 2.40 (s, 3H), 2.02-1.89 (m, 2H),
1.35-1.25 (m, 2H), 0.86 (t, J = 7.3 Hz, 3H). 13C NMR (100
MHz, CDCl3) δ 155.0, 149.4, 143.8, 136.0, 134.2, 132.0,
131.1, 129.9, 129.6, 129.0, 128.5, 127.6, 127.0, 126.8, 125.4, 4-methyl-N-(3'-phenyl-3-(p-tolyl)-3H-spiro[benzofuran-
125.1, 125.0, 124.7, 121.0, 112.3, 110.2, 100.4, 48.8, 30.6,
21.7, 21.3, 14.5. HRMS (ESI) m/z: calcd for [C32H30NO4S]+
requires: 524.1896 [M+H]+; found: 524.1893.
N-(3'-phenyl-3-propyl-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)benzenesulfonamide (4o)
2,1'-isochromen]-5-yl)benzenesulfonamide (4s)
White solid, 78.9 mg, 69% yield; mp: 213-214 oC. 1H NMR
(400 MHz, CDCl3) δ 7.68 (d, J = 7.5 Hz, 1H), 7.63-7.61 (m,
2H), 7.44-7.34 (m, 4H), 7.32-7.26 (m, 4H), 7.26-7.21 (m,
2H), 7.07 (d, J = 8.1 Hz, 2H), 7.02-6.93 (m, 3H), 6.87 (s,
1H), 6.72 (d, J = 8.4 Hz, 1H), 6.51 (s, 1H), 6.44 (s, 1H), 5.42
(s, 1H), 2.43 (s, 3H), 2.27 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 155.9, 149.6, 143.8, 137.4, 136.0, 134.0, 131.9,
131.8, 130.5, 130.0, 129.9, 129.7, 128.9, 128.8, 128.3, 127.6,
127.1, 126.2, 125.7, 125.4, 124.9, 124.7, 122.0, 112.5, 110.7,
100.3, 56.2, 21.7, 21.2. HRMS (ESI) m/z: calcd for
[C36H30NO4S]+ requires: 572.1896 [M+H]+; found:
White solid, 77.5 mg, 76% yield; mp: 195-196 oC. 1H NMR
(400 MHz, CDCl3) δ 7.78-7.76 (m, 2H), 7.59-7.55 (m, 3H),
7.50-7.40 (m, 4H), 7.37-7.27 (m, 5H), 7.11 (s, 1H), 6.75-
6.73 (m, 1H), 6.64 (s, 2H), 6.56 (d, J = 8.4 Hz, 1H), 4.27-
4.15 (m, 1H), 2.05-1.87 (m, 2H), 1.32 (tt, J = 13.6, 6.7 Hz,
2H), 0.85 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
δ 155.0, 149.4, 138.9, 134.2, 133.0, 132.0, 131.1, 129.9,
129.5, 129.0, 128.5, 127.5, 127.0, 126.8, 125.4, 125.1, 125.0, 572.1895.
124.7, 121.0, 112.3, 110.3, 100.4, 48.8, 30.5, 21.3, 14.5.
HRMS (ESI) m/z: calcd for [C31H28NO4S]+ requires:
510.1739 [M+H]+; found: 510.1741.
N-(3-(4-chlorophenyl)-3'-phenyl-3H-spiro[benzofuran-
2,1'-isochromen]-5-yl)-4-methylbenzenesulfonamide
(4t)
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701149
Advanced Synthesis & Catalysis
White solid, 83.0 mg, 70% yield; mp: 174-175 oC. 1H NMR
(400 MHz, CDCl3) δ 7.65-7.63 (m, 1H), 7.60 (d, J = 8.1 Hz,
2H), 7.44-7.40 (m, 1H), 7.38-7.33 (m, 3H), 7.30-7.26 (m,
3H), 7.25-7.20 (m, 3H), 7.13 (d, J = 8.3 Hz, 2H), 7.08 (d, J
= 8.4 Hz, 2H), 6.97-6.92 (m, 1H), 6.84 (s, 1H), 6.73 (d, J =
8.4 Hz, 1H), 6.42 (d, J = 5.6 Hz, 2H), 5.38 (s, 1H), 2.41 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 155.9, 149.6, 143.9,
White solid, 59.1 mg, 53% yield; mp: 217-218 oC. 1H NMR
(400 MHz, CDCl3) δ 7.68 (d, J = 7.6 Hz, 1H), 7.61 (d, J =
8.2 Hz, 2H), 7.45-7.41 (m, 1H), 7.40-7.34 (m, 3H), 7.30-
7.23 (m, 6H), 7.22-7.16 (m, 5H), 6.96 (dd, J = 8.5, 1.2 Hz,
1H), 6.88 (s, 1H), 6.73 (d, J = 8.4 Hz, 1H), 6.42 (s, 2H), 5.44
(s, 1H), 2.42 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 155.9,
149.6, 143.8, 136.0, 135.1, 133.9, 131.7, 130.2, 130.1, 130.0,
136.0, 133.8, 133.7, 133.6, 131.6, 131.3, 130.2, 130.0, 129.8, 129.9, 129.7, 128.8, 128.3, 128.2, 127.8, 127.6, 127.1, 126.2,
129.7, 129.0, 128.4, 128.3, 127.5, 127.2, 126.0, 125.4, 124.8, 125.8, 125.3, 124.9, 122.0, 112.6, 110.7, 100.2, 56.8,
124.5, 121.8, 112.4, 110.9, 100.3, 56.3, 21.7.HRMS (ESI)
m/z: calcd for [C35H27ClNO4S]+ requires: 592.1349 [M+H]+;
found: 592.1345.
21.7.HRMS (ESI) m/z: calcd for [C35H27NO4SNa]+ requires:
580.1558 [M+Na]+; found: 580.1553.
N-(3,3'-diphenyl-3H-spiro[benzofuran-2,1'-
N-(3-(4-bromophenyl)-3'-phenyl-3H-spiro[benzofuran-
2,1'-isochromen]-5-yl)-4-methylbenzenesulfonamide
(4u)
isochromen]-5-yl)benzenesulfonamide (4y)
White solid, 62.0 mg, 57% yield; mp: 174-175 oC. 1H NMR
(400 MHz, CDCl3) δ 7.79-7.72 (m, 2H), 7.69 (d, J = 7.6 Hz,
1H), 7.63-7.57 (m, 1H), 7.50-7.40 (m, 3H), 7.40-7.34 (m,
3H), 7.31-7.26 (m, 3H), 7.24-7.12 (m, 6H), 7.02-6.99 (m,
1H), 6.86 (dd, J = 2.1, 1.2 Hz, 1H), 6.74 (d, J = 8.5 Hz, 1H),
6.64 (s, 1H), 6.43 (s, 1H), 5.44 (s, 1H). 13C NMR (100 MHz,
CDCl3) δ 156.0, 149.6, 138.8, 135.0, 133.9, 133.0, 131.7,
130.3, 130.1, 130.0, 129.7, 129.1, 128.9, 128.3, 128.2, 127.8,
127.5, 127.1, 125.9, 125.4, 124.9, 124.7, 122.0, 112.6, 110.8,
White solid, 91.5 mg, 72% yield; mp: 161-162 oC. 1H NMR
(400 MHz, CDCl3) δ 7.65-7.63 (m, 1H), 7.62-7.60 (m, 2H),
7.45-7.41 (m, 1H), 7.39-7.34 (m, 3H), 7.31-7.28 (m, 5H),
7.25-7.22 (m, 2H), 7.03 (dd, J = 8.7, 2.0 Hz, 2H), 6.95 (dd,
J = 8.3, 2.1 Hz, 1H), 6.86 (d, J = 12.3 Hz, 1H), 6.76-6.71
(m, 1H), 6.43 (d, J = 6.0 Hz, 2H), 5.37 (s, 1H), 2.43 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 155.9, 149.6, 143.9, 136.0,
134.2, 133.8, 131.7, 131.6, 131.4, 130.2, 130.0, 129.7, 129.0, 100.3, 56.6. HRMS (ESI) m/z: calcd for [C34H26NO4S]+
128.4, 127.5, 127.2, 126.0, 125.4, 124.8, 124.5, 121.8, 112.4, requires: 544.1583 [M+H]+; found: 544.1581.
110.9, 100.4, 56.4, 21.7. HRMS (ESI) m/z: calcd for
[C35H27BrNO4S]+ requires: 636.0844 [M+H]+; found:
636.0842.
4-chloro-N-(3,3'-diphenyl-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)benzenesulfonamide (4z)
White solid, 63.6 mg, 55% yield; mp: 192-193 oC. 1H NMR
(400 MHz, CDCl3) δ 7.68 (d, J = 7.3 Hz, 1H), 7.67-7.61 (m,
2H), 7.47-7.41 (m, 3H), 7.40-7.34 (m, 3H), 7.32-7.26 (m,
3H), 7.26-7.20 (m, 4H), 7.18-7.10 (m, 2H), 7.02-6.99 (m,
1H), 6.81 (dd, J = 2.1, 1.2 Hz, 1H), 6.76 (d, J = 8.5 Hz, 1H),
6.44 (d, J = 11.8 Hz, 2H), 5.44 (s, 1H). 13C NMR (100 MHz,
CDCl3) δ 156.2, 149.6, 139.6, 137.3, 134.9, 133.9, 131.7,
130.5, 130.1, 129.32 (d, J = 3.7 Hz), 129.0), 128.3, 127.9,
127.1, 126.1, 125.4, 124.8, 124.6, 122.1, 112.6, 110.9, 100.3,
56.7, 31.0. HRMS (ESI) m/z: calcd for [C34H25ClNO4S]+
requires: 578.1193 [M+H]+; found: 578.1190.
4-methyl-N-(3-phenyl-3'-(p-tolyl)-3H-spiro[benzofuran-
2,1'-isochromen]-5-yl)benzenesulfonamide (4v)
White solid, 67.5 mg, 59% yield; mp: 173-174 oC. 1H NMR
(400 MHz, CDCl3) δ 7.70-7.68 (m, 1H), 7.61-7.59 (m, 2H),
7.45-7.34 (m, 4H), 7.30-7.26 (m, 4H), 7.25-7.23 (m, 1H),
7.22-7.17 (m, 1H), 7.08-7.06 (m, 2H), 6.99 (d, J = 8.0 Hz,
2H), 6.96-6.94 (m, 1H), 6.86 (s, 1H), 6.72 (d, J = 8.4 Hz,
1H), 6.44 (s, 1H), 6.27 (s, 1H), 5.42 (s, 1H), 2.43 (s, 3H),
2.26 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 155.9, 149.6,
143.8, 137.5, 136.0, 134.0, 131.8, 130.6, 130.0, 129.8, 129.6, 4-chloro-N-(3-(4-chlorophenyl)-3'-phenyl-3H-
128.9, 128.3, 127.5, 127.1, 126.2, 125.8, 125.4, 124.9, 124.6, spiro[benzofuran-2,1'-isochromen]-5-
122.1, 112.5, 110.7, 100.3, 56.1, 21.7, 21.2. HRMS (ESI)
m/z: calcd for [C36H29NO4SNa]+ requires: 594.1715
[M+Na]+; found: 594.1721.
N-(3'-(3-fluorophenyl)-3-phenyl-3H-spiro[benzofuran-
2,1'-isochromen]-5-yl)-4-methylbenzenesulfonamide
(4w)
yl)benzenesulfonamide (4aa)
White solid, 50.2 mg, 41% yield; mp: 201-202 oC. 1H NMR
(400 MHz, DMSO-d6) δ 9.96 (s, 1H), 7.97 (d, J = 7.7 Hz,
1H), 7.68-7.55 (m, 4H), 7.41 (t, J = 7.4 Hz, 1H), 7.35-7.26
(m, 7H), 7.05 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.4 Hz, 1H),
6.77 (s, 1H), 6.71 (d, J = 8.5 Hz, 1H), 6.62 (s, 1H), 5.85 (s,
1H). 13C NMR (100 MHz, DMSO-d6) δ 154.7, 148.6, 138.3,
134.7, 133.8, 132.9, 132.2, 131.9, 131.4, 130.7, 130.5, 129.7,
129.4, 129.1, 128.7, 127.8, 126.1, 125.5, 124.7, 120.1, 112.3,
110.9, 101.2, 53.8. HRMS (ESI) m/z: calcd for
[C34H24Cl2NO4S]+ requires: 612.0803 [M+H]+; found:
612.0801.
White solid, 54.1 mg, 47% yield; mp: 174-175 oC. 1H NMR
(400 MHz, CDCl3) δ 7.67 (d, J = 7.5 Hz, 1H), 7.60 (d, J =
8.3 Hz, 2H), 7.42 (td, J = 7.4, 1.4 Hz, 1H), 7.37 (td, J = 7.5,
1.5 Hz, 1H), 7.27 (s, 1H), 7.25 (s, 1H), 7.22 (d, J = 1.0 Hz,
1H), 7.21-7.14 (m, 5H), 7.11 (dd, J = 7.7, 1.7 Hz, 2H), 7.01-
6.91 (m, 3H), 6.86 (s, 1H), 6.74 (d, J = 8.4 Hz, 1H), 6.40 (d,
J = 4.5 Hz, 2H), 5.40 (s, 1H), 2.42 (s, 3H). 13C NMR (100
MHz, CDCl3) δ 164.1, 155.8, 148.30 (d, J = 2.9 Hz), 143.9,
136.22 (d, J = 8.2 Hz), 135.9, 135.0, 131.2, 130.1 (d, J =
3.0Hz), 128.3, 127.9, 127.56 (d, J = 3.1 Hz), 126.5, 125.9,
125.5, 124.7, 122.0, 120.4 (d, J = 2.9 Hz), 115.7, 115.4,
112.5, 111.9, 111.7, 110.7, 101.1, 77.37 (d, J = 11.4 Hz),
77.1, 76.8, 60.5, 57.0, 21.7, 21.2, 14.3. HRMS (ESI) m/z:
calcd for [C35H26FNO4SNa]+ requires: 598.1464 [M+Na]+;
found: 598.1473.
Acknowledgements
We are grateful for financial support from the NSFC (Nos.
21332005, 21672100 and 21702103), 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 Jiangsu Education
Committee, Robert A. Welch Foundation (D-1361, USA), Texas
Tech University research promotion fund (to BJ).
N-(3,3'-diphenyl-3H-spiro[benzofuran-2,1'-
isochromen]-5-yl)-4-methylbenzenesulfonamide (4x)
9
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701149
Advanced Synthesis & Catalysis
References
2016, 5747; c) R. Bandichhor, A. N. Lowell, M. C.
Kozlowski, J. Org. Chem. 2011, 76, 6475; d) M.
Wilsdorf, D. Leichnitz, H.-U. Reissig, Org. Lett. 2013,
15, 2494; e) M. Wilsdorf, D. Lentz, H.-U. Reissig, Eur.
J. Org. Chem. 2016, 2016, 1555.
[1] a) F. Perron, K. F. Albizati, Chem. Rev. 1989, 89, 1617;
b) J. E. Aho, P. M. Pihko, T. K. Rissa, Chem. Rev. 2005,
105, 4406; c) J. Sperry, Z. E. Wilson, D. C. K. Rathwell,
M. A. Brimble, Nat. Prod. Rep. 2010, 27, 1117; d) M.
Brasholz, S. Scrgel, C. Azap, H.-U. Reissig, Eur. J. Org.
Chem. 2007, 2007, 3801; e) K. T. Mead, B. N. Brewer,
Curr. Org. Chem. 2003, 7, 227. f) M. T. Fletcher, W.
Kitching, Chem. Rev. 1995, 95, 789; g) Y. K. Booth, W.
Kitching, J. J. De Voss, Nat. Prod. Rep. 2009, 26, 490;
h) R. Rios, Chem. Soc. Rev. 2012, 41, 1060.
[12] a) G. Zhou, J. Zhu, Z. Xie, Y. Li, Org. Lett. 2008, 10,
721; b) M. A. Marsini, Y. Huang, C. C. Lindsey, K.-L.
Wu, T. R. R. Pettus, Org. Lett. 2008, 10, 1477.
[13] a) X. Wang, S. Dong, Z. Yao, L. Feng, P. Daka, H.
Wang, Z. Xu Org. Lett. 2014, 16, 22; b) M. Liang, S.
Zhang, J. Jia, C.-H. Tung, J. Wang, Z. Xu, Org. Lett.
2017, 19, 2526.
[2] H. Rahman, M. Shaaban, K. A. Shaaban, M. Saleem, E.
Helmke, I. Gruen-Wollny, H. Laatsch, Nat. Pro. Comm.
2009, 4, 965.
[14] For selected examples, see: (a) S.-Y. Yu, H. Zhang, Y.
Gao, L. Mo, S. Wang, Z.-J. Yao, J. Am. Chem. Soc. 2013,
135, 11402; b) S. Zhu, H. Huang, Z. Zhang, T. Ma, H.
Jiang, J. Org. Chem. 2014, 79, 6113; c) Q. Xu, P. Gu, F.
Wang, M. Shi, Org. Chem. Front. 2015, 2, 1475; d) R.
Liang, T. Ma, S. Zhu, Org. Lett. 2014, 16, 4412; e) J.
Sun, J.-K. Qiu, Y.-N. Wu, W.-J. Hao, C. Guo, G. Li, S.-
J. Tu, B. Jiang, Org. Lett. 2017, 19, 754; f) J. Zhang, Y.
Xiao, K. Chen, W. Wu, H. Jiang, S. Zhu, Adv. Synth.
Catal. 2016, 358, 2684; g) F. Liu, J.-Y. Wang, P. Zhou,
G. Li, W.-J. Hao, S.-J. Tu, B. Jiang, Angew. Chem., Int.
Ed. 2017, 56, 15570.
[3] Z. Yunt, K. Reinhardt, A. Li, M. Engeser, H. M. Dahse,
M. Guetschow, T. Bruhn, G. Bringmann, J. Piel, J. Am.
Chem. Soc. 2009, 131, 2297.
[4] Z. Lin, M. M. Zachariah, L. Marett, R. W. Hughen, R.
W. Teichert, G. P. Concepcion, M. G. Haygood, B. M.
Olivera, A. R. Light, E. W. Schmidt, J. Nat. Prod. 2014,
77, 1224.
[5] a) J. Sperry, Y.-C. Liu, Z. E. Wilson, J. G. Hubert, M. A.
Brimble, Synthesis 2011, 1383; b) Y.-C. Liu, J. Sperry,
D. C. K. Rathwell, M. A. Brimble, Synlett 2009, 793; c)
Z. E. Wilson, J. G. Hubert, M. A. Brimble, Eur. J. Org.
Chem. 2011, 2011, 3938; d) J. Xue, H. Zhang, T. Tian,
K. Yin, D. Liu, X. Jiang, Y. Li, X. Jin, X. Yao, Adv.
Synth. Catal. 2016, 358, 370; e) W. Wei, L. Li, X. Lin,
H. Li, J. Xue, Y. Li, Org. Biomol. Chem. 2012, 10, 3494;
f) Z. Xin, Y. Zhang, H. Tao, J. Xue, Y. Li, Synlett 2011,
1579; g) L. Wei, J. Xue, H. Liu, W. Wang, Y. Li, Org.
Lett. 2012, 14, 5302.
[15] N. Asao, K. Takahashi, S. Lee, T. Kasahara, Y.
Yamamoto, J. Am. Chem. Soc. 2002, 124, 12650.
[16] a) Z. B. Guo, Y. Zhou, L. Zhang, R. Hua, J. Org. Chem.
2015, 80, 7635; b) K. Saito, Y. Kajiwara, T. Akiyama,
Angew. Chem., Int. Ed. 2013, 52, 13284; c) M. Terada,
F. Li, Y. Toda, Angew. Chem., Int. Ed. 2014, 53, 235; d)
N. Chernyak, S. I. Gorelsky, V. Gevorgyan, Angew.
Chem., Int. Ed. 2011, 50, 2342; e) H. Luo, K. Chen, H.
Jiang, S. Zhu, Org. Lett. 2016, 18, 5208; f) R. Liang, H.
Jiang, S. Zhu, Chem. Commun. 2015, 51, 5530.
[6] a) Y. Zhang, J. Xue, Z. Xin, Z. Xie, Y. Li, Synlett 2008,
940; b) R. Quach, D. P. Furkert, M. A. Brimble,
Tetrahedron Lett. 2013, 54, 5865.
[17] S. Liu, X.-C. Lan, K. Chen, W.-J. Hao, G. Li, S.-J. Tu,
B. Jiang, Org. Lett. 2017, 19, 3831.
[7] a) S. P. Waters, M. W. Fennie, M. C. Kozlowski,
Tetrahedron Lett. 2006, 47, 5409; b) S. Soergel, C. Azap,
H.-U. Reissig, Org. Lett. 2006, 8, 4875; c) S. P. Waters,
M. W. Fennie, M. C. Kozlowski, Org. Lett. 2006, 8,
3243; d) T. Capecchi, C. B. de Koning, J. P. Michael,
Perkin 1 2000, 2681; f) T. Capecchi, C. B. De Koning,
J. P. Michael, Tetrahedron Lett. 1998, 39, 5429.
[18] a) D. B. England, M. A. Kerr, J. Org. Chem. 2005, 70,
6519; b) F. Xu, L. Zhang, Y. Jia, X. Wang, X. Li, Q.
Wen, Y. Zhang, W. Xu, Eur. J. Med. Chem. 2013, 69,
191; c) S. K. Jackson, S. C. Banfield, M. A. Kerr, Org.
Lett. 2005, 7, 1215; d) J.-Z. Wang, J. Zhou, C. Xu, H.
Sun, L. Kurti, Q.-L. Xu, J. Am. Chem. Soc. 2016, 138,
5202.
[8] a) T. Tian, L. Li, J. Xue, J. Zhang, Y. Li, J. Org. Chem.
2015, 80, 4189; b) X. Li, J. Xue, C. Huang, Y. Li, Chem.-
Asian J. 2012, 7, 903.
[19] CCDC 11571031 (4x) contains the supplementary
crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge
Crystallographic Data Centre.
[9] I. Sharma, J. M. Wurst, D. S. Tan, Org. Lett. 2014, 16,
2474.
[20] a) D. Wang, S. Liu, X.-C. Lan, A. Paniagua, W.-J. Hao,
G. Li, S.-J. Tu, B. Jiang, Adv. Synth. Catal. 2017, 359,
3186; b) S. Liu, K. Chen, X.-C. Lan, W.-J. Hao, G. Li,
S.-J. Tu, B. Jiang, Chem. Commun. 2017, 53, 10692.
[10] a) K. Y. Tsang, M. A. Brimble, Tetrahedron 2007, 63,
6015; b) K. Y. Tsang, M. A. Brimble, J. B. Bremner,
Org. Lett. 2003, 5, 4425.
[11] a) C. Venkatesh, H.-U. Reissig, Synthesis 2008, 3605;
b) M. Wilsdorf, H.-U. Reissig, Eur. J. Org. Chem. 2016,
10
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701149
Advanced Synthesis & Catalysis
FULL PAPER
Oxidative Catalytic Spiroketalization Leading to
Diastereoselective Spiro[benzofuran-2,1'-
isochromene]s
Adv. Synth. Catal. Year, Volume, Page – Page
Jiang-Kai Qiu, Wen-Juan Hao, Guigen Li,* and Bo
Jiang*
11
This article is protected by copyright. All rights reserved.