Cp?CoIII-Catalyzed C-H Alkenylation/Annulation to Afford Spiro Indenyl Benzosultam

Article abstract of DOI:10.1021/acs.joc.6b00976

Cp?Co^III-catalyzed tandem inert C-H alkenylation/annulation of N-sulfonyl ketimines with alkynes is revealed. A series of spiro indenyl benzosultams were facilely prepared in good yields under mild reaction conditions.

Full text of DOI:10.1021/acs.joc.6b00976

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Note
Cp*CoIII-Catalyzed C-H Alkenylation/
Annulation to Afford Spiro Indenyl Benzosultam
Hui Liu, Jie Li, Miao Xiong, Jijun Jiang, and Jun Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00976 • Publication Date (Web): 24 Jun 2016
Downloaded from http://pubs.acs.org on June 24, 2016
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Cp*CoIII-Catalyzed C-H Alkenylation/Annulation to Afford Spiro
Indenyl Benzosultam
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Hui Liu, Jie Li, Miao Xiong, Jijun Jiang, and Jun Wang*
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School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou
510275, P. R. China; e-mail: wangjun23@mail.sysu.edu.cn
Abstract: Cp*CoIII catalyzed tandem inert C-H alkenylation/annulation of N-sulfonyl
ketimines with alkynes is revealed. A series of spiro indenyl benzosultams were facilely
prepared in good yields under mild reaction conditions.
Transition-metal-catalyzed directing-group-assisted inert C-H bond activation has drawn
substantial attentions for their great utilities in the syntheses of drugs, materials, and
natural products.1 Noble metals such as rhodium,2 ruthenium,3 and palladium4 have
played dominant roles in realizing those transformations. However, due to their high
costs, developing more abundant and less expensive metal based catalysts becomes more
and more desirable. In this context, first-row transition metals5 such as iron,6 cobalt,7
nickel,7c, 8 and copper9 have gained much attention and been successfully developed as
attractive alternatives to the noble metal catalysts. Especially worth of noting is the recent
booming development of Cp*CoIII catalyzed inert C-H bond functionalizations, which is
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initiated by the Matsunaga and Kanai's pioneering works on the Cp*CoIII catalyzed
addition of 2-arylpyridines to imines and α,β-unsaturated carbonyl compounds10 as well
as C2-selective addition of 2-pyrimidyl indoles to imines.11
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Benzosultams12 and indanes/indenes13 possess diverse biological activities. Accordingly,
spiro benzosultam derivatives 3 comprising both of these motifs hold great potential for
biological and pharmaceutical studies (Scheme 1). Till now, only few approaches are
available to get access to this skeleton.14, 15 Thereinto, the intermolecular annulations via
transition-metal-catalyzed C-H activation constitute one of the most convenient and
efficient ways.15 Namely, they could be constructed in a single step by reacting cyclic
sulfonyl ketimine 1 with alkene15a or alkyne15b, 15c in the presence of iridium or rhodium
catalyst, which were reported by Nishimura's and Dong's groups, respectively. Moreover,
an asymmetric version of this reaction was also revealed recently by Cramer’s group with
a chiral rhodium catalyst.15d In view of the importance of spiro indenyl benzosultam
derivatives, and encouraged by the effectiveness of Cp*CoIII catalysts in the alkenylation
with alkynes as well as alkenylation/annulation reactions,16 we investigated and report
herein the Cp*CoIII catalyzed syntheses of spiro benzosultams with cyclic sulfonyl
ketimines and alkynes (Scheme 1).
Scheme 1. Synthesis of spiro benzosultam derivatives
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Preliminary studies showed that in the presence of [Cp*CoCl2]2 (2.5 mol%) and
AgSbF6 (10 mol%), the annulation of cyclic N-sulfonyl ketimine 1a with diphenyl
acetylene 2a occurred in dichloroethane (DCE) at 100 °C to afford the spiro indenyl
benzosultam 3aa in 71% yield (Table 1, entry 1). Solvent screening indicated that
solvents such as THF, toluene, and acetonitrile were not suitable for this reaction,
probably due to either strong coordination abilities or solubility reasons (Table 1, entries
2-4). Employing Cu(OAc)2·H2O, Ag2CO3, or KOAc as additive could not improve yield
(Table 1, entries 5-7). Investigation of different ratios of 1a to 2a for the reaction revealed
that 2:1 was superior, giving 99% yield (Table 1, entries 8-11). Reducing the amount of
catalyst loading from 2.5 to 1.0 mol% decreased the yield dramatically to 22% (Table 1,
entry 12). We tried to perform the reaction at lower temperature, and found that the
product was obtained in 99% yield at 80 °C and 70% yield at 60 °C (Table 1, entries
13-14). Though shortening the reaction time from 14 hours to 8 hours did not affect the
yield (99%), further shortening to 4 hours decreased the yield to 70% (Table 1, entries
15-16).
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Table 1. Optimizations of reaction conditionsa
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entry
1
1a:2ab
1:2
1:2
1:2
1:2
1:2
1:2
1:2
2:3
1:1
3:2
2:1
2:1
2:1
2:1
2:1
2:1
solvent
DCE
THF
t (h)
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T (°C)
100
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100
100
80
yield (%)c
71
2
trace
trace
trace
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3
toluene
CH3CN
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
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5d
6e
7f
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trace
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32
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12g
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99
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aReaction conditions: [Cp*CoCl2]2 (2.5 mol%), AgSbF6 (10 mol%), solvent (0.4 mL).
b0.1 mmol 1a was used for entries 1-8, and 0.1 mmol 2a was used for entries 9-16.
cDetermined by H NMR analysis of the crude reaction mixture by using methyl
1
d
4-iodobenzoate as the internal standard. Cu(OAc)2·H2O (0.05 mmol) as additive.
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f
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eAg2CO3 (0.05 mmol) as additive. KOAc (0.05 mmol) as additive. [Cp*CoCl2]2 (1.0
6
mol%), AgSbF6 (4 mol%).
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Under the optimized reaction conditions, we investigated various substituted cyclic
N-sulfonyl ketimines 1 (Scheme 2). N-sulfonyl ketimines (1a-1e) with either
electron-withdrawing or electron–donating R2 substituents at the para-position of phenyl
ring Ar2 were studied. It was observed that the electronic effects influenced the reaction
significantly, and the electron–donating group such as methyl and methoxyl groups
benefited the reaction (3aa–3ea). The substituted fashion also affected the reactivity. For
example, in contrast to the ketimine 1e with a 4-methoxyl phenyl group, the ketimine 1f
with a 2-methoxyl phenyl group afforded the corresponding products only in 22% yield
(3fa). The low yield may be attributed to the coordination of the ortho methoxyl group to
the CoIII species, which would deactivate the catalyst, or possibly by the steric repulsion
of methoxyl group with Ar1 group, which may destabilize the metallacycle intermediate.
To determine which one is dominant, ketimine 1h bearing an ortho methyl phenyl group
was tried and 17% yield was obtained, which indicated the steric hindrance might be the
major reason. The corresponding meta methoxyl ketimine 1g reacted smoothly to give the
product in 80% yield with excellent regioselectivity (10:1). The structure of the major
isomer was determined unambiguously by single crystal X-ray diffraction. The C-H
activation preferentially occurs at the para position of the methoxyl group. To our delight,
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ketimine 1i showed complete regioselectivity and the corresponding products 3ia was
obtained in 99% yield. Ketimines 1j-l with either electron-withdrawing or
electron–donating R1 group on Ar1 ring were also evaluated, affording corresponding
products in 33-87% yield. When the ketimine with Ar2 as 2-pyridyl was taken as the
substrate, no product was obtained. It may be attributed to the strong coordination of
N-atom to the CoIII species, causing deactivation of the catalyst.
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Scheme 2. Substrate scope of N-sulfonyl ketiminesa, b
aReaction conditions unless otherwise specified: 1 (0.2 mmol), 2 (0.1 mmol),
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b
[Cp*CoCl2]2 (2.5 mol%), AgSbF6 (10 mol%), DCE (0.4 mL), 80 °C, 8 hours. Isolated
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yield. cReacted at 100 °C for 14 hours. dThe major isomer is shown.
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Then, a series of internal alkynes 2 were studied (Scheme 3). The diaryl acetylenes
2b-2e with substituents on the para positions of both aryl rings provided products in high
yields, regardless of the substituent electronic properties. Interestingly, while the diaryl
acetylene bearing two 4-nitrophenyl groups (2e) was transformed in good yield of 87%,
the isomeric alkyne with two 3-nitrophenyl groups (2f) gave moderate yield (59%), and
the one having two 2-nitrophenyl groups (2g) merely gave trace amount of product.
When decyne 2h was treated in this reaction, the desired products was isolated in 99%
yield. Additionally, the unsymmetrical alkyne 2i reacted well with ketimine 1a to give the
mixture of isomers in good yield (99%) with good regioselectivity (3:1). The structure of
the minor isomer 3ai was determined unambiguously by single crystal X-ray diffraction.
Terminal alkynes were also investigated. When trimethylsiylacetylene was used, the
product was obtained as the single regioisomer in 35% yield, and the structure of which
was determined to be 3aj by NOE spectrum. Unexpectedly, phenylacetylene failed to
give any desired product. We also attempted to synthesize multi-substituted spiro indenyl
benzosultams by reacting several substituted N-sulfonyl ketimines with substituted
internal alkynes. The corresponding products 3dc, 3eb, 3kc and 3hd were all obtained in
excellent yields. It is noteworthy that the product 3hd was obtained as the sole
regioisomer with the structure determined unambiguously by single crystal X-ray
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diffraction. The single crystal structures of compounds 3ga, 3ai and 3hd are shown in
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Supporting Information.
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Scheme 3. Substrate scope of alkynesa, b
aReaction conditions unless otherwise specified: 1 (0.2 mmol), 2 (0.1 mmol),
b
[Cp*CoCl2]2 (2.5 mol%), AgSbF6 (10 mol%), DCE (0.4 mL), 80 °C, 8 hours. Isolated
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yield. cReacted at 100 for 14 hours. dThe minor regioisomer is shown.
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A probable catalytic cycle is proposed as shown in Scheme 4. Firstly, [Cp*CoCl2]2
reacts with AgSbF6 in situ to generate the catalytically active species A. Then the
N-sulfonyl ketimine 1a coordinates to the species A to afford the five-membered
intermediate B with loss of a proton. Subsequently, the alkyne coordinates to CoIII and
undergoes a migratory insertion to give the intermediate D, which further undergoes a
Grignard-type addition to the C=N bond to form the intermediate E. Lastly, protonation
of intermediate E delivers the desired product 3aa and regenerates the catalyst species A.
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In summary, we have disclosed an efficient Cp*CoIII-catalyzed syntheses of spiro
indenyl benzosultams via directed C-H alkenylation/annulations of N-sulfonyl ketimines
with internal alkynes. Various N-sulfonyl ketimines and alkynes could be applied in this
reaction, and the corresponding products were obtained in good yields.
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Scheme 4. Proposed catalytic cycle
Experimental Section
General Experimental Methods. Unless otherwise noted, all commercially available
reagents were used as received without purification. Dichloroethane was dried over
anhydrous Na2SO4 before use. [Cp*CoCl2]2,17 N-sulfonyl ketimines 1a-1i, 18 N-sulfonyl
ketimines 1j-1l,19 and alkynes 2b-2g20 were synthesized according to the literature
procedures. Alkynes 2a, and 2h-j are commercially available. Flash column
chromatography was performed with silica gel (100-200 mesh). Chemical shifts are given
in dimensionless δ values and frequency referenced relative to TMS in 1H and 13C NMR
spectra. HRMS data were recorded on ESI-Q-TQF mass spectrometer.
General Procedure for the Synthesis of Spiro Indenyl Benzosultam. All reactions
were carried out in dry reaction vessels with Teflon screw caps in nitrogen atmosphere.
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Sulfonyl ketimine 1 (0.2 mmol, 2.0 equiv), alkyne 2 (0.1 mmol, 1.0 equiv), [Cp*CoCl2]2
(1.3 mg, 2.5 mol%) and AgSbF6 (3.4 mg, 10 mol%) were stirred in DCE (0.4 mL) at
80°C or 100°C for 8-14 hours. The reaction mixture was directly subjected onto silica gel
column chromatography and eluted by petroleum ether/dichloromethane (1:2) to pure
DCM to afford the product 3.
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2',3'-Diphenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3aa). Known
compound.15d White solid, 42 mg, 99% yield. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.88
– 7.86 (m, 1H), 7.60 – 7.50 (m, 2H), 7.45 – 7.30 (m, 8H), 7.24 – 7.20 (m, 1H), 7.15 –
7.06 (m, 4H), 6.91 – 6.89 (m, 2H), 4.84 (s, 1H).
5'-Fluoro-2',3'-diphenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3ba).
Known compound.15d White solid, 8 mg, 18% yield. 1H NMR (400 MHz, CDCl3): δ (ppm)
7.88 – 7.86 (m, 1H), 7.65 – 7.51 (m, 2H), 7.40 – 7.39 (m, 6H), 7.15 – 7.13 (m, 2H), 7.10
– 7.03 (m, 3H), 6.89 – 6.87 (m, 3H), 4.85 (s, 1H).
5'-Chloro-2',3'-diphenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene] 1,1-dioxide (3ca).
1
White solid, 22 mg, 48% yield. H NMR (400 MHz, CDCl3): δ (ppm) 7.88 – 7.86 (m,
1H), 7.60 – 7.55 (m, 2H), 7.41 – 7.36 (m, 6H), 7.31 (m, 1H), 7.19 – 7.06 (m, 5H), 6.88 –
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6.87 (m, 2H), 4.87 (s, 1H). C NMR (100 MHz, CDCl3): δ (ppm) 145.6, 144.3, 144.0,
142.5, 138.9, 135.4, 135.3, 134.0, 133.1, 131.8, 130.0, 129.1, 129.0, 128.6, 128.5, 128.4,
127.5, 124.4, 123.3, 121.9, 121.8, 74.6. HRMS (ESI) [M+Na]+ calcd. for
C27H18ClNO2SNa 478.0639, found 478.0638.
5'-Methyl-2',3'-diphenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3da).
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White solid, 42 mg, 97% yield. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.86 – 7.84 (m, 1H),
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7.56 – 7.49 (m, 2H), 7.40 (m, 5H), 7.32 – 7.30 (m, 1H), 7.14 – 7.01 (m, 6H), 6.90 – 6.89
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(m, 2H), 4.84 (s, 1H), 2.34 (s, 3H). C NMR (100 MHz, CDCl3): δ (ppm) 144.6, 143.4,
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143.2, 142.4, 139.8, 139.4, 135.3, 133.9, 133.8, 132.5, 129.7, 129.3, 129.2, 128.8, 128.3,
128.2, 128.1, 123.4, 123.0, 122.3, 121.8, 75.0, 21.6. HRMS (ESI) [M+Na]+ calcd. for
C28H21NO2SNa 458.1185, found 458.1184.
5'-Methoxy-2',3'-diphenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide
(3ea). Known compound.15d White solid, 45 mg, 99% yield. 1H NMR (400 MHz, CDCl3):
δ (ppm) 7.87 – 7.80 (m, 1H), 7.60 – 7.47 (m, 2H), 7.46-7.29 (m, 6H), 7.19 – 7.00 (m, 4H),
6.97 – 6.83 (m, 3H), 6.76 – 6.64 (m, 1H), 4.84 (s, 1H), 3.78 (s, 3H).
7'-Methoxy-2',3'-diphenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3fa).
White solid, 10 mg, 22% yield. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.77 – 7.75 (m, 1H),
7.51 – 7.49 (m, 2H), 7.38 – 7.29 (m, 6H), 7.12 – 7.04 (m, 4H), 7.01 – 6.99 (m, 1H), 6.88
– 6.87 m, 2H), 6.77 – 6.75 (m, 1H), 5.04 (s, 1H), 3.67 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ (ppm) 155.1, 146.5, 144.9, 141.4, 138.3, 136.4, 133.7, 133.2, 132.5, 131.5,
131.4, 129.7, 129.4, 129.3, 128.5, 128.0, 127.9, 123.1, 121.4, 114.2, 110.5, 75.3, 55.4.
HRMS (ESI) [M+Na]+ calcd. for C28H21NO3SNa 474.1134, found 474.1139.
6'-Methoxy-2',3'-diphenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3ga)
and 4'-methoxy-2',3'-diphenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide
(3ga') (3ga : 3ga' = 10 : 1). White solid, 36 mg, 80% yield.
6'-Methoxy-2',3'-diphenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide
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(3ga). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.88 – 7.87 (m, 1H), 7.59 – 7.52 (m, 2H),
7.39 – 7.37 (m, 5H), 7.26 – 7.24 (m, 1H), 7.17 – 7.04 (m, 5H), 6.86 – 6.84(m, 3H), 4.88
(s, 1H), 3.75 (s, 3H). 13C NMR (100 MHz, CDCl3): δ (ppm) 159.9, 149.4, 143.2, 140.8,
139.9, 135.3, 134.7, 133.9, 133.8, 132.5, 129.8, 129.2, 129.1, 128.7, 128.3, 128.2, 127.9,
123.5, 122.2, 121.8, 114.6, 109.5, 74.9, 55.6. HRMS (ESI) [M+Na]+ calcd. for
C28H21NO3SNa 474.1134, found 474.1139.
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4'-methoxy-2',3'-diphenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide
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(3ga'). H NMR (400 MHz, CDCl3): δ (ppm) 7.86 – 7.84 (m, 1H), 7.56 – 7.54 (m, 2H),
7.35 – 7.34 (m, 2H), 7.29 – 7.27 (m, 3H), 7.20 – 7.17 (m, 2H), 7.09 – 7.00 (m, 4H), 6.86
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– 6.84 (m, 1H), 6.80 – 6.78 (m, 2H), 4.85 (s, 1H), 3.62 (s, 3H). C NMR (100 MHz,
DMSO-d6): δ (ppm) 154.7, 150.0, 143.4, 142.7, 138.4, 136.2, 135.8, 134.1, 133.8, 130.3,
130.0, 129.8, 129.3, 128.8, 127.9, 127.8, 127.7, 127.6, 123.7, 121.6, 115.9, 113.5, 75.0,
55.9. HRMS (ESI) [M+Na]+ calcd. for C28H21NO3SNa 474.1134, found 474.1139.
7'-Methyl-2',3'-diphenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene] 1,1-dioxide (3ha).
White solid, 7 mg, 17% yield. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.80 – 7.78 (m, 1H),
7.59 – 7.57 (m, 2H), 7.31 – 7.28 (m, 6H), 7.23 – 7.21 (m, 1H), 7.15 – 7.13 (m, 2H), 7.09
– 7.05 (m, 2H), 7.02 – 7.00 (m, 1H), 6.72 – 6.70 (m, 2H), 4.75 (s, 1H), 2.05 (s, 3H). 13C
NMR (100 MHz, DMSO-d6): δ (ppm) 146.5, 143.6, 143.5, 141.3, 136.8, 136.6, 134.8,
134.0, 133.9, 133.4, 130.5, 130.4, 129.9, 129.7, 129.5, 128.9, 128.3, 127.9, 123.7, 121.5,
118.9, 75.9, 17.3. HRMS (ESI) [M+Na]+ calcd. for C28H21NO2SNa 458.1185, found
458.1192.
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de (3ia). Known compound.15d White solid, 47 mg, 99% yield. H NMR (400 MHz,
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CDCl3): δ (ppm) 7.90 (d, J = 7.7 Hz, 1H), 7.85 (s, 1H), 7.78 (m, 2H), 7.71 (s, 1H), 7.61 –
7.36 (m, 9H), 7.20 – 7.05 (m, 4H), 6.96 – 6.94 (m, 2H), 4.92 (s, 1H).
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5-Chloro-2',3'-diphenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3ja).
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White solid, 15 mg, 33% yield. H NMR (400 MHz, CDCl3): δ (ppm) 7.80 – 7.78 (m,
1H), 7.52 – 7.50 (m, 1H), 7.46 – 7.44 (m, 1H), 7.43 – 7.34 (m, 7H), 7.2 – 7.21 (m, 1H),
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7.19 – 7.05 (m, 4H), 6.94 – 6.92 (m, 2H), 4.90 (s, 1H). C NMR (100 MHz, CDCl3): δ
(ppm) 146.8, 143.8, 142.3, 142.1, 141.8, 140.3, 133.9, 133.4, 132.0, 130.5, 129.5, 129.2,
129.1, 128.8, 128.5, 128.4, 127.9, 123.5, 123.3, 123.1, 121.8, 74.7. HRMS (ESI)
[M+Na]+ calcd. for C27H18ClNO2SNa 478.0639, found 478.0643.
5-Methyl-2',3'-diphenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3ka).
White solid, 36 mg, 83% yield. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.76 – 7.74 (m, 1H),
7.48 – 7.30 (m, 9H), 7.24 – 7.20 (m, 1H), 7.16 – 7.03 (m, 3H), 6.90 – 6.89 (m, 3H), 4.81
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(s, 1H), 2.34 (s, 3H). C NMR (100 MHz, CDCl3): δ (ppm) 147.6, 145.0, 143.3, 142.9,
142.2, 139.9, 133.8, 132.7, 132.3, 131.0, 129.3, 129.2, 129.1, 128.8, 128.4, 128.3, 128.1,
127.7, 123.3, 123.2, 121.6, 121.5, 75.0, 21.8. HRMS (ESI) [M+Na]+ calcd. for
C28H21NO2SNa 458.1185, found 458.1191.
5-Methoxy-2',3'-diphenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3la).
White solid, 39 mg, 87% yield. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.78 – 7.76 (m, 1H),
7.49 – 7.47 (m, 1H), 7.44 – 7.27 (m, 7H), 7.23 – 7.20 (m, 1H), 7.11 – 7.03 (m, 4H), 6.94
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– 6.93 (m, 2H), 6.51 (m, 1H), 4.85 (s, 1H), 3.73 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
(ppm) 164.1, 147.6, 143.3, 142.8, 142.3, 142.1, 133.8, 132.3, 129.3, 129.2, 128.8, 128.4,
128.3, 128.2, 127.7, 127.6, 123.4, 123.3, 121.5, 116.5, 107.2, 74.8, 55.8. HRMS (ESI)
[M+Na]+ calcd. for C28H21NO3SNa 474.1134, found 474.1137.
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2',3'-Di-p-tolyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide(3ab).
White
solid, 41 mg, 91% yield. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.87 – 7.85 (m, 1H), 7.56
– 7.49 (m, 2H), 7.44 – 7.42 (m, 1H), 7.35 – 7.29 (m, 4H), 7.21 – 7.17(m, 3H), 7.13 – 7.11
(m, 1H), 6.89 – 6.87 (m, 2H), 6.78 – 6.76 (m, 2H), 4.86 (s, 1H), 2.37 (s, 3H), 2.19 (s, 3H).
13C NMR (100 MHz, CDCl3): δ (ppm) 147.4, 142.8, 142.4, 142.3, 140.0, 138.1, 137.9,
135.4, 133.8, 130.8, 129.7, 129.5, 129.4, 129.14, 129.11, 129.0, 127.5, 123.5, 123.2,
121.8, 121.4, 75.1, 21.4, 21.2. HRMS (ESI) [M+Na]+ calcd. for C29H23NO2SNa 472.1342,
found 472.1344.
2',3'-Bis(4-chlorophenyl)-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3ac).
White solid, 46 mg, 94% yield. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.87 – 7.85 (m, 1H),
7.58 – 7.50 (m, 2H), 7.44 – 7.29 (m, 7H), 7.25 – 7.21 (m, 1H), 7.08 – 7.06 (m, 3H), 6.90
– 6.88 (m, 2H), 4.87 (s, 1H). 13C NMR (100 MHz, CDCl3): δ (ppm) 147.1, 142.5, 142.5,
141.6, 138.4, 135.1, 134.5, 134.3, 134.0, 131.8, 130.7, 130.6, 130.5, 130.0, 129.5, 129.3,
128.7, 128.1, 123.4, 123.3, 121.9, 121.4, 75.1. HRMS (ESI) [M+Na]+ calcd. for
C27H17Cl2NO2SNa 512.0249, found 512.0258.
2',3'-Bis(4-fluorophenyl)-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3ad).
White solid, 42 mg, 92% yield. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.87 – 7.85 (m, 1H),
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7.58 – 7.50 (m, 2H), 7.44 – 7.42 (m, 1H), 7.38 – 7.31 (m, 4H), 7.26 – 7.21 (m, 1H), 7.13
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– 7.09 (m, 3H), 6.94 – 6.91 (m, 2H), 6.81 – 6.77 (m, 2H), 4.86 (s, 1H). C NMR (100
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MHz, CDCl3): δ (ppm)162.6 (d, 1JC-F = 247 Hz), 162.3 (d, 1JC-F = 247 Hz), 147.1, 142.5,
142.2, 141.9, 138.6, 135.2, 133.9, 131.1, 131.0, 129.9, 129.4, 128.44, 128.41, 127.9,
123.4, 123.3, 121.9, 121.3, 116.2, 115.9, 115.6, 115.4, 75.2. HRMS (ESI) [M+Na]+ calcd.
for C27H17F2NO2SNa 480.0840, found 480.0836.
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2',3'-Bis(4-nitrophenyl)-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3ae).
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Yellow solid, 44 mg, 87% yield. H NMR (400 MHz, CDCl3): δ (ppm) 8.32 – 8.30 (m,
2H), 7.98 – 7.96 (m, 2H), 7.89 – 7.87 (m, 1H), 7.62 – 7.54 (m, 4H), 7.48 – 7.41 (m, 2H),
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7.35 – 7.32 (m, 2H), 7.17 – 7.16 (m, 2H), 7.10 – 7.08 (m, 1H), 4.91 (s, 1H). C NMR
(100 MHz, CDCl3): δ (ppm) 147.9, 147.4, 146.9, 143.8, 143.4, 140.5, 139.6, 138.9, 137.0,
135.1, 134.2, 130.5, 130.2, 130.1, 130.0, 129.1, 124.3, 123.7, 123.1, 122.2, 121.7, 75.3.
HRMS (ESI) [M+Na]+ calcd. for C27H17N3O6SNa 534.0730, found 534.0726.
2',3'-Bis(3-nitrophenyl)-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3af).
Yellow solid, 30 mg, 59% yield. 1H NMR (400 MHz, CDCl3): δ (ppm) 8.31 (s, 1H), 8.27
(d, J = 8.1 Hz, 1H), 8.00 (d, J = 8.0 Hz, 1H), 7.85 – 7.83 (m, 1H), 7.73 – 7.68 (m, 2H),
7.63 – 7.59 (m, 3H), 7.47 – 7.40 (m, 3H), 7.36 – 7.30 (m, 3H), 7.16 – 7.14 (m, 1H), 5.13
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(s, 1H). C NMR (100 MHz, CDCl3): δ (ppm) 148.6, 147.9, 146.6, 143.6, 142.5, 140.8,
136.9, 135.3, 135.2, 134.5, 134.3, 133.7, 130.5, 130.4, 130.0, 129.7, 128.9, 124.3, 124.0,
123.8, 123.7, 123.4, 123.2, 122.1, 121.5, 75.3. HRMS (ESI) [M+Na]+ calcd. for
C27H17N3O6SNa 534.0730, found 534.0730.
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2',3'-Dibutyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3ah). White solid,
38 mg, 99% yield.1H NMR (400 MHz, CDCl3): δ (ppm) 7.86 – 7.84 (m, 1H), 7.54 – 7.50
(m, 1H), 7.46 – 7.42 (m, 1H), 7.34 – 7.20 (m, 3H), 7.10 – 7.07 (m, 1H), 6.82 – 6.80 (m,
1H), 4.63 (s, 1H), 2.57 – 2.53 (m, 2H), 2.33 – 2.27 (m, 1H), 2.07 – 2.00 (m, 1H), 1.65 –
1.60 (m, 2H), 1.52 – 1.43 (m, 2H), 1.28 – 1.20 (m, 3H), 1.10 – 1.6 (m, 1H), 1.02 – 0.98 (t,
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J = 7.2 Hz, 3H), 0.79 – 0.76 (t, J = 7.0 Hz, 3H). C NMR (100 MHz, CDCl3): δ (ppm)
146.6, 144.6, 143.7, 141.1, 139.2, 135.3, 133.3, 129.5, 129.1, 126.2, 123.6, 122.5, 121.4,
119.4, 75.2, 31.7, 30.8, 25.5, 24.8, 23.1, 23.0, 14.0, 13.7. HRMS (ESI) [M+Na]+ calcd.
for C23H27NO2SNa 404.1655, found 404.1655.
2'-Methyl-3'-phenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3ai') and
3'-methyl-2'-phenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3ai) (3ai' :
3ai = 3 : 1). White solid, 35 mg, 99% yield.
3'-methyl-2'-phenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3ai).
1H NMR (400 MHz, CDCl3): δ (ppm) 7.83 – 7.81 (m, 1H), 7.53 – 7.46 (m, 3H), 7.40 –
7.35 (m, 4H), 7.26 – 7.24 (m, 1H), 7.21 – 7.17 (m, 1H), 7.07 – 7.00 (m, 3H), 4.74 (s, 1H),
2.27 (s, 3H). 13C NMR (100 MHz, DMSO-d6): δ (ppm) 147.8, 143.5, 142.6, 139.0, 138.9,
136.0, 134.1, 133.9, 130.2, 129.4, 129.3, 128.5, 128.0, 127.4, 123.6, 122.6, 121.5, 120.6,
75.0, 12.3. HRMS (ESI) [M+Na]+ calcd. for C22H17NO2SNa 382.0872, found 382.0875.
2'-Methyl-3'-phenyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3ai').
1H NMR (400 MHz, CDCl3): δ (ppm) 7.90 – 7.88(m, 1H), 7.58 – 7.41 (m, 7H), 7.34 –
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7.23 (m, 3H), 7.16 – 7.13 (m, 1H), 6.94 – 6.92 (m, 1H), 4.82 (s, 1H), 1.80 (s, 3H). C
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NMR (100 MHz, CDCl3): δ (ppm) 146.2, 143.4, 142.7, 140.5, 138.7, 135.5, 133.8, 133.5,
129.8, 129.3, 128.8, 128.7, 128.2, 126.6, 123.3, 123.2, 121.6, 120.5, 75.1, 10.1. HRMS
(ESI) [M+Na]+ calcd. for C22H17NO2SNa 382.0872, found 382.0875.
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3'-(trimethylsilyl)-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dioxide (3aj). White
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foaming solid, 12 mg, 35% yield. H NMR (400 MHz, CDCl3): δ (ppm) 7.86 – 7.85 (m,
1H), 7.55 – 7.45 (m, 2H), 7.41 – 7.28 (m, 3H), 7.19 – 7.15 (m, 1H), 6.83 – 6.81 (m, 1H),
6.51 (s, 1H), 4.81 (s, 1H), 0.34 (s, 9H). 13C NMR (100 MHz, CDCl3): δ (ppm) 149.0,
148.5, 148.3, 146.8, 139.8, 136.7, 134.9, 130.9, 130.8, 128.3, 124.9, 124.6, 124.3, 122.8,
75.7, 0.00. HRMS (ESI) [M+Na]+ calcd. for C18H19NO2SSiNa 364.0803, found
364.0800.
2',3'-Bis(4-chlorophenyl)-5'-methyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dio
xide (3dc). White solid, 47 mg, 93% yield. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.85 –
7.83 (m, 1H), 7.58 – 7.48 (m, 2H), 7.41 – 7.39 (m, 2H), 7.35 – 7.27 (m, 3H), 7.06 (m,
5H), 6.90 – 6.88 (m, 2H), 4.81 (s, 1H), 2.35 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
(ppm) 144.3, 142.8, 142.5, 141.8, 139.7, 138.7, 135.0, 134.4, 134.2, 133.9, 131.9, 130.8,
130.6, 130.5, 130.0, 129.3, 128.7, 128.6, 123.2, 123.1, 122.1, 121.9, 74.9, 21.6. HRMS
(ESI) [M+Na]+ calcd. for C28H19Cl2NO2SNa 526.0406, found 526.0406.
5'-Methoxy-2',3'-di-p-tolyl-2H-spiro[benzo[d]isothiazole-3,1'indene]1,1-dioxide
(3eb). Yellow solid, 46 mg, 96% yield. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.85 – 7.83
(m, 1H), 7.54 – 7.48 (m, 2H), 7.33 – 7.25 (m, 3H), 7.21 – 7.19 (m, 2H), 7.13 – 7.11 (m,
1H), 6.88 – 6.86 (m, 3H), 6.78 – 6.76 (m, 2H), 6.69 – 6.67 (m, 1H), 4.81 (s, 1H), 3.77 (s,
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3H), 2.39 (s, 3H), 2.18 (s, 3H). 13C NMR (100 MHz, CDCl3): δ (ppm) 160.8, 144.1,
143.6, 142.5, 140.3, 139.3, 138.0, 137.9, 135.2, 133.8, 130.8, 129.6, 129.5, 129.4, 129.1,
129.0, 124.0, 123.4, 121.7, 111.9, 108.0, 74.7, 55.6, 21.5, 21.2. HRMS (ESI) [M+Na]+
calcd. for C30H25NO3SNa 502.1447, found 502.1445.
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2',3'-Bis(4-chlorophenyl)-5-methyl-2H-spiro[benzo[d]isothiazole-3,1'-indene]1,1-dio
xide (3kc). White solid, 46 mg, 92% yield. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.75 –
7.73 (m, 1H), 7.44 – 7.41 (m, 3H), 7.35 – 7.30 (m, 5H), 7.25 – 7.21 (m, 1H), 7.08 – 7.06
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(m, 2H), 6.90 – 6.88 (m, 2H), 6.81 (s, 1H), 4.82 (s, 1H), 2.33 (s, 3H). C NMR (100
MHz, CDCl3): δ (ppm) 147.3, 145.2, 142.5, 142.4, 141.5, 138.8, 134.5, 134.2, 132.6,
131.9, 131.2, 130.8, 130.6, 130.4, 129.4, 129.3, 128.8, 128.1, 123.4, 123.1, 121.7, 121.3,
75.0, 21.9. HRMS (ESI) [M+Na]+ calcd. for C28H19Cl2NO2SNa 526.0406, found
526.0410.
6',7'-Bis(4-fluorophenyl)-2H-spiro[benzo[d]isothiazole-3,5'-indeno[5,6-d][1,3]dioxole]
1,1-dioxide (3hd). White solid, 46 mg, 92% yield. 1H NMR (400 MHz, CDCl3): δ (ppm)
7.82 – 7.81 (m, 1H), 7.55 – 7.53 (m, 2H), 7.39 – 7.35 (m, 2H), 7.14 – 7.13 (m, 1H), 7.04
– 7.00 (m, 2H), 6.93 – 6.87 (m, 3H), 6.80 – 6.76 (m, 2H), 6.67 – 6.65 (m, 1H), 5.96 –
5.94 (d, J = 8 Hz, 2H), 4.79 (s, 1H). 13C NMR (100 MHz, CDCl3): δ (ppm) 162.6 (d, 1JC-F
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= 247 Hz), 162.4 (d, JC-F = 250 Hz), 149.8, 143.3, 141.0, 140.9, 139.6, 139.1, 134.8,
134.0, 131.56 (d, 3JC-F = 8.0 Hz), 131.23 (d, 3JC-F = 8.0 Hz), 129.9, 129.22 (d, 4JC-F = 3.3
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Hz ), 128.41 (d, JC-F = 3.4 Hz), 123.4, 123.1, 121.8, 117.0, 115.56 (d, JC-F = 21.6 Hz),
2
115.3 (d, JC-F = 21.6 Hz), 107.0, 101.6, 75.2. HRMS (ESI) [M+Na]+ calcd. for
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C28H17F2NO4SNa 524.0739, found 524.0738.
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Acknowledgments
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We thank the National Natural Science Foundation of China (Grant No. 21402244),
Foundation for the Author of National Excellent Doctoral Dissertation of P. R. China
(Grant No. 201425), the "Start-up Funding from Sun Yat-Sen University" and the "One
Thousand Youth Talents Plan" for financial support. We thank Hong Xia and Yuanhong
Liu for their valuable suggestions during preparation of this manuscript.
Supporting Information
1
The X-ray crystallographic data for compounds 3ga, 3ai, and 3hd, copies of H NMR,
13C NMR spectra are available free of charge on the ACS Publications website.
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