Stereoselective and Regioselective Assembly of Spirooxindole [2,1-b]furan Motifs through a Tandem Friedel–Crafts Alkylation/5-exo-dig-Cyclization

Article abstract of DOI:10.1002/ejoc.201601030

3-Alkynyl-3-OBoc (Boc = tert-butoxycarbonyl) oxindole derivatives underwent a Cu^II-mediated stereo- and regioselective Friedel–Crafts alkylation/5-exo-dig-cyclization with 2-naphthols or cyclic 1,3-diketones. This gave spirooxindole [2,1-b]furan motifs in good to excellent yields under ambient conditions, and the process has a wide substrate scope.

Full text of DOI:10.1002/ejoc.201601030

A Journal of
Accepted Article
Title: Stereo and Regioselective Assembly of Spirooxindole [2,1-b]furan Motifs via
Tandem Friedel-Craft Alkylation/5-exo-dig-Cyclization
Authors: Kesavan Venkitasamy; Kumarswamyreddy Nandarapu
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601030
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Stereo and Regioselective Assembly of Spirooxindole [2,1-
b]furan Motifs via Tandem Friedel-Craft Alkylation/5-exo-dig-
Cyclization
Nandarapu Kumarswamyreddy and Venkitasamy Kesavan*
Abstract: 3-Alkynyl-3-OBoc oxindole derivatives underwent Cu(II)
mediated stereo and regio selective Friedel-Craft alkylation/5-exo-
dig-cyclization with 2-naphthols and cyclic 1,3-diketones to yield
spirooxindole [2,1-b]furan motifs for the first time in literature with
wide substrate scope in good to excellent yields at ambient
conditions.
Introduction
Lewis acid mediated cycloaddition reactions have tremendous
applications in synthetic organic chemistry.1 The cycloaddition
reaction of propargylic compounds is an important tool for C−C
bond formation and the products are useful precursors for the
Figure 1. Biologically Active Oxa-spirooxindoles
construction of various bioactive molecules and natural
products.2 Moreover, it is also one of the most robust way to
Naphtho[2,1-b]furan scaffolds prevalent among various
construct furan structural motifs which are present in structurally
medicinally important compounds and bioactive natural
products.16 Although furan fused spiroxindoles were reported in
diverse pharmaceutically active molecules and natural
products.3 During the last decade substantial advances were
literature, synthesis of naphtho[2,1-b] furan fused with oxindoles
made using propargyl alcohols to construct furan containing
heterocycles through metal catalysis.4 Pioneering work by Miura
et al, enabled the synthesis of fluorescent dihydrofuran
derivatives through rhodium catalysis followed by base mediated
cyclization.5 Cao group developed electrophilic cyclization of o-
anisole substituted ynamides with 1,1-diarylprop-2-yn-1-ols for
the synthesis of 3-Alkyl- or 3-Allenyl-2-amidobenzofurans using
is yet to be accomplished. Inspired by the biological activity of
oxindoles and naphthofuran motifs, we were intrigued to design
and synthesis of spirooxindoles IV (Scheme 1). To the best of
our knowledge there is no synthetic protocol exists in the
literature for the synthesis of the same.
Brønsted acid/Lewis acid/Metal mediated alkylation/endo-dig
cyclization of propargylic alcohols/derivatives with 2-naphthols
give rise to pyran ring derivatives either via propargyl cation A or
allenyl carbocation B (Scheme 1).17 However synthesis of
naphtho[2,1-b]furan scaffolds via similar route are very rare.18
Motivated by the reaction of propargylic alcohol derivatives with
2-naphthols, we decided to employ 3-hydroxy-3-alkynyl oxindole
derivatives III to enable the synthesis of our target molecules IV
(Scheme 1).
ZnBr2.6
Silver-catalyzed heteroaromatization reaction of
propargylic alcohols with p-toluenesulfonylmethyl isocyanide
resulted in the modular synthesis of sulfonyl benzoheteroles.7
However, these methods require expensive reagents and
additives.
Diversity of spirooxindole derivatives is responsible for their wide
biological activity.8 Intrigued by the biological importance of
oxindole skeleton chemist have synthesized various furan
containing spirooxindoles.9 These oxa-spirooxindole motifs are
widely embedded in many natural products and numerous
pharmaceutically important compounds (Figure 1).10
Scheme 1. Strategy to Access Furan Ring System from Propargyl
Alcohols
Traditional synthetic approaches of oxa-spirooxindoles include
Prins-type
cyclization,11
Rauhut-Currier-type
reaction12,
Intramolecular tandem Heck cyclization/carbonylation13, [3+2]
cycloaddition/annulation reactions of isatin derived Morita-
Baylis-Hillman adduct/carbonates.14 Other methods require
multistep synthesis for the preparation of 3-oxa-spiroxindole
derivatives.15
[a]
Nandarapu Kumarswamyreddy and Venkitasamy Kesavan*
Chemical Biology Laboratory, Department of Biotechnology, Bhupat
and Jyoti Mehta School of Biosciences, Indian Institute of
Technology Madras, Chennai-600036, India
We hypothesised that the proposed reaction sequence would
enable the C-C bond formation followed by triple bond activation
and cyclization, which would result in the formation of the
Email: vkesavan@iitm.ac.in
Supporting information for this article is given via a link at the end of
the document.
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European Journal of Organic Chemistry
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expected product IV (Scheme 1). However identification of
suitable catalyst for this endeavour is a formidable task.
intermediate C, which in turn undergo exo-dig cyclization to
afford product 4a.
Scheme 2. Plausible mechanism for Friedel-Craft Alkylation/Cyclization
Reaction
Results and Discussion
Investigation were commenced by screening various Lewis
acids. 3-hydroxy-1-methyl-3-(phenylethynyl)indolin-2-one (1a)19
was treated with 2-naphthol in the presence of 10 mol% of InBr3
in dichloromethane at ambient temperature. No product
formation was observed under Lewis acid conditions.20 Since, 3-
alkynyl-3-hydroxy oxindole may not facilitate the formation of
carbocation which is essential for further reaction sequence. We
decided to employ corresponding 3-OBoc oxindole derivative 3a.
As we expected introduction of OBoc facilitated the formation of
the envisioned product 4a in the presence of 10 mol% of InBr3.
Motivated by these results screening of various Lewis acids was
undertaken (Table 1, entries 1-19). It is evident from the table 1
that Cu(OTf)2 is responsible for the facile formation of oxindole
fused with naphthofuran 4a. The expected product was isolated
with 92% yield in 4 hours at room temperature.
Table 2. Substrate Diversity for Fridel-Craft Alkylation/Cyclization[a]
Table 1. Optimization of Lewis acid for Friedel-Craft Alkylation/Cyclization
Entry[a]
Lewis acid
Time [h]
Yield[b](%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
InBr3
BF3:Et2O
SnCl2
SnCl4
ZnCl2
6
12
12
6
10
4
24
24
24
6
9
4
5
10
12
10
10
6
39
16
29
41
34
42
nr
FeCl3
Cu(OAc)2
Fe(OAc)2
Zn(OAc)2
Fe(OTf)2
Yb(OTf)3
Sc(OTf)3
Sn(OTf)2
In(OTf)3
Ce(OTf)3
AgOTf
nr
nr
67
65
59
65
63
54
47
nr
Hg(CF3COO)2
Cu(OTf)
Cu(OTf)2
57
92
4
[a] Friedel-Craft alkylation /cyclization reaction was performed between 3a
(0.275 mmol) and 2a (0.275 mmol) with 10 mol% of Lewis acid in 1mL of dry
CH2Cl2 at rt. [b] Isolated yield of the product. nr = no reaction.
It is expected that carbocation C formed from compound 3a may
react with 2-naphthol or would lead to the formation of allenyl
carbocation D which in turn would react with 2-naphthol
(Scheme 2). Formation of observed product indicates that
Friedel-Craft alkylation of 2-naphthol with carbocation
[a] Friedel-Craft alkylation /cyclization reaction was performed between 3 (1.0
equiv) and 2 (1.0 equiv) with 10 mol% of Cu(OTf)2 in 1mL of dry CH2Cl2 at rt
for 4h. [b] CCDC 1469851
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European Journal of Organic Chemistry
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Dong et al. employed solvent free ball-milling conditions to
achieve the synthesis of naphthopyrans using indium(III)
chloride.17d Only one substrate of spiroxindole-naphthopyran
was synthesized using 1.5 equivalents of indium(III) chloride. In
our optimized conditions formation of oxindole fused with
naphthofuran 4a was observed with a use of 10 mol % of
Cu(OTf)2. Difference in the products observed can be attributed
to the difference in starting material, reagents and reaction
conditions.
The reaction proceeded smoothly to yield only alkylated product
6 with 87% yield (Scheme 3). In our efforts to synthesize
structurally diverse spirooxindole [2,1-b] furan motifs, the
product was subjected to cyclization using I2 under basic
conditions. This metal free protocol afforded expected product
7a in 90% yield in dichloroethane under reflux condition
(Scheme 3).
1,3-cyclohexanedione 5b underwent alkylation followed by
cyclization to afford product 7b without need of I2/NaHCO3 in
83% yield at ambient temperature (Table 3). Close proximity of
reactive centres might have facilitated the exo-dig cyclization to
yield the product without requirement of additives. Under the
optimized conditions different cyclic 1,3-diketones such as
dimedone 5c, 1,3-pentanedione 5d, 4-Hydroxy-6-methyl-2-
pyrone 5e and 4-Hydroxycoumarin 5f furnished corresponding
products 7c-f in 71-85% (Table 3). The structure of compounds
4f, 7a, 7b and 7f were further confirmed by single-crystal XRD
(Table 2, Table 3 and Scheme 3).20
Encouraged by the positive outcome, we started to evaluate the
substrate scope of this transformation using various
substitutions on 3-alkynyl-3-OBoc oxindole derivatives 3 as well
as differently substituted 2-naphthols 2 (Table 2). First, the
influence of nitrogen protection on 3-alkynyl-3-OBoc oxindoles 3
was studied. Different nitrogen protected 3-alkynyl-3-OBoc
oxindoles like benzyl 3b, allyl 3c, and propargylic 3d provided
corresponding products 4b-d in very good yields (84-90%). Thus
these results indicate that the presence of different N1-protecting
groups did not affect efficacy of the reaction. Tert-butyl 3-((tert-
butoxycarbonyl)oxy)-2-oxo-3-(phenylethynyl)indoline-1-
Table 3. Substrate Diversity of the Reaction for Cyclic 1,3-Diketones[a]
carboxylate 3e underwent Friedel-Craft alkylation/cyclization to
give rise to expected product 4e in 67% yield (Table 2). This
outcome illustrates that the better yields are possible only with
N1-protection. Consequently, we moved to study the effect of the
electronic nature of the substitutions on aryl part of oxindole
moiety. The effect of halogens and electron rich substituents on
the reactivity was minimal, because the reactants underwent
Friedel-Craft alkylation/cyclization to afford products 4f-k with
very good yields in the range of 83-95% (Table 2). After
investigating the influence of various substituents on aryl part of
oxindole moiety, the impact of substitution on alkyne
functionality was explored. Gratifyingly, the methyl and tert- butyl
groups present at para- position on phenyl ring did not show any
negative effect on the reaction and corresponding products 4l
and 4m were isolated in 81% and 84% yield (Table 2). Presence
of di-fluoro substitution at ortho and para-position on phenyl ring
of alkyne moiety slightly affected catalytic efficiency and the
product 4n was isolated with 75% yield. Not only alkyne bearing
aryl ring the alkynes processing strained aliphatic cyclopropane
too afforded 4o in excellent yield of 90% (Table 2).
The tolerability of differently substituted 2-naphthols was also
examined under the optimized conditions. No significant
reduction in yields of the products 4p-s was observed for 7-OMe,
6-Br, 6-Ph and 6-(1-Nap) 2-naphthol substituents (Table 2).
In order to increase the diversity of structures accessed using
this methodology, 1,3-diketones were used as a nucleophiles.
Initially, the reaction was carried out between acetyl acetone 5a
and 3a under the established reaction conditions (Scheme 3).
[a] Friedel-Craft alkylation /cyclization reaction was performed between 3a (1
equiv, 0.275 mmol) and cyclic 1,3-diketones 5b-f (1.0 equiv, 0.275 mmol) with
10 mol% Cu(OTf)2 in 1mL of dry CH2Cl2 at rt for 5h. [b] CCDC 1469853 [c]
CCDC 1471421.
Conclusions
In summary, we have developed a concise synthetic route to
spirooxindole [2,1-b] furan derivatives via Friedel-Craft
alkylation/5-exo-dig-cyclization. This is the first example for
construction of the oxindole fused [2,1-b] furan scaffolds from
alkyne functionality at C-3 position of oxindole via electrophilic
cyclization. Wide range of differently substituted 2-naphthols and
variety of cyclic 1,3-diketones afforded desired products in good
to excellent yields. This strategy would be a powerful tool for
Scheme 3. Synthesis of Spirooxindole Furan Motifs from 1,3-Diketones
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European Journal of Organic Chemistry
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745, 703; HRMS (ESI): Exact mass calcd C29 H21O2N [M+Na]+
438.1465, Found 438.1465.
=
accessing various pharmaceutically relevant spirooxindole
compounds.
(Z)-2'-benzylidene-1-(prop-2-yn-1-yl)-2'H-spiro[indoline-3,1'-
naphtho[2,1-b]furan]-2-one(4d)
Experimental Section
White solid, Isolated yield 93 mg (0.22 mmol, 87%), m.p. 168-174 °C; 1H
NMR (500MHz, CDCl3) δ = 7.94 (d, J = 8.0 Hz, 1H), 7.81 (d, J = 8.5 Hz,
1H), 7.74 (d, J = 9.0 Hz, 1H), 7.70 - 7.66 (m, 2H), 7.59 (d, J = 9.0 Hz, 1H),
7.54 - 7.49 (m, 2H), 7.44 (ddd, J = 8.0, 7.0, 1.0 Hz, 1H), 7.38 - 7.33 (m,
3H), 7.17 (d, J = 7.5 Hz, 1H), 7.13 - 7.08 (m, 2H), 4.95 (s, 1H), 4.72 (dd,
J = 18.0, 2.5 Hz, 1H), 4.38 (dd, J = 18.0, 2.5 Hz, 1H), 2.31 (t, J = 2.5 Hz,
1H); 13C NMR (125MHz, CDCl3) δ = 172.7, 152.0, 147.4, 142.3, 132.7,
130.9, 130.8, 130.5, 129.0, 128.9, 128.8, 128.6, 128.2, 128.0, 126.7,
126.1, 125.9, 124.6, 124.4, 123.4, 123.2, 123.1, 121.9, 112.4, 109.4,
76.8, 72.5, 62.4, 29.6; IR(ν, cm-1): 3047, 2916, 2128, 1805, 1721, 1659,
1615, 1488, 1466, 1344, 1313, 1194, 1140, 1013, 950, 900, 808, 753,
702; HRMS (ESI): Exact mass calcd C29H19O2N [M+Na]+ = 436.1308,
Found 436.1308.
Typical experimental procedure for the synthesis of Spirooxindole
fused [2,1-b]furan derivatives:
To a stirred solution of 3-ethynyl-3-OBoc-oxindoles 1 in anhydrous
dichloromethane, 10 mol% of Cu(OTf)2 and corresponding 2-Napthol 2
and cyclic 1,3-diketones in dried closed vial was added under the argon
atmosphere. The reaction mixture was then stirred at room temperature
for 1-2h (monitored by TLC). The solvent was then removed under
reduced pressure. The crude mixture was purified by column
chromatography over silica gel to furnish pure products 4a-4t and 7b-7f.
(Z)-2'-benzylidene-1-methyl-2'H-spiro[indoline-3,1'-naphtho[2,1-
b]furan]-2-one (4a)
(Z)-2'-benzylidene-2'H-spiro[indoline-3,1'-naphtho[2,1-b]furan]-2-
one(4e)
White solid, Isolated yield 98 mg (0.25 mmol, 92%), m.p. 230-236 °C; 1H
NMR (500MHz, CDCl3) δ = 7.91 (d, J = 9.0 Hz, 1H), 7.85 (d, J = 8.0 Hz,
1H), 7.66 (dd, J = 10.5, 1.0 Hz, 2H), 7.51 (d, J = 9.0 Hz, 1H), 7.46 (td, J =
7.5, 1.5 Hz, 1H), 7.38 - 7.33 (m, 2H), 7.33 - 7.29 (m, 1H), 7.26 - 7.20 (m,
2H), 7.15 - 7.10 (m, 2H), 7.07 (td, J = 10.5, 0.5 Hz, 1H), 6.80 (d, J = 8.0
Hz, 1H), 5.25 (s, 1H), 3.47 (s, 3H); 13C NMR (125MHz, CDCl3) δ = 175.1,
157.3, 156.9, 143.7, 134.4, 132.0, 131.5, 130.7, 129.4, 129.3, 129.1,
128.5, 128.3, 127.7, 126.6, 125.1, 124.0, 123.9, 121.1, 118.5, 112.0,
108.6, 103.7, 62.1, 27.1; IR(ν, cm-1): 3059, 2927, 1719, 1624, 1485, 1461,
1369, 1352, 1271, 1224, 1029, 1006, 863, 801, 750, 702; HRMS (ESI):
Exact mass calcd C27H19O2N[M+Na]+ = 412.1308, Found 412.1315.
White solid, Isolated yield 72 mg (0.19 mmol, 67%), m.p. 206-210 °C; 1H
NMR (500MHz, CDCl3) δ = 9.01 (s, 1H), 7.94 (d, J = 8.5 Hz, 1H), 7.83 (d,
J = 8.2 Hz, 1H), 7.78 - 7.73 (m, 2H), 7.71 - 7.69 (m, 1H), 7.59 (d, J = 8.8
Hz, 1H), 7.56 - 7.51 (m, 2H), 7.45 (ddd, J = 1.3, 6.9, 8.2 Hz, 1H), 7.38 -
7.34 (m, 1H), 7.22 - 7.18 (m, 2H), 7.11 (d, J = 7.6 Hz, 1H), 7.00 (dt, J =
0.9, 7.6 Hz, 1H), 6.91 (d, J = 7.9 Hz, 1H), 4.92 (s, 1H); 13C NMR
(125MHz, CDCl3) δ = 176.4, 152.0, 147.6, 141.5, 132.8, 130.9, 130.8,
130.5, 129.0, 128.9, 128.7, 128.4, 128.3, 128.1, 127.5, 126.0, 125.9,
124.7, 124.4, 123.1, 122.7, 112.4, 110.3, 62.2; IR(ν, cm-1): 3210, 3056,
1710, 1617, 1523, 1485, 1446, 1392, 1324, 1258, 1207, 1155, 1128,
1098, 1072, 980, 934, 865, 805, 776, 747, 701; HRMS (ESI): Exact mass
calcd C26H17O2N[M+Na]+ = 398.1152, Found 398.1151.
(Z)-1-benzyl-2'-benzylidene-2'H-spiro[indoline-3,1'-naphtho[2,1-
b]furan]-2-one(4b)
White solid, Isolated yield 94 mg (0.20 mmol, 89%), m.p. 178-182 °C; 1H
NMR (500MHz, CDCl3) δ = 7.94 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 8.5 Hz,
1H), 7.79 - 7.73 (m, 2H), 7.70 (d, J = 8.0 Hz, 1H), 7.61 - 7.50 (m, 4H),
7.44 (ddd, J = 8.0, 7.0, 1.0 Hz, 1H), 7.40 - 7.32 (m, 6H), 7.25 - 7.20 (m,
1H), 7.15 (d, J = 7.5 Hz, 1H), 7.01 (td, J = 7.5, 1.0 Hz, 1H), 6.79 (d, J =
8.0 Hz, 1H), 5.08 - 4.85 (m, 3H); 13C NMR (125MHz, CDCl3) δ = 173.9,
152.0, 147.8, 143.4, 135.6, 132.8, 131.0, 130.8, 130.5, 129.0, 128.9,
128.8, 128.7, 128.6, 128.2, 127.7, 127.4, 126.9, 126.0, 125.8, 124.6,
124.3, 123.4, 123.1, 122.8, 121.9, 112.4, 109.4, 62.3, 54.9; IR(ν, cm-1):
3057, 2924, 1715, 1610, 1488, 1465, 1377, 1354, 1267, 1227, 1030,
1004, 866, 806, 748, 701; HRMS (ESI): Exact mass calcd
C33H23O2N[M+Na]+ = 488.1621, Found 488.1623.
(Z)-2'-benzylidene-5-fluoro-1-methyl-2'H-spiro[indoline-3,1'-
naphtho[2,1-b]furan]-2-one (4f)
White solid, Isolated yield 94 mg (0.23 mmol, 88%), m.p. 160-162 °C; 1H
NMR (500MHz, CDCl3) δ = 7.94 (d, J = 9.0 Hz, 1H), 7.87 (d, J = 8.0 Hz,
1H), 7.68 (dd, J = 8.5, 1.0 Hz, 2H), 7.52 (d, J = 9.0 Hz, 1H), 7.40 - 7.35
(m, 2H), 7.35 - 7.31 (m, 1H), 7.31 - 7.26 (m, 1H), 7.26 - 7.22 (m, 1H),
7.16 (td, J = 9.0, 3.0 Hz, 1H), 7.06 (dd, J = 9.0, 4.0 Hz, 1H), 6.88 (dd, J =
7.5, 2.5 Hz, 1H), 6.80 (d, J = 8.5 Hz, 1H), 5.27 (s, 1H), 3.46 (s, 3H); 13
C
NMR (125MHz, CDCl3) δ = 174.9, 159.8(d, J = 241.2Hz), 157.4, 156.4,
139.6, 134.1, 133.5(d, J = 7.5 Hz), 131.8, 130.7, 129.4, 129.0, 128.6,
128.4, 127.9, 126.8, 124.2, 120.9, 117.9, 116.0, 115.9(d, J = 23.7 Hz),
113.2(d, J = 12.5 Hz), 112.0, 109.3(d, J = 7.5 Hz), 104.1, 62.3, 27.3; IR(ν,
cm-1): 3059, 2928, 1722, 1682, 1522, 1492, 1464, 1345, 1253, 1230,
1183, 1123, 1092, 1027, 996, 956, 875, 811, 747, 696 659; HRMS (ESI):
Exact mass calcd C27H18O2NF [M+Na]+ = 430.1214, Found 430.1211.
The CCDC Number 1469851
(Z)-1-allyl-2'-benzylidene-2'H-spiro[indoline-3,1'-naphtho[2,1-
b]furan]-2-one(4c)
White solid, Isolated yield 96 mg (0.23 mmol, 90%), m.p. 138-142 °C; 1H
NMR (500MHz, CDCl3) δ = 7.88 (d, J = 8.0 Hz, 1H), 7.76 (d, J = 8.5 Hz,
1H), 7.69 - 7.65 (m, 2H), 7.57 - 7.51 (m, 2H), 7.51 - 7.44 (m, 2H), 7.42 -
7.35 (m, 1H), 7.31 - 7.24 (m, 2H), 7.11 (d, J = 7.5 Hz, 1H), 7.03 - 6.97 (m,
1H), 6.85 (d, J = 8.0 Hz, 1H), 5.83 (ddt, J = 17.0, 10.5, 5.0 Hz, 1H), 5.33 -
5.21 (m, 2H), 4.89 (s, 1H), 4.40 (ddt, J = 16.5, 5.5, 2.0 Hz, 1H), 4.31 (ddt,
J = 16.5, 5.5, 2.0 Hz, 1H); 13C NMR (125MHz, CDCl3) δ = 173.5, 151.9,
147.8, 143.5, 132.8, 131.2, 131.0, 130.8, 130.5, 129.0, 128.9, 128.7,
128.6, 128.2, 126.9, 126.0, 125.8, 124.6, 124.3, 123.1, 122.8, 122.0,
117.7, 112.4, 109.3, 62.0, 42.7; IR(ν, cm-1): 3055, 2920, 1714, 1610,
1522, 1488, 1465, 1353, 1264, 1227, 1134, 1095, 1002, 927, 866, 805,
(Z)-2'-benzylidene-5-chloro-1-methyl-2'H-spiro[indoline-3,1'-
naphtho[2,1-b]furan]-2-one(4g)
White solid, Isolated yield 90 mg (0.21 mmol, 85%), m.p. 162-136 °C; 1H
NMR (500MHz, CDCl3) δ = 7.94 (d, J = 9.0 Hz, 1H), 7.88 (d, J = 8.0 Hz,
1H), 7.68 (d, J = 7.5 Hz, 2H), 7.58 (dd, J = 8.0, 2.0 Hz, 1H), 7.51 (d, J =
9.0 Hz, 1H), 7.40 - 7.29 (m, 4H), 7.27 - 7.21 (m, 2H), 7.01 (d, J = 8.5 Hz,
1H), 6.80 (d, J = 8.0 Hz, 1H), 5.26 (s, 1H), 3.46 (s, 3H); 13C NMR
(125MHz, CDCl3) δ = 174.6, 157.4, 156.2, 142.7, 134.1, 133.9, 132.4,
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European Journal of Organic Chemistry
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FULL PAPER
131.9, 130.7, 129.4, 129.0, 128.6, 128.4, 128.2, 128.0, 126.8, 124.2,
120.9, 117.8, 116.5, 112.0, 110.1, 104.1, 62.0, 27.2; IR(ν, cm-1): 3060,
2927, 1724, 1683, 1630, 1521 , 1484, 1463, 1354, 1256, 1227, 1133,
1093, 1028, 996, 958, 859, 810, 748, 694; HRMS (ESI): Exact mass
calcd C27H18O2NCl [M+Na]+ = 446.0918, Found 446.0921.
144.9, 142.9, 132.5, 130.8, 130.4, 128.9, 128.5, 128.2, 128.2, 128.0,
126.1, 126.1, 124.4, 123.3, 123.1, 122.0, 121.9, 118.6, 112.3, 108.6,
61.5, 26.7; IR(ν, cm-1): 3060, 2929, 1722, 1655, 1620, 1495, 1467, 1395,
1368, 1345, 1254, 1218, 1163, 1089, 1055, 1030, 1005, 981, 891, 849,
805, 751, 702, 624; HRMS (ESI): Exact mass calcd C28H18O3NF3[M+Na]+
= 496.1131, Found 496.1133.
(Z)-2'-benzylidene-5-bromo-1-methyl-2'H-spiro[indoline-3,1'-
naphtho[2,1-b]furan]-2-one (4h)
(Z)-1-methyl-2'-(4-methylbenzylidene)-2'H-spiro[indoline-3,1'-
naphtho[2,1-b]furan]-2-one(4l)
White solid, Isolated yield 87 mg (0.18 mmol, 83%), m.p. 170-174 °C; 1H
NMR (500MHz, CDCl3) δ = 7.94 (d, J = 9.0 Hz, 1H), 7.88 (d, J = 8.0 Hz,
1H), 7.68 (dd, J = 8.0, 2.0 Hz, 2H), 7.58 (dd, J = 8.0, 2.0 Hz, 1H), 7.51 (d,
J = 9.0 Hz, 1H), 7.40 - 7.36 (m, 2H), 7.36 - 7.29 (m, 2H), 7.28 - 7.24 (m,
1H), 7.24 (q, J = 2.0 Hz, 1H), 7.01 (d, J = 8.5 Hz, 1H), 6.80 (d, J = 8.0 Hz,
1H), 5.26 (s, 1H), 3.46 (s, 3H); 13C NMR (125MHz, CDCl3) δ = 174.6,
157.4, 156.2, 142.7, 134.1, 133.9, 132.4, 131.9, 130.7, 129.4, 129.0,
128.6, 128.4, 128.2, 128.0, 126.8, 124.2, 120.9, 117.8, 116.5, 112.0,
110.1, 104.1, 62.0, 27.2; IR(ν, cm-1): 3057, 2930, 1718, 1681, 1630, 1578,
1483, 1462, 1420, 1379, 1353, 1253, 1226, 1131, 1091, 1056, 1027, 995,
957, 915, 860, 809, 777, 738, 694, 673, 654; HRMS (ESI): Exact mass
calcd C27H18O2NBr [M+Na]+ = 490.0413, Found 490.0414.
White solid, Isolated yield 86 mg (0.21 mmol, 81%), m.p. 184-188 °C; 1H
NMR (500MHz, CDCl3) δ = 7.93 (d, J = 8.0 Hz, 1H), 7.87 (dd, J = 8.5,
1.0 Hz, 1H), 7.72 (d, J = 9.0 Hz, 1H), 7.58 (dd, J = 8.5, 5.0 Hz, 3H), 7.43
(ddd, J = 8.0, 7.0, 1.0 Hz, 1H), 7.41 - 7.30 (m, 4H), 7.15 (d, J = 7.5 Hz,
1H), 7.09 - 7.03 (m, 1H), 6.89 (d, J = 8.0 Hz, 1H), 4.91 (s, 1H), 3.27 (s,
3H), 2.51 (s, 3H); 13C NMR (125MHz, CDCl3) δ = 173.8, 151.9, 147.8,
144.2, 137.9, 130.8, 130.4, 129.7, 129.6, 129.3, 128.8, 128.7, 128.1,
127.0, 125.9, 125.7, 124.5, 124.3, 123.2, 122.8, 122.0, 112.4, 108.4,
62.3, 26.6, 21.4; IR(ν, cm-1): 3052, 2921, 1710, 1609, 1491, 1468, 1392,
1369, 1344, 1262, 1224, 1171, 1124, 1084, 1036, 1004, 979, 927, 868,
846, 805, 707, 667; HRMS (ESI): Exact mass calcd C28H21O2N [M+Na]+ =
426.1465, Found 426.1465.
(Z)-2'-benzylidene-5-iodo-1-methyl-2'H-spiro[indoline-3,1'-
naphtho[2,1-b]furan]-2-one (4i)
(Z)-2'-(4-(tert-butyl)benzylidene)-1-methyl-2'H-spiro[indoline-3,1'-
naphtho[2,1-b]furan]-2-one(4m)
White solid, Isolated yield 91 mg (0.18 mmol, 87%), m.p. 154-158 °C; 1H
NMR (500MHz, CDCl3) δ = 7.94 (d, J = 9.0 Hz, 1H), 7.88 (d, J = 8.0 Hz,
1H), 7.76 (dd, J = 8.0, 1.5 Hz, 1H), 7.69 (dd, J = 8.0, 1.0 Hz, 2H), 7.52 (d,
J = 9.0 Hz, 1H), 7.41 - 7.37 (m, 3H), 7.36 - 7.29 (m, 2H), 7.27 - 7.23 (m,
1H), 6.91 (d, J = 8.0 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 5.27 (s, 1H), 3.44
(s, 3H); 13C NMR (125MHz, CDCl3) δ = 174.4, 157.4, 156.3, 143.3, 138.4,
134.2, 134.1, 133.6, 131.9, 130.7, 129.4, 129.0, 128.6, 128.4, 128.0,
126.8, 124.2, 121.0, 117.9, 112.0, 110.7, 104.1, 86.4, 61.8, 27.2; IR(ν,
cm-1): 3057, 2919, 1722, 1680, 1632, 1521 , 1482, 1462, 1353, 1255,
1227, 1138, 1016, 951, 809, 750, 697; HRMS (ESI): Exact mass calcd
C27H18O2NI[M+Na]+ = 538.0274, Found 538.0274.
White solid, Isolated yield 91 mg (0.20 mmol, 84%), m.p. 228-234 °C; 1H
NMR (500MHz, CDCl3) δ = 7.93 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 8.0 Hz,
1H), 7.73 (d, J = 9.0 Hz, 1H), 7.62 - 7.55 (m, 4H), 7.53 - 7.47 (m, 1H),
7.44 (td, J = 7.5, 1.0 Hz, 1H), 7.39 - 7.31 (m, 2H), 7.15 (d, J = 7.5 Hz, 1H),
7.05 (t, J = 7.5 Hz, 1H), 6.86 (d, J = 7.5 Hz, 1H), 4.92 (s, 1H), 3.24 (s,
3H), 1.45 (s, 9H); 13C NMR (125MHz, CDCl3) δ = 173.8, 151.9, 151.0,
147.9, 144.2, 130.8, 130.5, 130.1, 129.6, 128.8, 128.7, 128.2, 127.1,
126.0, 125.7, 125.6, 125.4, 124.5, 124.3, 123.3, 123.1, 122.7, 122.1,
112.4, 108.3, 61.9, 34.7, 31.5, 26.6; IR(ν, cm-1): 3053, 2960, 2903, 2868,
1712, 1611, 1492, 1468, 1393, 1369, 1303, 1263, 1170, 1123, 1084,
1005, 979, 927, 868, 839, 805, 747, 707, 667; HRMS (ESI): Exact mass
calcd C31H27O2N[M+Na]+ = 468.1934, Found 468.1929.
(Z)-2'-benzylidene-5-methoxy-1-methyl-2'H-spiro[indoline-3,1'-
naphtho[2,1-b]furan]-2-one (4j)
(Z)-2'-(2,4-difluorobenzylidene)-1-methyl-2'H-spiro[indoline-3,1'-
naphtho[2,1-b]furan]-2-one(4n)
White solid, Isolated yield 101 mg (0.24 mmol, 95%), m.p. 106-110 °C;
1H NMR (500MHz, CDCl3) δ = 7.92 (d, J = 9.0 Hz, 1H), 7.86 (d, J = 8.0
Hz, 1H), 7.68 (d, J = 7.5 Hz, 2H), 7.51 (d, J = 9.0 Hz, 1H), 7.36 (t, J = 8.0
Hz, 2H), 7.31 (td, J = 7.5, 1.5 Hz, 1H), 7.26 (td, J = 7.5, 1.5 Hz, 1H), 7.24
- 7.20 (m, 1H), 7.04 (d, J = 9.0 Hz, 1H), 6.98 (dd, J = 8.5,2.0 Hz, 1H),
6.84 (d, J = 8.0 Hz, 1H), 6.71 (d, J = 2.5 Hz, 1H), 5.27 (s, 1H), 3.68 (s,
3H), 3.44 (s, 3H); 13C NMR (125MHz, CDCl3) δ = 174.9, 157.3, 157.0,
156.9, 137.0, 134.4, 133.2, 131.5, 130.7, 129.3, 129.2, 128.6, 128.3,
127.8, 126.6, 124.0, 121.2, 118.5, 114.5, 112.0, 111.5, 109.2, 103.8,
62.5, 55.7, 27.2; IR(ν, cm-1): 3057, 2935, 2835, 1712, 1682, 1630, 1577,
1494, 1463, 1379, 1349, 1282, 1232, 1204, 1129, 1092, 1050, 1027, 995,
955, 916, 869, 810, 743, 697, 673, 659; HRMS (ESI): Exact mass calcd
C28H21O3N[M+Na]+ = 442.1414, Found 442.1411.
White solid, Isolated yield 80 mg (0.18 mmol, 75%), m.p. 248-252 °C; 1H
NMR (500MHz, DMSO-d6) δ = 8.21 (q, J = 7.0 Hz, 1H), 8.08 (d, J = 9.0
Hz, 1H),7.99(d, J = 8.0 Hz, 1H), 7.67 (d, J = 8.5 Hz, 1H), 7.48(t, J = 7.0
Hz, 1H), 7.38 - 7.31(m, 3H), 7.23 - 7.17 (m, 2H), 7.10 - 7.04(m, 2H),
6.75(d, J = 8.0 Hz, 1H), 5.32(s, 1H), 3.45(s, 3H); 13C NMR (125MHz,
DMSO-d6) δ = 179.1, 163.6, 161.5, 148.8, 137.1, 136.2, 135.6, 135.1,
134.6, 133.5, 133.4, 129.6, 129.5, 129.0, 125.7, 123.5, 117.0, 115.1,
109.1, 97.9, 97.9, 84.4, 84.2, 83.9, 66.9, 32.2; IR(ν, cm-1): 3063, 1719,
1685, 1610, 1498, 1466, 1366, 1277, 1252, 1190, 1128, 1088, 1049,
1025, 996, 961, 850, 814, 750, 696, 625; HRMS (ESI): Exact mass calcd
C27H17O2NF2 [M+Na]+ = 448.1120, Found 448.1119.
(Z)-2'-benzylidene-1-methyl-5-(trifluoromethoxy)-2'H-spiro[indoline-
3,1'-naphtho[2,1-b]furan]-2-one (4k)
(Z)-2'-(cyclopropylmethylene)-1-methyl-2'H-spiro[indoline-3,1'-
naphtho[2,1-b]furan]-2-one(4o)
White solid, Isolated yield 88 mg (0.18 mmol, 83%), m.p. 126-130 °C; 1H
NMR (500MHz, CDCl3) δ = 7.93 (d, J = 8.0 Hz, 1H), 7.75 (dd, J = 8.5,
5.0 Hz, 2H), 7.63 - 7.57 (m, 3H), 7.57 - 7.52 (m, 1H), 7.50 - 7.46 (m, 2H),
7.43 (ddd, J = 8.0, 7.0, 1.0 Hz, 1H), 7.33 (ddd, J = 8.0, 7.0, 1.0 Hz, 1H),
7.20 (dt, J = 6.5, 0.5 Hz, 1H), 7.03 (s, 1H), 6.81 (d, J = 8.5 Hz, 1H), 4.91
(s, 1H), 3.23 (s, 3H); 13C NMR (125MHz, CDCl3) δ = 173.4, 152.0, 146.8,
White solid, Isolated yield 97 mg (0.27 mmol, 90%), m.p. 158-162 °C;1H
NMR (500MHz, CDCl3) δ = 8.93 (d, J = 8.5 Hz, 1H), 7.96 (d, J = 8.0 Hz,
1H), 7.70 - 7.62 (m, 2H), 7.55 - 7.46 (m, 2H), 7.39 (t, J = 8.0 Hz, 1H),
7.14 (d, J = 7.0 Hz, 1H), 7.08 (t, J = 7.5 Hz, 1H), 6.97 (d, J = 8.0 Hz, 1H),
5.38 (s, 1H), 3.36 (s, 3H), 2.28 - 2.21 (m, 1H), 1.26 - 1.20 (m, 2H), 1.10 -
1.03 (m, 1H), 0.91 - 0.85 (m, 1H); 13C NMR (125MHz, CDCl3) δ = 173.8,
This article is protected by copyright. All rights reserved

European Journal of Organic Chemistry
10.1002/ejoc.201601030
FULL PAPER
151.9, 148.5, 144.4, 130.7, 128.8, 128.7, 128.6, 127.0, 126.0, 125.4,
124.3, 124.2, 124.1, 123.2, 122.8, 122.4, 112.4, 108.5, 61.6, 26.7, 7.6,
7.4, 6.6; IR(ν, cm-1): 3049, 2985, 2911, 2819, 1723, 1609, 1495, 1463,
1387, 1364, 1314, 1267, 1175, 1109, 1097, 1024, 981, 933, 866, 841,
(125MHz, CDCl3) δ = 175.1, 157.5, 156.9, 143.7, 138.1, 136.8, 134.4,
133.7, 132.6, 132.0, 131.9, 131.1, 129.6, 128.6, 128.5, 128.4, 128.3,
128.2, 127.8, 127.7, 127.5, 126.7, 126.4, 126.0, 125.9, 125.5, 125.1,
124.0, 121.7, 118.6, 112.5, 108.7, 103.9, 62.1, 27.2; IR(ν, cm-1): 3054,
2937, 1722, 1682, 1609, 1574, 1491, 1470, 1365, 1341, 1299, 1252,
1230, 1127, 1088, 1035, 999, 957, 888, 856, 815, 749, 694; HRMS (ESI):
Exact mass calcd C37H25O2N [M+Na]+ = 538.1778, Found 538.1785.
745, 712, 657; HRMS (ESI): Exact mass calcd C24H19O2N[M+Na]+
376.1308, Found 376.1310.
=
(Z)-2'-benzylidene-8'-methoxy-1-methyl-2'H-spiro[indoline-3,1'-
naphtho[2,1-b]furan]-2-one(4p)
3-(1-methyl-2-oxo-3-(phenylethynyl)indolin-3-yl)pentane-2,4-dione
(6)
White solid, Isolated yield 108 mg (0.26 mmol, 94%), m.p. 174-178 °C;
1H NMR (500MHz, CDCl3) δ = 7.81 (d, J = 8.8 Hz, 1H), 7.73 (d, J = 8.8
Hz, 1H), 7.71 - 7.66 (m, 2H), 7.45 (td, J = 8.0, 1.5 Hz, 1H), 7.39 - 7.35 (m,
3H), 7.26 - 7.20 (m, 1H), 7.19 - 7.15 (m, 1H), 7.14 - 7.08 (m, 2H), 6.94
(dd, J = 9.0, 2.5 Hz, 1H), 6.07 (d, J = 2.5 Hz, 1H), 5.30 (s, 1H), 3.49 (s,
3H), 3.46 (s, 3H); 13C NMR (125MHz, CDCl3) δ = 175.1, 158.8, 157.7,
156.7, 143.8, 134.4, 131.7, 131.1, 130.8, 130.4, 129.5, 128.6, 128.3,
126.6, 126.1, 125.4, 124.1, 117.7, 116.5, 109.3, 108.2, 103.9, 99.6, 62.1,
54.7, 27.0; IR(ν, cm-1): 3055, 2927, 2819, 1718, 1657, 1622, 1568, 1491,
1457, 1377, 1351, 1279, 1230, 1204, 1125, 1097, 1032, 1012, 994, 957,
912, 864, 810, 741, 688, 673, 651; HRMS (ESI): Exact mass calcd
C28H21O3N[M+Na]+ = 442.1414, Found 442.1415.
The product 6 was synthesized according to the general experimental
procedure I, White solid, Isolated yield 82 mg (0.24 mmol, 87%), m.p.
136-142 °C; 1H NMR (500MHz, CDCl3) δ = 7.40 - 7.37 (m, 3H), 7.36 -
7.26 (m, 4H), 7.09 (td , J =7.5, 1.0 Hz, 1H), 6.90 (d, J = 7.5 Hz, 1H), 4.7
(s, 1H), 3.30 (s, 3H), 2.58 (s, 3H), 2.20 (s, 3H); 13C NMR (125MHz,
CDCl3) δ = 203.2, 200.5, 173.5, 143.6, 131.8, 129.2, 128.8, 128.3, 128.1,
124.5, 123.1, 108.7, 85.1, 84.9, 70.4, 46.4, 33.2, 30.2, 27.0.
(E)-4-acetyl-2-(iodo(phenyl)methylene)-1',5-dimethyl-2H-spiro[furan-
3,3'-indolin]-2'-one(7a)
To a stirred solution of compound 6 (1 equiv) in dichloroethane,
molecular I2(1.5 equiv) and NaHCO3 (2 equiv) in dried closed vial was
added under the argon atmosphere. The reaction mixture was then
stirred at 85 °C for 3h (monitored by TLC). The solvent was then
removed under reduced pressure. The crude mixture was purified by
column chromatography over silica gel to furnish pure products 7a as
White solid, Isolated yield 122 mg (0.26 mmol, 90%), m.p. 156-160 °C;
1H NMR (500MHz, CDCl3) δ = 7.44 - 7.37 (m, 3H), 7.34 - 7.31 (m, 2H),
7.27 (td , J =7.5, 1.0 Hz, 1H), 7.15 – 7.10 (m, 2H), 6.90 (d, J = 8.0 Hz,
1H), 3.36 (s, 3H), 2.40 (s, 3H), 2.10 (s, 3H); 13C NMR (125MHz, CDCl3)
δ = 190.8, 172.8, 166.1, 153.2, 145.7, 139.5, 129.6, 129.4, 128.4, 128.2,
128.0, 123.3, 123.0, 119.5, 108.2, 74.8, 64.0, 29.0, 26.7, 15.2; IR(ν, cm-
1): 3045, 2985, 1724, 1719, 1649, 1512, 1463, 1421, 1294, 1189, 1075,
1019, 974, 816, 729, 698; HRMS (ESI): Exact mass calcd
C22H18O3NI[M+Na]+ = 494.0224, Found 494.1230. The CCDC Number:
1486473.
(Z)-2'-benzylidene-7'-bromo-1-methyl-2'H-spiro[indoline-3,1'-
naphtho[2,1-b]furan]-2-one(4q)
White solid, Isolated yield 110 mg (0.23 mmol, 86%), m.p. 186-192 °C;1H
NMR (500MHz, CDCl3) δ = 8.03 (d, J = 1.9 Hz, 1H), 7.64 - 7.57 (m, 5H),
7.49 - 7.43 (m, 2H), 7.37 - 7.32 (m, 1H), 7.32 - 7.26 (m, 2H), 7.12 - 7.08
(m, 1H), 7.03 - 6.97 (m, 1H), 6.83 (d, J = 8.0 Hz, 1H), 4.84 (s, 1H), 3.20
(s, 3H); 13C NMR (125MHz, CDCl3) δ = 173.5, 151.9, 148.4, 144.3, 132.4,
132.1, 130.8, 130.4, 129.2, 129.0, 128.9, 128.7, 128.6, 128.4, 128.3,
126.7, 124.8, 124.7, 124.5, 122.8, 118.1, 113.5, 108.4, 62.7, 26.6; IR(ν,
cm-1): 3056, 2927, 1717, 1680, 1630, 1576, 1485, 1461, 1416, 1377,
1353, 1254, 1223, 1137, 1093, 1053, 1025, 993, 955, 857, 807, 765, 741,
692, 663, 652; HRMS (ESI): Exact mass calcd C27H18O2NBr [M+Na]+ =
490.0413, Found 490.0412.
(Z)-2'-benzylidene-1-methyl-7'-phenyl-2'H-spiro[indoline-3,1'-
naphtho[2,1-b]furan]-2-one(4r)
(Z)-2-benzylidene-1'-methyl-6,7-dihydro-2H-spiro[benzofuran-3,3'-
indoline]-2',4(5H)-dione (7b)
White solid, Isolated yield 102 mg (0.22 mmol, 80%), m.p. 136-140 °C;
1H NMR (500MHz, CDCl3) δ = 8.06 (s, 1H), 7.98 (d, J = 8.5 Hz, 1H), 7.70
(d, J = 8.0 Hz, 2H), 7.63 (d, J = 7.5 Hz, 2H), 7.55 (d, J = 9.0 Hz, 2H), 7.51
- 7.44 (m, 3H), 7.43 - 7.35 (m, 3H), 7.25 (t, J = 7.5 Hz, 1H), 7.19 - 7.13
(m, 2H), 7.13 - 7.07 (m, 1H), 6.91 (d, J = 9.0 Hz, 1H), 5.30 (s, 1H), 3.50
(s, 3H); 13C NMR (125MHz, CDCl3) δ = 175.1, 157.4, 156.9, 143.7, 140.8,
136.9, 134.4, 132.0, 131.8, 131.0, 129.6, 128.9, 128.6, 128.4, 128.3,
127.6, 127.3, 127.2, 126.7, 125.1, 124.0, 121.6, 118.6, 112.4, 108.7,
103.8, 62.1, 27.2; IR(ν, cm-1): 3055, 2931, 1723, 1682, 1608, 1574, 1493,
1469, 1342, 1255, 1229, 1127, 1087, 1023, 999, 956, 916, 890, 856, 816,
751, 695; HRMS (ESI): Exact mass calcd C33H23O2N [M+Na]+ = 488.1621,
Found 488.1622.
White solid, Isolated yield 81 mg (0.22 mmol, 83%), m.p. 162-166 °C; 1H
NMR (500MHz, CDCl3) δ = 7.56 - 7.48 (m, 2H), 7.39 - 7.29 (m, 3H), 7.26
- 7.19 (m, 1H), 7.13 - 7.04 (m, 2H), 6.96 (d, J = 8.0 Hz, 1H), 5.26 (s, 1H),
3.34 (s, 3H), 2.93 - 2.83 (m, 2H), 2.42 - 2.36 (m, 2H), 2.25 (dd, J = 13.0,
7.0 Hz, 1H), 2.19 (td, J = 8.0, 5.5 Hz, 1H); 13C NMR (125MHz, CDCl3) δ
= 192.1, 176.6, 174.4, 155.5, 144.1, 133.5, 130.7, 129.2, 128.7, 128.4,
127.2, 123.7, 123.3, 117.5, 108.6, 106.1, 59.5, 36.6, 27.0, 23.6, 21.5;
IR(ν, cm-1): 3054, 2976, 2854, 2811, 1721, 1675, 1609, 1492, 1470,
1376, 1346, 1264, 1166, 1088, 994, 730, 702; HRMS (ESI): Exact mass
calcd C23H19O3N [M+Na]+ = 380.1257, Found 380.1256. The CCDC
Number: 1469853.
(Z)-2'-benzylidene-1-methyl-7'-(naphthalen-1-yl)-2'H-spiro[indoline-
3,1'-naphtho[2,1-b]furan]-2-one(4s)
(Z)-2-benzylidene-1',6,6-trimethyl-6,7-dihydro-2H-spiro[benzofuran-
3,3'-indoline]-2',4(5H)-dione (7c)
White solid, Isolated yield 110 mg (0.21 mmol, 78%), m.p. 246-252 °C;
1H NMR (500MHz, CDCl3) δ = 8.18 (d, J = 1.5 Hz, 1H), 8.07 (d, J = 1.6
Hz, 1H), 8.01 (d, J = 9.0 Hz, 1H), 7.96 - 7.88 (m, 3H), 7.79 (dd, J = 8.5,
2.0 Hz, 1H), 7.72 - 7.66 (m, 3H), 7.58 - 7.55 (m, 1H), 7.55 - 7.47 (m, 3H),
7.41 - 7.36 (m, 2H), 7.27 - 7.22 (m, 1H), 7.19 - 7.15 (m, 2H), 7.14 - 7.09
(m, 1H), 6.94 (d, J = 8.5 Hz, 1H), 5.31 (s, 1H), 3.51 (s, 3H); 13C NMR
White solid, Isolated yield 90 mg (0.23 mmol, 85%), m.p. 188-192 °C; 1H
NMR (500MHz, CDCl3) δ = 7.53 - 7.49 (m, 2H), 7.36 (td, J = 7.5, 1.5 Hz,
1H), 7.34 - 7.30 (m, 2H), 7.22 (tt, J = 7.5, 1.0 Hz, 1H), 7.11 - 7.05 (m, 2H),
6.96 (d, J = 8.0 Hz, 1H), 5.26 (s, 1H), 3.34 (s, 3H), 2.74 (d, J = 12.5 Hz,
2H), 2.28 (d, J = 8.0 Hz, 2H), 1.25 (s, 3H), 1.22 (s, 3H); 13C NMR
(125MHz, CDCl3) δ = 191.6, 175.5, 174.4, 155.7, 144.1, 133.5, 130.6,
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129.2, 128.8, 128.7, 128.4, 127.2, 123.6, 123.3, 116.0, 108.6, 106.1,
51.0, 37.4, 34.8, 28.6, 28.6, 27.0; IR(ν, cm-1): 3055, 2958, 2873, 1716,
1690, 1660, 1642, 1608, 1492, 1468, 1387, 1370, 1342, 1262, 1223,
1159, 1126, 1083, 1016, 947, 749, 696; HRMS (ESI): Exact mass calcd
C25H23O3N [M+H]+ = 386.1751, Found 386.1750.
Keywords: Friedel-Craft Alkylation • 5-exo-dig-Cyclization • 2-
Naphthol • Cyclic 1,3-diketone • Spirooxindole [2,1-b]furans.
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(Z)-2-benzylidene-1'-methyl-5,6-dihydro-2H,4H-
spiro[cyclopenta[b]furan-3,3'-indoline]-2',4-dione (7d)
White solid, Isolated yield 71 mg (0.20 mmol, 75%), m.p. 190-196 °C; 1H
NMR (500MHz, CDCl3) δ = 7.67 - 7.60 (m, 2 H), 7.44 - 7.38 (m, 3 H),
7.34 (td, J = 8.0, 1.5 Hz, 1 H), 7.15 - 7.10 (m, 1 H), 7.10 - 7.04 (m, 1 H),
6.92 (d, J = 8.0 Hz, 1 H), 5.33 (s, 1 H), 3.33 (s, 3 H), 2.92 (dt, J = 6.5, 4.0
Hz, 2 H), 2.56 - 2.44 (m, 2 H); 13C NMR (125MHz, CDCl3) δ = 200.8,
179.8, 176.4, 151.1, 143.3, 132.9, 132.2, 129.5, 129.1, 128.5, 125.0,
124.5, 123.0, 114.9, 108.4, 100.7, 46.8, 33.3, 26.8, 26.1; IR(ν, cm-1):
3056, 2929, 2857, 1707, 1671, 1626, 1607, 1489, 1467, 1372, 1346,
1271, 1230, 1107, 1082, 1051, 1009, 969, 912, 755, 734, 696; HRMS
(ESI): Exact mass calcd C22 H17O3N[M+H]+ = 344.1281, Found 344.1281.
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(Z)-2-benzylidene-1',6-dimethyl-2H,4H-spiro[furo[3,2-c]pyran-3,3'-
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White solid, Isolated yield 80 mg (0.21 mmol, 79%), m.p. 202-208 °C; 1H
NMR (500MHz, CDCl3) δ = 7.55 - 7.50 (m, 2H), 7.40 - 7.38 (m, 1H), 7.33
(t, J = 7.5 Hz, 2H), 7.26 - 7.22 (m, 1H), 7.16 - 7.13 (m, 1H), 7.12 - 7.08
(m, 1H), 6.99 (d, J = 8.0 Hz, 1H), 6.33 (d, J = 1.0 Hz, 1H), 5.34 (s, 1H),
3.35 (s, 3H), 2.34 (s, 3H); 13C NMR (125MHz, CDCl3) δ = 173.8, 170.7,
167.7, 158.4, 155.2, 144.1, 133.0, 129.7, 129.5, 128.9, 128.4, 127.5,
124.8, 124.2, 123.6, 108.9, 107.2, 95.2, 58.8, 27.1, 20.8; IR(ν, cm-1):
3057, 2932, 1718, 1582, 1447, 1346, 1250, 1088, 1022, 986, 829, 753,
694; HRMS (ESI): Exact mass calcd C23H17O4N[M+Na]+ = 394.1050,
Found 394.1043
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m.p. 224-230 °C; 1H NMR (500MHz, CDCl3) δ = 8.03 (dd, J = 8.0, 1.0 Hz,
1H), 7.71 - 7.65 (m, 3H), 7.52 (d, J = 8.5 Hz, 1H), 7.44 - 7.41 (m, 3H),
7.39 - 7.34 (m, 2H), 7.16 (d, J = 7.5 Hz, 1H), 7.05 (t, J = 7.5 Hz, 1H), 6.98
(d, J = 7.5 Hz, 1H), 5.42 (s, 1 H), 3.42 (s, 3H); 13C NMR (125MHz,
CDCl3) δ = 177.1, 176.1, 161.7, 153.0, 148.9, 143.5, 142.9, 133.8, 133.3,
131.2, 129.8, 129.1, 128.6, 126.0, 125.5, 124.8, 124.1, 123.0, 117.3,
108.2, 101.4, 96.9, 48.5, 27.0; IR(ν, cm-1): 3059, 2930, 1716, 1622, 1467,
1410, 1371, 1347, 1281, 1255, 1081, 1032, 756, 692; HRMS (ESI): Exact
mass calcd C26H17O4N [M+Na]+ = 430.1050, Found 430.1049. The CCDC
Number: 1471421.
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Acknowledgements
We acknowledge the Indo-French Centre for Promotion of
Advanced Research (IFCPAR) (IFC/4803-4), New Delhi for
financial support. N.K thanks Council of Scientific & Industrial
Research (CSIR) for fellowship. We thank Dr. Sudha Devi for
crystallographic analysis SAIF-IIT Madras and SAIF-IIT Madras
for spectral analysis (NMR and IR). We thank Department of
Biotechnology IIT Madras for LCMS.
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Entry for the Table of Contents (Please choose one layout)
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Page No. – Page No.
Title
Operationally simple Cu(II) mediated stereo and regio selective Friedel-Craft
alkylation/5-exo-dig-cyclization of 3-alkynyl-3-OBoc oxindoles with 2-naphthols and
cyclic 1,3-diketones to access spirooxindole [2,1-b]furan motifs with wide substrate
scope in good to excellent yields under mild conditions at ambient temperature.
* Friedel-Crafts Alkylation/5-exo-dig-cyclization
((Insert TOC Graphic here; max. width: 11.5 cm; max. height: 2.5 cm; NOTE: the
final letter height should not be less than 2 mm.))
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