New fluoride-promoted hypoiodite-catalytic oxidative cycloetherification to aromatic spiroketals

Article abstract of DOI:10.1039/c2ob25085c

A new catalytic application of hypoiodite reagents generated in situ from iodide ions is found, which succeeded in the synthesis of bisbenzannelated spiroketal cores for the first time. Fluoride was proven to be obligatory for this spiroketalization, which is the first fluoride-promoted oxidative cycloetherification to aromatic spiroketals.

Full text of DOI:10.1039/c2ob25085c

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PAPER
New fluoride-promoted hypoiodite-catalytic oxidative cycloetherification to
aromatic spiroketals†
Wei Wei, Liqi Li, Xiaohong Lin, Haifeng Li, Jijun Xue* and Ying Li*
Received 12th January 2012, Accepted 27th February 2012
DOI: 10.1039/c2ob25085c
A new catalytic application of hypoiodite reagents generated in situ from iodide ions is found, which
succeeded in the synthesis of bisbenzannelated spiroketal cores for the first time. Fluoride was proven to
be obligatory for this spiroketalization, which is the first fluoride-promoted oxidative cycloetherification
to aromatic spiroketals.
compounds, such as lyscidicins, pinnatifinosides, berkelic acid,
Introduction
rubromycin family (Fig. 1), etc.7,8 They play important roles in
Organohypervalent iodine reagents have attracted significant
recent interest as versatile and environmentally benign oxidants
with many applications in organic synthesis.1 The most impress-
ive recent achievements in this field include the development of
new hypervalent iodine reagents and reagent systems and the
discovery of catalytic applications of organoiodine compounds.2
In 2005, Ochiai and co-workers reported the first PhI catalyzed
reaction.3 Since then, several other reactions based on the gener-
ation of iodine(III) species have been reported.1b,c,4 However,
most of the hypervalent species generated from iodoarenes. In
2010, Ishihara and co-workers reported the chiral quaternary
ammonium iodide catalyst for oxidative cycloetherification of
ketophenol4b and subsequently an intramolecular and intermole-
cular oxidative coupling reactions of carbonyl compounds with
carboxylic acids catalyzed by in situ generated tetrabutylammo-
nium hypoiodite.5 These are the only cases using organoiodide
salts as the sources of hypervalent iodite, which is a new orga-
noiodine species with very high application potency, so explor-
ing more new iodide catalysts and developing their applications
are necessary and significant.
Significant attention is currently being paid to the applications
of hypervalent iodine is α-oxyacetylation and α-oxyalkylation of
carbonyl compounds to construct lactones, pyrans, furans, and
even aliphatic spiroketal or spirolactone cores.6 However, to the
best of our knowledge, there is only one report on α-oxyphenyla-
tion and no reports on the catalytic application of organoiodide
on the construction of bisbenzannelated spiroketal cores. As a
fundamental building block of synthetic organic chemistry, spir-
oketal cores widely exist in natural and unnatural bioactive
the structure–activity relationship. There is a strong requirement
for developing some novel mild spirocyclisation methodologies,
which can be widely employed, for the traditional methods are
limited by the scope of its substrate and less efficient multi-steps
conversion.
Results and discussion
During our investigation9 of the synthesis of rubromycin
families, intramolecular α-oxyphenylation of carbonyl com-
pounds catalyzed by tetrabutylammonium iodide in the presence
of oxidants was proposed to constitute the spiroketal cores and
an approach via a hypoiodite system was found, which includes
a fluoride reagent as a promoting reagent and organoiodide salts
as the source of hypoiodite.
The investigation was initialized from the cyclization of com-
pound 1a. To our delight, bisbenzannulated spiroketals 2a
formed smoothly from compound 1a in the presence of TBAI
and m-chlorobenzoic acid (mCPBA) in THF as solvent. Initially,
compound 1a was treated with TBAI and mCPBA in THF. In
0.5 h, a trace of 2a was found when 5 mol% TBAI and 2.0 eq.
mCPBA were used (Table 1, entry 1). The yield increased to
42% when TBAI increased to 15 mol% (Table 1, entry 2). To
our surprise, a significant increase in yield was observed when
TBAF was introduced to the system. 20 mol% TBAF, 15 mol%
State Key Laboratory of Applied Organic Chemistry, Lanzhou
University, Lanzhou, 730000 Gansu, P.R. of China. E-mail: liying@lzu.
edu.cn; Fax: +86-931-8912582; Tel: +86-931-8912788
†Electronic supplementary information (ESI) available. See DOI:
10.1039/c2ob25085c
Fig. 1 Benzannulated spiroketal natural products.
3494 | Org. Biomol. Chem., 2012, 10, 3494–3499
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Table 1 Optimization of the reaction conditions
Reaction
time
TBAI
(mol%)
Yield
(%)
Entry
Oxidanta
Additive (eq.)
1
2
3
4
5
6
7
mCPBA
mCPBA
mCPBA
mCPBA
mCPBA
mCPBA
mCPBA
None
None
TBAF (0.2)
TBAF (1.0)
TBAF (2.0)
KF (2.0)
0.5 h
0.5 h
0.5 h
5 min
5 min
5 min
5 min
5
Trace
42
56
77
89
15
15
15
15
15
15
Trace
KF (2.0)
71b
Scheme 1 The proposed catalytic cycle.
18-crown-6 (2.0)
NaHCO3 (2.0)
Imidazole (2.0)
TBAF (2.0)
TBAF (2.0)
8
9
10
11
mCPBA
mCPBA
TBHP
5 min
5 min
5 min
5 min
15
15
15
15
Trace
13
63
fluoride partially transfer negative charge upon hydrogen bond
formation, which made the oxidation tendency of hydrogen-
bonded-complex lower than the free anion of substrate and
increase the selectivity and yield of oxidative nucleophilic
substitution.
H2O2
68
a The dosage of oxidant is 2.0 equivalent. b The procedure see ref. 12.
TBAI and 2.0 eq. mCPBA gave 2a in 56% yield (Table 1, entry
3). 77% and 89% yield of 1a formed in only 5 minutes when 1.0
eq. and 2.0 eq. of TBAF were used, respectively (Table 1,
entries 4, 5). When TBHP or H2O2 took the place of mCPBA,
the yield decreased slightly (Table 1, entries 10 and 11). So a
new condition was found for the α-oxyphenylation of ketone to
construct spiroketal 2a: 2.0 eq. of TBAF as additive, 15 mol% of
TBAI as catalyst source, and 2.0 eq. of mCPBA as oxidant were
stirred at room temperature with 1a in THF as solvent in
5 minutes (Table 1, entry 5).
According to the literature,3,4b it is clear that TBAI can be oxi-
dized to iodite(I) or iodite(III) and will be reduced to iodide or
iodite(I) in reactions, based on which a catalytic cycle was
hypothesized as Scheme 1. The reaction of mCPBA and TBAI
formed iodous acid or hypoiodous acid, which reacted as an
electrophile with the double bond of 3a obtained from the enoli-
zation of 1a, and formed iodo or hypoiodo substituted 4a. A
similar process has been reported by Ochiai and Kita.3 The fol-
lowed SN1 displacement of iodo or hypoiodo group in 1a by
phenolic hydroxyl group activated by hydrogen bond with
fluoride affords spiroketal 2a. During this process, when bases
were used to take the place of fluoride reagent (Table 1, entries
8, 9), less efficient results were observed, for iodous acid or
hypoiodous acid reacted with bases and formed iodite salt or
hypoiodite salt which has no electrophilicity.
Based on the above modified conditions, more substrates were
screened with different substituted 1 and the corresponding
yields of spiroketals ranged from good to excellent within a
short period of time and [5,5], [5,6] even [5,7] spiroketal cores
were obtained. Compared to the formation of [5,5] spiroketals,
the formation of [5,6] and [5,7] spiroketals take longer times and
was slightly less efficiency. The reaction of 1a gave 89% yield
of 2a in 5 minutes (Table 2, entry 1). However in 5 minutes, 2l
and 2m formed from 1l (Table 2, entry 12) and 1m (Table 2,
entry 14) in only 27% and 17% yields, respectively. After
12 hours, the yields of 2l and 2m just reach to 62% and 43%
(Table 2, entries 13, 15), which are much lower than that of 2a.
So it could be concluded that this reaction favored the formation
of smaller rings.
Now it is necessary to make clear the role of TBAF. Another
potential fluoride source, potassium fluoride, was used to take
the place of TBAF. However, it does not seem to benefit the
reaction (Table 1, entry 6). Considering the solubility, 18-crown-
6 was added to the reaction as a phase transfer catalyst to
increase the solubility of KF, and it apparently increase the yield
to 71% (Table 1, entry 7). These controlled experiments show
that fluoride is obligatory for the transformation and it is respon-
sible for the increasing of the yield. A detailed review of orga-
nofluoride chemistry shows that fluoride was mainly used as a
base and an activator of C–Si bonds for oxidation.10 Much
research also shows the significant role of fluoride ion in varied
oxidations, especially the oxidative nucleophilic aromatic substi-
tution of hydrogen. In 2001, Marquet and co-workers11 reported
direct coupling of nucleophiles with nitro aromatic compounds
via fluoride-promoted oxidative nucleophilic aromatic substi-
tution for hydrogen. However, there is still no report on the
detailed explanation of the role of fluoride. We hypothesized that
fluoride in this present spiroketalization maybe take as a hydro-
gen-bond acceptor to increase the nucleophilicity of aromatic
hydroxyl group of 1a and accelerate the spiroketalization
(Scheme 1). Fluoride is not easily oxidized and can form very
strong hydrogen bonds, even with hydrogen bonded to carbon.
In the spiroketalization of 1a, fluoride may bond to H–O on aro-
matic ring of 4a, which may increase the nucleophilicity of OH
group and accelerate the cycloetherification. At the same time
In the formation of [5,5] spiroketals, all cases gave very excel-
lent results. However, a slightly different electron effect is shown
between the two aromatic rings. The electron effects of substi-
tutions on the right aromatic ring have more obvious effect than
that on the left ring. For the left benzofuranone, electron-donat-
ing group on R1 or R2 position will decrease the efficiency
of spiroketalization. When R1 or R2 is methoxyl group, the
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Table 2 Synthesis of [5,X] spiroketals with α-oxyphenylation of
carbonyl compounds
Conclusions
In summary, a new catalytic application of hypoiodite reagents
generated in situ from TBAI, an easily available organoiodide
source, was found in the construction of bisbenzannelated spiro-
ketal cores. Using this hypoiodite, a series of spiroketals were
synthesized efficiently, which is the first report on the transform-
ation using a hypoiodite reagent as catalyst. At the same time,
fluoride was found to be obligatory for this cycloetherification as
an activator of SN1 displacement, which is the first case using
fluoride to activate the oxidative cycloetherification to aromatic
spiroketals. This work also showed high potency in the stereo-
selective synthesis of enantiomeric spiroketals, the main chal-
lenge for the synthesis of natural products like rubromycins, for
chiral hypoiodite compounds generated from chiral tetraalkylam-
monium iodide and oxidants have proven to be efficient for the
enantiomeric α-oxyalkylation.4b So the spiroketalization system,
in this context, is a high potential approach for the synthesis of
enantiomeric natural spiroketal products, the explorations of
which are under way in our laboratory.
Entry
N
R1
R2
R3
Products Yieldab (%)
1
2
3
4
5
6
7
8
1 (1a)
1 (1b)
1 (1c)
1 (1d)
1 (1e)
1 (1f)
1 (1g)
1 (1h)
1 (1i)
1 (1j)
1 (1k)
2 (1l)
2 (1l)
3 (1m)
3 (1m)
1 (1c)
3 (1m)
H
H
H
H
H
H
H
MeO
MeO
Br
Br
H
H
H
H
H
H
H
H
H
H
H
H
2a
2b
2c
2d
89
81
76
92
Me
MeO
Br
COOEt 2e
2f
MeO COOEt 2g
87
MeO Br
82
88
83
H
H
H
H
H
H
H
H
H
H
Br
COOEt 2i
Br 2j
COOEt 2k
H
H
H
H
MeO
H
2h
9
85
86
10
11
12
13
14
15
16
17
84
2l
2l
2m
2m
2c
27
62a
17
43a
87b
48ab
Experimental
2m
a The reaction time was increased to 12 hours. b The dosage of TBAI
was increased to 30 mol%.
Materials
All reactions under standard conditions were monitored by thin-
layer chromatography (TLC) on GF254 plates. The silica gel
(200–300 meshes) was used for column chromatography, and the
distillation range of petroleum ether was 60–90 °C. THF was
1
dried by distillation over Na–K alloy. H and 13C NMR spectra
were recorded in CDCl3 or DMSO-d6 solution on Bruker
AX-400 MHz instruments and spectral data were reported in
ppm relative to tetramethylsilane (TMS) as internal standard.
Mass spectra (MS) were measured on spectrometer by direct
inlet at 70 eV and signals were given in m/z with relative inten-
sity (%) in brackets. High-resolution mass spectral analysis
(HRMS) data were measured on the Bruker Apex II by means of
the ESI technique.
Scheme 2 The cycloetherification of aliphatic OH group.
corresponding yield of spiroketal is slightly lower than that R1 or
R2 is hydrogen. When R1 or R2 is bromide, no obvious effect
was observed. Whereas R3 is electron-donating group, such as
methyl or methoxyl group, obvious decreases of yields were
found and electron withdrawing R3 (Table 2, entries 5, 7, 9, and
11) gave a much better yield than electron donating ones
(Table 2, entries 2, 3).
Moreover, increasing the dosage of iodide will increase the
yield, too. When TBAI increased from 15 mol% to 30 mol%,
the yield of 1c also increased from 76% to 87% (Table 2, entries
3, 16). From Table 1, we know that increase of TBAF can
increase the yield, too. Hence, higher efficiency of this trans-
formation can be obtained from the larger dosage of reagents.
As a comparison to the present similar transformation,3 as
well as to make clear the role of fluoride, some controlled exper-
iments were done with ketoalcohols. As shown in Scheme 2,
these conditions appear to prefer the oxidative nucleophile sub-
stitution of the phenolic hydroxyl group rather than the alco-
hols’. This may be because the iodo group is on a tertiary carbon
of 4a and the cyclization reaction of 4a is an intramolecular SN1
displacement. Phenol is favored for SN1 reaction as a nucleophi-
lic reagent, but the aliphatic OH group, especially primary
alcohol, is favored for SN2 reaction.
Synthesis of starting materials
Known compounds 1a, 1b, 1d–1k13 and new compounds
1c, 1l, 1m were prepared following the known procedure
(Scheme 3).9a,14
2-(2-Hydroxy-5-methoxybenzyl)benzofuran-3(2H)-one
(1c).
1H NMR (400 MHz, DMSO-d6, ppm): δ 9.09 (s, 1H), 7.71
(m, 1H), 7.65 (dd, 1H, J1 = 0.8 Hz, J2 = 8.0 Hz), 7.25 (d, 1H,
J = 8.4 Hz), 7.13 (m, 1H), 6.73–6.76 (m, 2H), 6.66 (dd, 2H,
J1 = 3.2 Hz, J2 = 8.8 Hz), 5.06 (dd, 1H, J1 = 4.0 Hz, J2 = 10.0
Hz), 3.64 (s, 1H), 3.20 (dd, 1H, J1 = 3.6 Hz, J2 = 14.4 Hz), 2.72
(dd, 1H, J1 = 10.0 Hz, J2 = 14.4 Hz); 13C NMR (100 MHz,
DMSO-d6, ppm): δ 200.70, 171.93, 151.86, 149.21, 138.25,
123.91, 123.53, 121.95, 120.47, 116.63, 115.33, 113.62, 112.56,
84.16, 55.26, 31.73; IR (KBr, cm−1): 3369, 2926, 2853, 2837,
1818, 1704, 1609, 1460, 1216, 1147, 857, 795, 751; HRMS
+
(ESI): Calcd For C16H15O4 [M + H]+: 271.0965, found
271.0961.
3496 | Org. Biomol. Chem., 2012, 10, 3494–3499
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Scheme 3 Synthesis of compound 1.
2-(2-Hydroxyphenethyl)benzofuran-3(2H)-one (1l). 1H NMR
(400 MHz, DMSO-d6, ppm): δ 9.38 (s, 1H), 7.72–7.74 (m, 1H),
7.62–7.64 (m, 1H), 7.31 (d, 1H, J = 8.4 Hz), 7.15 (t, 1H, J = 7.2
Hz), 6.99–7.05 (m, 2H), 6.78 (d, 1H, J = 7.6 Hz), 6.70 (t, 1H, J
= 7.2 Hz), 4.75 (dd, 1H, J1 = 4.0 Hz, J2 = 8.4 Hz), 2.66–2.70
(m, 2H), 2.13–2.18 (m, 2H), 1.86–1.91 (m, 1H); 13C NMR
(100 MHz, DMSO-d6, ppm): δ 201.30, 172.07, 155.20, 138.37,
129.90, 127.26, 126.69, 123.90, 122.02, 120.67, 118.98, 114.96,
113.59, 84.69, 30.85, 25.41; IR (KBr, cm−1): 3431, 2926, 2853,
1726, 1605, 1460, 1279, 1128, 747; HRMS (ESI): Calcd For
C16H14O3Na+ [M + Na]+: 277.0835, found 277.0832.
128.58, 125.23, 124.82, 123.88, 122.93, 122.40, 118.82, 113.33,
110.54, 110.19, 37.82; IR (KBr, cm−1): 2926, 2853, 1720,
1600, 1475, 1460, 1325, 1220, 750; HRMS (ESI): Calcd For
C15H11O3+ [M + H]+: 239.0703, found 239.0701.
5′-Methyl-3H,3′H-2,2′-spirobi[benzofuran]-3-one (2b). Fol-
lowing the procedure of 2a, the reaction gives 2b (81%) as a
1
solid, m.p.: 105–106 °C. H NMR (400 MHz, CDCl3, ppm): δ
7.74 (d, 1H, J = 0.8 Hz), 7.67 (m, 1H), 7.14 (t, 1H, J = 7.6 Hz),
7.10 (s, 1H), 7.06 (d, 1H, J = 8.4 Hz), 7.01 (t, 1H, J = 8.0 Hz),
6.82 (d, 1H, J = 8.4 Hz), 3.65 (d, 1H, J = 16.8 Hz), 3.36 (d, 1H,
J = 16.8 Hz), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm):
δ 195.83, 170.50, 155.62, 139.29, 131.85, 128.93, 125.35,
125.20, 123.85, 122.85, 118.89, 113.33, 110.82, 109.69, 37.36,
20.84; IR (KBr, cm−1): 3390, 2926, 2853, 1725, 1610, 1465,
1460, 1325, 1200, 880, 860, 760; HRMS (ESI): Calcd For
C16H13O3+ [M + H]+: 253.0859, found 253.0864.
1
2-(3-(2-Hydroxyphenyl)propyl)benzofuran-3(2H)-one (1m). H
NMR (400 MHz, DMSO-d6, ppm): δ 9.21 (s, 1H), 7.71 (m,
1H), 7.62 (d, 1H, J = 7.6 Hz), 7.27 (d, 1H, J = 7.6 Hz), 7.13 (t,
1H, J = 7.2 Hz), 6.96–7.02 (m, 2H), 6.76 (d, 1H, J = 8.0 Hz),
6.68 (t, 1H, J = 7.6 Hz), 4.82 (dd, 1H, J1 = 4.0 Hz, J2 = 7.6 Hz),
2.53–2.57 (m, 2H), 1.83–1.93 (m, 1H), 1.58–1.73 (m, 3H); 13C
NMR (100 MHz, DMSO-d6, ppm): δ 201.39, 172.04, 155.03,
138.31, 129.86, 127.63, 126.85, 123.78, 121.93, 120.63, 118.82,
114.89, 113.46, 84.90, 30.46, 29.26, 24.50; IR (KBr, cm−1):
3435, 2932, 2863, 1726, 1601, 1466, 1279, 1132, 751; HRMS
5′-Methoxy-3H,3′H-2,2′-spirobi[benzofuran]-3-one (2c). Fol-
lowing the procedure of 2a, the reaction gives 2c (76%) as a
1
solid, m.p.: 117–119 °C. H NMR (400 MHz, CDCl3, ppm): δ
7.71–7.65 (m, 2H), 7.14 (m, 1H), 7.06 (d, 1H, J = 8.4 Hz), 6.86
(m, 2H), 6.75 (dd, 1H, J1 = 2.8 Hz, J2 = 8.8 Hz), 3.78 (s, 3H),
3.67 (d, 1H, J = 16.8 Hz), 3.36 (d, 1H, J = 16.8 Hz); 13C NMR
(100 MHz, CDCl3, ppm): δ 195.64, 170.45, 155.56, 151.70,
139.31, 125.19, 124.87, 122.85, 118.83, 113.58, 113.31, 111.02,
110.95, 110.18, 55.98, 37.72; IR (KBr, cm−1): 2926, 2853,
2850, 1730, 1605, 1480, 1460, 1405, 1290, 875, 805, 730;
HRMS (ESI): Calcd For C16H13O4+ [M + H]+: 269.0808, found
269.0813.
+
(ESI): Calcd For C17H17O3 [M + H]+: 269.1172, found
269.1168.
Synthesis of [5,X] spiroketalswith α-oxyphenylation of carbonyl
compounds
5′-Bromo-3H,3′H-2,2′-spirobi[benzofuran]-3-one
(2d). Fol-
lowing the procedure of 2a, the reaction gives 2d (92%) as a
1
solid, m.p.: 111–112 °C. H NMR (400 MHz, CDCl3, ppm): δ
7.67–7.72 (m, 2H), 7.41 (s, 1H), 7.34 (dd, 1H, J1 = 0.8 Hz, J2 =
8.4 Hz), 7.17 (t, 1H, J = 7.2 Hz), 7.09 (d, 1H, J = 8.4 Hz), 6.82
(d, 1H, J = 8.4 Hz), 3.68 (d, 1H, J = 17.2 Hz), 3.40 (d, 1H, J =
16.8 Hz); 13C NMR (100 MHz, CDCl3, ppm): δ 195.03,
170.39, 156.80, 139.46, 131.44, 127.83, 126.40, 125.30, 123.12,
118.63, 114.46, 113.29, 111.65, 110.63, 36.96; IR (KBr, cm−1):
2926, 2853, 1737, 1612, 1460, 1458, 1414, 1246, 910, 820,
754, 527; HRMS (ESI): Calcd For C15H13BrNO3+ [M + NH4]+:
334.0073, found 334.0075.
3H,3′H-2,2′-Spirobi[benzofuran]-3-one (2a). TBAI
5
mg
(15 mol%) was added to a stirring solution of compound 1a
24 mg (0.1 mmol) in 5 mL THF and then the solution of
mCPBA 20 mg (2.0 eq.) and TBAF 32 mg (2.0 eq.) in 5 mL
THF at room temperature was added dropwise in 5 min. The
resulting solution was quenched with water, extracted (DCM),
washed with Na2SO3, NaHCO3 and brine, dried with Na2SO4,
filtered, and concentrated. Chromatography on silica gel (pet-
roleum ether–EtOAc 16 : 1, v/v) of the crude product afforded
1
2a (89%) as a solid, m.p.: 117–118 °C. H NMR (400 MHz,
Ethyl 3′-oxo-3H,3′H-2,2′-spirobi[benzofuran]-5-carboxylate (2e).
Following the procedure of 2a, the reaction gives 2e (87%) as
CDCl3, ppm): δ 7.73 (d, 1H, J = 7.6 Hz), 7.66 (m, 1H), 7.21 (t,
1H, J = 8.0 Hz), 7.14 (t, 1H, J = 7.6 Hz), 7.07 (d, 1H, J = 8.4
Hz), 7.00 (t, 1H, J = 7.6 Hz), 6.93 (d, 1H, J = 8.0 Hz), 3.67 (d,
1H, J = 17.2 Hz), 3.39 (d, 1H, J = 16.8 Hz); 13C NMR
(100 MHz, CDCl3, ppm): δ 195.76, 170.49, 157.61, 139.36,
1
oil. H NMR (400 MHz, CDCl3, ppm): δ 7.99–8.01 (m, 2H),
7.74 (d, 1H, J = 7.2 Hz), 7.34 (m, 1H), 7.18 (t, 1H, J = 7.2 Hz),
7.09 (d, 1H, J = 8.4 Hz), 6.96 (d, 1H, J = 8.4 Hz), 4.37 (q, 2H,
J = 7.2 Hz), 3.70 (d, 1H, J = 16.8 Hz), 3.45 (d, 1H, J = 16.8
This journal is © The Royal Society of Chemistry 2012
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Hz), 1.39 (t, 3H, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3,
ppm): δ 195.01, 170.41, 166.08, 161.22, 139.50, 131.34,
126.59, 125.34, 125.12, 124.46, 123.20, 118.60, 113.30, 110.84,
109.82, 60.86, 36.53, 14.33; IR (KBr, cm−1): 2984, 2926, 2907,
2853, 1719, 1664, 1616, 1460, 1447, 1440, 1436, 1257, 1249,
1460, 1375, 1279, 1165, 861, 828, 762; HRMS (ESI): Calcd
For C19H20NO6+ [M + NH4]+: 358.1285, found 358.1279.
5,5′-Dibromo-3H,3′H-2,2′-spirobi[benzofuran]-3-one (2j). Fol-
lowing the procedure of 2a, the reaction gives 2j (86%) as a
1
+
solid, m.p.: 146–147 °C. H NMR (400 MHz, CDCl3, ppm): δ
1154, 905, 864, 758; HRMS (ESI): Calcd For C18H15O5 [M +
H]+: 311.0914, found 311.0917.
7.84 (d, 1H, J = 2.0 Hz), 7.76 (dd, 1H, J1 = 8.8 Hz, J2 = 2.0
Hz), 7.40 (s, 1H), 7.34 (d, 1H, J = 8.8 Hz), 6.99 (d, 1H, J = 8.8
Hz), 6.81 (d, 1H, J = 8.4 Hz), 3.67 (d, 1H, J = 17.2 Hz), 3.40 (d,
1H, J = 16.8 Hz); 13C NMR (100 MHz, CDCl3, ppm): δ
193.77, 169.08, 156.61, 141.94, 131.56, 127.84, 127.76, 126.09,
120.27, 115.63, 115.10, 114.67, 111.69, 111.14, 37.03; MS (EI)
m/z (%): 398 (M+ + 4, 3), 396 (M+ + 2, 7), 394 (M+, 3), 211
(11), 205 (11), 200 (19), 198 (26), 169 (13), 165 (10), 155 (15),
149 (31), 141 (27), 139 (35), 127 (24), 113 (32), 112 (12), 111
(26), 99 (33), 85 (71), 71 (91), 57 (100), 43 (63); IR (KBr,
cm−1): 2926, 2853, 1737, 1665, 1460, 1425, 1275, 1161, 846,
809, 765, 490.
5′-Bromo-7-methoxy-3H,3′H-2,2′-spirobi[benzofuran]-3-one (2f).
Following the procedure of 2a, the reaction gives 2f (82%) as a
1
solid, m.p.: 136–137 °C. H NMR (400 MHz, CDCl3, ppm): δ
7.37 (s, 1H), 7.29 (m, 2H), 7.19 (d, 1H, J = 7.6 Hz), 7.09 (t, 1H,
J = 7.8 Hz), 6.79 (d, 1H, J = 8.4 Hz), 3.92 (s, 3H), 3.68 (d, 1H,
J = 17.2 Hz), 3.45 (d, 1H, J = 16.8 Hz); 13C NMR (100 MHz,
CDCl3, ppm): δ 195.09, 160.22, 156.77, 145.97, 131.28,
127.69, 126.33, 123.56, 120.12, 119.52, 116.08, 114.37, 111.63,
110.84, 56.15, 37.03; IR (KBr, cm−1): 2926, 2853, 2582, 1854,
1733, 1605, 1460, 1279, 1158, 864, 808, 738, 523; HRMS
+
(ESI): Calcd For C16H12BrO4 [M + H]+: 346.9913, found
346.9916.
Ethyl 5′-bromo-3′-oxo-3H,3′H-2,2′-spirobi[benzofuran]-5-car-
boxylate (2k). Following the procedure of 2a, the reaction gives
2k (84%) as oil. H NMR (400 MHz, CDCl3, ppm): δ 8.01 (s,
1
Ethyl 7′-methoxy-3′-oxo-3H,3′H-2,2′-spirobi[benzofuran]-5-
carboxylate (2g). Following the procedure of 2a, the reaction
gives 2g (88%) as oil. H NMR (400 MHz, CDCl3, ppm): δ
1H), 7.99 (s, 1H), 7.85 (d, 1H, J = 2.0 Hz), 7.77 (dd, 1H, J1 =
8.8 Hz, J2 = 2.4 Hz), 7.00 (d, 1H, J = 8.8 Hz), 6.95 (d, 1H, J =
9.2 Hz), 4.37 (q, 2H, J = 7.2 Hz), 3.69 (d, 1H, J = 17.2 Hz),
3.44 (d, 1H, J = 17.2 Hz), 1.39 (t, 3H, J = 7.2 Hz); 13C NMR
(100 MHz, CDCl3, ppm): δ 193.68, 169.13, 166.00, 161.05,
141.94, 131.44, 127.83, 126.61, 125.38, 124.22, 120.33, 115.73,
115.10, 111.38, 109.87, 60.90, 36.62, 14.34; IR (KBr, cm−1):
2962, 2926, 2872, 2853, 1891, 1748, 1719, 1460, 1375, 1253,
1161, 861, 828, 758, 516; HRMS (ESI): Calcd For
C18H14BrO5+ [M + H]+: 389.0019, found 389.0005.
1
7.99 (s, 1H), 7.97 (s, 1H), 7.33 (dd, 1H, J1 = 7.6 Hz, J2 = 0.8
Hz), 7.21 (d, 1H, J = 7.2 Hz), 7.12 (t, 1H, J = 7.6 Hz), 6.95 (d,
1H, J = 8.4 Hz), 4.36 (q, 2H, J = 7.2 Hz), 3.95 (s, 3H), 3.71 (d,
1H, J = 17.2 Hz), 3.51 (d, 1H, J = 16.8 Hz), 1.40 (t, 3H, J = 7.2
Hz); 13C NMR (100 MHz, CDCl3, ppm): δ 195.15, 166.11,
161.26, 160.30, 146.03, 131.26, 126.53, 125.06, 124.44, 123.70,
120.21, 119.59, 116.22, 111.09, 109.88, 60.86, 56.24, 36.68,
14.31; IR (KBr, cm−1): 2962, 2926, 2872, 2853, 1920, 1735,
1715, 1704, 1460, 1375, 1282, 1279, 1158, 1092, 879, 809,
+
743; HRMS (ESI): Calcd For C19H17O6 [M + H]+: 341.1020,
found 341.1025.
3H-Spiro[benzofuran-2,2′-chroman]-3-one (2l). Following the
1
procedure of 2a, the reaction gives 2l (27%) as oil. H NMR
(400 MHz, CDCl3, ppm): δ 7.67–7.63 (m, 2H), 7.15 (m, 3H),
7.06 (d, 1H, J = 8.4 Hz), 6.96 (m, 1H), 6.87 (d, 1H, J = 1.2 Hz),
3.23–3.14 (m, 1H), 2.94 (m, 1H), 2.28 (m, 1H), 2.05 (m, 1H);
13C NMR (100 MHz, CDCl3, ppm): δ 195.73, 170.50, 151.92,
139.05, 129.19, 127.77, 125.44, 122.60, 122.04, 121.04, 118.93,
117.12, 113.54, 102.35, 25.49, 20.45; IR (KBr, cm−1): 2926,
2853, 1726, 1616, 1460, 1436, 1227, 1158, 751; HRMS (ESI):
Calcd For C16H13O3+ [M + H]+: 253.0859, found 253.0864.
5′-Bromo-5-methoxy-3H,3′H-2,2′-spirobi[benzofuran]-3-one (2h).
Following the procedure for 2a, the reaction gives 2h (83%) as a
solid, m.p.: 129–131 °C. H NMR (400 MHz, CDCl3, ppm): δ
1
7.39 (s, 1H), 7.28–7.33 (m, 2H), 7.11 (d, 1H, J = 2.8 Hz), 7.00
(d, 1H, J = 8.8 Hz), 6.80 (d, 1H, J = 8.4 Hz), 3.81 (s, 1H), 3.66
(d, 1H, J = 17.2 Hz), 3.38 (d, 1H, J = 16.8 Hz); 13C NMR
(100 MHz, CDCl3, ppm): δ 195.31, 165.63, 156.75, 155.63,
131.34, 129.03, 127.77, 126.41, 118.45, 114.35, 114.17, 111.58,
111.27, 105.17, 55.89, 36.99; IR (KBr, cm−1): 2926, 2853,
1848, 1876, 1737, 1711, 1460, 1275, 1161, 809, 747, 534;
4,5-Dihydro-3H,3′H-spiro[benzo[b]oxepine-2,2′-benzofuran]-3′-
one (2m). Following the procedure of 2a, the reaction gives 2m
HRMS (ESI): Calcd For C16H12BrO4 [M + H]+: 346.9913,
+
1
(17%) as oil. H NMR (400 MHz, CDCl3, ppm): δ 7.74 (m,
found 346.9909.
1H,), 7.62 (m, 1H), 7.19–6.87 (m, 6H), 3.17–3.10 (m, 1H),
2.88–2.82 (m, 1H), 2.27–2.19 (m, 1H), 2.13–2.05 (m, 1H),
2.01–1.95 (m, 1H), 1.91–1.82 (m, 1H); 13C NMR (100 MHz,
CDCl3, ppm): δ 196.53, 170.32, 153.00, 138.64, 134.46,
129.62, 127.45, 125.56, 124.97, 122.92, 122.57, 118.91, 113.38,
104.28, 32.22, 31.90, 19.92; IR (KBr, cm−1): 2926, 2853, 1920,
1737, 1620, 1460, 1227, 1165, 754; HRMS (ESI): Calcd For
C17H15O3+ [M + H]+: 267.1016, found 267.1009.
Ethyl 5′-methoxy-3′-oxo-3H,3′H-2,2′-spirobi[benzofuran]-5-
carboxylate (2i). Following the procedure of 2a, the reaction
gives 2i (85%) as oil. 1H NMR (400 MHz, CDCl3, ppm): δ 8.00
(s, 1H), 7.98 (s, 1H), 7.31 (dd, 1H, J1 = 9.2 Hz, J2 = 2.8 Hz),
7.13 (d, 1H, J = 2.4 Hz), 7.02 (d, 1H, J = 8.8 Hz), 6.96 (d, 1H, J
= 8.0 Hz), 4.37 (q, 2H, J = 7.2 Hz), 3.83 (s, 3H), 3.69 (d, 1H, J
= 16.8 Hz), 3.44 (d, 1H, J = 17.2 Hz), 1.39 (t, 3H, J = 7.2 Hz);
13C NMR (100 MHz, CDCl3, ppm): δ 195.37, 166.11, 165.73,
161.25, 155.76, 131.32, 129.13, 126.58, 125.04, 124.51, 118.50,
114.24, 111.54, 109.82, 105.26, 60.86, 55.97, 36.62, 14.33; IR
(KBr, cm−1): 2962, 2926, 2872, 2853, 2844, 1917, 1737, 1708,
Acknowledgements
This work was supported by the NSFC (Nos. 21072084).
3498 | Org. Biomol. Chem., 2012, 10, 3494–3499
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ution is quenched with saturated NaHCO3, extracted (DCM), washed
with Na2SO3, NaHCO3 and brine, dried with Na2SO4, filtered, and con-
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This journal is © The Royal Society of Chemistry 2012
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