Metal-free tandem Friedel-Crafts/lactonization reaction to benzofuranones bearing a quaternary center at C3 position

Article abstract of DOI:10.1021/jo300395x

A metal-free tandem Friedel-Crafts/lactonization reaction to 3,3-diaryl or 3-alkyl-3-aryl benzofuranones catalyzed by HClO₄ was reported. A variety of tertiary α-hydroxy acid esters could readily react with substituted phenols to afford the des

Full text of DOI:10.1021/jo300395x

Article
pubs.acs.org/joc
Metal-Free Tandem Friedel−Crafts/Lactonization Reaction to
Benzofuranones Bearing a Quaternary Center at C3 Position
Long Chen, Feng Zhou, Tao-Da Shi, and Jian Zhou*
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry, East China Normal University,
3663 N. Zhongshan Road, Shanghai, 200062, P. R. China
S
* Supporting Information
ABSTRACT: A metal-free tandem Friedel−Crafts/lactonization
reaction to 3,3-diaryl or 3-alkyl-3-aryl benzofuranones catalyzed by
HClO4 was reported. A variety of tertiary α-hydroxy acid esters
could readily react with substituted phenols to afford the desired
products in rich diversity. The synthetic utility of the products was
1
demonstrated by the synthesis of polycyclic compounds. H NMR
studies supported that this tandem reaction proceeded via tandem Friedel−Crafts/lactonization sequence.
reaction step, which resulted from the net destabilizing effect of
the electron-withdrawing ester group. Despite achievements in
the catalytic arylation of tertiary alcohols,7 the use of tertiary
alcohols with an α-electron-withdrawing-substitutent for
reaction development is limited to alcohols that could form
reactive vinylogous iminium or oxonium intermediates.7e,8
INTRODUCTION
■
The 3,3-disubstituted benzofuranone is a prominent structural
motif in many natural bioactive products, such as yuccaol A,
hopeahainol A, radulifoline, and rosmadial.1 It also serves as a
synthon for the synthesis of bioactive natural products such as
aplysin, isolaurinterol, and isoaplysin (Figure 1).2
While several methods had been developed, including the
condensation of benzil with phenols to symmetrical 3,3-diaryl
benzofuranones,3 transition metal catalyzed coupling reactions,
and the functionalization of 3-substituted benzofuranones,4
these methods suffered from narrow substrate scope or the
difficulty in the synthesis of starting materials. In addition,
methods to unsymmetrical 3,3-diaryl benzofuranones were very
limited. Accordingly, it is valuable to develop new catalytic cost-
effective methods to enable the synthesis of this framework in
rich structural diversity from simple starting materials to
facilitate structure−activity relationship studies for drug
discovery.
RESULTS AND DISCUSSION
■
Most recently, we have reported that Hg(ClO4)2·3H2O could
catalyze a highly efficient Friedel−Crafts arylation of 3-alkyl or
3-arylhydroxyoxindoles.9 On the basis of this result, we tried to
develop an efficient catalytic version of this tandem reaction to
3,3-disubstituted benzofuranones. The reaction of α-hydroxy
ester 1a and phenol 2a was undertaken for condition
optimization, and typical results were shown in Table 1.
We first screened a variety of cheap and easy to handle metal
perchlorate hydrates,10 known powerful Lewis acids. When
reaction was run in CH3NO2 at 60 °C using 1.5 equiv of phenol
2a, only perchlorate hydrates of Hg(II), In(III), Fe(III), and
Zr(III) could work, and Zr(ClO4)2·8H2O seemed to be the
most reactive, affording 3a in 43% yield (Table 1, entries 1−4).
Brønsted acids were also tried, and only HOTf and HClO4
could give product 3a in moderate yield (Table 1, entries 5−6).
Next, Zr(ClO4)2·8H2O and HClO4 were used for further
optimization. Interestingly, when increasing the temperature
from 60 to 70 °C, the reaction catalyzed by HClO4 could finish
within 24 h, giving product 3a in 85% yield (Table 1, entry 8),
superior to that catalyzed by Zr(ClO4)2·8H2O (Table 1, entry
7). Reaction at 80 °C resulted in the formation of side products
and lower yield of 3a (Table 1, entry 9). The use of 1.2 equiv of
2a gave 3a in lower yield (Table 1, entry 10). The solvent
effects were also evaluated, and CH3NO2 turned out to be the
best. For example, no reaction took place in toluene or
tBuOMe, and reaction in CH3CN or ethyl acetate afforded
The tandem reaction5 from α-hydroxy acid esters 1 and
phenols 2, possibly through Friedel−Crafts/lactonization
sequence (path a in Scheme 1) or ester exchange/Friedel−
Crafts reaction cascade (path b), was an efficient method to
prepare unsymmetric 3,3-disubstituted benzofuranones. The
major advantages of this tandem reaction include the ready
access of starting materials and the rich diversity of the desired
product 3 by varying the substituents of R, R1, and R2. This
reaction was discovered in 2010 by Nicolaou et al. during the
total synthesis of hopeahainol A.6 They found that the use of
3.0 equiv of p-tolunesulfonic acid could promote the reaction of
3.0 equiv of resorcinol with 1.0 equiv of an ester 1 to form the
corresponding product 3, which they proposed to proceed
through path a.6 However, the substrate scope remained
unexplored. To date, no catalytic version of this reaction and no
systematic studies into this efficient reaction have been
reported. To develop a catalytic version, the main challenge
is to overcome the difficulty in the formation of the
carbocationic intermediate i or iv for the Friedel−Crafts
Received: February 24, 2012
Published: March 29, 2012
© 2012 American Chemical Society
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Figure 1. Representative natural products.
Scheme 1. Tandem Reaction to 3,3-Disubstituted Benzofuranones
position of phenyl ring, the reaction proceeded smoothly to
afford the product in high yield (Table 3, entries 1, 2 and 4).
With only one electron-withdrawing group, esters 1e and 1f
worked well to afford the desired products 3n and 3o in good
yield. However, with two CF3 groups, ester 1g reacted very
slowly to give product 3p in 46% yield after 120 h (Table 3,
entries 5−7). To our delight, this protocol could be extended to
α-alkyl α-aryl hydroxy acid esters 1i−l, which provided the
corresponding 3-alkyl-3-aryl benzofuranones 3r−u in good
yield (Table 3, entries 9−12).
We also tried to synthesize 3,3-dialkyl benzofuranones by this
protocol. Unfortunately, even in the presence of 100 mol % of
HClO4, α,α-dialkyl hydroxy acid ester 1m failed to react with
phenols to give the desired product, possibly because 1m
underwent elimination reaction under this condition.
Table 1. Condition Optimization
temp
time
(h)
yield
b
a
entry
catalyst
solvent
X
(°C)
(%)
1
Hg(ClO4)2·3H2O
In(ClO4)3·8H2O
Fe(ClO4)3·xH2O
Zr(ClO4)2·8H2O
HOTf
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3CN
EtOAc
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.2
1.5
1.5
60
60
60
60
60
60
70
70
80
70
70
70
36
36
36
36
36
36
24
24
24
24
24
24
31
20
23
43
28
34
48
85
79
56
57
44
2
3
4
5
6
HClO4
7
Zr(ClO4)2·8H2O
HClO4
8
9
HClO4
10
11
12
HClO4
HClO4
HClO4
a
b
On a 0.10 mmol scale. Isolated yield.
In addition to being interesting targets for medicinal
chemistry, the thus obtained 3,3-disubstituted benzofuranones
with a phenol or bromo substituent were versatile for further
elaboration (Scheme 2). For example, product 4, obtained from
3e in 82% yield, could be readily converted to compound 5 and
6 via Pd-catalyzed coupling reactions. After protecting the
phenol hydroxy group of product 3v with suitable functional
groups, the resulting products 7 and 8 could be readily
transformed into interesting polycyclic compounds 9−11 in
reasonable yields.
Since the reaction of 1d and 2e proceeded rapidly at 25 °C
to give product 3m in 78% yield after 24 h (Table 3, entry 4), it
offered the premise to investigate the reaction mechanism by
NMR studies. Accordingly, the reaction of 1d and 2e was
subjected to NMR studies using CD3NO2 as the solvent at 25
°C, in the presence of 10 mol % HClO4. As shown in Figure 2,
no obvious change happened after mixing 1d and 2e, except the
peak of OH group of 1d shifted from 4.53 to 4.63 (Figure 2c).
product 3a in lower yield (Table 1, entries 11−12). The
evaluation of substrate scope was then carried out in CH3NO2
at 70 °C, using 10 mol % of HClO4 as the catalyst.
Different substituted phenols were first examined (Table 2).
Generally, electron-rich phenols such as 2c and 2e−f worked
well to give the desired products in excellent yield (Table 2,
entries 1, 3, 5 and 6). Bromo-substituted phenols 2b and 2d
could also afford products 3b and 3d in good yield (Table 2,
entries 2 and 4), but the reaction time was much longer.
Phenols 2g−j with a methyl group on different positions were
also tried, and the corresponding products 3g−j were obtained
in good yield (Table 2, entries 7−10).
Then different substituted α-hydroxy acid esters 1a−l were
tried (Table 3), and the electronic effects of substituents on
reaction rate were obvious. In the case of α,α-diaryl esters 1a,
1b, and 1d with electron-rich substituent on the ortho or para
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Table 2. Substrate Scope of Different Phenols
a
b
On a 0.3 mmol scale. Isolated yield.
In contrast, two new peaks at 3.88 and 3.76 appeared with 1:1
ratio after adding 10 mol % of HClO4 for 10 min (Figure 2d),
which possibly correlated to the methyl ester and methoxy
group of the Friedel−Crafts adduct v, which we tried in vain to
isolate from the reaction mixture. This observation, together
with the fact that only trace amount of MeOH could be
detected at the first 10 min (Figure 2d) and the characteristic
peak of MeOH at 3.45 is much weaker than the two peaks at
3.88 and 3.76 even after one hour (Figure 2e), suggested that
this reaction began with an intermolecular Friedel−Crafts
reaction, followed by lactone formation (for the full NMR
spectra, see the Supporting Information). A weak new peak at
3.66 correlated to methoxy group of 3m was also observed at
the first 10 min, which gradually developed. For comparison,
the NMR changes of the individual starting materials 2e and 1d
when independently mixed with 10 mol % of HClO4 in
CD3NO2 at 25 °C were also examined, and the results are
provided in the Supporting Information.
evaluation and studies on the structure−activity relationship.
The usefulness of the products has been demonstrated by the
facile transformation to interesting polycyclic compounds. The
NMR studies supported that the reaction proceeded via the
sequential Friedel−Crafts/lactonization reaction. The use of
simple and inexpensive catalyst and starting materials, together
with the usefulness of the products, made our method
potentially useful.
EXPERIMENTAL SECTION
■
General Information. Reactions were monitored by thin layer
chromatography using UV light to visualize the course of reaction.
Purification of reaction products were carried out by flash
chromatography on silica gel. Chemical yields refer to pure isolated
substances. All reactions were run in air except noted. Anhydrous
CH3NO2 was prepared by drying over anhydrous Na2SO4 and then
distilling under reduced pressure. Commercially available HClO4
(70%, aq) was used as received. α-Hydroxy acid esters 16,11 and 4-
bromobenzene-1,2-diol12 were prepared using literature procedures.
Caution! Although the use of HClO4 (70%, aq) as the catalyst could
reduce the potential danger associated with HClO4, special care should
still be taken during the reaction course when heating the
nitromethane solution containing HClO4.
CONCLUSION
■
A simple and highly efficient tandem reaction from easily
available α-hydroxy acid esters and substituted phenols has
been developed, allowing ready synthesis of both 3,3-diaryl and
3-alkyl-3-aryl benzofuranones with hindered all-carbon quater-
nary centers, in high structural diversity for biological
General Procedure for the Tandem Friedel−Crafts/Lactoni-
zation Reaction. Unless mentioned, the reaction was carried out in
air. To a 5-mL vial were added α-hydroxy acid esters 1 (0.3 mmol),
phenols 2 (0.45 mmol, 1.5 equiv.), and 0.5 mL of anhydrous CH3NO2.
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Table 3. Substrate Scope of Different α-Hydroxy Acid Esters
a
b
On a 0.3 mmol scale. Isolated yield.
After adding HClO4 (solution in CH3NO2), the reaction mixture was
stirred at 70 °C until almost full conversion of 1, confirmed by TLC
analysis. The reaction mixture was directly subjected to column
chromatography on silica gel using petroleum ether/ethyl acetate as
the eluent to afford the desired product 3.
5-tert-Butyl-3-phenyl-3-p-tolylbenzofuran-2(3H)-one (3a). Reac-
tion was run under N21atmosphere. White solid: 91.2 mg, isolated yield
85%; mp 84−86 °C; H NMR (400 MHz, CDCl3) δ 7.29−7.16 (m,
7H), 7.08−7.02 (m, 5H), 2.24 (s, 3H), 1.21 (s, 9H); 13C NMR (100
MHz, CDCl3) δ 177.4, 150.4, 147.7, 141.0, 137.9, 137.6, 130.7, 129.4,
128.6, 128.1, 128.0, 127.7, 126.0, 122.91, 110.3, 61.4, 34.7, 31.5, 21.0;
IR (neat) 2954, 1800, 1613, 1486, 1140, 1056, 746, 698 cm−1; GC−
MS (EI) 356 (M+, 21), 313 (100). HRMS (EI) Exact mass calcd for
C25H24O2 [M]+: 356.1776. Found: 356.1771.
5-Bromo-3-phenyl-3-p-tolylbenzofuran-2(3H)-one (3b). Yellow
oil: 68.0 mg, isolated yield 60%; 1H NMR (400 MHz, CDCl3) δ
7.41−7.38 (m, 1H), 7.30−7.25 (m, 4H), 7.18−7.15 (m, 2H), 7.09−
7.01 (m, 5H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 176.2,
151.5, 140.0, 138.1, 137.0, 133.4, 132.2, 129.6, 129.1, 128.9, 128.1,
128.0, 127.9, 117.1, 112.8, 61.2, 21.0; IR (neat) 2963, 1806, 1699,
1486, 1261, 1057, 928, 696, 623 cm−1; GC−MS (EI) 378, 380 (M+,
22, 21), 335 (100). HRMS (EI) Exact mass calcd for C21H15O279Br
[M]+: 378.0255. Found: 378.0253.
5-Hydroxy-3-phenyl-3-p-tolylbenzofuran-2(3H)-one (3c). White
solid: 80.0 mg, isolated yield 86%; mp 149−150 °C; H NMR (400
1
MHz, CDCl3) δ 7.30−7.26 (m, 5H), 7.13 (m, 4H), 7.06−7.04 (m,
1H), 6.79−6.75 (m, 2H), 4.91 (s, br, 1H), 2.32 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 177.4, 152.6, 146.4, 140.6, 137.8, 137.5, 132.4,
129.4, 128.7, 128.1, 128.0, 127.9, 115.8, 113.3, 111.8, 61.7, 21.0; IR
(neat) 3430, 2961, 1762, 1609, 1490, 1337, 1072, 801, 698 cm−1;
GC−MS (EI) 316 (M+, 20), 273 (100). HRMS (EI) Exact mass calcd
for C21H16O3 [M]+: 316.1099. Found: 316.1100.
5-Bromo-6-hydroxy-3-phenyl-3-p-tolylbenzofuran-2(3H)-one
1
(3d). Yellow solid: 79.4 mg, isolated yield 68%; mp 174−176 °C; H
NMR (400 MHz, CDCl3) δ 7.23−7.21 (m, 4H), 7.15−7.13 (m, 2H),
7.03 (s, 4H), 6.80 (s, 1H), 5.77 (s, 1H), 2.22 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 176.6, 153.1, 152.9, 140.4, 137.9, 137.3, 129.5, 128.8,
128.0, 127.9, 127.8, 127.2, 124.8, 105.3, 99.8, 60.8, 21.0; IR (neat)
3386, 3031, 2923, 1778, 1632, 1491, 1290, 1090, 960, 761, 696 cm−1;
GC−MS (EI) 394, 396 (M+, 34, 36), 353 (100). HRMS (EI) Exact
mass calcd for C21H15O379Br [M]+: 394.0205. Found: 394.0215.
6-Hydroxy-3-phenyl-3-p-tolylbenzofuran-2(3H)-one (3e). White
1
solid: 89.0 mg, isolated yield 94%; mp 195−197 °C; H NMR (400
MHz, CDCl3) δ 7.80 (s, br, 1H), 7.30−7.24 (m, 5H), 7.14−7.10 (m,
4H), 7.07 (ABd, J = 8.0 Hz, 1H), 6.73 (s, 1H), 6.67 (ABd, J = 8.0 Hz,
1H), 2.31 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.7, 157.4,
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Scheme 2. Product Elaboration
1
Figure 2. H NMR analysis of the reaction of 1d and 2e in CD3NO2 at 25 °C.
153.3, 141,1, 138.0, 137.5, 129.3, 128.6, 128.0, 127.9, 127.6, 126.6,
122.3, 111.8, 99.1, 60.7, 21.0; IR (neat) 3430, 3056, 1783, 1621,1452,
1133, 1064, 970, 794, 635 cm−1; GC−MS (EI) 316 (M+, 6), 273
(100). HRMS (EI) Exact mass calcd for C21H16O3 [M]+: 316.1099.
Found: 316.1096.
4,6-Dihydroxy-3-phenyl-3-p-tolylbenzofuran-2(3H)-one (3f).
White solid: 96.9 mg, isolated yield 97%; mp 110−112 °C; 1H
NMR (400 MHz, CDCl3) δ 7.33 (m, 5H), 7.21−7.14 (m, 4H), 6.36
(d, J = 2.0 Hz, 1H), 6.12 (d, J = 2.0 Hz, 1H), 5.40 (s, br, 1H), 4.91 (s,
1H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 178.0, 157.9,
153.7, 153.1, 138.7, 138.0, 135.6, 129.5, 128.7, 128.4, 128.2, 128.1,
109.3, 99.9, 92.5, 60.7, 21.0; IR (neat) 3333, 1777, 1626, 1460, 1130,
995, 928, 811, 696 cm−1; GC−MS (EI) 332 (M+, 4), 149 (100).
HRMS (EI) Exact mass calcd for C21H16O4.[M]+:332.1049. Found:
332.1050.
4,6-Dimethyl-3-phenyl-3-p-tolylbenzofuran-2(3H)-one (3g).
White solid: 60.0 mg, isolated yield 61%; mp 137−138 °C; 1H
NMR (400 MHz, CDCl3) δ 7.21−7.15 (m, 5H), 7.09−7.03 (m, 4H),
6.81 (s, 1H), 6.67 (s, 1H), 2.28 (s, 3H), 2.24 (s, 3H), 1.79 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 178.3, 152.8, 139.6, 138.2, 137.7, 136.2,
134.8, 129.1, 129.0, 128.9, 128.4, 127.8, 127,5, 126.8, 109.3, 61.5, 21.5,
21.0, 18.6; IR (neat) 2961, 1791, 1631, 1494, 1262, 1026, 869, 636
cm−1; GC−MS (EI) 328 (M+, 16), 285 (100). HRMS (EI) Exact mass
calcd for C23H20O2 [M]+: 328.1463. Found: 328.1464.
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1
5,7-Dimethyl-3-phenyl-3-p-tolylbenzofuran-2(3H)-one (3h). Re-
action was run under N2 atmosphere. White solid: 54.2 mg, isolated
yield 56%; mp 114−116 °C; 1H NMR (400 MHz, CDCl3) 7.22−7.18
(m, 5H), 7.08−7.03 (m, 4H), 6.87 (s, 1H), 6.79 (s, 1H), 2.25 (s, 6H),
2.21 (s, 3H); 13C NMR (100 MHz, CDCl3) 177.5, 149.0, 141.0, 138.0,
137.5, 133.8, 131.1, 130.7, 129.3, 128.6, 128.2, 128.1, 127.7, 123.7,
120.9, 61.6, 21.2, 21.0, 15.1; IR (neat) 2924, 1794, 1673, 1486, 1381,
1254, 1099, 936, 736, 699 cm−1; GC−MS (EI) 328 (M+, 29), 285
(100). HRMS (EI) Exact mass calcd for C23H20O2 [M]+: 328.1463.
Found: 328.1465.
5-Methyl-3-phenyl-3-p-tolylbenzofuran-2(3H)-one (3i). Reaction
was run under N2 atmosphere. White solid: 66 mg, isolated yield 70%;
mp 154−155 °C; 1H NMR (400 MHz, CDCl3) δ 7.21−7.19 (m, 5H),
7.08−7.03 (m, 5H), 7.00−6.97 (m, 2H), 2.24 (s, 6H); 13C NMR (100
MHz, CDCl3) δ 177.3, 150.5, 140.9, 137.8, 137.6, 134.2, 131.2, 129.6,
129.4, 128.6, 128.2, 128.0, 127.7, 126.4, 110.70, 61.2, 21.2, 21.0; IR
(neat) 3028, 2951, 1797, 1602, 1487, 1139, 1064, 936, 697, 632 cm−1;
GC−MS (EI) 314 (M+, 34), 271 (100). HRMS (EI) Exact mass calcd
for C22H18O2 [M]+: 314.1307. Found: 314.1306.
186 °C; H NMR (400 MHz, CDCl3) δ 7.58 (ABd, J = 8.4 Hz, 2H),
7.39 (ABd, J = 8.0 Hz, 2H), 7.35−7.32 (m, 3H), 7.24−7.22 (m, 2H),
7.12−7.10 (m, 1H), 6.75−6.74 (m, 1H), 6.70−6.67 (m, 1H), 5.36 (s,
1H); 13C NMR (100 MHz, CDCl3 + DMSO-d6) δ 176.8, 159.0, 153.2,
145.2, 140.5, 129.2 (q, J = 73.0 Hz), 128.0, 127.9, 126.4, 125.52,
125.48, 125.3, 122.5, 120.1, 112.3, 99.2, 60.8; 19F NMR (376 MHz,
CDCl3) δ −62.7; IR (neat) 3444, 2925, 2854, 1787, 1620, 1064, 959,
834, 633 cm−1; GC−MS (EI) 370 (M+, 45), 341 (100). HRMS (EI)
Exact mass calcd for C21H13O3F3 [M]+: 370.0817. Found: 370.0818.
3-(3,5-Bis(trifluoromethyl)phenyl)-6-hydroxy-3-phenylbenzofur-
an-2(3H)-one (3p). White solid: 61.0 mg, isolated yield 46%; mp
1
144−146 °C; H NMR (400 MHz, CDCl3) δ 7.85 (s, 1H), 7.74 (m,
2H), 7.35 (m, 3H), 7.19−7.18 (m, 2H), 7.11 (ABd, J = 8.0 Hz, 1H),
6.78 (s, 1H), 6.72 (ABd, J = 8.0 Hz, 1H), 5.64 (s, 1H); 13C NMR (100
MHz, CDCl3) 176.2, 157.5, 153.4, 143.3, 139.7, 132.1 (q, J = 34.0 Hz),
129.3, 128.6, 128.4, 127.6, 126.6, 122.9 (q, J = 271.0 Hz), 122.1, 121.1,
112.4, 99.8, 60.8; 19F NMR (376 MHz, CDCl3) δ −62.8; IR (neat)
3452, 2925, 1785, 1626, 1276, 1071, 681 cm−1; GC−MS (EI) 438
(M+, 39), 409 (100). HRMS (EI) Exact mass calcd for C22H12O3F6
[M]+: 438.0691. Found: 438.0693.
5,6-Dimethyl-3-phenyl-3-p-tolylbenzofuran-2(3H)-one (3j).
White solid: 78.0 mg, isolated yield 80%; mp 170−171 °C; 1H
NMR (400 MHz, CDCl3) δ 7.19−7.14 (m, 5H), 7.07−7.02 (m, 4H),
6.92−6.89 (m, 2H), 2.22 (s, 3H), 2.19 (s, 3H), 2.13 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 177.5, 150.8, 141.1, 138.0, 137.9, 137.5, 132.7,
129.3, 128.6, 128.4, 128.1, 128.0, 127.6, 126.7, 111.9, 61.1, 21.0, 20.2,
19.6; IR (neat) 2922, 2853, 1459, 1799, 1628, 1459, 1057, 959, 760,
696 cm−1; GC−MS (EI) 328 (M+, 26), 285 (100). HRMS (EI) Exact
mass calcd for C23H20O2 [M]+: 328.1463. Found: 328.1461.
6-Hydroxy-3-(4-methoxyphenyl)-3-phenylbenzofuran-2(3H)-one
6-Hydroxy-3-(naphthalen-2-yl)-3-phenylbenzofuran-2(3H)-one
(3q). White solid: 101.0 mg, isolated yield 96%; mp 174−176 °C; H
1
NMR (400 MHz, CDCl3) δ 7.81−7.79 (m, 2H), 7.75−7.74 (m, 1H),
7.68 (s, 1H), 7.57 (s, 1H), 7.48−7.46 (m, 2H), 7.41−7.39 (m, 1H),
7.31−7.26 (m, 5H), 7.15 (ABd, J = 8.4 Hz, 1H), 6.78 (s, 1H), 6.70
(ABd, J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 177.4, 157.7,
153.4, 140.9, 138.2, 132.9, 132.6, 128.71, 128.66, 128.2, 128.1, 127.8,
127.5, 126.8, 126.7, 126.5, 126.4, 126.0, 122.0, 111.9, 99.3, 61.1; IR
(neat) 3067, 1783, 1623, 1451, 1294, 1054, 963, 857, 698 cm−1; GC−
MS (EI) 352 (M+, 48), 289 (100). HRMS (EI) Exact mass calcd for
C24H16O3 [M]+: 352.1099. Found: 352.1098.
1
(3k). White solid: 87.2 mg, isolated yield 88%; mp 184−185 °C; H
NMR (400 MHz, CDCl3) δ 8.13 (s, br, 1H), 7.30−7.23 (m, 5H), 7.17
(ABd, J = 7.6 Hz, 2H), 7.05 (ABd, J = 8.4 Hz, 1H), 6.83 (ABd, J = 8.4
Hz, 2H), 6.73 (s, 1H), 6.67 (ABd, J = 8.4 Hz, 1H), 3.77 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 177.8, 159.0, 157.7, 153.2, 141.4, 132.9,
129.3, 128.6, 127.9, 127.6, 126.5, 122.2, 113.9, 111.8, 99.1, 60.3, 55.2;
IR (neat) 3434, 2950, 2833, 1781, 1621, 1453, 1253, 1064, 970, 832,
635 cm−1; GC−MS (EI) 332 (M+, 46), 303 (100). HRMS (EI) Exact
mass calcd for C21H16O4 [M]+: 332.1049. Found: 332.1048.
6-Hydroxy-3-methyl-3-phenylbenzofuran-2(3H)-one (3r). Brown
solid: 48.0 mg, isolated yield 71%; mp 94−96 °C; H NMR (400
1
MHz, CDCl3) δ 7.28−7.17 (m, 5H), 6.96 (ABd, J = 8.0 Hz, 1H), 6.64
(s, 1H), 6.59 (ABd, J = 8.0 Hz, 1H), 6.03 (s, br, 1H), 1.79 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 179.9, 156.7, 153.4, 139.6, 128.8, 127.8,
126.4, 125.1, 124.1 111.7, 99.2, 50.7, 24.9; IR (neat) 3393, 2978, 1780,
1629, 1281, 1025, 959, 731, 632 cm−1; GC−MS (EI) 240 (M+, 14),
211 (100). HRMS (EI) Exact mass calcd for C15H12O3
[M]+:240.0786. Found: 240.0785.
6-Hydroxy-3-(3-methoxyphenyl)-3-phenylbenzofuran-2(3H)-one
1
(3l). Colorless oil: 47.0 mg, isolated yield 47%; H NMR (400 MHz,
6-Hydroxy-3-(4-methoxyphenyl)-3-methylbenzofuran-2(3H)-one
(3s). Colorless oil: 60.0 mg, isolated yield 75%; H NMR (400 MHz,
CDCl3) δ 7.31−7.21 (m, 6H), 7.10−7.08 (m, 1H), 6.84−6.80 (m,
3H), 6.70 (s, 1H), 6.65−6.62 (m, 1H), 5.76 (s, 1H), 3.73 (s, 3H); 13C
NMR (100 MHz, CDCl3) 177.5, 159.6, 156.8, 153.3, 142.2, 140.6,
129.7, 128.7, 128.0, 127.8, 126.8, 122.7, 120.5, 114.4, 112.9, 111.8,
99.2, 61.0, 55.2; IR (neat) 3391, 2837, 1802, 1628, 1489, 1256, 1056,
965, 735, 695 cm−1; GC−MS (EI) 332 (M+, 63), 273 (100). HRMS
(EI) Exact mass calcd for C21H16O4 [M]+: 332.1049. Found: 332.1048.
6-Hydroxy-3-(2-methoxyphenyl)-3-phenylbenzofuran-2(3H)-one
1
CDCl3) δ 7.24−7.22 (m, 2H), 7.04 (ABd, J = 8.0 Hz, 1H), 6.86−6.84
(m, 2H), 6.70 (s, 1H), 6.67 (ABd, J = 8.0 Hz, 1H), 6.17 (s, br, 1H),
3.77 (s, 3H), 1.84 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 180.0,
159.1, 156.7, 153.5, 131.8, 127.7, 125.1, 124.3, 114.1, 111.6, 99.2, 55.3,
50.0, 25.0; IR (neat) 3394, 2976, 2838, 1781, 1629, 1252, 1026, 959,
727, 621 cm−1; GC−MS (EI) 270 (M+, 68), 241 (100). HRMS (EI)
Exact mass calcd for C16H14O4 [M]+: 270.0892. Found: 270.0893.
3-(4-Fluorophenyl)-6-hydroxy-3-methylbenzofuran-2(3H)-one
1
(3m). White solid: 95.0 mg, isolated yield 95%; mp 213-214 °C; H
NMR (400 MHz, CDCl3) 7.46−7.45 (m, 2H), 7.36−7.33 (m, 3H),
7.26−7.23 (m, 1H), 7.08 (s, 1H), 6.88−6.81 (m, 4H), 6.71−6.70 (m,
1H), 6.62−6.60 (m, 1H), 3.63 (s, 3H); 13C NMR (100 MHz, CDCl3 +
DMSO-d6) δ 178.1, 158.3, 156.7, 154.2, 137.9, 131.8, 129.4, 129.2,
129.0, 128.3, 128.2, 126.2, 120.8, 120.4, 112.2, 111.0, 98.5, 57.4, 55.8;
IR (neat) 3382, 3055, 1777, 1619, 1456, 1066, 967, 766, 695 cm−1;
GC−MS (EI) 332 (M+, 46), 303 (100). HRMS (EI) Exact mass calcd
for C21H16O4 [M]+: 332.1049. Found: 332.1048.
1
(3t). Yellow oil: 51.3 mg, isolated yield 69%; H NMR (400 MHz,
CDCl3) δ 7.32−7.28 (m, 2H), 7.06−6.98 (m, 3H), 6.73 (s, 1H),
6.70−6.68 (m, 1H), 6.14 (s, 1H), 1.86 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 179.6, 163.5, 161.0, 156.8, 153.4, 135.4 (d, J = 3.0 Hz),
128.3 (d, J = 8.0 Hz), 125.1, 123.8, 115.7 (d, J = 2.0 Hz), 111.8, 99.3,
50.1, 25.2; 19F NMR (376 MHz, CDCl3) δ −114.4; IR (neat) 3409,
2981, 1781, 1630, 1456, 1142, 960, 830, 627 cm−1; GC−MS (EI) 258
(M+, 47), 229 (100). HRMS (EI) Exact mass calcd for C15H11O3F
[M]+: 258.0692. Found: 258.0693.
3-(4-Fluorophenyl)-6-hydroxy-3-phenylbenzofuran-2(3H)-one
1
(3n). White solid: 73.1 mg, isolated yield 76%; mp 166−168 °C; H
3-Benzyl-6-hydroxy-3-phenylbenzofuran-2(3H)-one (3u). Yellow
solid: 58.0 mg, isolated yield 62%; mp 183−185 °C; H NMR (400
NMR (400 MHz, CDCl3) δ 7.31−7.23 (m, 7H), 7.08−7.00 (m, 3H),
6.73 (s, 1H), 6.68−6.66 (m, 1H), 6.00 (s, br, 1H); 13C NMR (100
MHz, CDCl3) δ 177.8, 163.5, 161.0, 156.90, 153.2, 140.8, 136.4 (d, J =
3.0 Hz), 129.9, (d, J = 8.0 Hz), 128.8, 127.9 (d, J = 13.0 Hz), 126.7,
126.6, 115.6 (d, J = 21.0 Hz), 112.0, 99.3, 60.5; 19F NMR (376 MHz,
CDCl3) δ −114.2; IR (neat) 3419, 3066, 2962, 1776, 1625, 1457,
1298, 1070, 973, 696 cm−1; GC−MS (EI) 320 (M+, 4), 291(100).
HRMS (EI) Exact mass calcd for C20H13O3F [M]+: 320.0849. Found:
320.0850.
1
MHz, CDCl3 + DMSO-d6) 8.66 (s, br, 1H), 7.45−7.43 (m, 2H),
7.30−7.20 (m, 3H), 7.01−7.00 (m, 3H), 6.92−6.90 (m, 1H), 6.80−
6.78 (m, 2H), 6.60−6.58 (m, 1H), 6.40 (s, 1H), 3.58 (AB, J = 13.2 Hz,
1H), 3.38 (AB, J = 13.2 Hz, 1H); 13C NMR (100 MHz, CDCl3 +
DMSO-d6) δ 178.3, 158.4, 153.9, 139.3, 135.3, 130.2, 128.8, 128.0,
127.9, 127.1, 127.0, 126.5, 119.1, 111.4, 98.9, 57.1, 45.1; IR (neat)
3444, 3032, 2923, 1798, 1624, 1290, 1057, 961, 698 cm−1; GC−MS
(EI) 316 (M+, 6), 225 (100). HRMS (EI) Exact mass calcd for
C21H16O3 [M]+: 316.1099. Found: 316.1100.
6-Hydroxy-3-phenyl-3-(4(trifluoromethyl)phenyl)benzofuran-
2(3H)-one (3o). White solid: 85.0 mg, isolated yield 77%; mp 184−
4359
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Article
5-Bromo-6-hydroxy-3-(2-methoxyphenyl)-3-phenylbenzofuran-
temperature. After this time, the inorganic salts were filtered, and the
solvent was evaporated under reduced pressure. The residue was taken
up in ether, washed with 2 N NaOH and water, and dried over
anhydrous Na2SO4. The solvent was removed under reduced pressure,
and the residue was purified by chromatography on silica gel
(petroleum ether/ethyl acetate = 10/1) to afford the product 7
2(3H)-one (3v). Prepared from 2d and 1d on a 2.0 mmol scale. White
1
solid: 732 mg, isolated yield 89%; mp 236−238 °C; H NMR (400
MHz, CDCl3) δ 7.43−7.35 (m, 5H), 7.30−7.24 (m, 1H), 7.11 (s, 1H),
6.89−6.80 (m, 4H), 5.85 (s, 1H), 3.65 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 177.1, 156.5, 153.9, 152.8, 136.8, 130.8, 129.44, 129.4,
129.1, 128.5, 128.40, 128.35, 123.8, 120.9, 112.0, 104.3, 99.3, 57.4,
55.7; IR (neat) 3339, 2974, 1779, 1618, 1287, 1048, 761, 695 cm−1;
MS (EI) 410, 412 (M+, 21, 22), 351 (100). HRMS (EI) Exact mass
calcd for C21H15O479Br [M]+: 410.0154. Found: 410.0155.
1
(135 mg, 88% yield) as white solid: mp 194−197 °C; H NMR (400
MHz, CDCl3) δ 7.42−7.36 (m, 5H), 7.30−7.26 (m, 1H), 7.22 (s, 1H),
7.08 (dt, J = 15.6 Hz, 3.6 Hz, 1H), 6.90−6.86 (m, 2H), 6.82−6.81 (m,
1H), 6.75 (s, 1H), 6.37 (d, J = 15.6 Hz, 1H), 4.79−4.78 (d, J = 1.6 HZ,
2H), 3.78 (s, 3H), 3.65 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
176.9, 166.3, 156.4, 154.7, 153.5, 141.1, 136.8, 130.6, 129.9, 129.5,
129.4, 129.0, 128.5, 128.4, 123.7, 122.1, 120.9, 112.0, 106.1, 96.8, 67.6,
57.5, 55. 7, 51.7; IR (neat) 3001, 2949, 2836, 1816, 1727, 1484, 1177,
975, 755 cm−1; MS (EI) 508, 510 (M+, 33, 37), 451 (100). HRMS
(EI) Exact mass calcd for C26H21O679Br [M]+: 508.0521. Found:
508.0525.
Procedure for the Preparation of 4 from 3e.13 A solution of
Tf2O (169.2 mg, 0.6 mmol) in CH2Cl2 was added dropwise to a
solution of pyridine (79 mg, 1.0 mmol) and 3e (197 mg, 0.5 mmol) in
anhydrous CH2Cl2 at 0 °C. The mixture was warmed to room
temperature naturally and allowed to stir until almost full conversion
of 3e, confirmed by TLC analysis. The mixture was then diluted with
Et2O, quenched with saturated NH4Cl, and washed with saturated
NaHCO3 and brine. After drying with anhydrous Na2SO4, the solvent
was removed under reduced pressure, and the residue was purified by
column chromatography to give 4 (184.0 mg, 82% yield) as a white
solid: mp 99−101 °C; 1H NMR (400 MHz, CDCl3) δ 7.36−7.24 (m,
4H), 7.23−7.21 (m, 2H), 7.17−7.09 (m, 6H), 2.33 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 175.7, 153.0, 149.1, 139.8, 138.3, 136.7, 131.7,
129.7, 128.9, 128.2, 128.0, 127.8, 127.4, 118.7 (q, J = 319.0 Hz), 117.5,
105.5, 60.8, 21.0; 19F NMR (376 MHz, CDCl3) δ −72.7; IR (neat)
3331, 2975, 1811, 1422, 1055, 959, 696 cm−1; GC−MS(EI) 448 (M+,
45), 405 (100). HRMS (EI) Exact mass calcd for C22H15O5SF3[M]+:
448.0592. Found: 448.0589.
Procedure for the Preparation of 9 from 7.17 To a stirred
solution of compound 7 (76 mg, 0.15 mmol) in anhydrous benzene (2
mL) at reflux was added AIBN (3 mg, 0.015 mmol). A solution of
Bu3SnH (52 mg, 0.18 mmol) in anhydrous benzene (4 mL) was added
over 1.5 h. The reaction was maintained at reflux until full conversion
of 7, confirmed by TLC analysis. The solvent was removed by rotary
evaporation, and the residue was dissolved in 1 mL of Et2O and an
aqueous solution of potassium fluoride (60%, w/v). The mixture was
stirred vigorously overnight. The precipitate that formed was removed
by vacuum filtration, and the two layers of the filtrate were separated.
The aqueous layer was extracted with ether. The filtrate was
evaporated and subjected to flash chromatography (petroleum
ether/ethyl acetate = 10/1 to 6/1) to give the desired product 9
Procedure for the Preparation of 5 from 4. The compound 5
was prepared according to the literature procedure.14 A mixture of 4
(67.2 mg, 0.15 mmol), phenylacetylene (30.6 mg, 0.3 mmol), Et3N
(0.2 mL), and Pd(PPh3)2Cl2 (11 mg, 0.015 mmol) in 0.5 mL of
anhydrous DMF was stirred at 90 °C under N2 atmosphere until full
conversion of 4, confirmed by TLC analysis. The reaction mixture was
then diluted with water, extracted with Et2O (3 × 10 mL), washed
with water (3 × 10 mL), dried over anhydrous Na2SO4, and
evaporated under reduced pressure. Column chromatography of the
residue on silica gel to afford the desired product 5 (47 mg, 78% yield)
1
with 1:1 dr (55 mg, 85% yield) as white solid: mp 84−86 °C; H
NMR (400 MHz, CDCl3) 7.42−7.33 (m, 5H), 7.27−7.22 (m, 1H),
6.88−6.82 (m, 3H), 6.77−6.75 (m, 1H), 6.64 (s, 1H), 4.83−4.74 (m,
1H), 4.35−4.29 (m, 1H), 3.91−3.72 (m, 1H), 3.69 (s, 1.5 H), 3.66 (s,
1.5 H), 3.64 (s, 1.5 H), 3.49 (s, 1.5 H), 2.73 (ABd, J = 16.8 Hz, 5.6 Hz,
1H), 2.54 (ABd, J = 16.2 Hz, 6.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3) 177.7, 172.0, 160.2, 156.7, 156.6, 153.8, 137.8, 137.7, 131.7,
131.6, 129.4, 129.3, 129.14, 129.08, 129.0, 128.3, 128.1, 124.3, 124.2,
121.9, 121.7, 121.13, 120.99, 120.8, 112.3, 112.1, 93.85, 93.82, 77.6,
57.5, 55.8, 55.7, 51.8, 51.6, 39.5, 39.2, 38.0, 37.9; IR (neat) 2951, 1802,
1733, 1619, 1481, 1253, 1140, 952, 792, 698 cm−1; MS (EI) 430 (M+,
36), 371 (100). HRMS (EI) Exact mass calcd for C26H22O6 [M]+:
430.1416. Found: 430.1417.
1
as a brown oil: H NMR (400 MHz, CDCl3) δ 7.44−7.43 (m, 2H),
7.28−7.14 (m, 11H), 7.13−7.05 (m, 4H), 2.24 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 176.6, 152.4, 140.3, 137.9, 137.2, 131.7, 131.4,
129.5, 128.8, 128.64, 128.56, 128.4, 128.1, 128.0, 127.95, 126.0, 124.3,
122.7, 113.9, 90.5, 88.3, 61.0, 21.0; IR (neat) 2962, 1806, 1619, 1573,
1494, 1260, 1055, 961, 690 cm−1; MS (EI) 400 (M+, 24). HRMS (EI)
Exact mass calcd for C29H20O2 [M]+: 400.1463. Found: 400.1461.
Procedure for the Preparation of 6 from 4. The compound 6
was prepared according to the literature procedure.15 A solution of 4
(44.8 mg, 0.1 mmol), phenylboronic acid (24.4 mg, 0.2 mmol), K2CO3
(2M, 1.0 mL), and Pd(PPh3)4 (12.4 mg, 0.01 mmol) in 1.0 mL of 1,4-
dioxane was stirred at 130 °C for 5 h under N2 atmosphere. To the
reaction mixture was then added 10 mL of H2O, which was then
extracted with CH2Cl2 (3 × 20 mL), washed with water (2 × 10 mL),
dried over anhydrous Na2SO4, and evaporated under reduced pressure.
Column chromatography of the residue on silica gel affordeed the
desired product 6 (30 mg, 80% yield) as white solid: mp 216−218 °C;
1H NMR (400 MHz, CDCl3) δ 7.58−7.56 (m, 2H), 7.47−7.30 (m,
5H), 7.37−7.34 (m, 6H), 7.19 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.0 Hz,
2H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.0, 153.0,
142.8, 140.7, 140.0, 137.8, 137.6, 130.1, 129.4, 128.9, 128.7, 128.1,
128.0, 127.9, 127.8, 127.2, 126.2, 123.5, 109.8, 61.0, 21.0; IR (neat)
2926, 1798, 1417, 1259, 1083, 953, 808, 764, 697 cm−1; MS (EI) 376
(M+, 37), 43 (100). HRMS (EI) Exact mass calcd for C27H20O2 [M]+:
376.1463. Found: 376.1465.
Procedure for the Preparation of 8 from 3v.18 To a solution of
3v (187 mg, 0.45 mmol) and potassium carbonate (124 mg, 0.9
mmol) in anhydrous acetone (3 mL) was added propargyl bromide
(64 mg, 0.54 mmol). The mixture was then stirred at reflux until full
conversion of 3u, confirmed by TLC analysis. After filtration through
Celite and washing with Et2O, the solvent was removed under reduced
pressure, and the residue was chromatographed on silica gel
(petroleum ether/ethyl acetate = 20/1) to afford the product 8
1
(199 mg, 99% yield) as white solid: mp 244−246 °C; H NMR (400
MHz, CDCl3) δ 7.43−7.30 (m, 5H), 7.28−7.25 (m, 1H), 7.22 (s, 1H),
6.98 (s, 1H), 6.90−6.85 (m, 2H), 6.82−6.80 (m, 1H), 4.82−4.81 (d, J
= 2.0 Hz, 2H), 3.65 (s, 3H), 2.59 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 176.9, 156.5, 154.4, 153.4, 136.8, 130.7, 129.9, 129.5, 129.0,
128.6, 128.3, 124.1, 120.9, 112.0, 106.2, 97.8, 77.2, 76.8, 57.5, 57.3,
55.7; IR (neat) 3282, 2923, 1621, 1476, 1287, 1066, 954, 754, 631
cm−1; GC−MS (EI) 448 (M+, 45), 405 (100). HRMS (EI) Exact mass
calcd for C24H17O479Br [M]+: 448.0310. Found: 448.0313.
Procedure for the Preparation of 10 from 8.19 A mixture of 8
(89.6 mg, 0.2 mmol) in bromobenzene (1 mL) was heated at 200 °C
for 16 h in a sealed tube. After cooling to room temperature, the
reaction mixture was directly subjected to column chromatography
using petroleum ether/ethyl acetate (40/1 to 30/1) as the eluent to
afford the desired product 10 (65 mg, 73% yield) as white solid: mp
Procedure for the Preparation of 7 from 3v.16 A mixture of 3v
(123 mg, 0.3 mmol) and anhydrous potassium carbonate (41.4 mg, 0.3
mmol) in dry acetone (3 mL) was stirred at 0 °C for 15 min. To this
mixture was added a solution of methyl 4-bromocrotonate (82 mg,
0.36 mmol) in acetone (6 mL) drop by drop over a period of about 1
h; the mixture was maintained at 0 °C during the addition. After the
addition was over, the reaction mixture was stirred overnight at room
1
225−227 °C; H NMR (400 MHz, CDCl3) δ 7.45−7.30 (m, 5H),
7.28−7.25 (m, 1H), 6.97 (s, 1H), 6.89−6.88 (m, 2H), 6.80−6.79 (m,
1H), 6.68 (d, J = 10.0 Hz, 1H), 5.88 (dt, J = 10.0 Hz, 3.6 Hz, 1H),
5.04−4.96 (m, 2H), 3.67 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
4360
dx.doi.org/10.1021/jo300395x | J. Org. Chem. 2012, 77, 4354−4362

The Journal of Organic Chemistry
Article
176.9, 156.5, 150.6, 148.2, 136.8, 130.6, 129.4, 129.1, 128.5, 128.4,
123.8, 122.8, 120.9, 117.8, 112.0, 108.2, 103.7, 66.5, 57.6, 55.7; IR
(neat) 3007, 2838, 1809, 1645, 1488, 1375, 1070, 944, 754, 699 cm−1;
MS (EI) 448, 450 (M+, 16, 16), 391 (100). HRMS (EI) Exact mass
calcd for C24H17O479Br [M]+: 448.0310. Found: 448.0307.
anones, see: (f) Cassani, C.; Tian, X.; Escudero-Adan, E. C.;
́
Melchiorre, P. Chem. Commun. 2011, 47, 233. (g) Liu, C.; Tan, B.-
X.; Jin, J.-L.; Zhang, Y.-Y.; Dong, N.; Li, X.; Cheng, J.-P. J. Org. Chem.
2011, 76, 5838. (h) Luo, W.-M.; Yu, Q.-S.; Holloway, H. W.; Parrish,
D.; Greig, N. H.; Brossi, A. J. Org. Chem. 2005, 70, 6171. (i) Peris, G.;
Vedejs, E. J. Org. Chem. 2008, 73, 1158. (j) Li, X.; Hu, S.-S.; Xi, Z.-G.;
Zhang, L.; Luo, S.-Z.; Cheng, J.-P. J. Org. Chem. 2010, 75, 8697. (k) Li,
X.; Xi, Z.-G.; Luo, S.-Z.; Cheng, J.-P. Adv. Synth. Catal. 2010, 352,
1097. (l) Fuerst, D. E.; Stoltz, B. M.; Wood, J. L. Org. Lett. 2000, 2,
3521. (m) Zhu, C.-L.; Zhang, F.-F.; Meng, W.; Nie, J.; Cahard, D.; Ma,
J.-A. Angew. Chem., Int. Ed. 2011, 50, 5869. For miscellaneous
reactions, see: (n) Hills, I. D.; Fu, G. C. Angew. Chem., Int. Ed. 2003,
42, 3921. (o) Shaw, S. A.; Aleman, P.; Vedejs, E. J. Am. Chem. Soc.
2003, 125, 13368. (p) Magnus, P.; Venable, J. D.; Shen, L.; Lynch, V.
Tetrahedron Lett. 2005, 46, 707. (q) Booker, J. E.; Boto, M. A.;
Churchill, G. H.; Green, C. P.; Ling, M.; Meek, G.; Prabhakaran, J.;
Sinclair, D.; Blake, A. J.; Pattenden, G. Org. Biomol. Chem. 2006, 4,
4193.
Procedure for the Preparation of 11 from 8.20 A suspension of
8 (67.2 mg, 0.15 mmol) and CsF (32 mg, 0.21 mmol) in N,N-
diethylaniline (0.5 mL) was heated at 200 °C for 5 h under N2
atmosphere with stirring. The mixture was directly subjected to
column chromatography using petroleum ether/ethyl acetate (100/1
to 40/1) as the eluent to afford the desired product 11 (27 mg, 40%
yield) as white solid: mp 214−216 °C; 1H NMR (400 MHz, CDCl3) δ
7.44−7.35 (m, 5 H), 7.35−7.26 (m, 1H), 7.01 (s, 1H), 6.93−6.85 (m,
3H), 6.59 (s, 1H), 3.61 (s, 3H), 2.54 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 177.4, 157.4, 156.6, 153.0, 144.5, 137.4, 131.1, 129.5, 129.4,
129.2, 128.5, 128.3, 124.4, 122.5, 121.0, 115.2, 112.1, 100.1, 97.7, 57.9,
55.7, 14.2; IR (neat) 2935, 1812, 1589, 1487, 1250, 1044, 943, 793,
698 cm−1; MS (EI) 448, 450 (M+, 14, 13), 391 (100). HRMS (EI)
Exact mass calcd for C24H17O479Br [M]+: 448.0310. Found: 448.0309.
́
(5) For reviews on tandem reactions, see: (a) Ramon, D. J.; Yus, M.
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ASSOCIATED CONTENT
■
Seayad, J. In Multicomponent Reactions; Zhu, J., Bienayme,
Wiley-VCH: Weinheim, 2005; pp 277. (d) Enders, D.; Grondal, C.;
́
H., Eds.;
S
* Supporting Information
1
Experimental procedures and characterizations, copies of H
Huttl, M. R. M. Angew. Chem., Int. Ed. 2007, 46, 1570. (e) Dondoni,
NMR and 13C NMR of new compounds, and details about the
NMR analysis of the reaction mechanism. This material is
available free of charge via the Internet at http://pubs.acs.org.
̈
A.; Massi, A. Angew. Chem., Int. Ed. 2008, 47, 4638. (f) Zhou, J.
Chem.Asian J. 2010, 4, 422.
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Am. Chem. Soc. 2010, 132, 7540.
AUTHOR INFORMATION
Corresponding Author
*E-mail: jzhou@chem.ecnu.edu.cn.
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■
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The financial support from the 973 program (2011CB808600),
NSFC (20902025, 21172075), Specialized Research Fund for
the Doctoral Program of Higher Education (20090076120007),
Innovation Program of SMEC (12ZZ046), and the Funda-
mental Research Funds for the Central Universities (East China
Normal University 11043) is highly appreciated.
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