Domino One-Pot Process for the Synthesis of Isobenzofuran-1(3 H)-ones via [Cu]-Catalysis Using Water as the Green Solvent

Article abstract of DOI:10.1021/acs.joc.5b00888

An efficient domino one-pot strategy via [Cu]-catalyzed intermolecular "cyanation" of o-bromobenzyl alcohols → in situ intramolecular "nucleophilic attack" → "hydrolysis" is presented, for the synthesis of isobenzofuran-1(3H)-ones. Significantly, the reaction is successfully carried out under environmentally benign conditions, using water as sole green solvent.

Full text of DOI:10.1021/acs.joc.5b00888

Article
pubs.acs.org/joc
Domino One-Pot Process for the Synthesis of Isobenzofuran-
(3H)‑ones via [Cu]-Catalysis Using Water as the Green Solvent
1
Lodi Mahendar and Gedu Satyanarayana*
Department of Chemistry, Indian Institute of Technology Hyderabad, Ordnance Factory Estate Campus, Yeddumailaram-502 205,
Medak District, Telangana, India
*
S Supporting Information
ABSTRACT: An efficient domino one-pot strategy via [Cu]-catalyzed intermolecular “cyanation” of o-bromobenzyl alcohols →
in situ intramolecular “nucleophilic attack” → “hydrolysis” is presented, for the synthesis of isobenzofuran-1(3H)-ones.
Significantly, the reaction is successfully carried out under environmentally benign conditions, using water as sole green solvent.
INTRODUCTION
■
Domino one-pot processes are ideal for the synthesis of
complex molecules by permitting the construction of more than
one chemical bond, as they encompass eliminating tedious
isolations and purification techniques of the intermediate
1
product(s). Hence, such domino processes enable synthetic
chemists to save time, energy and unwanted waste generation.
In this context, transition-metal catalysis plays an important
role for the development of new synthetic methods through the
efficient construction of C−C and C−heteroatom bonds with
2
increasing molecular complexity. In continuation of our
ongoing research interest, for the development of one-pot
3
,4
domino processes under transition-metal catalysis,
we
developed an efficient one-pot domino [Cu]-catalyzed
intermolecular Sonogashira coupling and intramolecular 55-
exo-dig oxacyclization for the synthesis of isobenzofurans.
Herein, we present an efficient domino one-pot method for the
synthesis of isobenzofuran-1(3H)-ones. Notably, unlike estab-
lished methods for the simple cyanation, particularly, using
transition-metal catalyzed cyanation with nontoxic cyanating
agents, we aimed at one-pot cyanation → intramolecular
nucleophilic oxa-cyclization → hydrolysis sequence for the
formation of isobenzofuran-1(3H)-ones. Isobenzofuran-1(3H)-
ones are an important bicyclic lactone present in many natural
Figure 1. Representative examples of isobenzofuran-1(3H)-ones based
drugs and natural products.
nitrile group is ultimately transformed into a carbonyl group
with the aid of the pre-existing internal nucleophile (hydroxyl)
and hydrolysis sequence; (3) the nontoxic cyanide source
assists as a chemical equivalent of highly toxic carbon monoxide
10
(
CO) gas (Scheme 1); (4) most importantly, the reaction
6
operates under environmentally benign conditions using water
as the sole green solvent.
products that exhibit broad spectrum of biological activity and
are versatile building blocks for the synthesis of natural as well
7
Notably, the synthesis of talopram (a norepinephrine
transporter inhibitor) was accomplished using isobenzofuran-
as pharmaceutically important products (Figure 1). In this
context, there were some interesting reports on the synthesis of
8d
8
1(3H)-one 2a as the synthetic precursor (Scheme 1).
isobenzofuran-1(3H)-ones (Scheme 1). Significantly, the
present method has some notable advantages such as (1)
[
Cu]-catalyzed intermolecular cyanation using a nontoxic
Received: April 28, 2015
9
hexacyanoferrate(II) cyanide source; (2) the newly formed
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00888
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Scheme 1. Reported Approach to Norepinephrine
Transporter Inhibitor Talopram from 2a
RESULTS AND DISCUSSION
■
We assumed that the suitably positioned pre-existing
nucleophile (hydroxyl group) of the aryl halide would promote
an internal nucleophilic addition onto the newly formed cyano
group under [Cu]-catalysis in one-pot. The required α,α-
disubstituted (2-bromophenyl)methanols 1a, were synthesized
3
,5
using the established protocol. To identify the optimized
reaction conditions, α,α-dimethyl-(2-bromophenyl)methanol
1
a was screened under different reaction conditions. Beller et
9
al. showed that imidazoles are ideal ligands to improve the
stability and selectivity of the [Cu]-catalyst. Therefore, the
reaction was explored with the imidazole-based ligands.
Gratifyingly, the reaction of 1a with 50 mol % potassium
hexacyanonferrate(II) in the presence of CuI (10 mol
%)/imidazole (L1, 200 mol %), in toluene furnished the
lactone product 2a in good yield (71%, Table 1, entry 1). To
Certainly, the preparation of aryl nitriles is indispensable in
synthetic chemistry, as the cyano group is a ubiquitous
11
functionality in many natural/unnatural organic compounds.
Among the most common classical methods for the preparation
of aryl nitriles are the Rosenmund−von Braun reaction of aryl
12
halides and the Sandmeyer reaction of aryl diazonium salts.
While stoichiometric amounts of various metal cyanides
AgCN, KCN, NaCN, TMSCN and Zn(CN) ] were also
employed as cyanide sources. Very recently, Sudalaia
reported copper mediated one-pot cyanation followed by
cyclization to give lactones/amides (Scheme 2). However, the
[
2
13
13f
Table 1. Optimization One-Pot Cyanation → Internal
Nucleophilic Attack → Hydrolysis Protocol
Scheme 2. Present Study vs Representative Previous
Approaches for the Synthesis of Isobenzofuranones
[
Cu] (10
ligand (200
mol %)
base
(2 equiv)
2a
(%)
a
b
entry
mol %)
solvent
1
2
3
4
5
6
7
8
CuI
L1
L1
L2
L1
toluene
DMF
−
−
−
−
71
64
CuI
c
CuI
toluene
toluene
toluene
toluene
toluene
58
c
CuBr
52
CuSO ·5H O L1
−
63
4
2
c
CuI
CuI
CuI
−
−
L1
Na CO
41
2
3
c
K CO
2
43
3
c
1,4-
dioxane
−
27
9
CuI
L3
L1
L1
toluene
toluene
−
−
−
−
68
d
10
11
12
None
CuI
CuI
SM
96
H O
2
L1 (TBAI 2
equiv)
H O
2
93
a
All reactions were carried out on a 0.5 mmol scale of 1a in 0.5 mL
b
solvent. Isolated yields of chromatographically pure products.
c
Starting material was also recovered along with the product isolation.
d
Starting material was recovered.
main drawback is the use of a highly toxic metal salt (NaCN) as
the source of cyano group. Similarly, Wang et al. reported the
synthesis of only one such example using toxic CuCN as
cyanating agent, during their synthesis of designed PAR-1
check the scope and limitations of the method, these conditions
were applied to 13 analogues as well. Notably, the reaction
scope was quite broad and gave the products 2, in comparable
yields (Table 2). Similarly, the reaction in DMF gave the
product 2a in modest yield (64%, Table 1, entry 2). There was
not much difference in the yield of 2a with 1-methylimidazole
(L2, 200%) (58%, Table 1, entry 3). However, the reaction
with other catalysts such as CuBr and CuSO ·5H O, gave the
1
3g
antagonist.
However, recent developments based on
transitionmetal mediated cyanation have demonstrated wide-
spread application, particularly, those with the use of less/
1
4,15
nontoxic cyanide sources.
disclosed the [Cu]-catalyzed cyanation of aryl bromides.
Notably, Buchwald et al.
4
2
16
product 2a in 52% and 63% yields, respectively (Table 1,
entries 4 and 5). The reaction was inferior in the presence of
the base (Na CO and K CO ) and without ligand(s) (Table 1,
Quite significantly, Beller and co-workers described the
formation of aryl nitriles from aryl bromides using nontoxic
2
3
2
3
17
cyanide source K [Fe(CN) ] under [Cu]-catalysis.
entries 6 and 7). On the other hand, 1,4-dioxane as reaction
4
6
B
DOI: 10.1021/acs.joc.5b00888
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The Journal of Organic Chemistry
Article
Table 2. Scope of One-Pot Cyanation → Internal Nucleophilic Attack → Hydrolysis to Give 2a,b
a
Reaction conditions: 1a−w (0.50 mmol), K Fe(CN) ·3H O (50 mol %), Imidazole (200 mol %), CuI (10 mol %), in 0.5 mL of H O, at 140 °C for
4
6
2
2
b
c
2
4 h. Isolated yields of chromatographically pure products. Reaction conditions: 1 (0.50 mmol), K Fe(CN) ·3H O (50 mol %), Imidazole (200
4 6 2
mol %), CuI (10 mol %), 0.5 mL of toluene, at 140 °C for 24 h; yields in the parentheses are isolated yields of chromatographically pure products.
medium, gave poor yield of the product 2a (Table 1, entry 8).
The ligand 1-butylimidazole (L3, 200%) also proved to be as
good as imidazole (L1), and gave the product 2a in modest
yield (68%, Table 1, entry 9). No progress of the reaction in the
absence of catalyst revealed the essence of [Cu]-catalyst to
drive the reaction (Table 1, entry 10). Gratifyingly, the use of
products 2u and 2v (Table 2). The structures of 2 were
confirmed by single-crystal X-ray diffraction analysis of 2d and
2f (see the Supporting Information). Interestingly, the reaction
was also successful to deliver the system 2w with electron
deactivating fluoro substituent on the aromatic ring as well
(Table 2).
We also presumed that interesting spiro-tricyclic systems
could be obtained by using this protocol. Thus, the tertiary
alcohol 1x was prepared using sonochemically accelerated
Barbier conditions by treating the methyl benzoate 8 with
excess amount of allyl bromide. Unfortunately, the ring closing
metathesis (RCM) reaction did not proceed with Gurbb’s first-
generation catalyst under different conditions. However, RCM
reaction was smooth in the presence of Gurbb’s second-
generation in refluxing benzene and gave the cyclic tertiary
alcohol 1y in excellent yield 93%. Finally, as expected, the spiro-
tricyclic lactone 2x was accomplished in excellent yield 94%,
under standard conditions (Scheme 3).
The scope of the reaction was extended to include aryl
substitution at the benzylic position. To our delight, the
reaction provided consistent yields with those established
systems (Table 2) and led to the formation of analogous
lactone products 4a−s (Table 3). It is noteworthy that this
protocol was quite successful in delivering diversified lactone
products 4a−s containing a quaternary carbon atom bearing
methyl-phenyl, methyl-(3-methoxylphenyl), methyl-(2-thio-
phene), allyl-phenyl and diphenyl substituents apart from the
H O as the sole green solvent proved to be the best and
2
furnished the product 2a in excellent yield (96%, Table 1, entry
11). The use of phase transfer catalyst as an additive, offered no
advantage (93%, Table 1, entry 12). It is worth mentioning that
low catalytic loading (5 mol % of CuI) or with 20 mol % of
K [Fe(CN) ] as cyanating agent or catalytic amount of
4
6
imidazole ligands (20 mol %), always lead to recovery of
starting material 1a along with product 2a formation, for the
standard duration of time (24 h).
Among all reaction conditions screened, the conditions in
entry 11 of Table 1 were found best. Therefore, to check the
scope and generality of the method these optimized conditions
were applied to other 2-bromobenzyl tertiary alcohols 1a−w.
Delightfully, the reaction showed broad substrate scope and
furnished the corresponding cyclic lactones 2a−w in very good
to excellent yields (Table 2). Interestingly, this method was
amenable to 2-bromobenzyl tertiary alcohols 1 with simple to
dense electron-rich 2-bromoaryl ring and variety of alkyl
substituents connected to the benzylic carbon of alcohols 1a−w
(
i.e., gem-dialkyl groups). The reaction was also amenable with
allyl group on the benzylic carbon and gave the corresponding
C
DOI: 10.1021/acs.joc.5b00888
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The Journal of Organic Chemistry
Article
Scheme 3. Approach for the Synthesis of Spiro Cyclic
Isobenzofuranone
CONCLUSIONS
■
[
In conclusion, we have developed an efficient one-pot domino
Cu]-catalyzed intermolecular cyanation → oxa-cyclization →
hydrolysis strategy for the synthesis of isobenzofuran-1(3H)
ones. The present method uses environmentally benign water
as the sole green solvent. Notably, the [Cu]-catalyzed cyanation
was accomplished using cheap and nontoxic cyanide source,
potassium hexacyanoferrate(II) (K [Fe(CN) ]) and eliminates
4
6
the use of highly toxic carbon-monoxide gas to synthesis
products. The reaction was quite successful on wide variety of
2
-bromobenzyl tertiary alcohols.
EXPERIMENTAL SECTION
■
General Considerations. IR spectra were recorded on a FTIR
1
spectrophotometer. H NMR spectra were recorded on 400 MHz
spectrometer at 295 K in CDCl ; chemical shifts (δ ppm) and
3
coupling constants (Hz) are reported in standard fashion with
reference to either internal standard tetramethylsilane (TMS) (δ
0
=
H
.00 ppm) or CHCl3 (δH = 7.25 ppm). 13C NMR spectra were
recorded on 100 MHz spectrometer at RT in CDCl ; chemical shifts
simple to electron rich 2-bromoaryl moiety (Table 3).
However, the reactions of primary and secondary 2-
bromobenzyl alcohols were not successful under the established
conditions. Whereas the presence of N,N′-dimethylethylenedi-
amine (DMEDA), promoted the simple oxidation of alcohol
moiety. It may be a favorable gem-dialkyl effect (Thorpe−
Ingold effect) to assisting this cyclization.
3
(
δ ppm) are reported relative to CHCl [δ = 77.00 ppm (central line
3 C
13
of triplet)]. In the C NMR, the nature of carbons (C, CH, CH , and
CH ) was determined by recording the DEPT-135 spectra and is given
in parentheses and noted as s = singlet (for C), d = doublet (for CH),
t = triplet (for CH ) and q = quartet (for CH ). In the H NMR, the
following abbreviations were used throughout: s = singlet, d = doublet,
t = triplet, q = quartet, qui = quintet, m = multiplet and br s. = broad
2
3
1
2
3
Table 3. Scope of One-Pot Cyanation → Internal Nucleophilic Attack → Hydrolysis to Give 4a,b
a
Reaction conditions: 4a−s (0.50 mmol), K Fe(CN) ·3H O (50 mol %), Imidazole (200 mol %), CuI (10 mol %), in 0.5 mL of H O, at 140 °C for
4
6
2
2
b
2
4 h. Isolated yields of chromatographically pure products.
D
DOI: 10.1021/acs.joc.5b00888
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The Journal of Organic Chemistry
Article
singlet. The assignment of signals was confirmed by H, 13C CPD
(
1
(dd, 1H, J = 7.8 and 2.0 Hz), 7.57 (dd, 1H, J = 7.8 and 2.0 Hz), 7.28
(dd, 1H, J = 7.8 and 1.5 Hz), 7.08 (ddd, 1H, J = 7.8, 7.3, and 1.5 Hz),
5.65−5.45 (m, 2H), 5.20−4.95 (m, 4H), 3.40−3.25 (m, 2H), 2.68−
carbon proton decoupled), and DEPT spectra. High-resolution mass
spectra (HR-MS) were recorded using Q-TOF multimode source.
Melting points were determined on an electrothermal melting point
apparatus and are uncorrected. Benzaldehydes, immidazole, aryl
halides, methyl iodide, bromoethane, Mg metal and Na SO were
commercially available (local made) used without further purification,
CuI, K [Fe(CN) ]·3H O, Cs CO purchased from Sigma-Aldrich. All
dry solvents were used; diethyl ether, toluene and THF were dried
over sodium metal, and DCM and DMF were dried over calcium
hydride.
2.55 (m, 2H), 2.50 (br. s, 1H) ppm; 13C NMR (CDCl , 100 MHz) δ =
3
143.5 (C ), 134.9 (CH), 133.4 (2C, 2 × CH), 129.4 (CH), 128.6
q
(CH), 127.2 (CH), 119.6 (C ), 118.9 (2C, 2 × CH ), 76.1 (C ), 43.5
2
4
q
2
q
−1
(2C, 2 × CH ) ppm; IR (MIR-ATR, 4000−600 cm ) ν = 3545,
2977, 1638, 1432, 1340, 1284, 1149, 1018, 915, 739, 693 cm ; HR-
MS (ESI+) m/z calculated for [C H Br] = [(M + H) − H O]
2
max
−1
4
6
2
2
3
79
14
+
+
13
2
249.0273, found 249.0268.
1-(2-Bromophenyl)cyclopent-3-enol (1y). To a magnetically
stirred solution of the diene 1x (200 mg, 0.74 mmol) in anhydrous
benzene (15 mL), a solution of second-generation Grubbs’s catalyst
(19 mg, 3 mol %) in anhydrous benzene (15 mL) was added, and the
reaction mixture was refluxed for 30 min. Evaporation of the solvent
under reduced pressure and purification of the residue on a silica-gel
All the solvents (diethyl ether, THF, DCM, DMF) are commercially
available (LR grade). All small scale dry reactions were carried out
using standard syringe-septum technique. Reactions were monitored
by TLC on silica gel using a combination of petroleum ether and ethyl
acetate as eluents. Solvents were distilled prior to use; petroleum ether
with a boiling range of 40 to 60 °C was used. Acme’s silica gel (60−
column using ethyl acetate−hexane (1:9) as eluent furnished the
1
1
20 mesh) was used for column chromatography (approximately 20 g
tertiary alcohol 1y (166 mg, 93%) as colorless oil. H NMR (CDCl
3
per one gram of crude material).
400 MHz) δ = 7.86 (dd, 1H, J = 7.8 and 1.5 Hz), 7.58 (dd, 1H, J = 7.8
and 1.5 Hz), 7.32 (ddd, 1H, J = 8.8, 7.3, and 1.0 Hz), 7.11 (ddd, 1H, J
= 7.8, 7.3, and 1.5 Hz), 5.82 (s, 2H), 3.39 (d, 2H, J = 16.6 Hz), 2.59
2
-(2-Bromophenyl)-3-methylbutan-2-ol (1t). To a cold (0 °C),
magnetically stirred solution of a ketone 3a (500 mg, 2.20 mmol) in
(d, 2H, J = 16.6 Hz) ppm. 13C NMR (CDCl , 100 MHz) δ = 144.3
dry ether (30 mL) was added methylmagnesium iodide (8.81 mmol)
3
[
(
prepared from magnesium (211 mg, 8.81 mmol) and methyl iodide
1.250 g, 8.81 mmol) in 10 mL of dry ether]. The reaction mixture
(C ), 134.6 (CH), 128.5 (CH), 128.2 (2C, 2 × CH), 127.6 (CH),
q
127.2 (CH), 121.0 (C ), 81.9 (C ), 48.8 (2C, 2 × CH ) ppm. IR
q
q
2
−1
was stirred at −10 to 0 °C for 3 h. It was then poured into saturated
(MIR-ATR, 4000−600 cm ) ν = 3450, 2930, 1613, 1457, 1332,
1282, 1142, 1031, 908, 767, 694 cm . HR-MS (ESI+) m/z calculated
for [C H Br] = [(M + H) − H O] 220.996, found 220.9954.
max
−1
aqueous NH Cl solution and extracted with ethyl acetate (3 × 15).
4
79
+
+
The ethyl acetate extract was dried with Na SO . Evaporation of the
2
4
11 10
2
solvent and purification of the residue over a silica gel column using
petroleum ether/ethyl acetate as eluent furnished the tertiary alcohol
(2-Bromophenyl)(3-methoxyphenyl)phenylmethanol (3s). To a
cold (0 °C), magnetically stirred solution of a o-bromobenzophenone
5b (1.72 mmol) in dry THF (2 mL) was added phenylmagnesium
bromide (6.88 mmol) [prepared from magnesium (6.88 mmol) and
bromobenzene (6.88 mmol) and a catalytic amount of iodine in 10 mL
of dry THF or dry ether]. The reaction mixture was stirred at 0 °C to
room temperature for 3 h. It was then poured into saturated aqueous
1
at as colorless oil 97% yield (502 mg): [TLC (petroleum ether/ethyl
1
acetate 9:1, R (3a) = 0.50, R (1at) = 0.40, UV detection]. H NMR
f
f
(
CDCl 400 MHz) δ = 7.63 (dd, 1H, J = 7.8 and 2.0 Hz), 7.53 (dd,
3
1
(
1
H, J = 7.8 and 2.0 Hz), 7.25 (ddd, 1H, J = 8.8, 7.3, and 1.5 Hz), 7.04
ddd, 1H, J = 8.8, 7.3, and 1.5 Hz), 2.90−2.74 (m, 1H), 2.36 (br. s,
H), 1.63 (s, 3H), 0.88 (d, 3H, J = 6.8 Hz), 0.75 (d, 3H, J = 6.8 Hz)
NH Cl solution and extracted with ethyl acetate (3 × 15 mL). The
4
13
ppm. C NMR (CDCl , 100 MHz) δ = 145.8 (C ), 135.1 (CH),
combined organic layers were dried (Na SO ) and concentrated in
3
q
2
4
1
28.6 (CH), 128.2 (CH), 127.1 (CH), 119.8 (C ), 78.0 (C ), 33.8
vacuo. The crude tertiary alcohol 3s was purified by column
chromatography on silica using petroleum ether/ethyl acetate as
eluent furnished the tertiary alcohol 3s as colorless viscous liquid 77%
q
q
(
4
9
CH ), 24.2 (CH), 17.1 (CH ), 17.0 (CH ) ppm. IR (MIR-ATR,
3
3
3
−1
000−600 cm ) ν = 3432, 2979, 2930, 1336, 1286, 1132, 1041,
−1
max
05, 764, 695 cm . HR-MS (ESI+) m/z calculated for [C H
yield (492 mg): [TLC (petroleum ether/ethyl acetate 9:1, R (5b) =
11
15
f
7
9
+
+
1
BrOK] = [M + K] 282.9918, found 282.9915.
0.50, R (3s) = 0.45, UV detection]. H NMR (CDCl 400 MHz) δ =
f
3
1
-(2-Bromo-4,5-dimethoxyphenyl)-1-phenylbut-3-en-1-ol (3p).
7.65−7.59 (m, 1H), 7.38−7.26 (m, 3H), 7.27−7.19 (m, 3H), 7.16−
7.10 (m, 2H), 6.90 (dd, 1H, J = 2.4 and 1.5 Hz), 6.84 (dd, 1H, J = 2.4
and 2.4 Hz), 6.76 (d, 1H, J = 6.8 Hz), 6.74−6.67 (m, 1H), 4.57 (s,
1H), 3.75 (s, 3H) ppm; 13C NMR (CDCl , 100 MHz) δ = 159.4 (C ),
Allyl bromide (0.60 mL, 6.52 mmol) in THF (1 mL) was added
dropwise to a sonicated suspension of zinc dust (423 mg, 6.52 mmol)
in THF (2 mL) at room temperature, and the mixture was further
sonicated for 30 min, and then ortho-bromobenzophenone 5c (500
mg, 1.62 mmol) in THF (3 mL) was added and continued sonication
at room temperature for 2 h. Progress of the reaction was monitored
by TLC. The reaction mixture was quenched by addition of aqueous
3
q
147.2 (C ), 145.4 (C ), 144.9 (C ), 134.8 (CH), 131.9 (CH), 129.2
q
q
q
(CH), 128.8 (CH), 128.0 (2 × CH), 127.8 (2 × CH), 127.4 (CH),
126.9 (CH), 122.9 (C ), 120.5 (CH), 113.7 (CH), 112.7 (CH), 83.1
q
−1
(C ), 55.1 (CH ) ppm; IR (MIR-ATR, 4000−600 cm ) ν = 3541,
3043, 1553, 1442, 1358, 1265, 1153, 1024, 890, 756, 698 cm ; HR-
MS (ESI+) m/z calculated for [C H BrO] = [(M + H) − H O]
351.0379, found 351.0376.
q
3
max
−1
NH Cl solution and extracted with ethyl acetate (3 × 15 mL). The
4
79
+
+
collected organic layers were dried (Na SO ) and concentrated in
2
4
20 16
2
vacuo. Purification of the residue on a silica gel column
chromatography (petroleum ether/ethyl acetate) as eluent furnished
homoallylic alcohol 3p as colorless solid 96% yield (546 mg): mp 82−
General Procedure (For the Synthesis of Benzofuranones) (2
and 4). In an oven-dried Schlenk tube 2-bromobenzyl tertiary alcohol
8
(
1
1
(
1
1
×
1
(
1
4 °C; [TLC (petroleum ether/ethyl acetate 9:1, R (5c) = 0.50, R
1 (0.5 mmol), finely ground K [Fe(CN) ]·3H O (0.25 mmol), copper
4 6 2
f
f
1
3p) = 0.50, UV detection]. H NMR (CDCl 400 MHz) δ = 7.38 (s,
H), 7.30−7.15 (m, 5H), 6.94 (s, 1H), 5.78−5.60 (m, 1H), 5.12 (dd,
H, J = 17.2 and 1.4 Hz), 5.05 (d, 1H, J = 10.2 Hz), 3.87 (s, 3H), 3.81
iodide (0.05 mmol), imidazole (1 mmol) and solvent (toluene or
distilled water) (0.5 mL) were added. The resulting reaction mixture
was stirred at 140 °C for 24 h. The progress of the reaction was
monitored by TLC. After completion of reaction, the reaction mixture
was allowed to cool to room temperature, then diluted with (10 mL)
ethyl acetate, and water was added followed by extraction with ethyl
acetate. The organic layers were dried (Na SO ) and concentrated in
3
s, 3H), 3.42 (dd, 1H, J = 14.2 and 6.6 Hz), 3.06 (br. s, 1H), 2.98 (dd,
H, J = 14.2 and 7.3 Hz) ppm; 13C NMR (CDCl , 100 MHz) δ =
3
48.3 (C ), 147.6 (C ), 145.7 (C ), 136.3 (C ), 133.9 (CH), 128.0 (2
CH), 127.1 (CH), 126.5 (2 × CH), 118.6 (CH ), 117.7 (CH),
2
12.6 (CH), 111.9 (C ), 78.0 (C ), 56.1 (CH ), 44.7 (CH ) ppm; IR
MIR-ATR, 4000−600 cm ) ν = 3516, 2933, 1598, 1499, 1321,
208, 1149, 1030, 770, 698 cm ; HR-MS (ESI+) m/z calculated for
q
q
q
q
2
4
vacuo. Purification of the residue by silica gel column chromatography
using petroleum ether/ethyl acetate as the eluent furnished the
benzofuranone 2.
q
q
3
2
−1
max
−
1
79
+
+
[
C H BrO ] = [(M + H) − H O] 345.0485, found 345.0497.
3,3-Dimethyl-2-benzofuran-1(3H)-one (2a). This compound was
prepared according to the GP and isolated as colorless liquid 96% yield
(101 mg): [TLC (petroleum ether/ethyl acetate 9:1, R (1a) = 0.50, R
18
18
2
2
4
-(2-Bromophenyl)hepta-1,6-dien-4-ol (1x). This compound was
prepared according to the 3p and isolated as colorless liquid 92% yield
571 mg): [TLC (petroleum ether/ethyl acetate 9:1, R (8) = 0.50, R
1x) = 0.60, UV detection]. H NMR (CDCl 400 MHz) δ = 7.68
f
f
1
(
(
(2a) = 0.30, UV detection]. H NMR (CDCl 400 MHz) δ = 7.85 (d,
f
f
3
1
1H, J = 7.8 Hz), 7.65 (dd, 1H, J = 8.8 and 7.3 Hz), 7.49 (dd, 1H, J =
3
E
DOI: 10.1021/acs.joc.5b00888
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
8
.8 and 7.3 Hz), 7.39 (d, 1H, J = 7.3 Hz), 1.65 (s, 6H) ppm. 13C NMR
CDCl , 100 MHz) δ = 169.8 (C ), 155.0 (C ), 134.1 (CH), 128.9
pale yellow colored solid 94% yield (119 mg): mp 58−60 °C; [TLC
(petroleum ether/ethyl acetate 6:4, R (1g) = 0.50, R (2g) = 0.30, UV
(
(
3
q
q
f
f
1
CH), 125.7 (CH), 125.3 (C ), 120.6 (CH), 85.4 (C ), 27.3 (2C, 2 ×
detection]. H NMR (CDCl 400 MHz) δ = 6.52 (s, 1H), 4.11 (s,
q
q
3
−1
13
CH ) ppm. IR (MIR-ATR, 4000−600 cm ) ν = 2979, 2930, 1750,
1
3H), 3.94 (s, 3H), 3.84 (s, 3H), 1.59 (s, 6H) ppm. C NMR (CDCl3,
3
max
−1
614, 1467, 1336, 1286, 1132, 1041, 905, 764, 695 cm . HR-MS (ESI
) m/z calculated for [C H O Na] = [M + Na] 185.0573, found
100 MHz) δ = 167.2 (C ), 159.5 (C ), 152.9 (C ), 152.2 (C ), 141.5
q
q
q
q
+
+
+
1
(C ), 109.7 (C ), 98.2 (CH), 83.5 (C ), 62.2 (CH ), 61.3 (CH ), 56.4
10
10
2
q q q 3 3
−1
85.0572.
(CH ), 27.5 (2C, 2 × CH ) ppm. IR (MIR-ATR, 4000−600 cm )
−1
3
3
5
-(Benzyloxy)-3,3-dimethyl-2-benzofuran-1(3H)-one (2b). This
ν
= 2930, 1745, 1598, 1474, 1346, 1253, 1133, 1083, 930, 668 cm .
max
HR-MS (ESI+) m/z calculated for [C H O Na] = [M + Na]+
+
compound was prepared according to the GP and isolated as colorless
13 16 5
crystalline solid 94% yield (127 mg): mp 148−150 °C; [TLC
275.0890, found 275.0889.
3-Ethyl-3-methyl-2-benzofuran-1(3H)-one (2h). This compound
was prepared according to the GP and isolated as pale yellow colored
(
petroleum ether/ethyl acetate 8:2, R (1b) = 0.60, R (2b) = 0.40, UV
f
f
1
detection]. H NMR (CDCl 400 MHz) δ = 7.77 (d, 1H, J = 8.3 Hz),
3
7
2
.50−7.30 (m, 5H), 7.07 (dd, 1H, J = 8.3 and 2.4 Hz), 6.89 (d, 1H, J =
oil 95% yield (85 mg): [TLC (petroleum ether/ethyl acetate 9:1, R
f
13
1
.4 Hz), 5.14 (s, 2H), 1.62 (s, 6H) ppm. C NMR (CDCl , 100
(1h) = 0.50, R (2h) = 0.30, UV detection]. H NMR (CDCl 400
3
f
3
MHz) δ = 169.5 (C ), 163.8 (C ), 157.6 (C ), 135.7 (C ), 128.7 (2C,
MHz) δ = 7.83 (d, 1H, J = 7.3 Hz), 7.64 (dd, 1H, J = 8.8 and 7.3 Hz),
7.48 (dd, 1H, J = 8.8 and 7.3 Hz), 7.34 (d, 1H, J = 7.3 Hz), 2.13−1.97
(m, 1H), 1.95−1.83 (m, 1H), 1.61 (s, 3H),0.72 (t, 3H, J = 7.3 Hz)
q
q
q
q
2
1
× CH), 128.4 (CH), 127.6 (2C, 2 × CH), 127.4 (CH), 117.8 (Cq),
16.4 (CH), 106.1 (CH), 84.5 (C ), 70.6 (CH ), 27.3 (2C, 2 × CH )
q
2
3
−1
13
ppm. IR (MIR-ATR, 4000−600 cm ) ν = 2977, 1742, 1606, 1487,
ppm. C NMR (CDCl , 100 MHz) δ = 170.1 (C ), 153.6 (C ), 134.0
max
3
q
q
−
1
1306, 1227, 1160, 1039, 908, 743, 694 cm . HR-MS (ESI+) m/z
(CH), 128.8 (CH), 126.1 (C ), 125.6 (CH), 120.8 (CH), 88.0 (C ),
q
q
+
+
calculated for [C H O K] = [M + K] 307.0731, found 307.0732.
32.8 (CH ), 25.6 (CH ), 7.8 (CH ) ppm. IR (MIR-ATR, 4000−600
−1
17
16
3
2
3
3
5
-Methoxy-3,3-dimethyl-2-benzofuran-1(3H)-one (2c). This com-
pound was prepared according to the GP and isolated as colorless solid
0% yield (94 mg): mp 56−58 °C; [TLC (petroleum ether/ethyl
cm ) ν = 2974, 1749, 1614, 1465, 1345, 1286, 1129, 1060, 920,
max
−1
+
761, 695 cm . HR-MS (ESI+) m/z calculated for [C H O ] = [M
+ H] 177.0910, found 177.0907.
11
13
2
+
9
1
acetate 8:2, R (1c) = 0.50, R (2c) = 0.30, UV detection]. H NMR
5-(Benzyloxy)-3-ethyl-3-methyl-2-benzofuran-1(3H)-one (2i).
This compound was prepared according to the GP and isolated as
colorless solid 92% yield (131 mg): mp 88−90 °C; [TLC (petroleum
ether/ethyl acetate 8:2, R (1i) = 0.60, R (2i) = 0.40, UV detection].
f
f
(
CDCl 400 MHz) δ = 7.76 (d, 1H, J = 8.3 Hz), 6.99 (dd, 1H, J = 8.3
3
and 2.4 Hz), 6.79 (d, 1H, J = 2.4 Hz), 3.89 (s, 3H), 1.62 (s, 6H) ppm.
1
3
C NMR (CDCl , 100 MHz) δ = 169.5 (C ), 164.7 (C ), 157.7 (C ),
3
q
q
q
f
f
1
1
27.4 (CH), 117.6 (C ), 115.9 (CH), 104.9 (CH), 84.5 (C ), 55.8
H NMR (CDCl 400 MHz) δ = 7.77 (d, 1H, J = 8.3 Hz), 7.50−7.30
(m, 5H), 7.07 (dd, 1H, J = 8.3 and 2.0 Hz), 6.84 (d, 1H, J = 2.0 Hz),
3
q
q
−1
(
ν
CH ), 27.3 (2C, 2 × CH ) ppm. IR (MIR-ATR, 4000−600 cm )
max
3
3
= 2977, 1743, 1603, 1489, 1309, 1232, 1161, 1040, 913, 787, 696
5.14 (s, 2H), 2.10−1.95 (m, 1H), 1.92−1.78 (m, 1H), 1.59 (s, 3H),
−1
+
+
13
cm . HR-MS (ESI+) m/z calculated for [C H O ] = [M + H]
0.74 (t, 3H, J = 7.3 Hz) ppm. C NMR (CDCl , 100 MHz) δ = 169.8
11
13
3
3
1
93.0859, found 193.0858.
-(Benzyloxy)-6-methoxy-3,3-dimethyl-2-benzofuran-1(3H)-one
2d). This compound was prepared according to the GP and isolated
as yellow colored solid 91% yield (136 mg): mp 124−126 °C; [TLC
petroleum ether/ethyl acetate 8:2, R (1d) = 0.40, R (2d) = 0.30, UV
(C ), 163.8 (C ), 156.3 (C ), 135.7 (C ), 128.7 (2C, 2 × CH), 128.4
q
q
q
q
5
(CH), 127.6 (2C, 2 × CH), 127.3 (CH), 118.8 (C ), 116.3 (CH),
q
(
106.3 (CH), 87.1 (C ), 70.6 (CH ), 32.8 (CH2), 25.7 (CH ), 7.8
q
2
3
−1
(CH ) ppm. IR (MIR-ATR, 4000−600 cm ) ν
1590, 1462, 1365, 1245, 1102, 1023, 907, 754, 690 cm . HR-MS (ESI
+) m/z calculated for [C H O Na] = [M + Na] 305.1148, found
= 2990, 1753,
3
max
−1
(
f
f
1
+
+
detection]. H NMR (CDCl 400 MHz) δ = 7.44 (d, 2H, J = 6.8 Hz),
3
18 18 3
7
1
.39 (dd, 2H, J = 7.3 and 6.8 Hz), 7.34 (d, 1H, J = 6.8 Hz), 7.26 (s,
H), 6.79 (s, 1H), 5.21 (s, 2H), 3.91 (s, 3H), 1.57 (s, 6H) ppm.
305.1152.
13
C
3-Ethyl-5-methoxy-3-methyl-2-benzofuran-1(3H)-one (2j). This
compound was prepared according to the GP and isolated as pale
yellow colored viscus oil 94% yield (97 mg): [TLC (petroleum ether/
NMR (CDCl , 100 MHz) δ = 170.0 (C ), 153.9 (C ), 150.8 (C ),
3
q
q
q
1
2
49.3 (C ), 135.7 (C ), 128.7 (2C, 2 × CH), 128.3 (CH), 127.4 (2C,
q q
1
× CH), 117.4 (C ), 106.5 (CH), 104.2 (CH), 84.6 (C ), 71.2
ethyl acetate 8:2, R (1j) = 0.50, R (2j) = 0.30, UV detection]. H
q
q
f
f
(
6
9
CH ), 56.3 (CH ), 27.3 (2C, 2 × CH ) ppm. IR (MIR-ATR, 4000−
NMR (CDCl 400 MHz) δ = 7.74 (d, 1H, J = 8.8 Hz), 6.98 (dd, 1H, J
2
3
3
3
−
1
00 cm ) ν = 2926, 1741, 1600, 1497, 1310, 1200, 1175, 1034,
= 8.8 and 2.0 Hz), 6.74 (d, 1H, J = 2.0 Hz), 3.88 (s, 3H), 2.10−1.95
max
−
1
09, 803, 697 cm . HR-MS (ESI+) m/z calculated for
(m, 1H), 1.93−1.78 (m, 1H), 1.59 (s, 3H), 0.73 (t, 3H, J = 7.8 Hz)
+
+
13
[
C H O Na] = [M + Na] 321.1097, found 321.1083.
ppm. C NMR (CDCl , 100 MHz) δ = 169.9 (C ), 164.7 (C ), 156.3
18
18
4
3
q
q
7
,7-Dimethylfuro[3,4-f ][1,3]benzodioxol-5(7H)-one (2e). This
(C ), 127.2 (CH), 118.5 (C ), 115.8 (CH), 105.1 (CH), 87.1 (C ),
q
q
q
compound was prepared according to the GP and isolated as colorless
solid 94% yield (98 mg): mp 182−184 °C; [TLC (petroleum ether/
ethyl acetate 8:2, R (1e) = 0.60, R (2e) = 0.40, UV detection]. H
55.8 (CH ), 32.8 (CH ), 25.7 (CH ), 7.7 (CH ) ppm. IR (MIR-ATR,
3 2 3 3
−
1
4000−600 cm ) ν = 2974, 1744, 1604, 1490, 1320, 1225, 1147,
max
1
−1
f
f
1031, 923, 784, 696 cm . HR-MS (ESI+) m/z calculated for
[C H O ] = [M + H] 207.1016, found 207.1018.
+
+
NMR (CDCl 400 MHz) δ = 7.14 (s, 1H), 6.73 (s, 1H), 6.09 (s, 2H),
3
12 15 3
13
1
1
.59 (s, 6H) ppm. C NMR (CDCl , 100 MHz) δ = 169.3 (C ),
5-(Benzyloxy)-3-ethyl-6-methoxy-3-methyl-2-benzofuran-1(3H)-
one (2k). This compound was prepared according to the GP and
isolated as brown colored solid 93% yield (146 mg): mp 76−78 °C;
[TLC (petroleum ether/ethyl acetate 8:2, R (1k) = 0.60, R (2k) =
3
q
53.6 (C ), 151.8 (C ), 149.0 (C ), 118.8 (C ), 104.3 (CH), 102.5
q
q
q
q
(
CH), 100.6 (CH ), 84.4 (C ), 27.3 (2C, 2 × CH ) ppm. IR (MIR-
2 q 3
1
−
ATR, 4000−600 cm ) ν = 2932, 1746, 1598, 1489, 1274, 1131,
max
f
f
−
1
1
1028, 909, 729, 693 cm . HR-MS (ESI+) m/z calculated for
0.40, UV detection]. H NMR (CDCl 400 MHz) δ = 7.43 (d, 2H, J =
3
+
+
[
C H O ] = [M + H] 207.0652, found 207.0650.
6.8 Hz), 7.38 (dd, 2H, J = 7.3 and 6.8 Hz), 7.33 (d, 1H, J = 6.8 Hz),
7.26 (s, 1H), 6.73 (s, 1H), 5.21 (s, 2H), 3.92 (s, 3H), 2.04−1.92 (m,
1H), 1.85−1.73 (m, 1H), 0.54 (s, 3H), 0.68 (t, 3H, J = 7.3 Hz) ppm.
11
11
4
5
,6-Dimethoxy-3,3-dimethyl-2-benzofuran-1(3H)-one (2f). This
compound was prepared according to the GP and isolated as brown
colored solid 93% yield (104 mg): mp 142−144 °C; [TLC (petroleum
ether/ethyl acetate 7:3, R (1f) = 0.50, R (2f) = 0.30, UV detection].
13
C NMR (CDCl , 100 MHz) δ = 170.3 (C ), 153.7 (C ), 150.7 (C ),
3
q
q
q
f
f
147.8 (C ), 135.7 (C ), 128.7 (2C, 2 × CH), 128.3 (CH), 127.4 (2C,
q
q
1
H NMR (CDCl 400 MHz) δ = 7.24 (s, 1H), 6.75 (s, 1H), 3.97 (s,
2 × CH), 118.3 (C ), 106.5 (CH), 104.6 (CH), 87.2 (C ), 71.2
3
q
q
13
3H), 3.91 (s, 3H), 1.62 (s, 6H) ppm. C NMR (CDCl , 100 MHz) δ
(CH ), 56.3 (CH ), 32.8 (CH ), 25.7 (CH ), 7.8 (CH ) ppm. IR
2 3 2 3 3
3
−
1
=
170.0 (C ), 154.8 (C ), 150.2 (C ), 149.6 (C ), 117.1 (C ), 106.2
(MIR-ATR, 4000−600 cm ) ν = 2922, 1745, 1601, 1463, 1355,
q
q
q
q
q
max
−1
(
CH), 102.1 (CH), 84.6 (C ), 56.4 (CH ), 56.3 (CH ), 27.4 (2C, 2 ×
1285, 1170, 1043, 941, 722, 665 cm . HR-MS (ESI+) m/z calculated
for [C H O Na] = [M + Na] 335.1254, found 335.1256.
q
3
3
−
1
+
+
CH ) ppm. IR (MIR-ATR, 4000−600 cm ) ν = 2927, 1741, 1600,
3
max
19 20 4
−
1
1
497, 1310, 1200, 1175, 1024, 909, 730, 697 cm . HR-MS (ESI+) m/
7-Ethyl-7-methylfuro[3,4-f ][1,3]benzodioxol-5(7H)-one (2l). This
compound was prepared according to the GP and isolated as colorless
solid 93% yield (104 mg): mp 116−118 °C; [TLC (petroleum ether/
ethyl acetate 8:2, R (1l) = 0.50, R (2l) = 0.30, UV detection]. 1H
+
+
z calculated for [C H O K] = [M + K] 261.0524, found 261.0523.
12
14
4
5
,6,7-Trimethoxy-3,3-dimethyl-2-benzofuran-1(3H)-one (2g).
This compound was prepared according to the GP and isolated as
f
f
F
DOI: 10.1021/acs.joc.5b00888
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
NMR (CDCl 400 MHz) δ = 7.15 (s, 1H), 6.69 (s, 1H), 6.09 (s, 2H),
105.0 (CH), 90.0 (C ), 71.2 (CH ), 56.2 (CH ), 31.3 (2C, 2 × CH ),
3
q
2
3
2
−1
2
7
.10−1.97 (m, 1H), 1.90−1.75 (m, 1H), 1.57 (s, 3H), 0.74 (t, 3H, J =
7.4 (2C, 2 × CH ) ppm. IR (MIR-ATR, 4000−600 cm ) ν = 2922,
3
max
.3 Hz) ppm. 13C NMR (CDCl , 100 MHz) δ = 169.6 (C ), 153.6
1746, 1600, 1499, 1357, 1282, 1171, 1040, 941, 737, 697 cm . HR-
MS (ESI+) m/z calculated for [C H O ] = [M + H] 327.1591,
−1
3
q
+
+
(
C ), 150.4 (C ), 148.9 (C ), 119.7 (C ), 104.3 (CH), 102.5 (CH),
q
q
q
q
20 23 4
1
00.8 (CH ), 87.0 (C ), 32.8 (CH ), 25.8 (CH ), 7.8 (CH ) ppm. IR
found 327.1594.
2
q
2
3
3
−1
(
1
MIR-ATR, 4000−600 cm ) ν = 2977, 1732, 1611, 1476, 1308,
7,7-Diethylfuro[3,4-f ][1,3]benzodioxol-5(7H)-one (2r). This com-
pound was prepared according to the GP and isolated as brown
colored solid 90% yield (106 mg): mp 96−98 °C; [TLC (petroleum
ether/ethyl acetate 8:2, R (1r) = 0.50, R (2r) = 0.30, UV detection].
max
−
1
230, 1095, 943, 787, 625 cm . HR-MS (ESI+) m/z calculated for
+
+
[
C H O ] = [M + H] 221.0808, found 221.0809.
12 13 4
3
-Ethyl-5,6-dimethoxy-3-methyl-2-benzofuran-1(3H)-one (2m).
f
f
1
This compound was prepared according to the GP and isolated as
H NMR (CDCl 400 MHz) δ = 7.15 (s, 1H), 6.56 (s, 1H), 6.05 (s,
3
colorless solid 96% yield (113 mg): mp 128−130 °C; [TLC
2H), 2.05−1.88 (m, 2H), 1.85−1.66 (m, 2H), 0.68 (t, 3H, J = 7.3 Hz)
ppm. 13C NMR (CDCl , 100 MHz) δ = 167.9 (C ), 151.9 (C ), 148.6
(
petroleum ether/ethyl acetate 7:3, R (1m) = 0.50, R (2m) = 0.40,
f f
UV detection]. H NMR (CDCl 400 MHz) δ = 7.23 (s, 1H), 6.70 (s,
3
q
q
1
3
(C ), 144.7 (C ), 124.0 (C ), 103.0 (CH), 102.1 (CH), 100.8 (CH ),
q
q
q
2
1
1
1
H), 3.96 (s, 3H), 3.91 (s, 3H), 2.10−1.97 (m, 1H), 1.90−1.78 (m,
91.6 (C ), 32.0 (CH ), 7.5 (CH ) ppm. IR (MIR-ATR, 4000−600
−1
q
2
3
13
H), 1.59 (s, 3H), 0.72 (t, 3H, J = 7.3 Hz) ppm. C NMR (CDCl ,
cm ) ν = 2987, 1750, 1590, 1475, 1374, 1275, 1120, 1025, 908,
3
max
−1
+
00 MHz) δ = 170.3 (C ), 154.8 (C ), 150.2 (C ), 148.1 (C ), 118.0
750, 690 cm . HR-MS (ESI+) m/z calculated for [C H O ] = [M
13 15 4
+ H] 235.0965, found 235.0966.
q
q
q
q
+
(
C ), 106.1 (CH), 102.2 (CH), 87.2 (C ), 56.3 (CH ), 56.2 (CH ),
q
q
3
3
3
2.8 (CH ), 25.8 (CH ), 7.8 (CH ) ppm. IR (MIR-ATR, 4000−600
3,3-Diethyl-5,6-dimethoxy-2-benzofuran-1(3H)-one (2s). This
compound was prepared according to the GP and isolated as yellow
colored viscous liquid 93% yield (116 mg): [TLC (petroleum ether/
2
3
3
−1
cm ) ν = 2927, 1738, 1600, 1498, 1324, 1229, 1105, 1029, 922,
8
max
−1
+
04, 667 cm . HR-MS (ESI+) m/z calculated for [C H O Na] =
13 16 4
+
1
[
M + Na] 259.0941, found 259.0939.
-Ethyl-5,6,7-trimethoxy-3-methyl-2-benzofuran-1(3H)-one (2n).
ethyl acetate 7:3, R (1s) = 0.60, R (2s) = 0.40, UV detection]. H
f
f
3
NMR (CDCl 400 MHz) δ = 7.25 (s, 1H), 6.66 (s, 1H), 3.96 (s, 3H),
3
This compound was prepared according to the GP and isolated as
yellow colored viscous liquid 95% yield (125 mg): [TLC (petroleum
ether/ethyl acetate 6:4, R (1n) = 0.50, R (2n) = 0.40, UV detection].
3.92 (s, 3H), 2.15−1.97 (m, 2H), 1.94−1.76 (m, 2H), 0.69 (s, 6H)
ppm. 13C NMR (CDCl , 100 MHz) δ = 170.7 (C ), 154.8 (C ), 150.2
3
q
q
f
f
(C ), 146.3 (C ), 119.2 (C ), 106.0 (CH), 102.4 (CH), 90.1 (C ),
q
q
q
q
1
H NMR (CDCl 400 MHz) δ = 6.47 (s, 1H), 4.12 (s, 3H), 3.93 (s,
56.4 (CH ), 56.2 (CH ), 31.4 (2C, 2 × CH ), 7.5 (2C, 2 × CH ) ppm.
3 3 2 3
1
3
−
3
3
1
H), 3.85 (s, 3H), 2.10−1.97 (m, 1H), 1.88−1.75 (m, 1H), 1.57 (s,
IR (MIR-ATR, 4000−600 cm ) ν = 2924, 1741, 1601, 1499, 1354,
max
H), 0.76 (t, 3H, J = 7.3 Hz) ppm. 13C NMR (CDCl , 100 MHz) δ =
1284, 1170, 1042, 940, 804, 665 cm . HR-MS (ESI+) m/z calculated
for [C H O Na] = [M + Na] 273.1097, found 273.1098.
−1
3
+
+
67.6 (C ), 159.5 (C ), 152.2 (C ), 151.6 (C ), 141.5 (C ), 110.7
q
q
q
q
q
14 18 4
(
3
C ), 98.2 (CH), 86.1 (C ), 62.3 (CH ), 61.4 (CH ), 56.4 (CH ),
3-Isopropyl-3-methyl-2-benzofuran-1(3H)-one (2t). This com-
pound was prepared according to the GP and isolated as colorless
q
q
3
3
3
3.0 (CH ), 25.9 (CH ), 7.8 (CH ) ppm. IR (MIR-ATR, 4000−600
2
3
3
−
1
cm ) ν = 2977, 1732, 1611, 1477, 1308, 1230, 1095, 943, 881, 628
cm . HR-MS (ESI+) m/z calculated for [C H O Na] = [M + Na]
oil 89% yield (79 mg): [TLC (petroleum ether/ethyl acetate 9:1, R
max
f
−1
+
+
1
(1t) = 0.50, R (2t) = 0.40, UV detection]. H NMR (CDCl 400
14
18
5
f
3
2
89.1046, found 289.1047.
,3-Diethyl-2-benzofuran-1(3H)-one (2o). This compound was
prepared according to the GP and isolated as pale yellow colored solid
2% yield (88 mg): mp 56−58 °C; [TLC (petroleum ether/ethyl
MHz) δ = 7.85 (d, 1H, J = 7.3 Hz), 7.63 (dd, 1H, J = 8.8 and 7.3 Hz),
7.48 (dd, 1H, J = 8.8 and 7.3 Hz), 7.36 (d, 1H, J = 7.3 Hz), 2.23−2.08
(m, 1H), 1.62 (s, 3H), 0.98 (d, 3H, J = 6.8 Hz), 0.80 (d, 3H, J = 6.8
Hz) ppm. 13C NMR (CDCl , 100 MHz) δ = 170.3 (C ), 153.5 (C ),
3
9
3
q
q
1
acetate 9:1, R (1o) = 0.50, R (2o) = 0.40, UV detection]. H NMR
133.8 (CH), 128.8 (CH), 126.3 (C ), 125.6 (CH), 121.3 (CH), 90.1
f
f
q
(
CDCl 400 MHz) δ = 7.80 (d, 1H, J = 7.8 Hz), 7.52 (dd, 1H, J = 8.8
(C ), 36.5 (CH), 23.9 (CH ), 17.1 (CH ), 16.9 (CH ) ppm. IR (MIR-
3
q
3
3
3
−1
and 7.3 Hz), 7.42 (dd, 1H, J = 8.8 and 7.3 Hz), 7.19 (d, 1H, J = 7.8
Hz), 2.10−1.92 (m, 2H), 1.91−1.76 (m, 2H), 0.68 (t, 6H J = 7.3 Hz)
ppm. 13C NMR (CDCl , 100 MHz) δ = 168.3 (C ), 149.1 (C ), 131.9
ATR, 4000−600 cm ) ν = 2977, 1738, 1595, 1472, 1343, 1251,
max
−1
1131, 1078, 929, 831, 669 cm . HR-MS (ESI+) m/z calculated for
+
+
[C H O ] = [M + H] 191.1067, found 191.1065.
3
q
q
12 15
2
(
CH), 130.3 (C ), 128.4 (CH), 123.6 (CH), 120.9 (CH), 92.3 (C ),
3-Allyl-3-methyl-2-benzofuran-1(3H)-one (2u). This compound
was prepared according to the GP and isolated as colorless viscous
q
q
3
6
9
=
1.9 (2C, 2 × CH ), 7.8 (2C, 2 × CH ) ppm. IR (MIR-ATR, 4000−
2
3
−1
00 cm ) ν = 2969, 1735, 1599, 1497, 1363, 1249, 1156, 1030,
liquid 83% yield (79 mg): [TLC (petroleum ether/ethyl acetate 9:1, R
max
f
−1
+
1
14, 738, 697 cm . HR-MS (ESI+) m/z calculated for [C H ON]
(1u) = 0.50, R (2u) = 0.40, UV detection]. H NMR (CDCl 400
12
16
f
3
+
[(M + NH )+(-H O)] 190.1226, found 190.1224.
MHz) δ = 7.85 (d, 1H, J = 7.8 Hz), 7.64 (ddd, 1H, J = 7.3, 7.3, and 1.0
Hz), 7.49 (dd, 1H, J = 7.3 and 6.8 Hz), 7.37 (d, 1H, J = 7.8 Hz), 5.65−
5.49 (m, 1H), 5.04 (d, 2H, J = 11.7 Hz), 2.75−2.55 (m, 2H), 1.63 (s,
3H) ppm; 13C NMR (CDCl , 100 MHz) δ = 169.8 (C ), 153.4 (C ),
4
2
3
,3-Diethyl-5-methoxy-2-benzofuran-1(3H)-one (2p). This com-
pound was prepared according to the GP and isolated as pale yellow
colored oil 93% yield (102 mg): [TLC (petroleum ether/ethyl acetate
8
4
Hz), 6.71 (d, 1H, J = 2.0 Hz), 3.88 (s, 3H), 2.13−1.98 (m, 2H), 1.93−
1
MHz) δ = 170.2 (C ), 164.6 (C ), 154.6 (C ), 127.1 (CH), 119.6
3
q
q
1
:2, R (1p) = 0.50, R (2p) = 0.30, UV detection]. H NMR (CDCl
133.9 (CH), 131.0 (CH), 128.9 (CH), 126.0 (C ), 125.7 (CH), 121.1
f
f
3
q
00 MHz) δ = 7.75 (d, 1H, J = 8.3 Hz), 6.98 (dd, 1H, J = 8.3 and 2.0
(CH), 120.1 (CH ), 86.7 (C ), 44.3 (CH ), 25.4 (CH ) ppm; IR
2
q
2
3
−1
(MIR-ATR, 4000−600 cm ) ν = 2982, 1743, 1612, 1453, 1354,
1281, 1106, 1032, 730, 694 cm ; HR-MS (ESI+) m/z calculated for
[C H O ] = [M + H] 189.091, found 189.0912.
max
13
−1
.75 (m, 2H), 0.69 (t, 6H, J = 7.3 Hz) ppm. C NMR (CDCl , 100
3
+
+
q
q
q
12 13 2
(
C ), 115.6 (CH), 105.4 (CH), 90.0 (C ), 55.8 (CH ), 31.4 (CH ),
3-Allyl-5-methoxy-3-methyl-2-benzofuran-1(3H)-one (2v). This
compound was prepared according to the GP and isolated as colorless
viscous liquid 84% yield (92 mg): [TLC (petroleum ether/ethyl
q
q
3
2
−1
7
1
+
.4 (CH ) ppm. IR (MIR-ATR, 4000−600 cm ) ν = 2990, 1750,
3
max
−
1
598, 1463, 1365, 1255, 1132, 1024, 917, 750, 690 cm . HR-MS (ESI
) m/z calculated for [C H O ] = [M + H] 221.1172, found
+
+
1
acetate 9:1, R (1v) = 0.50, R (2v) = 0.40, UV detection]. H NMR
13
17
3
f
f
2
21.1174.
-(Benzyloxy)-3,3-diethyl-6-methoxy-2-benzofuran-1(3H)-one
2q). This compound was prepared according to the GP and isolated
(CDCl 400 MHz) δ = 7.74 (d, 1H, J = 8.8 Hz), 6.98 (dd, 1H, J = 8.3
3
5
and 2.0 Hz), 6.67 (d, 1H, J = 2.0 Hz), 5.66−5.50 (m, 1H), 5.06 (d, 1H,
J = 4.9 Hz), 5.03 (s, 1H), 3.88 (s, 3H), 2.74−2.55 (m, 2H), 1.60 (s,
3H) ppm; 13C NMR (CDCl , 100 MHz) δ = 169.5 (C ), 164.6 (C ),
(
as pale yellow colored oil 91% yield (149 mg): [TLC (petroleum
3
q
q
ether/ethyl acetate 8:2, R (1q) = 0.50, R (2q) = 0.40, UV detection].
156.1 (C ), 131.0 (CH), 127.2 (CH), 120.0 (CH ), 118.3 (C ), 115.9
f
f
q
2
q
1
H NMR (CDCl 400 MHz) δ = 7.42 (d, 2H, J = 7.3 Hz), 7.37 (dd,
(CH), 105.4 (CH), 85.9 (C ), 55.8 (CH ), 44.3 (CH ), 25.4 (CH )
q 3 2 3
3
−
1
2
1
2
1
2
H, J = 7.3 and 6.8 Hz), 7.33 (d, 1H, J = 7.3 Hz), 7.27 (s, 1H), 6.68 (s,
ppm; IR (MIR-ATR, 4000−600 cm ) ν = 2984, 1746, 1617, 1463,
max
−1
H), 5.22 (s, 2H), 3.92 (s, 3H), 2.07−1.92 (m, 2H), 1.85−1.70 (m,
1344, 1282, 1106, 1032, 731, 690 cm ; HR-MS (ESI+) m/z
calculated for [C H O ] = [M + H] 219.1016, found 219.1025.
H), 0.63 (t, 3H, J = 7.3 Hz) ppm. 13C NMR (CDCl , 100 MHz) δ =
+
+
3
13 15
3
70.6 (C ), 153.6 (C ), 150.7 (C ), 145.9 (C ), 135.7 (C ), 128.7 (2C,
5-Fluoro-3,3-dimethylisobenzofuran-1(3H)-one (2w). This com-
pound was prepared according to the GP and isolated as colorless solid
q
q
q
q
q
× CH), 128.3 (CH), 127.4 (2C, 2 × CH), 119.4 (C ), 106.4 (CH),
q
G
DOI: 10.1021/acs.joc.5b00888
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
6
2% yield (56 mg): mp 150−152 °C; [TLC (petroleum ether/ethyl
(C ), 140.7 (C ), 128.7 (2C, 2 × CH), 128.3 (CH), 125.2 (2C, 2 ×
q
q
1
acetate 8:2, R (1w) = 0.50, R (2w) = 0.45, UV detection]. H NMR
CH), 117.0 (C ), 106.1 (CH), 103.3 (CH), 86.8 (C ), 56.4 (CH ),
f
f
q
q
3
−
1
(
CDCl 400 MHz) δ = 7.85 (dd, 1H, J = 8.3 and 3.4 Hz), 7.18 (ddd,
56.3 (CH ), 26.8 (CH ) ppm. IR (MIR-ATR, 4000−600 cm ) ν
=
3
3
3
max
−
1
1
H, J = 8.8, 8.3, and 2.0 Hz), 7.05 (dd, 1H, J = 7.8 and 2.0 Hz), 1.65
2977, 1738, 1595, 1472, 1343, 1251, 1131, 1078, 929, 831, 669 cm .
HR-MS (ESI+) m/z calculated for [C H O ] = [M + H] 285.1121,
s, 6H) ppm. 13C NMR (CDCl , 100 MHz) δ = 168.6 (C ), 166.6
+
+
(
(
3
q
17 17 4
C , d, J = 254 Hz), 157.7 (d, J = 9.5 Hz), 128.2 (d, J = 10.3 Hz),
found 285.1121.
q
1
8
4
9
21.4 (C , J = 2.2 Hz), 117.1 (d, J = 23.5 Hz), 108.1 (d, J = 23.5 Hz),
5,6,7-Trimethoxy-3-methyl-3-phenyl-2-benzofuran-1(3H)-one
q
4.7 (C , J = 2.9 Hz), 27.2 (q, 2C, 2 × CH ) ppm. IR (MIR-ATR,
(4e). This compound was prepared according to the GP and isolated
q
3
−1
000−600 cm ) ν = 3060, 1742, 1602, 1482, 1307, 1208, 1086,
60, 890, 785, 692 cm . HR-MS (ESI+) m/z calculated for
as colorless solid 91% yield (156 mg): [TLC (petroleum ether/ethyl
max
−
1
1
acetate 6:4, R
(CDCl
(m, 3H), 6.53 (s, 1H), 4.15 (s, 3H), 3.89 (s, 3H), 3.85 (s, 3H), 1.99 (s,
3H) ppm. 13C NMR (CDCl
, 100 MHz) δ = 167.4 (C ), 159.7 (C ),
152.1 (C ), 141.7 (C ), 140.9 (C ), 128.7 (2C, 2 × CH), 128.3 (CH),
(3e) = 0.50, R
(4e) = 0.40, UV detection]. H NMR
f
f
+
+
[
C H FO ] = [M + H] 181.0659, found 181.0652.
3
400 MHz) δ = 7.42 (dd, 2H, J = 7.8 and 2.0 Hz), 7.38−7.27
10
10
2
3
H-Spiro[2-benzofuran-1,1′-cyclopent[3]en]-3-one (2x). This
compound was prepared according to the GP and isolated as colorless
solid 94% yield (88 mg): mp 110−112 °C; [TLC (petroleum ether/
ethyl acetate 8:2, R (1y) = 0.50, R (2x) = 0.40, UV detection]. H
3
q
q
q
q
q
1
125.1 (2C, 2 × CH), 109.5 (C ), 99.5 (CH), 85.8 (C ), 62.3 (CH ),
q q 3
f
f
NMR (CDCl 400 MHz) δ = 7.85 (d, 1H, J = 7.3 Hz), 7.66 (ddd, 1H,
61.4 (CH ), 56.4 (CH ), 27.0 (CH ) ppm. IR (MIR-ATR, 4000−600
3
3
3
3
−1
J = 7.8, 7.3, and 1.0 Hz), 7.50 (dd, 1H, J = 7.8 and 7.3 Hz), 7.46 (d,
cm ) ν = 2935, 1747, 1595, 1473, 1339, 1259, 1121, 1013, 922,
max
H, J = 7.3 Hz), 5.85 (s, 2H), 2.92 (s, 4H) ppm. 13C NMR (CDCl3,
00 MHz) δ = 169.9 (C ), 153.3 (C ), 134.3 (CH), 129.0 (CH),
772, 698 cm . HR-MS (ESI+) m/z calculated for [C H O Na] =
18 18 5
−1
+
1
1
1
×
+
[M + Na] 337.1046, found 337.1044.
q
q
28.2 (2C, 2 × CH), 125.4 (CH), 120.9 (CH), 92.8 (C ), 45.8 (2C, 2
3-(3-Methoxyphenyl)-3-methyl-2-benzofuran-1(3H)-one (4f).
This compound was prepared according to the GP and isolated as
pale green colored solid 92% yield (118 mg): mp 98−100 °C; [TLC
(petroleum ether/ethyl acetate 9:1, R (3f) = 0.50, R (4f) = 0.40, UV
q
−
1
CH ) ppm. IR (MIR-ATR, 4000−600 cm ) ν = 2930, 1754,
612, 1465, 1318, 1271, 1080, 905, 753, 691 cm . HR-MS (ESI+) m/
2
max
−
1
1
+
+
z calculated for [C H O ] = [M + H] 187.0754, found 187.0752.
12
11
2
f
f
1
3
-Methyl-3-phenyl-2-benzofuran-1(3H)-one (4a). This compound
detection]. H NMR (CDCl 400 MHz) δ = 7.88 (d, 1H, J = 7.8 Hz),
3
was prepared according to the GP and isolated as pale yellow colored
viscous liquid 88% yield (99 mg): [TLC (petroleum ether/ethyl
7.64 (dd, 1H, J = 8.8 and 7.3 Hz), 7.54−7.43 (m, 2H), 7.26 (dd, 1H, J
= 8.3 and 7.8 Hz), 7.07−6.94 (m, 2H), 6.87−6.78 (m, 1H), 3.77 (s,
1
13
acetate 9:1, R (3a) = 0.60, R (4a) = 0.40, UV detection]. H NMR
3H), 2.01 (s, 3H) ppm. C NMR (CDCl , 100 MHz) δ = 169.9 (C ),
f
f
3
q
(
CDCl 400 MHz) δ = 7.90 (d, 1H, J = 7.8 Hz), 7.65 (ddd, 1H, J =
159.7 (C ), 154.0 (C ), 142.3 (C ), 134.3 (CH), 129.7 (CH), 129.1
3
q q q
8
3
1
.8, 7.3, and 1.0 Hz), 7.55−7.40 (m, 4H), 7.38−7.27 (m, 3H), 2.03 (s,
(CH), 125.8 (CH), 124.9 (C ), 122.0 (CH), 117.3 (CH), 113.2 (CH),
q
H) ppm. 13C NMR (CDCl , 100 MHz) δ = 169.9 (C ), 154.1 (C ),
3
q
q
111.3 (CH), 87.4 (C ), 55.2 (CH ), 27.3 (CH ) ppm. IR (MIR-ATR,
q
3
3
−1
40.6 (C ), 134.3 (CH), 129.1 (CH), 128.7 (2C, 2 × CH), 128.3
4000−600 cm ) ν = 2981, 1754, 1599, 1465, 1261, 1125, 1028,
q
max
−
1
+
(
(
1
CH), 125.8 (CH), 125.0 (2C, 2 × CH), 122.0 (CH), 87.6 (C ), 27.2
916, 754, 700 cm . HR-MS (ESI+) m/z calculated for [C H O ] =
q
16 15 3
−1
+
CH ) ppm. IR (MIR-ATR, 4000−600 cm ) ν
= 2980, 1748,
[M + H] 255.1016, found 255.1017.
3
max
−1
597, 1451, 1346, 1285, 1103, 1038, 921, 737, 693 cm . HR-MS (ESI
5-Methoxy-3-(3-methoxyphenyl)-3-methyl-2-benzofuran-1(3H)-
one (4g). This compound was prepared according to the GP and
isolated as brown colored solid 97% yield (140 mg): mp 68−70 °C;
[TLC (petroleum ether/ethyl acetate 8:2, R (3g) = 0.50, R (4g) =
+
+
+
) m/z calculated for [C H O ] = [M + H] 225.091, found
15 13 2
225.0914.
5
-Methoxy-3-methyl-3-phenyl-2-benzofuran-1(3H)-one (4b).
f
f
1
This compound was prepared according to the GP and isolated as
0.40, UV detection]. H NMR (CDCl 400 MHz) δ = 7.79 (d, 1H, J =
3
yellow colored solid 90% yield (115 mg): mp 62−64 °C; [TLC
8.3 Hz), 7.26 (dd, 1H, J = 8.3 and 7.8 Hz), 7.05−6.91 (m, 3H), 6.88−
1
3
(
petroleum ether/ethyl acetate 8:2, R (3b) = 0.60, R (4b) = 0.40, UV
6.78 (m, 2H), 3.85 (s, 3H), 3.77 (s, 3H), 1.99 (s, 3H) ppm. C NMR
f
f
1
detection]. H NMR (CDCl 400 MHz) δ = 7.80 (d, 1H, J = 8.3 Hz),
(CDCl , 100 MHz) δ = 169.6 (C ), 164.8 (C ), 159.7 (C ), 156.8
3
3
q
q
q
7
.43 (dd, 2H, J = 8.3 and 1.5 Hz), 7.38−7.28 (m, 3H), 6.99 (dd, 1H, J
(C ), 142.3 (C ), 129.7 (CH), 127.4 (CH), 117.3 (CH), 116.1 (C ),
q
q
q
=
8.3 and 2.4 Hz), 6.83 (d, 1H, J = 2.4 Hz), 3.85 (s, 3H), 2.01 (s, 3H)
113.2 (CH), 111.3 (2C, 2 × CH), 106.3 (CH), 86.5 (C ), 55.8 (CH ),
q 3
13
−1
ppm. C NMR (CDCl , 100 MHz) δ = 169.7 (C ), 164.8 (C ), 156.9
55.3 (CH ), 27.0 (CH ) ppm. IR (MIR-ATR, 4000−600 cm ) ν
=
3
q
q
3
3
max
−1
(
C ), 140.7 (C ), 128.7 (2C, 2 × CH), 128.3 (CH), 127.4 (CH),
2935, 1753, 1599, 1465, 1284, 1124, 1028, 916, 754, 700 cm . HR-
q
q
+
+
1
5
2
25.1 (2C, 2 × CH), 117.3 (C ), 116.1 (CH), 106.3 (CH), 86.7 (C ),
MS (ESI+) m/z calculated for [C H O ] = [(M + H)(-H O)]
q
q
17 15 3 2
−1
5.8 (CH ), 26.9 (CH ) ppm. IR (MIR-ATR, 4000−600 cm ) ν
971, 1738, 1600, 1498, 1324, 1229, 1173, 1028, 922, 730, 666 cm .
=
267.1016, found 267.1017.
3
3
max
−
1
5-(Benzyloxy)-6-methoxy-3-(3-methoxyphenyl)-3-methyl-2-ben-
zofuran-1(3H)-one (4h). This compound was prepared according to
the GP and isolated as colorless viscous liquid 81% yield (159 mg):
[TLC (petroleum ether/ethyl acetate 8:2, R (3h) = 0.50, R (4h) =
+
+
HR-MS (ESI+) m/z calculated for [C H O Na] = [M + Na]
2
16
14
3
77.0835, found 277.0835.
-Methyl-7-phenylfuro[3,4-f ][1,3]benzodioxol-5(7H)-one (4c).
7
f
f
1
This compound was prepared according to the GP and isolated as
0.40, UV detection]. H NMR (CDCl 400 MHz) δ = 7.43 (d, 2H, J =
3
colorless crystalline solid 92% yield (125 mg): mp 130−132 °C; [TLC
6.8 Hz), 7.41−7.23 (m, 5H), 6.99 (d, 1H, J = 7.8 Hz), 6.95 (dd, 1H, J
(
petroleum ether/ethyl acetate 8:2, R (3c) = 0.50, R (4c) = 0.40, UV
= 2.4 and 1.9 Hz), 6.83 (dd, 1H, J = 8.3 and 1.9 Hz), 6.79 (s, 1H), 5.17
f
f
1
13
detection]. H NMR (CDCl 400 MHz) δ = 7.40 (dd, 2H, J = 8.3 and
(s, 2H), 3.93 (s, 3H), 3.77 (s, 3H), 1.98 (s, 3H) ppm. C NMR
3
1
=
=
.5 Hz), 7.38−7.27 (m, 3H), 7.18 (s, 1H), 6.76 (s, 1H), 6.09 (s, 2H, J
(CDCl , 100 MHz) δ = 170.1 (C ), 159.7 (C ), 149.5 (C ), 149.0
(C ), 142.4 (C ), 135.9 (C ), 129.7 (CH), 128.7 (2C, 2 × CH), 128.2
q q q
3
q
q
q
12.2 and 1.5 Hz), 1.99 (s, 3H) ppm. 13C NMR (CDCl , 100 MHz) δ
3
169.5 (C ), 153.8 (C ), 151.1 (C ), 149.2 (C ), 140.6 (C ), 128.7
(CH), 127.3 (2C, 2 × CH), 117.4 (CH), 116.7 (C ), 113.1 (CH),
q
q
q
q
q
q
(
(
(
1
2C, 2 × CH), 128.3 (CH), 125.0 (2C, 2 × CH), 118.6 (C ), 104.3
111.5 (CH), 108.0 (CH), 103.6 (CH), 86.6 (C ), 71.0 (C ), 56.4
q
q
q
CH), 102.6 (CH), 101.9 (CH ), 86.6 (C ), 26.9 (CH ) ppm. IR
(CH ), 55.3 (CH ), 27.0 (CH ) ppm. IR (MIR-ATR, 4000−600
2
q
3
3
3
3
−1
−1
MIR-ATR, 4000−600 cm ) ν = 2977, 1732, 1611, 1477, 1308,
230, 1095, 943, 787, 659 cm . HR-MS (ESI+) m/z calculated for
cm ) ν = 2980, 1748, 1618, 1466, 1346, 1285, 1038, 921, 737, 693
max
max
−
1
−1
+
+
cm . HR-MS (ESI+) m/z calculated for [C H O ] = [M + H]
24 23 5
+
+
[
C H O Na] = [M + Na] 291.0628, found 291.0622.
391.154, found 391.1543.
16
12
4
5
,6-Dimethoxy-3-methyl-3-phenyl-2-benzofuran-1(3H)-one (4d).
7-(3-Methoxyphenyl)-7-methylfuro[3,4-f ][1,3]benzodioxol-5(7H)-
one (4i). This compound was prepared according to the GP and
isolated as pale green colored solid 92% yield (138 mg): mp 86−88
°C; [TLC (petroleum ether/ethyl acetate 8:2, R (3i) = 0.40, R (4i) =
This compound was prepared according to the GP and isolated as
colorless viscous liquid 94% yield (134 mg): [TLC (petroleum ether/
ethyl acetate 7:3, R (3d) = 0.60, R (4d) = 0.50, UV detection]. H
1
f
f
f
f
1
NMR (CDCl 400 MHz) δ = 7.45−7.38 (m, 2H), 7.38−7.29 (m, 3H),
0.30, UV detection]. H NMR (CDCl 400 MHz) δ = 7.27 (dd, 1H, J
3
3
13
7
.28 (s, 1H), 6.76 (s, 1H), 3.92 (s, 6H), 2.01 (s, 3H) ppm. C NMR
= 8.3 and 7.3 Hz), 7.17 (s, 1H), 7.00 (d, 1H, J = 8.8 Hz), 6.95 (dd, 1H,
J = 2.4 and 2.0 Hz), 6.83 (dd, 1H, J = 8.3 and 2.4 Hz), 6.79 (s, 1H),
(
CDCl , 100 MHz) δ = 170.2 (C ), 154.9 (C ), 150.4 (C ), 148.9
3
q
q
q
H
DOI: 10.1021/acs.joc.5b00888
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
6
.09 (s, 1H), 6.06 (s, 1H), 3.78 (s, 3H), 1.97 (s, 3H) ppm. 13C NMR
1H) ppm. 13C NMR (CDCl , 100 MHz) δ = 169.8 (C ), 152.0 (C ),
3
q
q
(
(
1
CDCl , 100 MHz) δ = 169.4 (C ), 159.7 (C ), 153.7 (C ), 150.9
139.9 (C ), 134.1 (CH), 130.5 (CH), 129.1 (CH), 128.7 (2C, 2 ×
3
q
q
q
q
C ), 149.1 (C ), 142.2 (C ), 129.7 (CH), 118.3 (C ), 117.2 (CH),
CH), 128.3 (CH), 125.8 (C ), 125.7 (CH), 125.2 (2C, 2 × CH),
q
q
q
q
q
13.1 (CH), 111.2 (CH), 104.1 (CH), 102.6 (CH ), 101.8 (CH), 88.4
122.4 (CH), 120.5 (CH ), 89.1 (C ), 44.3 (CH ) ppm. IR (MIR-ATR,
2
2
q
2
−1
−1
(
ν
C ), 55.2 (CH ), 26.9 (CH ) ppm. IR (MIR-ATR, 4000−600 cm )
max
4000−600 cm ) ν = 2919, 1754, 1598, 1465, 1285, 1132, 1077,
q
3
3
max
−
1
−
1
+
= 2980, 1745, 1611, 1475, 1302, 1240, 1095, 943, 747, 627 cm .
982, 753, 698 cm . HR-MS (ESI+) m/z calculated for [C H O K]
17 14 2
+
+
+
HR-MS (ESI+) m/z calculated for [C H O K] = [M + K]
= [M + K] 289.0625, found 289.0637.
1
7
14
5
3
37.0473, found 337.0476.
,6-Dimethoxy-3-(3-methoxyphenyl)-3-methyl-2-benzofuran-
(3H)-one (4j). This compound was prepared according to the GP and
3-Allyl-5-methoxy-3-phenyl-2-benzofuran-1(3H)-one (4o). This
compound was prepared according to the GP and isolated as pale
yellow colored viscous liquid 88% yield (118 mg): [TLC (petroleum
ether/ethyl acetate 8:2, R (3o) = 0.50, R (4o) = 0.40, UV detection].
5
1
isolated as brown colored semi solid 95% yield (163 mg): [TLC
petroleum ether/ethyl acetate 7:3, R (3j) = 0.40, R (4j) = 0.30, UV
f
f
1
(
H NMR (CDCl 400 MHz) δ = 7.78 (d, 1H, J = 8.3 Hz), 7.49 (d, 2H,
f
f
3
1
detection]. H NMR (CDCl 400 MHz) δ = 7.30−7.20 (m, 2H),
3
J = 6.8 Hz), 7.35 (dd, 2H, J = 7.3 and 7.3 Hz), 7.30 (d, 1H, J = 7.3
Hz), 6.99 (dd, 1H, J = 8.8 and 2.4 Hz), 6.92 (d, 1H, J = 2.0 Hz), 5.56−
5.40 (m, 1H), 5.08 (dd, 1H, J = 17.1 and 2.0 Hz), 5.02 (dd, 1H, J =
10.8 and 2.0 Hz), 3.87 (s, 3H), 3.23−3.08 (m, 1H), 3.06−2.95 (m,
1H) ppm. 13C NMR (CDCl , 100 MHz) δ = 169.5 (C ), 164.7 (C ),
7
3
1
.00−6.90 (m, 2H), 6.84−6.78 (m, 1H), 6.75 (s, 1H), 3.90 (s, 6H),
.75 (s, 3H), 1.97 (s, 3H) ppm. 13C NMR (CDCl , 100 MHz) δ =
3
70.2 (C ), 159.7 (C ), 154.9 (C ), 150.4 (C ), 148.8 (C ), 142.4
q
q
q
q
q
(
C ), 129.8 (CH), 117.4 (CH), 116.8 (C ), 113.1 (CH), 111.5 (CH),
q
q
3
q
q
106.0 (CH), 103.3 (CH), 86.6 (C ), 56.4 (CH ), 56.3 (CH ), 55.3
154.8 (C ), 139.9 (C ), 130.6 (CH), 128.7 (2C, 2 × CH), 128.2
q
3
3
q q
−1
(
2
CH ), 26.9 (CH ) ppm. IR (MIR-ATR, 4000−600 cm ) ν
=
(CH), 127.3 (CH), 125.1 (2C, 2 × CH), 120.3 (CH ), 118.1 (C ),
2 q
3
3
max
−
1
977, 1732, 1611, 1477, 1308, 1230, 1095, 943, 747, 628 cm . HR-
115.8 (CH), 106.9 (CH), 88.2 (C ), 55.8 (CH ), 44.0 (CH ) ppm. IR
q 3 2
+
+
−1
MS (ESI+) m/z calculated for [C H O Na] = [M + Na] 337.1046,
found 337.1045.
-Methyl-3-thien-2-yl-2-benzofuran-1(3H)-one (4k). This com-
pound was prepared according to the GP and isolated as brown
colored oil 87% yield (101 mg): [TLC (petroleum ether/ethyl acetate
(MIR-ATR, 4000−600 cm ) ν = 2967, 1744, 1597, 1455, 1265,
−1
18
18
5
max
1112, 1067, 982, 753, 696 cm . HR-MS (ESI+) m/z calculated for
+
+
3
[C H O ] = [(M + H) − H O] 263.1067, found 263.1073.
18
15
2
2
3-Allyl-5,6-dimethoxy-3-phenyl-2-benzofuran-1(3H)-one (4p).
This compound was prepared according to the GP and isolated as
pale yellow colored viscous liquid 82% yield (122 mg): [TLC
(petroleum ether/ethyl acetate 8:2, R (3p) = 0.40, R (4p) = 0.30, UV
1
8
4
:2, R (3k) = 0.50, R (4k) = 0.30, UV detection]. H NMR (CDCl
f
f
3
00 MHz) δ = 7.90 (d, 1H, J = 7.3 Hz), 7.69 (dd, 1H, J = 8.8 and 7.3
f
f
1
Hz), 7.55 (dd, 1H, J = 8.8 and 7.3 Hz), 7.49 (d, 1H, J = 7.8 Hz), 7.27
detection]. H NMR (CDCl 400 MHz) δ = 7.46 (d, 1H, J = 6.8 Hz),
3
(
(
dd, 1H, J = 4.9 and 1.5 Hz), 6.99 (dd, 1H, J = 4.9 and 1.5 Hz), 6.94
dd, 1H, J = 4.9 and 1.5 Hz), 2.08 (s, 3H) ppm. C NMR (CDCl3,
7.36 (dd, 1H, J = 7.3 and 6.8 Hz), 7.31 (d, 1H, J = 6.8 Hz), 7.26 (s,
1H), 6.84 (s, 1H), 5.55−5.38 (m, 1H), 5.15−4.95 (m, 2H), 3.94 (s,
3H), 3.91 (s, 3H), 3.15 (dd, 1H, J = 14.7 and 7.3 Hz), 3.01 (dd, 1H, J
13
100 MHz) δ = 169.2 (C ), 153.3 (C ), 144.4 (C ), 134.4 (CH), 129.5
q
q
q
= 14.7 and 7.3 Hz) ppm. 13C NMR (CDCl , 100 MHz) δ = 170.1
(
1
CH), 126.9 (CH), 126.2 (CH), 125.9 (CH), 125.3 (CH), 125.1 (Cq),
22.1 (CH), 85.3 (C ), 28.1 (CH ) ppm. IR (MIR-ATR, 4000−600
3
q
3
(C ), 154.8 (C ), 150.4 (C ), 146.6 (C ), 139.9 (C ), 130.7 (CH),
q
q
q
q
q
−
1
cm ) ν = 2982, 1756, 1591, 1465, 1375, 1275, 1122, 1024, 907,
128.7 (2C, 2 × CH), 128.3 (CH), 125.2 (2C, 2 × CH), 120.3 (CH2),
max
−1
+
7
+
55, 691 cm . HR-MS (ESI+) m/z calculated for [C H O S] = [M
H] 231.0474, found 231.0477.
-Methoxy-3-methyl-3-thien-2-yl-2-benzofuran-1(3H)-one (4l).
117.8 (C ), 106.0 (CH), 103.7 (CH), 88.4 (C ), 56.4 (CH ), 56.2
13
11
2
q
q
3
+
−1
(CH ), 43.8 (CH ) ppm. IR (MIR-ATR, 4000−600 cm ) ν
2912, 1753, 1598, 1461, 1275, 1142, 1077, 980, 753, 696 cm . HR-
MS (ESI+) m/z calculated for [C H O ] = [M + H] 311.1278,
=
3
2
max
−
1
5
+
+
This compound was prepared according to the GP and isolated as
black colored viscous liquid 92% yield (121 mg): [TLC (petroleum
ether/ethyl acetate 8:2, R (3l) = 0.50, R (4l) = 0.30, UV detection].
19 19 4
found 311.1271.
f
f
3,3-Diphenyl-2-benzofuran-1(3H)-one (4q). This compound was
prepared according to the GP and isolated as pale yellow colored solid
87% yield (125 mg): mp 96−98 °C; [TLC (petroleum ether/ethyl
1
H NMR (CDCl 400 MHz) δ = 7.80 (d, 1H, J = 8.3 Hz), 7.27 (dd,
3
1H, J = 6.4 and 1.5 Hz), 7.04 (dd, 1H, J = 8.3 and 2.0 Hz), 7.00 (dd,
1H, J = 3.9 and 1.5 Hz), 6.95 (dd, 1H, J = 3.9 and 1.5 Hz), 6.87 (d,
1
H, J = 2.0 Hz), 3.88 (s, 3H), 2.06 (s, 3H) ppm. 13C NMR (CDCl3,
100 MHz) δ = 168.9 (C ), 164.9 (C ), 156.1 (C ), 144.5 (C ), 127.4
1
acetate 9:1, R (3q) = 0.50, R (4q) = 0.30, UV detection]. H NMR
f
f
(CDCl 400 MHz) δ = 7.94 (d, 1H, J = 7.3 Hz), 7.69 (dd, 1H, J = 8.8
3
1
3
and 7.3 Hz), 7.63−7.50 (m, 2H), 7.43−7.26 (m, 10H) ppm. C NMR
(CDCl , 100 MHz) δ = 169.7 (C ), 151.9 (C ), 140.8 (2C, 2 × C ),
134.1 (CH), 129.3 (CH), 128.5 (2C, 2 × CH), 128.4 (4C, 4 × CH),
127.1 (4C, 4 × CH), 126.0 (CH), 125.5 (C ), 124.1 (CH), 91.6 (C )
q
q
q
q
q
(
CH), 126.9 (CH), 126.2 (CH), 125.2 (CH), 117.4 (C ), 116.7 (CH),
06.2 (CH), 84.4 (C ), 55.9 (CH ), 28.1 (CH ) ppm. IR (MIR-ATR,
3
q
q
q
q
1
4
9
=
q 3 3
−1
000−600 cm ) ν = 2933, 1754, 1604, 1490, 1293, 1124, 1029,
q
max
−
1
+
−1
18, 837, 692 cm . HR-MS (ESI+) m/z calculated for [C H O S]
ppm. IR (MIR-ATR, 4000−600 cm ) νmax = 3060, 1754, 1597, 1446,
1250, 1106, 1073, 967, 750, 691 cm . HR-MS (ESI+) m/z calculated
for [C20H O ] = [M + H] 287.1067, found 287.1066.
14
13
3
+
−1
[M + H] 261.0580, found 261.0579.
,6-Dimethoxy-3-methyl-3-thien-2-yl-2-benzofuran-1(3H)-one
4m). This compound was prepared according to the GP and isolated
as amber colored viscous liquid 88% yield (109 mg): [TLC
petroleum ether/ethyl acetate 8:2, R (3m) = 0.50, R (4m) = 0.40,
+
+
5
15 2
(
5-Methoxy-3,3-diphenyl-2-benzofuran-1(3H)-one (4r). This com-
pound was prepared according to the GP and isolated as colorless solid
83% yield (131 mg): mp 136−138 °C; [TLC (petroleum ether/ethyl
(
f
f
1
1
UV detection]. H NMR (CDCl 400 MHz) δ = 7.30−7.23 (m, 2H),
acetate 8:2, R (3r) = 0.50, R (4r) = 0.30, UV detection]. H NMR
3
f
f
6
6
.98 (dd, 1H, J = 3.9 and 1.5 Hz), 6.93 (dd, 1H, J = 3.9 and 1.5 Hz),
(CDCl 400 MHz) δ = 7.85 (d, 1H, J = 8.3 Hz), 7.40−7.27 (m, 10H),
3
13
.82 (s, 1H), 3.93 (s, 3H), 3.92 (s, 3H), 2.05 (s, 3H) ppm. C NMR
7.05 (dd, 1H, J = 8.3 and 2.0 Hz), 6.96 (d, 1H, J = 2.0 Hz), 3.86 (s,
3H) ppm. 13C NMR (CDCl , 100 MHz) δ = 169.4 (C ), 164.6 (C ),
(
(
1
CDCl , 100 MHz) δ = 169.4 (C ), 154.9 (C ), 150.7 (C ), 147.9
C ), 144.6 (C ), 126.9 (CH), 126.2 (CH), 125.3 (CH), 117.1 (C ),
3
q
q
q
3
q
q
q
q
q
154.6 (C ), 140.9 (C ), 131.5 (CH), 130.0 (CH), 128.5 (2C, 2 ×
q q
05.9 (CH), 103.4 (CH), 84.4 (C ), 56.4 (CH ), 56.3 (CH ), 27.9
CH), 128.4 (3C, 3 × CH), 127.6 (CH), 127.1 (3C, 3 × CH), 126.9
q
3
3
−1
(
1
CH ) ppm. IR (MIR-ATR, 4000−600 cm ) ν
= 2982, 1746,
(C ), 117.9 (C ), 116.1 (CH), 108.8 (CH), 90.9 (C ), 55.9 (CH )
3
max
q
q
q
3
−
1
−1
617, 1466, 1285, 1154, 1027, 923, 845, 698 cm . HR-MS (ESI+) m/
ppm. IR (MIR-ATR, 4000−600 cm ) ν = 2943, 1755, 1597, 1490,
1341, 1269, 1109, 1023, 968, 725, 697 cm . HR-MS (ESI+) m/z
calculated for [C H O Na] = [M + Na] 339.0992, found 339.0991.
max
+
+
−1
z calculated for [C H O S] = [M + H] 291.0686, found 291.0686.
15
15
4
+
+
3
-Allyl-3-phenyl-2-benzofuran-1(3H)-one (4n). This compound
21 16 3
was prepared according to the GP and isolated as colorless oil 89%
3-(3-Methoxyphenyl)-3-phenyl-2-benzofuran-1(3H)-one (4s).
This compound was prepared according to the GP and isolated as
colorless viscous liquid 87% yield (138 mg): [TLC (petroleum ether/
yield (112 mg): [TLC (petroleum ether/ethyl acetate 9:1, R (3n) =
f
1
0
.40, R (4n) = 0.30, UV detection]. H NMR (CDCl 400 MHz) δ =
f
3
1
7
.88 (d, 1H, J = 7.8 Hz), 7.66 (dd, 1H, J = 8.8 and 7.3 Hz), 7.57−7.46
ethyl acetate 8:2, R (3s) = 0.50, R (4s) = 0.40, UV detection]. H
f
f
(
m, 4H), 7.36 (dd, 2H, J = 7.3 and 7.3 Hz), 7.33−7.27 (m, 1H), 5.55−
.38 (m, 1H), 5.12−4.95 (m, 2H), 3.24−3.12 (m, 1H), 3.08−2.98 (m,
NMR (CDCl 400 MHz) δ = 7.94 (d, 1H, J = 7.3 Hz), 7.69 (dd, 1H, J
3
5
= 7.3 and 7.3 Hz), 7.59 (d, 1H, J = 7.8 Hz), 7.55 (d, 1H, J = 7.8 and
I
DOI: 10.1021/acs.joc.5b00888
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
7
.3 Hz), 7.40−7.20 (m, 6H), 7.00−6.80 (m, 3H), 3.74 (s, 3H) ppm.
C NMR (CDCl , 100 MHz) δ = 169.7 (C ), 159.5 (C ), 151.8 (C ),
H.; Shao, W.-D. J. Org. Chem. 1995, 60, 6168−6172. (d) Eildal, J. N.
N.; Andersen, J.; Kristensen, A. S.; Jørgensen, A. M.; Bang-Andersen,
B.; Jørgensen, M.; Strømgaard, K. J. Med. Chem. 2008, 51, 3045−3048.
(e) Kondo, Y.; Asai, M.; Miura, T.; Uchiyama, M.; Sakamoto, T. Org.
Lett. 2001, 3, 13−15. (f) Murray, A. W.; Murray, N. D.; Reid, R. G. J.
Chem. Soc., Chem. Commun. 1986, 1230−1232. (g) Kushner, S.;
Morton, J.; Boothe, J. H.; Williams, J. H. J. Am. Chem. Soc. 1953, 75,
1097−1100.
1
3
3
q
q
q
1
42.3 (C ), 140.7 (C ), 134.1 (CH), 129.5 (CH), 129.3 (CH), 128.5
q q
(
CH), 128.4 (2C, 2 × CH), 127.0 (2C, 2 × CH), 126.0 (CH), 125.4
C ), 124.2 (CH), 119.4 (CH), 113.5 (CH), 113.2 (CH), 91.5 (C ),
(
q
q
−1
5
1
+
5.2 (CH ) ppm. IR (MIR-ATR, 4000−600 cm ) ν = 2987, 1745,
592, 1480, 1349, 1259, 1103, 1043, 967, 726, 693 cm . HR-MS (ESI
) m/z calculated for [C H O ] = [M] 316.1094, found 316.1124.
3
max
−
1
+
+
21
16
3
(
9) Schareina, T.; Zapf, A.; Mag
Chem. - Eur. J. 2007, 13, 6249−6254.
10) (a) Cowell, A.; Stille, J. K. J. Am. Chem. Soc. 1980, 102, 4193.
b) Kadnikov, D. V.; Larock, R. C. J. Org. Chem. 2003, 68, 9423−9432.
11) (a) Kleemann, A.; Engel, J.; Kutscher, B.; Reichert, D.
̈
̈
erlein, W.; Muller, N.; Beller, M.
ASSOCIATED CONTENT
Supporting Information
■
(
*
S
(
Experimental procedures and characterization for all new
compounds, copies of NMR spectra, and CIF files (for 2d
and 2f) provided. The Supporting Information is available free
of charge on the ACS Publications website at DOI: 10.1021/
acs.joc.5b00888.
(
Pharmaceutical Substance: Synthesis, Patents, Applications, 4th ed.;
Georg Thieme: Stuttgart, 2001. (b) Larock, R. C. In Comprehensive
Organic Transformations: A Guide to Functional Group Preparations;
Wiley-VCH: Weinheim, Germany, 1989; pp 819−995. (c) Fatiadi, A.
J. In Preparation and Synthetic Applications of Cyano Compounds; Patai,
S., Rappoport, Z., Eds.; Wiley-VCH: New York, NY, 1983.
AUTHOR INFORMATION
■
(
d) Rappoport, Z. In Chemistry of the Cyano Group; John Wiley &
Sons: London, U.K., 1970; pp 121−312.
12) (a) Sandmeyer, T. Ber. Dtsch. Chem. Ges. 1884, 17, 2650.
(b) Rosenmund, K. W.; Struck, E. Ber. Dtsch. Chem. Ges. B 1919, 52,
749.
13) (a) Zhang, G.; Zhang, L.; Hu, M.; Cheng. Adv. Synth. Catal.
011, 353, 291−294. (b) Ushkov, A. V.; Grushin, V. V. J. Am. Chem.
Corresponding Author
*
Fax: +91(40) 2301 6032. E-mail: gvsatya@iith.ac.in.
(
Notes
1
(
2
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Soc. 2011, 133, 10999−11005. (c) Schareina, T.; Zapf, A.; Beller, M. J.
Organomet. Chem. 2004, 689, 4576−4583. (d) Chatani, N.; Hanafusa,
T. J. Org. Chem. 1986, 51, 4714−4716. (e) Sundermeier, M.; Mutyala,
S.; Zapf, A.; Spannenberg, A.; Beller, M. J. Organomet. Chem. 2003,
684, 50−55. (f) Prasad, P. K.; Sudalaia, A. Adv. Synth. Catal. 2014, 356,
2231−2238. (g) Miao, H.-M.; Zhao, G.-L.; Zhang, L.-S.; Shao, H.;
Wang, J.-W. Helv. Chim. Acta 2011, 94, 1981−1993.
We are grateful to the Department of Science and Technology-
Science and Engineering Research Board (DST-SERB) [No.
SB/S1/OC-39/2014], New Delhi, for the financial support.
L.M. thanks CSIR, New Delhi, for the award of research
fellowship.
(14) (a) Wen, Q.; Jin, J.; Zhang, L.; Luo, Y.; Lu, P.; Wang, Y.
REFERENCES
■
Tetrahedron Lett. 2014, 55, 1271−1280. (b) Ellis, G. P.; Romney-
Alexander, T. M. Chem. Rev. 1987, 87, 779−794. (c) Anbarasan, P.;
Schareina, T.; Beller, M. Chem. Soc. Rev. 2011, 40, 5049−5067.
(
1) For reviews on domino reactions, see: (a) Tietze, L. F. Chem. Rev.
996, 96, 115−136. (b) Pellissier, H. Chem. Rev. 2013, 113, 442−524.
1
(
c) Zeng, X. Chem. Rev. 2013, 113, 6864−6900. (d) Shiri, M. Chem.
Rev. 2012, 112, 3508−3549.
2) (a) Hartwig, J. F. Organotransition Metal Chemistry: From Bonding
(15) (a) Schareina, T.; Zapf, A.; Beller, M. Chem. Commun. 2004,
1
388−1389. (b) Senecal, T. D.; Shu, W.; Buchwald, S. L. Angew.
(
Chem., Int. Ed. 2013, 52, 10035−10039. (c) Chen, G.; Weng, J.;
Zheng, Z.; Zhu, X.; Cai, Y.; Cai, J.; Wan, Y. Eur. J. Org. Chem. 2008,
to Catalysis; University Science Books: Sausalito, CA, 2010. (b) Beller,
M.; Bolm, C. Transition Metals for Organic Synthesis, 2nd ed.; Wiley-
VCH: Weinheim, Germany, 2004.
2
008, 3524−3528. (d) Weissman, S. A.; Zewge, D.; Chen, C. J. Org.
Chem. 2005, 70, 1508−1510. (e) Grossman, O.; Gelman, D. Org. Lett.
006, 8, 1189−1191. (f) Yeung, P. Y.; So, C. M.; Lau, C. P.; Kwong, F.
Y. Org. Lett. 2011, 13, 648−651. (g) Schareina, T.; Zapf, A.; Bgerlein,
W. M.; Muller, N.; Beller, M. Tetrahedron Lett. 2007, 48, 1087.
16) Zanon, J.; Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2003,
25, 2890−2891.
17) Schareina, T.; Zapf, A.; Beller, M. Tetrahedron Lett. 2005, 46,
585.
(
3) (a) Mahendar, L.; Krishna, J.; Reddy, A. G. K.; Ramulu, B. V.;
2
Satyanarayana, G. Org. Lett. 2012, 14, 628−631. (b) Mahendar, L.;
Satyanarayana, G. J. Org. Chem. 2014, 79, 2059−2074.
̈
(
4) (a) Krishna, J.; Reddy, A. G. K.; Satyanarayana, G. Synlett 2013,
(
2
4, 967−972. (b) Krishna, J.; Reddy, A. G. K.; Satyanarayana, G.
Tetrahedron Lett. 2014, 55, 861−864.
5) Mahendar, L.; Reddy, A. G. K.; Krishna, J.; Satyanarayana, Gedu
J. Org. Chem. 2014, 79, 8566−8576.
6) (a) Inubushi, Y.; Tsuda, Y.; Konita, T.; Matsumoto, S. Chem.
1
(
2
(
(
Pharm. Bull. 1964, 12, 749−750. (b) Lin, G.; Chan, S. S.-K.; Chung,
H.-S.; Li, S.-L. Chemistry and Biological Action of Natural Occurring
Phthalides. In Studies in Natural Products Chemistry; Atta-ur-Rahman,
Ed.; Elsevier: Amsterdam, 2005; Vol. 32, pp 611−669. (c) Beck, J. J.;
Chou, S. C. J. Nat. Prod. 2007, 70, 891−900. (d) Xioang, M.-J.; Li, Z.-
H. Curr. Org. Chem. 2007, 11, 833−844. (e) Beck, J. J.; Chou, S.-C. J.
Nat. Prod. 2007, 70, 891−900. (f) Mola, A. D.; Palombi, L.; Massa, A.
Curr. Org. Chem. 2012, 16, 2302−2320.
(
7) (a) Snieckus, V. Chem. Rev. 1990, 90, 879−933. (b) Mal, D.;
Pahari, P. Chem. Rev. 2007, 107, 1892−1918. (c) Karmakar, R.; Pahari,
P.; Mal, D. Chem. Rev. 2014, 114, 6213−6284. (d) Donner, C. D.
́ ́
Tetrahedron 2013, 69, 3747−3773. (e) Hernandez, E.; Velez, J. M.;
Vlaar, C. P. Tetrahedron Lett. 2007, 48, 8972−8975. (f) Rathwell, K.;
Brimble, M. A. Synthesis 2007, 2007, 643−662. (g) Mitchell, A. S.;
Russell, R. A. Tetrahedron 1995, 51, 5207−5236.
(
8) (a) Karthikeyan, J.; Parthasarathy, K.; Cheng, C.-H. Chem.
Commun. 2011, 47, 10461−10463. (b) Ito, M.; Osaku, A.; Shiibashi,
A.; Ikariya, T. Org. Lett. 2007, 9, 1821−1824. (c) Wu, H.-J.; Ying, F.-
J
DOI: 10.1021/acs.joc.5b00888
J. Org. Chem. XXXX, XXX, XXX−XXX