Phenol and aniline oxidative coupling with alkenes by using hypervalent iodine dimer for the rapid access to dihydrobenzofurans and indolines

Article abstract of DOI:10.3987/COM-14-S(K)14

A highly reactive hypervalent iodine dimer, [Ph(CF3COO)I]-O- [I(OCOCF3)Ph], is utilized as successful promoter in the oxidative phenolic coupling with styrenes leading to 2-aryldihydrobenzofurans. The extensions of the substrates in this study have led to the development of a new expeditious construction of the pyrroloindoline structure from aniline and enamide derivatives.

Full text of DOI:10.3987/COM-14-S(K)14

HETEROCYCLES, Vol. 90, No. 1, 2015
631
HETEROCYCLES, Vol. 90, No. 1, 2015, pp. 631 - 644. © 2015 The Japan Institute of Heterocyclic Chemistry
Received, 27th February, 2014, Accepted, 25th March, 2014, Published online, 4th April, 2014
DOI: 10.3987/COM-14-S(K)14
PHENOL AND ANILINE OXIDATIVE COUPLING WITH ALKENES BY
USING HYPERVALENT IODINE DIMER FOR THE RAPID ACCESS TO
DIHYDROBENZOFURANS AND INDOLINES
Toshifumi Dohi, Yosuke Toyoda, Tomofumi Nakae, Daichi Koseki, Hiroko
Kubo, Tohru Kamitanaka, and Yasuyuki Kita*
College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi,
Kusatsu, Shiga, 525-8577, Japan
*Corresponding author. Tel.: +81-77-561-5829; fax: +81-77-561-5829; e-mail:
kita@ph.ritsumei.ac.jp (Y. Kita)
Abstract – A highly reactive hypervalent iodine dimer, [Ph(CF3COO)I]-O-
[I(OCOCF3)Ph], is utilized as successful promoter in the oxidative phenolic
coupling with styrenes leading to 2-aryldihydrobenzofurans. The extensions of the
substrates in this study have led to the development of a new expeditious
construction of the pyrroloindoline structure from aniline and enamide
derivatives.
In Celebration of Professor Dr. Isao Kuwajima on His 77th Birthday
Phenolic oxidation is one of the pivotal steps frequently involved during the biosynthesis of naturally-
occurring products possessing a variety of interesting biological activities.1 Consequently, there already
exist continuing efforts in chemical processes for reproducing such transformations, and hypervalent
iodine reagents, specifically, PhI(OAc)2 [phenyliodine diacetate, PIDA] and PhI(OCOCF3)2 [phenyl
iodine bis(trifluoroacetate), PIFA], are found to be versatile synthetic tools for producing the valuable
quinone, quinol, and spirodienone-type compounds through the biomimetic phenolic oxidations under
mild conditions.2 In addition, many favorable characteristics, i.e., low toxicity, safety, ready availability,
easy handling, etc., have made these iodine reagents a useful and essential class as the oxidation tool in
modern organic synthesis developing the green chemistry that can replace toxic heavy-metal oxidizers,
such as lead, mercury, and thallium-based reagents.3 Over the past two decades, we have thoroughly
investigated the development of a series of hypervalent iodine-induced oxidative transformations

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HETEROCYCLES, Vol. 90, No. 1, 2015
accompanying the dearomatizations of phenols and related compounds by exploiting a wide array of new
reactivities and synthetic utility, and the products obtained by these protocols were utilized as key
intermediates for accomplishing the total syntheses of several complex natural products and related
functionalized molecules having interesting biological properties.4
In spite of the increased chemistry in the phenolic oxidation field of hypervalent iodine reagents, the
transformations accompanying some carbon-carbon bond formations were, on the other hand, only
slightly reported, especially involving the intermolecular reactions.5-9 One of the early examples
concerning this topic is the oxidative phenolic coupling with electron-rich styrenes to produce dihydro-
benzofuran products by the formal cycloaddition sequence.9,10 As the primary research, Swenton and
co-workers reported the reactions of a few combinations of p-methoxyphenols 1 with p-methoxystyrene
derivatives using PhI(OCOCF3)2 in acetonitrile (Scheme 1).9 A generally accepted reaction mechanism
includes the initial attack of the phenolic oxygen atom on the iodine center to form the phenoxyiodine(III)
intermediate. For the electron-rich phenols 1 having the cation-stabilizing methoxy group, this
intermediate would produce discrete quinonium ions in a polar solvent, such as acetonitrile, by the
smooth dissociation of iodobenzene and trifluoroacetic acid. The charged cationic species can now react
with the electron-rich styrenes 2 to afford the keto-type pre-cyclized intermediate, which is
simultaneously converted to the final dihydrobenzofuran products 3 by aromatization as the driving force.
The stepwise constructions of the carbon-carbon and carbon-oxygen bonds between the phenols 1 and
styrenes 2 would typically deliver the thermodynamically-favored cyclic isomers. This method could
indeed provide the corresponding dihydrobenzofuran products 3 in only one-step from these readily
available substrates, but it usually suffered from low yield formations of the products, thus still has
significant room for improvement.
Ph
Ar
R'
I
R'
OH
OCOCF3
O
O
O
Ar
I
2
Ph (OCOCF3)2
R
R
R
R
I
Ph ,
CF3CO2H
OMe
OMe
OMe
OMe
CF3CO2H
1
quinonium
3
dihydrobenzofuran
structures
Scheme 1. General mechanism of oxidative phenolic coupling with styrenes leading to
dihydrobenzofurans using hypervalent iodine reagent

HETEROCYCLES, Vol. 90, No. 1, 2015
633
During our continuous investigations of hypervalent iodine chemistry, we recently met the remarkable
high reactivities of hypervalent iodine dimers linked to each other via the oxygen bridge.11,12 Interestingly,
it was obvious that an alternative use of the PIFA dimer, i.e., [Ph(CF3COO)I]O[I(OCOCF3)Ph], instead of
PhI(OCOCF3)2 itself, can generally further enhance the productivities of a variety of typical phenolic
oxidation processes using a hypervalent iodine reagent.12 A plausible explanation of the high reactivity is
13
that the more polarized I(III)-OCOCF3 bonds compared to those of PhI(OCOCF3)2 would significantly
develop the positive characters of the iodine atoms in order to smoothly interact with the phenolic oxygen
and substrates. This encouraged us to examine in this study the PIFA dimer as a superior candidate in the
reported oxidative coupling of phenols as well as anilines 1 toward styrenes 2 leading to the dihydro-
benzofuran and indoline products 3.9,10 As our continuous focus on these types of -oxo bridged
hypervalent iodine reagents, herein, we now report initial experimental results using the PIFA dimer in
this transformations regarding the representative substrates, which have partial improvements in the
yields of the obtained benzoheterocycles that are higher than those by the conventional PhI(OCOCF3)2
used to synthesize the 2-aryldihydrobenzofurans.14 With a highly reactive reagent, the rapid access to the
physostigmine-type cyclic pyrroloindoline structure is also demonstrated by employing a combination of
the suitably protected anilide and cyclic enamide as an extension of the oxidative coupling strategy.
CF3COO
OCOCF3
I
I
Ar
R'
Ph
O
Ph
XH
X
PIFA dimer
R'
+
R
R
Ar
0 oC - rt
benzoheterocyclic
structures
2
OMe
OMe
1
3
X = O, NTs
(Ts = p-toluenesulfonyl)
o
The PIFA dimer 1 is a colorless solid (mp 108-111 C) not sensitive to air and moisture, which is thus
stable under protection from light and allows long-term storage in a refrigerator. Its preparation requires
only one-step from a commercially available material, and in this study, the high purity PIFA dimer can
be obtained in good yields from iodosobenzene (PhIO) by precipitation after the reaction with a
stoichiometric amount of trifluoroacetic acid in refluxing chloroform or alternatively, from the
corresponding monomer, that is, PIFA, by treatment with an equimolar base, such as potassium tert-
butoxide.13 This compound is readily soluble in various media, even in hot water, and the reactions can be
performed in many organic solvents.

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HETEROCYCLES, Vol. 90, No. 1, 2015
For comparison of the reactivities, our evaluation of the PIFA dimer during the phenolic oxidative
coupling with alkenes was started in the literature with the combination of substrates (Scheme 2). Thus, it
is known that the treatment of 4-methoxyphenol 1a and 4-vinyl anisole 2a with PhI(OCOCF3)2 produced
the 2-aryldihydrobenzofuran 3aa (corsifuran A) in 57% yield in acetonitrile after a detailed optimization
of the conditions.9 Similarly, we examined the same conversion of the substrates using the PIFA dimer.
An equimolar mixture of phenol 1a and styrene 2a in acetonitrile was thus treated with the PIFA dimer
under the same conditions for the same reaction time (see Experimental Section). We employed the dimer
oxidant in a 0.5 equivalent relative to the substrates considering the presence of the two active iodine sites
in the reagent molecule. In this case, our performance of the reaction, to our delight, the apparent
improvement of the isolated product was 76% yield after the same workup, which corresponds to about a
20% increase in the product yield in comparison to the reference work using the optimized method with
the conventional PhI(OCOCF3)2 reagent. In other higher or lower concentrations, the product 3aa was
also obtained in similar good yields at both 0 C and room temperature.
OMe
OH
O
hypervalent iodine reagent
+
MeCN
0 oC - rt
15 min
OMe
2a
OMe
3aa
(corsifuran A)
OMe
1a
3aa
hypervalent iodine reagent
yield of
57% refs.9a,b
PhI(OCOCF3)2
(PIFA)
76%
[Ph(CF3COO)I]O[I(OCOCF3)Ph]
PIFA dimer
(
)
Scheme 2. Reactions using PIFA and its -oxo dimer for the representative substrates
Conditions: phenol 1a (1 equiv), styrene 2a (1 equiv), hypervalent iodine reagent
(PIFA: 1 equiv; PIFA dimer: 0.5 equiv)
With this encouraging result, we next attempted to apply the oxidative coupling cyclizations using the
PIFA dimer with several other phenol (Eq. 1) and alkene (Eq. 2) substrates. Using the same procedures,
the reactions of the ortho-substituted phenols 1b and 1c having a bulky substituent or a weak

HETEROCYCLES, Vol. 90, No. 1, 2015
635
electron-withdrawing functionality toward the styrene 2a could afford the dihydrobenzofurans 3ba and
3ca in moderate yields. The decreased yield would suggest that the reactions are relatively sensitive to
both the steric and electronic effects of the ortho groups in the phenolic substrates. In addition, the -
substituent at the neighboring reaction site also seemed to influence the reaction progress. Thus, the 3,5-
dimethylphenol 1d produced the corresponding 4,6-disubstituted benzofuran 3da also in a moderate yield.
The phenol structure is more suitable for this reaction based on the result using the naphthol substrate 1e,
probably due to the undesired facile SET-oxidation sensitivity of the naphthalene ring.15 The reactions
were usually fast enough to be completed within half an hour.
OMe
OH
R1
R2
R2
O
56% (3ba: R1 = tBu, R2 = H)
OMe
R1
R2
1
2
3ca
51% (
: R = Cl, R = H)
1
t
2
45% (3da: R1 = H, R2 = Me)
1b
(R = Bu, R = H)
R2
1c (R1 = Cl, R2 = H)
1
2
1d
OMe
or
(R = H, R = Me)
PIFA dimer
or
+
(1)
OMe
MeCN
0 oC - rt
OMe
OH
2a
30 min
O
OMe
1e
42% (3ea)
OMe
Regarding the alkene coupling partners 2, p-alkylstyrene 2b similarly reacted with the reference phenol
1a in an expected manner to form the product 3ab. On the other hand, the conformationally restricted 2-

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HETEROCYCLES, Vol. 90, No. 1, 2015
mesitylbenzofuran 3ac was obtained in a lower yield (53%) by the reaction of vinyl mesitylene 2c. As the
disubstituted alkenes, anethole 2d and -methylstyrene 2e were employed to give the corresponding
cyclized products 3ad and 3ae in 76% and 63% yields, respectively, by the oxidative couplings. From the
trans and cis-mixture 2d, the product 3ad was obtained as a single trans-isomer.
Despite the low reaction yield, the standard styrene 2f could be coupled with the phenol 1a (Scheme 3).
For such a less reactive alkene, the use of a more polar solvent instead of acetonitrile effectively
improved the yield to some extent. Specifically, some fluoroalcohols can support the generation of the
cationic reaction intermediates by solvation throughout the reactions.16 To this end, the product 3af was
formed in 50% yield in 2,2,2-trifluoroethanol from the styrene 2f and the phenol 1a.
Ph
OH
O
PIFA dimer
(0.5 equiv)
+
Ph
2f
(1 equiv)
37% (acetonitrile)
solvent
0 oC - rt
30 min
50% (trifluoroethanol)
OMe
OMe
1a
3af
(1 equiv)
Scheme 3. Solvent effect
Besides, this reaction has an alternative synthetic route toward the construction of the indoline structures.
Accordingly, the method was applied to the suitably modified aniline derivatives, and it was clarified that
the N-tosylanilide 1f could also more smoothly combine with anethole 2d into the indoline product 3fd
(Scheme 4). Note that the yield was pleasantly higher when using the PIFA dimer (versus 83% by
PhI(OCOCF3)2 in our previous report under the same conditions10). Thus, the oxidative coupling in the
presence of excess alkene 2d (3 equiv) in dichloromethane with 2.5 x 1/2 equiv. of the PIFA dimer
afforded the indoline 3fd in the excellent yield of 93%.
OMe
TsNH
TsN
PIFA dimer
+
CH2Cl2
0 oC - rt, 3 h
OMe
2d
OMe
1f
OMe
3fd
93%
Scheme 4. Construction of indoline structure from anilide 1f
Ts = p-toluenesulfonyl

HETEROCYCLES, Vol. 90, No. 1, 2015
637
It is of particular importance that some naturally-occurring biologically active compounds belonging to
the pyrroloindoline families consist of the lead molecules in modern drug developments.17 The above-
demonstrated successful result in producing the indoline structure strongly motivated us to examine the
cyclic enamide as an extension of the alkene component in combination with the PIFA dimer for a new
one-step access to the pyrroloindoline structure. To validate, we confirmed that the typical procedure in
Scheme 4 allowed the oxidative coupling of the anilide 1f with N-tosyl cyclic enamide 2g (Scheme 5),
resulting in detection of the target bicyclic indoline 4. The starting anilide 1f disappeared after the
reaction. Thus, the low yield of the product 4 seems to be caused by the too low nucleophilicity of
enamide 2g as a coupling partner. This first outcome of the direct construction of the pyrroloindoline
structure from the aniline substrate might expect future progress of the method in this study as an
expeditious approach toward a series of physostigmine-type compounds.18
Ts
H
N
H
TsNH
TsN
N
O
Ts
N
N
PIFA dimer
H
O
+
N H
CH2Cl2
0 oC - rt, 3 h
pyrroloindoline
structure
2g
physostigmine
OMe
1f
OMe
22%
4
Scheme 5. One-step formation of pyrroloindoline 4 from anilide utilizing cyclic enamide 2g
The PIFA dimer employed in this study was revealed as a new good promoter for the oxidative couplings
of phenols with styrenes as well as anilides. The high reactivity is suitable for promoting the coupling
cyclization to 2-aryldihydrobenzofurans and indolines by directly furnishing the carbon-carbon and
carbon-oxygen or carbon-nitrogen bonds. Its utilization has led to some extensions of the reaction
substrates, which is featured in a partial success of the direct and one-step construction of the
physostigmine-type cyclic pyrroloindoline structure from the corresponding anilide and cyclic enamide.
EXPERIMENTAL
Melting point (mp) is uncorrected. All 1H- and 13C-NMR spectra of the obtained products were measured
13
in CDCl3 by NMR spectrometers operating at 400 MHz (100 MHz for C NMR) at 25 C. Chemical
shifts of 1H-NMR were recorded in parts per million (ppm, ) relative to tetramethylsilane ( = 0.00 ppm)
as an internal standard. Data are reported as follows: chemical shift in ppm (), multiplicity (s = singlet, d
= doublet, t = triplet, m = multiplet), coupling constant (J) in Hz, and integration. Chemical shifts of
13C-NMR were reported in ppm with the solvent as reference peak (CDCl3:  = 77.0 ppm). High

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HETEROCYCLES, Vol. 90, No. 1, 2015
resolution mass measurements were performed by the Elemental Analysis Section of Osaka University.
Flash column chromatography was performed with Merck Silica Gel 60 (230-400 mesh) eluting with
hexane and ethyl acetate for isolation of the products. Analytical thin-layer chromatography (TLC) was
carried out on Merk Silica Gel F254 plates (0.25 mm). The spots and bands were detected by UV light of
irradiation (254, 365 nm) and/or by staining with 5% phosphomolybdic acid followed by heating. Unless
otherwise noted, all experiments were carried out at room temperature in open flask without care of
moisture.
Materials
The protected aniline 1f was prepared by the standard protection method of 4-methoxyaniline with p-
toluenesulfonyl chloride under basic conditions. The cyclic enamide 2g was obtained according to the
literature.19 All other chemicals and solvents for the experiments and chromatography are commercially
available and used as received in this study without further purification.
Gram-Scale preparation of -oxodiphenylbis(trifluoroacetato-O)diiodine (PIFA dimer)
The preparation was performed by a modified synthetic procedure reported in the literature.13 Thus, to a
suspension of the iodosobenzene polymer (PhIO, 2.20 g, 10 mmol) in CHCl3 (75 mL) was added an
equimolar amount of trifluoroacetic acid (1.14 g, 10 mmol) and the resulting mixture was refluxed for
about 2 h. The reaction mixture was filtered and the solvent of the filtrate was evaporated. The residue in
a small amount of CHCl3 was triturated by adding hexane to precipitate the PIFA dimer (4.88 g, 75%) as
a colorless solid (mp 108-111 C [lit.,13 mp 110-112 C]).
Another preparation method was the treatment of PhI(OCOCF3)2 with a half equimolar amount of
potassium tert-butoxide in chloroform at room temperature for 1 h followed by a similar workup. The
PIFA dimer was obtained in 97% yield by this alternative method on the same scale.
Typical procedure for the oxidative coupling of phenols 1 with styrenes 2 using the PIFA dimer
leading to dihydrobenzofurans 3 (Schemes 2 and 3, Eqs 1 and 2)
To an ice-cooled solution of equimolar phenol 1a (24.8 mg, 0.20 mmol) and styrene 2a (27.6 mg, 0.20
mmol) in MeCN (0.5 mL), the PIFA dimer (65.0 mg, 0.10 mmol) was added in one portion at room
temperature. The reaction mixture was stirred for 30 min and then it was quenched with solid sodium
hydrogen carbonate. After filtration, solvent was removed in vacuo and the residue was purified by
column chromatography on silica-gel to give 2-aryldihydrobenzofuran 3aa (40.1 mg, 0.152 mmol) in
76% yield. We also confirmed the reaction in semi-gram scales.

HETEROCYCLES, Vol. 90, No. 1, 2015
639
2,3-Dihydro-5-methoxy-2-(4-methoxyphenyl)benzofuran (3aa, corsifuran A)9a,b
Colorless solid; 1H-NMR (400 MHz, CDCl3): 3.10 (dd, J = 16.5, 8.8 Hz, 1H), 3.45 (dd, J = 16.5, 8.8 Hz,
1H), 3.70 (s, 3H), 3.75 (s, 3H), 5.62 (t, J = 8.8 Hz, 1H), 6.56-6.73 (m, 4H), 6.78-6.86 (m, 2H), 7.22-7.33
13
(m, 2H) ppm; C-NMR (100 MHz, CDCl3): 38.7, 55.3, 56.0, 84.2, 109.2, 111.1, 113.0, 113.9, 127.3,
127.7, 133.9, 153.7, 154.2, 159.4 ppm.
The physical and spectral data of the products 3aa, 3ea, 3ad, 3ae, and 3af matched those previously
reported.
7-tert-Butyl-2,3-dihydro-5-methoxy-2-(4-methoxyphenyl)benzofuran (3ba)
Slightly orange-coloured oil; 1H-NMR (400 MHz, CDCl3): 1.37 (s, 3H), 3.09 (dd, J = 15.6, 8.8 Hz, 1H),
3.52 (dd, J = 15.6, 9.3 Hz, 1H), 3.76 (s, 3H), 3.80 (s, 3H), 5.66-5.71 (m, 1H), 6.62 (d, J = 2.4 Hz, 1H),
13
6.70 (d, J = 2.9 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 7.32 (d, J = 8.8 Hz, 2H) ppm; C-NMR (100 MHz,
CDCl3): 29.2, 34.2, 39.0, 55.2, 55.9, 83.3, 107.2, 111.5, 113.8, 126.9, 127.4, 133.4, 134.9, 151.6, 153.8,
159.1 ppm; HRMS (EI): calcd for C20H24O3 (M)+: 312.1725, found 312.1720.
7-Chloro-2,3-dihydro-5-methoxy-2-(4-methoxyphenyl)benzofuran (3ca)
1
Colorless oil; H-NMR (400 MHz, CDCl3): 3.23 (dd, J = 15.6, 8.3 Hz, 1H), 3.59 (dd, J = 15.6, 9.3 Hz,
1H), 3.73 (s, 3H), 3.79 (s, 3H), 5.74 (t, J = 8.8 Hz, 1H), 6.66-6.70 (m, 2H), 6.88 (d, 2H, J = 8.8 Hz), 7.31
(d, J = 8.8 Hz, 2H) ppm; 13C-NMR (100 MHz, CDCl3): 39.3, 55.3, 56.1, 84.7, 110.1, 113.0, 114.0, 114.3,
127.4, 129.0, 133.1, 149.8, 154.4, 159.5 ppm; HRMS (EI): calcd for C16H15ClO3 (M)+: 290.0710, found
290.0704.
2,3-Dihydro-5-methoxy-4,6-dimethyl-2-(4-methoxyphenyl)benzofuran (3da)
1
Slightly brown-coloured oil; H-NMR (400 MHz, CDCl3): 2.15 (s, 3H), 2.24 (s, 3H), 3.05 (dd, J = 15.6,
8.3 Hz, 1H), 3.45 (dd, J = 15.2, 9.3 Hz, 1H), 3.66 (s, 3H), 3.79 (s, 3H), 5.66 (m, 1H), 6.48 (s, 1H), 6.88 (d,
J = 8.8 Hz, 2H), 7.31 (d, J = 8.8 Hz, 2H) ppm; 13C-NMR (100 MHz, CDCl3): 13.2, 16.5, 37.8, 55.3, 60.2,
84.1, 108.3, 113.9, 124.3, 127.2, 127.3, 130.2, 134.2, 150.7, 155.0, 159.4 ppm; HRMS (EI): calcd for
C18H20O3 (M)+: 284.1412, found 284.1407.
2,3-Dihydro-5-methoxy-2-(4-methoxyphenyl)naphtha[1,2-b]furan (3ea)9b
Colorless solids; 1H-NMR (400 MHz, CDCl3): 3.34 (dd, J = 15.6, 7.8 Hz, 1H), 3.74 (dd, J = 15.6, 7.8 Hz,
1H), 3.79 (s, 3H), 3.94 (s, 3H), 5.86 (t, J = 15.6 Hz, 1H), 6.72 (s, 1H), 6.87-6.90 (m, 2H), 7.36-7.48 (m,
13
4H), 7.92-7.94 (m, 1H), 8.17-8.20 (m, 1H) ppm; C-NMR (100 MHz, CDCl3): 40.0, 55.2, 56.0, 84.0,

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HETEROCYCLES, Vol. 90, No. 1, 2015
101.5, 113.9, 118.1, 120.7, 121.2, 122.4, 124.9, 125.3, 126.0, 127.2, 134.5, 148.3, 150.0, 159.3 ppm.
2-(4-tert-Butylphenyl)-2,3-dihydro-5-methoxybenzofuran (3ab)
Colorless solids; mp 46-47 C; 1H-NMR (400 MHz, CDCl3): 1.31 (s, 9H), 3.22 (dd, J = 15.6, 8.3 Hz, 1H),
3.56 (dd, J = 15.6, 9.3 Hz, 1H), 3.76 (s, 3H), 5.71 (t, J = 8.8 Hz, 1H), 6.68-6.78 (m, 3H), 7.33-7.40 (m,
13
4H) ppm; C-NMR (100 MHz, CDCl3): 32.1, 35.4, 39.4, 56.8, 85.0, 110.0, 112.0, 113.7, 126.4, 126.5,
128.5, 139.6, 151.9, 154.6, 155.0 ppm; HRMS (EI): calcd for C19H22O2 (M)+: 282.1620, found 282.1622.
2,3-Dihydro-2-mesityl-5-methoxybenzofuran (3ac)
1
Colorless oil; H-NMR (400 MHz, CDCl3): 2.26 (s, 3H), 2.30 (s, 6H), 3.20-3.27 (m, 1H), 3.38-3.45 (m,
1H), 3.77 (s, 3H), 6.08-6.13 (m, 1H), 6.68-6.73 (m, 2H), 6.79 (d, J = 1.0 Hz, 1H), 6.85 (s, 2H) ppm;
13C-NMR (100 MHz, CDCl3): 20.3, 20.8, 36.4, 56.0, 81.6, 109.4, 110.9, 113.1, 128.0, 130.0, 133.4, 136.6,
137.3, 153.7, 154.0 ppm; HRMS (EI): calcd for C18H20O2 (M)+: 268.1463, found 268.1458.
trans-2,3-Dihydro-5-methoxy-2-(4-methoxyphenyl)-3-methylbenzofuran (3ad)9a,b
1
Colorless oil; H-NMR (400 MHz, CDCl3): 0.88 (d, J = 8.0 Hz, 3H), 2.90-2.93 (m, 1H), 3.29 (s, 3H),
3.31 (s, 3H), 4.58 (d, J = 8.0 Hz, 1H), 6.18-6.30 (m, 3H), 6.40-6.45 (m, 2H), 6.86 (d, J = 8.0 Hz, 2H)
ppm; 13C-NMR (100 MHz, CDCl3): 17.5, 45.6, 55.3, 56.0, 92.5, 109.3, 110.0, 112.8, 113.9, 127.6, 132.6,
133.0, 153.2, 154.4, 159.6 ppm.
2,3-Dihydro-5-methoxy-2-methyl-2-(4-methoxyphenyl)benzofuran (3ae)15e
1
Colorless oil; H-NMR (400 MHz, CDCl3): 1.74 (s, 3H), 2.32 (s, 3H), 3.45-3.27 (m, 2H), 3.74 (s, 3H),
6.74-6.63 (m, 2H), 6.78 (d, J = 8.8 Hz, 1H), 7.15 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H) ppm;
13C-NMR (100 MHz, CDCl3): 21.0, 29.2, 45.2, 56.0, 76.7, 77.0, 77.3, 89.2, 109.3, 111.3, 112.9, 124.5,
127.6, 129.0, 136.6, 143.9, 153.1, 154.1 ppm.
2,3-Dihydro-5-methoxy-2-phenylbenzofuran (3af)15f
1
Colorless oil; H-NMR (400 MHz, CDCl3): 3.16 (dd, J = 15.6, 8.3 Hz, 1H), 3.57 (dd, J = 15.6, 9.2 Hz,
1H), 3.73 (s, 3H), 5.70 (t, J = 8.8 Hz, 1H), 6.66-6.74 (m, 1H), 6.75-6.76 (m, 2H), 7.28-7.39 (m, 5H) ppm;
13C-NMR (100 MHz, CDCl3): 38.5, 55.6, 83.8, 108.8, 110.8, 112.6, 125.4, 127.1, 127.6, 128.2, 141.6,
153.4, 153.9 ppm.
Procedure for the oxidative coupling of aniline 1f with alkenes 2d and 2g using the PIFA dimer
leading to indoline 3fd and it derivatives (Schemes 4 and 5)

HETEROCYCLES, Vol. 90, No. 1, 2015
641
To a stirred solution of anilide 1f (27.7 mg, 0.10 mmol) and anethole 2d (44.5 mg, 0.30 mmol) or cyclic
enamide 2g (66.9 mg, 0.30 mmol) in CH2Cl2 (10 mL) was added dropwise a solution of the PIFA dimer
(82 mg, 0.125 mmol) in CH2Cl2 (10 mL) over 2 h by the syringe pump at room temperature. The reaction
mixture was then stirred for additional 1 h. The solvent was evaporated in vacuo and the residue was
purified by column chromatography on silica-gel to give pure indoline 3fd (44.0 mg, 0.093 mmol) or
pyrroloindoline 4 (11.0 mg, 0.022 mmol), respectively.
trans-2,3-Dihydro-5-methoxy-2-(4-methoxyphenyl)-3-methyl-1-[(4-methylphenyl)sulfonyl]-1H-
indole (3fd)10
1
Colorless oil; H-NMR (400 MHz, CDCl3): 0.78 (d, J = 7.0 Hz, 3H), 2.36 (s, 3H), 3.00-3.04 (m, 1H),
3.77 (s, 3H), 3.78 (s, 3H), 4.60 (d, J = 3.7 Hz, 1H), 6.56 (d, J = 2.4 Hz, 1H), 6.78-6.84 (m, 3H), 7.18-7.25
(m, 4H), 7.59 (d, J = 8.2 Hz, 2H), 7.68 (d, J = 8.9 Hz, 1H) ppm; 13C-NMR (100 MHz, CDCl3): 21.5, 21.6,
46.1, 55.3, 55.6, 72.6, 110.1, 113.1, 113.9, 116.8, 127.0, 127.3, 129.4, 134.5, 134.6, 134.9, 137.6, 143.8,
157.1, 159.0 ppm.
1,2,3,3a,8,8a-Hexahydro-5-methoxy-1,8-di[(4-methylphenyl)sulfonyl]pyrrolo[2,3-b]indole (4)
Colorless solid; mp 72-75 C; 1H-NMR (400 MHz, CDCl3): 1.87 (dd, J = 12.4, 4.9 Hz, 1H), 1.97-2.07 (m,
1H), 2.64-2.71 (m, 1H), 2.31 (s, 3H), 2.38 (s, 3H), 3.39 (m, 1H), 3.39 (t, J = 6.8 Hz, 1H), 3.70 (s, 3H),
3.70-3.75 (m, 1H), 6.19 (d, J = 6.6 Hz, 1H), 6.48 (d, J = 2.4 Hz, 1H), 6.67 (dd, J = 8.8, 2.7 Hz, 1H), 7.10
(d, J = 8.0 Hz, 2H), 7.22-7.27 (m, 3H), 7.44 (d, J = 8.3 Hz, 2H), 7.86 (d, J = 8.3 Hz, 2H) ppm; 13C-NMR
(100 MHz, CDCl3): 21.5, 31.4, 46.5, 46.8, 55.5, 81.4, 109.5, 113.6, 119.1, 127.3, 127.5, 129.3, 129.5,
134.4, 134.7, 135.2, 137.4, 143.2, 144.0, 158.0 ppm; HRMS (EI): calcd for C25H26N2O5S2Na (M + Na)+:
521.1181, found 521.1175.
ACKNOWLEDGEMENTS
This work was supported by a Grant-in-Aid for Scientific Research (A) and Encouragement of Young
Scientists (A) from the JSPS, a Grant-in-Aid for Scientific Research on Innovative Areas “Advanced
Molecular Transformations by Organocatalysts” from MEXT, and the Ritsumeikan Global Innovation
Research Organization (R-GIRO) Project. T.D. is grateful for financial support from the Asahi Glass
Foundation and the Industrial Technology Research Grant Program of NEDO of Japan. N.Y. thanks the
JSPS for Young Scientists for a research fellowship.
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