Investigation of the synthesis of benzofuroindolines from N-hydroxyindoles: An O-arylation/[3,3]-sigmatropic rearrangement sequence

Article abstract of DOI:10.1055/s-0034-1380346

Abstract We report the demonstration that sensitive N-hydroxyindoles can be O-arylated under transition-metal-free conditions with biaryliodonium salts. The subsequent spontaneous [3,3]-sigmatropic rearrangement delivers benzofuroindolines derived from tryptamine. We also describe the practical synthesis of N-hydroxyindoles by oxidation of indolines with m-CPBA.

Full text of DOI:10.1055/s-0034-1380346

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 1269–1275
letter
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Letter
Synlett
Investigation of the Synthesis of Benzofuroindolines from N-Hy-
droxyindoles: An O-Arylation/[3,3]-Sigmatropic Rearrangement
Sequence
Terry Tomakinian
R1
AcN
R2
Cyrille Kouklovsky
Guillaume Vincent*
NAc
R1
NAc
R1
Ar2IOTf
[3,3]
N
Univ Paris Sud and CNRS, Institut de Chimie Moléculaire
et des Matériaux d’Orsay (ICMMO), UMR8182, Equipe
Méthodologie, Synthèse & Molécules Thérapeutiques
(MS&MT), Bat. 410, 91405 Orsay, France
transition-
metal-free
N
O
R2
O
OH
N
H
H
guillaume.vincent@u-psud.fr
Dedicated to Dr. Patrick Y. S. Lam
Received: 22.12.2014
Accepted after revision: 16.02.2015
Published online: 01.04.2015
Diazonamide A as well as azonazine are benzofuroindo-
line-containing natural products which have peptidic bio-
genetic precursors 1 and 2 with tyrosine and tryptophan
residues (Scheme 1).1–3 Diazonamide A displays IC50 against
several cancer cell lines in the low nanomolar range as well
as reduced side effects as demonstrated on mice. This com-
pound seems to target indirectly but specifically the spin-
dle assembly in cancer cells via the inhibition of δ-ornithine
aminotransferase (OAT).1d,e
DOI: 10.1055/s-0034-1380346; Art ID: st-2014-d1051-l
Abstract We report the demonstration that sensitive N-hydroxyin-
doles can be O-arylated under transition-metal-free conditions with bi-
aryliodonium salts. The subsequent spontaneous [3,3]-sigmatropic re-
arrangement delivers benzofuroindolines derived from tryptamine. We
also describe the practical synthesis of N-hydroxyindoles by oxidation of
indolines with m-CPBA.
The very promising clinical potential against cancer of
diazonamide A which contains a benzofuro[2,3-b]indoline
motif has incited our group to launch a research program
Key words N-hydroxyindoles, diazonamide A, azonazine, benzofu-
roindoline, [3,3]-sigmatropic rearrangement
O
H
MeN
HO
HN
NH
H
NH
N
O
O
O
O
N
Cl
O
O
N
Cl
NH
H
Ac
O
N
H
diazonamide A
azonazine
Me
N
O
HO
HN
NH
HO
O
N
H
NH
H
N
O
CO2H
O
O
2
N
O
NH
H
1
OH
N
H
Scheme 1 Diazonamide A, azonazine and their postulated biogenetic peptidic precursors
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1269–1275

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T. Tomakinian et al.
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towards the synthesis of analogues of this natural product.
Therefore, we have recently designed new strategies to ac-
cess the benzofuro[2,3-b]indoline core 6 such as the hy-
droarylation of N-acetylindoles 3 by phenols 4 followed by
an oxidation stage4 or the pre-oxidation of indoles 7 into 3-
iodoindolines with NIS followed by a silver-mediated cou-
pling with phenols (Scheme 2).5 Regioisomeric benzofu-
ro[3,2-b]indolines 8 were also obtained by the coupling be-
tween phenols 4 and N-acetylindoles 3 mediated by DDQ
and FeCl3.6
11 to the corresponding indoline followed by oxidation to
the N-hydroxyindole catalyzed by a sodium tungstate cata-
lyst in the presence of hydrogen peroxide.9a,i We followed
Somei’s strategy to access N-hydroxytryptamine deriva-
tives 10a,b except that we discovered that the oxidation of
the indoline to the N-hydroxyindole could be performed
with m-CPBA in methanol which was more convenient and
efficient in our hands than the Na2WO4/H2O2 system
(Scheme 3).11,12
O
O
Unfortunately the strategies we designed are not well
suited for the synthesis of compounds derived from trypt-
amine or tryptophan such as benzofuroindoline 9, the tar-
get of the present communication.7
1. Et3SiH, TFA, 60 °C
R = H, 74%
R = Bn, 98%
N
R
N
R
N
N
2. m-CPBA, MeOH
0 °C to r.t.
R = H, 85%
H
In line with our investigation of electrophilic8 and/or
oxidized indoles and in order to obtain our benzofuroindo-
line target 9, we decided to focus our attention on N-hy-
droxyindoles such as 10 which have been extensively stud-
ied by Somei and co-workers (Scheme 2).9
OH
11a, R = H
11b, R = Bn
10a, R = H
10b, R = Bn
R = Bn, 95%
Scheme 3 Two-stage synthesis of N-hydroxyindoles 10 with a m-
CPBA-mediated oxidation
Several synthetic routes to N-hydroxyindoles have been
reported.10 Regarding the synthesis of N-hydroxytrypt-
amines 10 or N-hydroxytryptophan derivatives, Somei and
co-workers described the reduction of the indole nucleus
Having N-hydroxyindoles in hand, we then turned our
attention to the transformation of N-hydroxyindoles 10
into benzofuroindolines 9.
R4
R4
R4
R3
R3
R2
1. HCl (aq)
EtOH
R2
R3
R2
R1
R1
R1
4
OH
OH
O
2. oxidation
FeCl3
N
N
Ac
N
H
Ac
H
5
3
6
R4
R4
R2
NIS then
AgBF4, phenol, SnCl4
R1
R2
R3
+
R1
N
O
H
4
7
OH
N
R3
H
6
OH
R3
R3
O
R1
R1
+
FeCl3, DDQ
R
R4
N
N
H
Ac
4
8
3
Ac
our previous strategies are not applicable to the synthesis of the target 9 of this work
our new strategy
PGHN
NHPG
O
N
OH
N
H
10
H
9
Scheme 2 Our previous synthetic methods towards benzofuroindolines and our new strategy from N-hydroxyindoles towards tryptamine-derived
benzofuroindolines
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1269–1275

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We were interested in a report from Somei and co-
workers who described an intriguing SNAr reaction of a
highly electron-deficient 2,4-dinitrofluorobenzene (13)
with N-hydroxytryptophan derivative 12 which yielded the
arylated pyrroloindoline 15 through a [3,3]-sigmatropic re-
arrangement of transient intermediate 14 (Scheme 4).9b
In fact, N,O-disubstituted unsaturated hydroxylamines
16a–d are known to be unstable and to undergo [3,3]-sig-
matropic rearrangement (Scheme 4). For example the Bar-
toli indole synthesis proceeds by the rearrangement of N-
aryl-O-vinylhydroxylamines 16a obtained by the addition
of vinyl Grignard reagents to nitroarenes.13 Transient 16a
could also be generated by the O-addition of N-arylhydrox-
ylamines to alkynes or allenes14 or by the Chan–Lam cou-
pling between N-arylhydroxylamines and alkenyl boronic
acids.15 Benzofurans 18 are obtained by the rearrangement
of N-vinyl-O-arylhydroxylamines 16b which could be pro-
duced by the condensation of O-arylhydroxylamines and
ketones,16 analogous to the Fischer indole synthesis, or by
1,4-addition to α,β-unsaturated O-aryloximes17 or by O-
arylation of oximes.18 The synthesis of pyrroles 19 was de-
scribed from N-O-divinylhydroxylamine intermediate 16c
by direct O-vinylation19 of oximes or isomerisation of O-al-
lyl oximes.20 Recently, the Bartoli reaction has been extend-
ed to the synthesis of 2-amino-2′-hydroxy-1,1′-biaryls 20
through the generation of N,O-diarylhydroxylamines 16d
by addition of aryl Grignard reagents to nitroarenes.21
Somei described only one example of the SNAr–sigma-
tropic rearrangement sequence from N-hydroxyindoles. We
wished to expand this process to other electrophilic aryl
sources 21 (Scheme 4) since the SNAr requires highly elec-
tron-deficient fluorobenzene derivatives and/or high tem-
perature and the resulting product is the pyrroloindoline
and not the benzofuroindoline probably because the phe-
nol produced is not nucleophilic enough.
Transition-metal-free cross-coupling between bi-
aryliodonium salts and OH-containing substrates22 includ-
ing hydroxylamine derivatives or oximes23 are known.
During our own investigations, the groups of Kürti18 and
Olofsson16f reported the synthesis of benzofurans by the
NO2
NHAc
NHAc
MeO2C
MeO2C
OH
F
O2N
NO2
CO2Me
Et3N, THF
[3,3]
+
NAc
N
O
N
35%
N
H
H
NO2
OH
NO2
13
12
14
15
O2N
H
N
O
R1
R1
R
NH
R
N
R2
O
R2
[3,3]-sigmatropic rearrangement
OH
7 from 16a
18 from 16b
R
R4
R3
H
NH
N
17
OH
16a, N-aryl-O-vinyl-hydroxylamine
16b, N-vinyl-O-aryl-hydroxylamine
16c, N,O-bivinyl-hydroxylamine
16d, N,O-biaryl-hydroxylamine
R1
R2
20 from 16d
19 from 16c
this work
NHPG
NHPG
R
PGHN
[3,3]
+
N
N
O
R
R
O
OH
N
H
H
22
21
9
10
Scheme 4 [3,3]-Sigmatropic rearrangements of hydroxylamine derivatives N,O-disubstituted with unsaturated substituents
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1269–1275

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T. Tomakinian et al.
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metal-free O-arylation of oximes with biaryliodonium salts,
followed by a [3,3]-sigmatropic rearrangement of the tran-
After the optimization of the ratio of 9a/(11a + 24a), we
noticed that it was best to shorten the reaction time to 30
minutes and to avoid using more than 1.5 equivalents of bi-
aryliodonium triflate 23a in order to minimize the forma-
tion of arylated pyrroloindoline 25 (Table 2). After the O-
arylation of the N-hydroxyindole 10a and the sigmatropic
rearrangement, benzofuroindoline 9a and a free phenol-
containing pyrroloindoline could be present in equilibrium.
The latter could be subjected to the O-arylation of the phe-
nol to yield 25a. Benzofuroindolines 9a and 9b were ob-
tained in combination with 11 and 24 from biphenyliodoni-
um triflate 23a and bis(4-chlorophenyl)iodonium triflate
23b, respectively (Table 2, entries 1 and 2).12
In order to avoid the formation of pyrroloindolines 25,
the use of a tryptamine-derived N-hydroxyindole which
does not contain an N–H bond on the side chain was re-
quired. Therefore we decided to use N-benzyl acetamide
10b in the O-arylation reaction with biphenyliodonium tri-
flate 23a or bis(4-chlorophenyl)iodonium triflate 23b or
bis(4-methoxyphenyl)iodonium triflate 23c (Table 2, en-
tries 3 and 4). Indeed, benzofuroindolines 9c, 9d and 9e
were all obtained along with indole 11b.
sient
N-vinyl-O-arylhydroxylamines.
These
reports
prompted us to disclose our preliminary findings in the
synthesis of benzofuroindolines via the tandem metal-free
O-arylation of N-hydroxyindoles with biaryliodonium re-
agents followed by a [3,3]-sigmatropic rearrangement.
After an extensive screening of reaction conditions we
observed that with biphenyliodonium triflate 23a in MeOH
in the presence of base, the desired benzofuroindoline 9a
was formed along with indoles 11a and 24a (Table 1). In-
dole 11a arose from N–O bond cleavage while 24a was
probably produced by N-arylation of indole 11a. The diffi-
culty of this process is too keep the N–O bond intact since
the N-hydroxyindole seems to be sensitive in comparison
with other N–O containing substrates towards O-aryla-
tion.14–20,22–26 The mechanism of this N–O bond cleavage is
unclear to us. It should be noted that, above 0 °C, the in-
doles 11a and 24a are predominantly obtained and that 1.5
equivalents of the biphenyliodonium triflate were required
to ensure a good conversion. Potassium carbonate proved to
be the base of choice and the use of 2 equivalents was opti-
mal (Table 1, entries 1–4) since a 1:0.7 ratio of benzofuroin-
doline 9a and unwanted indoles (11a + 24a) was obtained.
Triethylamine, sodium hydrogenocarbonate and potassium
tert-butoxide were also able to mediate the formation of
benzofuroindoline 9a (Table 1, entries 5–9).
Preparative TLC on silica gel allowed us to isolate benzo-
furoindolines 9a and 9c as single components.
It is interesting to note that we also examined various
well-known metal-catalyzed O-arylation reactions such as
Ullmann,24 Buchwald–Hartwig16d or Chan–Lam15,16c,25,26
couplings with 10a (Scheme 5). Despite extensive efforts, it
turned out that the N–O bond of N-hydroxyindoles is par-
ticularly fragile and no benzofuroindolines were obtained.
Table 1 Optimization of the Base for the Synthesis of Benzofuroindo-
line 9a by the Metal-Free O-Arylation of N-Hydroxyindole 10a with Bi-
phenyliodonium Triflate 23a
O
NHAc
AcHN
‘Ullmann coupling’
N
H
CuI, PhI
or
Ph2IOTf (23a)
NHAc
no benzofuroindoline
(1.5 equiv)
N
‘Buchwald–Hartwig coupling’
OH
O
N
Pd°, PhI
or
‘Chan–Lam coupling’
PhB(OH)2, Cu salts
or
base, MeOH
0 °C, 2 h
N
OH
10a
N
H
H
R
>90%
conversion
10a
9a
11a, R = H
24a, R = Ph
Ph2IOTf, Cu salts
Scheme 5 Failed attempts of the O-arylation of N-hydroxyindoles by
metal-catalyzed coupling reactions
Entry
Base
Equiv
Ratio 9a/(11a + 24a)a
1
2
3
4
5
6
7
8
9
K2CO3
K2CO3
K2CO3
K2CO3
Et3N
0.5
1.5
2.0
4.0
1.0
1.5
2.0
1.5
1.5
1:2
1:1
In parallel to the O-arylation/sigmatropic strategy we
also investigated the C3-regioselective nucleophilic addi-
tion of phenols to N-hydroxyindoles. Somei and co-workers
have demonstrated that nucleophiles could be added at var-
ious positions of N-hydroxyindoles.9 The addition of indoles
or pyrroles nucleophiles at C-3 of N-hydroxyindoles by
mesylation is noteworthy (cf 26a and 26b, Scheme 6).9c,h
We therefore studied the addition of p-methylphenol or p-
methylanisole 4 to N-hydroxyindole 9a in the presence of
mesyl chloride without success (Scheme 6). Further investi-
1:0.7
complex mixture
1:2
Et3N
1:0.8
1:1
Et3N
NaHCO3
t-BuOK
1:1.2
1:1.2
a Determined by 1H NMR of the crude.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1269–1275

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T. Tomakinian et al.
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Table 2 Metal-Free Synthesis of Benzofuroindolines 9 from N-Hydroxyindoles 10 and Biaryliodonium Triflates 23
R1
R1
NAc
NAc
R1
AcN
R2
Ar2IOTf
OAr
R2
23a, Ar = Ph
23b, Ar = 4-ClC6H4
23c, Ar = 4-MeOC6H4
NAc
N
O
N
R3
11, R3 = H
24, R3 = Ar
K2CO3, MeOH
0 °C
N
H
H
OH
N
H
H
10a, R1 = H
10b, R1 = Bn
25 (if R1 = H)
9
Entry
R1
R2
9
Yields of 9/(11 + 24) (isolated as mixture)
25
Yield of 25
1
2
3
4
5
H
H
9a
9b
9c
9d
44%/36%
22%/40%
17%/41%
18%/30%
15%/27%
25a
25b
–
20%
trace
–
H
Cl
H
Bn
Bn
Bn
Cl
–
–
OMe
9e
–
–
gations of this type of coupling in acidic conditions also met
with failure. O-Acetyl-N-hydroxyindole 27 also did not lead
to the desired adducts.
In conclusion, we have investigated the synthesis of N-
hydroxyindoles and the transformation of these sensitive
substrates into tryptamine-derived benzofuroindolines
through different approaches. Finally a transition-metal-
Somei's addition of heteroarenes to N-hydroxyindoles
NHCOCF3
NH
NH
N
H
N
+
N
COCF3
COCF3
MsCl, Et3N
CHCl3
N
N
H
N
H
H
H
OH
26a
30%
26b
7%
10
our failed attempts towards benzofuroindoline 9 derived from tryptamine
OR
O
N
4 (R = H or Me)
H
no C3-addition
MsCl, Et3N
CH2Cl2
N
OH
10a
or
acidic conditions
Ac2O, Py 94%
O
N
OR
H
(R = H or Me)
4
N
OAc
no C3-addition
basic or
27
acidic conditions
Scheme 6 Somei’s addition of an indole nucleophile to the C3-position of N-hydroxyindole 10 and our failed attempts to add phenol derivatives to N-
hydroxyindoles
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1269–1275

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free O-arylation with biaryliodonium salts followed by a
spontaneous [3,3]-sigmatropic rearrangement delivered
the desired targets that we could not access with our previ-
ous methodologies.4–7 Improvement of this methodology
and application to the synthesis of natural-product-like
compounds will be pursued.
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Acknowledgment
We gratefully acknowledge the ANR (ANR-12-JS07-0002; ‘Programme
JCJC 2012’; project name ‘CouPhIn’) for a Graduate Fellowship (T.T.)
and financial support, and the Université Paris Sud and the CNRS for
financial support.
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Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380346.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
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F.; Sammakia, T. Angew. Chem. Int. Ed. 2010, 49, 2397.
(2) (a) For the isolation of azonazine, see: Wu, Q.-X.; Crews, M. S.;
Draskovic, M.; Sohn, J.; Johnson, T. A.; Tenney, K.; Valeriote, F.
A.; Yao, X.-J.; Bjeldanes, L. F.; Crews, P. Org. Lett. 2010, 12, 4458.
(b) For total synthesis, see: Zhao, J.-C.; Yu, S.-M.; Liu, Y.; Yao, Z.-J.
Org. Lett. 2013, 15, 4300.
(3) For reviews on the synthesis of benzofuroindolines, see:
(a) Beaud, R.; Tomakinian, T.; Denizot, N.; Pouilhès, A.;
Kouklovsky, C.; Vincent, G. Synlett 2015, 26, 432. (b) Ito, Y.;
Ueda, M.; Miyata, O. Heterocycles 2014, 89, 2029. (c) Lachia, M.;
Moody, C. J. Nat. Prod. Rep. 2008, 25, 227. For selected examples,
see: (d) Ghosh, S.; Kinthada, L. K.; Bhunia, S.; Bisai, A. Chem.
Commun. 2012, 48, 10132. (e) Austin, J. F.; Kim, S.-G.; Sinz, C. J.;
Xiao, W.-J.; MacMillan, D. W. C. Proc. Natl. Acad. Sci. U.S.A. 2004,
101, 5482. (f) Lozano, O.; Blessley, G.; Martinez del Campo, T.;
Thompson, A. L.; Giuffredi, G. T.; Bettati, M.; Walker, M.;
Borman, R.; Gouverneur, V. Angew. Chem. Int. Ed. 2011, 50,
(11) The DMDO-mediated oxidation of an indoline into an N-
hydroxyindole
related
to
the
stephacidins
was
reported:Hafensteiner, B. D.; Escribano, M.; Petricci, E.; Baran, P.
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(12) General Procedure for the Synthesis of N-Hydroxyindoles 10:
Et3SiH (1.12 mL, 7.00 mmol, 2 equiv) was added to a solution of
N-acetyltryptamine 11a (700 mg, 3.50 mmol, 1 equiv) in TFA
(10 mL) and the mixture was stirred at 60 °C for 24 h. After
evaporation of the solvent, the crude product was made basic
by adding sat. NaHCO3 under ice cooling and the mixture was
extracted with CH2Cl2–MeOH (95:5). The extract was washed
with brine, dried over MgSO4, filtered and evaporated under
reduced pressure. Purification by column chromatography
using EtOAc–MeOH (95:5) afforded the indoline as a yellow oil
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1269–1275

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Synlett
(528 mg, 2.59 mmol, 74%). This indoline (400 mg, 1.96 mmol, 1
equiv) in MeOH (1.5 mL) was added dropwise to a solution of
70% m-CPBA (675 mg, 3.91 mmol, 1.4 equiv) in MeOH (1.5 mL)
at 0 °C. The mixture was then warmed slowly to r.t. and stirred
for 12 h. Flash column chromatography purification (100%
EtOAc) led to N-hydroxyindole 10a as a white solid (364 mg,
1.67 mmol, 85%); Rf = 0.41 (MeOH–EtOAc, 5:95).
(13) (a) Bartoli, G.; Palmieri, G.; Bosco, M.; Dalpozzo, R. Tetrahedron
Lett. 1989, 30, 2129. (b) Dobbs, A. J. Org. Chem. 2001, 66, 638.
(14) (a) Wang, Y.; Ye, L.; Zhang, L. Chem. Commun. 2011, 47, 7815.
(b) Kawade, R. K.; Huang, P.-H.; Karad, S. N.; Liu, R.-S. Org.
Biomol. Chem. 2014, 12, 737.
(15) Wang, H.-Y.; Anderson, L. L. Org. Lett. 2013, 15, 3362.
(16) (a) Sheradasky, T. Tetrahedron Lett. 1966, 43, 5225. (b) Miyata,
O.; Takeda, N.; Naito, T. Org. Lett. 2004, 6, 1761. (c) Contiero, F.;
Jones, K. M.; Matts, E. A.; Porzelle, A.; Tomkinson, N. C. O. Synlett
2009, 3003. (d) Maimome, T. J.; Buchwald, S. L. J. Am. Chem. Soc.
2010, 132, 9990. (e) Liu, Y.; Quian, J.; Lou, S.; Xu, Z. J. Org. Chem.
2010, 75, 6300. (f) Ghosh, R.; Stridfeldt, E.; Olofsson, B. Chem.
Eur. J. 2014, 20, 8888.
N-Hydroxyindole 10a: 1H NMR (250 MHz, MeOD): δ = 8.07 (br
s, 1 H), 7.52 (d, J = 9.5 Hz, 1 H), 7.34 (d, J = 9.5 Hz, 1 H), 7.14 (t,
J = 6.7 Hz, 1 H), 7.11 (s, 1 H), 7.00 (t, J = 6.6 Hz, 1 H), 3.44 (t, J =
7.2 Hz, 2 H), 2.90 (t, J = 7.3 Hz, 2 H), 1.91 (s, 3 H). 13C NMR (90
MHz, MeOD): δ = 173.4, 135.8, 125.2, 124.5, 122.8, 119.8, 119.6,
109.4, 108.9, 41.7, 26.1, 22.7. IR (KBr): 3250, 3105, 1680, 1619,
1602, 1580, 743 cm–1. HRMS (ESI+): m/z [M + H]+ calcd for
[C12H15N2O2]+: 219.1089; found: 219.1128.
(17) Ueda, M.; Ito, Y.; Ichii, Y.; Kakiuchi, M.; Shono, H.; Miyata, O.
Chem. Eur. J. 2014, 20, 6763.
General Procedure for the Synthesis of Benzofuroindolines
9: To a solution of N-hydroxyindole 10a (50 mg, 0.229 mmol, 1
equiv) in MeOH (1 mL), K2CO3 (45 mg, 0.326 mmol, 1.4 equiv)
and then Ph2IOTf 23a (153 mg, 0.356 mmol, 1.5 equiv) were
added at 0 °C and the reaction mixture was stirred for 2 h at 0
°C. Flash column chromatography purification (cyclohexane–
EtOAc: 60:40 → 40:60) led to 25a (14 mg of pyrroloindoline,
20%) and 70 mg of a (1:0.7:0.4 ratio) mixture of benzofuroindo-
line 9a (44%), indoles 11a and 24a (36%). Preparative TLC on
silica gel (MeOH–EtOAc, 5:95) of the mixture allowed the isola-
tion of benzofuroindoline 9a as a single product. Benzofuroin-
doline 9a: Rf = 0.37 (MeOH–EtOAc, 5:95). 1H NMR (250 MHz,
CDCl3): δ = 7.28 (d, J = 7.2 Hz, 1 H), 7.18 (d, J = 7.3 Hz, 1 H), 7.06
(q, J = 7.9 Hz, 2 H), 6.87 (t, J = 7.0 Hz, 1 H), 6.77 (t, J = 7.2 Hz, 2 H),
6.65 (d, J = 7.9 Hz, 1 H), 6.27 (d, J = 2.5 Hz, 1 H), 5.25 (br s, 1 H, N
(18) Gao, H.; Xu, Q.-L.; Keene, C.; Kürti, L. Chem. Eur. J. 2014, 20,
8883.
(19) (a) Trofimov, B. A.; Schmidt, E. Y.; Zorina, N. V.; Senotrusova, E.
Y.; Protsuk, N. I.; Ushakov, I. A.; Mikhaleva, A.; Méallet-Renault,
R.; Clavier, G. Tetrahedron Lett. 2008, 49, 4362. (b) Trofimov, B.
A.; Mikhaleva, A.; Ivanov, A. V.; Shcherbakova, V. S.; Ushakov, I.
A. Tetrahedron 2015, 71, 124.
(20) Wang, H.-Y.; Mueller, D. S.; Sachwani, R. M.; Kapadia, R.;
Londino, H. N.; Anderson, L. L. J. Org. Chem. 2011, 76, 3203.
(21) Gao, H.; Ess, D. H.; Yousufuddin, M.; Kürti, L. J. Am. Chem. Soc.
2013, 135, 7081.
(22) Jalalian, N.; Petersen, T. B.; Olofsson, B. Chem. Eur. J. 2012, 18,
14140.
(23) (a) Laus, G.; Stadlweiser, J.; Klötzer, W. Synthesis 1989, 773.
(b) Ghosh, R.; Olofsson, B. Org. Lett. 2014, 16, 1830. (c) Misal
Castro, L. C.; Chatani, N. Synthesis 2014, 46, 2312.
H), 3.20 (q, J = 6.7 Hz, 2 H), 2.25–2.40 (m, 2 H), 1.79 (s, 3 H). 13
C
NMR (75 MHz, CDCl3): δ = 170.7, 158.7, 155.8, 147.5, 136.6,
128.6, 123.0, 122.3, 121.3, 119.8, 115.8, 110.0, 109.8, 101.8,
59.1, 36.6, 35.5, 23.3. IR (NaCl): 3033, 2960, 1691, 1599, 1492,
1426, 1378, 912, 753 cm–1. HRMS (ESI+): m/z [M + H]+ calcd for
[C18H19N2O2]+: 295.1441; found: 295.1447.
(24) De, P.; Nonappa; Pandurangan, K.; Maitra, U.; Wailes, S. Org.
Lett. 2007, 9, 2767.
(25) (a) Petrassi, H. M.; Sharpless, K. B.; Kelly, J. W. Org. Lett. 2001, 3,
139. (b) Wang, Z.; Zhang, J. Tetrahedron Lett. 2005, 46, 4997.
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J. Org. Chem. 2011, 76, 1013.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1269–1275

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