Furan ring opening-indole ring closure: SnCl2-induced reductive transformation of difuryl(2-nitroaryl)methanes into 2-(2-acylvinyl)indoles

Article abstract of DOI:10.1016/j.tet.2012.03.069

A simple and efficient method for the synthesis of 2-(2-acylvinyl)-3-(5- alkyl-2-furyl)indoles by reductive recyclization of bis(5-alkyl-2-furyl)(2- nitroaryl)methanes is reported. This transformation was carried out by heating the substrates with SnCl

Full text of DOI:10.1016/j.tet.2012.03.069

Tetrahedron 68 (2012) 4252e4258
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Furan ring openingeindole ring closure: SnCl2-induced reductive transformation
of difuryl(2-nitroaryl)methanes into 2-(2-acylvinyl)indoles
,
d
Maxim G. Uchuskin a, Natalia V. Molodtsova a, Vladimir T. Abaev b, Igor V. Trushkovc
,
,e,
*
Alexander V. Butin a
a Research Institute of Heterocyclic Compounds Chemistry, Kuban State Technological University, Moskovskaya 2, Krasnodar 350072, Russian Federation
b North-Ossetian State University, Vatutina 46, Vladikavkaz 362025, Russian Federation
c M.V. Lomonosov Moscow State University, Department of Chemistry, Leninskie Gory 1/3, Moscow 119991, Russian Federation
d Federal Research Center of Pediatric Hematology, Oncology and Immunology, Laboratory of Chemical Synthesis, Leninskii av. 117/2, Moscow 117997, Russian Federation
e Perm State University, Bukireva 15, Perm 614990, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and efficient method for the synthesis of 2-(2-acylvinyl)-3-(5-alkyl-2-furyl)indoles by reductive
recyclization of bis(5-alkyl-2-furyl)(2-nitroaryl)methanes is reported. This transformation was carried
out by heating the substrates with SnCl2$2H2O in ethanol. The intermediate nitrosoarene moiety in-
teracted with the furan ring via electrophilic nitrogen attack onto the C(2) position of the furan ring. It
was shown that the related bis(5-alkyl-2-thienyl)(2-nitroaryl)methanes under the same reaction con-
ditions failed to undergo the analogous recyclization and were transformed into bis(5-alkyl-2-thienyl)(2-
aminoaryl)methanes.
Received 14 December 2011
Received in revised form 28 February 2012
Accepted 19 March 2012
Available online 2 April 2012
Keywords:
Furans
Ring opening
Ring closure
Indoles
Ó 2012 Elsevier Ltd. All rights reserved.
Reduction
Nitroarenes
Nitrosoarenes
1. Introduction
example is the Cadogan indole synthesis and related processes
consisting of thermal deoxygenation of nitroarenes with various
For many years indoles have attracted the attention of organic
chemists due to their significant role in biology and medicine.1
Among the multiple approaches for the construction of indole
ring systems, an overwhelming majority of methods are based on
nitroarene transformations. Having an important practical advan-
tage, namely, ready availability of the starting compounds these
methods require a subsequent reduction step for incorporation
of the nitro-group nitrogen into the indole ring. The Leim-
grubereBatcho, Reissert, Makosza, and some other nitroarene-
into-indole transformations are based on the obvious reduction of
nitrobenzenes into anilines followed by spontaneous in situ cycli-
zation of the formed amino group onto an electrophilic carbon
atom.1,2 However, depending on the conditions, the quite common
reaction course consists of the interception of the products of in-
complete reduction of the nitro-group with appropriate internal
functional groups. Thus the intermediate hydroxylamine3 or
nitrosoarene4,5 can participate in the indole formation. Another
P(III) compounds6 in which the corresponding nitrenes have been
postulated as intermediates.
In 1979 deoxygenation of (2-nitrophenyl)bis(2-furyl)methanes 1
with triethyl phosphite affording furo[3,2-c]carbazoles 2 was repor-
ted (Scheme 1).7 The reaction was postulated to proceed through the
nitrene attack onto the furan ring followed by rearrangement of the
adduct to give a 2-(2-acylvinyl)-3-furylindole, an Arbuzov-like re-
action with one more triethyl phosphite molecule and a secondary
cyclizationgenerated furocarbazole 2. Underthe sameconditions, (2-
nitrophenyl)bis(pyrrol-2-yl)methane (3, R¼Me) yielded pyrrolo[3,2-
b]quinoline 4. (2-Nitrophenyl)bis(thienyl)methanes reacted simi-
larly to 3 furnishing the corresponding thienoquinolines.7,8
On the other hand, it was recently shown that 3 (R¼H) and its
derivatives are transformed into 4 on heating with SnCl2$2H2O in
methanol.9 Evidently, a nitrene cannot be involved in this process.
The authors rationalized the results by electrophilic attack of
a nitrosoarene or hydroxylamine intermediate onto the electron-
rich heteroaromatic substituent. Similarly, some years ago we
reported one example of the recyclization of 1a (R¼Me) into 2-(2-
acylvinyl)-3-furylindole 5a by treatment with SnCl2$2H2O
* Corresponding author. Fax: þ7 342 237 1480; e-mail addresses: alexander_
butin@mail.ru, av_butin@yahoo.com (A.V. Butin).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.03.069

M.G. Uchuskin et al. / Tetrahedron 68 (2012) 4252e4258
4253
Table 1
Synthesis of nitroarenes 1
H
N
NO2
P(O)(OEt)2
P(OEt)3
R
R 1
O
R 2
NO2
+
O
O
R 5
3
R
X
CHO
R4
R
R
2
1
7a X = O, R5 = Me;
7b X = O, R5 = Et;
7c X = O, R5 = t-Bu;
7d X = S, R5 = Me;
7e X = S, R5 = t-Bu
6a R1 = R2 = R3 = R4 = H;
6b R1 = R2 = R4 = H, R3 = Br;
6c R1 = R3 = R4 = H, R2 = Br;
6d R1 = R2 = R4 = H, R3 = Cl;
NO2
N
P(OEt)3
6e R1 = R3 = R4 = H, R2 = COOMe;
6f R1 = R4 = OMe, R2 = H, R3 = Me;
6g R1 = R4 = H, R2 = R3 = OMe;
6h R1 = R2 = R4 = H, R3 = OMe
N
R
N
R
R
R
N
N
R 1
4
3
R 2
NO2
Scheme 1. Reductions of bis(hetaryl)(2-nitrophenyl)methanes with triethyl phosphite.
HClO4
R 5
3
1,4-dioxane,
R
X
70 oC, 30-40 min
(Scheme 2) and proved that this reaction proceeded through for-
mation of a nitrosoarene.10 It is necessary to point out that com-
pounds of type 5 were proposed as intermediates in the formation
of 2 from 1 and triethyl phosphite.
R4
X
R 5
1a-n
Entry
X
R1
R2
R3
R4
R5
Yield, %
H
NO2
.
N
SnCl2 2H2O, aq. HCl
a
b
c
d
e
f
g
h
i
j
k
l
m
n
O
O
O
O
O
O
O
O
O
O
O
O
S
H
H
H
H
H
H
H
OMe
OMe
OMe
H
H
H
H
H
H
H
H
H
H
Br
H
Cl
H
Me
Me
Me
OMe
OMe
H
H
H
H
H
H
H
H
OMe
OMe
OMe
H
H
H
Me
Et
74
72
92
73
71
76
72
70
76
87
94
81
88
78
O
ether, rt, 6h
O
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
Me
O
O
Br
H
CO2Me
H
H
H
OMe
H
H
5a
1a
Et
Scheme 2. Reduction of bis(2-furyl)(2-nitrophenyl)methane 1a with SnCl2$2H2O.
t-Bu
t-Bu
t-Bu
t-Bu
Me
We supposed that 5a was formed through the intramolecular
DielseAlder reaction between the nitroso moiety and furan ring
followed by rearrangement of the cycloadduct. The similar process
cannot be realized for thienyl and pyrrolyl analogues due to the
much lower ability of these five-membered rings to react as dienes
in [4þ2]-cycloaddition reactions.
S
H
H
H
H
The different reactivity of furans and other (het)arenes was also
found in many intramolecular electrophilic reactions.11 Namely,
electrophiles usually attack at the ipso-position of 2,5-disubstituted
furans but at the unsubstituted ortho-atom in other (het)arenes.
Thus, 2-(acylamino)diphenylmethanes underwent cyclization to
The prepared difuryl(2-nitroaryl)methanes 1ael were treated
with SnCl2$2H2O under the reaction conditions applied earlier for
the transformation of 3 into 4.15 We found that the substrates 1aej
afforded 2-(2-acylvinyl)-3-furylindoles 5aej in moderate to good
yields (Table 2). Substitution of ethanol for methyl alcohol has no
effect on both the direction of reaction and yields of products.
Similarly to the pyrrolo[3,2-b]quinoline 4 formation, this trans-
formation is a fast process; full conversion of 1 was achieved after
heating the reaction mixture at reflux for 40e60 min.
On the contrary, (2-nitrophenyl)bis(thienyl)methanes 1m,n
were reduced by SnCl2 to the corresponding anilines 8. Similarly,
anilines were obtained in reaction of difuryl(2-nitrophenyl)meth-
anes 1k,l containing a strongly electron-donating methoxy sub-
stituent para to the nitro-group. It is interesting that an ortho-
methoxy group does not interfere the formation of indoles 5.
Comparison of the results obtained for various 2-alkylfurans,
demonstrates clearly that the better yields were obtained in re-
actions of 1ceh having 5-tert-butyl-substituted furyl groups. It can
be explained by the formation of side-products when the furan ring
contains methyl or ethyl group at the C(5) position. Presumably, it is
related to the possibility of deprotonation of the 5-alkyl group in
these cases. For substances 1a,i,j we did not identify by-products.
Careful separation of the reaction mixture obtained by reduction
of 1b allowed us to isolate in minor quantities triketoindole 9 along
with 3-furylindole 5b (Scheme 3). The analogous furan ring open-
ing of 3-(5-alkyl-2-furyl)indoles was found earlier in other acid-
catalyzed recyclizations of aryldifurylmethanes.17e,f
give dibenzazepines via BischlereNapieralski-like reactions.12
A
similar process was reported for 2-[2-(aminocarbamoyl)benzyl]
thiophenes.13 However, 2-[2-(acylamino)benzyl]furans were
transformed under these conditions into quinoline derivatives
rather than into furo[3,2-c][1]benzazepines.14 Another example is
an interaction of 2-(het)arylanilines with aldehydes under Pic-
teteSpengler conditions, which usually yield quinolines annulated
to an ortho-hetaryl group.15 Conversely, under the same conditions
2-(2-furyl)anilines undergo furan ring opening furnishing 3-(2-
acylvinyl)-2-(het)arylindoles.16 The report about the electrophilic
mechanism of cyclization in reaction of 3 with SnCl2 stimulated us
to study the corresponding reaction of 1 in more detail as a de-
velopment of our investigations of furan-into-indole recycliza-
tions.16,17 Herein, we report the results of this study.
2. Results and discussion
The parent difuryl(2-nitroaryl)methanes 1ael were synthesized
by HClO4-catalyzed condensation of 2-nitrobenzaldehydes 6 with
2-alkylfurans 7aec (Table 1). The analogous condensation of alde-
hydes 6a with 2-alkylthiophenes 7d,e provided (2-nitrophenyl)
bis(thienyl)methanes 1m,n.

4254
M.G. Uchuskin et al. / Tetrahedron 68 (2012) 4252e4258
Table 2
case of furans 1. The formed
s-complex 11 rearranges into 2-(2-
Preparation of indoles 5 by reductive cyclization of nitroarenes 1 with SnCl2$2H2O
acylvinyl)indole 5. It can also loose a proton from the alkyl group
at the C(5) atom of the furan ring if this is a methyl or ethyl group. It
explains the formation of various by-products and tar in reactions of
1a,b,i,j. Thiophenes are much less nucleophilic than furans or pyr-
roles. As a result, the intermediate nitroso group fails to attack the
thiophene ring in 10m,n and these compounds undergo smooth
reduction to anilines 8. The formation of 2-[bis(furyl)methyl]ani-
lines 8k,l is also consistent with this mechanism. In this case the
para-methoxy group strongly decreases the electrophilicity of the
nitrosoarene nitrogen. So, the reduction of 10k,l proceeds much
faster than cyclization, and only anilines were isolated.
R 1
R 2
NO2
.
R 5
SnCl2 H O
2
2
3
R
X
EtOH, reflux, 1h
R4
X
R 5
1a-n
R 1
R 1
R 2
H
N
The alternative mechanism including DielseAlder reaction10
between the furyl and nitroso moieties in 10 seems to be less
probable as it is inconsistent with better yields in reactions of 1ceh
having bulky tert-butyl group in comparison with 1a,b,i,j.
R 2
NH2
O
R 5
R 5
+
3
R
3
X
R
R4
R4
O
X
3. Conclusion
R 5
R 5
8k-n
R5
5a-j
In summary, we have demonstrated that the reduction of bis(2-
furyl)(2-nitrophenyl)methanes with SnCl2$2H2O at reflux in etha-
nol afforded 2-(2-acylvinyl)indoles as a result of the electrophilic
attack of the intermediate nitrosoarene onto the ipso-position of the
furan ring. We believe that the described procedure would be useful
for organic chemists as a simple route to these highly functionalized
indoles. Reduction of (2-nitrophenyl)bis(2-thienyl)methanes under
the above conditions leads to the formation of anilines.
These results and earlier reported transformation of (2-
nitrophenyl)bis(2-pyrrolyl)methane into pyrrolo[3,2-b]quinoline
under the same treatment can be explained by interception of the
intermediate electrophilic nitrosoarenes by the highly nucleophilic
furan and pyrrole rings. On the contrary, the less nucleophilic
thiophenes failed to react under these conditions resulting in fur-
ther reduction of the nitrosoarene intermediate to give the corre-
sponding anilines.
Entry
X
R1
R2
R3
R4
Yield, %
5
8
a
b
c
d
e
f
g
h
i
j
k
l
m
n
O
O
O
O
O
O
O
O
O
O
O
O
S
H
H
H
H
H
H
H
OMe
OMe
OMe
H
H
H
H
H
H
H
Br
H
CO2Me
H
H
H
H
H
H
Br
H
Cl
H
Me
Me
Me
OMe
OMe
H
H
H
H
H
H
H
H
OMe
OMe
OMe
H
H
H
Me
Et
37
40
60
65
61
73
62
67
30
44
d
d
d
d
d
d
d
d
d
d
d
51
55
54
63
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
Me
Et
OMe
H
H
t-Bu
t-Bu
t-Bu
Me
d
d
S
H
H
H
H
d
4. Experimental section
4.1. General
NO2
.
SnCl2 2H2O
EtOH, reflux
Melting points are uncorrected. 1H NMR and 13C NMR spectra
were recorded on Bruker DPX 300 and JEOL Delta ECA 400 spec-
O
O
trometers at room temperature; the chemical shifts
d were mea-
sured in parts per million with respect to the solvent (CDCl3, 1H:
d
¼7.26 ppm, 13C:
d
¼77.0 ppm; DMSO-d6, 1H:
d
¼2.50 ppm, 13C:
1b
d¼39.5 ppm). Coupling constants (J) are given in hertz. Splitting
H
H
N
patterns of an apparent multiplet associated with an averaged
coupling constants were designated as s (singlet), d (doublet), t
(triplet), q (quartet), m (multiplet), dd (doublet of doublets) and br
(broadened). IR spectra were measured as KBr plates on Prestige-21
FT-IR and Bruker Alpha FT-IR spectrophotometers. Mass spectra
were recorded on a Kratos MS-30 instrument with 70 eV electron
impact ionization at 200 ꢀC. Column chromatography was per-
N
+
O
O
O
O
O
formed on silica gel KSK (50e160 mm, LTD Sorbpolymer). The
5b
9
starting 2-nitrobenzaldehydes 6aed were commercial reagents.
Other aldehydes were synthesized according to published
procedures.20e22 2-tert-Butylfuran 7c was obtained by described
procedure.23 2-tert-Butylthiophene was synthesized similarly
starting from 5-tert-butylthiophene-2-carboxylic acid.24 All the
reactions were carried out using freshly distilled and dry solvents
from solvent stills.
Scheme 3. Preparation of 3-furylindole 5b and triketoindole 9.
The obtained results and previous data9,10 are consistent with the
mechanism demonstrated in Scheme 4. Reduction of nitroarene 1
leads to the formation of nitrosoarene 10, which attacks the
electron-enriched heteroaromatic ring. The electrophilic nature of
the nitrogen atom in nitrosoarenes is well-known; it was exploited
in the syntheses of both indoles18 and other heterocycles.19 In
the discussed reaction the nitrogen electrophilicity is possibly
increased by tin chloride or proton coordination to the nitroso group
oxygen. The electrophilic nitrogen attacks the ortho-position of the
pyrrole ring in 3 leading to compounds 4 but the ipso-position in the
4.2. General procedure for synthesis of nitroarenes 1aen
Aq. HClO4 (70%, 0.3 mL) was added to solution of 2-
nitrobenzaldehyde 6 (5 mmol) and compound 7 (12.5 mmol) in

M.G. Uchuskin et al. / Tetrahedron 68 (2012) 4252e4258
4255
R1
R1
R1
OM
NO2
R5
R2
R2
R2
NO
N
O
M+
SnCl2
+
R5
R5
3
3
3
M = H
or Sn
O
R
O
R
R
R 4
R 4
R 4
O
H
O
R5
O
R5
R5
1
10
11
R1
R1
R5
OM
N
O
R2
R2
H
N
SnCl2
O
3
3
R
R
R5
R 4
R 4
O
O
R5
R5
5
Scheme 4. Proposed mechanism of 2-(2-acylvinyl)indoles 5 formation.
1,4-dioxane (15 mL). The reaction mixture was stirred at 70 ꢀC for
40e60 min (TLC control), then poured into cold water (200 mL).
The product was extracted with ethyl acetate (3ꢁ50 mL). The
combined organic fractions were dried with Na2SO4 and evapo-
rated to dryness under reduced pressure. The product was purified
by flash chromatography using CH2Cl2/petroleum ether (1:9)
mixture as an eluent. Compounds 1beg,j,k,m,n were obtained as
light-yellow oils and used without additional purification.
3.40%. Rf¼0.61 (acetone/CH2Cl2/petroleum ether¼1:1:3); nmax (KBr)
2969, 1602, 1589, 1555, 1513, 1491, 1480, 1461, 1336, 1265, 1231,
1195, 1125, 1067, 1034, 1018, 838, 800, 790, 750 cmꢂ1
; dH (300 MHz,
CDCl3) 8.04 (1H, d, J 9.0 Hz, HAr), 6.83 (1H, dd, J 9.0, 2.7 Hz, HAr), 6.77
(1H, d, J 2.7 Hz, HAr), 6.40 (1H, s, CH) 5.90 (2H, d, J 3.0 Hz, HFur), 5.85
(2H, d, J 3.0 Hz, HFur), 3.77 (3H, s, OCH3), 1.22 (18H, s, C(CH3)3); dC
(75 MHz, CDCl3) 164.1 (2C), 163.2, 150.7 (2C), 141.8, 138.5, 127.8,
115.6,113.2,108.6 (2C),102.5 (2C), 55.8, 40.5, 32.8 (2C), 29.2 (6C); m/
z (EI, 70 eV) 411 (Mþ, 23), 394 (100), 272 (18), 216 (12), 57 (58), 43
(32).
4.2.1. Bis(5-methyl-2-furyl)(2-nitrophenyl)methane
(1a).11a Pale-
brown solid; yield 74% (1.10 g); mp 82e83 ꢀC; dH (300 MHz, CDCl3)
7.93e7.97 (1H, m, HAr), 7.61e7.69 (1H, m, HAr), 7.49e7.57 (1H, m,
HAr), 7.28e7.32 (1H, m, HAr), 6.16 (1H, s, CH), 5.96 (2H, d, J 3.2 Hz,
HFur), 5.88 (2H, d, J 3.2 Hz, HFur), 2.23 (6H, s, CH3).
4.3. General procedure for synthesis of indoles 5aej
A mixture of 1 (2 mmol), SnCl2$2H2O (2.26 g; 10 mmol) and
ethanol (20 mL) was heated at reflux for 40e60 min (TLC control).
Then the reaction mixture was poured into cold water (250 mL) and
aq NaHCO3 was added to be the neutral reaction. The precipitate
was filtered off. The aqueous layer was extracted with ethyl acetate
(3ꢁ30 mL). The precipitate was extracted with 1,4-dioxane
(4ꢁ50 mL). The combined organic fractions were dried with
Na2SO4 and evaporated to dryness under reduced pressure. Prod-
ucts were purified by column chromatography on silica gel using
CH2Cl2/petroleum ether (1:5) mixture as an eluent and recrystal-
lized from CH2Cl2/petroleum ether.
4.2.2. (2,5-Dimethoxy-3-methyl-6-nitrophenyl)bis(5-methyl-2-furyl)
methane (1h). Pale-green solid; yield 70% (1.30 g); mp 131e132 ꢀC.
Found: C, 64.45; H, 5.69; N, 3.73. C20H21NO6 requires C, 64.68; H,
5.70; N, 3.77%. Rf¼0.53 (acetone/CH2Cl2/petroleum ether¼1:1:3);
nmax (KBr) 1605,1566,1535,1479,1468,1402,1369,1325,1242,1215,
1140, 1096, 1036, 961, 810, 785 cmꢂ1
; dH (400 MHz, CDCl3) 6.78 (1H,
s, HAr), 5.98 (2H, d, J 3.2 Hz, HFur), 5.88 (2H, d, J 3.2 Hz, HFur), 5.82
(1H, s, CH), 3.80 (3H, s, OCH3), 3.47 (3H, s, OCH3), 2.33 (3H, s, CH3),
2.23 (6H, s, CH3); dC (100 MHz, CDCl3) 151.5 (2C), 150.2, 149.8 (2C),
147.0,140.2,134.3, 126.0, 114.0,109.7 (2C),106.6 (2C), 61.1, 56.7, 37.3,
17.1, 13.7 (2C); m/z (EI, 70 eV) 371 (Mþ, 38), 354 (100), 309 (50), 274
(45), 214 (20), 162 (20), 110 (25), 58 (18), 44 (63).
4.3.1. (3E)-4-[3-(5-Methyl-2-furyl)-1H-indol-2-yl]but-3-en-2-one
(5a). Pale-brown solid; yield 37% (0.20 g); mp 215e216 ꢀC. Found:
C, 77.07; H, 5.84; N, 5.27. C17H15NO2 requires C, 76.96; H, 5.70; N,
5.28%. Rf¼0.32 (acetone/CH2Cl2/petroleum ether¼1:1:3); nmax
4.2.3. Bis(5-ethyl-2-furyl)(2,5-dimethoxy-3-methyl-6-nitrophenyl)
methane (1i). Pale-brown solid; yield 76% (1.52 g); mp 105e106 ꢀC.
Found: C, 66.39; H, 6.30; N, 3.53. C22H25NO6 requires C, 66.15; H,
6.31; N, 3.51%. Rf¼0.59 (acetone/CH2Cl2/petroleum ether¼1:1:3);
nmax (KBr) 1604, 1562, 1537, 1476, 1404, 1371, 1329, 1254, 1233, 1182,
(KBr) 3296, 1640, 1602, 1326, 1269, 1234, 1032, 969, 743 cmꢂ1
; dH
(300 MHz, DMSO-d6) 11.74 (1H, s, NH), 7.99 (1H, d, J 16.2 Hz, ]CH),
7.88e7.85 (1H, m, HAr), 7.42e7.40 (1H, m, HAr), 7.31e7.26 (1H, m,
HAr), 7.15e7.09 (1H, m, HAr), 6.83 (1H, d, J 16.2 Hz, ]CH), 6.71 (1H,
d, J 3.3 Hz, HFur), 6.29 (1H, d, J 3.3 Hz, HFur), 2.41 (3H, s, CH3), 2.36
(3H, s, CH3); dC (75 MHz, DMSO-d6) 197.4, 151.3, 147.3, 137.8, 131.8,
129.5, 125.7, 125.0, 124.8, 120.8, 120.4, 112.0, 111.7, 108.8, 107.9, 27.2,
13.4; m/z (EI, 70 eV) 265 (Mþ, 100), 248 (25), 222 (78), 194 (95), 180
(38), 167 (16), 125 (11), 43 (27).
1103,1051,1018,1007, 966, 814, 787, 766 cmꢂ1
; dH (400 MHz, CDCl3)
6.78 (1H, s, HAr), 5.98 (2H, d, J 3.2 Hz, HFur), 5.89 (2H, d, J 3.2 Hz,
HFur), 5.84 (1H, s, CH), 3.80 (3H, s, OCH3), 3.46 (3H, s, OCH3), 2.58
(4H, q, J 7.6 Hz, CH2), 2.33 (3H, s, CH3), 1.18 (6H, t, J 7.6 Hz, CH3); dC
(100 MHz, CDCl3) 157.2 (2C), 150.2, 149.7 (2C), 147.0, 140.2, 134.3,
126.1, 114.0, 109.5 (2C), 105.0 (2C), 61.1, 56.7, 37.4, 21.5 (2C), 17.1, 12.4
(2C); m/z (EI, 70 eV) 399 (Mþ, 20), 382 (100), 323 (35), 288 (34), 258
(15), 228 (14), 123 (72), 101 (20), 59 (34), 43 (48).
4.3.2. (1E)-1-[3-(5-Ethyl-2-furyl)-1H-indol-2-yl]pent-1-en-3-one
(5b). Dark-yellow solid; yield 40% (0.23 g); mp 196e197 ꢀC. Found:
C, 77.92; H, 6.78; N, 4.77. C19H19NO2 requires C, 77.79; H, 6.53; N,
4.77%. Rf¼0.43 (acetone/CH2Cl2/petroleum ether¼1:1:3); nmax
(KBr) 3293, 2964, 1649, 1609, 1331, 1261, 1201, 1190, 1031, 959,
4.2.4. Bis(5-tert-butyl-2-furyl)(5-methoxy-2-nitrophenyl)methane
(1l). Dark-yellow solid; yield 81% (1.66 g); mp 69e70 ꢀC. Found: C,
70.23; H, 7.14; N, 3.38. C24H29NO5 requires C, 70.05; H, 7.10; N,
738 cmꢂ1
; dH (400 MHz, DMSO-d6) 11.74 (1H, s, NH), 8.05 (1H, d, J

4256
M.G. Uchuskin et al. / Tetrahedron 68 (2012) 4252e4258
16.0 Hz, ]CH), 7.86e7.84 (1H, m, HAr), 7.42e7.40 (1H, m, HAr),
7.31e7.26 (1H, m, HAr), 7.14e7.10 (1H, m, HAr), 6.90 (1H, d, J 16.0 Hz,
]CH), 6.70 (1H, d, J 3.2 Hz, HFur), 6.28 (1H, d, J 3.2 Hz, HFur), 2.76
(2H, q, J 7.6 Hz, CH2), 2.73 (2H, q, J 7.2 Hz, CH2), 1.29 (3H, t, J 7.6 Hz,
CH3), 1.07 (3H, t, J 7.2 Hz, CH3); dC (100 MHz, DMSO-d6) 199.7, 156.5,
147.3, 137.7, 130.5, 129.7, 124.9, 124.8, 124.6, 120.7, 120.4, 111.9, 111.6,
108.4, 106.5, 33.2, 20.9, 12.1, 8.3; m/z (EI, 70 eV) 293 (Mþ, 100), 264
(48), 236 (32), 222 (14), 208 (16), 57 (54), 44 (28).
m/z (EI, 70 eV) 385/383 (Mþ, 30/90), 370/368 (25/72), 326 (54), 312
(44), 271 (25), 242 (22), 207 (21), 57 (100), 43 (54).
4.3.7. Methyl 2-[(1E)-4,4-dimethyl-3-oxopent-1-enyl]-3-(5-tert-bu-
tyl-2-furyl)-1H-indole-6-carboxylate (5g). Yellow solid; yield 62%
(0.50 g); mp 218e219 ꢀC. Found: C, 73.61; H, 7.10; N, 3.31. C25H29NO4
requires C, 73.69; H, 7.17; N, 3.44%. Rf¼0.55 (acetone/CH2Cl2/petro-
leum ether¼1:1:3); nmax (KBr) 2964, 1706, 1673, 1596, 1508, 1436,
1365, 1309, 1292, 1272, 1214, 1081, 1007, 974, 776, 742 cmꢂ1
; dH
4.3.3. (1E)-1-[3-(5-tert-Butyl-2-furyl)-1H-indol-2-yl]-4,4-
dimethylpent-1-en-3-one (5c). Orange solid; yield 60% (0.42 g); mp
188e189 ꢀC. Found: C, 79.03; H, 7.62; N, 4.18. C23H27NO2 requires C,
79.05; H, 7.79; N, 4.01%. Rf¼0.61 (acetone/CH2Cl2/petroleum
ether¼1:1:3); nmax (KBr) 3316, 2966, 1659, 1573, 1475, 1327, 1283,
(300 MHz, CDCl3) 9.45 (1H, s, NH), 8.32 (1H, d, J 15.9 Hz, ]CH), 8.07
(1H, d, J¼1.5 Hz, HAr), 7.91 (1H, d, J 8.7 Hz, HAr), 7.81 (1H, dd, J 8.7,
1.5 Hz, HAr), 7.15 (1H, d, J 15.9 Hz, ]CH), 6.52(1H, d, J 3.3 Hz, HFur), 6.09
(1H, d, J3.3 Hz, HFur), 3.91 (3H, s, OCH3),1.37 (9H, s, C(CH3)3),1.22(9H, s,
C(CH3)3); dC (75 MHz, CDCl3) 204.1, 168.0, 164.4, 146.5, 136.7, 132.6,
131.7, 129.2, 126.2, 121.5, 121.1, 119.9, 114.0, 113.4, 109.0, 104.0, 52.3,
43.3, 33.0, 29.1 (3C), 26.4 (3C); m/z (EI, 70 eV) 407 (Mþ, 100), 392 (25),
350 (95), 334 (44), 294 (38), 266 (33), 234 (25), 69 (25), 57 (69), 42 (75).
1231, 1088, 1006, 737 cmꢂ1
; dH (300 MHz, DMSO-d6) 11.75 (1H, s,
NH), 8.20 (1H, d, J 15.6 Hz, ]CH), 7.85e7.83 (1H, m, HAr), 7.45 (1H,
d, J 15.6 Hz, ]CH), 7.45e7.42 (1H, m, HAr), 7.33e7.27 (1H, m, HAr),
7.16e7.10 (1H, m, HAr), 6.67 (1H, d, J 3.3 Hz, HFur), 6.25 (1H, d, J
3.3 Hz, HFur), 1.36 (9H, s, C(CH3)3), 1.20 (9H, s, C(CH3)3); dC (75 MHz,
DMSO-d6) 202.7, 162.8, 147.2, 137.6, 130.8, 130.2, 125.0, 124.7, 120.5,
120.4, 119.8, 111.9, 111.5, 108.0, 104.3, 42.7, 32.3, 28.9 (3C), 26.0 (3C);
m/z (EI, 70 eV) 349 (Mþ, 96), 334 (77), 292 (100), 277 (45), 248 (22),
236 (35), 209 (35), 180 (40), 85 (18), 69 (40), 57 (34), 42 (47).
4.3.8. 1-[3-(5-tert-Butyl-2-furyl)-4,7-dimethoxy-5-methyl-1H-indol-
2-yl]-4,4-dimethylpent-1-en-3-one (5h). Dark-orange solid; yield
67% (0.57 g); mp 225e226 ꢀC. Found: C, 73.61; H, 7.84; N, 3.19.
C26H33NO4 requires C, 73.73; H, 7.85; N, 3.31%. Rf¼0.57 (acetone/
CH2Cl2/petroleum ether¼1:1:3); nmax (KBr) 3268, 2964, 1664, 1576,
1318, 1270, 1223, 1195, 1095, 1042, 1006, 925, 805 cmꢂ1
; dH
4.3.4. (1E)-1-[5-Bromo-3-(5-tert-butyl-2-furyl)-1H-indol-2-yl]-4,4-
dimethylpent-1-en-3-one (5d). Orange solid; yield 65% (0.56 g); mp
212e213 ꢀC. Found: C, 64.38; H, 6.24; N, 3.16. C23H26BrNO2 requires
C, 64.49; H, 6.12; N, 3.27%. Rf¼0.53 (acetone/CH2Cl2/petroleum
ether¼1:1:3); nmax (KBr) 3283, 2968, 1659, 1566, 1477, 1365, 1273,
(400 MHz, DMSO-d6) 11.79 (1H, s, NH), 7.76 (1H, d, J 16.0 Hz, ]CH),
7.63 (1H, d, J 16.0 Hz, ]CH), 6.66 (1H, s, HAr), 6.46 (1H, d, J 3.2 Hz,
HFur), 6.16 (1H, d, J 3.2 Hz, HFur), 3.94 (3H, s, OCH3), 3.30 (3H, s,
OCH3), 2.27 (3H, s, CH3),1.33 (9H, s, C(CH3)3),1.17 (9H, s, C(CH3)3); dC
(100 MHz, DMSO-d6) 203.1, 163.2, 146.0, 144.7, 141.9, 131.8, 130.5,
127.9, 120.5, 120.4, 120.1, 111.2, 110.6, 107.5, 103.7, 60.3, 55.5, 42.8,
32.3, 28.9 (3C), 25.9 (3C), 15.4; m/z (EI, 70 eV) 423 (Mþ, 100), 408
(28), 366 (83), 293 (58), 282 (25), 265 (20), 236 (33), 222 (13), 208
(14), 194 (13), 180 (20), 167 (13), 57 (87), 44 (32).
1092, 967, 780 cmꢂ1
; dH (300 MHz, CDCl3) 8.63 (1H, s, NH), 8.29 (1H,
d, J 15.6 Hz, HAr), 8.04 (1H, d, J 1.8 Hz, HAr), 7.36 (1H, dd, J 8.7, 1.8 Hz,
HAr), 7.20 (1H, d, J 8.7 Hz, HAr), 6.94 (1H, d, J 15.6 Hz, ]CH), 6.51 (1H,
d, J 3.3 Hz, HFur), 6.10 (1H, d, J 3.3 Hz, HFur), 1.38 (9H, s, C(CH3)3), 1.24
(9H, s, C(CH3)3); dC (75 MHz, CDCl3) 203.7, 164.8, 146.6, 136.1, 131.9,
130.9, 128.4, 127.8, 124.4, 118.9, 114.3, 114.0, 112.6, 109.4, 104.2, 43.4,
33.0, 29.4 (3C), 26.7 (3C); m/z (EI, 70 eV) 429/427 (Mþ, 48/48), 414/
412 (15/14), 373/371 (62/60), 355 (15), 316 (12), 279 (20), 207 (24),
178 (12), 101 (24), 83 (16), 69 (30), 57 (100), 43 (72).
4.3.9. 4-[4,7-Dimethoxy-5-methyl-3-(5-methyl-2-furyl)-1H-indol-2-
yl]but-3-en-2-one (5i). Yellow solid; yield 30% (0.20 g); mp
234e235 ꢀC. Found: C, 70.90; H, 6.21; N, 4.08. C20H21NO4 requires C,
70.78; H, 6.24; N, 4.13%. Rf¼0.34 (acetone/CH2Cl2/petroleum
ether¼1:1:3); nmax (KBr) 3215, 1638, 1609, 1512, 1319, 1265, 1227,
4.3.5. (1E)-1-[6-Bromo-3-(5-tert-butyl-2-furyl)-1H-indol-2-yl]-4,4-
dimethylpent-1-en-3-one (5e). Orange solid; yield 61% (0.52 g); mp
211e212 ꢀC. Found: C, 64.33; H, 6.14; N, 3.01. C23H26BrNO2 requires C,
64.49; H, 6.12; N, 3.27%. Rf¼0.63 (acetone/CH2Cl2/petroleum
ether¼1:1:3); nmax (KBr) 3302, 2965, 1658, 1558, 1278, 1224, 1193,
1196,1045 cmꢂ1
; dH (400 MHz, DMSO) 11.78 (1H, s, NH), 7.62 (1H, d,
J 16.4 Hz, ]CH), 7.11 (1H, d, J 16.4 Hz, ]CH), 6.65 (1H, s, HAr), 6.46
(1H, d, J 3.2 Hz, HFur), 6.20 (1H, d, J¼3.2 Hz, HFur), 3.92 (3H, s, OCH3),
3.36 (3H, s, OCH3), 2.36 (3H, s, CH3), 2.27 (6H, s, CH3); dC (100 MHz,
CDCl3) 197.4, 151.4, 146.0, 144.6, 142.0, 131.2 (2C), 128.1, 125.9, 120.6,
120.3, 111.3, 111.2, 107.7, 107.4, 60.3, 55.5, 27.6, 15.4, 13.4; m/z (EI,
70 eV) 339 (Mþ, 100), 324 (66), 282 (15), 266 (15), 127 (10), 101 (14),
57 (14), 42 (27).
1091,1037,1010, 800 cmꢂ1
; dH (300 MHz, CDCl3) 8.40 (1H, s, NH), 8.27
(1H, d, J 15.6 Hz, HAr), 7.77 (1H, d, J 8.4 Hz, HAr), 7.49 (1H, d, J
1.8 Hz, HAr), 7.27 (1H, dd, J 8.4, 1.8 Hz, HAr), 6.90 (1H, d, J 15.6 Hz,
]CH), 6.51 (1H, d, J 3.3 Hz, HFur), 6.11 (1H, d, J 3.3 Hz, HFur), 1.39
(9H, s, C(CH3)3), 1.25 (9H, s, C(CH3)3); dC (75 MHz, CDCl3) 203.5,
164.8, 146.7, 138.2, 131.7, 130.4, 125.2, 124.6, 123.0, 119.3, 118.6,
114.7, 114.1, 109.5, 104.2, 43.4, 33.0, 29.4 (3C), 26.7 (3C); m/z (EI,
70 eV) 429/427 (Mþ, 38/38), 414/412 (24/25), 373/371 (59/59),
355 (29), 313 (29), 291 (15), 276 (17), 233 (15), 207 (22), 178 (22),
101 (28), 83 (19), 69 (32), 57 (100), 42 (98).
4.3.10. 1-[3-(5-Ethyl-2-furyl)-4,7-dimethoxy-5-methyl-1H-indol-2-
yl]pent-1-en-3-one (5j). Yellow solid; yield 44% (0.32 g); mp
211e212 ꢀC. Found: C, 71.88; H, 6.85; N, 3.88. C22H25NO4 requires C,
71.91; H, 6.86; N, 3.81%. Rf¼0.42 (acetone/CH2Cl2/petroleum
ether¼1:1:3); nmax (KBr) 3229, 1654, 1616, 1510, 1348, 1331, 1302,
1267, 1227, 1186, 1148, 1036, 797 cmꢂ1
; dH (400 MHz, DMSO) 11.77
(1H, s, NH), 7.67 (1H, d, J 16.4 Hz, ]CH), 7.20 (1H, d, J 16.4 Hz, ]CH),
6.65 (1H, s, HAr), 6.50 (1H, d, J 3.2 Hz, HFur), 6.24 (1H, d, J 3.2 Hz,
HFur), 3.92 (3H, s, OCH3), 3.34 (3H, s, OCH3), 2.67 (2H, q, J 7.6 Hz,
CH2), 2.58 (2H, q, J 7.2 Hz, CH2), 2.26 (3H, s, CH3), 1.23 (3H, t, J 7.6 Hz,
CH3), 1.00 (3H, t, J 7.2 Hz, CH3); dC (100 MHz, CDCl3) 200.3, 157.4,
146.6, 145.2, 142.6, 131.9, 130.6, 128.6, 125.3, 121.1, 120.8, 111.8, 111.5,
108.2, 106.5, 60.9, 56.1, 34.4, 21.5, 16.0, 12.8, 8.8; m/z (EI, 70 eV) 367
(Mþ, 100), 352 (73), 338 (40), 310 (20), 252 (12), 183 (10), 101 (10),
83 (10), 59 (14), 43 (32%).
4.3.6. (1E)-1-[5-Chloro-3-(5-tert-butyl-2-furyl)-1H-indol-2-yl]-4,4-
dimethylpent-1-en-3-one (5f). Pale-orange solid; yield 73% (0.56 g);
mp 209e210 ꢀC; Found: C, 72.08; H, 6.82; N, 3.67. C23H26ClNO2
requires C, 71.96; H, 6.83; N, 3.65%; Rf¼0.58 (acetone/CH2Cl2/pe-
troleum ether¼1:1:3); nmax (KBr) 3294, 2967,1661,1567,1476,1273,
1092, 1008, 968, 778 cmꢂ1
; dH (300 MHz, CDCl3) 8.90 (1H, s, NH),
8.33 (1H, d, J 15.9 Hz, ]CH), 7.87 (1H, s, HAr), 7.23 (2H, s, HAr), 6.99
(1H, d, J 15.9 Hz, ]CH), 6.49 (1H, d, J 3.3 Hz, HFur), 6.08 (1H, d, J
3.3 Hz, HFur), 1.36 (9H, s, C(CH3)3), 1.24 (9H, s, C(CH3)3); dC (75 MHz,
CDCl3) 203.9, 164.5, 146.4, 135.7, 131.9, 130.8, 126.9, 126.5, 125.7,
120.9, 118.5,113.9,112.0,109.0, 104.0, 43.2, 32.8, 29.1 (3C), 26.5 (3C);
4.3.11. 2-[Bis(5-tert-butyl-2-furyl)methyl]-4,5-dimethoxyaniline
(8k).17f Pale-yellow solid; yield 51% (0.42 g); mp 118e119 ꢀC; dH

M.G. Uchuskin et al. / Tetrahedron 68 (2012) 4252e4258
4257
(300 MHz, CDCl3) 6.44 (1H, s, HAr), 6.32 (1H, s, HAr), 5.89 (4H, s,
Supplementary data
HFur), 5.36 (1H, s, CH), 3.83 (3H, s, OCH3), 3.68 (3H, s, OCH3), 3.16
(2H, br s, NH2), 1.16 (18H, s, C(CH3)3).
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2012.03.069.
4.3.12. 2-[Bis(5-tert-butyl-2-furyl)methyl]-4-methoxyaniline
(8l). Dark-yellow solid; yield 55% (0.42 g); mp 76e77 ꢀC. Found: C,
75.46; H, 8.19; N, 3.52. C24H31NO3 requires C, 75.56; H, 8.19; N,
3.67%. Rf¼0.69 (acetone/CH2Cl2/petroleum ether¼1:1:3); nmax
(KBr) 3430, 3358, 2971, 1504, 1433, 1286, 1271, 1217, 1194, 1134,
References and notes
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6088e6114.
1102, 809, 796, 782, 730 cmꢂ1
; dH (300 MHz, CDCl3) 6.72 (1H, d, J
8.4 Hz, HAr), 6.67 (1H, dd, J¼8.4, 2.7 Hz, HAr), 6.47 (1H, d, J 2.7 Hz,
HAr), 5.87 (2H, d, J 3.3 Hz, HFur), 5.86 (2H, d, J 3.3 Hz, HFur), 5.45 (1H,
s, CH), 3.95 (2H, br s, NH2), 3.65 (3H, s, OCH3), 1.24 (18H, s, C(CH3)3);
dC (75 MHz, CDCl3) 163.9 (2C), 153.7, 151.3 (2C), 136.7, 128.2, 118.4,
114.5, 113.8, 108.2 (2C), 102.5 (2C), 55.7, 40.9, 32.7 (2C), 29.2 (6C);
m/z (EI, 70 eV) 381 (Mþ, 100), 324 (10), 282 (14), 200 (25), 57 (32),
43 (20).
4.3.13. 2-[Bis(5-tert-butyl-2-thiophenyl)methyl]aniline (8m). Pale-
yellow solid; yield 54% (0.41 g); mp 93e94 ꢀC. Found: C, 71.98; H,
7.65; N, 3.58; S, 16.93. C23H29NS2 requires C, 72.01; H, 7.62; N,
3.65; S, 16.72%. Rf¼0.63 (acetone/CH2Cl2/petroleum ether¼1:1:3);
nmax (KBr) 3434, 3357, 2964, 1625, 1487, 1456, 1364, 1256, 813,
4. (a) Bartoli, G.; Palmieri, G.; Bosco, M.; Dalpozzo, R. Tetrahedron Lett. 1989, 30,
2129e2132; (b) Dalpozzo, R.; Bartoli, G. Curr. Org. Chem. 2005, 9, 163e178; (c)
Buszek, K. R.; Brown, N.; Luo, D. Org. Lett. 2009, 11, 201e204.
794, 753 cmꢂ1
; dH (300 MHz, CDCl3) 7.14e7.09 (1H, m, HAr),
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Davies, I. W.; Smitrovich, J. H.; Sidler, R.; Qu, C.; Gresham, V.; Bazaral, C. Tet-
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7.04e7.01 (1H, m, HAr), 6.83e6.77 (1H, m, HAr), 6.76e6.74 (1H, m,
HAr), 6.64 (2H, d, J 3.6 Hz, HTh), 6.62 (2H, d, J 3.6 Hz, HTh), 5.78 (1H,
s, CH), 4.09 (2H, br s, NH2), 1.35 (18H, s, C(CH3)3); dC (75 MHz,
CDCl3) 157.1 (2C), 142.8 (2C), 130.1, 129.0, 128.1, 125.7 (2C), 121.7,
120.7 (2C), 119.6, 117.1, 43.0, 34.7 (2C), 32.6 (6C); m/z (EI, 70 eV)
383 (Mþ, 100), 368 (15), 326 (64), 242 (31), 186 (36), 97 (10), 57
(42), 43 (43).
€
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62e68.
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8933e8937; (b) Hashmi, A. S. K.; Frost, T. M.; Bats, J. W. J. Am. Chem. Soc. 2000,
122, 11553e11554; (c) Yamamura, K.; Kawabata, S.; Kimura, T.; Eda, K.; Ha-
shimoto, M. J. Org. Chem. 2005, 70, 8902e8906; (d) Tokumaru, K.; Arai, S.;
Nishida, A. Org. Lett. 2006, 8, 27e30; (e) Ueda, I.; Nishiura, M.; Takahashi, T.;
Eda, K.; Hashimoto, M.; Yamamura, K. Tetrahedron Lett. 2006, 47, 8535e8537; (f)
Abaev, V. T.; Tsiunchik, F. A.; Gutnov, A. V.; Butin, A. V. J. Heterocycl. Chem. 2008,
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Brice, H.; Clayden, J. Chem. Commun. 2009, 1964e1966; (i) Kaim, L. E.; Grimaud,
L.; Wagschal, S. Chem. Commun. 2011, 1887e1889.
4.3.14. 2-[Bis(5-methyl-2-thiophenyl)methyl]aniline (8n). Pale-green
solid; yield 63% (0.38 g); mp 91e92 ꢀC. Found: C, 68.06; H, 5.73; N,
4.52; S, 21.63. C17H17NS2 requires C, 68.19; H, 5.72; N, 4.68; S, 21.41%.
Rf¼0.58 (acetone/CH2Cl2/petroleum ether¼1:1:3); nmax (KBr) 3447,
3364, 1620, 1580, 1490, 1455, 1291, 1225, 1030, 813, 795, 770,
749 cmꢂ1
; dH (300 MHz, CDCl3) 7.13e7.07 (1H, m, HAr), 7.02e6.99
(1H, m, HAr), 6.78e6.73 (1H, m, HAr), 6.70e6.67 (1H, m, HAr), 6.63
(2H, d, J 3.6 Hz, HTh), 6.60 (2H, d, J 3.6 Hz, HTh), 5.71 (1H, s, CH), 3.61
(2H, s, NH2), 2.44 (6H, s, CH3); dC (75 MHz, CDCl3) 143.9, 143.7 (2C),
139.3 (2C), 129.2, 128.5, 127.9, 126.0 (2C), 124.7 (2C), 118.8, 116.4,
42.7, 15.4 (2C); m/z (EI, 70 eV) 299 (Mþ, 100), 284 (25), 266 (15), 207
(15), 200 (80), 101 (20), 76 (20), 59 (58), 43 (58).
12. (a) Umemiya, H.; Fukasawa, H.; Ebisawa, M.; Eyrolles, L.; Kawachi, E.;
Eisenmann, G.; Gronemeyer, H.; Hashimoto, Y.; Shudo, K.; Kagechika, H. J. Med.
Chem. 1997, 40, 4222e4234; (b) Andres, J. I.; Alcazar, J.; Alonso, J. M.; Diaz, A.;
Fernandez, J.; Gil, P.; Iturrino, L.; Matesanz, E.; Meert, T. F.; Megens, A.; Sipido,
V. K. Bioorg. Med. Chem. Lett. 2002, 12, 243e248; (c) Pawlowska, J.; Czarnocki,
Z.; Wojtasiewicz, K.; Maurin, J. K. Tetrahedron: Asymmetry 2003, 14, 3335e3342.
4.3.15. 1-[2-(3-Oxopent-1-enyl)-1H-indol-3-yl]hexane-1,4-dione
(9). Yellow solid; yield 12% (0.08 g); mp 200e201 ꢀC. Found: C,
73.13; H, 6.79; N, 4.64. C19H21NO3 requires C, 73.29; H, 6.80; N,
4.50%. Rf¼0.42 (acetone/CH2Cl2/petroleum ether¼1:1:3); nmax
€
13. Hunziker, F.; Fischer, R.; Kipfer, P.; Schmutz, J.; Burki, H. R.; Eichenberger, E.;
(KBr) 3280, 1709, 1660, 1441, 1409, 1363, 1201, 1161, 979, 749 cmꢂ1
;
White, T. G. Eur. J. Med. Chem. 1981, 16, 391e398.
14. Butin, A. V.; Tsiunchik, F. A.; Kostyukova, O. N.; Uchuskin, M. G.; Trushkov, I. V.
dH (300 MHz, CDCl3) 10.31 (1H, s, NH), 8.06 (1H, d, J 16.8 Hz, ]CH),
7.87e7.85 (1H, m, HAr), 7.44e7.41 (1H, m, HAr), 7.31e7.26 (1H, m,
HAr), 7.22e7.17 (1H, m, HAr), 6.64 (1H, d, J 16.8 Hz, ]CH), 3.36e3.32
(2H, m, CH2), 2.99e2.95 (2H, m, CH2), 2.67 (2H, q, J 7.5 Hz, CH2), 2.59
(2H, q, J 7.5 Hz, CH2), 1.18 (3H, t, J 7.5 Hz, CH3), 1.12 (3H, t, J 7.5 Hz,
CH3); dC (75 MHz, CDCl3) 211.8, 202.3, 195.9, 137.8, 137.0, 132.5,
129.2,126.5,125.0,122.7,121.8,117.6, 112.4, 37.5, 36.3, 36.0, 31.6, 8.2,
8.1; m/z (EI, 70 eV) 311 (Mþ, 8), 272 (12), 254 (100), 198 (18), 170
(18), 59 (12), 43 (20).
Synthesis 2011, 2629e2638.
15. (a) Kundu, B.; Sawant, D.; Chhabra, R. J. Comb. Chem. 2005, 7, 317e321; (b)
Duggineni, S.; Sawant, D.; Saha, B.; Kundu, B. Tetrahedron 2006, 62, 3228e3241;
(c) David, E.; Pellet-Rostaing, S.; Lemaire, M. Tetrahedron 2007, 63, 8999e9006;
(d) Agarwal, P. K.; Saifuddin, M.; Kundu, B. Tetrahedron 2010, 66, 862e870; (e)
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1153e1161.
16. Butin, A. V.; Uchuskin, M. G.; Pilipenko, A. S.; Tsiunchik, F. A.; Cheshkov, D. A.;
Trushkov, I. V. Eur. J. Org. Chem. 2010, 920e926.
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Acknowledgements
Financial support was provided by the Russian Foundation for
Basic Research (grant 10-03-00254-a), the Ministry of Education
and Science of the Russian Federation (grant 2.1.1/4628) and the
Ministry of Education of the Perm Krai.

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