One-pot regioselective synthesis of meta -terphenyls via [3 + 3] annulation of nitroallylic acetates with alkylidenemalononitriles

Article abstract of DOI:10.1021/jo501193h

A highly efficient one-pot method has been developed for the synthesis of meta-terphenyls via a regioselective [3 + 3] annulation-elimination sequence involving Morita-Baylis-Hillman (MBH) acetates of nitroalkenes and alkylidenemalononitriles. The reaction takes place in a regioselective manner under mild conditions (Et₃N, room temperature) to afford a wide variety of meta-terphenyls bearing aryl, heteroaryl and styrenyl groups. This novel [3 + 3] annulation takes advantage of the 1,3-bielectrophilic character of MBH acetates and 1,3-binucleophilic character of alkylidenemalononitriles and proceeds in a cascade fashion comprising an S_N2' substitution, intramolecular 6-endo-trig Michael addition and double elimination. Representative synthetic transformations of the products, for instance, to meta-terphenyl derived isoindolinones have also been demonstrated.

Full text of DOI:10.1021/jo501193h

Article
pubs.acs.org/joc
One-Pot Regioselective Synthesis of meta-Terphenyls via [3 + 3]
Annulation of Nitroallylic Acetates with Alkylidenemalononitriles
Elumalai Gopi and Irishi N. N. Namboothiri*
Department of Chemistry, Indian Institute of Technology, Bombay, Mumbai, Maharashtra 400 076, India
S
* Supporting Information
ABSTRACT: A highly efficient one-pot method has been
developed for the synthesis of meta-terphenyls via a
regioselective [3 + 3] annulation-elimination sequence
involving Morita−Baylis−Hillman (MBH) acetates of nitro-
alkenes and alkylidenemalononitriles. The reaction takes place
in a regioselective manner under mild conditions (Et3N, room
temperature) to afford a wide variety of meta-terphenyls bearing aryl, heteroaryl and styrenyl groups. This novel [3 + 3]
annulation takes advantage of the 1,3-bielectrophilic character of MBH acetates and 1,3-binucleophilic character of
alkylidenemalononitriles and proceeds in a cascade fashion comprising an SN2′ substitution, intramolecular 6-endo-trig Michael
addition and double elimination. Representative synthetic transformations of the products, for instance, to meta-terphenyl
derived isoindolinones have also been demonstrated.
mixture of m-terphenyls, with and without sulfone, is reported
based on the latter method.
INTRODUCTION
■
Synthesis of polysubstituted benzene derivatives via various
annulation strategies, viz [2 + 2 + 2], [3 + 3], [4 + 2] and [5 + 1],
often performed under acid/base or transition metal catalyzed
conditions, is well documented in the literature.1 However, the
scope of acid/base mediated annulations and conventional
functionalization methods is curtailed by poor regioselectivity
and requirement of harsh reaction conditions. Synthesis of
terphenyls, a chain of three benzene rings, is of particular interest
as these are part of many natural products present in the plant
kingdom, e.g., mushrooms, and exhibit various biological
activities such as anticoagulant, antithrombotic, immunosup-
pressant, lipoxygenase inhibitory, neuroprotective and cytotoxic
activities.2 While most of the terphenyl natural products are para-
derivatives and few are meta, no o-terphenyl natural products are
thus far reported in the literature.2 The few m-terphenyls that
were isolated from natural sources include trifucol 1 (from
seaweed Fucus vesiculosus),3 macranthol 2, dunnialol 3,
simonsinol 4 (from Chinese flowering plant Illicium macran-
thum),4 mulberrofuran R 5 (from mulberry tree Morus ihou
Koidz.)5 and dictyoterphenyl 6 (from the cellular slime mold
Dictyosteliumdiscoideum).6 Possible applications of m-terphenyl
derivatives as ligands in catalysis7 and as versatile synthetic
materials8 have been extensively explored in recent years (Figure
1).
In the above scenario, we embarked on the idea of employing a
[3 + 3] annulation strategy for the synthesis of m-terphenyls
using the 1,3-bielectrophilic MBH acetate 7 and the 1,3-
binucleophilic malononitrile derivative 8 as 3-carbon compo-
nents. In recent years, we and others have extensively exploited
the 1,3-bielectrophilic nature of 7 in the synthesis of a variety of
heterocycles.15 However, construction of carbocycles using 7 as
the 3-carbon component received much less attention16 and
aromatic compounds have never been the targets of such
approaches. Although malononitrile derivative 8 has been
employed as a 4-carbon nucleophile−electrophile in [4 + 2]
annulation with nitroalkenes,17 and as a 3-carbon component in
[3 + 2] annulations,18 the role of 8 as a 3-carbon binucleophile in
[3 + 3] annulation received much less attention19 and has not
been exploited, to our knowledge, in the synthesis of aromatics,
particularly, terphenyls (Figure 2).
RESULTS AND DISCUSSION
■
At the outset, MBH acetate 7a was treated with nitrile 8a in the
presence of different bases and in different solvents at room
temperature (Table 1). While the reaction remained incomplete
with 1 and 2 equiv of Et3N in THF even after 48 h (entries 1−2),
complete conversion was achieved upon increasing the amount
of Et3N to 3 and 4 equiv giving terphenyl 9a in 60 and 65% yields,
respectively (entries 3−4). Though there is only marginal
difference in these yields (entries 3−4), further improvement in
the yield to 73% and reaction time to 7 h was possible by
changing the solvent to CH2Cl2 by using 4 equiv of Et3N (entry
5). A hydrocarbon solvent such a toluene was not the best for our
Synthesis of m-terphenyls9 has been achieved via metal
catalyzed coupling,6,10 multicomponent reactions, including
cyclotrimerization,11 [3 + 3] annulation12,13 and Bronsted acid
catalyzed cyclization.14 As for [3 + 3] annulation, a four-step
method involving base mediated annulation of chalcone with
ethyl acetoacetate followed by hydrolysis and aromatization12
and a one-pot base mediated synthesis involving chalcone and
allyl p-tolyl sulfone13 are known in the literature. While a single
example is reported following the former multistep method, a
Received: May 29, 2014
© XXXX American Chemical Society
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Figure 1. m-Terphenyl natural products.
The above optimized conditions, viz Et3N (4 equiv),
(CH2)2Cl2, room temperature, were then employed to
investigate the scope of MBH acetates 7 using nitrile 8a as the
model binucleophile (Table 2). The reaction of nitrile 8a with
different MBH acetates 7a−k proceeded well to provide
cyanoesters 9a−k in 65−78% yield (entries 1−11). No
appreciable substituent effect was observed in these reactions
as MBH acetates with electron rich aryl 7a−e (entries 1−5),
electron deficient aryl 7g (entry 7), parent phenyl 7f (entry 6),
heteroaryl 7h−i (entries 8−9) and styrenyl 7j (entry 10)
afforded the cyanoesters 9a−j in good yields (70−78%) in 3−15
h. However, marginally lower yield was encountered with MBH
acetate 7k possessing unsubstituted styrenyl group (65%, entry
11) and only a complex mixture was isolated in the case of
aliphatic MBH acetate 7m (entry 12).
Figure 2. Proposed reactivity of MBH acetate 7 and alkylidenemalo-
nonitrile 8.
reaction (entry 6). Although other amine bases such as DABCO
and Huenig’s base (entries 7−8) as well as inorganic bases such
as K2CO3 and Cs2CO3 (entries 9−10) were screened, only
DABCO provided the desired terphenyl 9a, though in low yield
(entry 7). Having found Et3N to be the best base (entry 5), the
yield and the reaction time were further improved, though
marginally, from 73%, 7 h to 75%, 5 h, by changing the solvent
from CH2Cl2 to (CH2)2Cl2 (entries 5 and 11).
Subsequently, one of the MBH acetates 7h was adopted to
study the scope of nitriles 8 under our optimized conditions
(Table 3). Nitriles with electron rich aryl 8b−d (entries 1−3),
electron poor aryl 8e−h (entries 4−7), heteroaryl 8i (entry 8)
Table 1. Optimization Studies for the Synthesis of Terphenyl 9a from Alkylidenemalononitrile 8a and MBH Acetate 7a
a
entry
base (equiv)
solvent
time (h)
% yield
b
1
Et3N (1)
THF
48
48
20
12
7
15
b
2
Et3N (2)
THF
40
3
Et3N (3)
THF
60
65
73
50
33
4
Et3N (4)
THF
5
Et3N (4)
DCM
toluene
DCM
DCM
DCM
DCM
DCE
6
Et3N (4)
6
7
DABCO (4)
iPr2EtN (4)
K2CO3 (4)
Cs2CO3 (4)
Et3N (4)
3
c
8
3
−
−
−
d
9
1
d
10
11
1
5
75
a
b
c
d
Isolated yield after silica gel column chromatography. Incomplete conversion. Complex mixture. Product 10 was formed in 68−70% yield
presumably via elimination of β-nitroacrylate after the initial SN2′ reaction (see Scheme 1, vide infra).
B
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experimental conditions (entry 4). However, in a separate
experiment, DBU (1.5 equiv) was added to the reaction mixture
after complete conversion of 12a and 8c to 14d and the resulting
mixture was stirred for 1 h to achieve elimination of HCN from
14d to form terphenyl 13d in 62% yield (entry 4). Heteroaryl
MBH acetates 12b,c also reacted well with various nitriles 8a,
8c,d and 8f leading to 2,4-diarylbenzonitriles 13e−h in good to
excellent yield (70−83%, entries 5−8). Finally, MBH acetates
bearing an electron poor aryl group and parent phenyl group 12d
and 12e, respectively, were also subjected to [3 + 3] annulation
with a representative nitrile 8d to afford terphenyls 13i and 13j in
73−77% yield (entries 9−10). Unlike in the case of secondary
MBH acetates 7 where the reaction was complete in 15 h or less
(Tables 2 and 3), the reaction times for primary MBH acetates
12 were long (1−4 d) which are attributable to the active role the
electron withdrawing ester group played in the reaction of 7 (see
Scheme 1, vide infra).
Table 2. Synthesis of 2-Cyano-3,5-disubstituted Benzoates 9
from Alkylidenemalononitrile 8a and MBH Acetates 7
a
entry
7
R1
time (h)
9
% yield
1
7a
7b
7c
7d
7e
7f
4-OMeC6H4
2,4-(OMe)2C6H3
3,4-(OMe)2C6H3
5-Benzo[d][1,3]dioxole
4-MeC6H4
5
9a
9b
9c
9d
9e
9f
75
76
70
77
76
72
74
78
76
70
65
2
10
12
15
6
3
4
5
6
C6H5
6
7
7g
7h
7i
4-FC6H4
10
12
12
3
9g
9h
9i
8
2-Furyl
9
2-Thienyl
The structure of benzonitriles 9 and 11 were established by
extensive spectral analysis. That the two protons in the central
aromatic ring appearing, in general, as doublets at δ 8.20−8.40
and 7.70−7.90 are meta to each other was confirmed by their low
coupling constants (J = 1.4−1.8 Hz). The regiochemistry was
confirmed by 1H−1H 2D-NOESY experiment with 9a in that the
proton ortho to the ester group appearing at δ 8.26 had a positive
NOE with only the anisyl protons whereas the para-proton
exhibited NOE with both anisyl protons and phenyl protons (see
the Supporting Information). Further unambiguous structural
assignment was made by single crystal X-ray analysis of a
representative product 11f (see the Supporting Information). As
for benzonitrile 13, out of the three protons of the central
aromatic ring appearing, in general, in a narrow range of 7.60−
7.80, one appeared as a doublet with a small J value (1.5−1.8 Hz),
another as a doublet with a large J value (7.7−8.2 Hz) and the
third as a dd with a large and a small J value. This pattern was
consistent with the regiochemistry in 13 which was further
10
11
12
7j
2-OMeC6H4CHCH
C6H5CHCH
Cyclohexyl
9j
7k
7l
4
9k
9l
b
12
−
a
b
Isolated yield after silica gel column chromatography. Complex
mixture.
Table 3. Synthesis of 2-Cyano-3,5-disubstituted Benzoates 11
from (Ethylidene)malononitriles 8 and MBH Acetate 7h
a
entry
8
R2
time (h)
11
% yield
1
2
3
4
5
6
7
8
9
10
8b
8c
8d
8e
8f
4-MeC6H4
2-OMeC6H4
4-OMeC6H4
4-ClC6H4
5
11b
11c
11d
11e
11f
79
80
76
75
83
79
70
69
76
73
10
12
12
12
12
15
15
12
15
1
unambiguously established by H−1H 2D-COSY experiment
with a representative compound 13g. Thus, while the proton
ortho to cyano group appeared at δ 7.73 as a doublet with a J value
of 8.1 Hz, of the two meta-protons, one appeared as a doublet at δ
7.69 with a small J value (1.7 Hz) and the other as dd at δ 7.62
with large and small J values (8.1, 1.7 Hz). The observed
unsymmetrical 1H and 13C NMR pattern of 9f, 11i and 13c (Ar1
= Ar2) also ruled out regioisomers of terphenyls 9, 11 or 13.
Structural and regiochemical assignment of intermediate 14d
4-BrC6H4
8g
8h
8i
4-FC6H4
11g
11h
11i
3-BrC6H4
2-Furyl
8j
C6H5CHCH
11j
8k
4-FC6H4CHCH
11k
a
Isolated yield after silica gel column chromatography.
1
1
was performed based on H NMR and H−1H 2D-COSY
spectra. The CH2 protons of 14d appeared as a doublet at δ 3.15
coupled only to one olefinic proton appearing at δ 6.21 with a J
value of 4.3 Hz. Although the 4J coupling of this olefinic proton
with the other appearing at δ 6.74 is not measurable enough, the
cross-peaks are clearly observed in the COSY spectrum (see the
Supporting Information).
and styrenyl 8j−k (entries 9−10) groups reacted well with MBH
acetate 7h under our optimized conditions to furnish cyanoesters
11b−k in good to excellent yield (69−83%). Again, no
appreciable substituent effect was observed in these reactions
except that the yield was marginally lower in the case of nitrile
with a heteroaryl group 8i (69%, entry 8) and an electron poor
styrenyl group (73%, entry 10). The reaction time was
consistently 12−15 h (entries 2−10) except for nitrile 8b
(entry 1).
Having investigated the scope of MBH acetate 7 and nitrile 8
in the synthesis of 2-cyano-3,5-disubstituted benzoates 9 and 11,
we subjected primary MBH acetates 12 to the Et3N mediated
reaction with nitrile 8 in anticipation that 2,4-diarylbenzonitrile
13 would be formed (Table 4). Thus, treatment of acetate 12a
with various nitriles 8a,b and 8d delivered 2,4-diarylbenzonitriles
13a−c in 72−76% yield (entries 1−3). Interestingly, the reaction
of 12a with 8c provided intermediate 14d in 71% yield which did
not undergo aromatization via elimination of HCN under our
The proposed mechanism for the formation of benzonitrile 9,
11 or 13 is outlined in Scheme 1. Deprotonation of the methyl
group of nitrile 8 and addition of the resulting stabilized anion to
MBH acetate 7 or 12 in a Michael fashion followed by
elimination of the acetate in an overall SN2′ reaction generates
intermediate I. Deprotonation at the allylic position of
intermediate I generates a stabilized carbanion whose intra-
molecular Michael addition in a 6-endo-trig fashion to the newly
formed nitroalkene moiety in I provides the cyclized product II.
Finally, Et3N mediated elimination of HNO2 and HCN furnishes
the aromatized product 9, 11 or 13. This overwhelming
preference for the 6-endo-trig cyclization over 5-exo-trig
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Table 4. Addition of Various Alkylidenemalononitriles 8 to MBH Acetates 12
a
entry
12
Ar1
8
Ar2
C6H5
time (d)
13
% yield
1
2
3
4
5
6
7
8
9
10
12a
12a
12a
12a
12b
12c
12c
12c
12d
12e
4-OMeC6H4
4-OMeC6H4
4-OMeC6H4
4-OMeC6H4
2-Furyl
8a
8b
8d
8c
8a
8c
8d
8f
3.0
1.0
4.0
4.0
1.5
4.0
1.5
2.0
2.0
2.0
13a
13b
13c
13d
13e
13f
13g
13h
13i
76
75
72
62
79
80
83
70
77
73
b
c
4-MeC6H4
4-OMeC6H4
2-OMeC6H4
C6H5
2-Thienyl
2-Thienyl
2-Thienyl
4-ClC6H4
C6H5
2-OMeC6H4
4-OMeC6H4
4-BrC6H4
8d
8d
4-OMeC6H4
4-OMeC6H4
13j
a
b
c
Isolated yield after silica gel column chromatography. The reaction was carried out under microwave irradiation at 80 °C. The intermediate 14d
(71% isolated yield) underwent elimination to form 13d only after addition of DBU (1.5 equiv) and stirring at room temperature for 1 h.
Scheme 1. Proposed Mechanism for the [3 + 3] Annulation of MBH Acetate 7 or 12 and Alkylidenemalononitrile 8
cyclization obviously arises from the possibility of aromatization
of the initial cycloadduct II. In fact, this is for the first time, the
SN2′ products of secondary MBH acetates 7 deviated from their
normal cyclization mode of 5-exo-trig to 6-endo-trig.15 Additional
support for this mechanism emanated from the isolation of an
intermediate in one case (14d, entry 4, Table 4). The reluctance
of intermediate 14d to undergo elimination to 13d in the
presence of Et3N (pKa 10.8) is attributable to the poor acidity of
allylic proton in 14d due to the o-OMe group. Therefore, a
stronger base such as DBU (pKa 12.0) was needed for
elimination of HCN from 14d (entry 4, Table 4). An alternate
pathway followed by allylic anion derived from intermediate I in
the presence of Bronsted bases (entries 9−10, Table 1) to form
diene 10 is also shown in Scheme 1.
Scheme 2. Selected Synthetic Transformations of Terphenyl
A representative terphenyl 9h was subjected to LiOH
mediated selective hydrolysis of the ester group under mild
conditions to 2-cyano-3,5-diarylbenzoic acid 15 in excellent yield
(86%, Scheme 2). Preferential reactivity of cyano group was
demonstrated by indium mediated addition of allyl bromide to
9a and 9h under MW irradiation conditions. Interestingly, both
9a and 9h undergo a cascade double allylation−intramolecular
lactamization under these conditions to generate synthetically
useful isoindolinones 16a,b in high yield (77−81%, Scheme 2).
CONCLUSIONS
■
Polysubstituted m-terphenyls have been synthesized in high yield
(62−83%) through a one-pot [3 + 3] annulation of Morita−
Baylis−Hillman acetates of nitroalkenes and alkylidenemalono-
nitrile in the presence of Et3N at room temperature. The
annulation takes place via a regioselective cascade SN2′-
intramolecular Michael reaction, which was confirmed by
isolation of the intermediate cycloadduct, in one case, before
D
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360 (100), 342 (50); HRMS (ES+, Ar) calcd for C24H22NO4 (MH+)
388.1549, found 388.1549.
aromatization and its subsequent transformation to the
aromatized product. The scope of the reaction was demonstrated
using nitroallylic acetates and alkylidenemalononitriles bearing
aryl, heteroaryl and styrenyl groups at the β-position of the nitro/
cyano group. Representative transformations of meta-terphenyl
cyanoesters to corresponding carboxylic acids and isoindoli-
nones have also been carried out.
Ethyl 5-(benzo[d][1,3]dioxol-5-yl)-2-cyano-[1,1′-biphenyl]-3-
carboxylate (9d). Pale yellow solid: yield 77%, 49 mg; mp 104 °C; IR
(KBr, cm−1) 2988 (w), 2902 (w), 2225 (m), 1725 (s), 1597 (m), 1505
(m), 1494 (m), 1459 (m), 1446 (m), 1341 (m), 1250 (vs), 1229 (s),
1038 (s), 1016 (m), 929 (w), 734 (w), 702 (w); 1H NMR (400 MHz,
CDCl3) δ 8.21 (s, 1H), 7.77 (s, 1H), 7.57−7.49 (m, 5H), 7.15 (d, J = 8.1
Hz, 1H), 7.13 (s, 1H), 6.92 (d, J = 8.1 Hz, 1H), 6.04 (s, 2H), 4.51 (q, J =
7.0 Hz, 2H), 1.47 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
164.9, 148.8, 148.5, 144.7, 138.1, 134.9, 132.4, 131.8, 129.17, 129.22,
128.8, 127.9, 121.6, 116.9, 109.3, 109.1, 107.7, 101.8, 62.6, 14.3; MS
(ES+, Ar) m/z (rel intensity) 410 (MK+, 35), 394 (MNa+, 100); HRMS
(ES+, Ar) calcd for C23H17NO4Na (MNa+) 394.1050, found 394.1049.
Ethyl 4′-cyano-4-methyl-[1,1′:3′,1″-terphenyl]-5′-carboxy-
late (9e). Colorless solid: yield 76%, 44 mg; mp 102 °C; IR (KBr,
cm−1) 3027 (w), 2982 (m), 2923 (m), 2854 (w), 2225 (m), 1726 (vs),
1598 (m), 1458 (w), 1438 (w), 1369 (w), 1340 (w), 1280 (m), 1252 (s),
1175 (m), 1075 (m), 1014 (w), 820 (w), 788 (w), 702 (w); 1H NMR
(400 MHz, CDCl3) δ 8.29 (d, J = 1.9 Hz, 1H), 7.84 (d, J = 1.9 Hz, 1H),
7.59−7.56 (m, 4H), 7.54−7.48 (m, 3H), 7.31 (d, J = 7.9 Hz, 2H), 4.51
(q, J = 7.1 Hz, 2H), 2.42 (s, 3H), 1.47 (t, J = 7.1 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 164.9, 148.5, 145.0, 139.5, 138.2, 135.4, 134.9, 132.0,
130.1, 129.2, 129.1, 128.8, 128.1, 127.3, 117.0, 109.4, 62.6, 21.4, 14.3;
MS (ES+, Ar) m/z (rel intensity) 359 ([M + H2O]+, 57), 342 (MH+,
100), 314 (46), 296 (30); HRMS (ES+, Ar) calcd for C23H20NO2
(MH+) 342.1494, found 342.1508.
Ethyl 4′-cyano-[1,1′:3′,1″-terphenyl]-5′-carboxylate (9f). Col-
orless solid: yield 72%, 40 mg; mp 117 °C; IR (KBr, cm−1) 2923 (m),
2226 (w), 1728 (s), 1599 (w), 1456 (w), 1339 (w), 1279 (m), 1249 (m),
1206 (w), 1076 (w), 765 (m), 701 (m); 1H NMR (400 MHz, CDCl3) δ
8.30 (d, J = 1.9 Hz, 1H), 7.86 (d, J = 1.9 Hz, 1H), 7.68−7.65 (m, 2H),
7.58 (dd, J = 8.0, 1.6 Hz, 2H), 7.54−7.44 (m, 6H), 4.52 (q, J = 7.1 Hz,
2H), 1.48 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 164.9,
148.6, 145.1, 138.3, 138.1, 134.9, 132.3, 129.4, 129.3, 129.3, 129.2, 128.9,
128.4, 127.5, 116.9, 109.8, 62.6, 14.3; MS (ES+, Ar) m/z (rel intensity)
366 (MK+, 70), 350 (MNa+, 85), 345 ([M + H2O]+, 75), 328 (MH+,
100), 300 (38); HRMS (ES+, Ar) calcd for C22H18NO2 (MH+)
328.1338, found 328.1334.
Ethyl 4′-cyano-4-fluoro-[1,1′:3′,1″-terphenyl]-5′-carboxylate
(9g). Colorless solid: yield 74%, 43 mg; mp 101 °C; IR (KBr, cm−1)
2925 (m), 2852 (w), 2225 (w), 1727 (vs), 1604 (m), 1514 (m), 1340
(w), 1280 (m), 1248 (s), 1162 (w), 1076 (w), 838 (m), 701 (w), 529
(w); 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 1.9 Hz, 1H), 7.81 (d, J =
1.9 Hz, 1H), 7.65 (dd, J = 8.7, 5.2 Hz, 2H), 7.57 (dd, J = 7.9, 1.7 Hz, 2H),
7.54−7.48 (m, 3H), 7.20 (t, J = 8.7 Hz, 2H), 4.52 (q, J = 7.1 Hz, 2H),
1.48 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 164.8, 163.6 (d,
JC−F = 249.8 Hz), 148.7, 144.0, 138.0, 135.0, 134.5 (d, JC−F = 3.2 Hz),
132.1, 129.25, 129.34, 129.2 (d, JC−F = 2.9 Hz), 128.9, 128.2, 116.8,
116.5 (d, JC−F = 21.8 Hz), 109.9, 62.7, 14.3; 19F NMR (470 MHz,
CDCl3) δ −113.3; MS (ES+, Ar) m/z (rel intensity) 346 (MH+, 100),
319 (18), 318 (82), 300 (52), 274 (10), 213 (18), 196 (15); HRMS
(ES+, Ar) calcd for C22H17NO2F (MH+) 346.1243, found 346.1229.
Ethyl 2-cyano-5-(furan-2-yl)-[1,1′-biphenyl]-3-carboxylate
(9h). Pale yellow solid: yield 78%, 42 mg; mp 103 °C; IR (KBr,
cm−1) 2851 (vw), 2223 (m), 1725 (vs), 1608 (s), 1492 (vw), 1367 (w),
1333 (m), 1249 (m), 1199 (m), 1181 (m), 1073 (m), 1018 (s), 746 (s),
702 (m); 1H NMR (400 MHz, CDCl3) δ 8.31 (d, J = 1.6 Hz, 1H), 7.89
(d, J = 1.6 Hz, 1H), 7.56−7.55 (m, 2H), 7.53−7.48 (m, 4H), 6.91 (d, J =
3.3 Hz, 1H), 6.56 (dd, J = 3.3, 1.7 Hz, 1H), 4.51 (q, J = 7.1 Hz, 2H), 1.48
(t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 164.7, 151.4, 148.6,
144.3, 138.0, 135.0, 134.1, 129.17, 129.21, 128.8, 128.1, 124.7, 116.9,
112.6, 109.4, 109.1, 62.6, 14.3; MS (ES+, Ar) m/z (rel intensity) 318
(MH+, 100), 290 (71), 272 (88), 205 (25), 85 (25); HRMS (ES+, Ar)
calcd for C20H16NO3 (MH+) 318.1130, found 318.1122.
EXPERIMENTAL SECTION
■
General Methods. The melting points recorded are uncorrected.
NMR spectra were recorded with TMS as the internal standard for 1H,
1H decoupled 13C, 13C-APT, 1H−1H-2D-COSY and NOESY and
C6H5CF3 as the external standard for 19F. The coupling constants (J
values) are given in Hz. High resolution mass spectra were recorded
under ESI Q-TOF conditions. X-ray data were collected on a
diffractometer equipped with graphite monochromated Mo Kα
radiation. The structure was solved by direct methods shelxs97 and
refined by full-matrix least-squares against F2 using SHELXL97 software.
The secondary MBH acetates 7 (E = CO2Et)20 and the primary MBH
acetates 11 (E = H)21 were prepared from corresponding alcohols.22,23
Malononitrile derivatives 8 were prepared from corresponding methyl
ketone and malononitrile.24
General Procedure for the Synthesis of m-Terphenyls 9, 11,
13. To a stirred solution of MBH-acetate 7 or 12 (0.17 mmol) in DCE
(3 mL) at rt, was added alkylidene malononitrile 8 (0.17 mmol)
followed by triethylamine (0.1 mL, 69 mg, 0.68 mmol), and the
completion of the reaction was monitored by TLC. The crude product
was directly purified by silica gel column chromatography by eluting
with 5−20% EtOAc−pet ether (gradient elution). In the case of entry 4,
Table 4, the intermediate 14d was either isolated or treated in situ with
DBU (38 μL, 0.25 mmol) to afford 13d.
Ethyl 4′-cyano-4-methoxy-[1,1′:3′,1″-terphenyl]-5′-carboxy-
late (9a). Pale yellow solid: yield 75%, 46 mg; mp 101 °C; IR (KBr,
cm−1) 3176 (vw), 2852 (vw), 2225 (w), 1726 (m), 1643 (vs), 1520 (w),
1457 (w), 1257 (m), 1171 (w), 1023 (w), 834 (w), 768 (w); 1H NMR
(400 MHz, CDCl3) δ 8.26 (d, J = 1.9 Hz, 1H), 7.81 (d, J = 1.9 Hz, 1H),
7.62 (d, J = 8.8 Hz, 2H), 7.57 (dd, J = 7.9, 1.5 Hz, 2H), 7.54−7.47 (m,
3H), 7.02 (d, J = 8.8 Hz, 2H), 4.51 (q, J = 7.1 Hz, 2H), 3.86 (s, 3H), 1.47
(t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.0, 160.7, 148.5,
144.6, 138.3, 134.9, 131.6, 130.6, 129.2, 129.1, 128.8, 128.7, 127.8, 117.0,
114.8, 109.0, 62.6, 55.6, 14.3; MS (ES+, Ar) m/z (rel intensity) 375 ([M
+ H2O]+, 48), 358 (MH+, 100), 312 (21); HRMS (ES+, Ar) calcd for
C23H20NO3 (MH+) 358.1443, found 358.1444. Confirmed by 1H−1H-
2D-NOESY experiment.
Ethyl 4′-cyano-2,4-dimethoxy-[1,1′:3′,1″-terphenyl]-5′-car-
boxylate (9b). Dark yellow solid: yield 76%, 50 mg; mp 126 °C; IR
(KBr, cm−1) 2928 (m), 2224 (w), 1720 (vs), 1610 (vs), 1510 (m), 1465
(w), 1339 (m), 1306 (m), 1262 (m), 1209 (m), 1030 (m), 702 (m); 1H
NMR (400 MHz, CDCl3) δ 8.23 (d, J = 1.7 Hz, 1H), 7.81 (d, J = 1.7 Hz,
1H), 7.58 (dd, J = 8.0, 1.4 Hz, 2H), 7.52−7.46 (m, 3H), 7.31 (d, J = 8.3
Hz, 1H), 6.60 (dd, J = 8.3, 2.2 Hz, 1H), 6.58 (d, J = 2.2 Hz, 1H), 4.49 (q,
J = 7.1 Hz, 2H), 3.87 (s, 3H), 3.83 (s, 3H), 1.45 (t, J = 7.1 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 165.1, 161.8, 157.8, 147.6, 142.7, 138.4,
134.6, 134.1, 131.5, 130.7, 129.3, 128.9, 128.7, 120.6, 117.2, 108.7, 105.3,
99.2, 62.4, 55.8, 55.7, 14.3; MS (ES+, Ar) m/z (rel intensity) 426 (MK+,
31), 425 ([M − 1]K+, 45), 410 (MNa+, 65), 388 (MH+, 96), 360 (100),
342 (54), 298 (8), 279 (9), 213 (20), 196 (25); HRMS (ES+, Ar) calcd
for C24H22NO4 (MH+) 388.1549, found 388.1549.
Ethyl 4′-cyano-3,4-dimethoxy-[1,1′:3′,1″-terphenyl]-5′-car-
boxylate (9c). Dark yellow solid: yield 70%, 46 mg; mp 120 °C; IR
(KBr, cm−1) 2936 (m), 2223 (w), 1726 (m), 1596 (m), 1519 (m), 1464
(w), 1341 (w), 1264 (s), 1023 (m), 737 (w), 703 (w); 1H NMR (500
MHz, CDCl3) δ 8.25 (d, J = 1.9 Hz, 1H), 7.80 (d, J = 1.9 Hz, 1H), 7.58
(dd, J = 8.0, 1.5 Hz, 2H), 7.54−7.47 (m, 3H), 7.25 (dd, J = 8.4, 2.1 Hz,
1H), 7.14 (d, J = 2.1 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 4.52 (q, J = 7.1
Hz, 2H), 3.97 (s, 3H), 3.95 (s, 3H), 1.48 (t, J = 7.1 Hz, 3H); 13C NMR
(125 MHz, CDCl3) δ 165.0, 150.3, 149.7, 148.5, 144.9, 138.3, 134.9,
131.7, 131.1, 129.3, 129.2, 128.9, 127.9, 120.3, 116.9, 111.8, 110.4, 109.2,
62.6, 56.3, 56.2, 14 0.3; MS (ES+, Ar) m/z (rel intensity) 388 (MH+, 86),
Ethyl 2-cyano-5-(thiophen-2-yl)-[1,1′-biphenyl]-3-carboxy-
late (9i). Pale yellow solid: yield 76%, 43 mg; mp 132 °C; IR (KBr,
cm−1) 3054 (w), 2988 (w), 2226 (w), 1728 (m), 1598 (w), 1422 (w),
1323 (w), 1266 (s), 738 (vs), 704 (m); 1H NMR (400 MHz, CDCl3) δ
8.28 (d, J = 1.9 Hz, 1H), 7.83 (d, J = 1.9 Hz, 1H), 7.58−7.55 (m, 2H),
E
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7.54−7.49 (m, 4H), 7.44 (dd, J = 5.0, 0.8 Hz, 1H), 7.15 (dd, J = 5.0, 3.8
Hz, 1H), 4.52 (q, J = 7.1 Hz, 2H), 1.48 (t, J = 7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 164.6, 148.7, 141.2, 138.2, 137.9, 135.1, 130.3,
129.15, 129.24, 128.8 ( × 2), 127.9, 126.6, 126.1, 116.8, 109.3, 62.7, 14.3;
MS (ES+, Ar) m/z (rel intensity) 372 (MK+, 10), 356 (MNa+, 100), 301
(12), 193 (15), 148 (17), 102 (10); HRMS (ES+, Ar) calcd for
C20H15NO2SNa (MNa+) 356.0716, found 356.0718.
Ethyl (E)-2-cyano-5-(2-methoxystyryl)-[1,1′-biphenyl]-3-car-
boxylate (9j). Pale yellow solid: yield 70%, 46 mg; mp 142 °C; IR (KBr,
cm−1) 3062 (vw), 2925 (m), 2851 (w), 2223 (m), 1726 (vs), 1593 (m),
1489 (m), 1464 (m), 1439 (m), 1369 (w), 1340 (w), 1249 (vs), 1199
(m), 1108 (w), 1074 (w), 1025 (s), 754 (s), 701 (m); 1H NMR (400
MHz, CDCl3) δ 8.19 (d, J = 1.5 Hz, 1H), 7.75 (d, J = 1.5 Hz, 1H), 7.67
(d, J = 16.5 Hz, 1H), 7.61−7.46 (m, 6H), 7.32 (td, J = 8.4, 1.4 Hz, 1H),
7.18 (d, J = 16.5 Hz, 1H), 6.99 (t, J = 7.5 Hz, 1H), 6.93 (d, J = 8.4 Hz,
1H), 4.51 (q, J = 7.1 Hz, 2H), 3.91 (s, 3H), 1.48 (t, J = 7.1 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 165.0, 157.5, 148.3, 142.1, 138.2, 134.7,
131.1, 130.2, 129.2, 129.1, 128.8 ( × 2), 127.7, 127.2, 126.3, 125.1, 121.0,
117.1, 111.2, 109.0, 62.5, 55.6, 14.3; MS (ES+, Ar) m/z (rel intensity)
422 (MK+, 78), 415 ([M + MeOH]+, 100), 406 (MNa+, 92), 401 (41),
384 (24); HRMS (ES+, Ar) calcd for C25H21NO3Na (MNa+) 406.1414,
found 406.1417.
Ethyl (E)-2-cyano-5-styryl-[1,1′-biphenyl]-3-carboxylate (9k).
Pale yellow solid: yield 65%, 39 mg; mp 102 °C; IR (KBr, cm−1) 2876
(m), 2223 (m), 1725 (vs), 1635 (s), 1593 (w), 1449 (w), 1369 (w),
1267 (s), 1199 (s), 1073 (m), 1021 (m), 963 (m), 751 (vs), 701 (s); 1H
NMR (400 MHz, CDCl3) δ 8.19 (d, J = 1.5 Hz, 1H), 7.74 (d, J = 1.5 Hz,
1H), 7.58−7.48 (m, 7H), 7.42−7.32 (m, 3H), 7.32 (d, J = 16.2 Hz, 1H),
7.15 (d, J = 16.2 Hz, 1H), 4.52 (q, J = 7.1 Hz, 2H), 1.48 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 164.9, 148.5, 141.4, 138.1, 136.2,
134.8, 133.8, 131.3, 129.2, 129.2, 129.16, 129.20, 128.8, 127.6, 127.2,
125.9, 117.0, 109.4, 62.6, 14.3; MS (ES+, Ar) m/z (rel intensity) 392
(MK+, 100), 376 (MNa+, 32), 354 (41), 249 (9), 177 (13), 124 (8);
HRMS (ES+, Ar) calcd for C24H19NO2K (MK+) 392.1047, found
392.1047.
Ethyl 2-cyano-5-(furan-2-yl)-4′-methyl-[1,1′-biphenyl]-3-car-
boxylate (11b). Pale yellow solid: yield 79%, 45 mg; mp 140 °C; IR
(KBr, cm−1) 2954 (s), 2923 (vs), 2856 (m), 2222 (w), 1731 (m), 1608
(m), 1461 (m), 1377 (w), 1260 (m), 1019 (m), 744 (w); 1H NMR (400
MHz, CDCl3) δ 8.30 (d, J = 1.7 Hz, 1H), 7.88 (d, J = 1.7 Hz, 1H), 7.57
(d, J = 1.5 Hz, 1H), 7.46 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H),
6.91 (d, J = 3.4 Hz, 1H), 6.56 (dd, J = 3.4, 1.5 Hz, 1H), 4.51 (q, J = 7.1
Hz, 2H), 2.43 (s, 3H), 1.48 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 164.8, 151.4, 148.7, 144.3, 139.2, 135.1, 135.0, 134.0, 129.5,
129.0, 128.1, 124.5, 117.0, 112.6, 109.3, 109.0, 62.6, 21.5, 14.3; MS (ES+,
Ar) m/z (rel intensity) 354 (MNa+, 65), 332 (MH+, 100), 318 (22), 304
(74), 286 (92), 274 (40), 233 (83); HRMS (ES+, Ar) calcd for
C21H18NO3 (MH+) 332.1287, found 332.1280.
144.3, 135.1, 134.0, 130.5, 130.3, 128.0, 124.3, 117.2, 114.3, 112.6, 109.3,
108.9, 62.6, 55.5, 14.3; MS (ES+, Ar) m/z (rel intensity) 386 (MK+, 45),
370 (MNa+, 100); HRMS (ES+, Ar) calcd for C21H17NO4Na (MNa+)
370.1050, found 370.1049.
Ethyl 4′-chloro-2-cyano-5-(furan-2-yl)-[1,1′-biphenyl]-3-car-
boxylate (11e). Yellow solid: yield 75%, 45 mg; mp 171 °C; IR (KBr,
cm−1) 2936 (m), 1967 (m), 1728 (vs), 1608 (w), 1331 (w), 1249 (m),
1028 (m), 739 (s); 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 1.7 Hz,
1H), 7.86 (d, J = 1.7 Hz, 1H), 7.58 (d, J = 1.6 Hz, 1H), 7.53−7.47 (m,
4H), 6.93 (d, J = 3.5 Hz, 1H), 6.57 (dd, J = 3.5, 1.6 Hz, 1H), 4.51 (q, J =
7.1 Hz, 2H), 1.48 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
164.5, 151.2, 147.4, 144.5, 136.4, 135.6, 135.1, 134.3, 130.6, 129.2, 127.9,
125.0, 116.8, 112.7, 109.6, 109.0, 62.7, 14.3; MS (ES+, Ar) m/z (rel
intensity) 354 ([M + 2]H+, 8), 352 (MH+, 24), 338 (15), 336 (77), 326
(20), 324 (71), 308 (15), 306 (60), 279 (100), 278 (73), 262 (25), 205
(49), 149 (12); HRMS (ES+, Ar) calcd for C20H15NO3Cl (MH+)
352.0740, found 352.0738.
Ethyl 4′-bromo-2-cyano-5-(furan-2-yl)-[1,1′-biphenyl]-3-car-
boxylate (11f). Yellow solid: yield 83%, 56 mg; mp 178 °C; IR (KBr,
cm−1) 2991 (vw), 2911 (vw), 2221 (w), 1728 (vs), 1609 (m), 1509 (w),
1367 (w), 1332 (m), 1293 (w), 1249 (s), 1072 (w), 1025 (m), 836 (m),
737 (m); 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 1.7 Hz, 1H), 7.85
(d, J = 1.7 Hz, 1H), 7.64 (d, J = 8.5 Hz, 2H), 7.57 (d, J = 1.6 Hz, 1H),
7.43 (d, J = 8.5 Hz, 2H), 6.93 (d, J = 3.4 Hz, 1H), 6.56 (dd, J = 3.4, 1.6
Hz, 1H), 4.51 (q, J = 7.1 Hz, 2H), 1.47 (t, J = 7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 164.5, 151.1, 147.4, 144.5, 136.9, 135.1, 134.3,
132.1, 130.8, 127.8, 125.0, 123.8, 116.8, 112.7, 109.6, 108.9, 62.7, 14.3;
MS (ES+, Ar) m/z (rel intensity) 398 ([MH+2]+,100), 396 (MH+, 80),
369 (97), 367 (100), 351 (63), 349 (60), 302 (18), 242 (55); HRMS
(ES+, Ar) calcd for C20H15NO3Br (MH+) 396.0235, found 396.0239.
Selected X-ray Data: C20H14BrNO3, M = 396.23, Monoclinic, space
group P2(1)/n, a = 7.446(3) Å, b = 7.600(3) Å, c = 29.561(11) Å, α =
90.00°, β = 97.206(10) °, γ = 90.00°, V = 1659.6(11) Å3, Dc = 1.586 Mg/
m3, Z = 4, F(000) = 800, λ = 0.71073 Å, μ = 2.496 mm−1, Total/unique
reflections = 11437/3001 [R(int) = 0.0752], T = 100(2) K, θ range =
3.02−25.34°. Final R [I > 2σ(I)]: R1 = 0.0403, wR2 = 0.0876. R (all
data): R1 = 0.0513, wR2 = 0.0920.
Ethyl 2-cyano-4′-fluoro-5-(furan-2-yl)-[1,1′-biphenyl]-3-car-
boxylate (11g). Yellow liquid: yield 79%, 45 mg; IR (neat, cm−1)
2926 (m), 2214 (w), 1731 (vs), 1609 (m), 1364 (w), 1333 (m), 1251
1
(s), 1067 (w), 1025 (m), 900 (w), 840 (m), 737 (s); H NMR (400
MHz, CDCl3) δ 8.32 (d, J = 1.7 Hz, 1H), 7.87 (d, J = 1.7 Hz, 1H), 7.57
(d, J = 1.7 Hz, 1H), 7.54 (dd, J = 8.6, 5.2 Hz, 2H), 7.20 (t, J = 8.6 Hz,
2H), 6.93 (d, J = 3.4 Hz, 1H), 6.56 (dd, J = 3.4, 1.7 Hz, 1H), 4.51 (q, J =
7.1 Hz, 2H), 1.48 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
164.6, 163.4 (d, JC−F = 249.1 Hz), 151.2, 147.6, 144.4, 135.0, 134.2,
134.0 (d, JC−F = 3.3 Hz), 131.1 (d, JC−F = 8.5 Hz), 128.0, 124.8, 116.9,
115.9 (d, JC−F = 21.8 Hz), 112.7, 109.5, 109.1, 62.7, 14.3; 19F NMR (470
MHz, CDCl3) δ −113.4; MS (ES+, Ar) m/z (rel intensity) 336 (MH+,
27), 308 (84), 290 (100), 279 (25), 278 (19); HRMS (ES+, Ar) calcd for
C20H15NO3F (MH+) 336.1036, found 336.1033.
Ethyl 3′-bromo-2-cyano-5-(furan-2-yl)-[1,1′-biphenyl]-3-car-
boxylate (11h). Pale yellow solid: yield 70%, 47 mg; mp 89 °C; IR
(KBr, cm−1) 2953 (m), 2922 (vs), 2850 (m), 2222 (w), 1724 (w), 1640
(br, s), 1555 (w), 1463 (w), 1077 (w), 1252 (w), 1019 (w), 755 (w); 1H
NMR (400 MHz, CDCl3) δ 8.34 (d, J = 1.8 Hz, 1H), 7.86 (d, J = 1.8 Hz,
1H), 7.67 (t, J = 1.7 Hz, 1H), 7.62 (dd, J = 7.9, 1.7 Hz, 1H), 7.58 (d, J =
1.4 Hz, 1H), 7.52 (dd, J = 7.9, 1.7 Hz, 1H), 7.39 (t, J = 7.9 Hz, 1H), 6.94
(d, J = 3.4 Hz, 1H), 6.57 (dd, J = 3.4, 1.4 Hz, 1H), 4.52 (q, J = 7.1 Hz,
2H), 1.48 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 164.4,
151.0, 146.9, 144.5, 139.9, 135.0, 134.2, 132.2, 132.0, 130.3, 127.85,
127.92, 125.1, 122.8, 116.5, 112.7, 109.7, 109.0, 62.7, 14.2; MS (ES+, Ar)
m/z (rel intensity) 436 ([MK+2]+, 36), 434 (MK+, 36), 420 ([MNa
+2]+, 100), 418 (MNa+, 100), 415 (66), 413 (66); HRMS (ES+, Ar)
calcd for C20H14NO3BrNa (MNa+) 418.0049, found 418.0049.
Ethyl 2-cyano-5-(furan-2-yl)-2′-methoxy-[1,1′-biphenyl]-3-
carboxylate (11c). Pale yellow solid: yield 80%, 47 mg; mp 120 °C;
IR (KBr, cm−1) 2931 (w), 2225 (w), 1726 (s), 1608 (m), 1493 (w),
1
1464 (w), 1333 (w), 1254 (vs), 1021 (m), 753 (m); H NMR (500
MHz, CDCl3) δ 8.32 (d, J = 1.4 Hz, 1H), 7.85 (d, J = 1.4 Hz, 1H), 7.55
(d, J = 1.5 Hz, 1H), 7.44 (td, J = 7.7, 1.3 Hz, 1H), 7.29−7.24 (m, 1H),
7.07 (t, J = 7.7 Hz, 1H), 7.04 (d, J = 8.4 Hz, 1H), 6.88 (d, J = 3.3 Hz, 1H),
6.54 (dd, J = 3.3, 1.5 Hz, 1H), 4.50 (q, J = 7.1 Hz, 2H), 3.84 (s, 3H), 1.47
(t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 164.7, 156.7, 151.6,
145.8, 144.1, 134.1, 133.9, 130.9, 130.8, 128.9, 127.2, 124.6, 120.9, 116.8,
112.5, 111.5, 111.3, 109.0, 62.5, 55.7, 14.3; MS (ES+, Ar) m/z (rel
intensity) 348 (MH+, 100), 320 (27), 302 (64), 277 (8); HRMS (ES+,
Ar) calcd for C21H18NO4 (MH+) 348.1236, found 348.1233.
Ethyl 2-cyano-5-(furan-2-yl)-4′-methoxy-[1,1′-biphenyl]-3-
carboxylate (11d). Pale yellow solid: yield 76%, 45 mg; mp 121 °C;
IR (KBr, cm−1) 2988 (w), 2839 (w), 2223 (m), 1726 (vs), 1609 (s),
1515 (m), 1335 (m), 1287 (m), 1254 (vs), 1182 (m), 1074 (m), 1022
(m), 836 (m), 739 (m); 1H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 1.3
Hz, 1H), 7.87 (d, J = 1.3 Hz, 1H), 7.55−7.58 (unresolved m, 1H), 7.51
(d, J = 8.6 Hz, 2H), 7.03 (d, J = 8.6 Hz, 2H), 6.91 (d, J = 3.4 Hz, 1H),
6.58−6.52 (m, 1H), 4.51 (q, J = 7.1 Hz, 2H), 3.87 (s, 3H), 1.47 (t, J = 7.1
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 164.8, 160.4, 151.4, 148.3,
Ethyl 2-cyano-3,5-di(furan-2-yl)benzoate (11i). Colorless solid:
yield 69%, 36 mg; mp 121 °C; IR (KBr, cm−1) 2929 (w), 2221 (w), 1726
(s), 1607 (s), 1494 (m), 1367 (w), 1326 (m), 1297 (m), 1252 (vs), 1225
(m), 1073 (w), 1020 (s), 739 (s); 1H NMR (400 MHz, CDCl3) δ 8.34
(d, J = 1.7 Hz, 1H), 8.19 (d, J = 1.7 Hz, 1H), 7.60 (d, J = 1.5 Hz, 1H),
F
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7.59 (d, J = 1.5 Hz, 1H), 7.53 (d, J = 3.4 Hz, 1H), 6.95 (d, J = 3.4 Hz,
1H), 6.60 (dd, J = 3.4, 1.5 Hz, 1H), 6.57 (dd, J = 3.4, 1.5 Hz, 1H), 4.51
(q, J = 7.1 Hz, 2H), 1.48 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 164.7, 151.3, 149.1, 144.3, 143.8, 136.0, 135.6, 134.3, 124.06,
124.14, 117.4, 112.7, 112.6, 112.5, 109.4, 104.3, 62.6, 14.3; MS (ES+, Ar)
m/z (rel intensity) 330 (MNa+, 100), 213 (11); HRMS (ES+, Ar) calcd
for C18H13NO4Na (MNa+) 330.0737, found 330.0734.
Ethyl (E)-2-cyano-5-(furan-2-yl)-3-styrylbenzoate (11j). Pale
yellow solid: yield 76%, 44 mg; mp 133 °C; IR (KBr, cm−1) 2924 (m),
2852 (w), 2223 (w), 1726 (vs), 1634 (m), 1605 (m), 1369 (w), 1316
(w), 1316 (w), 1255 (w), 1021 (m), 964 (w), 754 (m); 1H NMR (400
MHz, CDCl3) δ 8.23 (ABq, J = 1.4 Hz, 2H), 7.66−7.60 (m, 4H), 7.43−
7.33 (m, 4H), 6.95 (d, J = 3.4 Hz, 1H), 6.58 (dd, J = 3.4, 1.8 Hz, 1H),
4.51 (q, J = 7.1 Hz, 2H), 1.48 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 164.5, 151.5, 144.2, 143.2, 136.1, 134.9, 134.5, 134.1, 129.3,
129.1, 127.5, 124.9, 124.0, 122.9, 116.4, 112.6, 109.2, 109.0, 62.6, 14.3;
MS (ES+, Ar) m/z (rel intensity) 389 ([M + 2Na]+, 14), 382 (MK+, 55),
366 (MNa+, 100); HRMS (ES+, Ar) calcd for C22H17NO3Na (MNa+)
366.1101, found 366.1100.
Ethyl (E)-2-cyano-3-(4-fluorostyryl)-5-(furan-2-yl)benzoate
(11k). Pale yellow solid: yield 73%, 45 mg; mp 154 °C; IR (KBr,
cm−1) 2989 (vw), 2216 (w), 1724 (s), 1635 (w), 1604 (m), 1508 (s),
1371 (w), 1259 (vs), 1231 (vs), 1028 (m), 738 (s); 1H NMR (400 MHz,
CDCl3) δ 8.19 (d, J = 4.0 Hz, 2H), 7.60−7.57 (m, 3H), 7.52 (d, J = 16.2
Hz, 1H), 7.29 (d, J = 16.2 Hz, 1H), 7.09 (t, J = 8.5 Hz, 2H), 6.94 (d, J =
3.3 Hz, 1H), 6.57 (dd, J = 3.3, 1.6 Hz, 1H), 4.50 (q, J = 7.1 Hz, 2H), 1.47
(t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 164.6, 163.3 (d, JC−F
= 249.6 Hz), 151.4, 144.3, 143.0, 134.4, 134.1, 133.6, 132.3 (d, JC−F = 3.3
(vs), 2223 (w), 1744 (s), 1683 (m), 1603 (s), 1580 (m), 1463 (vs), 1377
(m), 1291 (s), 1252 (vs), 1179 (m), 1162 (m), 1026 (m), 823 (m), 754
(m); 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.1 Hz, 1H), 7.64 (d, J =
1.7 Hz, 1H), 7.60 (dd, J = 8.1, 1.7 Hz, 1H), 7.58 (d, J = 8.6 Hz, 2H), 7.44
(td, J = 7.5, 1.6 Hz, 1H), 7.32 (dd, J = 7.5, 1.6 Hz, 1H), 7.08 (t, J = 7.5 Hz,
1H), 7.05 (d, J = 7.5 Hz, 1H), 7.00 (d, J = 8.6 Hz, 2H), 3.87 (s, 3H), 3.86
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.3, 156.7, 145.0, 143.1,
133.4, 131.9, 131.1, 130.5, 129.1, 128.6, 127.6, 125.6, 121.0, 119.1, 114.6,
111.5, 111.4, 55.7, 55.6; MS (ES+, Ar) m/z (rel intensity) 317 ([MH
+1]+, 48), 316 (MH+, 100), 315 ([MH − 1]+, 12); HRMS (ES+, Ar)
calcd for C21H18NO2 (MH+) 316.1332, found 316.1332.
5-(Furan-2-yl)-[1,1′-biphenyl]-2-carbonitrile (13e). Colorless
solid: yield 79%, 33 mg; mp 98 °C; IR (KBr, cm−1) 3107 (w), 3074
(w), 2958 (w), 2934 (w), 2837 (w), 2221 (s), 1609 (s), 1600 (s), 1515
(m), 1484 (m), 1295 (m), 1252 (vs), 1180 (m), 1028 (m), 833 (s), 736
(s), 705 (s); 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 1.6 Hz, 1H),
7.75, 7.70 (ABq, J = 8.2 Hz, the shielded half further split into d, 1.6 Hz,
2H), 7.61−7.58 (m, 2H), 7.54−7.44 (m, 4H), 6.84 (dd, J = 3.4, 0.6 Hz,
1H), 6.54 (dd, J = 3.4, 1.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
152.1, 146.2, 143.9, 138.2, 134.8, 134.3, 129.0, 128.87, 128.93, 125.0,
122.6, 119.0, 112.4, 109.4, 108.5; MS (ES+, Ar) m/z (rel intensity) 268
(MK+, 14), 247 ([M + 2]+, 21), 246 (MH+, 100), 214 (5), 158 (7);
HRMS (ES+, Ar) calcd for C17H12NO (MH+) 246.0919, found
246.0920.
2′-Methoxy-5-(thiophen-2-yl)-[1,1′-biphenyl]-2-carbonitrile
(13f). Pale yellow liquid: yield 80%, 40 mg; IR (neat, cm−1) 2924 (vs),
2853 (s), 2224 (m), 1600 (s), 1582 (w), 1496 (m), 1482 (m), 1463 (m),
1434 (m), 1283 (m), 1250 (s), 1024 (m), 821 (m), 755 (s), 703 (m); 1H
NMR (400 MHz, CDCl3) δ 7.69 (ABq, J = 8.1 Hz, shielded half further
split into d, J = 1.6 Hz, 2H), 7.68 (d, J = 1.6 Hz Hz, 1H), 7.47−7.44 (m,
1H), 7.43 (dd, J = 3.6, 1.1 Hz, 1H), 7.39 (dd, J = 5.1, 1.1 Hz, 1H), 7.31
(dd, J = 7.5, 1.7 Hz, 1H), 7.12 (dd, J = 5.1, 3.6 Hz, 1H), 7.10 (dd, J = 7.5,
1.0 Hz, 1H), 7.07−7.04 (m, 1H), 3.87 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 156.6, 143.3, 142.4, 138.5, 133.5, 130.9, 130.7, 128.6, 128.0,
127.2, 127.0, 125.2, 124.5, 121.0, 118.8, 111.9, 111.5, 55.6; MS (ES+, Ar)
m/z (rel intensity) 330 (MK+, 11), 319 (8), 317 (33), 314 (MNa+, 100),
311 (4); HRMS (ES+, Ar) calcd for C18H13NOSNa (MNa+) 314.0610,
found 314.0610.
4′-Methoxy-5-(thiophen-2-yl)-[1,1′-biphenyl]-2-carbonitrile
(13g). Pale yellow solid: yield 83%, 41 mg; mp 93 °C; IR (KBr, cm−1)
3106 (vw), 2933 (vw), 2836 (vw), 2220 (m), 1600 (s), 1515 (m), 1483
(w), 1295 (m), 1251 (vs), 1180 (m), 1043 (w), 1028 (m), 832 (s), 736
(m), 736 (m), 705 (s); 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.1
Hz, 1H), 7.69 (d, J = 1.7 Hz, 1H), 7.62 (dd, J = 8.1, 1.7 Hz, 1H), 7.55 (d,
J = 8.7 Hz, 2H), 7.45 (dd, J = 3.6, 0.9 Hz, 1H), 7.40 (dd, J = 5.0, 0.9 Hz,
1H), 7.13 (dd, J = 5.0, 3.6 Hz, 1H), 7.04 (d, J = 8.7 Hz, 2H), 3.88 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 160.3, 146.0, 142.3, 138.7, 134.4, 130.4,
Hz), 129.2 (d, JC−F = 8.2 Hz), 124.8, 123.7, 122.8, 116.4, 116.1 (d, JC−F
=
21.8 Hz), 112.6, 109.3, 108.9, 62.6, 14.3; 19F NMR (376.5 MHz, CDCl3)
δ −111.7; MS (ES+, Ar) m/z (rel intensity) 400 (MK+, 64), 384 (MNa+,
100), 379 (39), 362 (23), 347 (9), 291 (9); HRMS (ES+, Ar) calcd for
C22H16FNO3Na (MNa+) 384.1006, found 384.1006.
4-Methoxy-[1,1′:3′,1″-terphenyl]-4′-carbonitrile (13a). Pale
yellow liquid: yield 76%, 37 mg; IR (neat, cm−1) 2924 (m), 2851 (w),
2221 (m), 1602 (vs), 1578 (w), 1518 (m), 1481 (w), 1294 (w), 1251
(vs), 1179 (m), 1027 (m), 824 (m); 1H NMR (400 MHz, CDCl3) δ 7.80
(d, J = 8.1 Hz, 1H), 7.68 (d, J = 1.7 Hz, 1H), 7.63−7.57 (m, 5H), 7.45−
7.55 (m, 3H), 7.01 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 160.4, 146.1, 145.4, 138.5, 134.3, 131.6, 128.9 ( × 2),
128.6, 128.3, 125.7, 119.1, 114.7, 109.2, 55.6; MS (ES+, Ar) m/z (rel
intensity) 308 (MH+, 100), 301 (31), 278 (29), 255 (8), 239 (9), 204
(19), 185 (22); HRMS (ES+, Ar) calcd for C20H15NONa (MNa+)
308.1046, found 308.1049.
4-Methoxy-4″-methyl-[1,1′:3′,1″-terphenyl]-4′-carbonitrile
(13b). Pale yellow solid: yield 75%, 38 mg; mp 86 °C; IR (KBr, cm−1)
2925 (m), 2853 (w), 2221 (m), 1601 (s), 1519 (m), 1483 (m), 1293
1
(m), 1251 (vs), 1179 (m), 1036 (w), 821 (vs); H NMR (400 MHz,
130.1, 128.7, 127.2, 126.9, 125.3, 124.2, 119.1, 114.4, 109.4, 55.5; MS
(ES+, Ar) m/z (rel intensity) 330 (MK, 18), 324 ([MH+MeOH]+, 29),
314 (MNa+, 100), 309 (9), 292 (11); HRMS (ES+, Ar) calcd for
C18H13NOSNa (MNa+) 314.0610, found 314.0610. Confirmed by
1H−1H COSY experiment.
CDCl3) δ 7.78 (d, J = 8.0 Hz, 1H), 7.67 (d, J = 1.8 Hz, 1H), 7.59 (dd, J =
8.0, 1.8 Hz, 1H), 7.58 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 8.0 Hz, 2H), 7.32
(d, J = 8.0 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 2.43 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 160.4, 146.1, 145.4, 138.9, 135.6, 134.3,
131.7, 129.6, 128.8, 128.6, 128.2, 125.5, 119.3, 114.7, 109.1, 55.6, 21.5;
MS (ES+, Ar) m/z (rel intensity) 338 (MK+, 60), 322 (MNa+, 100), 319
(53), 307 (26), 297 (21), 213 (19), 135 (14); HRMS (ES+, Ar) calcd for
C21H17NONa (MNa+) 322.1202, found 322.1203.
4,4″-Dimethoxy-[1,1′:3′,1″-terphenyl]-4′-carbonitrile (13c).
Pale yellow liquid: yield 72%, 39 mg; IR (neat, cm−1) 2957 (m), 2924
(s), 2851 (m), 2220 (m), 1608 (vs), 1600 (vs), 1578 (w), 1518 (s), 1482
(m), 1465 (w), 1291 (m), 1250 (s), 1178 (s), 1028 (s), 824 (vs), 758
(m), 536 (m); 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.1 Hz, 1H),
7.65 (d, J = 1.5 Hz, 1H), 7.59−7.55 (m, 5H), 7.03 (d, J = 8.8 Hz, 2H),
7.01 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 3.86 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 160.4, 160.3, 145.8, 145.4, 134.3, 131.7, 130.9, 130.2,
128.6, 128.1, 125.3, 119.4, 114.7, 114.4, 109.0, 55.6, 55.5; MS (ES+, Ar)
m/z (rel intensity) 354 (MK+, 10), 338 (MNa+, 49), 301 (100), 132
(41), 102 (19); HRMS (ES+, Ar) calcd for C21H17NO2Na (MNa+)
338.1151, found 338.1158.
4′-Bromo-5-(thiophen-2-yl)-[1,1′-biphenyl]-2-carbonitrile
(13h). Colorless solid: yield 70%, 40 mg; mp 183 °C; IR (KBr, cm−1)
3098 (vw), 2222 (s), 1601 (m), 1478 (m), 1269 (m), 1182 (w), 1074
(w), 837 (m), 818 (vs), 717 (vs); 1H NMR (400 MHz, CDCl3) δ 7.76
(d, J = 7.7 Hz, 1H), 7.68 (dd, J = 7.7, 1.8 Hz, 1H), 7.68 (d, J = 1.8 Hz,
1H), 7.65 (d, J = 8.3 Hz, 2H), 7.47 (d, J = 8.3 Hz, 2H), 7.46 (dd, J = 3.7,
0.9 Hz, 1H), 7.42 (dd, J = 5.0, 0.9 Hz, 1H), 7.14 (dd, J = 5.0, 3.7 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 145.1, 142.0, 139.0, 137.0, 134.5, 132.2,
130.5, 128.8, 127.5, 126.9, 125.6, 125.0, 123.7, 118.6, 109.5; MS (ES+,
Ar) m/z (rel intensity) 364 ([MNa+2]+, 100), 362 (MNa+, 100), 341
(33), 339 (35); HRMS (ES+, Ar) calcd for C17H10BrNSNa (MNa+)
361.9610, found 361.9609.
4-Chloro-4″-methoxy-[1,1′:3′,1″-terphenyl]-4′-carbonitrile
(13i). Pale yellow solid: yield 77%, 42 mg; mp 145 °C; IR (KBr, cm−1)
3054 (vw), 2937 (w), 2223 (m), 1601 (s), 1515 (s), 1478 (s), 1381 (m),
1294 (m), 1263 (s), 1251 (vs), 1178 (m), 1095 (w), 1033 (m), 1019
1
2″,4-Dimethoxy-[1,1′:3′,1″-terphenyl]-4′-carbonitrile (13d).
(w), 821 (vs), 809 (vs), 734 (w), 609 (w), 518 (m); H NMR (500
Pale yellow liquid: yield 62%, 33 mg; IR (neat, cm−1) 2929 (vs), 2857
MHz, CDCl3) δ 7.80 (d, J = 8.1 Hz, 1H), 7.65 (d, J = 1.5 Hz, 1H), 7.58
G
dx.doi.org/10.1021/jo501193h | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(dd, J = 8.1, 1.5 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.7 Hz,
2H), 7.46 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 8.7 Hz, 2H), 3.88 (s, 3H); 13C
NMR (125 MHz, CDCl3) δ 160.4, 146.0, 144.5, 137.8, 135.1, 134.4,
130.5, 130.2, 129.5, 128.7, 128.5, 125.7, 119.1, 114.5, 110.1, 55.6; MS
(ES+, Ar) m/z (rel intensity) 360 ([MK+2]+, 11), 345 ([M + 3]Na+, 6),
344 ([M + 2]Na+, 50), 343 ([M + 1]Na+, 15), 342 (MNa+, 100), 320
(3), 301 (6); HRMS (ES+, Ar) calcd for C20H14ClNONa (MNa+)
342.0656, found 342.0656.
General Procedure for Synthesis of 4-Phenylisoindolin-1-one
Derivatives 16. A stirred mixture of cyanoester 9 (0.140 mmol), allyl
bromide (68 mg, 48 μL, 4.0 equiv, 0.56 mmol), and indium powder (32
mg, 2 equiv, 0.28 mmol) in THF (0.5 mL) was heated to 90 °C under
microwave irradiation for 1−2 h. After completion of reaction, the crude
product was directly purified by silica gel column chromatography by
eluting with EtOAc−pet ether (gradient elution) to afford pure 16.
3,3-Diallyl-6-(4-methoxyphenyl)-4-phenylisoindolin-1-one
(16a). Off white solid: yield 81%, 45 mg; mp 181 °C; IR (KBr, cm−1)
3206 (br, w), 3074 (vw), 2929 (vw), 2836 (vw), 1696 (vs), 1609 (w),
1519 (vw), 1468 (m), 1442 (w), 1360 (w), 1288 (w), 1250 (m), 1179
(w), 1030 (vw), 921 (w); 1H NMR (500 MHz, CDCl3) δ 8.04 (d, J = 1.3
Hz, 1H), 7.60 (d, J = 8.7 Hz, 2H), 7.54 (d, J = 1.3 Hz, 1H), 7.46−7.45
(m, 3H), 7.36−3.35 (m, 2H), 6.97 (d, J = 8.7 Hz, 2H), 5.46 (ddt, J =
17.2, 10.1, 7.0 Hz, 2H), 5.03−4.99 (m, 4H), 3.84 (s, 3H), 2.48 (dd, J =
14.3, 7.0 Hz, 2H), 2.36 (dd, J = 14.3, 7.0 Hz, 2H); 13C NMR (125 MHz,
CDCl3) δ 170.2, 159.7, 143.6, 141.0, 139.8, 138.7, 134.0, 132.5, 132.1,
132.0, 129.2, 128.4, 128.17, 128.22, 120.8, 119.6, 114.5, 65.6, 55.5, 42.5;
MS (ES+, Ar) m/z (rel intensity) 436 ([M + CH3CN]+, 30), 418 (MNa+,
4″-Methoxy-[1,1′:3′,1″-terphenyl]-4′-carbonitrile (13j). Pale
yellow liquid: yield 73%, 36 mg; IR (neat, cm−1) 3053 (vw), 2924 (s),
2850 (w), 2221 (m), 1608 (s), 1601 (s), 1518 (s), 1483 (m), 1290 (s),
1251 (vs), 1178 (m), 1029 (m), 824 (s), 738 (vs), 704 (w), 535 (w); 1H
NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 1.6 Hz,
1H), 7.65−7.62 (m, 2H), 7.61 (dd, J = 8.0, 1.6 Hz, 1H), 7.57 (d, J = 8.7
Hz, 2H), 7.51−7.47 (m, 2H), 7.45−7.41 (m, 1H), 7.04 (d, J = 8.7 Hz,
2H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.3, 145.8, 145.8,
139.4, 134.3, 130.7, 130.2, 129.3, 128.8, 128.7, 127.4, 125.9, 119.2, 114.4,
109.7, 55.6; MS (ES+, Ar) m/z (rel intensity) 326 ([MK+2]+, 6), 309
([M + 1]Na+, 15), 308 (MNa+, 100), 301 (9), 286 (MH+, 9); HRMS
(ES+, Ar) calcd for C20H15NONa (MNa+) 308.1046, found 308.1047.
2″,4-Dimethoxy-[1,1′:3′,1″-terphenyl]-4′,4′(5′H)-dicarboni-
trile (14d). Pale yellow solid: yield 71%, 41 mg; mp 117 °C; IR (KBr,
cm−1) 2958 (m), 2923 (vs), 2851 (m), 2222 (w), 1726 (m), 1606 (m),
1513 (m), 1488 (w), 1462 (m), 1250 (s), 1180 (m), 1120 (w), 1025 (s),
834 (w), 756 (s); 1H NMR (400 MHz, CDCl3) δ 7.43 (t, J = 7.7 Hz,
1H), 7.38 (d, J = 8.5 Hz, 2H), 7.31 (dd, J = 7.7, 1.5 Hz, 1H), 7.04−6.99
(m, 2H), 6.90 (d, J = 8.5 Hz, 2H), 6.74 (s, 1H), 6.21 (t, J = 4.3 Hz, 1H),
3.99 (s, 3H), 3.82 (s, 3H), 3.15 (d, J = 4.3 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ 160.0, 157.1, 137.6, 131.2, 130.6, 130.3, 128.9, 127.1,
125.7, 121.3, 116.4, 115.6, 114.3, 111.1, 55.5, 54.8, 35.6, 35.1; MS (ES+,
Ar) m/z (rel intensity) 381 (MK+, 31), 365 (MNa+, 100); HRMS (ES+,
Ar) calcd for C22H18N2O2Na (MNa+) 365.1260, found 365.1258.
Confirmed by 1H−1H 2D-COSY experiment.
+
100); HRMS (ES+, Ar) calcd for C27H25NO2Na (MNa ) 418.1777,
found 418.1779.
3,3-Diallyl-6-(furan-2-yl)-4-phenylisoindolin-1-one (16b).
White solid: yield 77%, 38 mg; mp 218 °C; IR (KBr, cm−1) 3183 (w),
3072 (w), 2899 (w), 1691 (vs), 1436 (vw), 1353 (w), 1254 (vw), 1017
(vw), 995 (w), 923 (w); 1H NMR (500 MHz, CDCl3) δ 8.10 (d, J = 1.6
Hz, 1H), 7.67 (d, J = 1.6 Hz, 1H), 7.46−7.45 (m, 4H), 7.34−7.33 (m,
2H), 7.01−6.99 (br, 1H), 6.75 (dd, J = 3.3, 0.3 Hz, 1H), 6.48 (dd, J = 3.4,
1.8 Hz, 1H), 5.43 (ddt, J = 17.1, 10.1, 7.1 Hz, 2H), 5.01 (d, J = 17.1 Hz,
2H), 4.99 (d, J = 10.1 Hz, 2H), 2.44 (dd, J = 14.3, 7.1 Hz, 2H), 2.34 (dd, J
= 14.3, 7.1 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 169.9, 153.0, 144.0,
142.7, 139.5, 138.8, 134.1, 131.8, 131.2, 129.4, 129.1, 128.3 ( × 2), 119.6,
118.2, 112.0, 106.4, 65.9, 42.4; MS (ES+, Ar) m/z (rel intensity) 394
(MK+, 81), 378 (MNa+, 100), 369 (6), 353 (8); HRMS (ES+, Ar) calcd
for C24H21NO2Na (MNa+) 378.1464, found 378.1461.
(E)-2-(3-(4-Methoxyphenyl)-1-phenylallylidene)malono-
nitrile (10).25 To a stirred solution of MBH−acetate 7a (0.17 mmol) in
DCM (3 mL) at rt, was added alkylidene malononitrile 8 (0.17 mmol)
followed by K2CO3 (94 mg, 0.68 mmol) or Cs2CO3 (222 mg, 0.68
mmol) and the completion of the reaction was monitored by TLC. The
crude product was directly purified by silica gel column chromatography
by eluting with 3−10% EtOAc-pet ether (gradient elution). Yellow
solid: yield 68%, 32 mg (K2CO3, entry 9, Table 1), 70%, 37 mg (Cs2CO3,
entry 10, Table 1); mp 119 °C (lit 125 °C,25a 129 °C25b); IR (KBr,
cm−1) 2925 (m), 2854 (w), 2221 (m), 1594 (s), 1569 (m), 1521 (s),
1255 (vs), 1175 (s), 1105 (w), 1027 (m), 834 (w), 762 (br m); 1H NMR
(400 MHz, CDCl3) δ 7.60−7.44 (m, 6H), 7.37 (d, J = 6.7 Hz, 2H), 6.91
(d, J = 8.6 Hz, 2H), 6.83 (d, J = 15.4 Hz, 1H), 3.85 (s, 3H); 13C NMR
(125 MHz, CDCl3) δ 171.7, 162.9, 149.3, 133.5, 131.2, 131.0, 129.1,
129.0, 127.3, 122.4, 114.9, 113.9, 113.3, 80.8, 55.7; MS (ES+, Ar) m/z
(rel intensity) 328 ([MK+3]+, 11), 327 ([MK+2]+, 51), 310 ([MNa
+1]+, 23), 309 (MNa+, 100), 304 (8); HRMS (ES+, Ar) calcd for
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of NMR spectra for all the new compounds as well as CIF
for compound 11f. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: irishi@iitb.ac.in.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
1
C19H14N2ONa (MNa+) 309.0998, found 309.1000. IR and H NMR
■
data are broadly in agreement with literature.25
I.N.N.N. thanks DST India for financial assistance. E.G. thanks
CSIR India for a senior research fellowship. The authors thank
Mr. Kalisankar Bera, Department of Chemistry, IIT Bombay, for
X-ray data.
General Procedure for Selective Hydrolysis of Ester 9h.
Lithium hydroxide (26 mg, 1.103 mmol, 7 equiv) was added to a stirred
solution of cyanoester 9h (50 mg, 0.158 mmol) in THF/water (1:1, 1
mL) at room temperature. After overnight stirring, the reaction mixture
was poured into 1 N HCl and extracted with diethyl ether (3 × 10 mL).
The combined organic extracts were washed with brine (10 mL), dried
(Na2SO4), and concentrated in vacuo to give the title compound 15.
2-Cyano-5-(furan-2-yl)-[1,1′-biphenyl]-3-carboxylic acid (15).
Pale yellow solid: yield 86%, 39 mg; mp 223 °C; IR (KBr, cm−1) 3647
(br, w), 2926 (br, s), 2223 (w), 1705 (s), 1604 (m), 1468 (m), 1295
(m), 934 (br, s), 695 (vs); 1H NMR (400 MHz, DMSO) δ 13.97 (br s,
1H), 8.30 (unresolved, 1H), 8.00 (unresolved, 1H), 7.89 (unresolved,
1H), 7.58−7.52 (m, 5H), 7.41 (unresolved, 1H), 6.68 (unresolved, 1H);
13C NMR (100 MHz, DMSO) δ 165.5, 150.4, 147.8, 145.2, 137.7, 135.8,
133.5, 129.1, 128.9, 128.5, 127.4, 123.6, 116.6, 112.9, 110.6, 107.9; MS
(ES+, Ar) m/z (rel intensity) 328 (MK+, 23), 312 (MNa+, 100), 301 (6);
HRMS (ES+, Ar) calcd for C18H11NO3Na (MNa+) 312.0631, found
312.0634.
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