A facile approach to highly functional trisubstituted furans via intramolecular Wittig reactions

Article abstract of DOI:10.1039/c0ob00912a

An efficient and mild synthesis of trisubstituted furans, starting from α,β-unsaturated ketones, tributylphosphine, and acyl chlorides, is described. The strategy employs the intramolecular Wittig protocol as a key step to install the crucial furan ring,

Full text of DOI:10.1039/c0ob00912a

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PAPER
A facile approach to highly functional trisubstituted furans via intramolecular
Wittig reactions†
Ko-Wei Chen, Siang-en Syu, Yeong-Jiunn Jang and Wenwei Lin*
Received 21st October 2010, Accepted 6th December 2010
DOI: 10.1039/c0ob00912a
An efficient and mild synthesis of trisubstituted furans, starting from a,b-unsaturated ketones,
tributylphosphine, and acyl chlorides, is described. The strategy employs the intramolecular Wittig
protocol as a key step to install the crucial furan ring, leading to a wide variety of highly functional
furans in one step.
Our interest in this area is stimulated by the prospect of
Introduction
designing a complementary entry to this class of polysubstituted
The preparation of multi-substituted furans is of importance in
furans, which cannot be easily acquired by other known protocols,
organic synthesis because such a heterocyclic ring is found in
based on our previous report on an intramolecular Wittig
numerous interesting compounds, which exhibit a wide array
of activities and are also useful building blocks.1,2 Accordingly,
many powerful synthetic routes toward furan rings with specific
substitution patterns have been designed and well applied,1c,3
the majority of which include direct functionalization of furan
rings,4 cyclocondensation of 1,4-dicarbonyl compounds (Paal–
reaction. Inspired by our previous work, we herein report a novel
preparation of trisubstituted furans 1 starting from Bu3P, a,b-
unsaturated ketones 2, and acid chlorides 3 in the presence of Et3N
in one step, which is via the phosphorus ylides 4 as intermediates
(Scheme 1). Different kinds of 2 in combination with various acid
chlorides 3 should make this methodology an attractive approach
Knorr synthesis),5 Feist-Be´nary synthesis,6 and transition metal-
toward a wide diversity of substitution patterns in the furan rings.
catalyzed cycloisomerization of alkynyl or allenyl substrates.3a,7
Still, of these developed strategies,1–7,8 general and efficient
methodologies for the syntheses of trisubstituted furans from
simple and readily available precursors are of great value.7a,9
Recently, we have developed efficient syntheses of tetrasubsti-
tuted furans via intramolecular Wittig reactions.10 The zwitterion
intermediates, which resulted from the Michael additions of PBu3
to the corresponding Michael acceptors, are very stable and
can be formed effectively. The stabilities of the zwitterions were
attributed to the delocalization of the negative charge with a ketone
functionality and an electron-withdrawing group (Fig. 1).
Scheme 1 Syntheses of highly functionalized furans 1 from 2, acid
chlorides 3 and Bu3P in the presence of Et3N.
Results and discussion
At the outset of our investigations, chalcone (2a), Bu3P, Et3N, and
benzoyl chloride (3a) were chosen as a model study to optimize the
reaction conditions (Fig. 2). However, pilot studies disclosed that
our previously reported addition sequence of reactants proved
unsatisfactory and unsuccessful in constructing these series of
polysubstituted furans, being frustrated by the formation of messy
byproducts and much lower yields (Fig. 2, equations a and b). In
contrast to our previous report, the addition sequence of reactants
is critical for the success of these designed reactions, because a,b-
unsaturated ketones 2 are prone to undergo polymerization in the
presence of Bu3P. 10 Therefore, developing a different protocol was
Fig. 1 Stable zwitterion intermediates generated from Michael additions
of PBu3 toward the corresponding Michael acceptors.
Department of Chemistry, National Taiwan Normal University, 88, Section
4, Tingchow Road, Taipei 11677, Taiwan, Republic of China. E-mail:
wenweilin@ntnu.edu.tw
† Electronic supplementary information (ESI) available: General experi-
mental procedures, compound characterization data, and NMR spectra.
CCDC reference numbers 792216–792218. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c0ob00912a
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Fig. 2 Optimization of the addition sequence of reactants in the synthesis of 1aa.a
Table 1 Syntheses of furans 1 from 2 and benzoyl chloride (3a)a Table 2 Syntheses of furans 1 from 2 and benzoyl chloride (3a)a
R1 (2)
Time/min
Yield of 1 (%)b
Entry
R2 (2)
Time/min
Yield of 1 (%)b
Entry
1
2
3
4
5
6
7
8
4-NO2C6H4 (2l)
4-BrC6H4 (2m)
3-NO2C6H4 (2n)
2-BrC6H4 (2o)
4-CH3OC6H4 (2p)
t-butyl (2q)
10
10
10
10
10
60
60
30
1la, 55
1ma, 83
1na, 68c
1oa, 67d
1pa, 69
1qa, 52
1ra, 51
1sa, 55
1
2
3
4
5
6
7
8
C6H5 (2a)
30
10
10
10
10
10
10
60
240
10
20
1aa, 76
1ba, 82
1ca, 93
1da, 73c
1ea, 93
1fa, 84
1ga, 78
1ha, 70
1ia, 41d
1ja, 60
1ka, 68
4-NO2C6H4 (2b)
4-CN6H4 (2c)
4-BrC6H4 (2d)
4-CF3C6H4 (2e)
3-NO2C6H4 (2f)
3-ClC6H4 (2g)
2-NO2C6H4 (2h)
4-CH3OC6H4 (2i)
2-furyl (2j)
cyclohexyl (2r)
CO2Et (2s)e
9
10
11
a Reactions were carried out using 2 (0.5 mmol) in THF (2.5 mL) under
nitrogen at rt. b Yields of isolated products. c The reaction was carried out
in CH2Cl2 due to the poor solubility of 2n in THF. d The structure of 1oa
was confirmed by X-ray analysis (CCDC number: 792218).† e Ar = 2-furyl
2-thienyl (2k)
a Reactions were carried out using 2 (0.5 mmol) in THF (2.5 mL) under
nitrogen at rt. b Yields of isolated products. c The structure of 1da was
confirmed by X-ray analysis (CCDC number: 792217).† d 1.5 equiv of
Bu3P was used.
effects have a strong influence on the reactivity.11 The b-aryl-
substituted a,b-unsaturated ketones 2b–g, which bear an electron-
withdrawing group on the aromatic ring, reacted with Bu3P, Et3N,
and3aefficientlywithin10min(entries 2–7). However, thereaction
of Michael acceptor 2a, Bu3P, Et3N, and 3a took place in a
prolonged time (30 min) to lead to 1aa (entry 1). It took an even
longer time to proceed when 2i (R1 = 4-CH3OC6H4) was used
(4 h, entry 9). In addition, the steric effect of a,b-unsaturated
ketones 2 was observed. For example, the Michael acceptor 2b
(R1 = 4-NO2C6H4) reacted with Bu3P, Et3N, and 3a efficiently to
furnish 1ba within 10 min (entry 2). However, in the same reaction
conditions, a longer time was necessary for 2h (R1 = 2-NO2C6H4)
to afford 1ha (70% yield, 1 h) (entry 8).
necessary so that adducts between 2 and Bu3P would not react
further before trapping by acid chloride 3 to achieve 4. After the
optimization of the reaction conditions, we found that the best
results were given when the reactions were carried out by the
dropwise addition of 2 into the reaction mixture of Bu3P and 3,
and then followed by the addition of Et3N (Fig. 2, equation c).
Thus, chalcone (2a, 1.0 equiv), Bu3P (1.1 equiv), Et3N
(1.2 equiv), and benzoyl chloride (3a, 1.1 equiv) reacted smoothly
at room temperature within 30 min, furnishing the highly sub-
stituted furan 1aa in 76% yield (Table 1, entry 1). Other b-
aryl-subsituted a,b-unsaturated ketones, such as 2b–k (R1 = 4-
NO2C6H4, 4-CNC6H4, 4-BrC6H4, 4-CF3C6H4, 3-NO2C6H4, 3-
ClC6H4, 2-NO2C6H4, 4-CH3OC6H4, 2-furyl, or 2-thienyl), reacted
successfully with 3a within 10–240 min, leading to the correspond-
ing products 1 in 41–93% yields (entries 2–11). The electronic
The broad reaction scope of our protocol was demonstrated by
further studies disclosed in Table 2. It showed that in the presence
of Bu3P (1.1 equiv) and Et3N (1.2 equiv), the reactions of Michael
acceptors bearing a ketone function with different substituents,
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Table 3 Syntheses of furans 1 from 2c and acid chloride 3a
Scheme 2 Preparation of highly functionalized furans 1ta and 1tc.
Entry
R3(3)
Time/min
Yield of 1 (%)b
1
2
3
4
5
6
7
8
C6H5 (3a)
10
10
10
10
10
10
—
10
10
60
10
1800
60
—
1ca, 93
1ca, 64
1cc, 77
1cd, 80
1ce, 87
1cf, 67
1cg, —
1ch, 72
1ci, 67
1cj, 62
1ck, 72
1cl, 24c
1cm, 52
1cn, —
smoothly within 10 min at room temperature, giving rise to the
fully functionalized furans 1ta or 1tc in 70 or 60% yield.
On the basis of the experimental results, a plausible reaction
mechanism was proposed (Scheme 3). First, the regioselective
Michael addition of Bu3P toward 2t took place, providing the
corresponding zwitterion 5. The intermediate 5 was in situ acylated
with an acid chloride 3, leading to the formation of 6. Then
deprotonation of 6 by Et3N occurred, and the resulting ylide
7 underwent an intramolecular Wittig reaction, affording the
corresponding furan 1.
4-NO2C6H4 (3b)
4-ClC6H4 (3c)
4-CH3OC6H4 (3d)
4-CH3C6H4 (3e)
3-ClC6H4 (3f)
2-NO2C6H4 (3g)
2-ClC6H4 (3h)
2-BrC6H4 (3i)
2-furyl (3j)
9
10
11
12
13
14
2-thienyl (3k)
CH3 (3l)
i-propyl (3m)
CO2Et (3n)
a Reactions were carried out using 2c (0.5 mmol) in THF (2.5 mL) under
nitrogen at rt. b Yields of isolated products. c 1.5 equiv of Bu3P was used.
like 2l–s (R2 = 4-NO2C6H4, 4-BrC6H4, 3-NO2C6H4, 2-BrC6H4, 4-
CH3OC6H4, t-butyl, cyclohexyl, or CO2Et), and 3a (1.1 equiv),
took place in 10–60 min, leading to the corresponding adducts
1 in 51–83% yields (Table 2, entries 1–8). Remarkably, electronic
and steric effects of the R2 (R2 = Ar) group of 2 were hardly
observed because the conversion of 2l–p was complete within
10 min (entries 1–5). Furthermore, when the R2 group is an
aliphatic substituent, such as a t-butyl or cyclohexyl group, 2q
or 2r worked smoothly with 3a, Bu3P and Et3N within 60 min,
giving rise to the corresponding furan 1qa or 1ra in 52 or 51%
yield, respectively (entries 6 and 7). When the R2 group is an ester
functionality (Ar = 2-furyl), 2s also reacted successfully with 3a in
the same reaction conditions, leading to 1sa in 55% yield (entry
8).
Scheme 3 A proposed mechanism for the formation of 1ta or 1tc.
Next, we investigated the reaction scope of our protocol with
different kinds of acyl chlorides 3 (Table 3). All the aryl-substituted
acid chlorides 3a–f and 3h–k (R3 = C6H5, 4-NO2C6H4, 4-ClC6H4, 4-
CH3OC6H4, 4-CH3C6H4, 3-ClC6H4, 2-ClC6H4, 2-BrC6H4, 2-furyl,
and 2-thienyl) were applied nicely in our designed reaction with 2c
in the presence of Bu3P and Et3N within 10 or 60 min, providing
the corresponding furans 1 (62–93% yield) (entries 1–6 and 8–11).
Interestingly, when 3g (R3 = 2-NO2C6H4) was used, no desired
reaction took place probably due to the steric hindrance of the
nitro group, which retarded the occurrence of the intramolecular
Wittig reaction. Besides, under the same reaction conditions, 2c
reacted effectively with an alkyl-substituted acid chloride 3m (R3 =
i-propyl) within 60 min, furnishing 1cm in 52% yield (entry 13).
However, a poor result (1cl, 24% yield) was given when acetyl
chloride (3l) was used even with a prolonged time (30 h, entry
12). Ethyl oxalyl chloride (3n) was also examined in our protocol
(entry 14). However, no reaction was observed.
Surprisingly, the more electron-deficient alkene 2u, which was
expected to work efficiently in our protocol, reacted with Bu3P and
benzoyl chloride (3a) in the presence of Et3N in a relatively long
time (40 h) in comparison to that of the other alkenes 2a–t (10 min
to 4 h) (Scheme 4). In addition, the interesting compound 8, which
resulted from the trapping of the intermediate 9 with excess 3a,
was observed in our crude mixture and can be confirmed by X-ray
analysis.12 All these phenomena showed that delocalization of the
negative charge of 9 can account for the competitive formation of
8 and the relatively weak reactivity for the formation of 1ua.
In conclusion, our strategy based on an intramolecular Wittig
reaction represents a facile and versatile method for a poly-
substituted installation at the 2-, 3-, and 5-positions in furans.
Furthermore, the easy access to acid chlorides 3 as well as b-
aryl-substituted a,b-unsaturated ketones 2, makes our protocol
an efficient approach toward a wide diversity of substitution
patterns in the furan rings. Further studies and the extensions of
this concept in the preparation of other heterocycles are currently
underway in our laboratory.
Instead of using the Michael acceptor with a ketone func-
tionality (Tables 1–3), a substrate bearing both ketone and ester
functions, such as 2t, was also studied (Scheme 2). The reaction
of 2t and 3a or 3c in the presence of Bu3P and Et3N proceeded
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Scheme 4 Preparation of highly functionalized furans 1ua and the possible reaction mechanism.
THF (2.5 mL) [reaction conditions: rt for 10 min]. Purification
by flash chromatography (hexanes/ethyl acetate: 40/1; Rf: 0.41)
yielded 1ba as yellow solid (139.0 mg, 82%). mp.: 126.5–126.7 ◦C.
1H-NMR (400 MHz, CDCl3, 25 ◦C) d (ppm): 8.23 (d, 2H, J =
8.8 Hz), 7.81–7.74 (m, 2H), 7.64–7.54 (m, 4H), 7.44 (t, 2H, J =
8.0 Hz), 7.40–7.30 (m, 4H), 6.84 (s, 1H). 13C-NMR (100 MHz,
Experimental section
Typical procedure for syntheses of furans 1 from 2 and acid
chlorides 3 in the presence of Bu3P and Et3N. (TP for Tables 1–3,
Schemes 2 and 4)
A dry and nitrogen-flushed 10 mL Schlenk flask, equipped with a
magnetic stirring bar and a septum, was charged with a solution
of acid chloride 3 (1.1 equiv) and Bu3P (137.0 mL, 1.1 equiv) in dry
THF (0.5 mL). A solution of 2 (0.5 mmol) in dry THF (2.0 mL)
was added, which was followed by the addition of Et3N (84.0 mL,
1.2 equiv). The reaction mixture was stirred for the indicated
time at room temperature. Thereafter, the solvent was removed
by evaporation in vacuo. Purification by flash chromatography
furnished 1.
◦
CDCl3, 25 C) d (ppm): 153.4, 149.3, 146.7, 141.1, 130.2, 129.9,
129.0, 128.8, 128.6, 128.4, 127.9, 126.6, 123.9, 123.8, 122.2, 108.2.
+
-1
˜
MS (20 eV, EI) m/z (%): 342 [M+1] (100). IR (CH2Cl2) n (cm ):
3062 (w), 1598 (m), 1517 (s), 1344 (s). HRMS (ESI) for C22H16NO3,
[M+H]+ (342.1130) found: 342.1133.
4-(2,5-Diphenylfuran-3-yl)benzonitrile (1ca)9. Prepared ac-
cording to TP from 2c (116.6 mg, 0.5 mmol), Bu3P (137.0 mL,
1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL, 1.1 equiv) in
dry THF (2.5 mL) [reaction conditions: rt for 10 min]. Purification
by flash chromatography (hexanes/ethyl acetate: 40/1; Rf: 0.41)
yielded 1ca as white solid (149.4 mg, 93%). 1H-NMR (400 MHz,
CDCl3, 25 ◦C) d (ppm): 7.79–7.74 (m, 2H), 7.65 (d, 2H, J = 8.4 Hz),
7.57 (d, 4H, J = 4.2 Hz), 7.42 (t, 2H, J = 7.8 Hz), 7.40–7.29 (m,
4H), 6.82 (s, 1H). 13C-NMR (100 MHz, CDCl3, 25 ◦C) d (ppm):
153.3, 149.0, 139.1, 132.4, 130.3, 130.0, 129.0, 128.8, 128.6, 128.3,
127.9, 126.5, 123.8, 122.6, 118.8, 110.7, 108.2. MS (20 eV, EI) m/z
(%): 321[M]+ (100).
2,3,5-Triphenylfuran (1aa)7a. Prepared according to TP from
2a (104.3 mg, 0.5 mmol), Bu3P (137.0 mL, 1.1 equiv), Et3N
(84.0 mL, 1.2 equiv), and 3a (64.0 mL, 1.1 equiv) in dry THF
(2.5 mL) [reaction conditions: rt for 30 min]. Purification by flash
chromatography (hexanes; Rf: 0.56) yielded 1aa a◦s white solid
1
(112.4 mg, 76%). H-NMR (400 MHz, CDCl3, 25 C) d (ppm):
7.77 (d, 2H, J = 7.7 Hz), 7.61 (d, 2H, J = 7.3 Hz), 7.50–7.26 (m,
11H), 6.82 (s, 1H). 13C-NMR (100 MHz, CDCl3, 25 ◦C) d (ppm):
152.5, 147.9, 134.27, 131.1, 130.5, 128.8, 128.7, 128.6, 127.5, 127.4,
127.3, 126.1, 124.5, 123.8, 109.4. MS (20 eV, EI) m/z (%): 296 [M]+
(100).
3-(4-Bromophenyl)-2,5-diphenylfuran (1da). Prepared accord-
ing to TP from 2d (143.6 mg, 0.5 mmol), Bu3P (137.0 mL, 1.1 equiv),
Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL, 1.1 equiv) in dry
THF (2.5 mL) [reaction conditions: rt for 10 min]. Purification
by flash chromatography (hexanes; Rf: 0.58) yielded 1da as white
solid (136.5 mg, 73%). mp.: 127.3–127.5 ◦C. 1H-NMR (400 MHz,
3-(4-Nitrophenyl)-2,5-diphenylfuran (1ba). Prepared accord-
ing to TP from 2b (126.6 mg, 0.5 mmol), Bu3P (137.0 mL, 1.1 equiv),
Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL, 1.1 equiv) in dry
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CDCl3, 25 ◦C) d (ppm): 7.78 (d, 2H, J = 7.6 Hz), 7.62 (d, 2H, J =
7.3 Hz), 7.53 (d, 2H, J = 8.4 Hz), 7.45 (d, 2H, J = 7.6 Hz), ◦7.40–
7.27 (m, 6H), 6.80 (s, 1H). 13C-NMR (100 MHz, CDCl3, 25 C) d
(ppm): 152.8, 148.0, 133.2, 131.8, 130.8, 130.3, 130.2, 128.7, 128.5,
yielded 1ha as orange solid (119.1 mg, 70%). mp.: 127.0–127.5 ◦C.
1H-NMR (400 MHz, CDCl3, 25 ◦C) d (ppm): 7.99 (d, 1H, J =
8.0 Hz), 7.76 (d, 2H, J = 7.4 Hz), 7.63–7.50 (m, 2H), 7.50–7.39
(m, 5H), 7.◦35–7.21 (m, 4H), 6.71 (s, 1H). 13C-NMR (100 MHz,
CDCl3, 25 C) d (ppm): 152.8, 149.5, 148.7, 132.8, 130.1, 129.2,
128.8, 128.7, 128.5, 127.8, 127.7, 125.5, 124.5, 123.9, 119.3, 109.1.
127.7, 127.6, 126.2, 123.8, 123.2, 121.2, 108.9. MS (20 eV, EI) m/z
-1
(%): 376 [M+2]+ (100), 374 (64). IR (KBr) n (cm ): 3055 (m),
˜
3033 (m), 1547 (m), 1488 (s), 691 (m), 595 (m). HRMS (ESI) for
C22H16BrO, [M+H]+ (375.0385) found: 375.0380.
MS (20 eV, EI) m/z (%): 342 [M+1]+ (32), 105 (100). IR (CH2Cl2)
-1
˜
n (cm ): 3063 (w), 1524 (s), 1488 (m), 1457(m), 1347 (m). HRMS
(EI) for C22H16NO3, [M+H]+ (342.1130) found: 342.1139.
2,5-Diphenyl-3-(4-(trifluoromethyl)phenyl)furan
(1ea). Pre-
pared according to TP from 2e (138.1 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for
10 min]. Purification by flash chromatography (hexanes; Rf: 0.40)
yielded 1ea as white solid (152.1 mg, 93%). mp.: 103.1–103.9 ◦C.
1H-NMR (400 MHz, CDCl3, 25 ◦C) d (ppm): 7.79 (d, 2H, J =
7.6 Hz), 7.70–7.55 (m, 6H), 7.45 (t, 2H, J = 7.5 Hz), 7.41–7.29
(m, 4H), 6.84 (s, 1H). 13C-NMR (100 MHz, CDCl3, 25 ◦C) d
(ppm): 153.1, 148.6, 138.1, 130.6, 130.2, 129.4 (quartet, J =
32.0 Hz), 128.8, 128.7, 128.6, 128.0, 127.8, 126.4, 125.6 (quartet,
J = 4.0 Hz), 124.2 (quartet, J = 270.0 Hz), 123.9, 123.0, 108.8. MS
3-(4-Methoxyphenyl)-2,5-diphenylfuran (1ia)13a
. Prepared ac-
cording to TP from 1ia (119.1 mg, 0.5 mmol), Bu3P (187.0 mL,
1.5 equiv), Et3N (90.6 mL, 1.3 equiv), and 3a (64.0 mL, 1.1 equiv)
in dry THF (2.5 mL) [reaction conditions: rt for 2 h]. Purification
by flash chromatography (hexanes/ethyl acetate: 40/1; Rf: 0.44)
1
yielded 2ia as yellow oil (67.1 mg, 41%). H-NMR (400 MHz,
CDCl3, 25 ◦C) d (ppm): 7.79–7.74 (m, 2H), 7.65–7.61 (m, 2H),
7.45–7.21(m, 8H), 6.96–6.90 (m,◦2H), 6.78 (s, 1H), 3.84 (s, 3H).
13C-NMR (100 MHz, CDCl3, 25 C) d (ppm): 158.9, 152.4, 147.5,
131.2, 130.6, 129.8, 128.7, 128.4, 127.4, 127.3, 126.6, 126.0, 124.2,
123.8, 114.1, 109.6, 55.2. MS (20 eV, EI) m/z (%): 327 [M+1]+
(100), 312 (11), 221 (9), 105 (11).
+
-1
˜
(20 eV, EI) m/z (%): 364 [M] (100). IR (CH2Cl2) n (cm ): 3063
(w), 1617 (w), 1594 (w), 1495 (m), 1325 (s), 1167 (m), 1123 (m),
1067 (s). HRMS (ESI) for C23H16F3O, [M+H]+ (365.1153) found:
365.1156.
2¢,5¢-Diphenyl-2,3¢-bifuran (1ja). Prepared according to TP
from 2j (99.8 mg, 0.5 mmol), Bu3P (137.0 mL, 1.1 equiv), Et3N
(84.0 mL, 1.2 equiv), and 3a (63.8 mL, 1.1 equiv) in dry THF
(2.5 mL) [reaction conditions: rt for 10 min]. Purification by
flash chromatography (hexanes; Rf: 0.30) yielded 1ja as red solid
(86.4 mg, 60%). mp.: 70.8–72.4 ◦C. 1H-NMR (400 MHz, CDCl3,
25 ◦C) d (ppm): 7.87(d, 2H, J = 7.6 Hz), 7.81 (d, 2H, J = 7.6 Hz),
7.55–7.42 (m, 5H), 7.42–7.30 (m, 2H), 6.99 (s, 1H), 6.58 (d, 1H, J =
3 Hz), 6.54–6.47 (m, 1H). 13C-NMR (100 MHz, CDCl3, 25 ◦C) d
(ppm): 152.8, 148.3, 147.9, 141.5, 130.9, 130.2, 128.7, 128.4, 128.0,
3-(3-Nitrophenyl)-2,5-diphenylfuran (1fa). Prepared according
to TP from 2f (126.6 mg, 0.5 mmol), Bu3P (137.0 mL, 1.1 equiv),
Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL, 1.1 equiv) in dry
THF (2.5 mL) [reaction conditions: rt for 10 min]. Purification
by flash chromatography (hexanes/ethyl acetate: 40/1; Rf: 0.38)
yielded 1fa as yellow solid (143.5◦mg, 84%). mp.: 126.6–126.8 ◦C.
1H-NMR (400 MHz, CDCl3, 25 C) d (ppm): 8.36–8.34 (m, 1H),
8.21–8.15 (m, 1H), 7.81–7.75 (m, 3H), 7.60–7.50 (m, 3H), 7.44 (t,
2H, J = 7.3 Hz), 7.39–7.29 (m, 4H), 6.86 (s, 1H). 13C-NMR (100
127.7, 126.7, 123.9, 114.8, 111.2, 107.1, 107.0. MS (20 eV, EI) m/z
-1
(%): 286 [M]+ (100). IR (CH2Cl2) n (cm ): 3114 (w), 3055 (m),
˜
◦
MHz, CDCl3, 25 C) d (ppm): 153.2, 148.8, 148.5, 136.0, 134.5,
3033 (w), 1606 (m), 1484 (s), 1359 (w), 1148 (s). HRMS (EI) for
C20H14O2, [M]+ (286.0994) found: 286.0987.
130.2, 130.0, 129.5, 128.7, 128.6, 128.2, 127.8, 126.3, 123.8, 123.2,
122.0, 121.9, 108.4. MS (20 eV, EI) m/z (%): 341 [M]+ (100). IR
2,5-Diphenyl-3-(thiophen-2-yl)furan (1ka)13b
. Prepared ac-
-1
˜
(CH2Cl2) n (cm ): 3055 (w), 1528 (s), 1488 (m), 1440 (w), 1351 (s).
cording to TP from 2k (107.0 mg, 0.5 mmol), Bu3P (137.0 mL,
1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL, 1.1 equiv) in
dry THF (2.5 mL) [reaction conditions: rt for 20 min]. Purification
by flash chromatography (hexanes/ethyl acetate: 40/1; Rf: 0.41)
yielded 1ka◦as yellow solid (103.0 mg, 68%). 1H-NMR (400 MHz,
CDCl3, 25 C) d (ppm): 7.78 (t, 4H, J = 7.5 Hz), 7.50–7.28 (m,
7H), 7.19 (d, 1H, J = 3.2 Hz), 7.13–7.06 (m, 1H), 6.86 (s, 1H).
13C-NMR (100 MHz, CDCl3, 25 ◦C) d (ppm): 152.5, 148.5, 135.5,
130.7, 130.2, 128.7, 128.4, 127.9, 127.7, 127.4, 126.4, 126.0, 125.1,
123.8, 117.5, 109.6. MS (20 eV, EI) m/z (%): 302 [M]+ (100).
HRMS (EI) for C22H16NO3, [M+H]+ (342.1130) found: 342.1139.
3-(3-Chlorophenyl)-2,5-diphenylfuran (1ga). Prepared accord-
ing to TP from 2g (121.4 mg, 0.5 mmol), Bu3P (137.0 mL, 1.1 equiv),
Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL, 1.1 equiv) in dry
THF (2.5 mL) [reaction conditions: rt for 10 min]. Purification by
flash chromatography (hexanes; Rf: 0.5) yielded 1ga as yellow oil
(128.8 mg, 78%). H-NMR (400 MHz, CDCl3, 25◦◦C) d (ppm):
1
7.69 (d, 2H, J = 7.4 Hz), 7.55–7.50 (m, 2H), 7.40 (s, 1H), 7.35 (t,
2H, J = 7.7 Hz), 7.30–7.16 (m, 7H), 6.72 (s, 1H). 13C-NMR (100
◦
MHz, CDCl3, 25 C) d (ppm): 152.8, 148.3, 136.2, 134.5, 130.7,
4-(5-(4-Nitrophenyl)-2-phenylfuran-3-yl)benzonitrile
(1la).
130.3, 129.9, 128.8, 128.6, 128.5, 127.8, 127.7, 127.4, 126.9, 126.2,
Prepared according to TP from 2l (139.1 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for
10 min]. Purification by flash chromatography (hexanes/ethyl
acetate: 20/1; Rf: 0.50) yielded 1la as yellow oil (100.9 mg, 55%).
mp.: 210.5–212.5 ◦C. 1H-NMR (400 MHz, CDCl3, 25 ◦C) d
(ppm): 8.29 (d, 2H, J = 8.2 Hz), 7.87 (d, 2H, J = 8.6 Hz), 7.68 (d,
2H, J = 7.8 Hz), 7.56 (d, 4H, J = 7.4◦Hz), 7.38 (s, 3H), 7.05 (s,
1H). 13C-NMR (100 MHz, CDCl3, 25 C) d (ppm): 151.2, 150.9,
146.7, 138.3, 135.6, 132.6, 129.6, 129.1, 129.0, 128.8, 126.8, 124.4,
123.8, 128.1, 109,0. MS (20 eV, EI) m/z (%): 333[(M+2)+1]+ (15),
+
-1
˜
331 [M+1] (100). IR (CH2Cl2) n (cm ): 3055 (w), 1591 (m), 1561
(m), 1488 (s), 1148 (s), 765 (s), 695 (s). HRMS (EI) for C22H15ClO,
[M]+ (330.0811) found: 330.0811.
3-(2-Nitrophenyl)-2,5-diphenylfuran (1ha). Prepared accord-
ing to TP from 2h (126.6 mg, 0.5 mmol), Bu3P (137.0 mL, 1.1 equiv),
Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL, 1.1 equiv) in dry
THF (2.5 mL) [reaction conditions: rt for 60 min]. Purification
by flash chromatography (hexanes/ethyl acetate: 40/1; Rf: 0.24)
2102 | Org. Biomol. Chem., 2011, 9, 2098–2106
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124.0, 123.2, 118.6, 112.1, 111.3. MS (20 eV, EI) m/z (%): 367
(s, 1H), 3.85 (s, 3H). 13C-NMR (100 MHz, CDCl3, 25 ◦C) d (ppm):
159.4, 153.4, 148.3, 139.2, 132.4, 130.4, 130.0, 128.6, 128.0, 126.4,
125.3, 123.0, 122.5, 118.8, 114.2, 110.5, 106.7, 55.3. MS (20 eV,
+
-1
˜
[M+1] (100). IR (CH2Cl2) n (cm ): 3107 (w), 2221 (m), 1598 (s),
1543 (m), 1510 (s), 1443 (m), 1333 (s), 1100 (s). HRMS (EI) for
C23H14N2O3, [M]+ (366.1004) found: 366.0999.
+
-1
˜
EI) m/z (%): 351 [M] (100). IR (CH2Cl2) n (cm ): 3063 (w), 2229
(s), 1609 (s), 1502 (s), 1303 (m), 1252 (s). HRMS (MALDI) for
C24H18NO2, [M+H]+ (352.1337) found: 352.1341.
4-(5-(4-Bromophenyl)-2-phenylfuran-3-yl)benzonitrile
(1ma).
Prepared according to TP from 2m (156.1 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for
10 min]. Purification by flash chromatography (hexanes/ethyl
acetate: 40/1; Rf: 0.25)◦yielded 1ma as white solid (165.8 mg,
4-(5-tert-Butyl-2-phenylfuran-3-yl)benzonitrile
(1qa). Pre-
pared according to TP from 2q (106.5 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for
60 min]. Purification by flash chromatography (hexanes/ethyl
acetate: 40/1; Rf: 0.27) yielded 1qa as white solid (78.1 mg, 52%).
mp.: 152.8–153.7 ◦C. 1H-NMR (400 MHz, CDCl3, 25 ◦C) d
(ppm): 7.58 (d, 2H, J = 8.1 Hz), 7.52–7.42 (m, 4H), 7.36–7.26
(m, 3H), 6.14 (s, 1H), 1.35 (s, 9H). 13C-NMR (100 MHz, CDCl3,
25 ◦C) d (ppm): 164.1, 147.7, 139.8, 132.3, 131.0, 128.9, 128.5,
127.8, 126.4, 120.9, 119.0, 110.2, 105.6, 32.7, 29.0. MS (20 eV,
◦
1
83%). mp.: 145.0–146.5 C. H-NMR (400 MHz, CDCl3, 25 C)
d (ppm): 7.69–7.44 (m, 10H), 7◦.41–7.28 (m, 3H), 6.78 (s, 1H).
13C-NMR (100 MHz, CDCl3, 25 C) d (ppm): 152.1, 149.2, 138.7,
132.4, 131.8, 130.0, 128.9, 128.8, 128.6, 128.4, 126.5, 125.2, 122.6,
121.6, 118.7, 110.8, 108.7. MS (20 eV, EI) m/z (%): 401 [M+2]+
(100), 399[M]+ (72). IR (CH2Cl2) n (cm ): 3055 (w), 2229 (s),
-1
˜
1609 (s), 1488 (s), 1148 (m), 1008 (m), 695 (s). HRMS (EI) for
C23H14BrNO, [M]+ (399.0251) found: 399.0259.
+
-1
˜
EI) m/z (%): 302 [M+1] (100), 286 (73). IR (CH2Cl2) n (cm ):
3055 (w), 2229 (s), 1609 (m), 1558 (m), 1510 (m). HRMS (EI) for
C21H19NO, [M]+ (301.1467) found: 301.1469.
4-(5-(3-Nitrophenyl)-2-phenylfuran-3-yl)benzonitrile
(1na).
Prepared according to TP from 2n (139.1 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL,
1.1 equiv) in dry CH2Cl2 (4.0 mL) [reaction conditions: rt for
10 min]. Purification by flash chromatography (hexanes/ethyl
acetate: 10/1; Rf: 0.27)◦yielded 1na as yellow solid (124.4 mg,
4-(5-Cyclohexyl-2-phenylfuran-3-yl)benzonitrile
(1ra). Pre-
pared according to TP from 2r (83.1 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for
60 min]. Purification by flash chromatography (hexanes/ethyl
acetate: 40/1; Rf: 0.38) yielded 1ra as white solid (83.1 mg, 51%).
mp.: 161.3–162.1 ◦C. 1H-NMR (400 MHz, CDCl3, 25 ◦C) d
(ppm): 7.54 (d, 2H, J = 8.2 Hz), 7.48–7.37 (m, 4H), 7.29–7.18 (m,
3H), 6.09 (s, 1H), 2.70–2.60 (m, 1H), 2.10–2.01 (m, 2H), 1.83–1.64
(m, 3H), 1.44–1.16 (m, 5H). 13C-NMR (100 MHz, CDCl3, 25 ◦C)
d (ppm): 160.9, 147.6, 139.8, 132.3, 130.9, 128.9, 128.5, 127.8,
◦
1
68%). mp.: 185.5–187.3 C. H-NMR (400 MHz, CDCl3, 25 C)
d (ppm): 8.53 (s, 1H), 8.12 (dd, 2H, J = 8.1, 1.7 Hz), 7.66 (d,
2H, J = 8.2 Hz), 7.63–7.51 (m, 5H), 7.41–7.32 (m, 3H), 6.98 (s,
1H). 13C-NMR (100 MHz, CDCl3, 25 ◦C) d (ppm): 150.7, 150.3,
148.7, 138.4, 132.5, 131.5, 129.8, 129.7, 129.1, 129.0, 128.8, 128.7,
126.7, 122.8, 122.1, 118.6, 118.4, 111.1, 110.4. MS (20 eV, EI) m/z
+
-1
˜
(%): 367 [M+1] (100). IR (CH2Cl2) n (cm ): 3048 (s), 2303 (m),
2229 (s), 1558 (m), 1532 (m). HRMS (ESI) for C23H14N2NaO,
[M+Na]+ (389.0902) found: 389.0910.
126.4, 120.9, 118.9, 110.2, 106.4, 37.2, 31.4, 26.0, 25.8. MS (20 eV,
-1
EI) m/z (%): 327 [M]+ (100), 285 (21). IR (CH2Cl2) n (cm ):
˜
3055 (m), 2221 (s), 1602 (s), 1558 (s), 1448 (s), 1255 (m). HRMS
(MALDI) for C23H22NO, [M+H]+ (328.1711) found: 328.1701.
4-(5-(2-Bromophenyl)-2-phenylfuran-3-yl)benzonitrile
(1oa).
Prepared according to TP from 2o (156.1 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for 10 min].
Purification by flash chromatography (hexanes/ethyl acetate:
40/1; Rf: 0.39) yielded 1oa as lemon yellow solid (133.9 mg, 67%).
mp.: 124.5–126.1 ◦C. 1H-NMR (400 MHz, CDCl3, 25 ◦C) d
(ppm): 7.95–7.86 (m, 1H), 7.73–7.50 (m, 7H), 7.45–7.29 (m, 5H),
7.22–7.11 (m, 1H). 13C-NMR (100 MHz, CDCl3, 25 ◦C) d (ppm):
150.6, 149.2, 138.9, 134.3, 132.4, 130.4, 130.1, 129.1, 128.8, 128.7,
128.6, 128.5, 127.5, 126.7, 122.3, 119.6, 118.8, 113.7, 110.8. MS
Ethyl-2¢-phenyl-2,3¢-bifuran-5¢-carboxylate
(1sa). Prepared
according to TP from 2s (179.0 mg, 0.5 mmol), Bu3P (137.0 mL,
1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL, 1.1 equiv) in
dry THF (2.5 mL) [reaction conditions: rt for 0.5 h]. Purification
by flash chromatography (hexanes/ethyl acetate: 40/1; Rf: 0.30)
yielded 1sa◦as colorless oil (132.0 mg, 55%). 1H-NMR (400 MHz,
CDCl3, 25 C) d (ppm): 7.78 (d, 2H, J = 6.5 Hz), 7.44–7.40 (m,
5H), 6.50–6.49 (m, 1H), 6.45–6.44 (m, 1H), 4.40 (quartet, 2H, J =
7.0 Hz), 1.40 (t, 3H, J = 7.0 Hz). 13C-NMR (100 MHz, CDCl3,
25 ◦C) d (ppm): 158.7, 152.2, 146.6, 143.4, 142.0, 129.8, 129.3,
128.4, 127.5, 119.1, 114.7, 111.3, 107.7, 61.1, 14.4. MS (20 eV, EI)
(20 eV, EI) m/z (%): 402 [(M+2)+1] + (59), 400 [M+1]+ (100). IR
-1
˜
(CH2Cl2) n (cm ): 3063 (m), 2229 (s), 1613 (s), 1469 (s), 1156
(m), 1023 (s), 694 (s). HRMS (ESI) for C23H15BrNO, [M+H]+
(400.0337) found: 400.0341.
m/z (%): 282 [M] (100), 254 (39), 181 (10). IR (CH2Cl2) n (cm ):
2988 (w), 1723 (s), 1476 (s), 1321 (s), 1177 (m). HRMS (MALDI)
for C17H15O4, [M+H]+ (283.0970) found: 283.0979.
+
-1
˜
4-(5-(4-Methoxyphenyl)-2-phenylfuran-3-yl)benzonitrile (1pa).
Prepared according to TP from 2p (131.7 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for
10 min]. Purification by flash chromatography (hexanes/ethyl
acetate:20/1; Rf:0.30) yielded 1pa as lemon yellow solid (121.2mg,
69%). mp.: 121.5–123.5 ◦C. 1H-NMR (400 MHz, CDCl3, 25 ◦C) d
(ppm): 7.68 (d, 2H, J = 8.6 Hz), 7.63 (d, 2H, J = 8.1 Hz), 7.54 (d,
4H, J = 8.3 Hz), 7.39–7.27 (m, 3H), 6.96 (d, 2H, J = 8.6 Hz), 6.67
4-(2-(4-Nitrophenyl)-5-phenylfuran-3-yl)benzonitrile
(1cb).
Prepared according to TP from 2c (116.6 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3b (74.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for
10 min]. Purification by flash chromatography (hexanes/ethyl
acetate: 10/1; Rf: 0.32) yielded 1cb as yellow solid (119.6 mg,
65%). mp.: 197.2-199.2 ◦C. 1H-NMR (400 MHz, CDCl3, 25 ◦C) d
(ppm): 8.16 (d, 2H, J = 7.9 Hz), 7.88–7.30 (m, 11H), 6.84 (s, 1H).
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13C-NMR (100 MHz, CDCl3, 25 ◦C) d (ppm): 155.0, 146.6, 146.1,
4-(2-(3-Chlorophenyl)-5-phenylfuran-3-yl)benzonitrile
(1cf).
Prepared according to TP from 2c (116.6 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3f (72.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for 10 min].
Purification by flash chromatography (hexanes/ethyl acetate:
40/1; Rf: 0.28) yielded 1cf as lemon yellow solid (118.4 mg, 67%).
mp.: 105.5–107.5 ◦C. 1H-NMR (400 MHz, CDCl3, 25 ◦C) d
(ppm): 7.73 (d, 2H, J = 7.4 Hz), 7.65 (d, 2H, J = 8.3 Hz), 7.58–7.56
(m, 1H), 7.52 (d, 2H, J = 8.3 Hz), 7.42 (t, 2H, J = 7.8 Hz),
7.36–7.29 (m, 2H), 7.28–7.19 (m, 2H), 6.78 (s, 1H). 13C-NMR
(100 MHz, CDCl3, 25 ◦C) d (ppm): 153.8, 147.2, 138.6, 134.7,
132.5, 132.0, 129.8, 129.7, 129.1, 128.8, 128.2, 128.1, 126.2, 124.3,
123.9, 123.6, 118.7, 111.1, 108.5. MS (20 eV, EI) m/z (%): 357
138.3, 136.1, 132.8, 129.3, 129.3, 129.0, 128.7, 126.4, 126.1, 124.1,
124.2, 118.4, 111.9, 109.4. MS (20 eV, EI) m/z (%): 367 [M+1]+
-1
˜
(100). IR (CH2Cl2) n (cm ): 3113 (w), 3061 (w), 2227 (s), 1598
(s), 1544 (m), 1515 (s), 1338 (s), 1110 (m). HRMS (MALDI) for
C23H15N2O3, [M+H]+ (367.1077) found: 367.1093.
4-(2-(4-Chlorophenyl)-5-phenylfuran-3-yl)benzonitrile
(1cc).
Prepared according to TP from 2c (116.6 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3c (70.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for
10 min]. Purification by flash chromatography (hexanes/ethyl
acetate: 20/1; Rf: 0.32)◦ yielded 1cc as white solid (137.3 mg,
◦
1
77%). mp.: 138.1–139.0 C. H-NMR (400 MHz, CDCl3, 25 C)
d (ppm): 7.74 (d, 2H, J = 7.4 Hz), 7.65 (d, 2H, J = 8.3 Hz),
7.52–7.40 (m, 6H), 7.37–7.28 (m, 3H), 6.79 (s, 1H). 13C-NMR
(100 MHz, CDCl3, 25 ◦C) d (ppm): 153.5, 147.7, 138.7, 134.0,
132.5, 129.7, 129.0, 128.9, 128.8, 128.7, 128.1, 127.6, 123.8, 123.1,
118.7, 111.0, 108.4. MS (20 eV, EI) m/z (%): 357 [M+2]+ (74),
+
+
-1
˜
[M+2] (34), 356 [M+1] (100). IR (CH2Cl2) n (cm ): 3120 (w),
3064 (m), 2227 (s), 1608 (s), 1592 (s), 1254 (m), 1149 (s), 762 (s).
HRMS (MALDI) for C23H14ClNO, [M+H]+ (356.0842) found:
356.0851.
4-(2-(2-Chlorophenyl)-5-phenylfuran-3-yl)benzonitrile
(1ch).
+
-1
˜
355 [M] (100). IR (CH2Cl2) n (cm ): 3063 (w), 2229 (s), 1609 (s),
1491 (s), 1266 (m), 1097 (m), 957 (m), 821 (s), 761 (m), 691 (m).
HRMS (MALDI) for C23H15ClNO, [M+H]+ (356.0842) found:
356.0851.
Prepared according to TP from 2c (116.6 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3h (70.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for
10 min]. Purification by flash chromatography (hexanes/ethyl
acetate: 40/1; Rf: 0.25)◦ yielded 1ch as white solid (118.1 mg,
4-(2-(4-Methoxyphenyl)-5-phenylfuran-3-yl)benzonitrile (1cd).
Prepared according to TP from 2c (116.6 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3d (78.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for
10 min]. Purification by flash chromatography (hexanes/ethyl
acetate: 20/1; Rf: 0.32) yielded 1cd as yellow solid (139.4 mg,
80%). mp.: 145.0–147.0 ◦C. 1H-NMR (400 MHz, CDCl3, 25 ◦C) d
(ppm): 7.74 (d, 2H, J = 7.6 Hz), 7.63 (d, 2H, J = 8.2 Hz), 7.54 (d,
2H, J = 8.2 Hz), 7.49 (d, 2H, J = 8.7 Hz), 7.43 (t, 2H, J = 7.5 Hz),
7.35–7.27 (m, 1H), 6.90 (d, 2H, J = 8.7 Hz), 6.80 (s, 1H), 3.84 (s,
3H). 13C-NMR (100 MHz, CDCl3, 25 ◦C) d (ppm): 159.7, 152.8,
149.2, 139.2, 132.3, 130.1, 128.8, 128.7, 128.1, 127.7, 123.7, 123.0,
121.2, 118.9, 114.1, 110.4, 108.0, 55.2. MS (20 eV, EI) m/z (%): 352
◦
1
72%). mp.: 118.8–119.4 C. H-NMR (400 MHz, CDCl3, 25 C)
d (ppm): 7.77 (d, 2H, J = 7.8 Hz), 7.56 (d, 2H, J = 8.2 Hz),
7.53–7.29 (m, 9H), 6.98 (s, 1H). 13C-NMR (100 MHz, CDCl3,
25 ◦C) d (ppm): 154.3, 147.0, 138.2, 133.9, 132.3, 132.1, 130.6,
130.4, 129.9, 129.8, 128.7, 128.0, 127.6, 126.9, 124.5, 123.9, 118.8,
110.3, 106.0. MS (20 eV, EI) m/z (%): 357 [M+2]+ (34), 356
+
-1
˜
[M+1] (100). IR (CH2Cl2) n (cm ): 3117 (w), 3064 (m), 2227 (s),
1610 (s), 1557 (m), 1384 (m), 1182 (s), 1151 (s), 762 (s). HRMS
(MALDI) for C23H15ClNO, [M+H]+ (356.0842) found: 356.0854.
4-(2-(2-Bromophenyl)-5-phenylfuran-3-yl)benzonitrile
(1ci).
Prepared according to TP from 2c (116.6 mg 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3i (74.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for
10 min]. Purification by flash chromatography (hexanes/ethyl
acetate: 40/1; Rf: 0.25) yielded 1ci as white solid (122.0 mg, 67%).
mp.: 122.2–123.2 ◦C. 1H-NMR (400 MHz, CDCl3, 25 ◦C) d
(ppm): 7.80–7.75 (m, 2H), 7.74–7.69 (m, 1H), 7.59–7.53 (m, 2H),
7.47–7.29 (m, 8H), 6.98 (s, 1H). 13C-NMR (100 MHz, CDCl3,
25 ◦C) d (ppm): 154.3, 148.6, 138.1, 133.8, 132.5, 132.4, 132.1,
131.0, 130.0, 128.9, 128.2, 127.8, 127.6, 124.2, 124.1, 124.0, 118.9,
110.4, 105.9. MS (20 eV, EI) m/z (%): 401 [M+2]+ (93), 400
+
-1
˜
[M+1] (100), 336 (10). IR (CH2Cl2) n (cm ): 3113 (w), 3061 (m),
3002 (m), 2962 (m), 2939 (m), 2906 (m), 2227 (s), 1608 (s), 1570
(m), 1516 (s), 1492 (s), 1385 (m), 1301 (m), 1254 (s), 1177 (s), 1028
(s). HRMS (MALDI) for C24H17NO2, [M+H]+ (352.1337) found:
352.1345.
4-(5-Phenyl-2-p-tolylfuran-3-yl)benzonitrile (1ce). Prepared
according to TP from 2c (116.6 mg, 0.5 mmol), Bu3P (137.0 mL,
1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3e (74.0 m L, 1.1 equiv)
in dry THF (2.5 mL) [reaction conditions: rt for 10 min].
Purification by flash chromatography (hexanes/ethyl acetate:
40/1 Rf: 0.42) yielded 1ce as lemon yellow solid (145.5 mg, 87%).
mp.: 169.5–170.9 ◦C. 1H-NMR (400 MHz, CDCl3, 25 ◦C) d
(ppm): 7.76 (d, 2H, J = 7.6 Hz), 7.63 (d, 2H, J = 8.1 Hz), 7.55
(d, 2H, J = 8.2 Hz), 7.50–7.39 (m, 4H), 7.36–7.29 (m, 1H), 7.18
(d, 2H, J = 7.9 Hz), 6.81 (s, 1H), 2.41 (s, 3H). 13C-NMR (100
+
-1
˜
[M+1] (100). IR (CH2Cl2) n (cm ): 3120 (w), 3064 (m), 2227 (s),
1607 (s), 1487 (s), 1462 (m), 1267 (m), 1241 (m), 1147 (s), 1028 (s),
689 (s). HRMS (MALDI) for C23H15BrNO, [M+H]+ (400.0337)
found: 400.0348.
4-(5-Phenyl-2,2¢-bifuran-3-yl)benzonitrile (1cj)9. Prepared ac-
cording to TP from 2c (116.6 mg, 0.5 mmol), Bu3P (137.0 mL,
1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3j (55.0 mL, 1.1 equiv) in
dry THF (2.5 mL) [reaction conditions: rt for 60 min]. Purification
by flash chromatography (hexanes/ethyl acetate: 40/1; Rf: 0.28)
◦
MHz, CDCl3, 25 C) d (ppm): 153.1, 149.4, 139.3, 138.5, 132.5,
130.2, 129.5, 129.1, 128.9, 127.9, 127.6, 126.7, 123.9, 122.1, 119.0,
110.6, 108.2, 21.3. MS (20 eV, EI) m/z (%): 336 [M+1]+ (100).
-1
1
˜
IR (CH2Cl2) n (cm ): 3061 (w), 3031 (w), 2923 (w), 2867 (w),
yielded 1cj◦as red solid (79.0 mg, 62%). H-NMR (400 MHz,
2227 (s), 1608 (s), 1516 (m), 1493 (s), 1384 (w), 1148 (m), 1051
(m). HRMS (MALDI) for C24H18NO, [M+H]+ (336.1388) found:
336.1395.
CDCl3, 25 C) d (ppm): 7.74 (d, 2H, J = 7.5 Hz), 7.70–7.63 (m,
4H), 7.48–7.38 (m, 3H), 7.41 (t, 1H, J = 7.4 Hz), 6.81 (s, 1H),
6.69 (d, 1H, J = 3.4 Hz), 6.53–6.47 (m, 1H). 13C-NMR (100 MHz,
2104 | Org. Biomol. Chem., 2011, 9, 2098–2106
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◦
CDCl3, 25 C) d (ppm): 153.4, 145.6, 142.4, 141.1, 137.9, 132.0,
129.2, 128.7, 128.3, 128.0, 127.9, 123.9, 115.7, 107.9, 60.5, 14.2.
129.7, 129.1, 128.8, 128.1, 123.9, 122.7, 118.9, 111.5, 110.7, 108.3,
107.7. MS (20 eV, EI) m/z (%): 312 [M+1]+ (100).
MS (20 eV, EI) m/z (%): 292 [M]+ (100).
Ethyl-2-(4-chlorophenyl)-5-phenylfuran-3-carboxylate (1tc)13c
.
4-(5-Phenyl-2-(thiophen-2-yl)furan-3-yl)benzonitrile
(1ck).
Prepared according to TP from 2t (92.0 mL, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3c (70.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for
10 min]. Purification by flash-chromatography (hexanes/ethyl
acetate: 20/1; Rf: 0.54) yielded 1tc as white solid (98.0 mg, 60%).
1H-NMR (400 MHz, CDCl3, 25 ◦C) d (ppm): 8.06 (d, 2H, J =
8.6 Hz), 7.73 (d, 2H, J = 7.6 Hz), 7.50–7.37 (m, 4H), 7.36–7.28
(m, 1H), 7.08 (s, 1H), 4.34 (quartet, 2H, J = 7.1 Hz), 1.38 (t, 3H,
J = 7.1 Hz). 13C-NMR (100 MHz, CDCl3, 25 ◦C) d (ppm): 163.4,
155.1, 152.5, 135.2, 129.5, 128.8, 128.4, 128.2, 124.0, 116.2, 108.0,
67.7, 14.2. MS (20 eV, EI) m/z (%): 328 [M+2]+ (28), 326 (100).
Prepared according to TP from 2c (116.6 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3k (62.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for
10 min]. Purification by flash chromatography (hexanes/ethyl
acetate: 40/1; Rf: 0.32)◦ yielded 1ck as green solid (117.9 mg,
◦
1
72%). mp.: 115.1–115.5 C. H-NMR (400 MHz, CDCl3, 25 C)
d (ppm): 7.74–7.64 (m, 6H), 7.43 (t, 2H, J = 7.4 Hz), 7.37–7.27
(m, 2H), 7.25–7.19 (m, 1H), 7.◦06–6.98 (m, 1H), 6.78 (s, 1H).
13C-NMR (100 MHz, CDCl3, 25 C) d (ppm): 153.1, 144.4, 138.4,
132.4, 132.2, 129.7, 129.2, 128.8, 128.0, 127.5, 125.7, 125.0, 123.8,
122.4, 118.8, 111.0, 108.1. MS (20 eV, EI) m/z (%): 327 [M]+
(2,5-Diphenylfuran-3-yl)(phenyl)methanone (1ua)13d
.
Prepared
-1
˜
(100). IR (CH2Cl2) n (cm ): 3110 (w), 3071 (w), 2227 (s), 1608
according to TP from 2u (118.1 mg, 0.5 mmol), Bu3P (137.0 mL,
1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 1a (64.0 mL, 1.1 equiv)
in dry THF (2.5 mL) [reaction conditions: rt for 40 h]. Purification
by flash chromatography (hexanes/ethyl acetate: 40/1; Rf: 0.33)
yielded 1ua◦as yellow liquid (94.6 mg, 58%). 1H-NMR (400 MHz,
CDCl3, 25 C) d (ppm): 7.92 (d, 2H, J = 7.5 Hz), 7.86–7.74 (m,
4H), 7.59–7.28 (m, 9H), 6.95 (s, 1H). 13C-NMR (100 MHz, CDCl3,
25 ◦C) d (ppm): 191.6, 154.8, 152.4, 137.9, 132.8, 129.7, 128.9,
128.8, 128.3, 128.2, 128.1, 127.3, 124.0, 122.7, 108.6. MS (20 eV,
EI) m/z (%): 324 [M]+ (100), 247 (78), 105 (71).
(s), 1556 (w), 1525 (w), 1495 (m), 1248 (w), 1146 (m). HRMS
(MALDI) for C21H14NOS, [M+H]+ (328.0796) found: 328.0801.
4-(2-Methyl-5-phenylfuran-3-yl)benzonitrile (1cl). Prepared
according to TP from 2c (126.6 mg, 0.5 mmol), Bu3P (187.0 mL,
1.5 equiv), Et3N (84.0 mL, 1.2 equiv), and 3l (40.0 mL, 1.1 equiv) in
dry THF (2.5 mL) [reaction conditions: rt for 30 h]. Purification
by flash chromatography (hexanes/ethyl acetate: 40/1; Rf: 0.25)
yielded 1cl as white solid (28.0 mg, 24%). mp.: 134.9–136.0 ◦C.
1H-NMR (400 MHz, CDCl3, 25 ◦C) d (ppm): 7.72–7.63 (m, 4H),
7.52 (d, 2H, J = 8.2 Hz), 7.39 (t, 2H, J = 7.6 Hz), 7.30–7.23 (m,
1H), 6.77 (s, 1H), 2.53 (s, 3H). 13C-NMR (100 MHz, CDCl3,
25 ◦C) d (ppm): 152.4, 148.9, 138.9, 132.4, 130.3, 128.7, 127.7,
127.5, 123.5, 121.7, 119.0, 109.8, 105.5, 13.5. MS (20 eV, EI) m/z
(E)-4-(3-(4-Nitrophenyl)-3-oxoprop-1-enyl)benzonitrile (2l)13e
.
The compound 2l was yielded as orange solid (1.15 g, 35%)
1
according to the procedure of the reported literature. H-NMR
(400 MHz, CDCl3, 25 ◦C) d (ppm): 8.37 (d, 2H, J = 8.8 Hz),
8.16 (d, 2H, J = 8.8 Hz), 7.83 (d, 1H, J = 15.7 Hz), 7.75 (s, 4◦H),
7.40 (d, 1H, J = 15.7 Hz). 13C-NMR (100 MHz, CDCl3, 25 C)
d (ppm): 188.3, 150.3, 143.9, 142.3, 138.5, 132.8, 129.5, 128.9,
+
-1
˜
(%): 260 [M+1] (19), 259 [M] (100). IR (CH2Cl2) n (cm ): 3062
(w), 1598 (m), 1517 (s), 1344 (s). HRMS (EI) for C18H13NO, [M]+
(259.0997) found: 259.0993.
4-(2-Isopropyl-5-phenylfuran-3-yl)benzonitrile
(1cm). Pre-
124.2, 124.0, 118.2, 114.1. MS (20 eV, EI) m/z (%): 277 [M-1]+
pared according to TP from 2c (116.6 mg, 0.5 mmol), Bu3P
(137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3m (60.0 mL,
1.1 equiv) in dry THF (2.5 mL) [reaction conditions: rt for
60 min]. Purification by flash chromatography (hexanes/ethyl
acetate: 40/1; Rf: 0.29) yielded 1cm as white solid (75.0 mg, 52%).
mp.: 112.1–122.9 ◦C. 1H-NMR (400 MHz, CDCl3, 25 ◦C) d
(ppm): 7.67 (d, 4H, J = 7.9 Hz), 7.48 (d, 2H, J = 8.1 Hz), 7.39 (t,
2H, 7.6 Hz), 7.26 (t, 1H, J = 7.4 Hz), 6.71 (s, 1H), 3.24 (septet,
1H, J = 6.8◦Hz), 1.37 (d, 6H, J = 6.8 Hz). 13C–NMR (100 MHz,
CDCl3, 25 C) d (ppm): 157.0, 152.0, 139.1, 132.4, 130.4, 128.7,
128.3, 127.4, 123.5, 120.1, 119.0, 110.0, 105.7, 26.8, 21.6. MS
-1
˜
(100), 260 (7), 231 (15), 156 (7). IR (CH2Cl2) n (cm ): 3047 (w),
2221 (s), 1731(w), 1672 (s), 1609 (s), 1524 (s), 1333 (s). HRMS
(EI) for C16H10N2O3, [M]+ (278.0691) found: 278.0695.
(E)-4-(3-(3-Nitrophenyl)-3-oxoprop-1-enyl)benzonitrile (2n)13e
.
The compound 2n was yielded as brown solid (0.79 g, 56%)
1
according to the procedure of the reported literature. H-NMR
(400 MHz, CDCl3, 25 ◦C) d (ppm): 8.84 (s, 1H), 8.51–8.44 (m,
1H), 8.37 (d, 1H, J = 7.8 Hz), 7.87 (d, 1H, J = 15.7 Hz), 7.80–7.70
(m, 5H), 7.61 (d, 1H, J = 15.6 Hz). 13C-NMR (100 MHz, CDCl3,
25 ◦C) d (ppm): 187.4, 148.5, 143.9, 138.9, 138.5, 134.1, 132.8,
130.1, 129.0, 127.5, 123.6, 123.3, 118.2, 114.2. MS (20 eV, EI) m/z
(20 eV, EI) m/z (%): 287 [M]+ (100), 272 (77). IR (CH2Cl2) n
˜
+
-1
(cm-1): 3055 (w), 2229 (s), 1609 (s), 1488 (s), 1075 (m), 761 (m).
HRMS (EI) for C20H17NO, [M]+ (287.1310) found: 287.1307.
˜
(%): 277 [M-1] (100). IR (CH2Cl2) n (cm ): 3092 (w), 3041 (w),
2229 (s), 1668 (s), 1609 (s), 1528 (s), 1432 (m), 1347 (s), 1336 (s).
HRMS (MALDI) for C16H11N2O3, [M+H]+ (279.07769) found:
279.0775.
Ethyl-2,5-diphenylfuran-3-carboxylate (1ta)13c
. Prepared ac-
cording to TP from 2t (92.0 mL, 0.5 mmol), Bu3P (137.0 mL,
1.1 equiv), Et3N (84.0 mL, 1.2 equiv), and 3a (64.0 mL, 1.1 equiv) in
dry THF (2.5 mL) [reaction conditions: rt for 10 min]. Purification
by flash chromatography (hexanes/ethyl acetate: 50/1; Rf: 0.38)
yielded 1ta as white solid (101.3 mg, 70%). 1H-NMR (400 MHz,
CDCl3, 25 ◦C) d (ppm): 8.12 (d, 2H, J = 7.2 Hz), 7.76 (d, 2H,
J = 7.5 Hz), 7.53–7.40 (m, 5H), 7.37–7.30 (m, 1H), 7.11(s, 1H),
4.36 (quartet, 2H, J = 7.1 Hz), 1.39 (t, 3H, J = 7.1 Hz). 13C-NMR
(100 MHz, CDCl3, 25 ◦C) d (ppm): 163.4, 156.4, 152.3, 129.7,
(E)-4-(3-(2-Bromophenyl)-3-oxoprop-1-enyl)benzonitrile (2o)13e
.
The compound 2o was yielded as yellow solid (2.08 g, 67%)
according to the procedure of the reported literature. mp.: 130.2–
131.1 ◦C. 1H-NMR (400 MHz, CDCl3, 25 ◦C) d (ppm): 7.70–7.60
(m, 5H), 7.47–7.31 (m, 4H), 7.17 (d, 1H, J = 16.1 Hz). 13C-NMR
(100 MHz, CDCl3, 25 ◦C) d (ppm): 193.6, 143.0, 140.5, 138.6,
133.4, 132.6, 131.8, 129.3, 128.7, 127.4, 119.4, 118.2, 113.6. MS
(20 eV, EI) m/z (%): 313 [M+2]+ (92), 311 [M]+ (100), 232(51), 156
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-1
˜
(30). IR (CH2Cl2) n (cm ): 3063 (w), 2221 (s), 1668 (s), 1602 (s),
1333 (s), 665 (m), 629 (m). HRMS (MALDI) for C16H11BrNO,
[M+H]+ (312.0024) found: 312.0032.
Pergamon: Oxford, 2008; Vol. 19, pp 176; (b) B. A. Keay, P. W. Dibble,
Comprehensive Heterocyclic Chemistry II A. R. Katritzky, C. W. Rees,
E. F. V. Scriven, ed.; Elsevier: Oxford, 1997; Vol. 2, pp 395; (c) X. L.
Hou, H. Y. Cheung, T. Y. Hon, P. L. Kwan, T. H. Lo, S. Y. T. Tong and
H. N. C. Wong, Tetrahedron, 1998, 54, 1955; (d) B. A. Keay, Chem. Soc.
Rev., 1999, 28, 209; (e) T. L. Gilchrist, J. Chem. Soc., Perkin Trans. 1,
1999, 2849.
2 (a) B. H. Lipshutz, Chem. Rev., 1986, 86, 795; (b) H. N. C. Wong, P. Yu
and C.-Y. Yick, Pure Appl. Chem., 1999, 71, 1041; (c) H.-K. Lee, K.-F.
Chan, C.-W. Hui, H.-K. Yim, X.-W. Wu and H. N. C. Wong, Pure Appl.
Chem., 2005, 77, 139; (d) H. Heaney, Natural Products Chemistry K.
Nakanishi, Ed.; Kodansha: Tokyo, 1974, pp 297.
(E)-4-(3-(4-Methoxyphenyl)-3-oxoprop-1-enyl)benzonitrile (2p)13e
The compound 2p was yielded as lemon yellow solid (1.96 g, 75%)
according to the procedure of the reported literature. H-NMR
.
1
(400 MHz, CDCl3, 25 ◦C) d (ppm): 8.06–8.01 (m, 2H), 7.78–7.67
(m, 5H), 7.61 (d, 1H, J = 15.6 Hz), 7.02–6.97 (m, 2H), 3.90 (s, 3H).
13C-NMR (100 MHz, CDCl3, 25 ◦C) d (ppm): 187.8, 163.8, 141.2,
139.4, 132.6, 130.9, 130.5, 128.6, 125.0, 118.4, 114.0, 113.2, 55.5.
MS (20 eV, EI) m/z (%): 263 [M]+ (100), 135 (49), 108 (7).
3 For recent reviews, see: (a) S. F. Kirsch, Org. Biomol. Chem., 2006, 4,
2076; (b) R. C. D. Brown, Angew. Chem., Int. Ed., 2005, 44, 850; (c) S.
Cacchi, J. Organomet. Chem., 1999, 576, 42.
4 For recent examples, see: (a) L. Melzig, C. B. Rauhut and P. Knochel,
Chem. Commun., 2009, 3536; (b) K. Sne´garoff, J.-M. L’Helgoual’ch,
G. Bentabed-Ababsa, T. T. Nguyen, F. Chevallier, M. Yonehara, M.
Uchiyama, A. Derdour and F. Mongin, Chem.–Eur. J., 2009, 15, 10280;
for selected reviews, see: (c) H. Ila, O. Baron, A. J. Wagner and P.
Knochel, Chem. Commun., 2006, 583; (d) Handbook of functionalized
organometallics, P. Knochel, Ed.; Wiley-VCH: Weinheim, 2005.
5 G. Minetto, L. F. Raveglia, A. Sega and M. Taddei, Eur. J. Org. Chem.,
2005, 5277 and references cited therein.
6 For selected examples, see: (a) G. Mross, E. Holtz and P. Langer, J.
Org. Chem., 2006, 71, 8045; (b) F. Feist, Ber. Dtsch. Chem. Ges., 1902,
35, 1537; (c) E. Be´nary, Ber. Dtsch. Chem. Ges., 1911, 44, 489.
7 For selected examples starting from allenyl ketones, see: (a) A. S.
Dudnik and V. Gevorgyan, Angew. Chem., Int. Ed., 2007, 46, 5195;
(b) A. S. K. Hashmi, Angew. Chem., Int. Ed. Engl., 1995, 34, 1581; for
examples from alkynyl ketone, see: (c) A. S. K. Hashmi, L. Schwarz, J.-
H. Choi and T. M. Frost, Angew. Chem., Int. Ed., 2000, 39, 2285; (d) J.
A. Marshall and G. S. Bartley, J. Org. Chem., 1994, 59, 7169; (e) S.
Ma, J. Zhang and L. Lu, Chem.–Eur. J., 2003, 9, 2447; (f) for examples
from alkynyl epoxide, see: A. S. K. Hashmi and P. Sinha, Adv. Synth.
Catal., 2004, 346, 432; (g) for electrophilic cyclization, see: A. Sniady,
K. A. Wheeler and R. Dembinski, Org. Lett., 2005, 7, 1769; (h) for
examples from alkynyl alcohols, see: Y. Liu, F. Song, Z. Song, M. Liu
and B. Yan, Org. Lett., 2005, 7, 5409; (i) for examples from alkynyl
cyclopropyl ketones, see: J. Zhang and H.-G. Schmalz, Angew. Chem.,
Int. Ed., 2006, 45, 6704; for examples from other substrates, see: (j) L.
Peng, X. Zhang, M. Ma and J. Wang, Angew. Chem., Int. Ed., 2007,
46, 1905; (k) M. Zhang, H.-F. Jiang, H. Neumann, M. Beller and P. H.
Dixneuf, Angew. Chem., Int. Ed., 2009, 48, 1681.
8 For recent selected examples of other tetrasubstituted furans using 2-
(1-alkynyl)-2-alken-1-ones as substrates catalyzed by transition metal,
see: (a) R. Liu and J. Zhang, Chem.–Eur. J., 2009, 15, 9303; (b) Y. Xiao
and J. Zhang, Adv. Synth. Catal., 2009, 351, 617; (c) Y. Xiao and J.
Zhang, Chem. Commun., 2009, 3594; (d) F. Liu and J. Zhang, Angew.
Chem., Int. Ed., 2009, 48, 5505; (e) J. Gao, X. Xhao, Y. Yu and J.
Zhang, Chem.–Eur. J., 2010, 16, 456; (f) Y. Zhang, Z. Chen, Y. Xiao
and J. Zhang, Chem.–Eur. J., 2009, 15, 5208.
9 For the examples of trisubstituted furans bearing three aryl groups, see:
R. U. Braun and T. J. J. Mu¨ller, Synthesis, 2004, 2391.
10 T.-T. Kao, S. Syu and W. Lin, Org. Lett., 2010, 12, 3066. In this work,
the addition sequence of reactants has no influence on the results of the
formation of furans.
(E)-4-(3-Cyclohexyl-3-oxoprop-1-enyl)benzonitrile (2r)13e
. The
compound 2r was yielded as white solid (0.21 g, 20%) according
to the procedure of the reported literature. mp.: 93.8–94.6 ◦C. 1H-
NMR (400 MHz, CDCl3, 25 ◦C) d (ppm): 7.69–7.61 (m, 4H), 7.55
(d, 1H, J = 16.0 Hz), 6.88 (d, 1H, J = 16.0 Hz), 2.68–2.58 (m, 1H),
1.95–1.78 (m, 4H), 1.75–1.66◦(m, 1H), 1.49–1.17 (m, 5H). 13C-
NMR (100 MHz, CDCl3, 25 C) d (ppm): 202.32, 139.6, 139.1,
132.6, 128.5, 127.5, 118.3, 113.3, 48.8, 28.5, 25.8, 25.6. MS (20 eV,
EI) m/z (%): 240 [M+1]+ (100), 184 (14), 171 (35), 156 (58), 130
-1
˜
(11), 83 (5). IR (CH2Cl2) n (cm ): 3063 (w), 2982 (w), 2944 (w),
2223 (m), 1661 (s), 1613 (s), 1510 (m). HRMS (EI) for C16H18NO,
[M+H]+ (240.1388) found: 240.1398.
((1Z,3E)-1,4-Bis(benzoyloxy)-1,4-diphenylbuta-1,3-dien-2-yl)-
tributylphosphonium chloride (8). A dry and nitrogen-flushed 10-
mL Schlenk flask, equipped with a magnetic stirring bar and a
septum, was charged with a solution of 3a (128.0 mL, 2.2 equiv),
Bu3P (137.0 mL, 1.1 equiv), Et3N (84.0 mL, 1.2 equiv) and
2u (118.1 mg, 0.5 mmol) in dry THF (2.5 mL). The reaction
mixture was stirred for 10 min at rt. Thereafter, the solvent
was removed by evaporation in vacuo. Purification by simply
washing with pentane and ethyl acetate, then recrystallization
(dichloromethane/hexanes) furnishes the adduct 8 and NEt3·HCl.
1H-NMR (500 MHz, CDCl3, 25 ◦C) d (ppm): 7.81 (d, 2H, J =
7.9 Hz), 7.74 (d, 2H, J = 7.9 Hz), 7.61 (quartet, 2H, J = 7.3 Hz),
7.49–7.34 (m, 9 Hz), 7.30–7.21 (m, 5H), 6.81 (d, 1H, 4.5 Hz), 2.68–
2.54 (m, 6H), 1.32–1.27 (m, 12H), 0.75 (t, 9H, 7.2 Hz). 13C-NMR
(125 MHz, CDCl3, 25 ◦C) d (ppm): 163.4, 162.8, 162.2, 150.9 (d,
J = 8 Hz), 135.2, 134.3, 133.2 (d, J = 7 Hz), 132.9, 131.1, 129.9,
129.7, 129.4, 129.2, 128.6 (d, J = 3 Hz), 128.5, 127.7, 127.5, 126.7,
124.9, 107.9 (d, J = 3 Hz), 103.8 (d, J = 58 Hz), 24.0 (d, J =
3 Hz), 23.9 (d, J = 5 Hz), 21.1 (d, J = 38 Hz), 13.1. 31P-NMR (200
MHz, CDCl3, 25 ◦C) d (ppm): 32.7. MS (20 eV, ESI) m/z (%): 648
[M-34]+ (37), 647 [M-35]+ (100). HRMS (FAB) for C42H48O4P, [M
- Cl]+ (647.3285) found: 647.3290. X-Ray analysis: CCDC 792216.
11 The acidity of benzylic position, which is decided by the substituent
on the aromatic ring (R1), indeed has influence on the formation of the
corresponding phosphorus ylide 4.
12 The formation of the compound 8 was clearly observed without the
formation of 1ua when excess of3a (2.2 equiv) was used according to our
protocol. Notably, it is the first time that the formation of compound
8, in addition to that of 1ua, can confirm the existence of the Wittig
intermediate 9. (CCDC number of the compound 8: 792216).
13 (a) K. R. Gopidas, B. B. Lohray, S. Rajadurai, P. K. Das and M. V.
George, J. Org. Chem., 1987, 52, 2831; (b) B. J. Morrison and O. C.
Musgrave, J. Chem. Soc., Perkin Trans. 1, 2002, 1944; (c) S. Kajikawa,
Y. Noiri, H. Shudo, H. Nishino and K. Kurosawa, Synthesis, 1998,
1457; (d) H. Perrier, C. Bayly, F. Laliberte, Z. Huang, R. Rasori, A.
Robichaud, Y. Girard and D. Macdonald, Bioorg. Med. Chem. Lett.,
1999, 9, 323; (e) S. Sebti, A. Solhy, R. Tahir, S. Boulaajaj, J. A. Mayoral,
J. M. Fraile, A. Kossir and H. Oumimoun, Tetrahedron Lett., 2001, 42,
7953.
Acknowledgements
We thank the National Science Council of the Republic of China
(NSC Grant No. 99-2113-M-003-004-MY2) and National Taiwan
Normal University (99T3030-6) for financial support.
References
1 For recent reviews, see: (a) X. L. Hou, Z. Yang, H. N. C. Wong,
Progress in Heterocyclic ChemistryG. W. Gribble, J. A. Joule, ed.;
2106 | Org. Biomol. Chem., 2011, 9, 2098–2106
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