Palladium-catalyzed alkenylation of fluoro-substituted furans via C-H activation to form tetrasubstituted furans

Article abstract of DOI:10.1016/j.tet.2010.08.064

A palladium-catalyzed oxidative Heck reaction of fluoro-substituted furans with alkenes was developed to afford tetrasubstituted furans in moderate to good yields.

Full text of DOI:10.1016/j.tet.2010.08.064

Tetrahedron 66 (2010) 8387e8391
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Palladium-catalyzed alkenylation of fluoro-substituted furans via CeH activation
to form tetrasubstituted furans
,
,
a,
*
Peng Li a b, Ji-Wei Gu a, Yin Ying c, Yu-Ming He a, Hong-fei Zhang a, Gang Zhao b , Shi-Zheng Zhu
*
a Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
b Key Laboratory of Modern Synthetic Organic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
c School of Chemistry and Environment, Key Lab of Technology on Electrochemical Energy Storage and Power Generation in Guangdong Universities, South China Normal University,
Guangzhou 510006, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 July 2010
Received in revised form 25 August 2010
Accepted 27 August 2010
Available online 20 Septmeber 2010
A palladium-catalyzed oxidative Heck reaction of fluoro-substituted furans with alkenes was developed
to afford tetrasubstituted furans in moderate to good yields.
Crown Copyright Ó 2010 Published by Elsevier Ltd. All rights reserved.
Keywords:
Oxidative Heck reaction
Fluoro-substituted furans
CeH activiation
Alkenylation
1. Introduction
heterocycles. Moreover, in contrast to a very recent report on the
direct vinylation of perfluoroarenes,9 no reports have dealt with the
The CeC bond formation through catalytic direct activation of
normally inert CeH bond is of a privileged way in that such process
precludes the need for a prior functionalization step of the reactant,
making the overall chemical transformation highly efficient and
atom-economic. In this rapidly developing field, the oxidative Heck
reaction via direct CeH activation has gain tremendous interests
during the past decades.1 To date, most strategies deal with elec-
tron-rich arenes,2e5 in which an electrophilic attack of a Pd(II)
complex to the reactant is usually involved as a key step. Probably
due to the difficulty for electron-deficient arenes to undergo this
step and their poor coordination with Pd catalysts, reports using
these substrates are relatively rare.6 In together, these prior works
have demonstrated the power of this methodology in the con-
struction of molecules from simple starting material.
On the other hand, vinylated or arylated furans as well as
thiophenes are of interest for their photo- and electrochemical
properties as well as biological activities.7 Although direct vinyl-
ations of furans and thiophenes via Pd-catalyzed direct CeH acti-
vation have been reported recently,4d,8 such processes are
restricted to the electronically favored 2- and/or 5-positions of the
fluorinated counterparts of these five-membered heterocycles.
Based on our previous study on the direct arylation of 3-fluo-
rofurans,10 we reasoned that the direct vinylation at the C4-position
of furans may be also possible and would allow an atom-econom-
ical access to vinylated tetrasubstituted furans. Herein, we present
the details of this study.
2. Results and discussion
Initially, the reaction between fluoro-substituted furan 1a and
butyl acrylate 2a was chosen as the model reaction for the opti-
mization of reaction conditions (Table 1). Of the several palladium
sources examined, Pd(OAc)2 showed the best reactivity, giving the
product 3a in 65% yield in DMF with Cu(OAc)2 as the oxidant (Table
1, entry 6). In order to improve the yield further, several other
solvents and oxidants were screened but all with inferior results.
t-BuOOBz was first tried but no reaction took place (entry 15), then
some silver salts were tested in this reaction but the yield was not
improved apparently (entries 16e18).2e5 Moreover, some ligands
were added to the system to improve the yield, but they showed
low efficiency (entries 19e20).2e5 Since positive effects of the use of
lithium salts, such as LiOAc and LiCl have been observed in related
previous studies,4d we also tried these two additives and were
pleased to find that the addition of 3 equiv of LiCl enhanced the
* Corresponding authors. Tel.: þ86 21 54925183; fax: þ86 21 64166128; e-mail
address: zhusz@mail.sioc.ac.cn (S.-Z. Zhu).
0040-4020/$ e see front matter Crown Copyright Ó 2010 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.08.064

8388
P. Li et al. / Tetrahedron 66 (2010) 8387e8391
Table 1
Optimization of reaction conditions for the coupling reaction of 1a and butyl acrylate 2aa
Pd Cat. (10 mol %),
O
O
Oxidant (1.5 eq.)
Ph
CF3
Ph
CF3
n
COO Bu
Additive (3 eq.)
Sol, 120 oC
F
F
n
BuOOC
3a
2a
1a
Entry
Pd Cat.
Oxidant
Additive
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
PdCl2þAgOTf
PdCl2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
t-BuOOBz
Ag2CO3
None
None
None
None
None
None
None
None
None
None
None
None
None
None
None
None
None
None
PPh3
DMF
DMF
DMF
DMF
DMF
DMF
CH3CN
AcOH
DME
1,4-Dioxane
DMA
Toluene
DMSO
NMP
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
46
52
54
47
42
65
45
38
35
47
61
46
58
21
NR
18
37
35
52
47
63
73
PdCl2(CH3CN)2
PdCl2(PPh3)2
Pd2(dba)3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
9
10
11
12
13
14
15
16
17
18
19
20
21
22
Ag2O
AgOAc
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Pyridine
LiOAc
LiCl
a
Unless otherwise specified, the reaction was carried on 0.1 mmol scale in 0.8 mL of solvent.
Isolated yield after flash column chromatography.
b
yield of 3a to 73% (entry 22). It is speculated that the addition of
(OAc)2eCu(OAc)2eLiCl system. This protocol provides an easy
access to functionalized tetrasubstituted fluorinated furans.
lithium chloride is to provide the ligand to prevent the deactivation
of Pd(0) to non-reactive metallic species.11
Having established the optimal conditions for the oxidative
Heck reaction of fluoro-substituted furans 1a with butyl acrylate 2a,
we next explored the scope of the substrates and representative
results are listed in Table 2. The examination of different acrylates
revealed that relative bulkier substituents, such as n- or t-butyl
group were more favored than methyl or ethyl groups in this re-
action (Table 2, entries 1e4). For substrates 1bee bearing different
R1 substituents, moderate to good yields were consistently
obtained irrespective of the electronic nature of the substituents on
the arene ring (entries 5e8). Notably, when R2 was an alkyl group,
the reaction still proceeded smoothly to give the desired product in
61% yield (entry 9). Moreover, in addition to acrylic esters, styrenes
also proved suitable reaction partners in this reaction system, and
the desired products were obtained in good yields from their re-
actions with furan 1a (entries 10e12). However, when (E)-ethyl
but-2-enoate with a non-terminal CeC double bond was subjected
to the same reaction conditions, no reaction was detected.
A plausible mechanism for the direct coupling reaction of flu-
oro-substituted furans 1 with acrylate 2 is illustrated in Scheme 1.
The first step may involve electrophilic attack of Pd(OAc)2 to 1 to
form intermediate I.2e5 Next, coordination of the complex I with
alkene 2 followed by syn insertion gives intermediate II, which then
underwent b-hydrogen elimination to give the product 3 and a Pd
(0) species. The latter then would be re-oxidized to Pd(II) by the
oxidant to complete the catalytic cycle.
4. Experimental
4.1. General
1H and 13C NMR spectra were recorded at 300 and 100 MHz,
respectively, with TMS as the internal standard. 19F NMR spectra
were recorded at 282 MHz with CFCl3 as the external standard. IR
spectra were recorded in cmꢀ1. Melting points were uncorrected.
All solvents were distilled prior to use unless otherwise noted. All
reactions sensitive to moisture or oxygen were conducted under an
atmosphere of nitrogen or argon.
Compounds 1aef were prepared according to known
procedures.10
4.1.1. 3-Fluoro-5-phenyl-2-(4-(trifluoromethyl)phenyl)furan
(1a). White solid; IR (CH2Cl2 film): 1695, 1628, 1410, 1331, 1115,
1067, 920, 841, 689 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d
¼7.84e7.82
(m, 2H), 7.71e7.64 (m, 4H), 7.45e7.25 (m, 3H), 6.68 (s, 1H) ppm; 13C
NMR (100 MHz, CDCl3) 151.8 (d, 1J¼245.2 Hz), 151.4 (d, 3J¼8.7 Hz),
134.6 (d, 2J¼20.4 Hz), 132.1 (m), 129.8 (m), 128.9, 128.6, 125.7 (q),
124.3 (q, 1J¼270.5 Hz), 123.9, 123.3, 123.2, 99.3 (d, 2J¼19.7 Hz) ppm;
19F NMR (282.3 MHz, CDCl3):
d
¼ꢀ62.9, ꢀ158.6 ppm; MS (EI) (m/z):
306 (Mþ); Anal. Calcd for C17H10F4O: C, 66.67; H, 3.29. Found: C,
66.62; H, 3.65.
4.2. General procedure for the oxidative Heck reaction of 1
with 2
3. Conclusion
In summary, we have realized direct alkenylation of fluoro-
substituted furans at the C4-position via CeH activation using a Pd
A mixture of compound 1 (0.1 mmol), Pd(OAc)2 (2.25 mg,
0.01 mmol), Cu(OAc)2 (27 mg, 0.15 mmol), and LiCl (12.6 mg,

P. Li et al. / Tetrahedron 66 (2010) 8387e8391
8389
Table 2
The Heck reaction of fluorine-substitute furans 1 with alkenes 2a
O
R2
R1
Pd(OAc)2 (10 mol %)
Cu(OAc)2 (1.5 eq.)
O
R2
R1
R3
F
LiCl (3 eq.)
R3
DMF, 120 oC
F
3
1
2
Entry
1
R1
R2
R3
Product
Yieldb (%)
O
Ph
CF3
4-CF3eC6H4 (1a)
Ph
COOnBu
72
F
n
BuOOC
Ph
3a
O
O
CF3
CF3
CF3
2
3
4
4-CF3eC6H4 (1a)
4-CF3eC6H4 (1a)
4-CF3eC6H4 (1a)
Ph
Ph
Ph
COOMe
COOEt
44
53
65
F
MeOOC
Ph
3b
3c
3d
F
EtOOC
O
Ph
COOtBu
F
t
BuOOC
Cl
O
Ph
Cl
5
2,4-Cl2eC6H3(1b)
Ph
COOnBu
65
F
n
BuOOC
Ph
3e
3f
O
F
6
7
8
4-FeC6H4(1c)
Ph (1d)
Ph
Ph
Ph
COOnBu
COOnBu
COOnBu
76
67
66
F
n
BuOOC
O
Ph
Ph
F
n
BuOOC
Ph
3g
O
OMe
4-MeOeC6H4(1e)
F
n
BuOOC
3h
O
Ph
9
Ph(1f)
C5H11
COOnBu
61
F
n
BuOOC
3i
O
Ph
CF3
10
11
4-CF3eC6H4(1a)
4-CF3eC6H4(1a)
Ph
Ph
Ph
76
91
F
Ph
3j
4-FeC6H4
O
Ph
CF3
F
12
4-CF3eC6H4(1a)
Ph
4-CF3eC6H4
74
F3C
3l
a
Unless otherwise specified, the reaction was carried on 0.1 mmol scale in 0.8 mL of solvent. The reaction time was 24 h.
Isolated yield after flash column chromatography.
b

8390
P. Li et al. / Tetrahedron 66 (2010) 8387e8391
J¼269.8 Hz), 123.7 (d, J¼5.1 Hz), 121.4 (d, J¼6.5 Hz), 111.1 (d,
O
R2
R1
2J¼13.1 Hz), 60.7, 14.3 ppm. 19F NMR (282.3 MHz, CDCl3):
¼ꢀ63.0,
d
ꢀ159.1 ppm; MS (ESI): 405.2 (MþHþ); HRMS calcd for C22H16F4O3:
404.1036, found: 427.0928 ([MþNaþ]).
F
1
O
R2
R1
[O]
Pd0
4.2.4. (E)-tert-Butyl 3-(4-fluoro-2-phenyl-5-(4-(trifluoromethyl)phe-
nyl)furan-3-yl)acrylate (3d). Yield: 65%; light yellow solid; IR: 3420,
Pd(OAc)2
F
R3
3
2924, 1613, 1504, 1451, 1325, 1166, 1064, 960, 834 cmꢀ1 1H NMR
;
(300 MHz, CDCl3):
d
¼7.80e7.77 (m, 2H), 7.63e7.60 (m, 5H),
7.44e7.40 (m, 3H), 6.48 (d,1H, J¼15.9 Hz),1.47 (s, 9H) ppm. 13C NMR
(100 MHz, CDCl3) 166.3, 151.6 (d, 3J¼6.5 Hz), 149.7 (d, 1J¼261.0 Hz),
135.2 (d, 2J¼19.7 Hz), 131.4 (q), 130.6 (q), 129.6, 129.4, 129.1, 127.2,
125.8 (q), 124.1 (q, J¼269.8 Hz), 123.7 (d, J¼5.9 Hz), 123.2
(d, J¼7.3 Hz), 111.1 (d, 2J¼13.2 Hz), 80.8, 28.1 ppm. 19F NMR
O
R1
R2
O
R1
R2
F
AcOPd
AcOPd
F
I
(282.3 MHz, CDCl3):
d¼ꢀ63.0, ꢀ158.9 ppm; MS (ESI): 455.2
II
R3
(MþNaþ); HRMS calcd for C24H20F4O3: 432.1349, found: 455.1241
([MþNaþ]).
R3
Scheme 1. A plausible mechanism for the reaction.
4.2.5. (E)-Butyl 3-(5-(2,4-dichlorophenyl)-4-fluoro-2-phenylfuran-
3-yl)acrylate (3e). Yield: 65%; white solid; mp: 52e54 ꢁC; IR: 2957,
1723, 1649, 1475, 1310, 1268, 1186, 1055, 850, 683 cmꢀ1 1H NMR
;
(400 MHz, CDCl3):
d
¼7.71e7.66 (d, 1H), 7.60e7.58 (m, 2H),
7.48e7.35 (m, 5H), 7.27e7.25 (d, 1H), 6.53 (d, 1H, J¼16.0 Hz) 4.14 (t,
2H, J¼6.8 Hz), 1.61 (m, 2H, J¼7.2 Hz), 1.35 (m, 2H, J¼7.2 Hz), 0.89
(m, 3H, J¼7.2 Hz) ppm. 13C NMR (100 MHz, CDCl3) 167.1, 152.4 (d,
3J¼6.6 Hz), 148.8 (d, 1J¼259.6 Hz),135.2, 133.7 (d, 2J¼21.2 Hz), 133.8,
131.9, 130.6, 129.6, 129.5, 129.1, 127.3, 125.5 (d, J¼4.4 Hz), 121.1
(d, J¼7.3 Hz), 110.4 (d, 2J¼13.9 Hz), 64.5, 30.8, 19.2, 13.8 ppm. 19F
0.3 mmol) in 0.8 mL of DMF was stirred for 20 min at rt before 2
(0.3 mmol) was added to the system via a microsyringe. Then the
mixture was heated to 120 ꢁC for 24 h. After cooling to rt, the re-
action was quenched by adding saturated aqueous NH4Cl. After
extraction with Et2O and drying with Na2SO4, the organic layer was
concentrated under reduced pressure and the residue was purified
by column chromatography on silica gel to afford the desired
products.
NMR (282.3 MHz, CDCl3):
d¼ꢀ156.2 ppm; MS (ESI): 455.2
(MþNaþ); HRMS calcd for C23H19Cl2FO3: 432.0695, found:
455.0588 ([MþNaþ]).
4.2.1. (E)-Butyl 3-(4-fluoro-2-phenyl-5-(4-(trifluoromethyl)phenyl)-
furan-3-yl)acrylate (3a). Yield: 72%; yellow oil; IR (CH2Cl2 film):
4.2.6. (E)-Butyl 3-(4-fluoro-5-(4-fluorophenyl)-2-phenylfuran-3-yl)-
acrylate (3f). Yield: 76%; white solid; mp: 73e74 ꢁC; IR: 2967, 1706,
2960, 2873, 1717, 1644, 1618, 1325, 1067, 1017, 842 cmꢀ1
;
1H NMR
1640, 1510, 1308, 1262, 1188, 1019, 840, 681 cmꢀ1 1H NMR
;
(300 MHz, CDCl3):
d
¼7.70e7.34 (m, 9H), 7.24e7.17 (m, 1H), 6.53 (d,
(400 MHz, CDCl3):
d
¼7.69e7.63 (m, 3H), 7.60e7.57 (m, 2H),
1H, J¼16 0.2 Hz), 4.14 (t, 2H, J¼6.8 Hz), 1.63e1.61 (m, 2H), 1.39e1.34
(m, 2H), 0.89 (t, 3H, J¼6.8 Hz) ppm. 13C NMR (100 MHz, CDCl3)
167.0, 151.8 (d, 3J¼6.6 Hz), 149.6 (d, 1J¼260.3 Hz), 135.3 (d,
2J¼19.0 Hz), 131.6 (m), 131.3 (m), 129.7, 129.4, 129.3, 129.1, 127.3,
125.8 (m), 124.1 (q, J¼269.8 Hz), 123.7 (d, J¼5.1 Hz), 121.4 (d.
J¼7.3 Hz), 110.1 (d, J¼13.1 Hz), 64.6, 30.8, 19.2, 13.7 ppm. 19F NMR
7.41e7.33 (m, 3H), 7.08e7.04 (t, 2H), 6.52 (d, 1H, J¼16.0 Hz) 4.14
(t, 2H, J¼6.8 Hz), 1.61 (m, 2H, J¼7.2 Hz), 1.35 (m, 2H, J¼7.2 Hz), 0.89
(m, 3H, J¼7.2 Hz) ppm. 13C NMR (100 MHz, CDCl3) 167.2, 162.1 (d,
1J¼248.7 Hz), 150.8 (d, 3J¼5.9 Hz), 148.0 (d, 1J¼258.1 Hz), 135.9
(d, 2J¼19.7 Hz), 132.1, 129.6, 129.4, 129.0, 127.2, 125.7 (dd), 124.5
(m), 120.9 (d, J¼7.3 Hz), 116.0 (d, J¼21.9 Hz), 110.9 (d, 2J¼13.1 Hz),
(282.3 MHz, CDCl3):
d¼ꢀ63.0, ꢀ159.1 ppm; MS (EI) (m/z): 432
64.5, 30.8, 19.2, 13.7 ppm. 19F NMR (282.3 MHz, CDCl3):
d
¼ꢀ113.3,
(Mþ); HRMS calcd for C24H20F4O3: 432.1349, found: 432.1345.
ꢀ163.0 ppm; MS (ESI): 405.2 (MþNaþ); HRMS calcd for
C23H20F2O3: 383.1381, found: 383.1453.
4.2.2. (E)-Methyl
3-(4-fluoro-2-phenyl-5-(4-(trifluoromethyl)phe-
nyl)furan-3-yl)acrylate (3b). Yield: 44%; light yellow solid; mp:
4.2.7. (E)-Butyl 3-(4-fluoro-2,5-diphenylfuran-3-yl)acrylate (3g).
Yield: 67%; light oil; IR (CH2Cl2 film): 2958, 1712, 1640, 1441, 1289,
101e102 ꢁC; IR: 2948, 1719, 1641, 1614, 1448, 1328, 1171, 1065, 848,
699 cmꢀ1
;
1H NMR (300 MHz, CDCl3):
d
¼7.88e7.80 (d, 2H),
1249, 1180, 764, 691 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d¼7.70e7.35
7.78e7.67 (m, 5H), 7.53e7.49 (m, 3H), 6.63 (d, 1H, J¼16.2 Hz), 3.83
(s, 3H) ppm. 13C NMR (100 MHz, CDCl3) 167.4, 151.9 (d, 3J¼6.6 Hz),
149.6 (d, 1J¼260.3 Hz), 135.4 (d, 2J¼19.0 Hz), 131.9 (m), 131.4 (m),
129.7,129.5,129.3,129.1,127.3,125.8 (q),124.1 (q, J¼273.4 Hz),123.8
(m, 9H), 7.24e7.17 (m, 1H), 6.53 (d, 1H, J¼16.0 Hz), 4.14 (t, 2H,
J¼6.8 Hz),1.62 (m, 2H, J¼2.8 Hz),1.36 (m, 2H, J¼6.4 Hz), 0.89 (m, 3H,
J¼7.6 Hz) ppm. 13C NMR (100 MHz, CDCl3) 167.2, 150.9 (d,
3J¼6.6 Hz), 148.4 (d, 1J¼258.1 Hz), 136.7 (d, 2J¼19.7 Hz), 132.2 (d,
J¼3.6 Hz), 129.7, 129.3, 129.0, 128.9, 128.2 (d, J¼5.1 Hz), 127.8, 127.2,
123.8 (d, J¼5.1 Hz), 120.8 (d, J¼6.7 Hz), 111.1 (d, J¼12.9 Hz), 64.5,
(d, J¼5.9 Hz), 120.9 (d, J¼6.6 Hz), 111.0 (d, 2J¼12.4 Hz), 51.8 ppm. 19
F
NMR (282.3 MHz, CDCl3):
d¼ꢀ63.0, ꢀ159.1 ppm; MS (ESI): 413.1
(MþNaþ); HRMS calcd for C21H14F4O3: 390.0879, found: 413.0771
([MþNaþ]).
30.8, 19.2, 13.8 ppm. 19F NMR (282.3 MHz, CDCl3):
d
¼ꢀ162.1 ppm;
MS (EI) (m/z): 364 (Mþ); HRMS calcd for C23H21FO3: 364.1475,
found: 364.1479.
4.2.3. (E)-Ethyl 3-(4-fluoro-2-phenyl-5-(4-(trifluoromethyl)phenyl)-
furan-3-yl)acrylate (3c). Yield: 53%; white solid; mp: 57e60 ꢁC; IR:
4.2.8. (E)-Butyl
3-yl)acrylate (3h). Yield: 66%; white solid; mp: 55e57 ꢁC; IR: 2959,
1714, 1628, 1510, 1462, 1253, 1176, 1032, 831, 767 cmꢀ1 1H NMR
(400 MHz, CDCl3):
(m, 2H), 7.44e7.40 (m, 1H), 6.99 (d, 2H, J¼8.0 Hz) 6.61 (d, 1H,
J¼16.0 Hz), 4.22 (t, 2H, J¼8.0 Hz), 3.86 (s, 3H),1.71 (m, 2H, J¼8.0 Hz),
1.45 (m, 2H, J¼8.0 Hz), 0.98 (m, 3H, J¼8.0 Hz) ppm. 13C NMR
3-(4-fluoro-5-(4-methoxyphenyl)-2-phenylfuran-
3403, 2975, 1711, 1644, 1453, 1328, 1112, 1064, 841, 692, cmꢀ1 1H
;
NMR (300 MHz, CDCl3):
d
¼7.81e7.60 (m, 7H), 7.48e7.39 (m, 3H),
;
6.55 (d, 1H, J¼16.5 Hz), 4.20 (q, 2H, J¼6.9 Hz), 1.28 (t, 3H,
J¼6.9 Hz) ppm. 13C NMR (100 MHz, CDCl3) 166.9, 151.8
(d, 3J¼6.5 Hz), 149.6 (d, 1J¼161 Hz), 135.3 (d, 2J¼19.7 Hz), 131.6
(q), 131.3 (q), 126.7, 129.4, 129.3, 129.1, 127.3, 125.8 (q), 124.1 (q,
d
¼7.78 (s, 1H), 7.75e7.66 (m, 4H), 7.51e7.50

P. Li et al. / Tetrahedron 66 (2010) 8387e8391
8391
(100 MHz, CDCl3) 167.3, 159.2, 150.2 (d, 3J¼6.5 Hz), 147.3
(d, 1J¼255.2 Hz), 136.8 (d, 2J¼19.6 Hz), 132.4, 129.9, 129.1, 129.0,
127.1, 125.4 (d, J¼5.1 Hz), 121.1 (d, J¼5.2 Hz), 120.5 (d, J¼7.3 Hz),
114.4, 111.1 (d, 2J¼12.9 Hz), 64.5, 55.4, 30.8, 19.2, 13.8 ppm. 19F NMR
CDCl3) 149.8 (d, 1J¼258.9 Hz), 149.4 (d, 3J¼6.5 Hz), 140.7, 135.0
(d, 2J¼18.9 Hz), 130.84, 130.77, 130.2, 129.1, 129.0, 127.0, 126.5,
125.9e125.7 (m), 124.19 (q, J¼269.8 Hz), 124.11 (q, J¼270.5 Hz),
123.7 (d, J¼5.8 Hz), 118.4 (d, J¼3.6 Hz), 112.6 (d, J¼12.4 Hz) ppm. 19F
(282.3 MHz, CDCl3):
d
¼ꢀ164.8 ppm; MS (EI) (m/z): 394 (Mþ);
NMR (282.3 MHz, CDCl3):
d
¼ꢀ62.9, ꢀ159.4 ppm; MS (EI) (m/z): 476
HRMS calcd for C24H23FO4: 394.1580, found: 394.1578.
(Mþ); HRMS calcd for C26H15F7O 476.1011, found: 476.1016.
4.2.9. (E)-Butyl
3-(4-fluoro-2-pentyl-5-phenylfuran-3-yl)acrylate
Acknowledgements
(3i). Yield: 61%; oil; IR (CH2Cl2 film): 2957, 2928, 1716, 1650, 1443,
1287, 1174, 975, 761 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d
¼7.67e7.65
This research was supported by the National Natural Science
Foundation of China (No.21032006, 20172064), the QT Program,
Shanghai Natural Science Council.
(m, 2H), 7.47e7.39 (m, 3H), 7.27e7.24 (m, 1H), 6.44 (d, 1H,
J¼16.0 Hz), 4.20 (m, 2H, J¼6.8 Hz), 2.74 (m, 2H, J¼7.6 Hz), 1.72e1.65
(m, 4H), 1.47e1.42 (m, 2H), 1.41e1.25 (m, 4H), 0.98e0.87 (m,
6H) ppm. 13C NMR (100 MHz, CDCl3) 167.5, 155.6 (d, 3J¼5.9 Hz),
147.7 (d, 1J¼257.3 Hz), 135.7 (d, 2J¼20.4 Hz), 131.8, 128.7, 128.5
(d, J¼5.2 Hz), 127.3, 123.5 (d, J¼5.8 Hz), 118.3 (d, J¼6.6 Hz), 110.7
(d, 2J¼13.1 Hz), 64.4, 31.2, 30.8, 27.9, 27.0, 22.3, 19.2, 13.9, 13.7 ppm.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2010.08.064. These data in-
clude MOL files and InChIKeys of the most important compounds
described in this article.
19F NMR (282.3 MHz, CDCl3):
d
¼ꢀ163.7 ppm; MS (EI) (m/z): 358
(Mþ); HRMS calcd for C22H27FO3: 358.1944, found: 358.1946.
4.2.10. (E)-3-Fluoro-5-phenyl-4-styryl-2-(4-(trifluoromethyl)phenyl)-
furan (3j). Yield: 76%; white solid; mp: 128e130 ꢁC; IR: 3404,
References and notes
1617, 1491, 1448, 1325, 1173, 1110, 837, 692 cmꢀ1
;
1H NMR
1. (a) Alberico, D.; Scott,M.E.;Lautens, M.Chem. Rev. 2007,107,174; (b) Campeau,L.-C.;
Stuart, D. R.;Fagnou, K. Aldrichimica Acta 2007, 40, 35; (c)Seregin, I. V.;Gevorgyan, V.
Chem. Soc. Rev. 2007, 36,1173; (d) Lewis, J. C.; Bergman, R. G.; Ellman, J. A. Acc. Chem.
Res. 2008, 41,1013; (e) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010,110,
624.
2. For olefination of indoles, see: (a) Ferreira, E. M.; Stoltz, B. M. J. Am. Chem. Soc.
2003, 125, 9578; (b) Liu, C.; Widenhoefer, R. A. J. Am. Chem. Soc. 2004, 126,
10250; (c) Grimster, N. P.; Gauntlett, C.; Godfrey, C. R. A.; Gaunt, M. J. Angew.
Chem., Int. Ed. 2005, 44, 3125; (d) Capito, E.; Brown, J. M.; Ricci, A. Chem.
Commun. 2005, 1854; (e) GarÍa-Rubia, A.; Arrayás, R. G.; Carretero, J. C. Angew.
Chem., Int. Ed. 2009, 48, 6511.
(400 MHz, CDCl3):
d
¼7.79e7.77 (m, 2H), 7.63e7.58 (m, 4H),
7.43e7.39 (m, 4H), 7.36e7.32 (m, 1H), 7.30e7.28 (m, 1H), 7.27e7.00
(m, 3H), 6.99e6.96 (d, 1H) ppm. 13C NMR (100 MHz, CDCl3) 150.1
(d, 1J¼258.9 Hz), 148.7 (d, 3J¼7.3 Hz), 137.3, 134.8 (d, 2J¼19.7 Hz),
132.67,132.61,131.9 (m),130.4,128.9,128.8,128.0,126.8,126.5,125.8
(q),124.2 (q,1J¼280 Hz),123.6 (d, J¼5.6 Hz),115.8 (d, J¼3.6 Hz),113.1
(d, 2J¼13.1 Hz) ppm. 19F NMR (282.3 MHz, CDCl3):
d¼ꢀ62.3,
ꢀ158.7 ppm; MS (EI) (m/z): 408 (Mþ); HRMS calcd for C25H16F4O:
408.1137, found: 408.1136.
3. For olefination of pyridine N-oxides, see Cho, S. H.; Hwang, S. J.; Chang, S. J. Am.
Chem. Soc. 2008, 130, 9254.
4. For olefination of other electron-rich reactants, see: (a) Aouf, C,; Thiery, E.; Bras,
J. L.; Muzart, J. Org. Lett. 2009, 11, 4096; (b) Rauf, W.; Thompson, A. L.; Brown, J.
M. Chem. Commun. 2009, 3874; (c) Beck, E. M.; Grimster, N. P.; Hatley, R.; Gaunt,
M. J. J. Am. Chem. Soc. 2006, 128, 2528; (d) Maehara, A.; Satoh, T.; Miura, M.
Tetrahedron 2008, 64, 5982; (e) Wu, J.; Cui, X.; Chen, L.; Jiang, G.; Wu, Y. J. Am.
Chem. Soc. 2009, 131, 13888.
5. The application of oxidative Heck reaction, see: (a) Beck, E. M.; Hatley, R.;
Gaunt, M. J. Angew. Chem., Int. Ed. 2008, 47, 3004; (b) Cheng, D.; Gallagher, T.
Org. Lett. 2009, 11, 2639.
4.2.11. (E)-Butyl 3-(4-fluoro-5-(4-methoxyphenyl)-2-phenylfuran-3-
yl)acrylate (3k). Yield: 91%; white solid; mp: 118e120 ꢁC; IR: 3420,
3054, 2925, 1613, 1448, 1416, 1328, 1118, 834, 761 cmꢀ1 1H
;
NMR (300 MHz, CDCl3):
d
¼7.76e7.74 (m, 2H), 7.58 (s, 4H),
7.43e7.34 (m, 5H), 7.15e7.09 (d, 1H), 6.99e6.83 (d, 3H) ppm. 13C
NMR (100 MHz, CDCl3) 162.6 (d, 1J¼246.4 Hz), 150.0 (d,
1J¼261.7 Hz), 148.6 (d, 3J¼8.8 Hz), 134.8 (d, 2J¼19.7 Hz), 134.5
(d, J¼3.7 Hz), 131.8 (q), 131.6, 131.3 (q), 130.4, 129.0, 128.8, 128.2,
128.0, 126.8, 125.8 (q, J¼3.7 Hz), 124.2 (q, 1J¼280.5 Hz), 115.8
(d, J¼19.5 Hz), 115.5 (d, J¼3.7 Hz), 112.9 (d, 2J¼13.1 Hz) ppm. 19F
6. Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S. Chem. Rev. 2007, 107,
5318.
7. (a) Nesterov, E. E.; Skoch, J.; Hyman, B. T.; Klunk, W. E.; Bacskai, B. J.; Swager, T.
M. Angew. Chem., Int. Ed. 2005, 44, 5452; (b) Sun, Y.; Liu, Y.; Zhu, D. J. Mater.
Chem. 2005, 15, 53; (c) Perepichaka, I. F.; Perepichaka, D. F.; Meng, H.; Wudl, F.
Adv. Mater. 2005, 17, 2281; (d) Ginocchietti, G.; Galiazzo, G.; Mazzucato, U.;
Spalletti, A. Photochem. Photobiol. Sci. 2005, 4, 547.
NMR (282.3 MHz, CDCl3):
d
¼ꢀ62.9, ꢀ113.9, ꢀ159.4 ppm; MS (EI)
(m/z): 426 (Mþ); HRMS calcd for C25H15F5O 426.1043, found:
8. (a) Fujiwara, Y.; Maruyama, O.; Yoshidomi, M.; Taniguchi, H. J. Org. Chem.
1981, 46, 851; (b) Jia, C.; Lu, W.; Kitamura, T.; Fujiwara, Y. Org. Lett. 1999, 1,
2097; (c) Tani, M.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2004, 69, 1221.
9. Zhang, X.; Fan, S.; He, C.-Y.; Wan, X.; Min, Q.-Q.; Yang, J.; Jiang, Z.-X. J. Am. Chem.
Soc. 2010, 132, 4506.
426.1049.
4.2.12. (E)-3-Fluoro-5-phenyl-2-(4-(trifluoromethyl)phenyl)-4-(4-
(trifluoromethyl)styryl)furan (3l). Yield: 74%; oil; IR (CH2Cl2 film):
3411, 2966, 1714, 1639, 1451, 1328, 1181, 1115, 837 cmꢀ1 1H NMR
;
10. (a) Li, P.; Chai, Z.; Zhao, G.; Zhu, S.-Z. Tetrahedron 2009, 65, 1673; (b) Li, P.; Chai,
Z.; Zhao, G.; Zhu, S.-Z. Synlett 2008, 16, 2547.
11. Amatore, C.; Jutand, A. J. Organomet. Chem. 1999, 576, 254 and references
therein.
(300 MHz, CDCl3):
d
¼7.87e7.84 (d, 2H), 7.69e7.44 (m, 11H),
7.30e7.25 (m, 1H), 7.16e7.10 (m, 1H) ppm. 13C NMR (100 MHz,