Copper-catalyzed ring opening of furans as a concise route to polysubstituted furans under mild conditions

Article abstract of DOI:10.1055/s-0032-1317683

A range of polysubstituted furans were synthesized from furan derivatives involving copper-catalyzed ring opening of the furan ring. This synthetic method possesses the advantages of readily available starting materials, mild reaction conditions, and shor

Full text of DOI:10.1055/s-0032-1317683

PAPER
▌3735
paper
Copper-Catalyzed Ring Opening of Furans as a Concise Route to
Polysubstituted Furans under Mild Conditions
Synthesis of Polysubstituted Furans
Biaolin Yin,*a Huiyue Yu,a,b Zhengrong Li,a Weiqiang Zhong,a Wenxiang Gub
a
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, P. R. of China
Fax +86(20)87113735; E-mail: blyin@scut.edu.cn
b
Department of Applied Chemistry, College of Science, South China Agricultural University, Guangzhou, 510642, P. R. of China
Received: 31.08.2012; Accepted after revision: 01.11.2012
chain containing a nucleophile at the other α-position.8
These studies disclosed that some copper(II) salts facili-
tate the dearomatization of the furan ring [Scheme 1 (b)].
We envisioned that a general method for the synthesis of
polysubstituted furans 7 could be developed under suit-
able conditions from furans 5 carrying an activated meth-
ylene at their C-2 side chains, which could form an enolic
hydroxyl functionality when exposed to an acidic medium
[Scheme 1 (c)]. In continuation of our interest in the syn-
thesis of heterocyclic compounds based on the dearomati-
zation of furan ring,8,9 we report here a practical and
concise route to polysubstituted furans under mild condi-
tions involving copper-catalyzed ring opening of the furan
ring.
Abstract: A range of polysubstituted furans were synthesized from
furan derivatives involving copper-catalyzed ring opening of the fu-
ran ring. This synthetic method possesses the advantages of readily
available starting materials, mild reaction conditions, and short
steps.
Key words: polysubstituted furan, ring-opening of furan, ring-
opening/rearomatization, copper-catalyzed
Polysubstituted furans represent an important class of
five-membered heterocycles prevalent in a number of bio-
active natural products as well as in various pharmaceuti-
cals and agrochemicals.1 Due to the low Dewar resonance
energy of 4.3 kcal/mol and the fact that furan ring contains
masked functionalities of olefin, diene, enol ether, and
1,4-dicarbonyl, furans are also particularly useful build-
ing blocks in synthetic organic chemistry. The dearomati-
zation of furan ring has attracted considerable attention
because it provides a simple method to achieve function-
alized alicyclic synthetic building blocks, which can be
utilized for the construction of more complex com-
pounds.2 As a consequence, on the one hand, numerous
transformations have been specifically designed to syn-
thesize polysubstituted furans.3 On the other hand, a num-
ber of different methods that, with unequal scope, have
been developed for the dearomatization of the furan ring
and used extensively in the synthesis of useful com-
pounds.4,5 Therefore, the development of flexible and pre-
dictable approach to diversely substituted furans starting
from inexpensive and readily available furans via ring
opening of furans is practically significant.
R2
R1OC
protic acid
HX
R2
X
(a)
R1
O
2
1
our previous work:
HNu
Nu
(b)
R
Cu(II)
O
O
R
OH
3
4
this work:
R3
E
HO
R3
O
(c)
R1
R1
E
O
O
R2
R2
5
6
It is well known that alkylfurans can be hydrolyzed to 1,4-
dicarbonyl compounds under acidic conditions.6 This
property is widely exploited in organic synthesis. In par-
ticular, a general approach to the synthesis of benzoannu-
lated heterocyclic compounds was developed based on
ring-opening/rearomatization of ortho-substituted benzyl-
furans [Scheme 1 (a)].7 However, this transformation usu-
ally required strong protic acid such as HCl and higher
reaction temperature. Recently, we have developed ac-
cesses to bioactive spiro compounds via copper(II) salt-
promoted dearomatization of α-furylcarbinols with a side
O
R3
O
R1
Cu(II)
mild conditions
R2
E
7
Scheme 1 Accesses to heterocyclic compounds via dearomatization
of the furan rings
At the outset, the precursors 5 was prepared via the reac-
tion of 2-furylcarbinols 8 with activated methylene com-
pounds 9 in dichloromethane in the presence of Yb(OTf)3
(10 mol%) as the catalyst (Scheme 2). To optimize the re-
action conditions for the ring opening/rearomatization, 5a
was used as the substrate under the influence of various
SYNTHESIS 2012, 44, 3735–3742
Advanced online publication: 16.11.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1317683; Art ID: SS-2012-H0696-OP
© Georg Thieme Verlag Stuttgart · New York

3736
B. Yin et al.
PAPER
Table 1 Optimization of the Reaction Conditionsa,b
Lewis acids (1 equiv) as the catalyst. As shown in Table
1, CuCl2, CuSO4, Cu(OAc)2, CuBr, FeCl2, and ZnCl2 led
to no reaction, while CuBr2, Cu(OTf)2, and FeCl3 gave
rise to the desired compounds 7a in 63%, 51%, and 36%
yield, respectively. CuBr2 was found to be the suitable
catalyst for this reaction. The solvent screening proved
that MeCN was optimal. Gratifyingly, when the amount
of CuBr2 was reduced to 0.2 equivalent and the reaction
temperature was increased to 50 °C, 7a was produced in
88% yield (Table 1, entry 15).
O
O
COOEt
O
O
COOEt
5a
7a
Entry
Catalyst
Solvent
Yield (%)c
1
CuCl2
CuSO4
Cu(OAc)2
CuBr
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DCE
NRd
NRd
NRd
NRd
63
2
3
O
R3
E
Yb(OTf)3 (10 mol%)
CH2Cl2, reflux
E
R2
4
R1
O
+
R1
COR3
O
OH
5
CuBr2
Cu(OTf)2
FeCl3
8
R2
9
5
6
51
41–91%
R
R
1 = Me, Bn, Ph
2 = H, Et, Bn, Ph, 4-MeC6H4,
7
36
4-MeOC6H4, 4-O2NC6H4, 2-thienyl
8
FeCl2
NRd
NRd
67
9: MeCOCH2COMe, MeCOCH2COOEt, PhCOCH2COPh
PhCOCH2CN, PhCOCH2CONHPh
9
ZnCl2
Scheme 2 Synthesis of precursor furans 5
10e
11e
CuBr2
CuBr2
CuBr2
CuBr2
40
With the optimized reaction conditions in hand, various
furans 5 with different R1, R2, R3, and E groups were test- 12e
THF
0
ed to investigate the reaction scope, and the results are
13e
CH2Cl2
MeCN
MeCN
30
presented in Table 2. Initially, with the fixation of R1 and
R2 groups (R1 = Me, R2 = H), the scopes of R3 and E 14e
CuBr2
70
f
groups were investigated. When R3 is a Me or Ph group
and E is an electron-withdrawing group such as ester, cy-
f
15e,g
88
CuBr2
anide, acyl, and amide group, compounds 5 were trans- a All reactions were carried out on a 0.3 mmol scale.
b Unless otherwise noted, 1 equiv of the catalyst was used. The reac-
tions were performed at r.t.
formed into the desired 7 in moderate to good yields
(Table 2, entries 1–5). For 5f, due to its sterically bulky R3
group of tert-butyl, the reaction system was complicated
and none of the product 7f was isolated. We guessed that
the bulky tert-butyl group might impede the attacking of
the carbonyl group at the α-position of the furan ring. In
contrast, if R3 is an ethyloxy group as in 5g, the corre-
sponding product 7g was not isolated. The failure might
result from the instability of 7g or the low acidity of the
hydrogen of the activated methylene group, which led to
the low content of enol under this reaction conditions. The
nature of R1 also influenced remarkably on the yields of
the products. When R1 is an alkyl group such as Me or Bn,
the transformation proceeded smoothly. If R1 is a phenyl
group, low yield of 31% was obtained (entry 9). In con-
c Isolated yield.
d NR: no reaction.
e CuBr2 used: 0.2 equiv.
f The reaction temperature was 50 °C.
g AcOH (10 mol%) was added.
Scheme 3. Initially, the coordination of the carbonyl
group of 5 with CuBr2 produces carbocation 10, which
gets deprotonated to form the intermediate 11. Cyclization
of the intermediate 11 and subsequent ring-opening leads
to the intermediate 12, which is transferred into 7 via a
1,3-H migration and a subsequent isomerization step.
trast, if R1 is H, the reaction system was very complicated In summary, we have developed a practical method for the
and none of the desired compound was isolated (entry 10).
Finally, a series of 5 with variable R2 group including
alkyl, heteroaryl, and phenyl groups with an electron-
preparation of polysubstituted and functionalized furans
involving copper-catalyzed ring opening of furans. This
protocol possesses the advantages of readily available
donating or electron-withdrawing substituent were starting materials, mild reaction conditions, and short
screened. All of them were transformed into the tetra- steps. Importantly, this protocol provides an efficient ac-
substituted furans (entries 11–19). Notably, the yields of cess to tetrasubstituted furans, which are usually synthe-
the products with R2 as an alkyl group were generally sized through multiple steps under harsher reaction
higher than those with a phenyl or heteroaryl group at R2
(entries 11–13 vs entries 14–19).
conditions.10 Further studies on the synthesis of polysub-
stituted and functionalized thiophenes and pyrroles using
this protocol are under way in our laboratory and the re-
sults will be reported in due course.
Based on the experimental results shown above, a tenta-
tive mechanism for the formation of 7 is proposed in
Synthesis 2012, 44, 3735–3742
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Polysubstituted Furans
3737
Table 2 Synthesis of Furans 7a,b
CuBr2 (0.2 equiv)
AcOH (10 mol%)
MeCN, 50 °C
O
R3
R3
O
R1
E
O
R1
O
R2
E
R2
5
7
Entry
R1
R2
R3
E
5
7
Yield (%)c
1
Me
Me
Me
Me
Me
Me
Me
Bn
Ph
H
H
H
H
H
H
H
H
Et
H
Et
Bn
Me
Me
Ph
CO2Et
COMe
COPh
CN
5a
7a
7b
7c
7d
7e
7f
83
2
5b
75
3
5c
41
4
Ph
5d
41
5
Me
t-Bu
CONHPh
CO2Et
CO2Et
CO2Et
CO2Et
COMe
CO2Et
CO2Et
COMe
COMe
CO2Et
COMe
CO2Et
COMe
CO2Et
5e
65
6
5f
NDd
NDd
79
7
CO2Et
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
5g
7g
7h
7i
8
5h
9
5i (8:7)
5j
31
10
11
12
13
14
15
16
17
18
19
H
7j
trace
84
Me
Me
Me
Me
Me
Me
Me
Me
Me
5k (8:7)
5l (8:7)
5m (1.2:1)
5n
7k
7l
88
c-Hex
7m
7n
7o
7p
7q
7r
7s
84
Ph
Ph
71
5o (1:1)
5p
70
4-MeOC6H4
4-MeC6H4
4-O2NC6H4
2-thienyl
38
5q (8:7)
5r
85
35
5s (1:1)
57
a All reactions were carried out on a 0.3 mmol scale.
b The ratios in the parentheses refer to the diastereoselectivities.
c Isolated yield.
d ND: not detected.
Br
Br
Cu
IR spectra were recorded with PerkinElmer1 983 or Shimadzu IR-
1
440 spectrometers. H and 13C NMR spectra were recorded on an
BrCu
BrCu
AMX-300, DPX-300, Gemini-2000, or IN-OVA-600 spectrometer
with TMS as the internal standard. Mass spectra were taken with a
Mariner (PE, for ESI), HP5973N or HP5989A instrument. HRMS
(EI or ESI) spectra were obtained using a Kratos CONCEPT 1H or
Bruker APEXIII 7.0 TESLA mass spectrometer. Optical rotations
were measured with a PerkinElmer 241 MC polarimeter. Elemental
analyses were carried out in a Heraeus CHN-O-RAPID Elemental
Analyzer. Melting points were determined on X-4 Mel-Temp appa-
ratus and are uncorrected. Flash column chromatography was per-
formed on silica gel H (1040 μm) with petroleum ether–EtOAc
system as the eluent. Petroleum ether (PE) used refers to the fraction
boiling at 30–60 °C.
O
R3
E
R3
O
R3
E
O
+
R1
O
R1
E
R1
O
O
R2
H
R2
5
10
11
R2
O
R3
O
BrCu
R1
R3
1,3-H-
migration
R1
OH
O
H
E
E
12
H
O
R3
R1
Furans 5; General Procedure
7
OH
To a stirred solution of 8 (3 mmol) and 9 (3 mmol) in anhyd CH2Cl2
(20 mL) was added Yb(OTf)3 (186 mg, 0.3 mmol). The mixture was
refluxed for 30 min and concentrated under reduced pressure. The
E
Scheme 3 Plausible mechanism for the formation of 7
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3735–3742

3738
B. Yin et al.
PAPER
residue was purified by silica gel column chromatography using
PE–EtOAc (10:1) as the eluent to afford 5.
13C NMR (101 MHz, CDCl3): δ = 206.4, 166.0, 151.4, 149.2, 137.6,
128.9, 124.6, 120.1, 107.9, 106.2, 60.5, 29.4, 28.8, 13.4.
HRMS (ESI): m/z calcd for C16H18NO3 [M + H]+: 272.1287; found:
272.1269.
5a
Yield: 407 mg (91%); colorless oil.
IR (film): 2985, 2926, 1718, 1643, 1567, 1364, 1021, 1147, 785,
735 cm–1.
5h
Yield: 456 mg (76%); colorless oil.
1H NMR (400 MHz, CDCl3): δ = 5.88 (d, J = 2.8 Hz, 1 H), 5.80 (d,
J = 2.0 Hz, 1 H), 4.18 (q, J = 6.8 Hz, 2 H), 3.82 (t, J = 7.5 Hz, 1 H),
3.12 (d, J = 7.2 Hz, 2 H), 2.22 (s, 3 H), 2.21 (s, 3 H), 1.24 (t, J = 7.2
Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 202.1, 168.8, 151.0, 149.9, 107.2,
106.0, 105.5, 61.5, 58.4, 29.3, 26.6, 14.1, 14.0, 13.4.
IR (film): 2983, 2895, 1718, 1563, 1453, 1363, 1246, 1199, 1148,
1017, 787, 707, 465 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.31–7.23 (m, 2 H), 7.22–7.15 (m,
3 H), 5.92 (s, 1 H), 5.86 (s, 1 H), 4.25–4.08 (m, 2 H), 3.87 (s, 2 H),
3.81 (t, J = 7.5 Hz, 1 H), 3.13 (d, J = 5.7 Hz, 2 H), 2.14 (s, 3 H), 1.20
(t, J = 7.0 Hz, 3 H).
HRMS (ESI): m/z calcd for C12H17O4 [M + H]+: 225.1127; found:
13C NMR (101 MHz, CDCl3): δ = 201.8, 168.6, 153.3, 150.6, 137.9,
225.1139.
128.4, 128.3, 126.2, 107.1, 106.8, 61.3, 58.0, 34.3, 29.2, 26.5, 13.8.
HRMS (ESI): m/z calcd for C18H21O4 [M + H]+: 301.1440; found:
301.1455.
5b
Yield: 353 mg (91%); colorless syrup.
IR (film): 2925, 1700, 1649, 1541, 1456, 1421, 1215, 1020, 784,
669, 420 cm–1.
5i
Yield: 251 mg (40%); colorless syrup.
1H NMR (400 MHz, CDCl3): δ = 5.87 (d, J = 2.9 Hz, 0.3 H), 5.84–
5.78 (m, 2 H), 4.03 (t, J = 7.5 Hz, 0.3 H), 3.50 (s, 2 H), 3.10 (d, J =
7.6 Hz, 1 H), 2.23 (s, 3 H), 2.21 (s, 1 H), 2.16 (s, 2 H), 2.14 (s, 5 H).
13C NMR (101 MHz, CDCl3): δ = 203.2, 191.8, 151.8, 151.2, 151.1,
149.7, 107.4, 106.7, 106.1, 105.9, 67.1, 29.2, 26.8, 26.6, 23.05,
13.5, 13.4.
IR (film): 2966, 2856, 1714, 1649, 1541, 1019, 758, 689 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.61 (d, J = 5.6 Hz, 2 H), 7.36 (t,
J = 7.1 Hz, 2 H), 7.29–7.16 (m, 1 H), 6.53 (d, J = 3.0 Hz, 1 H), 6.17
(dd, J = 5.9, 3.2 Hz, 1 H), 4.23 (q, J = 7.1 Hz, 1.06 H), 4.01 (q, J =
7.2 Hz, 0.94 H), 3.94 (dd, J = 13.7, 10.4 Hz, 1 H), 3.58–3.44 (m, 1
H), 2.29 (s, 1.40 H), 2.05 (s, 1.60 H), 1.79–1.61 (m, 2 H), 1.29 (t,
J = 7.1 Hz, 1.60 H), 1.06 (t, J = 7.1 Hz, 1.40 H), 0.92–0.81 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 202.1, 201.8, 168.2, 168.0, 154.0,
153.5, 152.9, 152.8, 130.9, 130.8, 128.6, 128.6, 127.1, 127.0, 123.4,
123.4, 109.7, 109.4, 105.6, 105.4, 64.0, 63.7, 61.5, 61.3, 40.7, 40.4,
29.7, 29.6, 25.2, 25.0, 14.0, 13.8, 11.7, 11.5.
HRMS (ESI): m/z calcd for C11H15O3 [M + H]+ 195.1021; found:
195.1007.
5c
Yield: 553 mg (87%); colorless gum.
HRMS (ESI): m/z calcd for C19H23O4 [M + H]+: 315.1596; found:
315.1587.
IR (film): 3062, 2922, 1695, 1565, 1450, 1336, 1270, 1213, 1016,
943, 781, 688, 585 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 7.9 Hz, 4 H), 7.54 (t,
J = 7.4 Hz, 2 H), 7.42 (t, J = 7.7 Hz, 4 H), 5.89 (d, J = 2.4 Hz, 1 H),
5.73 (d, J = 2.4 Hz, 1 H), 5.66 (t, J = 7.0 Hz, 1 H), 3.42 (d, J = 7.0
Hz, 2 H), 2.17 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 195.3, 150.9, 150.0, 136.0, 133.4,
128.8, 128.6, 107.9, 106.1, 55.8, 28.2, 13.4.
5k
Yield: 206 mg (41%); colorless oil.
IR (film): 2969, 1718, 1562, 1457, 1363, 1244, 1156, 1021, 784
cm–1.
1H NMR (400 MHz, CDCl3): δ = 5.91 (dd, J = 5.6, 3.0 Hz, 1 H),
5.80 (s, 1 H), 4.18 (q, J = 7.1 Hz, 1.04 H), 4.00 (q, J = 7.1 Hz, 0.96
H), 3.81 (t, J = 6.4 Hz, 1 H), 3.42–3.28 (m, 1 H), 2.24 (s, 1.40 H),
2.21 (s, 3 H), 2.00 (s, 1.60 H), 1.26 (t, J = 7.1 Hz, 1.60 H), 1.10 (t,
J = 7.1 Hz, 1.40 H), 0.83–0.75 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 202.4, 202.1, 168.4, 168.1, 152.6,
151.8, 151.0, 150.9, 108.2, 107.8, 105.9, 105.7, 64.2, 63.8, 61.4,
61.2, 40.6, 40.3, 29.7, 29.4, 25.1, 24.8, 14.0, 13.8, 13.4, 13.4, 11.6,
11.4.
HRMS (ESI): m/z calcd for C21H19O3 [M + H]+: 319.1334; found:
319.1350.
5d
Yield: 339 mg (71%); colorless syrup.
IR (film): 2923, 2247, 1694, 1448, 1266, 1220, 1020, 961, 786, 693
cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.32–8.26 (m, 2 H), 7.96 (t, J = 7.5
Hz, 1 H), 7.84 (t, J = 7.8, 2 H), 6.43 (d, J = 3.0 Hz, 1 H), 6.24–6.15
(m, 1 H), 5.03 (dd, J = 8.4, 6.4 Hz, 1 H), 3.67 (dd, J = 15.2, 6.2 Hz,
1 H), 3.58 (dd, J = 15.2, 8.4 Hz, 1 H), 2.55 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 189.8, 151.9, 147.2, 134.4, 133.9,
128.9, 128.7, 116.7, 109.0, 106.3, 38.9, 28.3, 13.3.
HRMS (ESI): m/z calcd for C15H14NO2 [M + H]+: 240.1025; found:
240.1033.
HRMS (ESI): m/z calcd for C14H21O4 [M + H]+: 253.1440; found:
253.1451.
5l
Yield: 301 mg (48%); colorless oil.
IR (film): 2924, 1741, 1715, 1649, 1559, 1456, 1148, 1020, 784,
698 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.23–7.13 (m, 3 H), 6.99 (d, J =
4.5 Hz, 2 H), 5.79–5.65 (m, 2 H), 4.22 (d, J = 7.1 Hz, 1.06 H), 4.03
(d, J = 7.1 Hz, 0.94 H), 3.92 (d, J = 10.3 Hz, 1 H), 3.86 (d, J = 9.5
Hz, 1 H), 3.80–3.64 (m, 1 H), 3.00–2.84 (m, 2 H), 2.27–2.22 (m,
1.40 H), 2.02 (s, 1.60 H), 1.30 (t, J = 7.1 Hz, 1.60 H), 1.12 (t, J = 7.1
Hz, 1.40 H).
13C NMR (101 MHz, CDCl3): δ = 202.2, 201.2, 168.7, 168.0, 151.5,
151.0, 150.9, 139.0, 138.9, 129.1, 128.1, 128.0, 126.2, 108.8, 108.3,
106.0, 105.8, 63.4, 63.3, 61.5, 61.4, 50.1, 41.1, 40.4, 38.4, 37.9,
30.1, 29.8, 29.5, 14.1, 14.1, 13.9, 13.5, 13.5.
5e
Yield: 482 mg (89%); colorless syrup.
IR (film): 3309, 2922, 1722, 1660, 1601, 1542, 1498, 1442, 1357,
1246, 1022, 949, 785, 755, 693, 503 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.22 (s, 1 H), 7.47 (d, J = 7.9 Hz,
2 H), 7.31 (t, J = 7.8 Hz, 2 H), 7.11 (t, J = 7.4 Hz, 1 H), 5.95 (d, J =
2.6 Hz, 1 H), 5.84 (s, 1 H), 3.84 (t, J = 7.4 Hz, 1 H), 3.25 (d, J = 7.6
Hz, 2 H), 2.25 (s, 3 H), 2.21 (s, 3 H).
Synthesis 2012, 44, 3735–3742
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Polysubstituted Furans
3739
HRMS (ESI): m/z calcd for C19H23O4 [M + H]+: 315.1596; found:
315.1584.
5q
Yield: 439 mg (70%); colorless syrup.
IR (film): 2924, 1717, 1513, 1455, 1360, 1216, 1154, 1022, 782
cm–1.
5m
Yield: 275 mg (45%); colorless syrup.
1H NMR (400 MHz, CDCl3): δ = 7.19 (t, J = 8.2 Hz, 2 H), 7.08 (d,
J = 7.8 Hz, 2 H), 5.93 (d, J = 3.0 Hz, 0.46 H), 5.89 (d, J = 3.0 Hz,
0.54 H), 5.82–5.79 (m, 1 H), 4.72 (d, J = 3.3 Hz, 0.46 H), 4.69 (d,
J = 3.3 Hz, 0.54 H), 4.36 (d, J = 2.9 Hz, 0.54 H), 4.33 (d, J = 3.0 Hz,
0.46 H), 4.12 (q, J = 7.1 Hz, 0.94 H), 3.93 (q, J = 7.1 Hz, 1.06 H),
2.29 (s, 3 H), 2.22 (s, 1.60 H), 2.20 (s, 3 H), 2.01 (s, 1.40 H), 1.18
(t, J = 7.1 Hz, 1.40 H), 1.00 (t, J = 7.1 Hz, 1.60 H).
13C NMR (101 MHz, CDCl3): δ = 201.5, 201.3, 167.6, 167.2, 152.8,
152.4, 151.3, 151.2, 136.8, 136.7, 136.2, 136.0, 129.3, 129.1, 128.1,
128.1, 107.2, 106.7, 106.2, 106.0, 64.5, 64.3, 61.5, 61.3, 44.4, 44.4,
30.2, 29.4, 21.0, 13.9, 13.7, 13.5, 13.4.
IR (film): 2927, 2854, 1716, 1560, 1451, 1361, 1153, 1021, 784
cm–1.
1H NMR (400 MHz, CDCl3): δ = 5.88 (d, J = 3.0 Hz, 0.44 H), 5.85
(d, J = 3.0 Hz, 0.56 H), 5.81 (s, 1 H), 4.20 (q, J = 7.1 Hz, 1.10 H),
4.06 (t, J = 11.3 Hz, 1 H), 3.98 (q, J = 7.1 Hz, 0.90 H), 3.46–3.38
(m, 2 H), 2.26 (s, 1.31 H), 2.21 (s, 3 H), 2.02 (s, 1.69 H), 1.70–1.51
(m, 6 H), 1.29–0.81 (m, 7 H).
13C NMR (101 MHz, CDCl3): δ = 202.4, 202.1, 200.6, 168.5, 168.2,
151.7, 151.1, 150.7, 150.5, 108.8, 108.3, 105.9, 105.7, 61.7, 61.4,
61.3, 61.3, 61.2, 50.1, 44.4, 44.1, 39.9, 39.5, 32.1, 31.9, 30.1, 29.3,
29.1, 28.4, 28.2, 26.5, 26.5, 26.4, 26.3, 26.2 14.1, 13.8, 13.5, 13.5.
HRMS (ESI): m/z calcd for C18H21O3 [M + H]+ 285.1491; found:
285.1487.
HRMS (ESI): m/z calcd for C17H25O3 [M + H]+: 277.1804; found:
277.1816.
5r
5n
Yield: 415 mg (66%); colorless syrup.
Yield: 351 mg (65%); colorless syrup.
IR (film): 2923, 1733, 1702, 1602, 1520, 1421, 1349, 1148, 1021,
952, 856, 788, 734, 697, 524 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.14 (d, J = 8.7 Hz, 2 H), 7.47 (d,
J = 8.7 Hz, 2 H), 5.96 (d, J = 2.8 Hz, 1 H), 5.84 (d, J = 2.8 Hz, 1 H),
4.91 (d, J = 11.9 Hz, 1 H), 4.61 (d, J = 11.9 Hz, 1 H), 2.20 (s, 3 H),
2.16 (s, 3 H), 1.99 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 201.3, 201.0, 152.4, 150.3, 147.1,
146.6, 129.1, 124.0, 108.3, 106.5, 72.90, 44.4, 30.3, 28.7, 13.4.
HRMS (ESI): m/z calcd for C17H18NO5 [M + H]+: 316.1185; found:
316.1196.
IR (film): 2923, 1743, 1699, 1558, 1367, 1243, 1148, 1022, 913,
783, 731, 698 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.27 (t, J = 4.5 Hz, 1 H), 5.89 (d,
J = 3.0 Hz, 1 H), 5.81 (d, J = 2.1 Hz, 1 H), 4.79 (d, J = 12.0 Hz, 1
H), 4.57 (d, J = 12.0 Hz, 1 H), 2.20 (s, 1 H), 2.17 (s, 1 H), 1.92 (s, 1
H).
13C NMR (101 MHz, CDCl3): δ = 202.4, 202.2, 152.2, 151.6, 139.0,
128.7, 128.2, 127.3, 107.4, 106.2, 73.4, 45.1, 30.2, 28.8, 13.4.
HRMS (ESI): m/z calcd for C17H19O3 [M + H]+: 271.1334; found:
271.1344.
5s
5o
Yield: 342 mg (56%); colorless syrup.
Yield: 366 mg (61%); colorless syrup.
IR (film): 2974, 1718, 1560, 1516, 1456, 1361, 1213, 1146, 1021,
1146, 1021, 785, 696 cm–1.
IR (film): 2985, 1704, 1648, 1559, 1559, 1363, 1144, 1020, 782,
697, 526 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.14 (d, J = 4.9 Hz, 1 H), 6.95–
6.86 (m, 2 H), 6.00 (d, J = 2.9 Hz, 0.50 H), 5.97 (d, J = 2.9 Hz, 0.50
H), 5.83 (s, 1 H), 5.09 (d, J = 5.0 Hz, 0.50 H), 5.06 (d, J = 5.0 Hz,
0.50 H), 4.36 (d, J = 4.1 Hz, 0.52 H), 4.33 (d, J = 4.1 Hz, 0.50 H),
4.10 (q, J = 7.1 Hz, 1 H), 4.03 (q, J = 7.1 Hz, 1 H), 2.22 (s, 3 H),
2.19 (s, 1.50 H), 2.11 (s, 1.50 H), 1.16 (t, J = 7.1 Hz, 1.50 H), 1.09
(t, J = 7.1 Hz, 1.50 H).
13C NMR (101 MHz, CDCl3): δ = 200.8, 167.0, 166.9, 151.7, 151.5,
151.4, 151.3, 142.2, 142.0, 126.7, 126.5, 126.0, 125.6, 124.7, 124.5,
107.6, 107.1, 106.3, 106.1, 65.3, 65.0, 61.6, 39.7, 30.4, 29.5, 13.9,
13.78, 13.5, 13.4.
1H NMR (400 MHz, CDCl3): δ = 7.34–7.24 (m, 4 H), 7.22–7.17 (m,
1 H), 5.95 (d, J = 3.0 Hz, 0.50 H), 5.91 (d, J = 3.0 Hz, 0.50 H), 5.81
(s, 1 H), 4.76 (d, J = 3.8 Hz, 0.50 H), 4.73 (d, J = 3.8 Hz, 0.50 H),
4.39 (d, J = 4.3 Hz, 0.50 H), 4.36 (d, J = 4.3 Hz, 0.50 H), 4.12 (q,
J = 4.12 Hz, 1 H), 3.91 (q, J = 4.12 Hz, 1 H), 2.23 (s, 1.50 H), 2.20
(s, 3 H), 1.99 (s, 1.50 H), 1.18 (t, J = 7.1 Hz, 1.50 H), 0.96 (t, J = 7.1
Hz, 1.50 H).
13C NMR (101 MHz, CDCl3): δ = 201.3, 201.0, 167.5, 167.1, 152.5,
152.1, 151.3, 151.2, 139.2, 138.9, 128.6, 128.3, 128.2, 128.2, 127.1,
127.1, 107.3, 106.8, 106.2, 106.0, 64.4, 64.1, 61.5, 61.3, 44.7, 44.7,
30.2, 29.3, 13.9, 13.6, 13.39, 13.4.
HRMS (ESI): m/z calcd for C16H19O4S [M + H]+ 307.1004; found:
307.1007.
HRMS (ESI): m/z calcd for C18H21O4 [M + H]+: 301.1440; found:
301.1428.
Polysubstituted Furans 7; General Procedure
5p
A mixture of 5 (0.3 mmol), AcOH (10 mol%), CuBr2 (10% mol),
and MeCN (5 mL) was stirred at 50 °C until the disappearance of
the starting material according to TLC (eluent: PE–EtOAc, 8:1).
The reaction was quenched with H2O (5 mL) and extracted with
EtOAc (3 × 5 mL). The combined organic extracts were washed
with brine (5 mL), dried (Na2SO4), filtered, and concentrated. The
residue was purified by flash chromatography on silica gel (eluent:
PE–EtOAc, 20:1).
Yield: 336 mg (56%); colorless gum.
IR (film): 2926, 2838, 1700, 1610, 1560, 1511, 1459, 1357, 1251,
1180, 1029, 953, 837, 786, 542 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.17 (d, J = 8.7 Hz, 2 H), 6.77 (d,
J = 8.7 Hz, 2 H), 5.84 (d, J = 3.0 Hz, 1 H), 5.77 (d, J = 3.0 Hz, 1 H),
4.72 (d, J = 12.0 Hz, 1 H), 4.52 (d, J = 12.0 Hz, 1 H), 3.69 (s, 3 H),
2.14 (s, 3 H), 2.12 (s, 3 H), 1.89 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 202.2, 202.0, 158.5, 152.5, 151.2,
7a
Yield: 55.7 mg (83%); colorless oil.
IR (film): 2925, 1713, 1584, 1420, 1367, 1227, 1082, 777 cm–1.
1H NMR (400 MHz, CDCl3): δ = 6.23 (s, 1 H), 4.25 (q, J = 7.1 Hz,
2 H), 2.83 (t, J = 7.2 Hz, 2 H), 2.75 (t, J = 7.2 Hz, 2 H), 2.50 (s, 3
H), 2.16 (s, 3 H), 1.32 (t, J = 7.1 Hz, 4 H).
130.9, 129.0, 113.9, 106.9, 106.0, 73.3, 54.8, 44.1, 30.0, 28.6, 13.2.
HRMS (ESI): m/z calcd for C18H21O4 [M + H]+: 301.1440; found:
301.1449.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3735–3742

3740
B. Yin et al.
PAPER
13C NMR (101 MHz, CDCl3): δ = 206.8, 164.2, 157.8, 152.4, 114.0,
106.0, 60.0, 41.4, 29.9, 21.8, 14.3, 13.6.
13C NMR (101 MHz, CDCl3): δ = 206.4, 164.1, 157.8, 152.2, 133.9,
129.3, 128.7, 127.1, 113.9, 106.0, 59.9, 50.2, 39.6, 21.8, 14.3, 13.6.
HRMS (ESI): m/z calcd for C12H16O4 [M + H]+: 255.1121; found:
255.1122.
HRMS (ESI): m/z calcd for C18H20O4 [M + H]+: 301.1434; found:
301.1434.
7b
7i
Yield: 48 mg (83%); colorless oil.
Yield: 29 mg (31%); colorless oil.
IR (KBr): 2920, 1714, 1673, 1563, 1398, 1363, 948, 672 cm–1.
1H NMR (400 MHz, CDCl3): δ = 6.20 (s, 1 H), 2.83 (t, J = 6.8 Hz,
2 H), 2.76 (t, J = 6.8 Hz, 2 H), 2.51 (s, 3 H), 2.34 (s, 3 H), 2.16 (s, 3
H).
13C NMR (100 MHz, CDCl3): δ = 206.8, 194.16, 157.0, 152.3,
122.0, 105.9, 41.3, 29.9, 29.0, 21.7, 14.3.
HRMS (ESI): m/z calcd for C11H14O3 [M + H]+: 195.1016; found:
195.1015.
IR (KBr): 2966, 2932, 1708, 1578, 1453, 1286, 1205, 1092, 740,
689 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 7.2 Hz, 2 H), 7.56 (t,
J = 7.4 Hz, 1 H), 7.46 (t, J = 7.6 Hz, 2 H), 4.28 (q, J = 7.2 Hz, 2 H),
3.28 (t, J = 7.6 H, 2 H), 2.98 (t, J = 7.6 Hz, 2 H), 2.57 (q, J = 7.4 Hz,
2 H), 2.49 (s, 3 H), 1.34 (t, J = 7.1 Hz, 3 H), 1.10 (t, J = 7.4 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 198.8, 164.7, 158.0, 147.9, 136.7,
133.1, 128.6, 128.0, 121.76, 77.3, 77.00 76.7, 59.7, 37.3, 20.2, 17.5,
15.5, 14.3.
HRMS (ESI): m/z calcd for C19H22O4 [M + H]+: 315.1591; found:
315.1590.
7c
Yield: 36 mg (38%); colorless syrup.
IR (KBr): 2986, 2256, 1737, 1651, 1374, 1243, 1047, 913, 732, 692
cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.81 (d, J = 7.6 Hz, 2 H), 7.63 (d,
J = 6.0 Hz, 2 H), 7.49 (t, J = 7.1 Hz, 1 H), 7.37 (d, J = 7.5 Hz, 2 H),
6.32 (s, 1 H), 3.00 (t, J = 7.1 Hz, 2 H), 2.87 (t, J = 7.2 Hz, 2 H), 2.20
(s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 206.6, 191.8, 154.6, 153.6, 138.0,
132.7, 129.8, 129.6, 128.7, 128.2, 128.2, 127.3, 121.6, 109.4, 41.3,
29.9, 21.9.
7k
Yield: 64 mg (84%); colorless oil.
IR (KBr): 2971, 2898, 1712, 1581, 1422, 1367, 1290, 1167, 1093,
911, 739 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.26 (q, J = 7.1 Hz, 2 H), 2.79 (t,
J = 6.4 Hz, 2 H), 2.72 (t, J = 6.8 Hz, 2 H), 2.52 (q, J = 7.4 Hz, 2 H),
2.47 (s, 3 H), 2.14 (s, 3 H), 1.33 (t, J = 7.1 Hz, 3 H), 1.07 (t, J = 7.4
Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 207.0, 164.1, 157.6, 149.0, 132.8,
129.9, 127.6, 126.9, 121.8, 113.7, 59.7, 41.7, 29.7, 20.2, 14.0, 13.8.
HRMS (ESI): m/z calcd for C14H20O4 [M + H]+: 253.1434; found:
253.1431.
HRMS (ESI): m/z calcd for C21H18O3 [M + H]+: 319.1329; found:
319.1328.
7d
Yield: 30 mg (41%); colorless oil.
7l
IR (KBr): 2920, 2223, 1714, 1601, 1555, 1451, 1303, 1260, 1155,
913, 807, 771, 688 cm–1.
Yield: 83 mg (88%); colorless oil.
IR (KBr): 2984, 2924, 1711, 1582, 1423, 1365, 1290, 1161, 1099,
780, 705 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.23 (t, J = 7.4 Hz, 2 H), 7.13 (t,
J = 8.2 Hz, 3 H), 4.15 (q, J = 7.1 Hz, 2 H), 3.97 (s, 2 H), 2.82 (t, J =
7.4 Hz, 1 H), 2.68 (t, J = 7.4 Hz, 1 H), 2.51 (s, 2 H), 2.11 (s, 1 H),
1.17 (t, J = 7.1 Hz, 2 H).
13C NMR (101 MHz, CDCl3): δ = 207.0, 164.5, 158.2, 149.4, 141.0,
128.1, 128.0, 125.6, 117.9, 113.4, 59.7, 41.6, 29.8, 29.6, 20.0, 14.2,
14.1.
1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 7.5 Hz, 2 H), 7.50–
7.35 (m, 3 H), 6.29 (s, 1 H), 2.97 (t, J = 7.2 Hz, 2 H), 2.84 (t, J = 7.2
Hz, 2 H), 2.20 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 206.1, 158.5, 151.0, 130.0, 129.0,
128.2, 125.1, 115.0, 108.8, 91.9, 41.0, 29.9, 21.7.
HRMS (ESI): m/z calcd for C10H11NO2 [M + H]+: 177.0790; found:
177.0782.
7e
HRMS (ESI): m/z calcd for C19H22O4 [M + H]+: 315.1591; found:
Yield: 53 mg (65%); colorless syrup.
315.1590.
IR (KBr): 3320, 2922, 2853, 1712, 1651, 1527, 1439, 1384, 1316,
1231, 1070, 808, 692 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.56 (d, J = 7.9 Hz, 2 H), 7.47 (s,
1 H), 7.32 (t, J = 7.9 Hz, 2 H), 7.10 (t, J = 7.4 Hz, 1 H), 6.16 (s, 1
H), 2.86 (t, J = 7.0 Hz, 2 H), 2.78 (t, J = 6.8 Hz, 2 H), 2.56 (s, 3 H),
2.17 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 207.0, 162.2, 156.5, 152.6, 137.8,
129.0, 124.3, 120.2, 116.3, 103.9, 41.4, 30.0, 29.7, 21.8, 13.6.
HRMS (ESI): m/z calcd for C16H17NO3 [M + H]+: 272.1281; found:
272.1281.
7m
Yield: 77 mg (84%); colorless oil.
IR (KBr): 2927, 2854, 1713, 1616, 1575, 1416, 1366, 1289, 1164,
1090, 785, 572 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.24 (q, J = 7.1 Hz, 2 H), 2.86 (t,
J = 7.6 Hz, 3 H), 2.71 (d, J = 7.4 Hz, 2 H), 2.42 (s, 3 H), 2.14 (s, 3
H), 1.78–1.57 (m, 7 H), 1.39–1.22 (m, 6 H).
13C NMR (101 MHz, CDCl3): δ = 207.3, 164.8, 157.3, 147.4, 124.6,
113.3, 59.7, 42.3, 34.9, 32.3, 29.8, 27.1, 26.0, 21.4, 14.4, 14.3.
HRMS (ESI): m/z calcd for C18H26O4 [M + H]+: 307.1904; found:
307.1903.
7h
Yield: 71 mg (79%); colorless oil.
IR (KBr): 2924, 1711, 1584, 1412, 1225, 1081, 776, 735, 700 cm–1.
7n
1H NMR (400 MHz, CDCl3): δ = 7.36–7.24 (m, 3 H), 7.19 (d, J =
7.0 Hz, 2 H), 6.17 (s, 1 H), 4.25 (q, J = 7.1 Hz, 2 H), 3.70 (s, 2 H),
2.85–2.79 (m, 2 H), 2.79–2.73 (m, 2 H), 2.48 (s, 3 H), 1.32 (t, J =
7.1 Hz, 3 H).
Yield: 58 mg (71%); colorless oil.
IR (KBr): 2923, 1714, 1673, 1559, 1361, 1313, 1163, 952, 761, 701,
cm–1.
Synthesis 2012, 44, 3735–3742
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Polysubstituted Furans
3741
1H NMR (400 MHz, CDCl3): δ = 7.42–7.32 (m, 3 H), 7.24 (d, J =
7.8 Hz, 2 H), 2.75 (t, J = 6.4 Hz, 2 H), 2.70 (t, J = 6.4 Hz, 2 H), 2.51
(s, 3 H), 2.10 (s, 3 H), 1.88 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 206.9, 196.0, 156.5, 148.9, 133.2,
129.9, 128.5, 127.6, 123.0, 121.1, 41.6, 30.7, 29.8, 20.2, 14.2.
HRMS (ESI): m/z calcd for C17H18O3 [M + H]+: 271.1328, found:
271.1328.
1H NMR (400 MHz, CDCl3): δ = 7.31 (d, J = 5.2 Hz, 1 H), 7.02 (dd,
J = 5.1, 3.5 Hz, 1 H), 6.95 (d, J = 2.4 Hz, 1 H), 4.14 (q, J = 7.1 Hz,
2 H), 2.87 (t, J = 7.4 Hz, 2 H), 2.72 (t, J = 7.4 Hz, 2 H), 2.54 (s, 3
H), 2.12 (s, 3 H), 1.14 (t, J = 7.1 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 206.9, 163.8, 157.8, 150.9, 133.0,
127.9, 126.6, 125.6, 125.1, 114.5, 114.2, 59.9, 41.7, 29.8, 20.5,
14.0, 13.9.
HRMS (ESI): m/z calcd for C16H18O4S [M + H]+: 307.0999; found:
307.0994.
7o
Yield: 57 mg (70%); colorless oil.
IR (KBr): 2925, 1708, 1708, 1578, 1415, 1313, 1170, 1096, 758,
700 cm–1.
Acknowledgment
1H NMR (400 MHz, CDCl3): δ = 7.37–7.27 (m, 3 H), 7.22 (d, J =
7.0 Hz, 2 H), 4.08 (q, J = 7.1 Hz, 2 H), 2.80 (t, J = 7.0 Hz, 2 H), 2.70
(d, J = 7.2 Hz, 2 H), 2.56 (s, 3 H), 2.09 (s, 3 H), 1.05 (t, J = 7.1 Hz,
3 H).
This work was supported by the Fundamental Research Funds for
the Central Universities (2012ZZ043), the National Natural Science
Foundation of China (21072062, 21272078), and the Natural
Science Foundation of Guangdong Province, China
(10351064101000000).
13C NMR (101 MHz, CDCl3): δ = 207.0, 164.1, 157.6, 149.0, 132.8,
129.9, 127.6, 126.9, 121.8, 113.7, 59.7, 41.7, 29.7, 20.2, 14.0, 13.8.
HRMS (ESI): m/z calcd for C18H20O4 [M + H]+: 301.1434; found:
301.1433.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
itmnatr
7p
Yield: 34.2 mg (38%); colorless oil.
References
IR (KBr): 2925, 1710, 1674, 1605, 1563, 1512, 1361, 1172, 1029,
953, 836 cm–1.
(1) For selected reviews, see: (a) Keay, B. A.; Hopkins, J. M.;
Dibble, P. W. In Comprehensive Heterocyclic Chemistry III;
Vol. 3; Katritzky, A. R.; Ramsden, C. A.; Scriven, E. F. V.;
Taylor, R. J. K., Eds.; Elsevier: Amsterdam, 2008, 571.
(b) d’Ischia, M.; Napolitano, A.; Pezzella, A. In
1H NMR (400 MHz, CDCl3): δ = 7.17 (d, J = 8.5 Hz, 2 H), 6.93 (d,
J = 8.6 Hz, 2 H), 3.83 (s, 3 H), 2.79–2.72 (m, 2 H), 2.72–2.66 (m, 2
H), 2.51 (s, 3 H), 2.10 (s, 3 H), 1.90 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 207.0, 196.1, 159.1, 156.4, 148.9,
131.0, 125.3, 123.1, 120.7, 114.3, 114.0, 55.2, 41.6, 30.7, 29.8,
20.2, 14.3.
Comprehensive Heterocyclic Chemistry III; Vol. 3;
Katritzky, A. R.; Ramsden, C. A.; Scriven, E. F. V.; Taylor,
R. J. K., Eds.; Elsevier: Amsterdam, 2008, 353. (c) Lipshutz,
B. H. Chem. Rev. 1986, 86, 795.
HRMS (ESI): m/z calcd for C18H20O4 [M + H]+: 271.1329; found:
271.1329.
(2) For reviews concerning the dearomatization of furan ring,
see: (a) Roche, S. P.; Poreo, J. A. Jr. Angew. Chem., Int. Ed.
Engl. 1996, 35, 729. (b) Bur, S. K.; Padwa, A. Chem. Rev.
2004, 104, 2401.
7q
Yield: 81 mg (85%); colorless oil.
(3) (a) Cagniant, P.; Cagniant, D. In Advances in Heterocyclic
Chemistry; Vol. 18; Katritzky, A. R.; Boulton, A. J., Eds.;
Academic Press: New York, 1975, 337. (b) Dean, F. M.;
Sargent, M. V. In Comprehensive Heterocyclic Chemistry;
Vol. 4; Katritzky, A. R.; Rees, C. W., Eds.; Pergamon: New
York, 1984, 531. (c) Cacchi, S. J. Organomet. Chem. 1999,
576, 42. (d) Hou, X. L. H.; Cheung, Y.; Hon, T. Y.; Kwan,
P. L.; Lo, T. H.; Tong, S. Y.; Wong, H. N. C. Tetrahedron
1998, 54, 1955.
(4) For selected references concerning the dearomatization of
furans, see: (a) Toró, A.; Deslongchamps, P. J. Org. Chem.
2003, 68, 6847. (b) Liu, L.; Gao, Y.; Che, C.; Wu, N.; Wang,
D. Z.; Li, C.-C.; Yang, Z. Chem. Commun. 2009, 662.
(5) (a) Yim, H.-K.; Wong, H. N. C. J. Org. Chem. 2004, 69,
2892. (b) McDermott, P. J.; Stockman, R. A. Org. Lett.
2005, 7, 27. (c) Georgiou, T.; Tofi, M.; Montagnon, T.;
Vassilikogiannakis, G. Org. Lett. 2006, 8, 1945. (d) Zhou,
X.; Wu, W.; Liu, X.; Lee, C.-S. Org. Lett. 2008, 10, 5525.
(e) Abrams, J. N.; Babu, R. S.; Guo, H.; Le, D.; Le, J.;
Osbourn, J. M. G.; O’Doherty, A. J. Org. Chem. 2008, 73,
1935. (f) Bi, J.; Aggarwal, V. K. Chem. Commun. 2008, 120.
(g) Pavlakos, E.; Georgiou, T.; Tofi, M.; Montagnon, T.;
Vassilikogiannakis, G. Org. Lett. 2009, 11, 4556. (h) Dong,
J.-Q.; Wong, H. N. C. Angew. Chem. Int. Ed. 2009, 48, 2351.
(i) Hatano, M.; Mizuno, T.; Ishihara, K. Chem. Commun.
2010, 46, 5443. (j) Veits, G. K.; Wenz, D. R.; Read de
Alaniz, J. Angew. Chem. Int. Ed. 2010, 49, 9484.
IR (KBr): 2927, 2854, 1713, 1616, 1575, 1416, 1366, 1289, 1164,
1090, 785, 572 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.17 (m, 4 H), 4.11 (q, J = 7.1 Hz,
2 H), 2.79 (t, J = 7.0 Hz, 2 H), 2.70 (t, J = 6.6 Hz, 2 H), 2.55 (s, 3
H), 2.36 (s, 3 H), 2.09 (s, 3 H), 1.10 (t, J = 7.1 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 207.0, 164.1, 157.4, 148.9, 136.5,
129.8, 129.7, 128.4, 121.7, 113.7, 59.7, 41.7, 29.7, 21.1, 20.3, 14.1,
13.9.
HRMS (ESI): m/z calcd for C19H22O4 [M + H]+: 315.1591; found:
315.1590.
7r
Yield: 33 mg (35%); colorless oil.
IR (KBr): 2924, 2825, 1715, 1673, 1598, 1561, 1517, 1347, 1165,
956, 854 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.24 (d, J = 8.8 Hz, 2 H), 7.44 (d,
J = 8.7 Hz, 2 H), 2.75 (br, 4 H), 2.54 (s, 3 H), 2.12 (s, 3 H), 2.04 (s,
3 H).
13C NMR (101 MHz, CDCl3): δ = 206.4, 194.4, 157.0, 149.9, 147.1,
140.5, 130.7, 123.5, 122.8, 119.7, 401.0, 30.7, 29.8, 12.0, 14.5.
HRMS (ESI): m/z calcd for C17H17NO5 [M + H]+: 316.1180; found:
316.1172.
7s
Yield: 52 mg (57%); colorless oil.
(k) Noutsias, D.; Kouridaki, A.; Vassilikogiannakis, G. Org.
Lett. 2011, 13, 1166. (l) Egan, B. A.; Paradowski, M.;
IR (KBr): 2926, 1701, 1649, 1540, 1515, 1459, 1422, 1395, 671
cm–1.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3735–3742

3742
B. Yin et al.
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© Georg Thieme Verlag Stuttgart · New York