Formal [2+2+1] Synthesis of Tetrasubstituted Furans from Aldehydes, Acetylenedicarboxylates, and Acyl Compounds

Article abstract of DOI:10.1002/ejoc.201900806

A combination of 4-picoline and Ph₃P (or ⁿBu₃P) efficiently promotes a formal [2+2+1] synthesis of tetrasubstituted furans from aldehydes, acetylenedicarboxylates and acyl compounds under the metal-free and mild conditions. The present method can be applied not only to acyl chlorides but also trifluoroacetic anhydride as the acyl compounds. These furan products were formed in moderate to excellent yields via O-acylation of the α,β-enone intermediates followed by intramolecular Wittig reaction. From the results of control experiments, it was found that 4-picoline would serve as a promoter in the formation of both α,β-enones and O-acyl intermediates as well as a base for capturing of the generated acid.

Full text of DOI:10.1002/ejoc.201900806

A Journal of
Accepted Article
Title: Formal [2+2+1] Synthesis of Tetrasubstituted Furans from
Aldehydes, Acetylenedicarboxylates and Acyl Compounds
Authors: Keiichiro Tateishi, Yuri Matsumoto, and Akio Saito
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900806
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10.1002/ejoc.201900806
European Journal of Organic Chemistry
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Formal [2+2+1] Synthesis of Tetrasubstituted Furans from
Aldehydes, Acetylenedicarboxylates and Acyl Compounds
Keiichiro Tateishi,[a] Yuri Matsumoto,[a] and Akio Saito*[a]
Dedication ((optional))
Abstract: A combination of 4-picoline and Ph3P (or nBu3P) efficiently
promotes a formal [2+2+1] synthesis of tetrasubstituted furans from
aldehydes, acetylenedicarboxylates and acyl compounds under the
metal-free and mild conditions. The present method can be applied
not only to acyl chlorides but also trifluoroacetic anhydride as the
acyl compounds. These furan products were formed in moderate to
excellent yields via O-acylation of the α,β-enone intermediates
followed by intramolecular Wittig reaction. From the results of control
experiments, it was found that 4-picoline would serve as promoters
in both formation of α,β-enones and O-acyl intermediates as well as
a base for capture of acid.
conditions (Scheme 1a, method A).[13] This strategy was
extended to the synthesis of 2-trifluoromethylfurans, which are
useful as basic structures of pharmacologically active
compounds,[1c-f] from enones and trifluoroacetic anhydride
(TFAA, method B) by Xu et al.[14] Very recently, He et al.
developed a three-component approach for the furan synthesis
via direct generation of phosphonium enolate zwitterions,[15]
which are similar intermediates to those of Lin’s method,[12] from
dialkyl acetylenedicarboxylates and aldehydes with nBu3P
(Scheme 1b).[16] Unfortunately, there is still room for
improvement of the product yields in He’s method, which was
not applied to carboxylic anhydrides instead of acyl chlorides.
Introduction
Highly functionalized furan rings are very important fundamental
heterocyclic motifs found broad applications in medicinal,
agrochemical, and material science.[1] Furans have also been
frequently used as building blocks in synthetic chemistry.[2]
Therefore, many synthetic routes toward furan rings with specific
substitution patterns have been developed.[3] For the
construction of tetrasubstituted furans, Paal-Knorr synthesis and
its variants,[4] Feist-Bénary synthesis and its variants,[5] metal-
catalyzed cyclization of highly substituted unsaturated ketones
and alcohols,[6] formal [3+2] annulation of 1,3-dicarbonyl
compounds with propargyl ester or alcohol[7] and oxidative
annulation of 1,3-dicarbonyl compounds with alkenes or
alkynes[8] have been well studied.[9] However, the preparation of
the highly substituted precursors requires multiple steps.
Although
metal-mediated/catalyzed
formal
[2+2+1]
annulations[10] and metal-free methods using isocyanides[11]
have been known as facile assembly tools of tetrasubstituted
furans from relatively simple building blocks, these procedures
are met with complicated operations and/or substrate limitations.
Thus, the development of efficient synthetic methods of the
tetrasubstituted furans with flexible substituent patterns still has
been a challenging goal.
Lin et al. recently reported an elegant domino formation of
polysubstituted furans from α,β-enones and acyl chlorides in
single operation,[12] which proceed via nBu3P-mediated O-
acylation/intramolecular Wittig reaction sequence under mild
Scheme 1. Synthetic methods of polysubstituted furans.
As part of our continuing studies on the metal-free and domino
synthesis of heterocycles via the formation of α,β-enones from
alkynes and carbonyl compounds,[17] we disclosed the formal
[2+2+2] synthesis of pyrans based on the hetero-Diels-Alder
reactions of alkenes with enones formed from aldehydes and
acetylenedicarboxylates[18] by 2-picoline catalyst (Scheme
1c).[17e] As a further extension of our methods, we herein
describe formal [2+2+1] synthesis of tetrasubstituted furans from
aldehydes, acetylenedicarboxylates and acyl compounds using
4-picoline and Ph3P (or nBu3P). Although it is concerned that
[a]
K. Tateishi, Y. Matsumoto, Prof. Dr. A. Saito,
Division of Applied Chemistry, Institute of Engineering,
Tokyo University of Agriculture and Technology,
Koganei, Tokyo 184-8588, Japan
E-mail: akio-sai@cc.tuat.ac.jp.
Homepage: http://web.tuat.ac.jp/~akio-sai/index.html
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/ejoc.201900806
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triaryl phosphine promotes the production of γ-butenolides from
To our surprise, although the use of Ph3P in the absence of
amine afforded γ-butenolide 4 (44%) from 1a and 2 as
expected,[19] the desired furans 3a was obtained in 54% yield as
a main product (entry 1). Furthermore, the addition of pyridine (1
or 2 equiv, entry 2 or 3) improved the yields of 3a up to 73%
(entry 3). On the other hands, when nBu3P or (PhO)3P was
employed instead of Ph3P (entry 4 or 5) and when relatively
acetylenedicarboxylates
with
aldehydes
or
carboxylic
anhydrides,[19] the present method can be applied not only to
acyl chlorides but also carboxylic anhydrides such as TFAA
(Scheme 1d). Furthermore, it was found from the results of
control experiments that enone intermediates would be involved
in these reactions.
strong bases (pKa
=
18.2–24.1)[20] such as 1,4-
(DABCO), 1,8-
diazabicyclo[2.2.2]octane
diazabicyclo[5.4.0]undec-7-ene (DBU), Et3N and N,N-dimethyl-
4-aminopyridine (DMAP) were added instead of pyridine (pKa =
12.5,[20] entries 6–9), the yields of 3a were reduced due to
slower reaction (recovery of 1a: 32%, entry 5) or complicated
mixtures (entries 4, 6–9). However, pyridines such as 2,4,6-
collidine, 2,6-lutidine and 4-picoline (pKa = 14.1–15.0)[20] in the
presence of Ph3P gave relatively good results (entries 10–12). In
particular, 4-picoline (2.5 equiv) improved the yields of 3a up to
84% without the detection of 4 (entry 13). It should be mentioned
that the combination of nBu3P and Et3N in THF reported by Lin[12]
and He[16] did not show better results (entry 15).
Results and Discussion
Based on our reports on the formal [2+2+2] annulations[17e] and
Xu’s synthesis of 2-trifluoromethylfurans[14] (Scheme 1a, c), we
attempted the formation of 2-trifluoromethylfurans 3a from
aldehyde 1a, dimethyl acetylenedicarboxylate (DMAD, 2, 1.2
equiv) and trifluoroacetic anhydride (TFAA, 1.5 equiv) in the
presence of various amine and phosphines (1.0 equiv) in
dichloromethane (DCM) at room temperature (Table 1).
Under the optimized reaction conditions, the scope for the
synthesis of 2-trifluoromethylfurans 3 from various aldehydes 1,
DMAD (2, 1.2 equiv) and TFAA (1.5 equiv) is summarized in
Table 2. Similar to 3-nitrobenzaldehyde (1a, entry 1), aromatic
aldehyde 1b–f bearing electron-withdrawing groups were
smoothly converted to the corresponding furans 3b–f within 24 h
in 73–83% yields (entries 2–6). On the other hand, in cases of
Table 1. Optimization of the reaction conditions.
n
Entry
1
R3P
Amine (equiv.)
None
3a [%]
54
4 [%]
44
31
23
22
0[b]
0
benzaldehyde (1g) and furfural (1h), the use of Bu3P instead of
Ph3P gave better results (3g: 42%, 3h: 53%, entries 7 and 8).
Ph3P
Ph3P
Ph3P
nBu3P
(PhO)3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
nBu3P
2
Pyridine (1.0)
Pyridine (2.0)
Pyridine (2.0)
Pyridine (2.0)
DABCO (2.0)
DBU (2.0)
65
Table 2. Scope for the synthesis of 2-CF3-substituted furans 3.
3
73
4
63
5
25[a]
54[a]
36[a]
38[a]
24[a]
50[a]
68[a]
81
6
Entry
1
R
3
Yield [%]
7
0
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
3-NO2C6H4
2-NO2C6H4
4-NO2C6H4
4-CNC6H4
4-CF3C6H4
4-BrC6H4
Ph
3a
3b
3c
3d
3e
3f
84
8
Et3N (2.0)
9[a]
ND[c]
16[a]
14[a]
9
76
9
DMAP (2.0)
83
10
11
12
13
14
15[d]
2,4,6-collidine (2.0)
2,6-lutidine (2.0)
4-picoline (2.0)
4-picoline (2.5)
4-picoline (3.0)
Et3N (1.2)
81
73
76
84
0
1g
1h
3g
3h
34 (42)[a]
39 (53)[a]
76
0
2-furyl
84
4
[a] Values in parentheses were yields using nBu3P instead of Ph3P.
[a] Yields were determined by 1H NMR analysis. [b] Recovery of 1a: 32%. [c]
Not determined. [d] nBu3P: 1.5 equiv, solvent: THF.
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10.1002/ejoc.201900806
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Notably, the present methods could not be applied to aliphatic
t
i
aldehydes such as BuCHO, PrCHO and EtCHO. It was known
that the base-catalyzed formation of a,b-enones from aliphatic
aldehydes and DMAD (2) did not proceed efficiently.18
In order to gain an insight into the involvement of α,β-enone 8 as
the intermediate, we carried out the formation of 8 from
aldehyde 1a with DMAD (2) as control experiments (Scheme 2).
By solely using 4-picoline (1 equiv) in DCM at room temperature,
enone 8 was obtained in good yield (75%). On the other hand,
regardless of the presence or absence of 4-picoline, Ph3P (1
equiv) afforded γ-butenolide 4 (40% or 27%) along with enone 8
(42% or 46%). However, when the amount of 4-picoline was
increased up to 2.5 equiv, the yield of 8 was increased up to
69% albeit γ-butenolide 4 was formed (31%). Considering that γ-
butenolides were not detected in the present synthesis of furans
3, 6 and 7 using Ph3P and 4-picoline, the formation process of
α,β-enone would be involved as a main route to the furans.
Notably, the both conversion of 8 into 4 by Ph3P and of 4 into 8
by 4-picoline were not actually observed. Therefore, 4-picoline
would play the role as a major promoter in the formation of 8
under the optimal conditions, although the involvement of Ph3P
Subsequently, we examined a formal [2+2+1] synthesis of other
substituted furans using various acyl chlorides 5 or other
carboxylic anhydrides (Table 3). To our delight, regardless of
aromatic and aliphatic acyl chlorides (1.5 equiv), the
combination of Ph3P and 4-picoline promoted the reaction of
aldehyde 1a and DMAD (2, 1.2 equiv) to give the corresponding
furans 6a–j in high yields (74%–quant) at room temperature
n
(entries 1-10). Also, by using Bu3P instead of Ph3P, furans 7c
and 7g were obtained from benzaldehyde (1g), DMAD (2) and
acyl chlorides 5c or 5g in better yields (7c: 56%, 7g: 50%,
entries 11 and 12). Unfortunately, even when 3 equiv of acetic
anhydride (Ac2O) was employed instead of acetyl chloride (5a),
the yield of 6a was reduced up to 58% along with the formation
of α,β-enone 8 in 26% yield (entry 1). Assuming that α,β-enone
8 is formed from 1a and 2[17e,18,19b,c] as an intermediate converted
to furans 6, this result suggest that the part of intermediate 8
would be recovered due to lower acylation ability of Ac2O.
n
cannot be ignored. On the other hand, the use of Bu3P instead
of Ph3P even in the presence of 4-picoline (2.5 equiv) gave
enone 8 in only 20%, albeit no formation of γ-butenolide 4
(Scheme 2). This result suggests that α,β-enone intermediates
would partially be involved in the 4-picoline/nBu3P-mediated
reactions. It is known that the phosphonium enolate zwitterions
(like intermediates shown in Scheme 1b), derived from
alkynoates and aldehydes with trialkylphosphines, are relatively
stable.[15]
Table 3. Scope for the synthesis of furans 6.
Entry
1
5
R
6 or 7
6a
6b
6c
6d
6e
6f
Yield [%]
74 (58)[a]
86
5a
5b
5c
5d
5e
5f
Me
2
iPr
3
tBu
quant
92
4
Ph
5
2-ClC6H4
3-ClC6H4
4-ClC6H4
4-NO2C6H4
4-MeC6H4
4-MeOC6H4
tBu
82
Scheme 2. Formations of 8 from 1a and 2.
6
87
Next, the conversions of 3a or 6d from α,β-enone 8 with TFAA
or PhCOCl were checked as part of control experiments
7
5g
5i
6g
6h
6i
89
8
89
(Scheme
3).
Similar
to
Xu’s
synthesis
of
2-
trifluoromethylfurans,[14] in the absence of 4-picoline, Ph3P led to
the formation of furan 3a from 8 and TFAA in quantitative yield
at room temperature within 5 min. Interestingly, the sole use of
Ph3P or nBu3P also promoted the reaction of 8 with benzoyl
chloride (5d) to give furans 6d in high yields (97% in both cases),
although amines were required for the deprotonation of O-acyl
intermediates to phosphonium ylides in the Lin’s furan synthesis
using nBu3P.[12] Therefore, the deprotonation to phosphonium
ylides would be occurred by chloride anions and thus amines
would essentially work as scavengers of the generated HCl in
the present methods.
9
5j
82
10
11
12
5k
5c
5g
6j
81
7c
7g
31 (56)[b]
32 (50)[b]
4-ClC6H4
[a] Value in parenthesis was yield using Ac2O (3 equiv) instead of 5a. In this
case, α,β-enone 7 was formed in 26% yield. [b] Values in parentheses were
yields using nBu3P instead of Ph3P.
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10.1002/ejoc.201900806
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Conclusions
We have developed
a
formal [2+2+1] synthesis of
tetrasubstituted furans from aldehydes, alkynoates and TFAA or
acyl chlorides using 4-picoline and Ph3P (or nBu3P) under metal-
free and mild conditions. Furthermore, from the results of control
experiments, we proposed that α,β-enones would be involved as
intermediates and 4-picoline would play not only the role of base
for capture of acid but also that of promoter in both formation of
α,β-enones and O-acyl intermediates. Although the similar
[2+2+1] method has been reported by He et al., our findings
provide an alternative procedure for the access to the
polysubstituted furans including 2-trifluoromethylfurans in
relatively good yields.
Scheme 3. Formations of 3a or 6d from 8 with TFAA or 5d.
On the basis of these results and previous reports of
phosphines-mediated syntheses of furans,[12–16] a mechanism for
the formal [2+2+1] synthesis of furans 3, 6 and 7 was proposed
(Scheme 4). Initially, DMAD (2) undergo a Michael-type addition
Experimental Section
n
with 4-picoline or R3P (R = Ph or Bu) to from enolates A, which
react with aldehydes 1 giving rise to intermediates B. Next, a C-
to-O 1,2-H-shift of the intermediates B followed by a O-to-C 1,4-
H-shift of the intermediates C afford α,β-enones E after an
elimination of 4-picoline or R3P in intermediates D (path a).
Since 4-picoline is mainly involved in a series of these
processes, γ-butenolide 4 would be not formed from the
intermediates B (path c).[19a–c] Subsequently, the α,β-enones E
are converted to intermediates F via the regeneration of the
intermediates D by R3P and an O-acylation of D with acyl
compounds. Part of the phosphonium intermediates D (B = R3P)
directly undergo the O-acylation with acyl compounds (path b).
Possibly, 4-picoline promotes the O-acylation of D via the
generation of N-acyl pyridinium intermediates.[21] Finally, after
deprotonation of the intermediates F along with capture of acid
(X = CF3COO or Cl) by 4-picoline, an intramolecular Wittig
reaction of the resulting ylides F occurs furans.
General information. 4-Picoline, triphenylphosphine tri-n-butylphosphine,
aldehydes 1a–h, dimethyl acetylenedicarboxylate (2), trifluoroacetic
anhydride (TFAA), and acyl chlorides 5a–j are commercially available.
Products 4[19b] and 8[18b] are known compounds. Dichloromethane (DCM)
was purchased as the “anhydrous” and used without further purification.
1H and 13C NMR spectra were measured at 500 (or 300) and 125 (or 75)
MHz in CDCl3, and the chemical shifts are given in ppm using CHCl3
(7.26 ppm) in CDCl3 for 1H NMR and CDCl3 (77.0 ppm) for 13C NMR as
an internal standard, respectively. Splitting patterns of an apparent
multiplet associated with an averaged coupling constant were designed
as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), and br
(broadened). Mass spectra (HRMS) were recorded by FAB methods. All
reactions were carried out under an argon atmosphere.
General procedure for synthesis of furans 3, 6 and 7: To a solution of
aldehyde 1a-h (0.4 mmol) and dimethyl acetylenedicarboxylate (2, 59.0
µL, 0.48 mmol) in DCM (2.0 ml) was added 4-picoline (95.5µL, 1.0 mmol),
triphenylphosphine (for 1a-1f, 105 mg, 0.4 mmol) or tributylphosphine (for
1g and 1h, 98.7 µL, 0.4 mmol) and TFAA (83.5 µL, 0.6 mmol) or acyl
chloride 5 (0.6 mmol) at room temperature. After being stirred at same
temperature for 20 h, the reaction mixture was quenched with sat.
NaHCO3 and then extracted with AcOEt. The organic layer was dried
over MgSO4 and concentrated in vacuo to dryness. The residue was
purified by medium-pressure liquid chromatography (MPLC,
hexane:AcOEt = 95:5 to 50:50, flow rate 20 mL/min) to give 3, 6 or 7.
Dimethyl 2-(3-nitrophenyl)-5-(trifluoromethyl)furan-3,4-dicarboxylate
(3a): MPLC: 24 min (hexane:AcOEt = 80:20). 125.4 mg (84%). White
solid. 1H NMR (500 MHz) δ ppm; 8.77 (s, 1H; Ar-H), 8.32 (d, J = 8.0 Hz,
1H; Ar-H), 8.22 (d, J = 8.0 Hz, 1H; Ar-H), 7.68 (t, J = 8.0 Hz, 1H; Ar-H),
3.94 (s, 3H; CH3), 3.89 (s, 3H; CH3). 13C NMR (125 MHz) δ ppm; 162.1
(C=O), 161.5 (C=O), 154.6 (C), 148.6 (C), 140.4 (q, JC,F = 44.0 Hz; C-
CF3), 134.1 (CH), 130.0 (CH), 129.1 (C), 125.5 (CH), 123.5 (CH), 122.0
(q, JC,F = 2.4 Hz, C), 118.2 (q, JC,F = 269.5 Hz; CF3), 115.8 (C), 53.0
(CH3), 52.8 (CH3). The 1H and 13C NMR spectra of 3a were identical to
data reported in the literature.[14]
Dimethyl 2-(2-nitrophenyl)-5-(trifluoromethyl)furan-3,4-dicarboxylate
(3b): MPLC: 22 min (hexane:AcOEt = 67:33). 113.5 mg (76%). Colorless
oil. IR (neat) ν cm-1; 1741, 1622, 1533, 1443, 1351, 1237, 1156. 1H NMR
(500 MHz) δ ppm; 8.18 (dd, J = 8.0, 1.2 Hz, 1H; Ar-H), 7.79-7.69 (m, 2H;
Ar-H), 7.63 (dd, J = 7.5, 1.7 Hz, 2H; Ar-H), 3.94 (s, 3H; CH3), 3.69 (s, 3H;
CH3). 13C NMR (125 MHz) δ ppm; 161.8 (C=O), 161.2 (C=O), 155.1 (C),
Scheme 4. Proposed mechanism.
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10.1002/ejoc.201900806
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148.7 (C), 140.0 (q, JC,F = 43.5 Hz; C-CF3), 133.5 (CH), 132.9 (CH),
132.2 (CH), 125.2 (CH), 123.0 (C), 121.4 (C), 118.2 (q, JC,F = 268.7 Hz;
CF3), 115.5 (C), 53.1 (CH3), 52.2 (CH3). HRMS (FAB) m/z: Calcd for
C15H11F3NO7 [M+H]+ 374.0488; Found: 374.0517.
(q, JC,F = 2.0 Hz; C), 118.2 (q, JC,F = 269.0 Hz; CF3), 115.8 (CH), 112.3
1
(CH), 111.6 (C), 53.1 (CH3), 52.4 (CH3). The H and 13C NMR spectra of
3g were identical to data reported in the literature.[14]
Dimethyl 2-methyl-5-(3-nitrophenyl)furan-3,4-dicarboxylate (6a):
MPLC: 32 min (hexane:AcOEt = 95:5). 94.9 mg (74%). Pale yellow solid.
MP 111-112 ºC. IR (KBr) ν cm-1; 1736, 1719, 1528, 1449, 1348, 1245. 1H
NMR (500 MHz) δ ppm; 8.54 (t, J = 2.0 Hz, 1H; Ar-H), 8.19-8.15 (m, 1H;
Ar-H), 8.02-7.99 (m, 1H; Ar-H), 7.57 (t, J = 8.3 Hz, 1H; Ar-H), 3.93 (s, 3H;
CH3) , 3.85 (s, 3H; CH3), 2.63 (s, 3H; CH3). 13C NMR (125 MHz) δ ppm;
165.3 (C=O), 163.4 (C=O), 159.3 (C), 148.8 (C), 148.3 (C), 131.7 (CH),
130.6 (C), 130.1 (CH), 123.5 (CH), 121.0 (CH), 116.5 (C), 115.0 (C), 52.7
(CH3), 51.8 (CH3), 13.3 (CH3). HRMS (FAB) m/z: Calcd for C15H14NO7
[M+H]+ 320.0770; Found: 320.0741.
Dimethyl 2-(4-nitrophenyl)-5-(trifluoromethyl)furan-3,4-dicarboxylate
(3c): MPLC: 21 min (hexane:AcOEt = 80:20). 123.9 mg (83%). Pale
yellow solid. MP 86-87 ºC. IR (neat) ν cm-1; 1737, 1624, 1526, 1442,
1345, 1255, 1173. 1H NMR (500 MHz) δ ppm; 8.31 (d, J = 8.8 Hz, 2H; Ar-
H), 8.06 (d, J = 8.8 Hz, 2H; Ar-H), 3.94 (s, 3H; CH3), 3.89 (s, 3H; CH3).
13C NMR (125 MHz) δ ppm; 162.3 (C=O), 161.3 (C=O), 154.2 (C), 149.0
(C), 141.0 (q, JC,F = 43.6 Hz; C-CF3), 133.2 (C), 129.2 (CH), 124.1 (CH),
121.9 (q, JC,F = 2.4 Hz; C), 118.2 (q, JC,F = 269.9 Hz; CF3), 116.6 (C),
53.1 (CH3), 52.8 (CH3). HRMS (FAB) m/z: Calcd for C15H11F3NO7 [M+H]+
374.0488; Found: 374.0511.
Dimethyl 2-isopropyl-5-(3-nitrophenyl)furan-3,4-dicarboxylate (6b):
MPLC: 23 min (hexane:AcOEt = 80:20). 119.2 mg (86%). Pale yellow
solid. MP 88-89 ºC. IR (KBr) ν cm-1; 1729, 1710, 1530, 1441, 1351, 1228.
1H NMR (300 MHz) δ ppm; 8.54 (br.s, 1H, Ar-H), 8.20 (br.d, J = 8.1 Hz,
1H; Ar-H), 8.02 (br.d, J = 8.1 Hz, 1H, Ar-H), 7.59 (t, J = 8.1 Hz, 1H; Ar-H),
3.93 (s, 3H; CH3), 3.86 (s, 3H; CH3), 3.70 (septet, J = 7.0 Hz, 1H; CH),
1.35 (d, J = 7.0 Hz, 6H; CH3). 13C NMR (75 MHz) δ ppm; 166.5 (C=O,
165.0 (C=O), 163.0 (C), 148.5 (C), 147.8 (C), 131.6 (CH), 130.5 (C),
129.9 (CH), 123.4 (CH), 120.9 (CH), 116.2 (C), 113.1 (C), 52.8 (CH3),
52.0 (CH3), 27.2 (CH), 20.6 (CH3). HRMS (FAB) m/z: Calcd for
C17H18NO7 [M+H]+ 348.1083; Found: 348.1080.
Dimethyl
2-(4-cyanophenyl)-5-(trifluoromethyl)furan-3,4-
dicarboxylate (3d): MPLC: 28 min (hexane:AcOEt = 80:20). 114.5 mg
(81%). White solid. 1H NMR (500 MHz) δ ppm; 7.98 (d, J = 8.6 Hz, 2H;
Ar-H), 7.75 (d, J = 8.6 Hz, 2H; Ar-H) 3.93 (s, 3H; CH3), 3.87 (s, 3H; CH3).
13C NMR (125 MHz) δ ppm; 162.3 (C=O), 161.3 (C=O), 154.5 (C), 140.7
(q, JC,F = 44.0 Hz; C-CF3), 133.6 (CH), 131.5 (C), 128.7 (CH), 121.8 (q,
JC,F = 2.4 Hz; C), 118.2 (CN), 118.1 (q, JC,F = 269.9 Hz; CF3), 116.2 (C),
114.3 (C), 53.0 (CH3), 52.7 (CH3). The 1H and 13C NMR spectra of 3d
were identical to data reported in the literature.[14]
Dimethyl 2-(trifluoromethyl)-5-(4-(trifluoromethyl)phenyl)furan-3,4-
dicarboxylate (3e): MPLC: 19 min (hexane:AcOEt = 90:10). 115.7 mg
(73%). Colorless oil. 1H NMR (500 MHz) δ ppm; 7.98 (d, J = 8.3 Hz, 2H;
Ar-H), 7.72 (d, J = 8.3 Hz, 2H; Ar-H) 3.94 (s, 3H; CH3), 3.87 (s, 3H; CH3).
13C NMR (125 MHz) δ ppm; 162.5 (C=O), 161.6 (C=O), 155.4 (C), 140.5
(q, JC,F = 43.6 Hz; C-CF3), 132.7 (q, JC,F = 32.8 Hz; C-CF3), 130.9 (C),
128.8 (CH), 125.9 (q, J = 3.6 Hz; CH), 123.9 (q, JC,F = 272.3 Hz; CF3),
121.8 (q, JC,F = 2.4 Hz; C), 118.2 (q, JC,F = 269.5 Hz; CF3), 115.6 (C),
53.0 (CH3), 52.6 (CH3). The 1H and 13C NMR spectra of 3e were identical
to data reported in the literature.[14]
Dimethyl 2-(tert-butyl)-5-(3-nitrophenyl)furan-3,4-dicarboxylate (6c):
MPLC: 18 min (hexane:AcOEt = 80:20). 148.1 mg (quant). Pale yellow
solid. MP 84-85 ºC. IR (KBr) ν cm-1; 1743, 1715, 1534, 1439, 1352, 1213.
1H NMR (300 MHz) δ ppm; 8.71 (t, J = 1.8 Hz, 1H; Ar-H), 8.21 (dt, J = 8.1,
1.8 Hz, 1H; Ar-H), 8.17 (dt, J = 8.1, 1.8 Hz, 1H; Ar-H), 7.61 (t, J = 8.1 Hz,
1H; Ar-H), 3.88 (s, 3H; CH3), 3.84 (s, 3H; CH3), 1.40 (s, 9H; CH3) 13C
NMR (75 MHz) δ ppm; 165.2 (C=O), 163.3 (C=O), 162.5 (C), 150.4 (C),
148.3 (C), 133.4 (CH), 130.7 (C), 129.4 (CH), 123.8 (CH), 122.7 (CH),
115.3 (C), 114.7 (C), 52.4 (CH3), 52.3 (CH3), 34.3 (C), 28.5 (CH3). HRMS
(FAB) m/z: Calcd for C18H20NO7 [M+H]+ 362.1240; Found: 362.1247.
Dimethyl
2-(4-bromophenyl)-5-(trifluoromethyl)furan-3,4-
dicarboxylate (3f): MPLC: 27 min (hexane:AcOEt = 95:5). 115.7 mg
(76%). 123.8 mg (73%). White solid. 1H NMR (500 MHz) δ ppm; 7.73 (d,
J = 8.9 Hz, 2H; Ar-H), 7.60 (d, J = 8.9 Hz, 2H; Ar-H) 3.93 (s, 3H; CH3),
3.85 (s, 3H; CH3). 13C NMR (125 MHz) δ ppm; 162.6 (C=O), 161.8 (C=O),
156.4 (C), 139.8 (q, JC,F = 43.6 Hz; C-CF3), 132.2 (C), 129.9 (CH), 126.5
(C), 125.8 (C), 121.8 (q, JC,F = 2.4 Hz; C), 118.4 (q, JC,F = 269.5 Hz; CF3),
114.5 (C), 52.9 (CH3), 52.5 (CH3). The 1H and 13C NMR spectra of 3f
were identical to data reported in the literature.[14]
Dimethyl 2-(3-nitrophenyl)-5-phenylfuran-3,4-dicarboxylate (6d):
MPLC: 29 min (hexane:AcOEt = 80:20). 140.4 mg (92%). Yellow solid.
MP 118-119 ºC. IR (KBr) ν cm-1; 1739, 1725, 1531, 1437, 1351, 1238. 1H
NMR (500 MHz) δ ppm; 8.76 (t, J = 1.7 Hz, 1H; Ar-H), 8.26-8.20 (m, 2H;
Ar-H), 7.87-7.81 (m, 2H; Ar-H), 7.62 (t, J = 8.1 Hz, 1H; Ar-H), 7.50-7.41
(m, 3H; Ar-H), 3.92 (s, 3H; CH3), 3.89 (s, 3H; CH3). 13C NMR (125 MHz)
δ ppm; 164.3 (C=O), 163.9 (C=O), 154.5 (C), 151.1 (C), 148.7 (C), 131.2
(CH), 130.4 (C), 130.3 (CH), 129.9 (CH), 128.9 (CH), 128.4 (C), 127.5
(CH), 124.2 (CH), 122.4 (CH), 117.1 (C), 115.8 (C), 52.5 (CH3), 52.4
(CH3). HRMS (FAB) m/z: Calcd for C20H16NO7 [M+H]+ 382.0927; Found:
382.0920.
Dimethyl 2-phenyl-5-(trifluoromethyl)furan-3,4-dicarboxylate (3g):
1
MPLC: 32 min (hexane:AcOEt = 95:5). 55.5 mg (42%). Colorless oil. H
NMR (500 MHz) δ ppm; 7.86-7.81 (m, 2H; Ar-H), 7.51-7.44 (m, 3H; Ar-H),
3.94 (s, 3H; CH3), 3.86 (s, 3H; CH3). 13C NMR (125 MHz) δ ppm; 162.9
(C=O), 161.9 (C=O), 157.4 (C), 139.7 (q, JC,F = 43.6 Hz; C-CF3), 131.1
(CH), 128.9 (CH), 128.4 (CH), 127.7 (C), 121.6 (q, JC,F = 2.4 Hz; C),
118.5 (q, JC,F = 269.5 Hz; CF3), 114.2 (C), 52.9 (CH3), 52.5 (CH3). The 1H
and 13C NMR spectra of 3g were identical to data reported in the
literature.[14]
Dimethyl 2-(2-chlorophenyl)-5-(3-nitrophenyl)furan-3,4-dicarboxylate
(6e): MPLC: 71 min (hexane:AcOEt = 90:10). 136.2 mg (82%). Pale
yellow solid. MP 127-128 ºC. IR (KBr) ν cm-1; 1725, 1531, 1434, 1355,
1255, 1080. 1H NMR (300 MHz) δ ppm; 8.69 (br.s, 1H; Ar-H), 8.26 (br.d,
J = 7.7 Hz, 1H; Ar-H), 8.17 (br.d, J = 8.4 Hz, 1H; Ar-H), 7.68-7.51 (m, 3H;
Ar-H), 7.50-7.36 (m, 2H; Ar-H), 3.97 (s, 3H; CH3), 3.77 (s, 3H; CH3). 13C
NMR (125 MHz) δ ppm; 163.9 (C=O), 162.4 (C=O), 152.9 (C), 150.6 (C),
148.4 (C), 134.0 (C), 132.4 (CH), 132.0 (CH), 131.48 (CH), 130.12 (C),
130.07 (CH), 129.8 (CH), 127.8 (C), 126.6 (CH), 123.9 (CH), 121.7 (CH),
118.0 (C), 116.4 (C), 52.9 (CH3), 52.3 (CH3). HRMS (FAB) m/z: Calcd for
C20H15ClNO7 [M+H]+ 416.0537; Found: 416.0570.
Dimethyl 5-(trifluoromethyl)-[2,2'-bifuran]-3,4-dicarboxylate (3h):
MPLC: 26 min (hexane:AcOEt = 95:5). 63.9 mg (53%). White solid. 1H
NMR (300 MHz) δ ppm; 7.61 (d, J = 1.5 Hz, 1H; Ar-H), 7.49 (d, J = 3.7
Hz, 1H; Ar-H), 6.57 (dd, J = 3.7, 1.5 Hz, 1H; Ar-H), 3.93 (s, 3H; CH3),
3.88 (s, 3H; CH3). 13C NMR (75 MHz) δ ppm; 161.6 (C=O), 161.4 (C=O),
149.1 (C), 145.2 (CH), 142.3 (C), 138.2 (q, JC,F = 43.5 Hz; C-CF3), 121.5
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900806
European Journal of Organic Chemistry
FULL PAPER
1
Dimethyl 2-(3-chlorophenyl)-5-(3-nitrophenyl)furan-3,4-dicarboxylate
(6f): MPLC: 62 min (hexane:AcOEt = 90:10). 144.1 mg (87%). Pale
yellow solid. MP 137-138 ºC. IR (KBr) ν cm-1; 1739, 1720, 1531, 1436,
1345, 1221, 1084. 1H NMR (300 MHz) δ ppm; 8.76 (t, J = 1.8 Hz, 1H; Ar-
H), 8.32-8.19 (m, 2H; Ar-H), 7.87-7.82 (m, 1H; Ar-H), 7.78-7.71 (m, 1H;
Ar-H), 7.65 (t, J = 8.1 Hz, 1H; Ar-H), 7.45-7.38 (m, 2H; Ar-H), 3.92 (s, 3H;
CH3) , 3.91 (s, 3H; CH3). 13C NMR (75 MHz) δ ppm; 163.6 (C=O), 163.4
(C=O), 152.6 (C), 151.2 (C), 148.4 (C), 134.8 (C), 133.1 (CH), 130.1
(CH), 130.0 (C), 129.80 (C), 129.77 (CH), 127.3 (CH), 125.5 (CH), 124.2
(CH), 122.4 (CH), 117.1 (C), 116.5 (C), 52.71 (CH3), 52.69 (CH3) (note
that two carbon peaks overlap with each other). HRMS (FAB) m/z: Calcd
for C20H15ClNO7 [M+H]+ 416.0537; Found: 416.0544.
cm-1; 1743, 1715, 1439, 1213. H NMR (300 MHz) δ ppm; 7.85-7.75 (m,
2H; Ar-H), 7.51-7.37 (m, 3H; Ar-H), 3.87 (s, 3H; CH3), 3.80 (s, 3H; CH3),
1.40 (s, 9H; CH3). 13C NMR (75 MHz) δ ppm; 165.6 (C=O), 163.9 (C=O),
161.7 (C), 153.1 (C), 129.4 (CH), 129.2 (C), 128.3 (CH), 127.7 (CH),
114.1 (C), 113.6 (C), 52.3 (CH3), 52.0 (CH3), 34.2 (C), 28.5 (CH3). HRMS
(FAB) m/z: Calcd for C18H21O5 [M+H]+ 317.1389; Found: 317.1382.
Dimethyl 2-(4-chlorophenyl)-5-phenylfuran-3,4-dicarboxylate (7g):
MPLC: 38 min (hexane:AcOEt = 95:5). 74.4 mg (50%). Colorless oil. IR
(neat) ν cm-1; 1728, 1487, 1221, 1092. H NMR (300 MHz) δ ppm; 7.88-
7.79 (m, 4H; Ar-H), 7.50-7.39 (m, 5H; Ar-H), 3.89 (s, 3H; CH3), 3.88 (s,
3H; CH3). 13C NMR (75 MHz) δ ppm; 164.1 (C=O), 164.0 (C=O), 153.64
(C), 153.58 (C), 135.7 (C), 129.8 (CH), 129.1 (C), 128.9 (CH), 128.8 (CH),
128.7 (CH), 128.6 (C), 127.3 (CH), 117.41 (C), 117.39 (C), 52.5 (CH3)
(note that two carbon peaks overlap with each other). HRMS (FAB) m/z:
Calcd for C20H16ClO5 [M+H]+ 371.0686; Found: 371.0693.
1
Dimethyl 2-(4-chlorophenyl)-5-(3-nitrophenyl)furan-3,4-dicarboxylate
(6g): MPLC: 24 min (hexane:AcOEt = 80:20). 148.6 mg (89%). White
solid. MP 129-130 ºC. IR (KBr) ν cm-1; 1723, 1531, 1437, 1351, 1236,
1092. 1H NMR (300 MHz) δ ppm; 8.75 (t, J = 1.6 Hz, 1H; Ar-H), 8.30-8.19
(m, 2H; Ar-H), 7.82 (d, J = 8.5 Hz, 2H; Ar-H), 7.65 (t, J = 8.0 Hz, 1H; Ar-
H), 7.45 (d, J = 8.5 Hz, 2H; Ar-H), 3.93 (s, 3H; CH3) , 3.90 (s, 3H; CH3).
13C NMR (75 MHz) δ ppm; 163.7 (C=O), 163.6 (C=O), 152.6 (C), 151.8
(C), 148.4 (C), 136.3 (C), 133.0 (CH), 130.4 (C), 130.1 (C), 129.8 (CH),
129.1 (CH), 128.8 (CH), 124.2 (CH), 122.3 (CH), 117.2 (C), 116.3 (C),
52.7 (CH3), 52.6 (CH3). HRMS (FAB) m/z: Calcd for C20H15ClNO7 [M+H]+
416.0537; Found: 416.0545.
Acknowledgments ((optional))
We are grateful for financial support from the JSPS Grants-in-
Aid for Scientific Research (C) (Grant No. 18K06573) and the
Shorai Foundation for Science and Technology.
Dimethyl 2-(3-nitrophenyl)-5-(4-nitrophenyl)furan-3,4-dicarboxylate
(6h): MPLC: 79 min (hexane:AcOEt = 80:20). 151.8 mg (89%). Yellow
solid. MP 176-177 ºC. IR (KBr) ν cm-1; 1739, 1720, 1528, 1438, 1348,
1234. 1H NMR (300 MHz) δ ppm; 8.78 (br.s, 1H; Ar-H), 8.40-8.22 (m, 4H;
Ar-H), 8.07 (d, J = 8.8 Hz, 2H; Ar-H), 7.69 (t, J = 8.1 Hz, 1H; Ar-H), 3.94
(s, 6H; CH3). 13C NMR (125 MHz) δ ppm; 161.1 (C=O), 160.9 (C=O),
158.5 (C), 154.2 (C), 148.1 (C), 147.8 (C), 133.2 (CH), 130.1 (C), 129.8
(CH), 129.7 (C), 127.9 (CH), 124.5 (CH), 124.0 (CH), 122.6 (CH), 118.3
(C), 117.4 (C), 53.0 (CH3), 52.9 (CH3). HRMS (FAB) m/z: Calcd for
C20H15N2O9 [M+H]+ 427.0778; Found: 427.0792.
Keywords: Annulation • Lewis bases • Multicomponent
reactions • Oxygen heterocycles • Wittig reactions
[1]
a) A. U. Rao, D. Xiao, X. Huang, W. Zhou, J. Fossetta, D. Lundell, F.
Tian, P. Trivedi, R. Aslanian, A. Palani, Bioorg. Med. Chem. Lett. 2012,
22, 1068–1072; b) F. Hasegawa, K. Niidome, C. Migihashi, M. Murata,
T. Negoro, T. Matsumoto, K. Kato, A. Fujii, Bioorg. Med. Chem. Lett.
2014, 24, 4266–4270; c) T. Inoue, S. Watanabe, T. Yamagishi, Y.
Arano, M. Morita, K. Shimada, WO2010137351, 2010; d) A. E. Gould,
P. D. Greenspan, T. J. Vos, WO 2008030448, 2008; e) D. R. Bolin, A.
W.-H. Cheung, F. Firooznia, M. M. Hamilton, S. Li, L. A. McDermott, Y.
Qian, W. Yun, WO 2007060140, 2007; f) M. Witschel, C. Zagar, E.
Hupe, T. Kuehn, W. K. Moberg, L. Parra Rapado, F. Stelzer, A. Vescovi,
M. Rack, R. Reinhard, B. Sievernich, K. Grossmann, T. Ehrhardt,
WO2006125687, 2006; g) C. Zeng, H. Seino, J. Ren, K. Hatanaka, N.
Yoshie, Polymer 2013, 54, 5351–5357; h) B. Song, K. Hu, A. Qin, B. Z.
Tang, Macromolecules 2018, 51, 7013–7018.
Dimethyl 2-(3-nitrophenyl)-5-(4-tolyl)furan-3,4-dicarboxylate (6i):
MPLC: 34 min (hexane:AcOEt = 85:15). 129.6 mg (82%). Yellow solid.
MP 129-130 ºC. IR (KBr) ν cm-1; 1730, 1525, 1444, 1348, 1229. 1H NMR
(500 MHz) δ ppm; 8.76 (t, J = 1.7 Hz, 1H; Ar-H), 8.26 (dt, J = 8.1, 1.7 Hz,
1H; Ar-H), 8.23 (dt, J = 8.1, 1.7 Hz, 1H; Ar-H), 7.75 (d, J = 8.0 Hz, 2H; Ar-
H), 7.64 (t, J = 8.1 Hz, 1H; Ar-H), 7.29 (d, J = 8.0 Hz, 2H; Ar-H), 3.93 (s,
3H; CH3), 3.89 (s, 3H; CH3), 2.42 (s, 3H; CH3). 13C NMR (75 MHz) δ
ppm; 164.0 (C=O), 163.8 (C=O), 154.8 (C), 150.4 (C), 148.4 (C), 140.5
(C), 132.9 (CH), 130.4 (C), 129.7 (CH), 129.4 (CH), 127.4 (CH), 125.5
(C), 123.9 (CH), 122.2 (CH), 117.0 (C), 115.0 (C), 52.6 (CH3), 52.5 (CH3),
21.4 (CH3). HRMS (FAB) m/z: Calcd for C21H18NO7 [M+H]+ 396.1083;
Found: 396.1097.
[2]
a) B. H. Lipshutz, Chem. Rev. 1986, 86, 795–819; b) H. N. C. Wong, P.
Yu, C.-Y. Yick, Pure Appl. Chem. 1999, 71, 1041–1044; c) H.-K. Lee,
K.-F. Chan, C.-W. Hui, H.-K. Yim, X.-W. Wu, H. N. C. Wong, Pure
Appl.Chem. 2005, 77, 139–143; d) D. Kalaitzakis, M. Triantafyllakis, I.
Alexopoulou, M. Sofiadis, G. Vassilikogiannakis, Angew. Chem. 2014,
126, 13417–13421; Angew. Chem. Int. Ed. 2014, 53, 13201–13205.
Recent reviews: a) S. F. Kirsch, Org. Biomol. Chem. 2006, 4, 2076–
2080; b) G. Balme, D. Bouyssi, N. Monteiro, Heterocycles 2007, 73,
87–124; c) N. T. Patil, Y. Yamamoto, ARKIVOC 2007, 121–141; d) A. V.
Gulevich, A. S. Dudnik, N. Chernyak, V. Gevorgyan, Chem. Rev. 2013,
113, 3084–3213.
[3]
[4]
Dimethyl
2-(4-methoxyphenyl)-5-(3-nitrophenyl)furan-3,4-
dicarboxylate (6j): MPLC: 14 min (hexane:AcOEt = 50:50). 132.2 mg
(81%). Pale yellow solid. MP 101-102 ºC. IR (neat) ν cm-1; 1727, 1525,
1444, 1348, 1258, 1229, 1053. 1H NMR (300 MHz) δ ppm; 8.74 (br.s, 1H;
Ar-H), 8.28-8.18 (m, 2H; Ar-H), 7.85 (d, J = 8.1 Hz, 2H; Ar-H), 7.63 (t, J =
8.1 Hz, 1H; Ar-H), 7.00 (d, J = 8.1 Hz, 2H; Ar-H), 3.93 (s, 3H; CH3), 3.88
(s, 3H; CH3), 3.88 (s, 3H; CH3). 13C NMR (75 MHz) δ ppm; 164.0 (C=O),
162.3 (C=O), 161.2 (C), 155.8 (C), 149.8 (C), 148.5(C), 132.7 (CH),
130.4 (C), 129.7 (CH), 129.4 (CH), 123.8 (CH), 122.0 (CH), 120.9 (C),
117.2 (C), 114.1 (CH), 114.0 (C), 55.4 (CH3), 52.7 (CH3), 52.4 (CH3).
HRMS (FAB) m/z: Calcd for C21H18NO8 [M+H]+ 412.1032; Found:
412.1058.
Reports since 2017: a) J. Yang, F. Mei, S. Fu, Y. Gu, Green Chem.
2018, 20, 1367–1374; b) L. I. Pilkington, S. M. Song, B. Fedrizzi, D.
Barker, Synlett 2017, 28, 1449–1452; c) J. Luo, D. Lu, Y. Peng, Q.
Tang, Asian J. Org. Chem. 2017, 6, 1546–1550; d) N. M. Chobanov, M.
G. Shaibakova, N. R. Popod'ko, L. O. Khafizova, U. M. Dzhemilev,
Tetrahedron 2017, 73, 5639–5645.
[5]
Selected examples: a) G. Mross, E. Holtz, P. Langer, J. Org. Chem.
2006, 71, 8045–8049; b) K. Komeyama, Y. Ohama, K. Takaki, Chem.
Lett. 2011, 40, 1103–1104; c) Y.-Y. Han, Y.-Y. Jiao, D. Ren, Z. Hu, S.
Dimethyl 2-(tert-butyl)-5-phenylfuran-3,4-dicarboxylate (7c): MPLC:
18 min (hexane:AcOEt = 90:10). 71.3 mg (56%). Colorless oil. IR (neat) ν
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900806
European Journal of Organic Chemistry
FULL PAPER
Shen, S. Yu, Asian J. Org. Chem. 2017, 6, 414–417; d) W.-Y. Huang,
Y.-C. Chen, K. Chen, Chem. Asian J. 2012, 7, 688–691.
Biomol. Chem. 2012, 10, 843–847; c) Y.-T. Lee, Y.-T. Lee, C.-J. Lee,
C.-N. Sheu, B.-Y. Lin, J.-H. Wang, W. Lin, Org. Biomol. Chem. 2013,
11, 5156–5161; d) C.-J. Lee, T.-H. Chang, J.-K. Yu, G. M. Reddy, M.-Y.
Hsiao, W. Lin, Org. Lett. 2016, 18, 3758–3761; e) Account: P. Karanam,
G. M. Reddy, W, Lin, Synlett 2018, 29, 2608–2622.
[6]
Selected examples: a) V. Belting, N. Krause, Org. Biomol. Chem. 2009,
7, 1221–1225; b) A. S. Dudnik, Y. Xia, Y. Li, V. Gevorgyan, J. Am.
Chem. Soc. 2010, 132, 7645–7655; c) M. H. Suhre, M. Reif, S. F.
Kirsch, Org. Lett. 2005, 7, 3925–3927; d) A. Saito, T. Konishi, Y.
Hanzawa, Org. Lett. 2010, 12, 372–374; e) X. Du, F. Song, Y. Lu, H.
Chen, Y. Liu, Tetrahedron 2009, 65, 1839–1845; f) C.-H. Cho, F. Shi,
D.-I. Jung, B. Neuenswander, G. H. Lushington, R. C. Larock, ACS
Comb. Sci. 2012, 14, 403–414.
[13] Other domino approaches for the synthesis of polysubstituted furans
via intramolecular Wittig reactions: a) I. Yavari, M. Anary-Abbasinejad,
A. Alizadeh, Tetrahedron Lett. 2002, 43, 4503–4505; b) C.-K. Jung, J.-
C. Wang, M. J. Krische, J. Am. Chem. Soc. 2004, 126, 4118–4119; c)
Review on the phosphine-mediated reactions: P. Karanam, G. M.
Reddy, S. R. Koppolu, W, Lin, Tetrahedron Lett. 2018, 59, 59–76.
[14] Y. Wang, Y.-C. Luo, X.-Q. Hu, P.-F. Xu, Org. Lett. 2011, 13, 5346–5349.
[15] Trialkyl phosphines were known to stabilize the phosphonium enolate
zwitterions. See; X.-F. Zhu, C. E. Henry, O. Kwon, J. Am. Chem. Soc.
2007, 129, 6722–6723.
[7]
Selected examples: a) M. Yoshida, S. Ohno, K. Shishido, Chem. Eur. J.
2012, 18, 1604–1607; b) X. Feng, Z. Tan, D. Chen, Y. Shen, C.-C. Guo,
J. Xiang, C. Zhu, Tetrahedron Lett. 2008, 49, 4110–4112; c) S. R.
Mothe, S. J. L. Lauw, P. Kothandaraman, P. W. H. Chan, J. Org. Chem.
2012, 77, 6937–6947; d) C. R. Reddy, S. Z. Mohammed, P. A.
Kumaraswamy, Org. Biomol. Chem. 2015, 13, 8310–8321; e) S.
Dhiman, S. S. V. Ramasastry, J. Org. Chem. 2013, 78, 10427–10436.
Selected examples: a) Y. R. Lee, J. Y. Suk, B. S. Kim, Org. Lett. 2000,
2, 1387–1389; b) A. Kadam, S. B. Buckley, T. Dinh, R. Fitzgerald, W.
Zhang, Synlett 2011, 11, 1608–1612; c) J. Lou, Q. Wang, K. Wu, P. Wu,
Z. Yu, Org. Lett. 2017, 19, 3287–3290; d) A. Deepthi, A. Sivan, V.
Nandialath, Synthesis 2011, 2466–2470; e) S. Wang, C. Liu, J. Jia, C.
Zha, M. Xie, N. Zhang, Tetrahedron 2016, 72, 6684–6691.
[16] a) W. Zou, Z.-R. He, Z. He, Chin. J. Org. Chem. 2015, 35, 1739–1745;
see also, b) J. Wang, R. Zhou, Z.-R. He, Z. He, Eur. J. Org. Chem.
2012, 6033–6041; c) R. Chen, X. Fan, Z. Xu, Z. He, Tetrahedron Lett.
2017. 58, 3722–3726.
[8]
[9]
[17] a) A. Saito, M. Umakoshi, M. Yagyu, Y. Hanzawa, Org. Lett. 2008, 10,
1783–1785; b) A. Saito, J. Kasai, Y. Odaira, H. Fukaya, Y. Hanzawa, J.
Org. Chem. 2009, 74, 5644–5647; c) A. Saito, J. Kasai, T. Konishi, Y.
Hanzawa, J. Org. Chem. 2010, 75, 6980–6982; d) K. Murai, K. Tateishi,
A. Saito, Org. Biomol. Chem. 2016, 14, 10352–10356; e) K. Tateishi, K.
Noguchi, A. Saito, Org. Biomol. Chem. 2018, 16, 5965–5968.
[18] Other pyridines-catalyzed formation of α,β-enones: a) V. Nair, A. R.
Sreekanth, N. Abhilash, A. T. Biju, B. R. Devi, R. S. Menon, N. P. Rath,
R. Srinivas, Synthesis 2003, 1895–1902; b) C.-Q. Li, M. Shi, Org. Lett.
2003, 5, 4273–4276.
Formal [3+2] annulations or cyclization of other substartes: a) Y.
Shibata, K. Noguchi, M. Hirano, K. Tanaka, Org. Lett. 2008, 10, 2825–
2828; b) Y. Zhao, S. Li, X. Zheng, J. Tang, Z. She, G. Gao, J. You,
Angew. Chem. 2017, 129, 4350–4353; Angew. Chem., Int. Ed. 2017,
56, 4286–4289; c) S. J. Gharpure, P. V. Prasath, Y. G. Shelke, Org.
Lett. 2019, 21, 223–227; d) Y. Wang, G. J. Pritchard, M. C. Kimber, Org.
Lett. 2019, 21, 4892–4895.
[19] a) K. Nozaki, N. Sato, K. Ikeda, H. Takaya, J. Org. Chem. 1996, 61,
4516–4519; b) M. Bayat, H. Imanieh, F. Hassanzadeh, Tetrahedron
Lett. 2010, 51, 1873–1875; c) J.-C. Deng, F.-W. Chan, C.-W. Kuo, C.-A.
Cheng, C.-Y. Huang, S.-C. Chuang, Eur. J. Org. Chem. 2012, 5738–
5747; d) M. Bayat, H. Imanieh, M. H. Farjam, Synth. Commun. 2010,
40, 2475–2482.
[10] a) N. Iwasawa, T. Ochiai, K. Maeyama, J. Org. Chem. 1998, 63, 3164–
3165; b) D. Suzuki, Y. Nobe, Y. Watai, R. Tanaka, Y. Takayama, F.
Sato, H. Urabe, J. Am. Chem. Soc. 2005, 127, 7474–7479; c) L. Wang,
J. Li, Y. Lv, G. Zhao, S. Gao, Synlett 2012, 23, 1074–1078.
[11] a) J. S. Yadav, B. V. Subba Reddy, S. Shubashree, K. Sadashiv, D.
Krishna Rao, J. Mol. Catal. A Chem. 2007, 272, 128–131; b) I. Yavari,
A. Mokhtarporyani-Sanandaj, L. Moradi, A. Mirzaei, Tetrahedron 2008,
64, 5221–5225; c) M. Bayat, H. Imanieh, N. Z. Shiraz, M. S. Qavidel,
Monatsh. Chem. 2010, 14, 1333–1338.
[20] The values represent pKa of conjugate acids of amines and phosphines
in acetonitrile. See; J.-N. Li, Y. Fu, L. Liu, Q.-X. Guo, Tetrahedron 2006,
62, 11801–11813.
[21] T. Furuta, T. Kawabata in Science of Synthesis: Asymmetric
Organocatalysis, Vol. 1 (Eds.: B. List, K. Maruoka), Georg Thieme KG,
Stuttgart, Germany, 2012, pp 497–546.
[12] a) T.-T. Kao, S.-e. Syu, Y.-W. Jhang, W. Lin, Org. Lett. 2010, 12, 3066–
3069; b) Y.-J. Jang, S.-e. Syu, Y.-J. Chen, M.-C. Yang, W. Lin, Org.
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10.1002/ejoc.201900806
European Journal of Organic Chemistry
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Multicomponent Annulation
Keiichiro Tateishi, Yuri Matsumoto, Akio
Saito*
Page No. – Page No.
Formal [2+2+1] Synthesis of
Tetrasubstituted Furans from
Aldehydes, Acetylenedicarboxylates
and Acyl Compounds
A combination of 4-picoline and Ph3P (or nBu3P) efficiently promotes a formal
[2+2+1] synthesis of tetrasubstituted furans from aldehydes,
acetylenedicarboxylates and acyl compounds via O-acylation of the α,β-enone
intermediates followed by intramolecular Wittig reaction under the metal-free and
mild conditions. The present method can be applied not only to acyl chlorides but
also trifluoroacetic anhydride as acyl compounds.
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