Mendeleev
Communications
Mendeleev Commun., 2011, 21, 229–230
Solvent-free synthesis of functionalized 5-imino-2,5-dihydrofurans
from isocyanides, activated acetylenes and alkyl cyanoformates
Issa Yavari,* Tayebeh Sanaeishoar and Leila Azad
Department of Chemistry, Science and Research Branch, Islamic Azad University, Ponak, Tehran, Iran.
Fax: +98 21 8288 3455; e-mail: yavarisa@modares.ac.ir
DOI: 10.1016/j.mencom.2011.07.020
The reaction between alkyl(aryl) isocyanides, dialkyl acetylenedicarboxylates and alkyl cyanoformates under solvent-free conditions
leads to dialkyl 2-cyano-5-alkyl(aryl)imino-2-alkoxy-2,5-dihydrofuran-3,4-dicarboxylates in high yields.
CO2R2
+
Reaction between isocyanides, electron-deficient acetylenes and
nucleophiles was first documented by Oakes in 1969 and 1973
by the example of dialkyl acetylenedicarboxylates and 1,1,1,4,4,4-
hexafluorobut-2-yne as acetylenic component and methanol as
NuH.1,2 Such an interesting transformation was nearly forgotten
until Yavari in 1996 extended its application to dibenzoylmethane
as NuH.3 Later on, more publications on such a reaction were
published differing mostly in the nature of NuH used.4–12 The
cyclization into furans was realized during the reaction between
isocyanides, electron-deficient acetylenes and activated carbonyl
compounds.4–12
Here, we report the results of our studies involving the trappng
of zwitterions derived from isocyanides 1 and dialkyl acetylene-
dicarboxylates 2 by alkyl cyanoformates 3, which constitutes a
new synthesis of functionalized 2,5-dihydrofurans 4 in good
yields (Scheme 1).†
R2O2C
R1N
R1
N
O
CO2R2
OR3
Solvent-free
OR3
+
NC
12 h, room
temprature
O
CO2R2
C
CN
1
2
3
4
R1
R3
R2
Yield of 4
Cyclohexyl
Cyclohexyl
91%
85%
87%
90%
85%
85%
95%
93%
90%
88%
88%
91%
a
Me
Et
Me
Et
Me
Et
Me
Et
Me
Et
Me
Et
Me
Me
Me
Me
Me
Me
Et
Et
Et
Et
Et
b
c
d
e
f
g
h
i
1,1,3,3-Tetramethylbutyl
1,1,3,3-Tetramethylbutyl
2,6-Dimethylphenyl
2,6-Dimethylphenyl
Cyclohexyl
Cyclohexyl
1,1,3,3-Tetramethylbutyl
1,1,3,3-Tetramethylbutyl
2,6-Dimethylphenyl
2,6-Dimethylphenyl
j
k
l
The structures of compounds 4a–l were deduced from their
Et
1
IR, H and 13C NMR spectral data. The mass spectra of these
Scheme 1
compounds displayed molecular ion peaks at the appropriate
m/z values. The 1H NMR spectrum of 4a exhibited three singlet
resonances identified as methoxy (d 3.70, 3.92 and 3.96 ppm)
and a multiplet for N–CH of cyclohexyl ring (d 3.69 ppm)
protons, along with multiplets for the cyclohexyl methylene protons
(d 1.27–1.79 ppm). The 1H-decoupled 13C NMR spectrum of 4a
showed 16 distinct resonances that confirm the proposed structure.
Three resonances at d 149.8, 159.4, and 161.0 ppm observed in the
13C NMR spectrum of 4a, are attributed to the imino and carbonyl
groups. The 1H and 13C NMR spectra of 4b–l are similar to those
for 4a except for the imino and ester moieties, which showed
characteristic resonances in appropriate regions of the spectrum.
Mechanistically, it is conceivable that the reaction involves
the initial formation of a 1,3-dipolar intermediate 5 between
isocyanide and the acetylenic compound, which reacts with cyano-
formates to produce 6 (Scheme 2). Cyclization of this zwitter-
ionic intermediate leads to 2-cyano-5-alkyl(aryl)imino-2-alkoxy-
2,5-dihydrofurans 4.
In conclusion, a simple and efficient method for synthesis
of 2-cyano-5-alkyl(aryl)imino-2-alkoxy-2,5-dihydrofurans is
described. This procedure is advantageous due to one-pot and
solvent-free performance.
†
Synthesis of compounds 4 (general procedure). A mixture of corre-
sponding alkyl cyanoformate 3 (1 mmol) and dialkyl acetylenedicarboxylate
2 (1 mmol) was stirred at room temperature. Then, isocyanide 1 (1 mmol)
was added slowly and the mixture was stirred at room temperature. After
completion of the reaction [12 h; TLC (hexane–EtOAc, 4:1)], the solvent
was removed under reduced pressure and the residue was purified by silica
gel column chromatography (Merck 230–400 mesh, hexane–EtOAc as an
eluent) to afford compound 4.
O
CO2R2
NC
OR3
R1
N
CO2R2
CO2R2
3
+
C
R1N
For 4a: pale yellow oil, yield 0.31 g (91%). IR (KBr, nmax/cm–1): 2930,
2852, 2245, 1740, 1680, 1269. 1H NMR (CDCl3, 300 MHz), d: 1.27–1.79
(m, 10H, 5CH2), 3.69 (m, 1H, CHN), 3.70 (s, 3H, MeO), 3.92 (s, 3H, MeO),
3.96 (s, 3H, MeO). 13C NMR (CDCl3, 75 MHz), d: 24.8 (CH2), 24.9 (CH2),
25.9 (CH2), 33.5 (CH2), 33.6 (CH2), 53.8 (MeO), 53.9 (MeO), 55.9 (MeO),
57.9 (CHN), 99.5 (C), 112.3 (CN), 136.8 (C), 140.3 (C), 149.8, 159.4 and
161.0 (C=N and 2C=O). MS (EI, 70 eV), m/z (%): 336 (M+, 100), 310
(18), 239 (65), 182 (15), 59 (15), 31 (10). Found (%): C, 57.4; H, 6.1; N,
8.5. Calc. for C16H20N2O6 (%): C, 57.14; H, 5.99; N, 8.33.
C
CO2R2
1
2
5
R2O2C
C
CO2R2
OR3
CN
R2O2C
R1N
CO2R2
OR3
R1N
O
O
CN
6
4
For characteristics of compounds 4b–l, see Online Supplementary
Materials.
Scheme 2
© 2011 Mendeleev Communications. All rights reserved.
– 229 –
Yavari, Issa
