A simple approach to the synthesis of dialkyl 5-tert-butylamino-[2, 2′]bifuranyl-3,4-dicarboxylates

Article abstract of DOI:10.1016/j.tetlet.2004.07.120

Reaction of tert-butyl isocyanide with electron-deficient acetylenic esters in the presence of N¹-[(Z)-1-benzoyl-3-oxo-3-phenyl-1-propenyl]-2- (2-furyl)-2-oxoacetamide leads to dialkyl 5-tert-butylamino-[2,2′] bifuranyl-3,4-dicarboxylates in mo

Full text of DOI:10.1016/j.tetlet.2004.07.120

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 7099–7101
A simple approach to the synthesis of dialkyl
5-tert-butylamino-[2,20]bifuranyl-3,4-dicarboxylates
Issa Yavari,* Farough Nasiri, Loghman Moradi and Hoorieh Djahaniani
Department of Chemistry, Tarbiat Modarres University, PO Box 14115-175, Tehran, Iran
Received 15 June 2004; revised 14 July 2004; accepted 23 July 2004
Available online 13 August 2004
Abstract—Reaction of tert-butyl isocyanide with electron-deficient acetylenic esters in the presence of N1-[(Z)-1-benzoyl-3-oxo-3-
phenyl-1-propenyl]-2-(2-furyl)-2-oxoacetamide leads to dialkyl 5-tert-butylamino-[2,20]bifuranyl-3,4-dicarboxylates in moderate
yields.
Ó 2004 Elsevier Ltd. All rights reserved.
The furan moiety is frequently found in natural prod-
ucts, such as the kallolides1 and combranolides2 and in
important pharmaceuticals as well as in flavouring and
fragrance compounds. It is often used as a building
block in organic synthesis and has been the driving force
for numerous synthetic efforts.3,4 Furans can be, in prin-
ciple, synthesized by either cyclization of acyclic precur-
sors or by derivatization of furan rings.5–7 Introduction
of the substituents at the 2- or 5-positions of furan is rel-
atively easy, while similar operations at the 3- or 4-posi-
tions is rather difficult. Thus, much attention has been
paid to the synthesis of polysubstituted furans from acy-
clic precursors.8–12 The usual methods for the prepara-
tion of bifurans lead to symmetrical bifurans.13–15 We
now wish to report that dialkyl acetylenedicarboxylates
1 react with N1-[(Z)-1-benzoyl-3-oxo-3-phenyl-1-prop-
enyl]-2-(2-furyl)-2-oxoacetamide16 2 in the presence of
tert-butyl isocyanide, to produce highly functionalized
dialkyl 5-tert-butylamino-[2,20]bifuranyl-3,4-dicarboxyl-
ates 3 in moderate yields (Scheme 1).
CO2R
Ph
O
RO2C
CO2R
O
+
_
C
C
CH2Cl2
r.t.
N
C
+
+
H
N
H
O
N
H
O
O
CO2R
O
Ph
O
1
3
2
1,3
a
R
Yield of 3 (%)
Me
Et
iPr
55
b
c
50
56
tBu
d
58
Scheme 1.
Keywords: Three-component reaction; Bifurans; tert-Butyl isocyanide; Acetylenic esters.
*
Corresponding author. Tel.: +92 21 8006631; fax: +98 21 8006544; e-mail: isayavar@yahoo.com
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.07.120

7100
I. Yavari et al. / Tetrahedron Letters 45 (2004) 7099–7101
CONHR'
O
+
N
_
C
2
O
CO2R
-
C
C
CO2R
+
N
CO2R
CO2R
C
4
5
H
N
R'
CO2R
O
_
R'N
C O
3
CO2R
O
O
COPh
N
-
R' =
C C
COPh
H
Scheme 2.
6. Hou, X. L.; Cheung, H. Y.; Hon, T. Y.; Kawan, P. L.; Lo,
T. H.; Tong, S. Y.; Wong, H. N. C. Tetrahedron 1998, 54,
1955.
7. Keay, B. A. Chem. Soc. Rev. 1999, 28, 209.
8. Marson, C. M.; Haper, S. J. Org. Chem. 1998, 63, 9223.
9. Luo, F. T.; Jeevanandam, A.; Bajji, A. C. Tetrahedron
Lett. 1999, 40, 121.
10. Frogione, P.; Wilson, P. D.; Fallis, A. G. Tetrahedron
Lett. 2000, 41, 17.
11. Ma, S.; Li, L. Org. Lett. 2000, 2, 941.
12. Gabriele, B.; Salerno, G.; Pascali, F. D.; Costa, M.;
Chiusoli, G. P. J. Org. Chem. 1999, 64, 7693.
13. Kretchmer, R. A.; Glowinski, R. J. Org. Chem. 1976, 41,
2661.
The structures of 3a–d were deduced from their elemen-
tal analyses and their IR, 1H NMR, and 13C NMR
spectroscopic data.16 The 1H NMR spectrum of 3a
exhibited four singlets identified as tert-butyl
(d = 1.46ppm), methoxy (d = 3.76 and 3.90ppm), and
NH (d = 6.84ppm) protons along with multiplets for
the furan ring system. The 13C NMR spectrum of 3a
showed fourteen distinct resonances in agreement with
the proposed structure. The mass spectra of compounds
3a–d displayed molecular ion peaks at appropriate m/z
values.
A plausible mechanism for the formation of the product
is proposed in Scheme 2. The reaction starts with addi-
tion of the isocyanide to the electron-deficient acetylenic
ester to form the zwitterionic intermediate 4, which at-
tacks the active carbonyl group of 2. Then, formation
of the second five-membered ring takes place via nucleo-
philic addition to the nitrile iminium moiety. Aromatiza-
tion of the second furan ring is achieved by loss of
isocyanate.
14. Krafft, T. E.; Rich, J. D.; McDermott, D. J. J. Org. Chem.
1996, 55, 5430.
15. Luo, F. T.; Bajji, A. C.; Jeevanandam, A. J. Org. Chem.
1999, 64, 1738.
16. Representative experimental procedure: Preparation of
N1-[(Z)-1-benzoyl-3-oxo-3-phenyl-1-propenyl]-2-(2-furyl)-
2-oxoacetamide 2. To a stirred solution of 2-(2-furyl)-2-
oxoacetamide (0.28g, 2mmol) and dibenzoylacetylene
(0.47g, 2mmol) in CH2Cl2 (10mL) was added dropwise
a mixture of triphenylphosphine (0.52g, 2mmol) in
CH2Cl2 (4mL) at 0°C over 10min. The reaction mixture
was then allowed to warm to room temperature and
stirred for 24h. The solvent was removed under reduced
pressure and the residue was triturated with ethyl acetate.
The product was obtained as a white powder, yield 0.56g
(75%), mp 216–218°C. IR (KBr): t = 3312 (NH), 1692 and
This reaction of acetylenic esters with N1-[(Z)-1-ben-
zoyl-3-oxo-3-phenyl-1-propenyl]-2-(2-furyl)-2-oxoacet-
amide in the presence of tert-butyl isocyanide provides a
simple one-pot entry into the synthesis of highly func-
tionalized dialkyl 5-tert-butylamino-[2,20]bifuranyl-3,4-
dicarboxylates of potential interest.
1665 (C@O)cmꢀ1
.
1H NMR (500.1MHz, CDCl3):
d = 6.52–7.99 (m, 14H, vinyl H, furan–CH, and Ar–H),
13.32 (s, 1H, NH), 13C NMR (125.7MHz, CDCl3):
d = 104.8 (CH, furan), 113.3 (N–C@C), 127.2 (CH),
128.3, 128.9, 128.9, and 129.2 (8CH), 133.6 and 134.1
(2CH), 135.0, 137.6, and 148.5 (3C), 148.9 (NAC@C),
150.1 (CH, furan), 158.4, 170.9, 190.2, and 191.6 (4C@O).
The procedure for the preparation of dimethyl
5-tert-butylamino-[2,20]bifuranyl-3,4-dicarboxylate 3a is
described as an example. To a stirred solution of
N1-[(Z)-1-benzoyl-3-oxo-3-phenyl-1-propenyl]-2-(2-furyl)-
2-oxoacetamide (0.75g, 2mmol) and dimethyl acetylene-
dicarboxylate (0.28g, 2mmol) in CH2Cl2 (10mL) was
added dropwise a mixture of tert-butyl isocyanide (0.45g,
2mmol) in CH2Cl2 (4mL) at 0°C over 10min. The
reaction mixture was then allowed to warm to room
temperature and stirred for 48h. The solvent was removed
References and notes
1. Look, S. A.; Burch, M. T.; Fenical, W.; Qi-tai, Z.; Clearly,
J. J. Org. Chem. 1985, 50, 5741.
2. Fenical, W.; Okeeda, R. K.; Basnadurraga, M. M.;
Culver, P.; Jacobs, R. S. Science 1981, 212, 1512.
3. Danheiser, R. L.; Stoner, E. J.; Koyama, H.; Yamashita,
D. S.; Klade, C. A. J. Am. Chem. Soc. 1989, 111,
4407.
4. Dean, F. M. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Rees, C. W., Eds.; Pergamon: New
York, 1984; Vol. 4, p 313.
5. Lipshutz, B. H. Chem. Rev. 1986, 86, 795.

I. Yavari et al. / Tetrahedron Letters 45 (2004) 7099–7101
7101
under reduced pressure and the residue was purified by
silica gel column chromatography (Merck 230–400 mesh)
using n-hexane–EtOAc (5:1) as eluent. The product 3a was
obtained as a light yellow powder, yield 0.35g, (55%), mp
170–172°C. IR (KBr): t = 3315 (NH), 1729 and 1665
Calcd for C18H23NO6 (349.4): C, 61.88; H, 6.64; N, 4.01.
Found: C, 61.9; H, 6.6; N, 4.0%. Compound 3c: light
yellow crystals, yield 0.42g, (56%), mp 86–88°C. IR
(KBr): t = 3311 (NH), 1721 and 1659 (C@O)cmꢀ1 1H
.
NMR (500.1MHz, CDCl3): d = 1.32 (d, 3JHH = 7Hz, 6 H,
CHMe2), 1.42 (d, 3JHH = 7Hz, 6 H, CHMe2), 1.48 (s, 9H,
CMe3), 5.01–5.49 (m, 2H, 2CHMe2) 6.48 (m, 1H, CH),
1
(C@O)cmꢀ1. H NMR (500.1MHz, CDCl3): d = 1.46 (s,
9H, CMe3), 3.76 (s, 3H, OMe), 3.90 (s, 3H, OMe), 6.42 (m,
3
3
1H, CH), 6.57 (d, 1H, JHH = 3Hz, CH), 6.84 (br s, 1H,
6.51 (d, JHH = 3Hz, 1H, CH), 6.90 (s, 1H, NH), 7.49 (s,
NH), 7.41 (s, 1H, CH). 13C NMR (125.7MHz, CDCl3):
d = 29.8 (CMe3), 51.1 (CMe3), 52.4 (OMe), 52.9 (OMe),
87.6 (NAC@C), 107.2 and 111.4 (2CH), 112.2 and 135.0
(2C), 142.5 (CH), 144.2 (C), 161.6 (NAC@C), 164.7 and
165.1 (2C@O). MS (EI, 70eV): m/z (%) = 322 (M+ + 1,
30), (321 (M+, 80), 290 (15), 265 (100), 233 (90), 201 (55),
175 (25), 95 (40), 57 (35), 41 (35). Anal. Calcd for
C16H19NO6 (321.3): C, 59.81; H, 5.96; N, 4.36. Found: C,
59.8; H, 6.0; N, 4.4%. Compound 3b: light yellow powder,
yield 0.35g, (50%), mp 143–145°C. IR (KBr): t = 3316
(NH), 1725 and 1664 (C@O)cmꢀ1. 1H NMR (500.1MHz,
1H, CH). 13C NMR (125.7MHz, CDCl3): d = 21.6
(CHMe2), 21.6 (CHMe2), 29.7 (CMe3), 52.8 (CMe3),
67.3(CHMe2), 69.2 (CHMe2), 88.1 (NAC@C), 106.3 and
111.6 (2CH), 113.6 and 134.3 (2C), 142.5 (CH), 145.1 (C),
162.0 (NAC@C), 164.8 and 165.1 (2C@O). MS (EI,
70eV): m/z (%) = 378 (M+ + 1, 35), 377 (M+, 100), 237
(50), 219 (55), 43 (20). Anal. Calcd for C20H27NO6 (377.4):
C, 63.65; H, 7.21; N, 3.71. Found: C, 63.6%; H, 7.2%; N,
3.7%. Compound 3d: light yellow powder, yield 0.47g,
(58%), mp 94–96°C. IR (KBr): t = 3310 (NH), 1717 and
1658 (C@O)cmꢀ1
.
1H NMR (500.1MHz, CDCl3):
3
CDCl3): d = 1.32 (t, JHH = 7Hz, 3H, CH3), 1.38 (t,
d = 1.45 (s, 9H, CMe3), 1.54 (s, 9H, CMe3), 1.60 (s, 9H,
3JHH = 7Hz, 3H, CH3), 1.48 (s, 9H, CMe3), 4.25 (q,
CMe3), 6.44 (m, 1H, CH), 6.52 (d, 1H, JHH = 3Hz, CH),
3
3
3JHH = 7Hz, 2H, OCH2), 4.39 (q, JHH = 7Hz, 2H,
6.86 (s, 1H, NH), 7.41 (s, 1H, CH). 13C NMR (125.7MHz,
CDCl3): d = 28.2 (CMe3), 28.6 (CMe3), 29.8 (CMe3), 52.5
(NCMe3), 80.3 (OCMe3), 81.9 (OCMe3), 89.0 (NAC@C),
106.4 and 111.2 (2CH), 114.7 and 134.1 (2C), 141.7 (CH),
144.9 (C), 161.3 (NAC@C), 162.8 and 164.4 (2C@O). MS
(EI, 70eV): m/z (%) = 406 (M+ + 1, 0), 405 (M+, 35), 237
(60), 219 (20), 57 (100). Anal. Calcd for C22H31NO6
(405.5): C, 65.17; H, 7.71; N, 3.45. Found: C, 65.2%; H,
7.7%; N, 3.4%.
3
OCH2), 6.45 (m, 1H, CH), 6.58 (d, JHH = 3Hz, 1H,
CH), 6.87 (br s, 1H, NH), 7.43 (s, 1H, CH). 13C NMR
(125.7MHz, CDCl3): d = 14.1 (Me), 14.3 (Me), 29.8
(CMe3), 52.8 (CMe3), 59.7 (OCH2), 61.4 (OCH2), 87.7
(NAC@C), 106.8 and 111.3 (2CH), 112.7 and 134.6 (2C),
142.3 (CH), 144.3 (C), 161.5 (NAC@C), 164.3 and 164.7
(2C@O). MS (EI, 70eV): m/z (%) = 350 (M+ + 1, 25), 349
(M+, 85), 293 (100), 247 (50), 219 (80), 191 (30). Anal.