Reaction of isocyanides, dialkyl acetylenedicarboxylates, and α-keto lactones: Unexpected participation of an ester carbonyl group in the isocyanide-based three-component reaction

Article abstract of DOI:10.1055/s-0028-1088042

The reaction of benzofuran-2,3-dione derivatives with dialkyl acetylenedicarboxylates and alkyl isocyanides results in a three-component addition reaction in which the ester carbonyl group is incorporated into a two-atom assembling unit to give highly fun

Full text of DOI:10.1055/s-0028-1088042

PAPER
1635
Reaction of Isocyanides, Dialkyl Acetylenedicarboxylates, and a-Keto
Lactones: Unexpected Participation of an Ester Carbonyl Group in the
Isocyanide-Based Three-Component Reaction
Isocyanide-Based
bThree-Comp
b
onent Reacti
a
Department of Chemistry, University of Birjand, P. O. Box 97175/615, Birjand, Iran
Fax +98(561)2502009; E-mail: aa_esmaeili@yahoo.com
Received 24 November 2008; revised 15 January 2009
ticipation of the keto carbonyl group25 (Scheme1). We
were not able to obtain the annulated product at the ester
carbonyl group.
Abstract: The reaction of benzofuran-2,3-dione derivatives with
dialkyl acetylenedicarboxylates and alkyl isocyanides results in a
three-component addition reaction in which the ester carbonyl
group is incorporated into a two-atom assembling unit to give high-
ly functionalized g-spiroiminolactones in good yield. This reaction
provides the first example of an ester carbonyl group participating
in an isocyanide-based multicomponent reaction.
CO2R2
CO2R2
R1
N
O
OR3
R1
N
C
O
CO2R2
OR3
+
Ph
+
Key words: ketones, dialkyl acetylenedicarboxylates, alkyl isocya-
nides, spiro compounds, lactones
O
Ph
CO2R2
O
1
2
3
4
Scheme 1
Multicomponent reactions (MCRs), by virtue of their con-
vergence, productivity, facile execution, and generally
high yields, have attracted much attention from the view-
point of combinatorial chemistry.1,2 Of pivotal importance
in this area are the isocyanide-based MCRs such as the
versatile Ugi and Passerini reactions.3,4 The reactivity of
nucleophilic carbenes such as isocyanides towards di-
methyl acetylenedicarboxylate (DMAD) is well docu-
mented.5,6 The initially formed zwitterionic intermediate
from DMAD and isocyanide has been shown to undergo
further reactions with different electrophilic reagents,
leading to a variety of complex heterocyclic compounds.
These reactions have been the subject of detailed investi-
gations by a number of research groups.7–10
Impressed by the success of the reaction, we turned our at-
tention to trapping the zwitterions with a-keto lactones
such as benzofuran-2,3-diones 5, as this would furnish g-
spiroiminolactone derivatives 6 if the reaction proceeded
similarly to that of alkyl phenylglyoxylates (Table 1).
However, the reaction followed an unexpected course, af-
fording g-spiroiminolactone derivatives 7 instead of 6 in
fairly high yields (Table 1). This is the first example of a
new type of isocyanide-based MCR in which the ester car-
bonyl group is incorporated as the carbon–oxygen unit.
The structures of the products were deduced from their IR,
1H NMR, and 13C NMR spectra. The mass spectra of these
compounds displayed molecular ion peaks at the appro-
priate m/z values. For example, the 1H NMR spectrum of
7a contained multiplet signals for a cyclohexyl ring
(d = 1.12–1.71), two singlets for the aryl methyl groups
(d = 2.36, 2.52), a multiplet for N–CH of the cyclohexyl
ring (d = 3.65), two singlets for two methoxy groups
(d = 3.65 and 3.90), a singlet for an aryl proton (d = 6.69,
R5 = H), and a singlet for the other aryl proton (d = 6.72).
The assignment is supported by the IR absorptions at
1752, 1736, 1730 (3 C=O), and 1684 (C=N) cm–1. The
proton-decoupled 13C NMR spectrum of 7a showed 23
distinct resonances, and partial assignment of these reso-
nances is given in the experimental section. The charac-
teristic 13C NMR signal due to the spiro carbon appeared
at d = 106.64, that of the two ester carbonyls at d = 161.1
and 171.13, and the ketone carbonyl at d = 191.12.
Recently, g-spiroiminolactones have become interesting
because of their properties as antibacterial agents, aldos-
terone inhibitors, and proper precursors for the prepara-
tion of a wide spectrum of natural compounds.11
Iminolactones could be hydrolyzed with aqueous hydro-
chloric acid to produce butenolides12 [also known as fu-
ran-2(5H)-ones], an important class of biologically active
natural products, which have been used in medicine and
agriculture.13–17 So far, several synthetic methods have
been reported for the preparation of iminolactones.18–24
The most widely used approach to iminolactone synthesis
is based on isocyanides.18–22
On the basis of our previous success with isocyanide-
based MCRs, we investigated the reactions of alkyl phe-
nylglyoxylates 3 as the a-keto ester components with
dialkyl acetylenedicarboxylates (DAAD) 2 and alkyl iso-
cyanides 1; the addition products 4 were obtained by par-
Although the mechanism of the reaction between the iso-
cyanide and dialkyl acetylenedicarboxylate in the pres-
ence of carbonyl groups has not been established
experimentally, a possible pathway is proposed in
Scheme 2. On the basis of the well-established chemistry
of isocyanides,26,27 it is reasonable to assume that a highly
SYNTHESIS 2009, No. 10, pp 1635–1638
x
x.
x
x
.
2
0
0
9
Advanced online publication: 25.03.2009
DOI: 10.1055/s-0028-1088042; Art ID: Z25508SS
© Georg Thieme Verlag Stuttgart · New York

1636
A. A. Esmaeili, H. Vesalipoor
PAPER
In summary, we have demonstrated the first example of
the participation of an ester carbonyl group in a multicom-
ponent reaction with DAAD and isocyanides to synthe-
size g-spiroiminolactone backbones. Although the ester
carbonyl group is known to be generally less reactive than
a ketone carbonyl group, the ester carbonyl group in a-
keto lactones 5 is sufficiently reactive to compete with the
ketone carbonyl group. The reason for the difference in re-
activity between the keto carbonyl group and the ester car-
bonyl group is not clear to us, but steric hindrance around
the keto moiety may retard the reactivity of the ketone
portion of the benzofuran-2,3-diones 5 in this reaction.
Fairly good yields of the products and the use of simple
starting materials are the main advantages of this method.
The reactions were performed under neutral conditions,
and the starting materials and reagents can be mixed with-
out any activation or modification.
Table 1 Reactions of Benzofuran-2,3-diones 5 with Dialkyl Acety-
lenedicarboxylates 2 and Isocyanides 1
R1
R3
N
R3
CO2R2
O
O
CO2R2
O
O
R4
O
R4
O
5
R5
CH2Cl2
reflux
R5
R3
6
+
+
CO2R2
R2O2C
O
N
R1
O
2
O
CO2R2
R4
R2O2C
R5
R1
N C:
1
7
7
R1
R2
R3
R4
R5
H
Yield (%)
7a
7b
7c
7d
7e
7f
Cy
Cy
Cy
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
65
60
65
70
55
70
75
70
65
Melting points were determined on an Electro thermal 9100 appara-
tus and are uncorrected. IR spectra were obtained on a Perkin–
Et
Me
Me
H
1
Elmer 783 infrared spectrophotometer. H and 13C NMR spectra
i-Pr
Et
were measured with a Bruker DRX-500 Avance spectrometer at
500.1 and 125.77 MHz, respectively. Mass spectra were recorded
on a Shimadzu GCMS-QP5050 mass spectrometer operating at an
ionization potential of 70 eV. Benzofuran-2,3-diones were prepared
by known methods.28 Isocyanides and acetylenic esters were ob-
tained from Merck (Germany) and Fluka (Buchs, Switzerland) and
all materials were used without further purification.
t-Bu
t-Bu
Me
Me
Me
Me
Me
Me
Et
Me
H
CMe2CH2t-Bu
CMe2CH2t-Bu
CMe2CH2t-Bu
CMe2CH2t-Bu
Et
7g
7h
7i
Me
Me
Et
H
Dialkyl 5¢-(Alkylimino)-3-oxospiro[benzofuran-2(3H),2¢(5¢H)-
furan]-3¢,4¢-dicarboxylates 7; General Procedure
Me
Me
A soln of isocyanide 1 (1.1 mmol) in anhyd CH2Cl2 (2 mL) was add-
ed over 10 min by syringe to a stirred soln of benzofuran-2,3-dione
5 (1.0 mmol) and dialkyl acetylenedicarboxylate 2 (1.1 mmol) in
anhyd CH2Cl2 (5 mL) at –10 °C. The reaction mixture was allowed
to warm to r.t. and was then refluxed for about 12 h. On completion
of the reaction, the solvent was removed under vacuum, and cold
Et2O (5 mL; for 7a–e) or cold hexane (5 mL; for 7f–i) was added to
the residue. This produced a solid precipitate, which was collected
by filtration and washed with cold EtOH (2 mL); this gave pure
product 7.
reactive 1:1 zwitterionic intermediate 8 initially forms by
a Michael-type addition reaction of isocyanide 1 with di-
alkyl acetylenedicarboxylate 2; subsequent addition of 8
to the ester carbonyl group of benzofuran-2,3-dione 5 re-
sults in the formation of 9, which undergoes intramolecu-
lar cyclization to deliver g-spiroiminolactone 7.
R2O2C
CO2R2
Dimethyl 5¢-(Cyclohexylimino)-4,6-dimethyl-3-oxospiro[benzo-
furan-2(3H),2¢(5¢H)-furan]-3¢,4¢-dicarboxylate (7a)
Yield: 0.276 g (65%); mp 148–149 °C.
R2O2C
R1
N
C
+
C
IR (KBr): 2966 (C–HSt), 1752, 1736, 1730 (3 C=O), 1684 (C=N)
cm–1.
CO2R2
N
1H NMR (500 MHz, CDCl3): d = 1.12–1.71 [m, 10 H, CH(CH2)5],
2.36 (s, 3 H, Ar-CH3), 2.52 (s, 3 H, Ar-CH3), 3.60 (m, 1 H, NCH),
3.65 (s, 3 H, OMe), 3.90 (s, 3 H, OMe), 6.69 (s, 1 H, H5), 6.72 (s, 1
H, H7).
R1
1
2
8
5
13C NMR (125 MHz, CDCl3): d = 17.68, 22.55 (2 Ar-CH3 ), 24.49,
24.53, 25.58, 32.99, 33.18 (5 CH2), 52.96, 53.2 (2 OCH3), 57.31 (N-
CH), 106.64 (CSpiro), 110.56, 114.94, 125.15, 136.71, 140.19,
140.55, 150.95, 151.46, 159.80 (C=N), 161.10, 171.13, 191.12 (3
C=O).
CO2R2
O
R2O2C
R5
CO2R2
O
R2O2C
R4
R5
C
N
O
R4
R1
O
R1
N
O
MS (EI, 70 eV): m/z (%) = 427 [M+] (12), 330 [M+ – C6H11N] (4),
O
R3
R3
286 [M+ + 1 – C6H6O4] (4), 279 [M+ – 2CO2Me – 2 CH3] (38), 149
7
9
+
[C9H8O2] (78), 91 [C7H8 ] (17), 59 [CO2Me+] (9).
Scheme 2
Diethyl 5¢-(Cyclohexylimino)-4,6,7-trimethyl-3-oxospiro[ben-
zofuran-2(3H),2¢(5¢H)-furan]-3¢,4¢-dicarboxylate (7b)
Yield: 0.281 g (60%); mp 153–155 °C.
Synthesis 2009, No. 10, 1635–1638 © Thieme Stuttgart · New York

PAPER
Isocyanide-Based Three-Component Reaction
1637
IR (KBr): 2987 (C–HSt), 1760, 1740, 1735 (3 C=O), 1685 (C=N)
cm–1.
IR (KBr): 2995 (C–HSt), 1735, 1725, 1720 (3 C=O), 1685 (C=N)
cm–1.
3
1H NMR (500 MHz, CDCl3): d = 1.00 (t, JHH = 7.1 Hz, 3 H,
1H NMR (500 MHz, CDCl3): d = 0.99 (t, 3JHH = 7.0 Hz, 3 H, CH3),
1.27 (s, 9 H, C(CH3)3), 1.34 (t, 3JHH = 7.0 Hz, 3 H, CH3) 2.11, 2.87,
2.5 (3 s, 9 H, 3 Ar-CH3), 4.05 (m, 2 H, OCH2CH3), 4.38 (q,
3JHH = 7.04 Hz, 2 H, OCH2CH3), 6.7 (s, 1 H, H5).
13C NMR (125 MHz, CDCl3): d = 10.34, 13.44 (2 CH2CH3), 14.05,
17.31, 20.33 (3 Ar-CH3), 29.62, [C(CH3)3], 55.74, [C(CH3)3],
61.87, 62.36 (2 OCH2), 107.21 (CSpiro), 115.00, 118.35, 126.30,
135.95, 136.97, 141.47, 148.89, 149.37, 159.33 (C=N), 161.09,
169.39, 192.21 (3 C=O).
CH2CH3), 1.35 (t, 3JHH = 7.1 Hz, 3 H, CH2CH3), 1.15–1.72 [m, 10
H, CH(CH2)5], 2.12, 2.28, 2.50 (3 s, 9 H, 3 Ar-CH3), 3.63 (m, 1 H,
NCH), 4.08 (m, 2 H, OCH2), 4.4 (q, 3JHH = 7.1 Hz, 2 H, OCH2), 6.7
(s, 1 H, H5).
13C NMR (125 MHz, CDCl3): d = 10.37, 13.45 (2 CH2CH3), 14.02,
17.32, 20.34 (3 Ar-CH3 ), 24.47, 24.52, 25.64, 32.98, 33.21 (5 CH2),
57.13 (N-CH), 61.93, 62.49 (2 OCH2), 106.77 (CSpiro), 114.98,
118.36, 126.38, 136.98, 137.04, 140.20, 149.01, 151.70, 159.28
(C=N), 160.83, 169.36, 192.17 (3 C=O).
MS (EI, 70 eV): m/z (%) = 443 [M+] (4), 387 [M+ + 1 – C(CH3)3]
(6), 341 [M+ – C(CH3)3 – 3 CH3] (10), 240 [M+ + 1 – CO2CH2CH3
– C(CH3)3] (2), 225 [M+ + 1–2CO2CH2CH3 – NC(CH3)3] (13), 163
MS (EI, 70 eV): m/z (%) = 469 [M+] (19), 372 [M+ – C6H11N] (7),
341 [M+ – 1 – C6H11N – 2CH3] (4), 307 [M+ – 1 – 2CO2CH2CH3 –
CH3] (47), 269 [M+ – C8H10O4 – 2CH3] (7), 225 [M+ – 1 – C6H11N
+
+
[C10H10O2 ] (100), 91 (C7H8 ,14).
+
– 2CO2CH2CH3] (100), 163 [C10H10O2 ] (87).
Diethyl 4,6-Dimethyl-3-oxo-5¢-[(1,1,3,3-tetramethylbutyl)imi-
no]spiro[benzofuran-2(3H),2¢(5¢H)-furan]-3¢,4¢-dicarboxylate
(7f)
Diisopropyl 5¢-(Cyclohexylimino)-4,7-dimethyl-3-oxo-
spiro[benzofuran-2(3H),2¢(5¢H)-furan]-3¢,4¢-dicarboxylate (7c)
Yield: 0.314 g (65%); mp 147–148 °C.
Yield: 0.340 g (70%); mp 145–146 °C.
IR (KBr): 2990 (C–HSt), 1765, 1750, 1740 (3 C=O), 1680 (C=N)
cm–1.
IR (KBr): 3000 (C–HSt), 1765, 1760, 1730 (3 C=O), 1688 (C=N)
cm–1.
3
1H NMR (500 MHz, CDCl3): d = 0.91 (d, JHH = 6.16 Hz, 6 H,
1H NMR (500 MHz, CDCl3): d = 0.96 (s, 9 H, CMe3), 1.01 (t,
CH(CH3)2), 0.95 (d, 3JHH = 6.21 Hz, 6 H, CH(CH3)2), 1.20–1.54 [m,
10 H, CH(CH2)5], 2.22, 2.53 (2 s, 6 H, 2 Ar-CH3), 3.63 (m, 1 H,
NCH), 4.91, 5.30 (2 m, 2 H, 2 OCH(CH3)2), 6.79 (d, 3JHH = 7.5 Hz,
1 H, H5), 7.30 (d, 3JHH = 7.49 Hz, 1 H, H7).
13C NMR (125 MHz, CDCl3): d = 13.81, 17.36 (2 Ar-CH3), 21.19,
21.30, 21.56, 21.72 (4 Me of 2 CH(CH3)2), 24.31, 24.35, 25.70,
32.98, 33.20, (5 CH2), 56.83 (N-CH), 69.92, 70.56 (2 OCH(CH3)2),
106.31 (CSpiro), 117.10, 119.96, 124.14, 136.83, 137.71, 139.16,
140.55, 151.47, 158.53 (C=N), 160.35, 169.30, 192.94 (3 C=O).
MS (EI, 70 eV): m/z (%) = 483 [M+] (13), 397 [M+ + 1 – CO2i-Pr]
(3), 386 [M+ – C6H11N] (13), 336 [M+ – 1 – CO2i-Pr – Oi-Pr] (10),
284 [M+ – 1 – C10H14O4] (10), 255 [M+ – C10H14O4 – 2CH3] (14),
211 [M+ + 1 – C6H11N – CO2i-Pr – Oi-Pr – 2CH3] (63), 149
3JHH = 7.0 Hz, 3 H, CH2CH3), 1.29, 1.31 (2 s, 6 H, CMe2), 1.34 (t,
2
3JHH = 7.7 Hz, 3 H, CH2CH3), 1.54, 1.59 (AB system, JHH = 14.3
Hz, 2 H, CH2), 2.37, 2.54 (2 s, 6 H, 2 Ar-CH3), 4.07 (q, 3JHH = 5.5
3
2
Hz, 2 H, OCH2), 4.35 (dq, JHH = 4.4 Hz, JHH = 4.5 Hz, 2 H,
OCH2), 6.70 (s, 1 H, H5), 6.72 (s, 1 H, H7).
13C NMR (125 MHz, CDCl3): d = 13.43, 14.03 (2 CH2CH3), 17.65,
22.52 (2 Ar-Me), 29.79 (CMe2), 31.55 (CMe3), 31.90 (CH2), 55.38
(CMe3), 59.26 (N-CMe2), 61.89, 62.26 (2 OCH2), 107.21 (CSpiro),
110.47, 115.25, 125.82, 135.34, 140.37, 141.74, 148.14, 150.60,
159.35 (C=N), 161.00, 171.17, 191.48 (3 C=O).
MS (EI, 70 eV): m/z (%) = 486 [M+ + 1] (5), 470 [M+ – CH3] (3),
439 [M+ – 1 – OCH2CH3] (4), 429 [M+ + 1 – C(CH3)3] (3), 414 [M+
– CH2 – C(CH3)3] (10), 358 [M+ – C8H17N] (6), 327 [M+ – C8H17N
– 2CH3] (21), 308 [M+ – 1 – 2CO2CH2CH3 – 2CH3] (9), 149
+
+
+
[C9H8O2 ] (95), 91 [C7H8 ] (16), 43 [CH(CH3)2 ] (100).
+
[C9H8O2 ] (100).
Diethyl 5¢-(tert-Butylimino)-4,6-dimethyl-3-oxospiro[benzofu-
ran-2(3H),2¢(5¢H)-furan]-3¢,4¢-dicarboxylate (7d)
Yield: 0.300 g (70%); mp 142–144 °C.
Dimethyl 4,6-Dimethyl-3-oxo-5¢-[(1,1,3,3-tetramethylbutyl)imi-
no]spiro[benzofuran-2(3H),2¢(5¢H)-furan]-3¢,4¢-dicarboxylate
(7g)
IR (KBr): 3000 (C–HSt), 1740, 1730, 1720 (3 C=O), 1680 (C=N)
cm–1.
Yield: 0.344 g (75%); mp 202–204 °C.
IR (KBr): 2990 (C–HSt), 1750, 1735, 1720 (3 C=O), 1685 (C=N)
cm–1.
3
1H NMR (500 MHz, CDCl3): d = 0.99 (t, JHH = 6.9 Hz, 3 H,
3
CH2CH3), 1.26 (s, 9 H, C(CH3)3), 1.33 (t, JHH = 6.9 Hz, 3 H,
CH2CH3), 2.36, 2.52 (2 s, 6 H, 2 Ar-CH3), 4.06 (q, 3JHH = 4.4 Hz, 2
1H NMR (500 MHz, CDCl3): d = 0.95 (s, 9 H, CMe3), 1.29, 1.31 (2
3
2
H, OCH2), 4.36 (q, JHH = 6.9 Hz, 2 H, OCH2), 6.91 (s, 1 H, H5),
s, 6 H, CMe2), 1.55, 1.59 (AB system, JHH = 14.3 Hz, 2 H, CH2),
6.71 (s, 1 H, H7).
2.38, 2.54 (2 s, 6 H, 2 Ar-CH3), 3.66, 3.89 (2 s, 6 H, 2 OCH3), 6.71
(s, 1 H, H5), 6.73 (s, 1 H, H7).
13C NMR (125 MHz, CDCl3): d = 13.42, 14.03 (2 CH2CH3), 17.64,
22.53 (2 Ar-CH3), 29.49, 29.61, 29.75 [C(CH3)3], 55.78 [C(CH3)3],
61.95, 62.34 (2 OCH2) 107.12 (CSpiro), 110.48, 115.18, 125.88,
135.74, 140.38, 141.53, 149.21, 150.72, 159.27 (C=N), 160.92,
171.17, 191.43 (3 C=O).
13C NMR (125 MHz, CDCl3): d = 17.53, 22.53 (2 Ar-CH3), 29.79,
(CMe2), 31.51 (CMe3), 31.94 (CH2), 52.83, 52.90 (2 OCH3), 55.42
(CMe3), 59.39 (N-CMe2), 107.17 (CSpiro), 110.52, 115.05, 125.98,
135.28, 140.43, 141.63, 148.02, 150.69, 159.93 (C=N), 161.40,
171.16, 191.23 (3 C=O).
MS (EI, 70 eV): m/z (%) = 429 [M+] (4), 373 [M+ + 1 – C(CH3)3]
(6), 327 [M+ + 1 – NC(CH3)3 – 2 CH3] (11), 255 [M+ – 1 –
NC(CH3)3 – CO2CH2CH3 – CH2CH3] (5), 225 [M+ – NC(CH3)3 –
MS (EI, 70 eV): m/z (%) = 458 [M+ + 1] (9), 442 [M+ – CH3] (3),
425 [M+ – 1 – OCH3] (3), 398 [M+ + 1 – CO2CH3] (3), 386 [M+ –
CH2 – C(CH3)3] (11), 345 [M+ – C(CH3)2 – CH2 – C(CH3)3] (5), 330
[M+ – NC(CH3)2 – CH2 – C(CH3)3] (5), 309 [M+ – 2CO2CH3 –
+
CO2CH2CH3 – OCH2CH3 – CH3] (14), 149 [C9H8O2 ] (100), 91
+
[C7H8 ] (6).
+
2CH3] (19), 149 [C9H8O2 ] (100).
Diethyl 5¢-(tert-Butylimino)-4,6,7-trimethyl-3-oxospiro[benzo-
furan-2(3H),2¢(5¢H)-furan]-3¢,4¢-dicarboxylate (7e)
Yield: 0.244 g (55%); mp 141–143 °C.
Synthesis 2009, No. 10, 1635–1638 © Thieme Stuttgart · New York

1638
A. A. Esmaeili, H. Vesalipoor
PAPER
(3) Ugi, I.; Lonberger, S.; Karl, R. Comprehensive Organic
Dimethyl 4,6,7-Trimethyl-3-oxo-5¢-[(1,1,3,3-tetramethylbu-
tyl)imino]spiro[benzofuran-2(3H),2¢(5¢H)-furan]-3¢,4¢-dicar-
boxylate (7h)
Synthesis, Vol. 2; Trost, B. M.; Fleming, I., Eds.; Pergamon:
Oxford, 1991, 1083.
Yield: 0.330 g (70%); mp 161–163 °C.
(4) Domling, A.; Ugi, I. Angew. Chem. Int. Ed. 2000, 39, 3168.
(5) Oakes, T. R.; David, H. G.; Nagel, F. J. Am. Chem. Soc.
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IR (KBr): 2995 (C–HSt), 1745, 1735, 1725 (3 C=O), 1685 (C=N)
cm–1.
(6) Ugi, I. Angew. Chem., Int. Ed. Engl. 1982, 21, 810.
(7) (a) Yavari, I.; Djahaniani, H.; Nasiri, F. Synthesis 2004,
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(8) (a) Alizadeh, A.; Rostamnia, S.; Esmaili, A. A. Synthesis
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Ghanbari-Niaki, A.; Mohebbi, A. R. Synthesis 2008, 2929.
(9) Esmaeili, A. A.; Darbanian, M. Tetrahedron 2003, 59, 5545.
(10) Yavari, I.; Esmaili, A. A.; Asghari, S.; Bijanzadeh, H. R.
J. Chem. Res., Synop. 1999, 368.
1H NMR (500 MHz, CDCl3): d = 0.96 (s, 9 H, CMe3), 1.29, 1.31 (2
s, 6 H, CMe2), 1.58, (s, 2 H, CH2), 2.12, 2.29, 2.51 (3 s, 9 H, 3 Ar-
CH3), 3.66, 3.89 (2 s, 6 H, 2 OCH3), 6.72 (s, 1 H, H5).
13C NMR (125 MHz, CDCl3): d = 10.30, 17.53, 22.53 (3 Ar-CH3),
29.77 (CMe2), 31.51 (CMe3), 31.91 (CH2), 52.81, 52.90 (2 OCH3),
55.92 (CMe3), 59.28 (N-CMe2), 107.21 (CSpiro), 114.87, 118.38,
126.39, 135.45, 137.06, 141.55, 148.24, 148.89, 159.95 (C=N),
161.54, 169.35, 191.97 (3 C=O).
MS (EI, 70 eV): m/z (%) = 471 [M+] (3), 456 [M+ – 1 – OCH3] (3),
412 [M+ – CO2CH3] (3), 400 [M+ – C5H11] (5), 359 [M+ – C8H17]
(5), 215 [M+ C8H17N] (6), 309 [M+ + 1–2CO2CH3 – 3CH3] (16), 163
+
+
[C10H10O2 ] (100), 91 [C7H8 ] (8).
(11) (a) Dider, V.; Liang, L. Synth. Commun. 2003, 33, 1575.
(b) Tang, Y.; Li, C. Tetrahedron Lett. 2006, 47, 3823.
(12) Beck, B.; Magnin-Lachaux, M.; Herdtweck, E.; Domling, A.
Org. Lett. 2001, 3, 2875.
(13) For reviews on furan-2(5H)-ones (but-2-en-4-olides), see:
(a) Rao, Y. S. Chem. Rev. 1964, 64, 353. (b) Rao, Y. S.
Chem. Rev. 1976, 76, 625. (c) Aretisyan, M.; Dangyan, M.
T. Russ. Chem. Rev. 1977, 46, 643.
(14) (a) Rupprecht, J. K.; Hui, Y. H.; Mclaughlin, J. L. J. Nat.
Prod. 1990, 53, 237. (b) Zeng, L.; Ye, Q.; Oberlis, G.; Shi,
N. H.; Gu, K. H.; Mclaughlin, J. L. Nat. Prod. Rep. 1996, 13,
275.
(15) Cavallito, C. J. Med. Chem. 1951, 1, 221.
(16) Restock, T. L.; Sell, H. M. J. Am. Chem. Soc. 1952, 74, 274.
(17) Payne, G. B. US Patent 3177224, 1965; Chem. Abstr. 1965,
63, 6866e.
Diethyl 4,6,7-Trimethyl-3-oxo-5¢-[(1,1,3,3-tetramethylbu-
tyl)imino]spiro[benzofuran-2(3H),2¢(5¢H)-furan]-3¢,4¢-dicar-
boxylate (7i)
Yield: 0.324 g (65%); mp 128–130 °C.
IR (KBr): 2995 (C–HSt), 1745, 1730, 1725 (3 C=O), 1680 (C=N)
cm–1.
1H NMR (500 MHz, CDCl3): d = 0.96 (s, 9 H, CMe3), 1.00 (t,
3JHH = 7.1 Hz, 3 H, CH2CH3 ), 1.30, 1.31 (2 s, 6 H, CMe2), 1.35 (t,
3JHH = 7.6 Hz, 3 H, CH2CH3), 1.58 (s, 2 H, CH2), 2.11, 2.28, 2.50 (3
3
2
s, 9 H, 3 Ar-CH3), 4.06 (dq, JHH = 5.5 Hz, 2 H, JHH = 4.5 Hz,
OCH2), 4.36 (dq, 3JHH = 4.4 Hz, 2 H, 2JHH = 4.5 Hz, OCH2), 6.71 (s,
1 H, H5).
13C NMR (125 MHz, CDCl3): d = 10.28, 13.44 (CH2CH3), 14.04
17.28, 20.28 (3 Ar-CH3), 29.80 (CMe2), 31.55 (CMe3), 31.90 (CH2),
55.31 (CMe2), 59.20 (N-CMe2), 61.90, 62.24 (2 OCH2), 107.21
(CSpiro), 115.05, 117.64, 125.82, 126.64, 135.57, 136.34, 140.35,
148.35, 159.37 (C=N), 161.13, 169.37, 192.21 (3 C=O).
(18) Ito, Y.; Kato, H.; Saegusa, T. J. Org. Chem. 1982, 47, 741.
(19) Winterfeldt, E.; Schumann, D.; Dillinger, H.-J. Chem. Ber.
1969, 102, 1656.
(20) Nair, V.; Vinod, A. U.; Abhilash, N.; Menon, R. S.; Santhi,
V.; Varma, R. L.; Viji, S.; Mathewa, S.; Srinivas, R.
Tetrahedron 2003, 59, 10279.
MS (EI, 70 eV): m/z (%) = 499 [M+] (5), 484 [M+ – CH3] (3), 453
[M+ – OCH2CH3] (11), 382 [M+ + 1 – CO2CH2CH3 – 3CH3] (16),
372 [M+ – C8H17N] (7), 337 [M+ + 1 – CO2CH2CH3 – 3CH3 –
+
(21) Chatani, N.; Oshita, M.; Tobisu, M.; Ishii, Y.; Murai, S.
J. Am. Chem. Soc. 2003, 125, 7812.
OCH2CH3] (13), 163 [C10H10O2 ] (100).
(22) Bez, B.; Zhao, C. G. Org. Lett. 2003, 5, 4991.
(23) Ma, S.; Xie, H. J. Org. Chem. 2002, 67, 6575.
(24) Ma, S.; Xie, H. Tetrahedron 2005, 61, 251.
(25) Esmaeili, A. A.; Zendegani, H. Tetrahedron 2005, 61, 4031.
(26) Nair, V.; Rajesh, C.; Vinod, A. U.; Bindu, S.; Speekanth, A.
R.; Mathen, J. S.; Balagopal, L. Acc. Chem. Res. 2003, 36,
899.
Acknowledgment
We gratefully acknowledge financial support from the Research
Council of the University of Birjand.
References
(27) Domling, A. Chem. Rev. 2006, 106, 17.
(1) Ugi, I. Isonitrile Chemistry; Academic Press: London, 1971.
(2) Ugi, I.; Domling, A.; Horl, W. Endeavour 1994, 18, 115.
(28) Chatani, N.; Amako, K.; Tobisu, M.; Asaumi, T.; Fukumoto,
Y.; Murai, S. J. Org. Chem. 2003, 68, 1591.
Synthesis 2009, No. 10, 1635–1638 © Thieme Stuttgart · New York