A highly diastereoselective five-component synthesis of 1-(alkylimino)-5,5-dicyano-3a-aryloctahydro-3-oxacyclobuta[cd]pentalene-1a,2,5a,5b(2H,3aH)-tetracarboxylates

Article abstract of DOI:10.1016/j.tetlet.2014.07.007

A novel one-pot, five-component synthesis of 1-(alkylimino)-5,5-dicyano-3a-aryloctahydro-3-oxacyclobuta[cd]pentalene-1a,2,5a,5b(2H,3aH)-tetracarboxylates is described. A mixture of phenacyl bromide, malononitrile, isocyanide, and two equivalents of a dial

Full text of DOI:10.1016/j.tetlet.2014.07.007

Tetrahedron Letters 55 (2014) 4983–4986
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A highly diastereoselective five-component synthesis
of 1-(alkylimino)-5,5-dicyano-3a-aryloctahydro-3-
oxacyclobuta[cd]pentalene-1a,2,5a,5b(2H,3aH)-tetracarboxylates
a
a
a
b
Mehdi Adib a, , Ehsan Sheikhi , Pouyan Haghshenas , Saideh Rajai-Daryasarei , Hamid Reza Bijanzadeh ,
⇑
Long-Guan Zhu c
a School of Chemistry, University College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran
b Department of Chemistry, Tarbiat Modarres University, PO Box 14115-175, Tehran, Iran
c Chemistry Department, Zhejiang University, Hangzhou 310027, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel one-pot, five-component synthesis of 1-(alkylimino)-5,5-dicyano-3a-aryloctahydro-3-oxacyclob-
uta[cd]pentalene-1a,2,5a,5b(2H,3aH)-tetracarboxylates is described. A mixture of phenacyl bromide,
malononitrile, isocyanide, and two equivalents of a dialkyl acetylenedicarboxylate undergoes a novel
1:1:1:2 addition reaction at ambient temperature in absolute ethanol to produce diastereoselectively
the title compounds in good yields.
Received 19 February 2014
Revised 10 June 2014
Accepted 3 July 2014
Available online 9 July 2014
Ó 2014 Published by Elsevier Ltd.
Keywords:
Isocyanides
Dialkyl acetylenedicarboxylates
Phenacyl bromides
Multicomponent reactions
3-Oxacyclobuta[cd]pentalenes
Diastereoselective synthesis
In multicomponent reactions (MCRs) several reactions are
combined into a single synthetic operation. MCRs have been
widely used in organic synthesis, as well as in combinatorial and
medicinal chemistry. Typically, purification of products resulting
from MCRs is also simple since all the organic reagents employed
are consumed and are incorporated into the target compound.
Maximization of yields, reduction of waste, and ecofriendly proce-
dures, thus make MCRs significant for the preparation of complex
molecules from readily accessible starting materials. Many new
3- and 4-component reactions have been reported, and efforts to
develop new MCRs are continuing.1 Isocyanide-based MCRs are
especially important in this area.2
The rich and attractive chemistry that stems from the addition
of nucleophiles to electron-deficient acetylenic compounds has
attracted significant attention. Usually the addition of nucleophiles
lacking acidic hydrogen atoms leads to a 1:1 zwitterionic interme-
diate that can undergo further transformations leading to a stabi-
lized product.3 It is known from the studies of various groups
that triphenylphosphine,4 pyridine,5 amines,6 dimethyl sulfoxide,7
phosphoranes,8 and isocyanides9 can lead to the formation of zwit-
terions. Isocyanides, however, differ in their reactivity profile due
to the presence of the divalent carbon atom and its pronounced
reactivity toward C (sp or sp2) electrophilic centers. In transforma-
tions involving these entities, this divalent carbon is converted into
a tetravalent state, which makes the addition irreversible. This
property of isocyanides was important for the successful develop-
ment of classical MCRs such as the Passerini 3CR and Ugi 4CR.2
Winterfeldt, in his pioneering work, had observed that isocya-
nides readily add to dimethyl acetylenedicarboxylate (DMAD).9
The initially formed 1:1 zwitterionic intermediate can undergo
further reaction with DMAD and an isocyanide in different molar
proportions leading to various adducts. Subsequently, George and
co-workers established the structure of adducts by the single-
crystal X-ray analysis.10 When the reaction was carried out in a
protic solvent such as ethanol, zwitterionic intermediate was
protonated and concomitant attack of the resulting nucleophile
generated an imino ester and a ketenimine.11
The Winterfeldt zwitterion has been intercepted by various O–
H, N–H, and C–H acids.12 We were intrigued by the possibility of
trapping this zwitterionic intermediate by a new CH-acid, 2-(2-
aryl-2-oxoethyl)malononitrile, leading to new carbo/heterocyclic
compounds.
⇑
Corresponding author. Tel./fax: +98 21 66495291.
E-mail address: madib@khayam.ut.ac.ir (M. Adib).
http://dx.doi.org/10.1016/j.tetlet.2014.07.007
0040-4039/Ó 2014 Published by Elsevier Ltd.

4984
M. Adib et al. / Tetrahedron Letters 55 (2014) 4983–4986
CO2R'
C
Thus a mixture of phenacyl bromide 1, malononitrile (2), isocyanide
O
Ar
CN
CN
O
_
3 and a dialkyl acetylenedicarboxylate 4 in the presence of
Et3N underwent a novel 1:1:1:2 addition reaction at ambient
temperature in absolute ethanol to afford 1-(alkylimino)-5,
5-dicyano-3a-aryloctahydro-3-oxacyclobuta[cd]pentalene-1a,2,5a,
5b(2H,3aH)-tetracarboxylates 5a–j in 50–79% yields (Scheme 1,
Table 1). All the reactions went to completion within a few hours.
1H NMR spectroscopic analysis of the reaction mixtures clearly
indicated the formation of the corresponding 3-oxacyclobuta[cd]
pentalenes 5 in good yields.15
Et3N
EtOH, r.t.
CN
CN
+
Ar
+
+
R
N
+ 2
+
HBr
C
E
E
C
Br
E
E
CO2R'
N
R
1
2
3
4
5, E = CO2R'
Scheme 1. Synthesis of 1-(alkylimino)-5,5-dicyano-3a-aryloctahydro-3-oxacyclob-
uta[cd]pentalene-1a,2,5a,5b(2H,3aH)-tetracarboxylates 5.
The structures of the isolated products 5a–j were deduced on the
basis of IR, 1H, and 13C NMR spectroscopies, mass spectrometry, and
elemental analysis. The IR spectrum of 5a showed absorptions at
1738 and 2188 cmÀ1 indicating the presence of ester and nitrile
functionalities. The mass spectrum of 5a displayed the molecular
ion (M+) peak at m/z = 551, which was consistent with the 1:1:1:2
adduct of 2-bromo-1-phenylethanone, malononitrile, tert-butyl
isocyanide, and dimethyl acetylenedicarboxylate with the loss of
a hydrogen bromide molecule. The 1H NMR spectrum of 5a
To the best of our knowledge there is only one report concern-
ing the synthesis of oxacyclobuta[cd]pentalenes in the literature. In
1987, Salomon et al. reported the Cu(I)-catalyzed intermolecular
photocycloaddition of monocyclic diallyl ethers leading to the
corresponding oxacyclobuta[cd]pentalene.13
As part of our current studies on the development of efficient
methods for the preparation of important carbo- and heterocyclic
compounds,14 herein we describe
a one-pot, five-component
synthesis of highly functionalized 3-oxacyclobuta[cd]pentalenes.
Table 1
Synthesis of 1-(alkylimino)-5,5-dicyano-3a-aryloctahydro-3-oxacyclobuta[cd]pentalene-1a,2,5a,5b(2H,3aH)-tetracarboxylates 5a–j
Product
Structure
mp (°C)
Yielda (%)
Product
Structure
mp (°C)
Yielda (%)
O
E
O
E
CN
CN
CN
CN
E
E
5a
195
58
5b
229
55
E
E
E
E
N
N
E = CO2Me
E = CO2Me
O
E
O
E
CN
CN
CN
CN
E
E
5c
215
50
5d
203
73
E
E
E
E
N
N
E = CO2Me
E = CO2Et
Ph
Ph
O
O
CN
CN
CN
CN
5e
211
70
5f
203
73
E
E
E
E
E
E
E
E
N
N
E = CO2Me
E = CO2Me
Ph
OMe
O
O
O
O
CN
CN
CN
CN
5g
207
66
5h
188
79
E
E
E
E
E
E
E
E
E
E
E
E
N
N
E = CO2Et
OMe
E = CO2Me
Ph
CN
CN
CN
CN
5i
189
76
5j
217
64
E
E
E
E
N
N
E = CO2Me
E = CO2Et
a
Isolated yields.

M. Adib et al. / Tetrahedron Letters 55 (2014) 4983–4986
4985
O
CN
E
O
exhibited six singlets arising from the CMe3 (d 1.36), four methoxy
groups (d 2.98, 3.73, 3.80, and 3.82), and the oxacyclopentane ring
CH (d 5.42) along with characteristic signals for the five phenyl
H-atoms. The two diastereotopic H atoms of the cyclopentane ring
were observed as two doublets (an AB system, dB 3.37 and dA 4.05,
2J = 16.3 Hz). The 1H decoupled 13C NMR spectrum of 5a showed
characteristic signals at d 29.9 and 60.2 (due to the tert-butyl
group), 42.7 [for the C(CN)2], 44.8 (for the CH2 of the cyclopentane
ring), 52.2, 52.6, 53.2, and 53.7 (for the four methoxy groups), 82.1
(due to the CHCO2CH3 moiety), 71.4, 74.3, 79.1, and 100.3 (arising
from the other four quaternary carbons of the oxacyclobuta[cd]pen-
talene ring). Characteristic resonances were also evident at d 112.9
and 115.4 (for the two CN groups), 165.6, 165.8, 166.3, and 168.2
(due to the four carbonyl groups), 145.0 (for C@N), along with four
other signals (for the three CHs and the ipso carbon of the phenyl
substituent) in the downfield region of the spectrum, in agreement
with the proposed structure.15
CN
Et3N
O
CN
_
+
E
8
CN
_
_
Ar
R
HBr
Ar
CN
CN
2
Ar
E
Br
1
6
E
R
+
N
E
_
E
+
H
_
C
N
+
E
E
N
E
4
R
E
E
3
9
E
7
4
O
+
Ar
Ar
CN
CN
CN
CN
Ar
O
R
E
_
E
CN
CN
_
O
E
E
E
E
E
E
E
E
E
E
+N
R
N
H
H
N
R
5
10
E = CO2R'
11
Single-crystal X-ray analysis of 5a conclusively confirmed its
structure, and by analogy, those of the other isolated products.
An ORTEP diagram of 5a is shown in Figure 1.16
Scheme 2. Possible mechanism for the formation of 3-oxacyclobuta[cd]pentalenes 5.
positions of C15 and C11 (Fig. 1), respectively. On the other hand,
in the tetrahydrofuran ring there is a hydrogen atom in the axial-
like and a carboalkoxy group in the equatorial-like positions of
C10, and an oxygen atom (O9) with no substituent in place of
C11 of the cyclopentane ring.
A mechanistic rationalization for this reaction is provided in
Scheme 2. At first, reaction of the phenacyl bromide with malono-
nitrile in the presence of Et3N produces 2-(2-aryl-2-oxoethyl)
malononitrile 6 with the loss of hydrogen bromide. Next, the
reactive 1:2 zwitterionic intermediate 7, generated in situ from
the addition reaction between the isocyanide 3 and the dialkyl
acetylenedicarboxylate 4,2,17,18 is protonated by 6. The highly
electron-deficient positively charged isonitrilium 1,3-butadiene
intermediate 9 may be attacked by the conjugate base of the acid
8 to form adduct 10. This adduct may undergo cyclization to give
the cyclopentoxide intermediate 11 via nucleophilic addition of
the stabilized allylic anion on the adjacent carbonyl group. Conju-
There are five chiral centers in the obtained highly strained
3-oxacyclobuta[cd]pentalenes and thus there would be a maxi-
mum of 32 stereoisomers or 16 pairs of enantiomers. Of these
possible 16 diastereomers only one stereoisomer namely 1aS, 2S,
3aS, 5aR, 5bS (or its enantiomer 1aR, 2R, 3aR, 5aS, 5bR) is formed
in this reaction. Thus the reaction is highly diastereoselective and
leads to a bowl-like stereoisomer with all four carboalkoxy groups
as well as the aryl substituent on the five chiral centers of the
molecule located on the same side of the tricyclic ring. Our
attempts to detect any other diastereomer in the reaction mixture
were not successful. The exclusive formation of the obtained geo-
metrical isomers is due to the fusion of the three rings. Strain
and crowding of the tricyclic fused ring and its substituents will
be increased by any change of configuration in each of the five
chiral centers of the molecule, some of which would be impossible.
There is also another stereogenic element in the obtained prod-
ucts, the imine moiety, in which the bulky R group on the N-atom
is oriented toward the less crowded tetrahydrofuran ring not the
cyclopentane ring. The imine group is nearly located at the edge
of the bowl. In the cyclopentane ring there are two cyanide groups
and two hydrogen atoms in the equatorial-like and axial-like
gate addition of the alkoxide ion to the adjacent
a,b-unsaturated
system and subsequent attack of the resulting enolate on the
nitrilium moiety may afford the isolated 3-oxacyclobuta[cd]
pentalene 5.
In conclusion, we have developed a novel, one-pot five-compo-
nent reaction between 2-bromoacetophenones, malononitrile,
isocyanides, and dialkyl acetylenedicarboxylates (a 1:1:1:2 addition
reaction) for the preparation of 1-(alkylimino)-5,5-dicyano-3a-aryl-
octahydro-3-oxacyclobuta[cd]pentalene-1a,2,5a,5b(2H,3aH)-tetra-
carboxylates. High bond formation efficiency, good yields of
products, the use of simple and readily available starting materials,
mild reaction conditions, and fairly short reaction times are the main
advantages of this method. The reaction is highly diastereoselective.
Of the 16 possible diastereomers only one, the bowl-like stereoiso-
mer, is formed in this reaction, in which all five substituents on chiral
centers of the molecule are located on the same side of the tricyclic
ring. Formation of a highly strained tricyclic 5:5:4 ring system and
the creation of six bonds, particularly five C–C bonds, make this
process very attractive from a chemical point of view.
Acknowledgement
This research was supported by the Research Council of the
University of Tehran.
References and notes
1. (a)Multicomponent Reactions; Zhu, J., Bienaymé, H., Eds.; Wiley-VCH:
Weinheim, 2005; (b) Jiang, B.; Yi, M. S.; Shi, F.; Tu, S. J.; Pindi, S.; McDowell,
P.; Li, G. Chem. Commun. 2012, 808–810; (c) Jiang, B.; Li, Q. Y.; Zhang, H.; Tu, S.
J.; Pindi, S.; Li, G. Org. Lett. 2012, 14, 700–703; (d) Han, X.; Li, H.; Hughes, R. P.;
Figure 1. ORTEP diagram of the molecular structure of 5a.

4986
M. Adib et al. / Tetrahedron Letters 55 (2014) 4983–4986
Wu, J. Angew. Chem., Int. Ed. 2012, 51, 10390–10393; (e) Knapp, J. M.; Zhu, J. S.;
1-(tert-butylimino)-5,5-dicyano-3a-phenyloctahydro-3-oxacyclobuta[cd]pentalene-
Tantillo, D. J.; Kurth, M. J. Angew. Chem., Int. Ed. 2012, 51, 10588–10591; (f) Roy,
S.; Reiser, O. Angew. Chem., Int. Ed. 2012, 51, 4722–4725; (g) Wen, L. R.; He, T.;
Lan, M. C.; Li, M. J. Org. Chem. 2013, 78, 10617–10628; (h) Cornier, P. G.;
Delpiccolo, C. M. L.; Boggián, D. B.; Mata, E. G. Tetrahedron Lett. 2013, 54, 4742–
4745; (i) Liu, Y. P.; Liu, J. M.; Wang, X.; Cheng, T. M.; Li, R. T. Tetrahedron 2013,
69, 5242–5247.
1a,2,5a,5b(2H,3aH)-tetracarboxylate (5a): Colorless crystals, mp 195 °C, yield:
0.320 g, 58%. IR (KBr) (m
max/cmÀ1): 2188 (CN), 1738 (C@O), 1434, 1365, 1288,
1240, 1128, 1035, 980, 930, 848, 818, 767, 704, 629. EI-MS, m/z (%): 551 (M+, 1),
495 (4), 464 (2), 436 (17), 404 (12), 372 (3), 309 (100), 281 (3), 184 (12), 128 (5),
105 (11), 57 (50), 41 (10). Anal. Calcd for C28H29N3O9 (551.55): C, 60.97; H, 5.30;
N, 7.62. Found: C, 60.8; H, 5.5; N, 7.4. 1H NMR (500.1 MHz, acetone-d6): d 1.36
[9H, s, C(CH3)3], 2.98 (3H, s, OCH3), 3.37 (1H, d, 2J = 16.3 Hz, CH), 3.73, 3.80 and
3.82 (9H, 3 s, 3OCH3), 4.05 (1H, br d, 2J = 16.3 Hz, CH), 5.42 (1H, s, CHCO2CH3),
7.40–7.42 (3H, m, 3CH), 7.89 (2H, br s, 2CH). 13C NMR (125.8 MHz, acetone-d6): d
29.9 [C(CH3)3], 42.7 [C(CN)2], 44.8 (CH2), 52.2, 52.6, 53.2 and 53.7 (4OCH3),
60.2 [C(CH3)3], 71.4, 74.3 and 79.1 (3C), 82.1 (CHCO2CH3), 100.3 (C), 112.9 and
115.4 (2CN), 128.2, 128.7 and 129.9 (3CH), 138.8 (C), 145.0 (C@N), 165.6, 165.8,
166.3 and 168.2 (4C@O). Tetramethyl 5,5-dicyano-1-(1,1,3,3-tetramethylbu-
tylimino)-3a-phenyloctahydro-3-oxacyclobuta[cd]pentalene-1a,2,5a,5b(2H,3aH)-
tetracarboxylate (5d): Colorless crystals, mp 202–203 °C, yield: 0.443 g, 73%. IR
2. (a) Dömling, A. Chem. Rev. 2006, 106, 17–89; (b) Dömling, A.; Ugi, I. Angew.
Chem., Int. Ed. 2000, 39, 3169–3210; (c) Wang, X.; Wang, S. Y.; Ji, S. J. Org. Lett.
2013, 15, 1954–1957; (d) Mercalli, V.; Meneghetti, F.; Tron, G. C. Org. Lett. 2013,
15, 5902–5905; (e) Soleimani, E.; Zainali, M.; Ghasemi, N.; Notash, B.
Tetrahedron 2013, 69, 9832–9838.
3. Winterfeldt, E. Angew. Chem., Int. Ed. Engl. 1967, 6, 423–434.
4. (a) Johnson, A. W.; Tebby, J. C. J. Chem. Soc. 1961, 2126–2130; (b) Tebby, J. C.;
Wilson, I. F.; Griffiths, D. V. J. Chem. Soc., Perkin Trans. 1 1979, 2133–2135; (c)
Butterfield, P. J.; Tebby, J. C.; Griffiths, D. V. J. Chem. Soc., Perkin Trans. 1 1979,
1189–1191; (d) Shaw, M. A.; Tebby, J. C.; Ward, R. S.; Williams, D. H. J. Chem.
Soc. (C) 1968, 2795–2801.
5. (a) Diels, O.; Alder, K. Liebigs Ann. Chem. 1932, 498, 16–49; (b) Acheson, R. M.
Adv. Heterocycl. Chem. 1963, 11, 125–165.
6. (a) Winterfeldt, E. Chem. Ber. 1964, 97, 1952–1958; (b) Winterfeldt, E.;
Dillinger, H. J. Chem. Ber. 1966, 99, 1558–1568.
(KBr) (m
max/cmÀ1): 2191 (CN), 1756 and 1730 (C@O), 1436, 1363, 1300, 1271,
1228, 1120, 1071, 986, 882, 763, 708. EI-MS, m/z (%): 607 (M+, <1), 496 (4), 436
(3), 326 (11), 309 (100), 294 (9), 267 (39), 252 (8), 235 (27), 217 (9), 170 (19), 138
(35), 105 (22), 77 (14), 57 (68), 41 (23). Anal. Calcd for C32H37N3O9 (607.65): C,
63.25; H, 6.14; N, 6.92. Found: C, 63.3; H, 6.1; N, 6.8%. 1H NMR (500.1 MHz,
acetone-d6): d 1.02 [9H, s, C(CH3)3], 1.32 and 1.41 [6H, 2s, C(CH3)2], 1.57 and 1.63
(2H, 2d, AB system, 2J = 15.2 Hz, CHAHB), 3.39 (3H, s, OCH3), 3.59 (1H, d,
2J = 14.5 Hz, CH), 3.71, 3.75 and 3.81 (9H, 3s, 3OCH3), 3.83 (1H, d, 2J = 14.5 Hz,
CH), 5.76 (1H, s, CHCO2CH3), 7.42 (1H, t, J = 7.5 Hz, CH), 7.46 (2H, dd, J = 7.6,
7.4 Hz, 2CH), 7.53 (2H, d, J = 7.4 Hz, 2CH). 13C NMR (125.8 MHz, acetone-d6): d
28.4 and 29.0 [C(CH3)2], 32.0 [C(CH3)3], 32.3 [C(CH3)3], 39.7 [C(CN)2], 40.6 (CH2),
52.2 (OCH3), 52.9 (CH2), 53.0, 53.4 and 53.5 (3OCH3), 56.5 [C(CH3)2], 68.4, 73.7
and 78.1 (3C), 84.8 (CHCO2CH3), 98.3 (C), 114.7 and 116.3 (2CN), 126.7, 129.7 and
130.1 (3CH), 136.7 (C), 140.9 (C=N), 166.2, 166.4, 166.5 and 166.9 (4C@O).
7. Winterfeldt, E. Chem. Ber. 1965, 98, 1581–1587.
8. (a) Bestmann, H. J.; Rothe, O. Angew. Chem. 1964, 76, 569; (b) Brown, G. W.;
Cookson, R. C.; Stevens, D. R. Tetrahedron Lett. 1964, 5, 1263–1266.
9. Winterfeldt, E.; Schumann, D.; Dillinger, H. J. Chem. Ber. 1969, 102, 1656–1664.
10. Junjappa, H.; Saxena, M. K.; Ramaiah, D.; Lohray, B. B.; Rath, N. P.; George, M. V.
J. Org. Chem. 1998, 63, 9801–9805.
11. (a) Dillinger, H. J.; Fengler, G.; Schumann, D.; Winterfeldt, E. Tetrahedron 1974,
30, 2553–2559; (b) Dillinger, H. J.; Fengler, G.; Schumann, D.; Winterfeldt, E.
Tetrahedron 1974, 30, 2561–2564; (c) Takizawa, T.; Obata, N.; Suzuki, Y.;
Yanagida, T. Tetrahedron Lett. 1969, 10, 3407–3410; (d) Suzuki, Y.; Obata, N.;
Takizawa, T. Tetrahedron Lett. 1970, 11, 2667–2670; (e) Oakes, T. R.; David, H.
G.; Nagel, F. J. J. Am. Chem. Soc. 1969, 91, 4761–4765; (f) Oakes, T. R.; Donovan,
D. J. Org. Chem. 1973, 38, 1319–1325; (g) Johnson, F. A.; Gulbenkian, A. H.;
Naustavicus, W. J. Chem. Soc., Chem. Commun. 1970, 608; (h) Krebs, A.; Guntner,
A.; Versteylen, S.; Schulz, S. Tetrahedron Lett. 1984, 25, 2333–2336.
12. Shaabani, A.; Maleki, A.; Rezayan, A. H.; Sarvary, A. Mol. Diversity 2011, 15, 41–
68.
13. Ghosh, S.; Raychaudhuri, S. R.; Salomon, R. G. J. Org. Chem. 1987, 52, 83–90.
14. (a) Adib, M.; Sheikhi, E.; Bijanzadeh, H. R.; Zhu, L. G. Tetrahedron 2012, 68,
3377–3383; (b) Adib, M.; Sheikhi, E.; Bagheri, M.; Bijanzadeh, H. R.; Amanlou,
M. Tetrahedron 2012, 68, 3237–3242; (c) Adib, M.; Sheikhi, E.; Rezaei, N.
Tetrahedron Lett. 2011, 52, 3191–3194; (d) Adib, M.; Ansari, S.; Bijanzadeh, H. R.
Synlett 2011, 619–622; (e) Adib, M.; Karimzadeh, M.; Mahdavi, M.; Sheikhi, E.;
Mirzaei, P. Synlett 2011, 834–836; (f) Adib, M.; Sheikhi, E.; Kavoosi, A.;
Bijanzadeh, H. R. Tetrahedron 2010, 66, 9263–9269; (g) Adib, M.; Sheikhi, E.;
Kavoosi, A.; Bijanzadeh, H. R. Synthesis 2010, 4082–4086; (h) Adib, M.;
Mohamadi, A.; Sheikhi, E.; Ansari, S.; Bijanzadeh, H. R. Synlett 2010, 1606–
1608; (i) Adib, M.; Sheibani, E.; Zhu, L. G.; Bijanzadeh, H. R. Tetrahedron Lett.
2009, 50, 4420–4422; (j) Adib, M.; Sheibani, E.; Bijanzadeh, H. R.; Zhu, L. G.
Tetrahedron 2008, 64, 10681–10686; (k) Adib, M.; Mohammadi, B.; Bijanzadeh,
H. R. Synlett 2008, 3180–3182.
15. General procedure for the preparation of compounds 5a–j, exemplified by 5a: A
solution of 2-bromoacetophenone (0.199 g, 1 mmol), malononitrile (0.066 g,
1 mmol), and Et3N (0.101 g, 1 mmol) in EtOH (3 mL) was stirred at ambient
temperature for 1 h. After addition of tert-butyl isocyanide (0.083 g, 1 mmol), a
solution of dimethyl acetylenedicarboxylate (0.284 g, 2 mmol) in EtOH (2 mL)
was added dropwise to the reaction mixture over 25 min, which was then stirred
at ambient temperature for 6 h. The solvent was removed under reduced
pressure, and the residue was purified by column chromatography (Merck
silica gel 230–240 mesh) using n-hexane–EtOAc (3:1) as eluent. Tetramethyl
Tetraethyl
oxacyclobuta[cd]pentalene-1a,2,5a,5b(2H,3aH)-tetracarboxylate (5j): Colorless
crystals, mp 217 °C, yield: 0.454 g, 64%. IR (KBr) (
max/cmÀ1): 2192 (CN), 1741
5,5-dicyano-1-(cyclohexylimino)-3a-(4-phenylphenyl)octahydro-3-
m
(C@O), 1450, 1370, 1243, 1109, 1039, 1014, 884, 770, 699. EI-MS, m/z (%): 709
(M+, 41), 635 (24), 628 (28), 620 (21), 555 (39), 508 (18), 480 (10), 437 (16), 413
(100), 391 (12), 339 (18), 311 (19), 224 (63), 181 (22), 142 (27), 83 (16), 55 (21),
41 (9). Anal. Calcd for C40H43N3O9 (709.78): C, 67.69; H, 6.11; N, 5.92. Found: C,
67.8; H, 6.3; N, 5.8%. 1H NMR (500.1 MHz, acetone-d6): d 0.72 (3H, t, J = 7.2 Hz,
OCH2CH3), 1.22–1.88 [9H, 3t (1.24, 1.30 and 1.36), J = 7.2 Hz, 3OCH2CH3; and
10H, m, CH(CH2)5], 3.27 (1H, dq, ABX3 system, 2J = 10.7, 3J = 7.2 Hz, OCHAHBCH3),
3.44 (1H, d, 2J = 16.5 Hz, CH), 3.62 (1H, dq, ABX3 system, 2J = 10.7, 3J = 7.2 Hz,
OCHAHBCH3), 3.82–3.90 (1H, m, NCH), 4.11 (1H, d, 2J = 16.5 Hz, CH), 4.13–4.23
(2H, m, OCH2CH3), 4.29–5.20 (4H, m, 2OCH2CH3), 5.20 (1H, s, CHCO2C2H5), 7.39
(1H, t, J = 7.4 Hz, CH), 7.48 (2H, dd, J = 7.9, 7.4 Hz, 2CH), 7.69 (2H, d, J = 7.9 Hz,
2CH), 7.72 (2H, d, J = 8.6 Hz, 2CH), 7.92 (2H, d, J = 8.6 Hz, 2CH). 13C NMR
(125.8 MHz, acetone-d6): d 13.4, 14.1, 14.2 and 14.7 (4OCH2CH3), 24.4, 24.5, 26.3,
32.7 and 33.6 [CH(CH2)5], 41.8 [C(CN)2], 44.7 (CH2), 61.9 [NCH(CH2)5], 62.1, 62.4,
63.1 and 63.4 (4OCH2CH3), 70.7, 73.1 and 75.1 (3C), 82.2 (CHCO2C2H5), 99.6 (C),
113.1 and 115.4 (2CN), 127.2, 127.8, 128.6, 128.8 and 129.8 (5CH), 137.6, 140.9
and 142.7 (3C), 151.6 (C@N), 164.6, 165.3, 165.4 and 167.1 (4C@O).
16. Selected X–ray crystallographic data for compound 5a: C28H29N3O9, triclinic,
space group = P-1, a = 9.4093(5) Å, b = 11.6447(8) Å, c = 13.1200(8) Å,
a
= 96.468(5)°, b = 102.596(5)°,
c
= 96.629(5)°, V = 1379.41(15) Å3, T = 295(2)
K, Z = 2, Dcalcd = 1.328 g cmÀ3 = 0.100 mmÀ1, 3310 observed reflections, final
, l
R1 = 0.041, wR2 = 0.113 and for all data R1 = 0.067, wR2 = 0.124. CCDC 858050
contains the supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
17. Ugi, I. Isonitrile Chemistry; Academic Press: London, 1971.
18. Walborsky, H. M.; Periasamy, M. P. In The Chemistry of Functional Groups,
Supplement C; Patai, S., Rappaport, Z., Eds.; Wiley: New York, 1983; pp 835–
837. Chap. 20.