A new iodonium ylide-based three-component reaction leading to 2-spirosubstituted dihydrofurans under microwave irradiation

Article abstract of DOI:10.1002/jhet.1732

A new iodonium ylide-based three-component reaction for the synthesis of highly functionalized 2-spirosubstituted dihydrofurans starting from readily available common reactants has been developed under microwave irradiation. The procedure is facile, avoid

Full text of DOI:10.1002/jhet.1732

436
A New Iodonium Ylide-Based Three-Component Reaction Leading to
2-Spirosubstituted Dihydrofurans under Microwave Irradiation
Vol 51
*
*
Xing-Chao Tu, Yan Yu, Man-Su Tu, Bo Jiang , Chao Li, and Shu-Jiang Tu
School of Chemistry & Chemical Engineering, and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional
Materials, Jiangsu Normal University, Xuzhou, Jiangsu, 221116, People’s Republic of China
*
E-mail: jiangchem@jsnu.edu.cn; laotu2001@263.net
Received February 14, 2012
DOI 10.1002/jhet.1732
Published online 19 November 2013 in Wiley Online Library (wileyonlinelibrary.com).
O
O
O
R
O
O
O
I
Ph
KOH
+
+
R-CHO
1,4-dioxane
O
O
A new iodonium ylide-based three-component reaction for the synthesis of highly functionalized
2-spirosubstituted dihydrofurans starting from readily available common reactants has been developed
under microwave irradiation. The procedure is facile, avoiding time-consuming and costly syntheses,
tedious work-up and purifications of precursors as well as protection/deprotection of functional groups.
This method is very efficient because of short reaction times and easy work-up and provides an
efficient strategy for the construction of the polysubstituted spiro dihydrofuran skeleton.
J. Heterocyclic Chem., 51, 436 (2014).
INTRODUCTION
them, phenyliodonium ylides, derived from b-dicarbonyl
compounds, constitute an interesting type of hypervalent
iodine compounds [8,9]. Because of their cheap and ready
availability, phenyliodonium ylides have been used exten-
sively in organic synthesis for a long time. To further
expand the application of iodonium ylide-based domino
reaction, in this article, we would like to report the challeng-
ing annulation of aromatic aldehydes 2 with dimidone 1 and
its phenyliodonium ylide 3 leading to multifunctionalized
spiro dihydrofuran derivatives (Scheme 1). The great aspect
of the present domino reaction is shown by the fact that
the formation of 2-spirosubstituted dihydrofuran skeleton
and its spiro-substitution were readily achieved via iodonium
ylide-based reaction in an intermolecular manner and in a
one-pot operation.
Substituted dihydrofurans occur frequently in numerous
natural compounds, displaying significant biological activi-
ties and wide applications in pharmaceutical use [1]. For
these reasons, the synthetic methodologies for dihydrofurans
have fascinated to chemists for many years. A methodology
to synthesize 2,3-dihydrofurans from the dehydration of
1,4-diols under high temperature and pressure conditions
was presented by Dimroth and Pasedach in 1960 [2]. Then
another way to generate 2,3-dihydrofuran moiety through
intramolecular cyclization of alkynyl alcohols in the pres-
ence of a pentacarbonylmolybdenum/triethylamine complex
was realized in 1993 [3]. The dihydrofuran moiety could also
be constructed by Rh-catalyzed reactions of alkenes with
diazo compounds or iodonium ylides [4]. More commonly,
oxidative cyclization of alkenes with active methylene
compounds promoted by metal salts, such as cerium(IV)
ammonium nitrate and manganese(III) acetate, to the
construct requisite dihydrofuran motif have been arousing
wide concern [5]. However, these reported procedures
often required severe reaction conditions or heavy metal
catalysts. Therefore, a methodology with a mild and
metal-free reaction process is highly desirable. Recently,
Wang et al. reported the synthesis of spiro dihydrofuran
derivatives through iodine-mediated reaction of aldehydes
with 5,5-dimethylcyclohexane-1,3-dione [6]. Still, general
and efficient methods for the synthesis of 2-spirosubstituted
dihydrofuran from simple and readily available precursors
are of great value.
RESULTS AND DISCUSSION
To optimize the reaction conditions for the formation
of the target compounds, we started this study by treating
4-chlorobenzaldehyde 2a and dimidone 1 with idonium
ylides 3 in a ratio of 1:1:1.1 using various bases in 1,
4-dioxane, such as NaHCO3, K2CO3, Et3N, piperidine,
and N,N-dimethyl- 4-aminopyridine (DMAP) under micro-
wave (MW) irradiation. Only a trace amount of 4a was
observed when NaHCO3 and K2CO3 were employed.
Other organic bases including Et3N, piperidine, and
DMAP facilitated the reaction to some extent, but 2-iodo-5,
5-dimethyl-3-phenoxycyclohex-2- enone 5 as the main
product was also isolated. It is well-known that the
phenyliodonium ylide 3 easily underwent rearrangement to
give the 2-iodo-5,5-dimethyl-3-phenoxycyclohex-2-enone
On the other hand, zwitterionic iodonium compounds, a
major class of polyvalent iodine compounds, are attractive
and versatile reagents in organic synthesis [7]. Among
© 2013 HeteroCorporation

March 2014
A Three-Component Reaction Leading to 2-Spirosubstituted Dihydrofurans
437
Scheme 1. Reaction of aldehydes with dimidone and its phenylidonium ylide.
O
O
O
R
O
O
I
Ph
KOH
+
+
R-CHO
1,4-dioxane
O
O
O
3
1
2
4
(Scheme 2) (Fig. 1). Thus, there is the urgent demand to
search the appropriate conditions including bases and
solvents to decease the yield of byproduct 5. Luckily,
KOH as a base resulted in a desired 2-spirosubstituted
dihydrofurans 4a as main product. The reaction media were
then examined carefully (Table 1, entries 1–6). 1,4-dioxane
as a solvent can provide the spiro[benzofuran-2(4H),
10-cyclohexane] derivatives in 45% chemical yield. Other
solvents, such as N,N-dimethylformamide (DMF), ethane-1,
2- diol and methanol, resulted in spiro[benzofuran-2(4H),
10-cyclo- hexane] derivatives in poor yields. This outcome
was also found in the case of solvent-free conditions.
To further optimize reaction conditions, the reaction was
performed in 1,4-dioxane and repeated many times at
different temperatures and the amount of bases in a sealed
vessel under microwave irradiation. The yield of product
4a was increased from 69 to 81% as the temperature varied
from 80 to 110ꢀC (Table 1, entries 6–8). Further increase of
reaction temperature failed to improve the yield of product
4a (Table 1, entry 9)
With the optimized conditions in hand, the scope and
generality of the reaction were explored. A variety of
substituents of different electronic properties reacted
smoothly and efficiently under the present conditions,
affording the corresponding spiro dihydrofuran products
in good yields. The aromatic aldehydes with an electron-
donating group exhibited less reactivity than that bearing
an electron-withdrawing group (Table 2, entries 1–12).
R-CHO
O
O
R
O
O
O
O
I
2a
I
Ph
Base
1,4-dioxane
+
+
Ph
O
O
O
O
3
4a
5
1
R = 4-Chlorophenyl
Scheme 2
Figure 1. X-ray crystallography structure of compound 5.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

438
X.-C. Tu, Y. Yu, M.-S. Tu, B. Jiang, C. Li and S.-J. Tu
Vol 51
Table 1
Optimized conditions for 4a under MW.
Entry
Solvent
CH3OH
KOH (equiv)
T (ꢀC)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
0.5
0.5
0.5
0.5
0.5
1.0
1.0
1.0
1.0
80
80
80
80
80
15
15
15
15
15
15
12
12
12
20
28
35
32
45
69
74
81
78
DMF
Ethane-1,2-diol
Solvent-free
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
80
100
110
120
Table 2
Synthesis of 2-spirosubstituted dihydrofurans 4.
Entry
R
4
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
4-Chlorophenyl (2a)
4-Fluorophenyl(2b)
2-Chlorophenyl(2c)
3,4-Dichlorophenyl(2d)
4-Tolyl(2e)
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
12
14
15
12
18
18
20
20
20
12
12
13
16
18
18
20
24
25
81
82
75
83
82
81
80
81
76
86
85
80
68
82
70
72
75
79
4-Methoxyphenyl(2f)
3,4-Dimethyphenyl(2g)
3,4-Dimethoxyphenyl(2h)
3,4,5-Trimethoxyphenyl(2i)
4-Nitrophenyl(2j)
3-Nitrophenyl(2k)
4-Cyanophenyl(2l)
Pyridin-2-yl(2m)
Thiophen-2-yl(2n)
Furan-2-yl(2o)
9
10
11
12
13
14
15
16
17
18
Ethyl(2p)
Propyl(2q)
Isobutyl(2r)
The reaction time was prolonged to 18–20 min, and the
corresponding products were obtained in good yields as
well. And then, the heteroaromatic aldehydes, such as
2-pyridinecarboxaldehyde, 2-thiophenecarboxaldehyde, and
2-furancarboxaldehyde, were also tolerated under the current
conditions, furnishing the spiro dihydrofuran products in
68–82% yields (Table 2, entries 13–15). Furthermore,
aliphatic aldehydes such as propionic aldehyde, butyralde-
hyde, and 3-methyl butyraldehyde were also investigated.
Smooth reactions were observed for these aldehydes and
delivered the final products in 70–79% yields (Table 2,
entries 16–18). When cyclohexane-1,3-dione was further
investigated, unfortunately, the spiro dihydrofuran products
failed to obtain, and the complex mixtures were generated.
The reason is not clear so far. Moreover, functional groups
like bromide and chloride were well tolerated. These func-
tional groups provide ample opportunity for further functional
group manipulations, for example, by modern cross-coupling
reactions. It is worthy to note that only microwave irradiation
can make the present multi-component domino reaction
to occur rapidly and efficiently, whereas normal heating
diminished both yield and speed [10–12].
The mechanism of this domino reaction is proposed in
Scheme 3. An initial condensation generated intermediate
A, which successively underwent intermolecular Michael
addition (A to B) and nucleophilic substitution (B to 4) to
give final products 4. In the reaction, the iodonium ylide first
acted as a nucleophile and followed to convert into the
electrophilic reagent.
All new products were fully characterized by spectro-
scopic analyses, and the IR, 1H NMR, HRMS data were
consistent with their structures (for the spectra of all pure
products, see the ESI). Furthermore, crystal of 4e was
obtained by careful recrystallization from a co-solvent of
DMF and ethanol, and its structure was unambiguously
confirmed by X-ray crystallography (Fig. 2) [13].
Besides a high efficiency in the formation of multiple
bonds as a domino process, this reaction has the following
advantages: (1) the starting materials are readily available,
and the reagents are very cheap; (2) the convenient work-
Journal of Heterocyclic Chemistry
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A Three-Component Reaction Leading to 2-Spirosubstituted Dihydrofurans
439
Scheme 3. The reasonable mechanism for the formations of 2-spirosub-
stituted dihydrofurans 4.
EXPERIMENTAL
Microwave irradiation was carried out with Initiator from
Biotage Company, Uppsala, Sweden. Melting points were
determined in open capillaries and are uncorrected. IR spectra were
recorded on an FT-IR-tensor 27 spectrometer. 1H NMR spectra were
measured on a DPX 400 MHz spectrometer (Bruker Company,
Ettlingen, Germany) using TMS as an internal standard and
DMSO-d6 as solvent. HRMS (ESI) was determined by using the
micrOTOF-Q II HPLC/MS instrument (Bruker Company, Ettlingen,
Germany). X-Ray crystallographic analysis was performed with a
Siemens SMART CCD and a Siemens P4 diffractometer (Siemens
Company, München, Germany).
Ph
I
O
O
O
R
O
O
O
H
R
O
2
base
3
O
H2O
O
A
1
O
Ph
I
R
O
O
O
O
R
Ph-I
O
O
O
Procedure for the synthesis of phenyliodonium ylide 3 [14]:.
To a solution of cyclic the dimedone 1 (20 mmol) in 30 mL
methanol, 10% KOH aqueous (20mL) was added at room
temperature, and followed by addition of a solution of diacetoxy
iodobenzene (21mmol) in 40 mL methanol. The reaction mixture
was stirred for 2 h at room temperature and then quenched with
ice cold water. The resulting white precipitate was filtered, and
mother liquor was extracted with dichloromethane, then washed
with water, dried over anhydrous sodium sulfate, filtered and
concentrated in vaccuo. The resultant white solid was mixed with
the first crop and the mixture recrystallized from DCM/Hexanes.
General procedure for the synthesis of 2-spirosubstituted
fused dihydrofurans 4 under microwave irradiation:. In a
10-mL reaction vial, aromatic aldehyde 1 (1mmol), dimidone 2
(1mmol), iodonium ylide 3 (1.1 mmol), KOH (1.0 mmol), and
1,4-dioxane (1.5mL) were mixed, capped and then stirred at room
temperature for 15min. The mixture was irradiated for a given
time at 110ꢀC. Upon completion as shown by TLC monitoring,
the reaction mixture was cooled to room temperature and
neutralized by protonic acids and then diluted with cold water.
The solid product was filtered, washed with water and acetone,
and subsequently dried and then recrystallized from 80% EtOH to
give the pure product.
4
B
3-(4-chlorophenyl)-4’,4’,6,6-tetramethyl-6,7-dihydro-3H-spiro
[benzofuran-2,1’-cyclohexane]-2’,4,6’(5H)-trione (4a). White
solid, mp: 265–266ꢀCIR (KBr, n, cmꢁ1): 2959, 2929, 2873, 1740,
1713, 1650, 1531, 1384, 1353, 1234, 1204, 1164, 1099, 1046,
730, 688, 613, 555.1H NMR (400MHz, DMSO-d6) d: 7.39
(d, J = 8.4Hz, 2H, ArH), 7.28 (d, J = 8.4 Hz, 2H, ArH), 4.82(s, 1H,
CH), 3.66 (d, J = 15.2Hz, 1H, CH2), 2.73-2.55 (m, 2H, CH2),
2.44-2.40 (m, 1H, CH2), 2.16-2.09 (m, 4H, CH2), 1.08-1.07 (m,
9H, CH3), 0.69 (S, 3H, CH3).13C NMR (100 MHz, CDCl3) (d,
ppm): 199.0, 198.7, 193.6, 176.8, 134.7, 134.6, 129.8, 129.3,
113.6, 103.5, 54.2, 53.9, 51.0, 50.0, 37.3, 34.3, 30.6, 30.5, 28.9,
28.4, 26.3.HRMS (ESI) m/z: calc. for C23H25ClO4: 423.1334
[M+ Na]+; found: 423.1311.
3-(4-fluorophenyl)-4’,4’,6,6-tetramethyl-6,7-dihydro-3H-
spiro[benzofuran-2,1’-cyclohexane]-2’,4,6’(5H)-trione (4b).
White solid, mp: 236–237ꢀCIR (KBr, n, cmꢁ1): 2962, 2928,
2873, 1747, 1718, 1644, 1468, 1390, 1193, 1138, 1039, 892, 839,
674, 614.1H NMR (400 MHz, DMSO-d6) d: 7.31-7.24 (m, 4H,
ArH), 4.78(s, 1H, CH), 3.65 (d, J = 14.8 Hz, 1H, CH2), 2.65 (dd,
J1 = 17.6 Hz, J2 = 30.4 Hz, 2H, CH2), 2.43 (d, J = 14.8 Hz, 1H, CH2),
2.12-2.06 (m, 4H, CH2), 1.10 (s, 3H, CH3), 1.08 (s, 6H, CH3), 0.68
(s, 3H, CH3).13C NMR (100 MHz, CDCl3) (d, ppm): 199.1, 198.8,
193.2, 176.7, 162.7 (1J CF = 248.1 Hz), 131.9 (4J= 3.3 Hz), 130.2
(3J= 8.3 Hz), 116.0 (2J= 21.7 Hz), 113.7, 103.5, 54.2, 53.9, 51.1,
50.0, 37.3, 34.3, 30.6, 30.5, 28.9, 28.4, 26.3.HRMS (ESI) m/z: calc.
for C23H25FO4: 407.1635 [M + Na]+; found: 407.1638.
Figure 2. X-ray crystallography structure of compound 4e.
up which only needs simple filtration because the products
directly precipitate out after the reaction system is neutralized
with acid and when its mixtures are diluted with cold water.
(3) This method requires a short reaction time; (4) the
regiospecific construction of 2-spirosubstituted dihydrofuran
skeleton. The novelty of the present three-component
domino reaction is shown by the fact that multiple chemical
bonds’ breaking and forming were simultaneously achieved
in an intermolecular manner.
In summary, we have described iodonium ylide-based
three-component heterocyclization reactions (aldehydes,
dimidone, and its phenylidonium ylide) as an alternative
method for efficient synthesis of 2-spirosubstitued dihydro-
furans under microwave irradiation. This methodology is
simple, practical, which is a regioselective and alternative
synthetic route to obtain good yields of 2-spirosubstituted
dihydrofuran derivatives. This method is much more effi-
cient because of short reaction times and easy work-up.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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X.-C. Tu, Y. Yu, M.-S. Tu, B. Jiang, C. Li and S.-J. Tu
Vol 51
3-(2-chlorophenyl)-4’,4’,6,6-tetramethyl-6,7-dihydro-3H-spiro
3-(Furan-2-yl)-40,40,6,6-tetramethyl-3,5,6,7-tetrahydro-spiro
[benzofuran-2(4H),10-cyclohexane]-20,4,60-trione (4o). Known
compoundmp 223–224ꢀC (lit. mp 222–223ꢀC) [6]
[benzofuran-2,1’-cyclohexane]-2’,4,6’(5H)-trione (4c). White
solid, mp: 253–254ꢀCIR (KBr, n, cmꢁ1): 2961, 2925, 2873, 1744,
1712, 1644, 1461, 1390, 1193, 1138, 1031, 892, 838, 674, 614.1H
NMR (400 MHz, DMSO-d6) d: 7.31 (d, J = 8.4 Hz, 1H, ArH),
7.09 (d, J = 6.0 Hz, 2H, ArH), 6.93 (s, 1H, ArH), 4.56 (s, 1H,
CH), 3.12 (s, 1H, CH2), 2.65 (d, J = 12.8Hz, 1H, CH2), 2.36 (d,
J = 12.0 Hz, 1H, CH2), 2.25 (d. 2H, CH2)2.12 (d, J = 9.6 Hz, 1H,
CH2), 2.05-2.06 (m, 2H, CH2), 1.03 (s, 3H, CH3), 0.99 (s, 3H,
CH3), 0.94 (s, 3H, CH3),0.85 (s, 3H, CH3).HRMS (ESI) m/z: calc.
for C23H25ClO4: 423.1334 [M +Na]+; found: 423.1311.
3-Ethyl-40,40,6,6-tetramethyl-3,5,6,7-tetrahydro-spiro[benzo-
furan-2(4H),10-cyclohexane]-20,4,60-trione (4p). Known compoundmp
150–152ꢀC (lit. mp 148–149ꢀC) [6]
40,40,6,6-Tetramethyl-3-propyl-3,5,6,7-tetrahydro-spiro[benzo-
furan-2(4H),10-cyclohexane]-20,4,60-trione (4q). Known compoundmp
165–167ꢀC (lit. mp 168–170ꢀC) [6]
3-isobutyl-4’,4’,6,6-tetramethyl-6,7-dihydro-3H-spiro[benzofuran-
2,1’-cyclohexane]-2’,4,6’(5H)-trione (4r). White solid, mp:
212–213ꢀCIR (KBr, n, cm–1): 2958, 2927, 2872, 1741, 1710,
1635, 1465, 1396, 1324, 1217, 1040, 945, 727, 676, 617, 4261H
NMR (400 MHz, DMSO-d6) d: 3.56-3.53 (m, 1H, CH), 3.48-3.44
(m, 1H, CH2), 2.94 (d, J. = 16.0 Hz, 2H, CH2) 2.68-2.67 (m, 1H, CH)
2.43-2.30 (m, 3H, CH2), 2.17 (d, J = 16.0 Hz, 1H, CH2), 2.06 (d,
J = 16.0 Hz, 1H, CH2 ) 1.17 (s, 3H, CH3), 1.14-1.09 (m, 2H, CH2),
1.04 (s, 3H, CH3), 1.03 (s, 3H, CH3), 0.96 (s, 3H, CH3), 0.78 (s,
3H, CH3), 0.72 (s, 3H, CH3).13C NMR (100 MHz, CDCl3) (d,
ppm): 199.8, 199.4, 194.1, 177.4, 114.9, 103.9, 54.7, 51.3, 50.2,
45.9, 41.7, 37.4, 34.0, 30.8, 30.5, 28.6, 28.4, 25.9, 25.3, 24.0,
21.7.HRMS (ESI) m/z: calc. for C21H30O4: 369.2042 [M + Na]+;
found: 369.2028.
3-(3,4-Dichlorophenyl)-40,40,6,6-tetramethyl-3,5,6,7-tetrahydro-
spiro[benzofuran-2(4H),10-cyclohexane]-20,4,60-trione (4d). Known
compoundmp 253–254 ꢀC (lit. mp 251–252ꢀC) [6]
4’,4’,6,6-tetramethyl-3-(p-tolyl)-6,7-dihydro-3H-spiro[benzofuran-
2,1’-cyclohexane]-2’,4,6’(5H)-trione (4e). White solid, mp: 248–
249ꢀCIR (KBr, n, cmꢁ1): 2959, 2871, 1740, 1712, 1640, 1512,
1393, 1243, 1180, 1043, 839, 673, 547;1H NMR (400 MHz,
DMSO-d6) d: 7.12 (d, J = 3.6 Hz, 4H, ArH), 4.73 (s, 1H, CH), 3.63
(d, J = 15.2 Hz, 1H, CH2), 2.65 (dd, J1 = 17.6 Hz, J2 = 28.4 Hz, 2H,
CH2), 2.41 (d, J = 15.2 Hz, 1H, CH2), 2.26 (s, 3H, CH3), 2.15-2.04
(m, 2H, CH2), 1.09 (s, 3H, CH3), 1.08 (s, 6H, CH3), 0.68 (s, 3H,
CH3).13C NMR (100 MHz, CDCl3) (d, ppm): 199.4, 199.0, 193.2,
176.5, 138.4, 133.0, 129.7, 128.4, 113.7, 103.9, 54.8, 53.8, 51.1,
50.0, 37.3, 34.2, 30.5, 30.5, 28.9, 28.4, 26.3, 21.2.HRMS (ESI)
m/z: calc. for C24H28O4: 403.1885 [M + Na]+; found: 403.1884.
3-(4-Methoxyphenyl)-40,40,6,6-tetramethyl-3,5,6,7-tetrahydro-
spiro[benzofuran-2(4H),10-cyclohexane]-20,4,60-trione (4f). Known
compoundmp 234–235ꢀC (lit. mp 230–231ꢀC) [6]
Acknowledgments. We are grateful for financial support from
the National Science Foundation of China (21072163 and
21102124), the Priority Academic Program Development of
Jiangsu Higher Education Institutions, Jiangsu Science and
Technology Support Program (No. BE2011045), and the
NSF of Jiangsu Education Committee (11KJB150016).
3-(3,4-Dimethylphenyl)-40,40,6,6-tetramethyl-3,5,6,7-tetrahydro-
spiro[benzofuran-2(4H),10-cyclohexane]-20,4,60-trione (4g). Known
compoundmp 245–246ꢀC (lit. mp 242–243ꢀC) [6]
3-(3,4-Dimethoxyphenyl)-40,40,6,6-tetramethyl-3,5,6,7-tetrahydro-
spiro[benzofuran-2(4H),10-cyclohexane]-20,4,60-trione (4h). Known
compoundmp 194–196ꢀC (lit. mp 194–196ꢀC) [6]
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Iodine; VCH: New York, 1992; (b) Spyroudis, S.; Tarantili, P. J Org Chem
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Yamada, Y.; Yamamoto, T.; Okawara, M. Tetrahedron Lett 1975, 16, 361;
(e) Hood, J. N. C.; Lloyd, D.; MacDonald, W. A.; Shepherd, T. M.
Tetrahedron 1982, 38, 3355; (f) Margaret, B. C.; Aurora, E. C.; Tabitha,
A. L.; JoAnn, P.-D. J Am Chem Soc 2000, 122, 5210; (g) Matveeva, E. D.;
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R.; Zefirov, N. S. J Org Chem 2009, 74, 9428; (h) Marcoux, D.; Goudreau,
S. R.; Charette, A. B. J Org Chem 2009, 74, 8939; (i) Matveeva, E. D.;
Podrugina, T. A.; Pavlova, A. S.; Mironov, A. V.; Zefirov, N. S. Russ Chem
Bull 2008, 57, 2237; (j) Li, H.-Y.; Hsung, R. P. Org Lett 2009, 11, 4462;
(k) Matveeva, E. D.; Podrugina, T. A.; Pavlova, A. S.; Mironov, A. V.; Gleiter,
R.; Zefirov, N. S. Eur J Org Chem 2009, 2323; (l) Elizabeth, M.-X.; Spyroudis,
S. Synlett 2008, 2725.
4’,4’,6,6-tetramethyl-3-(3,4,5-trimethoxyphenyl)-6,7-dihydro-3H-
spiro[benzofuran-2,1’-cyclohexane]-2’,4,6’(5H)-trione (4i). White
solid, mp: 224–225ꢀCIR (KBr, n, cmꢁ1): 2951, 2923, 2873, 1725,
1711, 1650, 1533, 1384, 1353, 1234, 1208, 1169, 1099, 1046, 731,
688, 623, 559.1H NMR (400 MHz, DMSO-d6) d: 8.55 (s, 2H, ArH),
4.69 (s, 1H, CH), 3.71 (s, 6H, OCH3), 3.63 (s, 3H, OCH3), 2.65 (dd,
J1 = 18.0 Hz, J2 = 16.8 Hz, 2H, CH2), 2.42 (d, J = 15.2 Hz, 1H, CH),
2. 20–2.09 (m, 5H, CH2), 1.11 (s, 3H, CH3), 1.08 (s, 6H, CH3), 0.69
(s, 3H, CH3).13C NMR (100 MHz, CDCl3) (d, ppm): 199.2, 199.1,
193.3, 176.6, 153.5, 131.8, 113.4, 105.7, 103.9, 60.9, 56.2, 55.6,
53.6, 51.1, 50.1, 37.3, 34.3, 30.6, 30.6, 29.1, 28.0, 26.3.HRMS
(ESI) m/z: calc. for C26H32O7: 479.2046 [M + Na]+; found: 479.2026.
40,40,6,6-Tetramethyl-3-(4-nitrophenyl)-3,5,6,7-tetrahydro-spiro
[benzofuran-2(4H),10-cyclohexane]-20,4,60-trione (4j). Known
compoundmp 266–267ꢀC (lit. mp 265–266ꢀC) [6]
40,40,6,6-Tetramethyl-3-(3-nitrophenyl)-3,5,6,7-tetrahydro-
spiro[benzofuran-2(4H),10-cyclohexane]-20,4,60-trione (4k).
Known compoundmp 202–203ꢀC (lit. mp 201–203ꢀC) [6]
3-(4-Cyanophenyl)-40,40,6,6-tetramethyl-3,5,6,7-tetrahydro-
spiro[benzofuran-2(4H),10-cyclohexane]-20,4,60-trione (4l).
Known compoundmp 247–248ꢀC (lit. mp 248–250ꢀC)[6]
40,40,6,6-Tetramethyl-3-(pyridin-2-yl)-3,5,6,7-tetrahydro-spiro
[benzofuran-2(4H),10-cyclohexane]-20,4,60-trione (4m). Known
compoundmp 201–202ꢀC (lit. mp 201–203ꢀC) [6]
40,40,6,6-Tetramethyl-3-(thiophen-2-yl)-3,5,6,7-tetrahydro-
spiro[benzofuran-2(4H),10-cyclohexane]-20,4,60-trione (4n).
Known compoundmp 246–247ꢀC (lit. mp 246–248ꢀC) [6]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2014
A Three-Component Reaction Leading to 2-Spirosubstituted Dihydrofurans
441
[8] (a) Koser, G. F. The Chemistry of Functional Groups; Wiley:
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(c) Hao, W.-J.; Jiang, B.; Tu, S.-J.; Cao, X.-D.; Wu, S.-S.; Yan, S.; Zhang,
X.-H.; Han, Z.-G.; Shi, F. Org Biomol Chem 2009, 7, 1410; (d) Jiang, B.;
Hao, W.-J.; Zhang, J.-P.; Tu, S.-J.; Shi, F. Org Biomol Chem 2009, 7, 2195;
(e) Jiang, B.; Shi, F.; Tu, S.-J. Curr Org Chem 2010, 14, 357.
New York, 1983; (b) Macikenas, D.; Skrzypczak-Jankun, E.; Protasiewicz,
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Gallos, J. K.; Tsipis, C. A. J Organomet Chem 2010, 695, 2030; (f) Moriarty,
R. M.; Tyagi, S.; Kinch, M. Tetrahedron 2010, 66, 5801; (g) Glinis, E.;
Malamidou-Xenikaki, E.; Skouros, H.; Spyroudis, S.; Tsanakopoulou, M.
Tetrahedron 2010, 66, 5786.
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(b) Papadopoulou, M.; Spyroudis, S.; Varvogliis, A. J Org Chem
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Ann Chem 1989, 167; (e) Moriarty, R. M.; Prakash, 0.; Vaid, R.
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[13] The single-crystal growth was carried out in co-solvent of DMF
and EtOH at room temperature. X-ray crystallographic analysis was
performed with a Siemens SMART CCD and a Siemens P4 diffractometer.
Crystal data for 4e: C24H28O4, crystal dimension 0.42ꢂ 0.13ꢂ 0.07 mm,
Liebigs Ann Chem 1986, 947; (g) Spyroudis, S.
J Org Chem
1986, 51, 3453; (h) Hadjiarapoglou, L.; Spyroudis, S.; Varvoglis,
A. J Am Chem Soc 1985, 107, 7178.
Monoclinic, space group P2(1)/c, a = 5.9587(7) Å, b = 17.6616(19)
3
Å, c = 20.450(2) Å, a = g = 90o, b = 95.2390(10)o, V = 2143.1(4) Å
,
[10] (a) Jiang, B.; Tu, S.-J.; Parminder, K.; Walter, W.; Li, G.
J Am Chem Soc 2009, 131, 11660; (b) Jiang, B.; Li, C.; Shi, F.;
Tu, S.-J.; Kaur, P.; Wever, W.; Li, G. J Org Chem 2010, 75,
2962; (c) Jiang, B.; Wang, X.; Shi, F.; Tu, S.-J.; Ai, T.; Ballew,
A.; Li, G. J Org Chem 2009, 74, 9486; (d) Ma, N.; Jiang, B.;
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Mr = 380.46, Z = 4, l = 0.71073 Å, m (Mo Ka) = 0.079 mm-1, F(000) = 816,
R1 = 0.0464, wR2 = 0.0681. Crystal data for 5: C14H15IO2, crystal
dimension 0.42 ꢂ 0.30 ꢂ 0.20 mm, Triclinic, space group P-1, a = 8.1650(8)
Å, b = 9.4514(10) Å, c = 9.8500(14) Å, a = 113.797(2)o, b = 101.1010(10)o,
g = 94.8510(10)o, V = 671.26(14) Å 3, Mr = 342.16, Z = 2, l = 0.71073 Å,
m (Mo Ka)=2.373 mm-1, F(000) = 336, R1 = 0.0288, wR2 = 0.0707.
[14] Moriarty, R. M.; Tyagi, S.; Ivanov, D.; Constantinescu, M. J
Am Chem Soc 2008, 130, 7564.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet