Polymer-supported selenium-induced electrophilic cyclization: Solid-phase synthesis of poly-substituted dihydrofurans and tetrahydrofurans

Article abstract of DOI:10.1016/j.tet.2004.08.042

Poly-substituted dihydrofurans and tetrahydrofurans have been synthesized through polymer-supported selenium-induced intramolecular electrophilic cyclization, followed by selenoxide syn-elimination or novel nucleophilic substitution cleavage of selenium resin with good yields and purities. Graphical Abstract

Full text of DOI:10.1016/j.tet.2004.08.042

Tetrahedron 60 (2004) 9963–9969
Polymer-supported selenium-induced electrophilic cyclization:
solid-phase synthesis of poly-substituted dihydrofurans and
tetrahydrofurans
a
E. Tang,a Xian Huanga,b, and Wei-Ming Xu
*
aDepartment of Chemistry, Zhejiang University (Xixi Campus), Hangzhou 310028, People’s Republic of China
bState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, People’s Republic of China
Received 12 May 2004; revised 5 August 2004; accepted 10 August 2004
Available online 11 September 2004
Abstract—Poly-substituted dihydrofurans and tetrahydrofurans have been synthesized through polymer-supported selenium-induced
intramolecular electrophilic cyclization, followed by selenoxide syn-elimination or novel nucleophilic substitution cleavage of selenium
resin with good yields and purities.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
dihydrofuran and tetrahydrofuran is reported by polystyrene-
supported selenium-induced regioselective intramolecular
electrophilic cyclization of allyl substituted 1,3-dicarbonyl
compounds. Evident advantages of this reaction are easy
operations, odorlessness and good purity of the products.
And also the resins can be regenerated and reused.
The preparation of diverse libraries of organic compounds is
an important fact of modern drug discovery programs. One
of the most commonly employed methods in library
production is solid phase organic synthesis (SPOS).1 It has
shown that compounds with biological activities are often
derived from heterocyclic structures.2
2. Results and discussion
Dihydrofurans and tetrahydrofurans are two important
classes of heterocycles with widespread occurrence in
nature.3 Possessing a variety of biological activities, they
are used as pharmaceutical, flavor, insecticidal, and fish
antifeedant agents.4 Despite having important biological
activities there are very few reports dealing with the
polymer-supported synthesis of libraries based on func-
tionalized dihydrofurans and tetrahydrofurans.5 And also,
most of the dihydrofurans and tetrahydrofurans prepared by
a solid-phase method are mono- or di-substituted.
We began our efforts from polystyrene-supported selenenyl
bromide7 (dark-red resin, Se: 1.02 mmol/g), which was
treated with a-allyl substituted 1,3-dicarbonyl compounds
1, followed by the conditions that Ferraz et al.10 had devised
in solution phase. The rapid decolorization of polystyrene-
supported selenenyl bromide occurred when 2.5 equiv of the
compound 1 were used (Scheme 1). After stirred at rt for
3 h, the ring-closure reaction on solid-phase completed,
which was determined by the elemental analysis of resin 2
(Br was undetectable). The reaction was also monitored by
Since the first organoselenium resin6 was reported in 1976,
several groups have developed organoselenium resins as
convenient linkers.7,8 Recently, our research group has been
interested in the application of organic selenium resins in
organic synthesis.9 A simple preparation of polysubstituted
Keywords: Solid phase synthesis; Selenium mediated intramolecular
cyclization; Allyl-substituted 1,3-dicarbonyls; Dihydrofurans;
Tetrahydrofurans.
* Corresponding author. Tel./fax: C86-571-88807077;
e-mail: huangx@mail.hz.zj.cn
Scheme 1.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.08.042

9964
E. Tang et al. / Tetrahedron 60 (2004) 9963–9969
Scheme 2.
FT-IR, which showed a strong peak of carbonyl absorption
between 1680–1730 cmK1
A significant feature of this novel nucleophilic substitution
cleavage reaction (Scheme 2 step c) was that a new
functional group (iodine), with versatile reactivities in
organic synthesis, was introduced during the cleavage stage.
Iodomethyl dihydrofurans 6 could be dehydrohalogenated
to afford the corresponding furans 8 by treated with DBU
followed by acid-catalyzed rearrangement (Scheme 3). The
results are summarized in Table 2.
.
In our reaction, the cleavage reaction of resins 2 was fully
determined by the substituents R3 and R5 (Scheme 2). When
R3 or R5 was not hydrogen, selenoxide syn-elimination
underwent smoothly to give poly-substituted dihydrofuran 3
and 5 respectively (Scheme 2 step a and b). The generated
resin 4 can be recycled and reused.9a But when R3 and R5
were both hydrogen, selenoxide syn-elimination did not
occur when we treated resin 2 with H2O2 even at 50 8C in
THF.
In order to expand the diversity of this method, g-allyl
substituted 1,3-dicarbonyl compounds 9 were used to
perform the intramolecular electrophilic cyclization with
polymer-supported selenenyl bromide (Scheme 4). It was
not surprised that resins 10 were obtained almost
Common cleavage protocols of selenium linkers11 have
been reported using two strategies: selenoxide syn-elimin-
n
ation and radical hydride transfer. Bu3SnH could be used
here as a good radical hydride transfer reagent, but it was
too toxic. Herein we report a new cleavage protocol using
CH3I/NaI in DMF under mild conditions that Corey et al.12
devised in the solution conditions (Scheme 2 step c).
Iodomethyl-substituted dihydrofurans 6 were obtained in
good yields and purities. The results are listed in Table 1.
Scheme 3.
Table 1. Synthesis of poly-substituted dihydrofurans
Producta
R1
R2
R3
H
R4
H
R5
Yieldb (%)
Purityc (%)
3ad
5ad
5bd
6a
6b
6c
6d
6e
6f
6g
OCH3
OCH3
OC2H5
-CH2CH2CH2-
-CH2C(CH3)2CH2-
OCH3
OC2H5
C6H5
CH3
CH3
CH3
CH3
CH3
H
H
H
H
H
H
H
H
85
80
82
89
88
80
78
76
79
86
90
87
82
89
87
95
95
90
86
92
-CH2CH2CH2-
-CH2CH2CH2-
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CH3
CH3
C6H5
C6H5
CH3
CH3
H
a
NaI, CH3I, DMF, 75 8C.
b
c
d
Overall yield based on the loading of selenium bromide resin (1.02 mmol/g).
Purity determined by HPLC.
H2O2 (30%), 7.0 equiv, THF, 0 8C–rt.

E. Tang et al. / Tetrahedron 60 (2004) 9963–9969
9965
Table 2. Synthesis of poly-substituted furans
3. Conclusion
Product
R1
R2
Yielda (%)
In conclusion, a novel preparation of poly-substituted
dihydrofurans and tetrahydrofurans has been developed by
a polystyrene-supported selenium induced regioselective
intramolecular cyclization, followed by the selenoxide syn-
elimination or a novel nucleophilic substitution cleavage of
selenium resin.
8a
8b
8c
8d
8e
8f
-CH2CH2CH2-
-CH2C(CH3)2CH2-
OCH3
OC2H5
CH3
80
78
74
71
72
79
CH3
CH3
C6H5
C6H5
C6H5
a
Isolated yield.
4. Experimental
quantitatively. Followed by the deselenenylation reaction
with methyl iodide and sodium iodide in DMF at 75 8C,
poly-substituted iodomethyl tetrahydrofurans 1113 were
obtained in good yields and purities. The results are
summarized in Table 3.
4.1. General
Starting materials were obtained from commercial suppliers
and used without further purification. THF was distilled
from sodium/benzophenone immediately prior to use.
Polystyrene (H 1000, 100–200 mesh, cross-linked with
1% divinylbenzene) for the preparation of selenenyl
bromide resin (1.02 mmol Br/g) according to the procedure
described by Nicolaou and co-workers7 was purchased from
commercial sources. Allyl substituted 1,3-dicarbonyl com-
pounds 1 and 9 were prepared according to the literature
procedures.14,15 1H NMR (400 MHz) and 13C NMR
(100 MHz) spectra were recorded on a Bruker Avance
(400 MHz) spectrometer, using CDCl3 as the solvent and
TMS as an internal standard. Mass spectra (EI, 70 eV) were
recorded on a HP5989B mass spectrometer. Infrared spectra
were recorded on a Shimadzu IR-408 spectrometer and
measured as thin film or in KBr. Elemental analyses were
performed on a Flash EA1112 instrument. HPLC was
performed on an Agilernt 1100 High performance liquid
chromatograph. The samples were further purified by TLC
for 13C NMR and microanalyses.
Table 3. Synthesis of poly-substituted tetrahydrofurans
Product
R1
R2
R3
Yielda (%) Purityb (%)
11a
11b
11c
11d
11e
11f
11g
11h
11i
CH3
CH3
CH3
CH3
H
H
H
C2H5
n-C4H9
H
PhCH2
H
H
H
H
85
80
73
72
86
86
78
82
83
95
95
90
86
88
95
93
93
87
H
CH2CH]CH2
CH3
H
H
CH3
C2H5
PhCH2
C2H5
C2H5
C2H5
C2H5
a
Overall yield based on the loading of selenium bromide resin (1.02 mmol/g).
Purity determined by HPLC.
b
It is noteworthy that polystyrene-supported methyl selenide
(resin 7) was generated after the cleavage stage. Resin 7
could be reused as the starting material and recycled in the
same reaction for several times without the loss of purities
of the products but with a slight decrease in yields. Results
are given in Table 4.
4.2. General procedure for the preparation of
dihydrofurans (3a, 5a, 5b)
To a suspension of the swellen polymer-supported selenium
bromide resin (1.0 g, 1.02 mmol/g) in dry THF (15 mL), a-
allyl-1, 3-dicarbonyl compounds (2.5 equiv) was added.
The suspension was stirred at rt for 3 h. The mixture was
filtered and the resin was washed with THF (10 mL!3) and
CH2Cl2 (10 mL!3) and dried in vacuum at 65 8C to afford
dry selenocyclic enol ether resin 2.
Table 4. Circulation of the polymer selenium resin
Substrate
Times
Yielda (%)
Purityb (%)
To a suspension of the swellen selenocyclic enol ether resin
2 (1.0 g) in THF (15 mL), 30% H2O2 (1.5 mL) was added at
0 8C. The suspension was stirred at 0 8C for 0.5 h and rt for
1.0 h, the mixture was filtered and the resin was washed
with CH2Cl2 (10 mL!3), the filtrate was washed with
saturated NaHCO3, and H2O, respectively, dried over
6a
6a
6a
6a
1
2
3
4
89
87
87
84
89
89
87
88
a
Overallyieldbasedontheloadingofseleniumbromideresin(1.02 mmol/g).
Purity determined by HPLC.
b
Scheme 4.

9966
E. Tang et al. / Tetrahedron 60 (2004) 9963–9969
MgSO4, and evaporated to dryness in vacuum to afford
dihydrofurans 3a, 5a and 5b.
(14), 55 (21), 53 (31), 52 (11), 51 (11), 43 (19), 42 (13), 41
(32). Anal. calcd for C9H11IO2: C, 38.87; H, 3.99; I, 45.63.
Found: C, 38.78; H, 4.06; I, 45.58%.
4.2.1. 2-Methyl-5-vinyl-4, 5-dihydro-furan-3-carboxylic
acid methyl ester (3a). The title compound was obtained as
a light yellow oil (85%). n (neat) 3078, 2975, 1695, 1645,
1226, 990 and 908 cmK1; dH 5.95–5.88 (1H, m), 5.30 (1H,
d, JZ17.2 Hz), 5.20 (1H, d, JZ10.4 Hz), 5.08–5.00 (1H,
m), 3.70 (3H, s), 3.05 (1H, dd, JZ12.4, 14.0 Hz), 2.67 (1H,
dd, JZ7.6, 14.0 Hz), 2.21 (3H, s); dC 168.8, 166.6, 135.6,
115.1, 101.2, 80.0, 50.8, 34.2, 13.4; m/z 169 (100%), 168
(MC, 27), 137 (16), 116 (8). Anal. calcd for C9H12O3: C,
64.27; H, 7.19. Found: C, 64.20; H, 7.08%.
4.3.2. 2-Iodomethyl-6, 6-dimethyl-3, 5, 6, 7-tetrahydro-
2H-benzofuran-4-one (6b). The title compound was
obtained as a light yellow oil (88%). n (neat) 2957, 1637,
1402, 1218, 1037, 731, 629 cmK1; dH 4.86–4.82 (1H, m),
3.31 (2H, d, JZ5.2 Hz), 2.92 (1H, dd, JZ14.0, 6.8 Hz),
2.53 (1H, dd, JZ14.0, 6.8 Hz), 2.24 (2H, s), 2.15 (2H, s),
1.11 (6H, s); dC 194.6, 175.6, 111.3, 83.3, 60.8, 37.6, 34.0,
32.4, 28.8, 28.5, 8.9; m/z 307 (100%), 306 (MC, 12), 250
(17), 180 (15), 179 (94) 123 (39), 95 926), 83 (25), 81 (29),
77 (13), 67 (29), 65 (14), 55 (43), 53 (52), 52 (17), 51 (17),
43 (32), 42 (12), 41 (77). Anal. calcd for C11H15IO2: C,
43.16; H, 4.94; I, 41.45. Found: C, 43.22; H, 4.87; I,
41.52%.
4.2.2. 2-Methyl-3a, 4, 5, 7a-tetrahydro-benzofuran-3-
carboxylic acid methyl ester (5a). The title compound was
obtained as a light yellow oil (80%). n (neat) 2978, 1694,
1649, 1444, 1380, 1224, 1084, 964, 758, 615 cmK1; dH
6.21–6.17 (1H, m), 5.92 (1H, d, JZ10.4 Hz), 4.71 (1H, d,
JZ8.8 Hz), 3.70 (3H, s), 3.04–2.96 (1H, m), 2.18 (3H, s),
2.13–2.20 (2H, m), 1.92–1.81 (1H, m), 1.28–1.17 (1H, m);
dC 168.6, 166.6, 134.5, 123.1, 107.6, 78.1, 50.5, 40.0, 24.9,
23.1, 14.5; m/z 195 (100%), 194 (MC, 52), 163 (39), 162
(22), 161 (12), 119 (15), 116 (34), 91 (53), 79 (15), 65 (13),
43 (85). Anal. calcd for C11H14O3: C, 68.02; H, 7.26. Found:
C, 68.12; H, 7.35%.
4.3.3. 5-Iodomethyl-3-methoxycarbonyl-2-methyl-4, 5-
dihydrofuran (6c). The title compound was obtained as a
light yellow oil (80%). n (neat) 2949, 1702, 1650, 1262,
1226, 1086, 981, 761, 613 cmK1; dH 4.72–4.67 (1H, m),
3.70 (3H, s), 3.34–3.26 (2H, m); 3.03 (1H, dd, JZ13.6,
11.2 Hz), 2.66 (1H, dd, JZ14.8, 6.8 Hz), 2.20 (3H, s); dC
167.4, 166.1, 101.5, 80.4, 50.9, 36.9, 14.0, 8.8; m/z 283
(49%), 282 (MC, 34), 251 (18), 155 (73), 123 (58), 113 (11),
95 (13), 81 (59), 59 (11), 53 (33), 43 (100), 41 (12). Anal.
calcd for C8H11IO3: C, 34.06; H, 3.93; I, 44.99. Found: C,
33.99; H, 3.85; I, 45.06%.
4.2.3. 2-Methyl-3a, 4, 5, 7a-tetrahydro-benzofuran-3-
carboxylic acid ethyl ester (5b). The title compound was
obtained as a light yellow oil (82%). n (neat) 2928, 1697,
1636, 1382, 1218, 1099, 1080, 954, 876, 840, 705 cmK1; dH
6.13 (1H, dt, JZ8.4, 6.8 Hz), 5.92 (1H, d, JZ9.6 Hz), 4.71
(1H, d, JZ7.6 Hz), 4.13 (2H, t, JZ7.2 Hz), 3.02–2.91 (1H,
m), 2.15 (3H, s), 2.02 (2H, t, JZ12 Hz), 1.93–1.85 (1H, m),
1.24 (3H, t, JZ8.0 Hz), 1.28–1.12 (1H, m); dC 168.2, 166.2,
134.4, 123.2, 107.8, 77.9, 59.2, 40.1, 24.9, 23.1, 14.4, 14.4;
m/z 209 (100%), 208 (MC, 39), 163 (33), 162 (15), 130 (12),
91 (27), 43 (44). Anal. calcd for C12H16O3: C, 69.21; H,
7.74. Found: C, 69.30; H, 7.63%.
4.3.4. 3-Ethoxycarbonyl-5-iodomethyl-2-methyl-4, 5-
dihydrofuran (6d). The title compound was obtained as a
light yellow oil (78%). n (neat) 2949, 2926, 1702, 1635,
1436, 1382, 1219, 1187, 1099, 994, 875 cmK1; dH 4.72–
4.64 (1H, m); 4.16 (2H, q, JZ7.2 Hz); 3.36–3.24 (2H, m);
3.04 (1H, dd, JZ14.4, 11.2 Hz), 2.65 (1H, dd, JZ14.4,
6.4 Hz), 2.19 (3H, s); 1.28 (3H, t, JZ7.2 Hz); dC 167.1,
166.7, 101.7, 80.4, 69.5, 36.9, 14.4, 14.0, 8.8; m/z 297
(100%), 296 (MC, 33), 251 (32), 169 (51), 123 (57), 95 (10),
81 (34), 53 (17), 43 (46). Anal. calcd for C9H13IO3: C,
36.51; H, 4.43; I, 42.86. Found: C, 36.60; H, 4.37; I,
42.91%.
4.3. General procedure for the preparation of
iodomethyldihydrofurans (6a–6g)
To a suspension of the swellen selenocyclic enol ether resin
2 (1.0 g), in dry DMF (15 mL), NaI (1.5 g) and CH3I
(1.5 mL) were added under nitrogen. The suspension was
stirred at 75 8C for 18 h. The mixture was filtered and the
resin was washed with CH2Cl2 (10 mL!3), the filtrate was
washed with saturated Na2S2O3 and H2O respectively and
extracted with CH2Cl2 (10 mL!3), dried over MgSO4, and
evaporated to dryness in vacuum to afford iodomethyldi-
hydrofurans 6a–6g.
4.3.5. 3-Benzoyl-5-iodomethyl-2-phenyl-4, 5-dihydro-
furan (6e).16 The title compound was obtained as a light
yellow oil (76%). n (neat) 1620, 1404, 1220, 1033, 734,
628 cmK1; dH 7.65–7.51 (2H, m), 7.48–7.41 (2H, m), 7.32–
6.98 (6H, m), 5.02 (1H, m), 3.43 (1H, dd, JZ9.2, 15.2 Hz),
3.40 (1H, dd, JZ5.6, 12.4 Hz), 3.23 (1H, dd, JZ7.2,
12.4 Hz), 3.12 (1H, dd, JZ7.2, 15.2 Hz); m/z 390 (MC,
11%), 263 (100), 43 (50).
4.3.6. 3-Acetyl-5-iodomethyl-2-phenyl-4, 5-dihydrofuran
(6f). The title compound was obtained as a light yellow oil
(79%). n (neat) 2923, 1624, 1592, 1491, 1378, 1243, 1115,
1070, 909, 698 cmK1; dH 7.55 (2H, d, JZ7.6 Hz), 7.51–
7.42 (3H, m), 4.82–4.74 (1H, m), 3.41 (2H, d, JZ5.2 Hz),
3.29 (1H, dd, JZ10.4, 15.2 Hz), 2.91 (1H, dd, JZ6.8,
15.2 Hz), 1.95 (3H, s); dC 194.4, 165.4, 130.7, 130.6, 129.1,
129.1, 126.4, 126.4, 114.5, 80.1, 37.7, 26.9, 8.9; m/z 328
(MC, 18%), 327 (25), 201 (15), 115 (12), 105 (100), 77 (60),
51 (23), 43 (95). Anal. calcd for C13H13IO2: C, 47.58; H,
3.99; I, 38.67. Found: C, 47.48; H, 4.07, I, 38.58%.
4.3.1. 2-Iodomethyl-3, 5, 6, 7-tetrahydro-2H-furan-
benzofuran-4-one (6a). The title compound was obtained
as a light yellow oil (89%). n (neat) 2946, 1631, 1402, 1231,
1179, 917, 731 cmK1; dH 4.82 (1H, ddt, JZ10.4, 6.8,
6.0 Hz); 3.33 (2H, d, JZ6.0 Hz); 2.96 (1H, dd, JZ14.4,
10.4 Hz); 2.56 (1H, dd, JZ14.4, 6.8 Hz); 2.42 (2H, t,
JZ6.0 Hz); 2.32 (2H, t, JZ6.0 Hz); 2.02 (2H, quintet,
JZ6.0 Hz); dC (CDCl3) 195.3, 176.6, 112.9, 83.5, 36.4,
32.5, 23.8, 21.6, 8.1; m/z 278 (MC, 10), 279 (100), 250 (8),
151 (78), 152 (11), 123 (14), 105 (8), 95 (21), 81 (23), 67

E. Tang et al. / Tetrahedron 60 (2004) 9963–9969
9967
4.3.7. 3-Acetyl-5-iodomethyl-2-methyl-4, 5-dihydro-
furan (6g). The title compound was obtained as a light
yellow oil (86%). n (neat) 2950, 1639, 1404, 1220, 1037,
732, 628 cmK1; dH 4.71–4.67 (1H, m); 3.32 (2H, d,
JZ6.0 Hz), 3.10 (1H, dd, JZ14.4, 10.8 Hz), 2.72 (1H, dd,
JZ14.4, 7.2 Hz), 2.23 (3H, s), 2.22 (3H, s); dC 194.2, 166.8,
111.9, 80.4, 36.7, 29.5, 15.0, 8.7; m/z 267 (MC1, 100%),
139 (11), 123 (13), 43 (58). Anal. calcd for C8H11IO2: C,
36.11; H, 4.17; I, 47.69. Found: C, 36.20; H, 4.25; I,
47.62%.
2926, 1673, 1557, 1234, 908, 733 cmK1; dH 7.70–7.72 (2H,
m), 7.47–7.36 (3H, m), 6.09 (s, 1H), 2.41 (s, 3H), 2.21 (s,
3H); dC 191.8, 158.0, 154.7, 139.3, 131.9, 128.9, 128.9,
128.2, 128.2, 121.1, 107.4, 14.1, 13.2; m/z 200 (MC, 13),
105 (100). Anal. calcd for C13H12O2: C, 77.98; H, 6.04.
Found: C, 77.90; H, 6.12%.
4.4.6. 3-Benzoyl-5-methyl-2-phenyl-furan (8f).18 The title
compound was obtained as a colorless oil (79%). n (neat)
2923, 1618, 1221, 986 cmK1; dH 7.9–7.75 (2H, m), 7.75–7.6
(2H, m), 7.6–7.15 (6H, m), 6.25 (s, 1H), 2.35 (s, 3H); m/z
262 (MC, 8), 105 (100).
4.4. General procedure for the preparation of
alkylidenedihydrofurans (8a–8e)
4.5. General procedure for the preparation of
iodomethyltetrahydrofurans (11a–11j)
The mixture of iodomethyldihydrofurans 6a–6e (0.7 mmol)
and DBU (2.1 mmol) was stirred under nitrogen for 12 h at
60 8C. The mixture was filtered and the resin was washed
with diluted HCl and CH2Cl2, the filtrate was extracted with
Et2O (10 mL!3). The organic layer was washed with brine
to neutrality, then dried over MgSO4. The solvent was
removed under reduced pressure and the crude product was
dissolved in dry Et2O (0.05 M) and a few drops of H2SO4
(10 M) were added. The solution was stirred under nitrogen
at rt until the completion of the reaction (TLC monitoring).
Then the solution was diluted with Et2O and washed with
brine. After the usual work-up the furan 8a–8e were
obtained.
To a suspension of the swellen selenocyclic enol ether resin
2 (1.0 g), in dry DMF (15 mL), NaI (1.5 g) and CH3I
(1.5 mL) were added under nitrogen. The suspension was
stirred at 75 8C for 18 h. The mixture was filtered and the
resin was washed with CH2Cl2 (10 mL!3), the filtrate was
washed with saturated Na2S2O3 and H2O respectively and
extracted with CH2Cl2 (10 mL!3), dried over MgSO4, and
evaporated to dryness in vacuum to afford iodomethyl-
tetrahydrofurans 11a–11j.
4.5.1. (5-Iodomethyl-dihydrofuran-2-ylidene)-acetic acid
methyl ester (11a). The title compound was obtained as a
light yellow oil (85%). n (neat) 2951, 1706, 1643, 1436,
1363, 1118 cmK1; dH 5.32 (1H, s), 4.50–4.48 (1H, m), 3.66
(3H, s), 3.37–3.24 (3H, m), 3.06–3.01 (1H, m), 2.36–2.30
(1H, m), 1.91–1.86 (1H, m); dC 175.6, 168.7, 90.0, 82.3,
50.7, 30.2, 29.7, 6.7; m/z 283 (100%), 282 (MC, 21), 251
(42), 155 (37), 123 (25), 101 (55), 99 (14), 95 (17), 85 (14),
81 (21), 71 (13), 69 (58), 67 (15), 59 (16), 57 (12), 55 (49),
54 (11), 53 (25), 43 (44), 42 (15), 41 (32). Anal. calcd for
C8H11IO3: C, 34.06; H, 3.93; I, 44.99. Found: C, 34.13; H,
3.84; I, 44.90%.
4.4.1. 2-Methyl-6, 7-dihydro-5H-benzofuran-4-one (8a).
The title compound was obtained as a colorless oil (80%). n
(neat) 1674, 1581, 1434, 1237, 1163, 1010, 913, 732 cmK1
;
dH 6.24 (1H, s), 2.83 (2H, t, JZ6.2 Hz), 2.46 (2H, t,
JZ6.2 Hz), 2.29 (3H, s), 2.15 (2H, quintet, JZ6.3 Hz); dC
194.6, 166.0, 152.6, 122.0, 101.7, 37.5, 23.3, 22.6, 13.3; m/z
150 (MC, 15%), 122 (59), 94 (90), 79 (11), 53 (13), 52 (11),
51 (26), 50 (22), 43 (100), 42 (16), 41 (14). Anal. calcd for
C9H10O2: C, 71.98; H, 6.71. Found: C, 71.90; H, 6.63%.
4.4.2. 2, 6, 6-Trimethyl-6, 7-dihydro-5H-benzofuran-4-
one (8b). The title compound was obtained as a colorless oil
(78%). n (neat) 1670, 1582, 474, 1252, 1034, 905 cmK1; dH
6.23 (1H, s), 2.69 (2H, s), 2.34 (2H, s), 2.29 (3H, s), 1.13
(6H, s); dC 194.0, 166.1, 162.8, 120.7, 101.7, 51.9, 37.3,
36.2, 28.5, 28.5, 13.4; m/z 178 (MC, 7%) 122 (100), 94 (97),
51 (11), 43 (81). Anal. calcd for C11H14O2: C, 74.13; H,
7.92. Found: C, 74.08; H, 8.01%.
4.5.2. 2-(5-Iodomethyl-dihydrofuran-2-ylidene)-butyric
acid methyl ester (11b). The title compound was obtained
as a light yellow oil (74%). n (neat) 2962, 1698, 1635, 1434,
1318, 1255, 1183, 1101, 1027, 780 cmK1; dH 4.47–4.44
(1H, m), 3.69 (3H, s), 3.38–3.22 (3H, m), 3.05–2.96 (1H,
m), 2.31 (3H, q, JZ7.2 Hz), 1.90–1.85 (1H, m), 0.99 (3H, t,
JZ7.2 Hz); dC 169.3, 169.2, 104.9, 81.4, 50.8, 30.8, 30.0,
19.4, 13.7, 7.6; m/z 311 (100%), 310 (MC, 21) 279 (42), 151
(23), 123 (10), 109 (12), 99 (17), 97 (18), 97 (17), 81 (35),
71 (19), 69 (39), 67 (16), 59 (50), 57 (55), 55 (92), 53 (38),
43 (90), 41 (80). Anal. calcd for C10H15IO3: C, 38.73; H,
4.87; I, 40.92. Found: C, 38.68; H, 4.80; I, 40.86%.
4.4.3. 2, 5-Dimethyl-3-methoxycarbonyl-furan (8c).17
The title compound was obtained as a colorless oil (74%).
n (neat) 2953, 1713, 1439, 1207, 1085, 734 cmK1; dH 6.21
(1H, s), 3.78 (3H, s), 2.51 (3H, s), 2.22 (3H, s); m/z 154
(MC, 53%), 139 (51), 123 (63), 94 (20), 81 (18), 53 (21), 43
(100).
4.5.3. 2-(5-Iodomethyl-dihydrofuran-2-ylidene)-hexa-
noic acid methyl ester (11c). The title compound was
obtained as a light yellow oil (80%). n (neat) 2954, 2859,
1699, 1634, 1434, 1182, 1113, 733 cmK1; dH 4.49–4.42
(1H, m), 3.68 (3H, s), 3.35 (1H, dd, JZ10.0, 4.8 Hz), 3.31–
3.21 (2H, m), 3.07–2.95 (1H, m), 2.30 (3H, t, JZ6.8 Hz),
1.93–1.80 (1H, m), 1.43–1.23 (4H, m), 0.90(3H, t, JZ7.2 Hz);
dC 169.5, 169.4, 103.5, 81.4, 50.8, 31.3, 30.9, 30.0, 25.6, 22.5,
14.0, 7.5; m/z 339 (100%), 338 (MC, 44), 307 (72), 295 (36),
211 (10), 179 (16), 151 (13), 133 (12), 113 (10), 81 (12), 55
4.4.4. 2, 5-Dimethyl-3-ethoxycarbonyl-furan (8d).17 The
title compound was obtained as a colorless oil (71%). n
(neat) 2926, 1713,, 1229, 1204, 1075, 988 cmK1; dH 6.25
(1H, s), 4.16 (2H, q, JZ7.2 Hz), 2.52 (3H, s), 2.24 (3H, s),
1.26 (3H, t, JZ7.2 Hz); m/z 168 (MC, 7), 153 (22), 137
(36), 123 (14), 95 (17), 51 (33), 43 (100).
4.4.5. 3-Acetyl-5-methyl-2-phenyl-furan (8e). The title
compound was obtained as a colorless oil (72%). n (neat)

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E. Tang et al. / Tetrahedron 60 (2004) 9963–9969
(32), 53 (18), 43 (27), 41 (45). Anal. calcd for C12H19IO3: C,
42.62; H, 5.66; I, 37.53. Found: C, 42.69; H, 5.74; I, 37.60%.
obtained as a light yellow oil (80%). n (neat) 2968, 2873,
1712, 1651, 1459, 1376, 1193, 1045, 1003, 804 cmK1; dH
(two diastereoisomers, ratio 51:49) 4.80 and 4.77 (1H, 2!
s), 4.80–4.73 and 4.57–4.50 (1H, 2!m), 4.19–4.07 (2H, m),
3.46 and 3.54 (1H, 2!dd, JZ10.0, 4.8 Hz), 3.21 and 3.15
(1H, 2!t, JZ9.6 Hz), 2.85–2.74 (1H, m), 2.59–2.50 and
2.11–1.99 (1H, 2!m), 2.11–1.99 and 1.89–1.75 (1H, 2!
m), 1.75–1.63 and 1.53–1.34 (1H, 2!m), 1.53–1.34 (1H,
m), 1.26 (3H, t, JZ7.2 Hz), 1.00 (3H, t, JZ7.2 Hz); m/z 325
(100%), 324 (MC, 23), 279 (54), 169 (12), 123 (15), 115
(29), 97 (15), 95 (23), 87 (19), 81 (31), 69 (59), 67 (19), 55
(47), 53 (24), 43 (38), 41 (68). Anal. calcd for C11H17IO3: C,
40.76; H, 5.29; I, 39.15. Found: C, 40.82; H, 5.20; I,
39.22%.
4.5.4. (3-Allyl-5-iodomethyl-dihydrofuran-2-ylidene)-
acetic acid methyl ester (11d). The title compound was
obtained as a light yellow oil (80%). n (neat) 2926, 1715,
1650, 1434, 1373, 1277, 1194, 1040, 999, 806 cmK1; dH
6.79–6.71 (1H, m), 6.15–5.10 (2H, m), 4.85 (1H, s), 4.57–
4.51 (1H, m), 3.68 (3H, s), 3.55 (1H, dd, JZ10.0, 4.0 Hz),
3.27 (1H, dd, JZ10.0, 8.8 Hz), 3.08–2.93 (1H, m), 2.57–
2.39 (2H, m), 2.27–2.12 (1H, m), 1.53–1.37 (1H, m); dC
173.3, 166.0, 134.2, 117.9, 88.1, 82.9, 50.7, 43.4, 36, 35.9,
6.2; m/z 322 (MC, 8%), 195 (12), 163 (40), 135 (30), 122
(14), 121 (35), 119 (16), 117 (27), 113 (10), 109 (33), 107
(27), 101 (72), 95 (66), 81 (97), 69 (100), 55 (77), 43 (80).
Anal. calcd for C11H15IO3: C, 41.01; H, 4.69; I, 39.39.
Found: C, 40.13; H, 4.59; I, 39.47%.
4.5.9. (5-Iodomethyl-3-benzyl-dihydrofuran-2-ylidene)-
acetic acid ethyl ester (11i). The title compound was
obtained as a light yellow oil (80%). n (neat) 1708, 1652,
1192, 1045, 911, 732 cmK1; dH (two diastereoisomers, ratio
55:45) 7.31 (2H, t, JZ7.2 Hz), 7.24 (1H, t, JZ7.2 Hz),
7.20–7.13 (2H, m), 4.92 and 4.83 (1H, 2!s), 4.67–4.60 and
4.48–4.42 (1H, 2!m), 4.19–4.08 (2H, m), 3.46 and 3.40
(1H, 2!dd, JZ10.4, 4.0 Hz), 3.20 (2H, q, JZ9.6 Hz), 3.11
and 2.96 (1H, 2!dd, JZ13.6, 4.4 Hz), 2.67 and 2.60 (1H,
2!dd, JZ13.6, 9.6 Hz), 2.31–2.22 and 2.10–2.01 (1H, 2!
m), 1.93–1.84 and 1.50–1.39 (1H, 2!m), 1.25 (3H, dd,
JZ12.0, 7.2 Hz); m/z 386 (MC, 10%), 341 (6), 145 (19),
115 (47), 91 (100), 69 (25), 41 (21). Anal. calcd for
C16H19IO3: C, 49.76; H, 4.96; I, 32.86. Found: C, 49.82; H,
4.89; I, 32.91%.
4.5.5. 2-(5-Iodomethyl-dihydrofuran-2-ylidene)-3-phe-
nyl-propionic acid methyl ester (11e). The title compound
was obtained as a light yellow oil (80%). n (neat) 1705,
1655, 1192, 1047, 913, 734 cmK1; dH 7.28–7.22 (2H, m),
7.20–7.11 (3H, m), 4.70–4.65 (1H, m), 3.69 (3H, s), 3.57–
3.52 (2H, m), 3.46 (1H, dd, JZ10.0, 4.5 Hz), 3.26 (1H, dd,
JZ5.2, 4.8 Hz), 2.83 (1H, dd, JZ10.0, 4.8 Hz), 2.73–2.67
(1H, m), 2.36–2.25 (1H, m),1.78–1.86 (1H, m); dC 168.3,
167.3, 140.4, 128.3, 128.3, 127.8, 127.8, 125.9, 99.7, 84.1,
51.2, 34.4, 30.5, 28.8, 6.9; m/z 373 (MC1, 100%), 341 (33),
213 (45), 143 (17), 131 (30), 91 (44), 55 (20), 43 (23). Anal.
calcd for C15H17IO3: C, 48.41; H, 4.60; I, 34.10. Found: C,
48.47; H, 4.51; I, 34.02%.
4.5.6. (5-Iodomethyl-dihydrofuran-2-ylidene)-acetic acid
ethyl ester (11f). The title compound was obtained as a light
yellow oil (80%). n (neat) 2978, 1710, 1653, 1199, 1138,
1044, 804 cmK1; dH 4.85 (1H, s), 4.76–4.68 (1H, m), 4.13
(2H, t, JZ6.8 Hz), 3.50 (1H, dd, JZ10.0, 3.6 Hz), 3.28 (1H,
dd, JZ10.0, 8.4 Hz), 2.85–2.72 (2H, m), 2.38–2.30 (1H, m),
1.91–1.82 (1H, m), 1.26 (3H, t, JZ6.8 Hz); dC 170.9, 166.6,
88.9, 84.8, 59.3, 31.8, 28.9, 14.4, 6.4; m/z 297 (57%), 296
(MC, 13), 251 (48), 169 (21), 123 (30), 115 (54), 99 (12), 95
(18), 87 (37), 81 (17), 69 (100), 67 (22), 55 (65), 54 (15), 53
(23), 43 (46), 42 (18), 41 (38). Anal. calcd for C9H13IO3: C,
36.51; H, 4.43; I, 42.86. Found: C, 36.57; H, 4.50; I,
42.78%.
Acknowledgements
We are grateful to the Natural Science Foundation of China
(Project No. 20332060, 20272050) and Zhejiang Province
Foundation of Member of Chinese Academy of Science).
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