Heterocycles from ylides. Reactivity of 2-acetyl-5-bromothiophene and -5-methylfuran with stabilised and non-stabilised ylides

Article abstract of DOI:10.1016/S0040-4020(00)00665-7

The title substrates 3 and 10 react with phosphonium salts 1a,b under phase-transfer catalysis conditions to afford phosphoranes 9a,b or pyrans 13, respectively, along with the corresponding 2,3-fused products with iso-furan rings 7a,b or 11a,b instead of the expected Wittig products. The reaction of 3 with stabilised phosphorus ylides 15a-c affords in the case of 15a,b, the stereoisomers (Z) 17 and (E) 18 in addition to the corresponding phosphonium salts. Compounds 10 and 15a,b yield, on the other hand, the iso-furans 23 and the dimeric products 22a,b as well, according to a sequence involving an initial Wittig reaction between 10 and 15a,b. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00665-7

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 7573–7580
Heterocycles from Ylides. Reactivity of
2-Acetyl-5-bromothiophene and -5-Methylfuran
with Stabilised and Non-stabilised Ylides
*
Wafaa M. Abdou and Azza A. Kamel
Department of Pesticide Chemistry, National Research Centre, Dokki, Cairo, Egypt
Received 10 April 2000; revised 6 July 2000; accepted 20 July 2000
Abstract—The title substrates 3 and 10 react with phosphonium salts 1a,b under phase-transfer catalysis conditions to afford phosphoranes
9a,b or pyrans 13, respectively, along with the corresponding 2,3-fused products with iso-furan rings 7a,b or 11a,b instead of the expected
Wittig products. The reaction of 3 with stabilised phosphorus ylides 15a–c affords in the case of 15a,b, the stereoisomers (Z) 17 and (E) 18 in
addition to the corresponding phosphonium salts. Compounds 10 and 15a,b yield, on the other hand, the iso-furans 23 and the dimeric
products 22a,b as well, according to a sequence involving an initial Wittig reaction between 10 and 15a,b. ᭧ 2000 Elsevier Science Ltd. All
rights reserved.
Introduction
(2a), prepared in situ from its bromide salt 1a in the presence
of sodium hydride in THF, afforded 4-methylthieno-
[3,2-c]5-methylfuran (7a) and 2-(5-methylidenetriphenyl-
phosphorane-2-thienyl)-propanol (9a) in 46 and 22%
yield, respectively (Scheme 1). The chemical structures of
7a and 9a were substantiated by elemental analyses and
spectral data. The IR spectrum of the diheteropentalene
product 7a showed the characteristic band due to the furan
nucleus at 1610 cmϪ1 and the disappearance of the band at
In recent years, the focus of our research has been on the
development of new synthetic methodology centred around
exploiting phosphorus ylide synthons and Wittig reac-
tions.1–3a,b We reported2 that reaction of 2-acetyl-(3H)-
naphtho[2,1-b]pyran-3-one with an appropriate phosphorus
ylide provides access to the corresponding-[2,1-b]-fused
substituted-benzenes, -cyclopentadienes and furocou-
marins. In continuation of our earlier work1a,3 exploring
the behaviour of furanyl- and thienyl- derivatives toward
various phosphorus reagents, the present investigation
deals with synthesis of new furo- and thieno[2,3-c]-fused
heterocycles by reacting some non-stabilised 2a,b and
stabilised phosphorus ylides 15a–c with 2-acetyl-5-
bromothiophene (3) and 2-acetyl-5-methylfuran (10), as
depicted in Schemes 1–4. The incentive for this application
was based on recorded biological potencies of numerous
substituted furans.4,5 In addition, furan derivatives are
added to tobacco to improve the flavour and aroma of the
tobacco,6 used in the crosslinking of polyesters with
styrene,7 and in photographic developing by diffusion trans-
fer process.8 The attention paid to thiophene substrates was
attributed to similar reasons.9,10
1
1673 cmϪ1 due to the acetyl group. An integrated H NMR
spectrum of this compound revealed the absence of the
signal at d 2.55 for the acetyl methyl protons and the
appearance of new signals at d 2.02 (O–C–CH3) and at d
2.21 (S–C–CH3). These two methyl groups were also
attested to by signals at dC 14.2 (O–C–CH3) and dC 15.6
(S–C–CH3) in the 13C NMR spectrum.11 The ylide structure
9a is assigned from its molecular weight determination and
its IR and NMR spectra. Its infrared spectrum exhibited an
absorption band at 3425 cmϪ1 due to the hydroxyl group. It
also revealed the presence of strong bands around 1680,
1510 cmϪ1 due to CvP stretching, and around 1430,
1
985 cmϪ1 for the P–C (phenyl) absorption. The H NMR
spectrum of 9a showed two doublets (JHHˆ7.2 Hz) at d 1.22
and 3.66 due to the methyl and the methylene protons,
respectively, and a singlet at d 4.35 assigned to the hydroxyl
proton. The two exocyclic methine protons appear as a
multiplet at d 4.03 (Me–CH–CH2OH) and as a doublet
(JHPˆ18.3 Hz) at d 7.08. In its 13C NMR spectrum, signals
were observed at dC 18.6 (CH3), 36.2 (Me–CH–CH2OH)),
63.6 (CH2OH) and 131.5 (d, JCPˆ98.2 Hz, CvP). The
Results and Discussion
Treatment of 2-acetyl-5-bromothiophene (3) with excess
(up to 2.2 mol/equiv.) of methylidenetriphenylphosphorane
Keywords: Wittig reaction; Diels–Alder reaction; thiophenes; furans; isofurans.
* Corresponding author. Tel.: ϩ202-3371-362; fax: ϩ202-3370-931; e-mail: wabdou@intouch.com
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00665-7

7574
W. M. Abdou, A. A. Kamel / Tetrahedron 56 (2000) 7573–7580
Scheme 1.
chemical shift of the 31P NMR signal of 9a is dP 19.7 ppm in
agreement with an ylide structure. The reaction products of
3 with ethyltriphenylphosphonium bromide (1b) under
phase-transfer catalysis conditions, as described for salt
1a, were assigned analogous structures 7b (47%) and 9b
(22%) on the basis of comparable spectroscopic arguments.
of the alkaline medium, yields the phosphorane inter-
mediate 4, which reacts further with a second ylide species
2 in two different ways affording finally compounds 7 and 9.
Michael addition of the phosphonium ylide carbon of 2 at
the 3-position of the thiophene, followed by cycloelimi-
nation of the formed betaine intermediates 5 gives the ylides
6. Further dehydrogenation of 6 gives the final products 7
through the action of a molecule of water on the ylide
system in 6 accompanied by elimination of triphenyl-
phosphine oxide. Conversely, Wittig reaction of the acetyl
carbonyl of 4 with 2 yields the intermediates 8, which are
stabilised by the addition of the elements of water (adven-
titious H2O) to give the products 9. The dehydrogenation
step can, however, be attributed to the long time of heating.
Analogous dehydrogenation processes were also
observed during some Wittig reactions11 and Diels–Alder
A mechanism that accounts for formation of the adducts 7
and 9 from the reaction of 2-acetyl-5-bromothiophene (3)
with non-stabilised ylides 2a,b can be assumed to follow the
series of reactions outlined in Scheme 1 which implies that
three positions in 3 are susceptible to nucleophilic attack:
the ring-site halogen, the 3-position of the thiophene and the
acetyl carbonyl group. Direct nucleophilic replacement of
the bromine atom of 3 by the carbanion centre of 2 and
abstraction of hydrogen bromide, enhanced by the presence
Scheme 2.

W. M. Abdou, A. A. Kamel / Tetrahedron 56 (2000) 7573–7580
7575
Scheme 3.
additions.11,12 Similarly, fused furans have also been synthe-
sised by us,2 on treatment of 3-acetyl-5,6-benzocoumarin
with alkylidene phosphoranes. Furthermore, this result is
along the lines previously reported2,13–15 for the tendency
of this type of Wittig reagent to undergo an addition-elimi-
nation process rather than an olefination reaction.
cycloelimination sequence followed by dehydrogenation
afforded the product 11. On the other hand, the formation
of pyran derivatives 13 can be envisaged as a hetero-Diels–
Alder addition of the substrate species 10 to the Wittig
products 12 initially formed to give the final adducts 13
via a prototropic rearrangement. It should be mentioned
that compounds 7, 11 and 23 (vide infra, Scheme 4) were
found to be stable under normal conditions. From the
chemical point of view, diheteropentalene systems (iso-
electronic with the pentalenedione), are usually quite
unstable. According to calculations there is—if at all—
only a low degree of aromatic stabilisation. Dioxahetero-
pentalenes of type 11 and 23 are especially rare and very
few compounds have been synthesised so far.16
Next, the behaviour of 2-acetyl-5-methylfuran (10) towards
the same non-stabilised ylides 2a,b was investigated
(Scheme 2). When 10 was caused to react with 2a (or 2b)
(1 mol/equiv.), prepared in situ from its bromide salt in the
presence of a base, in THF, the reaction afforded the unex-
pected furopyrans 13 (ϳ28%) along with furo-iso-furans 11
(ϳ39%). Both MS and NMR spectra of the latter products
favour structure 11 instead of the expected 2,3-dihydro-
derivatives. The structure of 2,4-dimethyl-2-(5-methyl-2-
furanyl) 8,9-dihydro-6-methylfuro[3,2-b]pyran 13a is
assigned from its molecular weight, and its 1H NMR
spectrum which showed two types of methyl groups: a
doublet (JHHˆ3 Hz) at d 1.95 (3H, C-4–CH3) and three
singlets in the range d 2.18–2.26 (9H, 3×CH3). The C-8-
and C-9 endo-protons are given as a doublet (JHHˆ5.5 Hz)
Furthermore, we have studied the reactions of 3 and 10 with
some stabilised phosphorus ylides 15a–c. A solution of
equimolar amounts of 3 and [(methoxycarbonyl)methyl-
ene]triphenylphosphorane (15a) in toluene was refluxed
for ϳ2 days to give the corresponding phosphonium salt
16a (32%) and a mixture (25%) of stereoisomers of the
Wittig products which could be further resolved by column
chromatography to give 17a (Z) (13%) and 18a (E) (8%).
The reaction is very slow and has been accelerated by using
a catalytic amount of benzoic acid as a protonating catalyst
in the reaction medium. The success of this procedure is
attributable to the protonation of the carbonyl group,
making it more electrophilic and therefore susceptible to
nucleophilic attack by the ylides 15. Structures of the
at d 4.23 and as a multiplet at d 4.48, respectively. The 13
C
NMR data are also in accord with the suggested structure.
When 13a was treated with N-bromosuccinimide, derivative
14 (78%) was isolated.
As with the reaction between 2 and 3 (Scheme 1, ‘B’),
Michael addition of 2 at the 3-position of the furan and
Scheme 4.

7576
W. M. Abdou, A. A. Kamel / Tetrahedron 56 (2000) 7573–7580
isolated products 16–18 were established on the basis of
elemental analysis, molecular weight determination (MS)
and the spectroscopic data.
In conclusion, the title reactions provide an easy synthetic
route to fused heterocycle derivatives in moderate yields.
The results also showed that the behaviour of 10 with either
the reactive ylides 2 or the stabilised ones 15 are in great
disparity with that of the thiophene species 3, which under-
goes an addition–elimination reaction or a simple Wittig
reaction toward the same synthons, respectively. This result,
however, is attributable to the lower aromaticity of the furan
ring, making its derivatives more reactive.16,21
The identity of cis- and trans-configuration for the isolated
compounds 17a,b (Z) and 18a,b (E) was suggested
1
according to H NMR chemical shifts and melting point
measurements. The determined chemical shifts of methyl
groups and olefinic protons in the recorded 1H NMR spectra
are: d 2.12 and 5.46 for 17a, mp 84–85ЊC; d 2.18 and 5.73
for 18, mp 60–62ЊC. In all cases the higher melting point
observed for the isomer suggested as cis- is greater than that
those of the corresponding trans isomer, in agreement with
the literature.17 Compounds 16b–18b were similarly
obtained by reacting 3 with [(ethoxycarbonyl)-methylene]-
triphenyl-phosphorane (15b) in boiling toluene containing
benzoic acid. Conversely, only the phosphonium salt 16c
was isolated in 70% yield when 3 was caused to react with
(acetylmethylene)triphenylphosphorane (15c) under the
same experimental conditions. Obviously, the b-ketoalkyl-
idenetriphenylphosphorane 15c which is less nucleophilic
comparatively to 15a,b failed to undergo either a conju-
gate addition or an olefination process. It should be
noted that the Wittig reaction of some ketones with
b-keto ylides (15, RvCH3, RvC6H5) has already
been tried by Ramirez and Dershowitz,18 however, with-
out success. The phosphonium salt 16c, which is taken
as a representative example, was converted readily into
the corresponding ylide 19 by the action of a base in
the usual manner. On treating 19 with an aldehyde (e.g.
p-NO2–C6H4–CHO), the normal Wittig reaction took
place to give the olefin 20 (Scheme 3).
Experimental
All melting points are uncorrected. IR spectra were recorded
on a Perkin–Elmer spectrophotometer model 197 (Grating)
using KBr disc. The 1H and 13C NMR spectra were run on a
Varian Gemini 200 (200 MHz) instrument, using TMS as an
internal reference. The 31P NMR spectra were recorded rela-
tive to external H3PO4 (85%) with a Varian CFT-80 instru-
ment. The mass spectra were performed at 70 eV on MS-50
Kratos (A.E.I.) spectrometer provided with data system. The
appropriate precautions in handling moisture-sensitive
compounds were observed. Materials and reagents were
purchased from Aldrich Company. Light petroleum refers
to the fraction 40–60ЊC.
I—Reaction of 2-acetyl-5-bromothiophene (3) with non-
stabilised ylides 2a,b
General procedure: A solution of the appropriate salt 1a,b
(4.2 mmol) and the ketone 3 (0.4 g, 2 mmol) in dry THF
(40 ml) was stirred by means of an efficient magnetic stirrer.
A solution of a slurry of 240 mg of NaH dispersion (57%
dispersion in oil) in 10 ml of dry THF was added in one
portion to the mixture and the system was stirred at room
temperature for 2 h and further was refluxed for 10–12 h
(TLC). The product mixture was poured into 300 mL of
distilled water, and extracted with 2×100 mL portion of
chloroform. The combined organic extracts were back-
washed with distd. water (50 mL), dried with Na2SO4 and
the solvent was removed under reduced pressure. The
residue was chromatographed on silica gel by using light
petroleum/ethyl acetate as the eluent.
In view of the above observations (3ϩ15a–c), it is evident
that in contrast with 2a,b, the reaction went through two
different pathways: a direct nucleophilic replacement of
the bromine atom by the carbanion centre of 15a–c to
give the phosphonium salt 16a–c or a Wittig olefination
(only with 15a,b) at the acetyl group to produce the stereo-
isomers 17 and 18. Furthermore, the foregoing results
showed that ring-site attack has predominated.
Finally, the reaction of 2-acetyl-5-methylfuran (10) with
stabilised ylides 15a,b represents another, even more inter-
esting variation of the Wittig reaction (Scheme 4). Treat-
ment of 10 with equimolar phosphorus ylide 15a (or 15b) in
boiling toluene containing benzoic acid gave the substituted
furofuran 23a (18%) (or 23b, 20%) and the dimer 22a (28%)
(or 22b, 31%). In contrast to the reaction between 15 and 3
(Scheme 3, ‘A’), the primary condensation products 21
seem to be unstable and highly reactive. However, stabili-
zation, as expected by trapping in a Michael type addition of
a second ylide species does not occur, instead the inter-
mediates 21 undergo [4ϩ2] intermolecular cycloaddition
to give the cycloadduct dimers 22.
(a) The reaction of 3 (0.4 g, 2 mmol) with methyltriphenyl-
phosphonium bromide (1a) (1.5 g, 4.2 mmol) gave
compounds 7a and 9a, respectively.
4-Methylthieno[3,2-c]5-methylfuran (7a). This compound
was obtained by (30% light petroleum/AcOEt)) as colour-
less crystals (137 mg, 46%), mp 68–70ЊC (n-pentane);
[Found: C, 63.24; H, 5.23; S, 21.18. C8H8OS requires C,
63.12; H, 5.3; S, 21.06%]; nmax (KBr) 1600–1610 cmϪ1
(–CvC–, furanyl); dH (CDCl3) 2.02, 2.21 (2s, 2×3H, 2×
CH3), 7.25, 7.38 (2d, JHHˆ1.5 Hz, 2×1H, Het-H); dC (CDCl3)
14.2 (O–C–CH3), 15.6 (S–C–CH3), 124.7 (C-3), 127.6
(C-7), 141.2 (C-2), 139.5 (S–C–CH3), 152.2 (O–C–CH3),
155.7 (C-6); MS (EI), m/z(%): Mϩ, found 152 (43). C8H8OS
requires 152.23.
An analogous dimerization reaction was also observed for the
reaction of 9,10-phenanthrenequinone19 and 10-(methoxy-
imino)phenanthrene-9-one20 with phosphorus ylides. The
structure 22 although not established with certainty, is
supported by the recorded elemental analysis and spectral
data. No reaction was observed, however, in a comparable
experiment, using the ylide 15c.
2(5-Methylidenetriphenylphosphorane-2-thienyl)propa-
nol (9a) This compound was obtained by (10% light petro-
leum/AcOEt) as colourless crystals (178 mg, 22%), mp

W. M. Abdou, A. A. Kamel / Tetrahedron 56 (2000) 7573–7580
7577
170–172ЊC (acetone/diethyl ether); [Found: C, 74.86; H,
5.96; P, 7.52; S, 7.64. C26H25OPS requires C, 74.97; H,
6.05; P, 7.43; S, 7.7%]; nmax (KBr) 3425 (OH), 1680,
1510 (CvP), 1430, 985 cmϪ1 (P–C); dH (d6-DMSO) 1.22
(d, JHHˆ7.2 Hz, 3H, CH3), 3.66 (d, JHHˆ7.2 Hz, 2H, CH2),
4.03 (m, 1H, CH–CH3), 4.35 (s, 1H, –CH2OH), 7.08 (d,
JHPˆ18.3 Hz, 1H, PvCH), 7.7–7.87 (m, 17H, Ar-H &
Het-H); dC (d6-DMSO) 18.6 (–C–CH3), 36.2 (Me–CH–
CH2OH), 63.6 (Me–CH–CH2OH), 124.7, 126.4 (C-3,
C-4), 121.3, 124.5, 127.9, 129.6 (CvC, Ph), 131.5 (d,
2×1H, Het-H); MS (EI), m/z (%): Mϩ, found 136 (65).
C8H8O2 requires 136.15.
2,4-Dimethyl-2(5-methyl-2-furanyl) 8,9-dihydro-6-methyl-
furo[3,2-b]pyran (13a). The compound was obtained by
(20% n-hexane/CHCl3) as brown material (310 mg, 39%),
mp 112–113ЊC (diethyl ether); [Found: C, 73.22; H, 7.29.
C15H18O3 requires C, 73.14; H, 7.36%]; nmax (KBr) 1150–
1125 (–C–O–C–), 1065 cmϪ1 (–CvC–O); dH (CDCl3)
1.95 (d, JHHˆ3 Hz, 3H, C-4–CH3), 2.18, 2.23, 2.26 (3s,
3×3H, 3×O–C–CH3), 4.23, 4.48 (q & d, diffused, 2×1H,
C-8–H & C-9–H), 6.88–7.56 (4d, diffused, 4×1H, Het-H);
dC (CDCl3) 13.4, 13.7, 14.2 (3×O–C–CH3), 15.8 (C-4–
CH3), 47.36, 49.82 (C-8–H& C-9–H), 106.2, 107.6, 108.6
(C-20, C–30, C-7), 133.1 (C-4), 136.4 (C-3), 149.7, 151.4,
155.5 (C-10, C-40,C-6); MS (EI), m/z (%): Mϩ, found 246
(13). C8H8O2 requires 246.31.
2
JCPˆ98.8 Hz, HCvP), 142.4 (d, JCPˆ8.8 Hz, C–CvP);
dP (d6-DMSO) 19.7 ppm; MS (EI), m/z (%): Mϩ, found
416 (30). C26H25OPS requires 416.53.
(b) The reaction of 3 (0.4 g, 2 mmol) with ethyltriphenyl-
phosphonium bromide (2b) (1.6 g, 4.2 mmol) yielded
compounds 7b and 9b.
4-Ethylthieno[3,2-c]2,5-dimethylfuran (7b). the com-
pound was obtained by (30% light petroleum/AcOEt) as
colourless crystals (164 mg, 47%), mp 68–70ЊC (n-pen-
tane); [Found: C, 66.71; H, 6.63; S, 17.69. C10H12OS
requires C, 66.63; H, 6.71; S, 17.78%]; nmax (KBr) 1600–
(b) The reaction of 10 (1 g, 8 mmol) with ethyltriphenyl-
phosphonium bromide (1b) (3.2 g, 8.5 mmol) afforded
compounds 11b and 13b.
4-Methylfuro[3,2-c]2,5-dimethylfuran (11b). This com-
pound was obtained by (90% n-hexane/CHCl3) as brown
crystals (300 mg, 25%), mp 100–102ЊC (light petroleum);
[Found: C, 71.84; H, 6.66. C9H10O2 requires C, 71.98; H,
6.71%]; nmax (KBr) 1590–1610 cmϪ1 (–CvC–, furanyl);
dH(CDCl3) 1.08, 1.22, 2.31 (3s, 3×3H, O–C–CH3), 7.15 (q,
diffused, 1H, Het-H); MS (EI), m/z (%): Mϩ, found 150
(100). C9H10O2 requires 150.18.
1610 cmϪ1 (–CvC–, furanyl); dH (CDCl3) 1.05 (t, JHH
ˆ
6.5 Hz, 3H, –CH2CH3), 2.08, 2.21 (2s, 2×3H, 2×CH3), 2.25
(q, JHHˆ6.5 Hz, 2H, C–CH2), 7.28, 7.37 (2d, JHHˆ1.5 Hz,
2×1H, Het-H); MS (EI), m/z(%): Mϩ, found 180 (65).
C10H12OS requires 180.27.
2(5-Ethylidenetriphenylphosphorane-2-thienyl)propanol
(9b). The compound was produced by (10% light petro-
leum/AcOEt) as colourless crystals (187 mg, 22%), mp
180–182ЊC (ethyl alcohol); [Found: C, 75.75; H, 6.44; P,
7.06; S, 7.3. C28H29OPS requires C, 75.64; H, 6.57; P 6.97; S
7.21%]; nmax (KBr) 3430 (OH), 1675, 1515 (CvP), 1440,
985 cmϪ1 (P–C); dH (d6-DMSO) 1.08–1.22 (m, 9H, 3×
–CH3), 4.05–4.12 (m, 2H, –CH & CHOH), 4.46 (br. 1H,
–OH), 7.23–7.78 (m, 17H, Ar-H & Het-H); dC (d6-DMSO)
13.8, 14.5, 17.7 (3×C–CH3), 62.6 (CHOH), 121.3, 124.5,
127.9, 129.6 (CvC, Ph), 124.7, 126.4 (C-3, C-4), 136.8
2,3,4-Trimethyl-2-(5-methyl-2-furanyl)8,9-dihydro-6-
methylfuro[3,2-b]pyran (13b). This compound was
obtained by (20% n-hexane/CHCl3) as brown material
(344 mg, 33%), mp 120–122ЊC (acetonitrile); [Found C,
73.93; H, 7.66. C16H20O3 requires C, 73.82; H, 7.74%];
nmax (KBr) 1145–1125 (–C–O–C–), 1042 cmϪ1
(–CvC–O); dH (CDCl3) 1.96 (d, JHHˆ2.5 Hz, 3H, C-4–
CH3), 2.04 (s, 3H, C-6–CH3), 2.16, 2.32, 2.35 (3s, 3×3H,
3×O–C–CH3), 4.17 (d of q, diffused, C-8–H); 4.25 (d,
JHHˆ5.5 Hz, C-9–H), 7.25–7.54 (3d, diffused, 3×1H,
Het-H); MS (EI), m/z(%): Mϩ, found: 260 (17). C16H20O3
requires 260.33.
2
1
(C-2), 142.4 (d, JCPˆ8.8 Hz, C–CvP), 143.3 (d, JCPˆ
104 Hz, PvC); dP (d6-DMSO) 19.3 ppm; MS (EI), m/z(%):
Mϩ, found 444 (22). C28H29OPS requires 444.58.
Reaction of 13a with NBS
II—Reaction of 2-acetyl-5-methylfuran (10) with non-
stabilised ylides (2a,b)
N-Bromosuccinimide (NBS) (54 mg, 0.3 mmol) and
benzoyl peroxide (7.2 mg, 0.04 mmol) were added to a solu-
tion of 13a (74 mg, 0.3 mmol) in 20 mL of dry CCl4. The
mixture was refluxed for 2 h and filtered while hot. Evapora-
tion of the solvent left a residue, which chromatographed
(silica gel, 1:1 CHCl3/ethyl acetate) to give the dehydro-
derivative 14 (57 mg, 78%), mp 87–88ЊC (cyclohexane);
[Found: C, 73.67; H, 6.73. C15H16O3 requires C, 73.75; H,
6.6%]; nmax (KBr) 1590–1610 (–CvC–, furanyl),
1055 cmϪ1 (–CvC–O); dH(CDCl3) 2.11–2.43 (m, 4×3H,
4×–CH3), 7.33–7.58 (4d, diffused, 4×1H, Het-H); MS (EI):
m/z (%): Mϩ, found 244 (16). C15H16O3 requires 244.29.
A THF solution of the appropriate salt 1a or 1b (8.5 mmol)
and the furan derivative 10 (1 g, 8 mmol) was treated with
sodium hydride (NaH) under the experimental conditions
described above for the general procedure. The product
residue was then separated by column chromatography
using n-hexane/chloroform as the eluent.
(a) The reaction of 10 (1 g, 8 mmol) with 1a (3.2 g,
8.5 mmol) afforded compounds 11a and 13a.
4-Methylfuro[3,2-c]5-methylfuran (11a). The compound
was obtained by (80% n-hexane/CHCl3) as brown crystals
(300 mg, 28%), mp 76–77ЊC (light petroleum); [Found: C,
70.44; H, 5.81. C8H8O2 requires C, 70.57; H, 5.92 %]; nmax
(KBr) 1600–1610 cmϪ1 (–CvC–, furanyl); dH (CDCl3)
1.93, 2.05 (2s, 6H, 2×CH3), 7.35, 7.65 (2d, JHHˆ1.5 Hz,
III—Reaction of 2-acetyl-5-bromothiophene (3) with
stabilised phosphorus ylides 15a–c
General procedure: A solution of compound 3 (1 g,

7578
W. M. Abdou, A. A. Kamel / Tetrahedron 56 (2000) 7573–7580
4.8 mmol) and the appropriate ylide 15a–c (5 mmol) in dry
toluene (30 mL) containing benzoic acid (0.2 g) was
refluxed for ϳ2 days (TLC). After evaporation of the
solvent, the remainder was subjected to a column previously
charged with silica gel suspended in n-hexane. The column
was then developed with n-hexane containing increasing
amounts of ethyl acetate.
(b) The reaction of 3 with [(ethoxycarbonyl)methylene]tri-
phenylphosphorane (15b) (1.7 g, 5 mmol) afforded two
fractions: The fractions that were collected up to 60%
light petroleum/CHCl3 indicated the presence of two
products (Z) 17b and (E)-18b. This eluent was re-evapo-
rated to dryness and the residue was chromatographed on
silica gel and eluted with light petroleum containing
increasing amounts of chloroform.
(a) The reaction of 3 (1 g, 4.8 mmol) with [(methoxy-
carbonyl)methylene]triphenylphosphorane (15a) (1.7 g,
5 mmol) gave two fractions:
Z-Ethyl 2(5-bromo-2-thienyl)prop-2-ene carboxylate
(17b). This compound was obtained by (80% light petro-
leum/CHCl3) as colourless crystals (214 mg, 16%, based on
3), mp 86ЊC (light petroleum); [Found: C, 44.53; H, 4.11;
Br, 28.96; S, 11.59. C10H11BrO2S requires C, 43.64; H, 4.03;
Br, 29.04; S, 11.65%]; nmax (KBr) 1725 (CvO, ester),
1613 cmϪ1 (CvCH); dH (CDCl3) 0.82 (t, JHHˆ5.5 Hz,
3H, O–C–CH3), 2.1 (d, JHHˆ1.5 Hz, 3H,vC–CH3), 3.85
(q, JHHˆ5.5 Hz, 2H, O–CH2), 5.48 (q, JHHˆ1.5 Hz,
1H,vCH), 6.58, 6.82 (2d, JHHˆ2.5 Hz, 2×1H, Het-H);
dC(CDCl3) 14.8 (O–C–CH3), 25.2 (vC–CH3), 62.3
(OCH2), 119.7, 122.8 (C-3, C-4), 128.8 (CvCH), 133.4
(CvCH), 147.8, 151.9 (C-5, C-2), 169.8 (CvO); MS
(EI), m/z(%): Mϩ, found 275 (100), Mϩϩ2, 277 (33).
C10H11BrO2S requires 275.18.
The fractions that were collected by (60% n-hexane/AcOEt)
afforded, after evaporation, a mixture (343 mg, 25%) of the
two constituents Z-17a and E-18a; dH (CDCl3) 2.13, 2.17
(2d, 2×3H, 2-CH3, 17a, 18a); 3.35, 3.36 (2s, 2×3H,
2×OCH3, 17a & 18a), 5.44, 5.73 (2q, 2×1H, 2×1H, 17a,
18a). The latter mixture was then injected to a silica gel
column had packed in light petroleum and eluted with
light petroleum–chloroform.
(Z)-Methyl 2(5-bromo-2-thienyl)prop-2-ene carboxylate
(17a). This compound was obtained by (80% light petro-
leum/CHCl3) as colourless crystals (178 mg, 13%, based on
3), mp 84–85ЊC (cyclohexane); [Found: C, 41.45; H, 3.33;
Br, 30.67; S, 12.31. C9H9BrO2S requires C, 41.39; H, 3.47;
Br, 30.6; S, 12.28%]; nmax (KBr) 1715 (CvO, ester),
1640 cmϪ1 (CvCH); dH (CDCl3) 2.12 (d, JHHˆ1.5 Hz,
3H, CH3), 3.37 (s, 3H, OCH3), 5.46 (q, JHHˆ1.5 Hz,
1H,vCH), 6.62, 6.88 (2d, JHHˆ2.5 Hz, Het-H), 3.37 (s,
(E)-Ethyl 2(5-bromo-2-thienyl)prop-2-ene carboxylate
(18b). This compound was obtained by (70% light petro-
leum/CHCl3) as colourless crystals (94 mg, 7%), mp 58–
60ЊC (pentane); [Found: C, 43.59; H, 3.88; Br, 28.93; S,
11.57. C10H11BrO2S requires C, 43.63; H, 4.03; Br, 29.04;
S, 11.65%]; nmax (KBr) 1715 (CvO, ester), 1622 cmϪ1
(CvCH); dH (CDCl3) 0.85 (t, JHHˆ5.5 Hz, 3H, OC–
3H, OCH3), 5.46 (s, 1H,vCH), 6.6. 6.88 (2d, JHH
ˆ
2.5 Hz, 2H, Het-H); dC (CDCl3) 25.2 (vC–CH3), 51.8
(OCH3), 121.6, 124.1 (C-3, C-4), 126.0 (CvCH), 148.9,
151.4 (C-5, C-2), 171.6 (CvO, ester); MS (EI), m/z(%):
Mϩ, found: 261 (100), Mϩϩ2, 263 (33). C9H9BrO2S
requires 261.15.
CH3), 2.14 (d, JHHˆ2 Hz, 3H, vC–CH3), 3.82 (q, JHH
ˆ
5.5 Hz, 2H, OC–CH2), 5.73 (q, JHHˆ2 Hz, 1H,vCH),
6.58, 6.81(2d, JHHˆ2.5 Hz, 2×1H, Het-H); dC (CDCl3)
15.3(O-C–CH3), 23.6 (vC–CH3), 63.4 (OCH2), 121.1,
123.3 (C-3, C-4), 128.2 (CvCH), 135.4 (CvCH), 147.3,
154.6 (C-5, C-2), 171.5 (CvO); MS (EI), m/z(%): Mϩ,
found 275 (100), Mϩϩ2, 277 (33). C10H11BrO2S requires
275.18.
(E)-Methyl 2(5-bromo-2-thienyl)prop-2-ene carboxylate
(18a). This compound was obtained by (70% light petro-
leum/CHCl3) as colourless crystals (93 mg, 8%, based on 3),
mp 62–64ЊC (pentane); [Found: C, 41.52; H, 3.38; Br,
30.54; S, 12.37. C6H9BrO2S requires C, 41.39; H, 3.47;
Br, 30.6; S, 12.28%]; nmax (KBr) 1720 (CvO, ester),
1635 cmϪ1 (CvCH); dH (CDCl3) 2.18 (d, JHHˆ2 Hz, 3H,
CH3), 3.32 (s, 3H, OCH3), 5.73 (q, JHHˆ2 Hz, 1H,vCH),
6.62, 6.86 (2d, JHHˆ2.5 Hz, 2×1H, Het-H); dC (CDCl3) 22.7
(vC–CH3), 53.4 (OCH3), 121.4, 123.5 (C-3, C-4), 128.4
(CvCH), 133.6 (CvCH), 148.2, 151.7 (C-5, C-2), 173.2
(CvO, ester); MS (EI), m/z (%): Mϩ, found 261(100),
[Mϩϩ2], 263 (33). C6H9BrO2S requires 261.15.
2-Acetylthienyl-5-[(ethoxycarbonyl)methylene]triphenyl-
phosphonium bromide (16b). This compound was
obtained by (10% light petroleum/CHCl3) as colourless
crystals (0.89 g, 33%), mp 265–266ЊC (dil. ethanol);
[Found: C, 61.63; H, 4.88; Br, 14.55; P 5.52; S, 5.86.
C28H26BrO3PS requires C, 60.76; H, 4.75; Br, 14.44; P,
5.6; S, 5.79%]; nmax (KBr) 1715 (CvO, ester), 1677
(CvO, acetyl), 1455, 980 cmϪ1 (P–C, phenyl); dH
(d6-DMSO) 1.07 (t, JHHˆ6.2 Hz, 3H, O–C–CH3), 2.26 (s,
3H, C(O)CH3), 3.88 (q, JHHˆ6.2 Hz, 2H, OCH2), 4.24 (d,
JHPˆ20.5 Hz, 1H, P–CH), 6.82–7.83 (m, 17H, Ar-H &
Het-H); dP (d6-DMSO) 15.5 ppm; MS (EI), m/z(%): Mϩ,
found 553 (6). C28H26BrO3PS requires 553.48.
2-Acetylthienyl-5-[(methoxycarbonyl)methyl]triphenyl-
phosphonium bromide (16a). The compound was obtained
(10% light petroleum/CHCl3) as colourless crystals (0.84 g,
32%), mp 285–287ЊC (dil. ethanol); [Found: C, 60.08; H,
4.42; Br, 14.68; P, 6.04; S, 5.83. C27H24BrO3PS requires C,
60.11; H, 4.48; Br, 14.81; P, 5.74; S, 5.94%]; nmax (KBr)
1722 (CvO, ester), 1675 (CvO, acetyl), 1455, 980 cmϪ1
(C–P, phenyl); dH (d6-DMSO) 2.52 (s, 3H, C(O)CH3), 3.35
(s, 3H, OCH3), 3.88 (d, JHPˆ18.5 Hz, 1H, P–CH), 7.25–
7.78 (m, 17H, Ar-H & Het-H); dP 14.83 ppm; MS (EI),
m/z(%): Mϩ, found 539 (18), Mϩϩ2, 541(6) C27H24BrO3PS
requires 539.45.
(c) The reaction of 3 with (acetylmethylene)triphenyl-
phosphorane (15c) (1.6 g, 5 mmol) gave only 2-acetyl-
thienyl-5(acetylmethylene)triphenylphosphonium bromide
(16c) which obtained by (10% light petroleum/CHCl3) as
colourless crystals (1.78 g, 70%), mpϾ300ЊC (AcOEt/
MeCN); [Found: C, 62.68; H, 4.13; Br, 15.01; P, 6.55; S,
5.38. C27H24BrO2P requires C, 62.75; H, 4.02; Br, 15.17; P,
5.62; S, 6.24%]; nmax (KBr) 1674, 1658 (2×C(O), acetyl),

W. M. Abdou, A. A. Kamel / Tetrahedron 56 (2000) 7573–7580
7579
1450, 988 cmϪ1 (P–C, phenyl); dH (d6-DMSO) 2.48,
2.51(2s, 2×3H, 2×C (O)CH3), 4.52 (d, JHPˆ20.2 Hz, 1H,
58–60ЊC (pentane); [Found: C, 64.31; H, 5.37. C11H12O4
requires C, 63.45; H, 5.8%]; nmax (KBr) 1720 cmϪ1
(CvO, ester); dH (CDCl3) 1.06 (t, JHHˆ6.5 Hz, 3H, CH3,
ester), 1.91, 2.13 (2s, 2×3H, 2×CH3, furanyls), 3.92 (q,
JHHˆ6.5 Hz, 2H, OCH2), 7.41(q, diffused, 1H, Het-H);
MS (EI), m/z (%): Mϩ, found 208 (26). C11H12O4 requires
208.22.
P–CH), 6.76–7.64 (m, 17H, Ar-H
& Het-H); dC
(d6-DMSO) 24.5, 25.2 (2×C(O)CH3), 68.5 (d, JCPˆ
104 Hz, HC–P), 120.7, 124.5, 128.4, 129.1 (CvC, Ph),
121.6, 124.1 (C-3, C-4), 144.8, 155.2 (C-5, C-2), 192.7,
194.3 [2×C(O)]; dP (d6-DMSO) 14.6 ppm; MS (EI),
m/z(%): Mϩ, found 523 (13), Mϩϩ2, 525 (5).
C27H24BrO2P requires 523.45.
The dimeric product 22a was obtained as yellow crystals
(400 mg, 28%), mp 203–205ЊC (dichloromethane); [Found:
C, 66.55; H, 6.65. C20H24O6 requires C, 66.65; H, 6.71%];
nmax (KBr) 1728, 1720 cmϪ1 (CvO, ester); dH (d6-DMSO)
0.55 (d, JHHˆ5.5 Hz, 3H, C-1–CH3), 0.66 (d, JHHˆHz, 3H,
C-4–CH3), 2.07, 2.15 (s, 2×3H, –CH3, furanyls), 3.56–3.86
(m, 9H, C-1–, C-2–, C-3–H & 2×OCH3), 6.55, 6.94
(2d, JHHˆ2.5 Hz, 2H, Het-H), 7.38 (q, difused, 1H,
Het-H); MS (EI), m/z(%): Mϩ, found 360 (20). C20H24O6
requires 360.4.
Alkaline treatment of the phosphonium salt 16c
A mixture of 16c (1.5 g) and 20 mL of Na2CO3 (10%, aq.)
was heated to reflux for one hour. The mixture was cooled,
diluted with dist. H2O (8 mL) and extracted with chloro-
form. The residue obtained on removal of CHCl3 was boiled
with light petroleum and then recrystallized from ethyl
alcohol to give the corresponding ylide 19 as colourless
crystals, mp 163ЊC (benzene); [Found: C, 73.37; H, 5.11;
P, 6.86; S, 7.34. C27H23O2PS requires C, 73.28; H, 5.24; P,
7.0; S, 7.24%]; nmax (KBr) 1670, 1656 cmϪ1 (2×CvO, ace-
tyl); dH (d6-DMSO) 2.35, 2.52 (2s, 2×3H, 2×C(O)CH3),
6.78–7.65 (m, 17H, Ar-H & Het-H); dP (d6-DMSO)
21.3 ppm; MS (EI), m/z (%): Mϩ, found 442 (25).
C27H23O2PS requires 442.53.
22b. It was obtained as yellow crystals (468 mg, 31%), mp
182–184ЊC (dichloromethane); [Found: C, 68.12; H, 7.34.
C22H28O6 requires C, 68.02; H, 7.26%]; nmax (KBr) 1735,
1730 cmϪ1(CvO, ester); dH (d6-DMSO) 0.52–1.23 (m,
12H, C-1–, C-4–CH3 & 2×CH3, ester); 2.05, 2.18 (2s,
2×3H, 2CH3, furanyl), 3.55–3.95 (m, 7H, C-1, C-2–,
C-3H & OCH3, ester), 6.57, 6.99 (2d, JHHˆ2.5 Hz, 2H,
Het-H), 7.31 (q, diffused, 1H, Het-H); MS (EI), m/z (%):
Mϩ, found 388 (20). C22H28O6 requires 388.46.
Wittig reaction of the produced ylide 19
To a solution of 19 (0.5 g, 1.3 mmol) in ethyl methyl ketone
(20 mL) containing triethylamine (0.2 mL), p-nitrobenz-
aldehyde (0.3 g, 2 mmol) was added. The reaction mixture
was refluxed for 8 h. and the solvent was evaporated.
Extraction of the residue with hot light petroleum gave on
cooling triphenylphosphine oxide, mp 155ЊC. Crystalliza-
tion of the residual substance from acetone yielded the
exocyclic olefin 20 (230 mg, 66%), mp 117ЊC; [Found: C,
61.81; H, 4.03; N, 4.31; S, 10.05. C16H13NO4S requires C,
60.94; H, 4.15; N, 4.44; S, 10.17%]; nmax (KBr) 1680, 1658
(2×C (O), acetyl), 616 cmϪ1 (CvCH, exocyclic); dH
(CDCl3) 2.34, 2.51(2s, 2×3H, 2× C(O)CH3), 6.89–7.56
(m, 7H, Ar-H, Het-H &vCH); MS (EI), m/z(%): Mϩ,
found 315 (42). C16H13NO4S requires 315.35.
Triphenylphosphine and its oxide were also isolated and
identified from this reaction.
When 10 (1 g, 8 mmol) was allowed to react with 15c (2.5 g,
8 mmol) under above same conditions and working up, the
edducts (10 and 15c) were recovered practically unchanged
(Ͼ80%).
References
1. For a recent accounts see references a–k: (a) Abdou, W. M.;
Elkhoshnieh, Y. O.; Kamel, A. A. Heteroatom Chem. 1999, 10,
481–496. (b) Abdou, W. M.; Ganoub, N. A.; Shaddy, A. M.
Tetrahedron 1998, 54, 9079–9088. (c) Abdou, W. M.; Ganoub,
N. A. Synth. Commun. 1998, 28, 3579–3589. (d) Abdou, W. M.;
Salem, M. A. I.; Sediek, A. A. J. Chem. Res., Synop. 1998, 28–29;
(Miniprint) 1998, 327–339. (e) Abdou, W. M.; Salem, M. A. I.;
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IV—Reaction of 2-acetyl-5-methylfuran (10) with
stabilised phosphorus ylides 15a–c
Treatment of compound 9 (1 g, 8 mmol) with the appro-
priate ylide 15a–c (8.2 mmol) in toluene containing benzoic
acid (0.2 g) was refluxed for ϳ2 days (TLC). The product
mixture was worked up as above whereupon triphenyl-
phosphine oxide along with 23a,b which eluted by (60%
light petroleum/CHCl3) and 22a,b which eluted by (10%
light petroleum/CHCl3), respectively, could be isolated.
The fused furan 23a was obtained as yellow crystals
(280 mg, 18%), mp 77–79ЊC (cyclohexane); [Found: C,
61.69; H, 5.26. C10H10O4 requires C, 61.85; H, 5.19%];
nmax (KBr) 1725 cmϪ1 (CvO, ester); dH (CDCl3) 1.95,
2.04 (2s, 2× 3H, 2× C–CH3), 3.48 (s, 3H, OCH3), 7.43 (q,
diffused, 1H, Het-H); MS (EI), m/z (%): Mϩ, found 194
(38). C10H10O4 requires 194.19.
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