Regioselective synthesis of ω-bromo-3-ketosulfones, ω-bromo-3-ketonitriles and 2-(ω-bromoalkyl)benzofurans based on a 'ring-closing/ring-opening' strategy

Article abstract of DOI:10.1016/j.tet.2007.08.112

ω-Bromo-3-ketosulfones, ω-bromo-3-ketonitriles and various functionalized 2-(ω-bromoalkyl)benzofurans were chemo- and regioselectively prepared by application of a 'ring-closing/ring-opening' strategy. The cyclization of 3-ketosulfone and 3-ketonitrile dianions with 1-bromo-2-chloroethane or 1,4-dibromobut-2-ene afforded functionalized 2-alkylidenetetrahydrofurans which were subsequently cleaved by reaction with boron tribromide or boron trichloride to give the final products.

Full text of DOI:10.1016/j.tet.2007.08.112

Tetrahedron 63 (2007) 11626–11635
Regioselective synthesis of u-bromo-3-ketosulfones,
u-bromo-3-ketonitriles and 2-(u-bromoalkyl)benzofurans
based on a ‘ring-closing/ring-opening’ strategy
Nasir Rasool,a Muhammad A. Rashid,a Helmut Reinke,a
Christine Fischerb and Peter Langera,b,
*
aInstitut fu€r Chemie, Universita€t Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
bLeibniz-Institut fu€r Katalyse e. V. an der Universita€t Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Received 30 July 2007; revised 31 August 2007; accepted 31 August 2007
Available online 6 September 2007
Abstract—u-Bromo-3-ketosulfones, u-bromo-3-ketonitriles and various functionalized 2-(u-bromoalkyl)benzofurans were chemo- and re-
gioselectively prepared by application of a ‘ring-closing/ring-opening’ strategy. The cyclization of 3-ketosulfone and 3-ketonitrile dianions
with 1-bromo-2-chloroethane or 1,4-dibromobut-2-ene afforded functionalized 2-alkylidenetetrahydrofurans which were subsequently
cleaved by reaction with boron tribromide or boron trichloride to give the final products.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Boron tribromide (BBr3) represents a widely used reagent
for the cleavage of methoxyarenes.1 Besides this well-
known application of BBr3, other reactions have only
scarcely been reported in the literature. u-Bromoalcohols2
and u-halocarboxylic acids3 were prepared by BBr3-
mediated ring opening of cyclic ethers and lactones,
respectively.3 Recently, we reported the synthesis of
6-bromo-3-oxoalkanoates by reaction of BBr3 with 2-alkyl-
idenetetrahydrofurans.4 The synthesis of benzofuran-3-carb-
oxylic esters containing a remote bromide group—based
on a BBr3-mediated ring transformation—has also been
reported.5 Herein, we report the synthesis of u-bromo-3-
ketosulfones, u-bromo-3-ketonitriles and 2-(u-haloalkyl)-
benzofurans based on the synthesis of 2-(sulfonylmethyl-
idene)- and 2-(cyanomethylidene)-tetrahydrofurans and
their subsequent BBr3-mediated cleavage. The products are
not readily available by other methods. Notably, functional-
ized benzofurans are of considerable pharmacological rele-
vance and represent versatile synthetic building blocks in
organic and medicinal chemistry.6 For example, the benzo-
furan amiodarone is used in the clinic as a potent antiarrythmic
and antianginal drug.7 Various benzofurans occur in natural
products. This includes, for example, longicaudatin,8 the
sessiliflorols A and B, flemistrictin E, tovophenone C,
vismiaguianone C or piperaduncin B.9
2.1. Reactions of 3-ketosulfone dianions
2-(2-Oxoalkylidene)tetrahydrofurans are available bycycliza-
tion10 of 1,3-dicarbonyl dianions or 1,3-bis(silyl enol ethers)
(‘masked dianions’) with various electrophiles, such as 1-bro-
mo-2-chloroethane,11 1,4-dibromobut-2-ene,12 or epoxides.13
2-(Sulfonylmethylidene)tetrahydrofurans were prepared, for
example, from b-iodovinyl sulfones,14 u-halo and u-hy-
droxy-b-ketosulfones,15 or u-hydroxypropargylic sulfones.16
Another approach relies on the cyclization of 3-ketosulfone
dianions with cyclic sulfates.17 Some years ago, we reported
the synthesis of 7-sulfonyl-2,3,3a,4,5,6-hexahydrobenzofur-
ans, which can be regarded as bicyclic 2-(sulfonylmethylide-
ne)tetrahydrofurans, by cyclization of cyclic 3-ketosulfone
dianions with 1,4-dibromobut-2-ene.12
The cyclization of the dianions of 3-ketosulfones 1a–c, gen-
erated by LDA (2.5 equiv), with 1-bromo-2-chloroethane af-
forded the 2-(sulfonylmethylidene)tetrahydrofurans 2a–c
(Scheme 1, Table 1). The reaction of a CH2Cl2 solution of
2a–c with BBr3 and subsequent addition of water afforded
the u-bromo-b-ketosulfones 3a–c. The formation of 3a–c
can be explained as follows. The interaction of BBr3 with
the sulfonyl group effects a dramatic increase of the electro-
philicity of carbon atom C-5 of the tetrahydrofuran moiety.
Nucleophilic attack of a BBr3-derived bromide ion onto car-
bon C-5 results in ring-opening and formation of an open-
chain boron enolate. The latter is subsequently protonated
* Corresponding author. Tel.: +49 381 4986410; fax: +49 381 4986412;
e-mail: peter.langer@uni-rostock.de
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.08.112

N. Rasool et al. / Tetrahedron 63 (2007) 11626–11635
11627
Table 1. Synthesis of 3a–c
the dianions of 7a–c with 1-bromo-2-chloroethane afforded
the 2-alkylidenetetrahydrofurans 8a–d. Treatment of 8a–
d with BBr3 afforded the 2-(g-bromoalkyl)-3-sulfonylben-
zofurans 9a–d (Scheme 3, Table 3). The reaction of 8a–c
with BCl3 gave 2-(g-hydroxypropyl)-3-sulfonylbenzofurans
9e–g. The formation of benzofurans 9 can be explained by
ring-opening of 8 and deprotection of the arylmethyl ether
to give intermediate A, hydrolysis upon aqueous work-up
(intermediate B) and subsequent acid mediated cyclization
by attack of the hydroxy onto the carbonyl group. In case
of 9e–g, the chloride group was hydrolyzed.
2,3
Ar
% (2)a
E/Z (2)b
% (3)a
a
b
c
Ph
4-MeC6H4
4-ClC6H4
45
45
40
7:3
7:3
6:4
95
92
65
a
Yields of isolated products.
By 1H NMR.
b
upon addition of water. Notably, products 3a–c are not di-
rectly available by reaction of 3-ketosulfone dianions with
1,2-dibromoethane, due to a competing SET process (oxida-
tive dimerization of the dianion and reduction of 1,2-dibro-
moethane to ethylene).18
O
MeO
MeO
O
Cl
R
O
i
Cl
SO2Ar
R
SO2Ar
7a-d
Br
SO2Ar
SO2Ar
2a-c
O
i
6a-c
1a-c
Br
ii
Cl
ii
4 BBr3
Br
Br
MeO
O
O
BX3
SO2Ar
O
SO2Ar
iii
SO2Ar
Br
3a-c
R
X
R
9a-g
8a-d
Scheme 1. Synthesis of u-bromo-3-ketosulfones 3a–c. (i) (1) 2.5 equiv
LDA, THF, 0 ꢀC, 1 h; (2) Br(CH2)2Cl, ꢁ78/20 ꢀC, 14 h, then reflux,
14 h; (ii) (1) 4.0 equiv BBr3, CH2Cl2, 0/20 ꢀC, 12 h, 20 ꢀC, 8 h; (2) H2O.
2-(Sulfonylmethylidene)-5-vinyltetrahydrofurans 4a–c were
prepared by cyclization of dilithiated 3-ketosulfones 1a–c
with 1,4-dibromobut-2-ene (Scheme 2, Table 2). The reac-
tion of 4a–c with BBr3 afforded the u-bromo-3-keto-
sulfones 5a–c. The products were formed by cleavage of
Br2BO
Br2BO
HO
O
H2O
SO2Ar
SO2Ar
X
R
X
R
0
the 2-alkylidenetetrahydrofuran by an SN reaction. Nota-
A
B
bly, the products are not available by direct reaction of
the dianions of 1a–c with 1,4-dibromobut-2-ene, due to
rapid cyclization.
Scheme 3. Synthesis of benzofurans 9a–e. (i) (1) 2.5 equiv LDA, THF, 0 ꢀC,
45 min; (2) acid chloride, ꢁ78/20 ꢀC, 14 h; (ii) (1) 2.5 equiv LDA, THF,
0 ꢀC, 1 h; (2) Br(CH2)2Cl, ꢁ78/20 ꢀC, 14 h, then reflux, 14 h; (iii) (1)
5.0 equiv BBr3, CH2Cl2, 0/20 ꢀC, 12 h, 20 ꢀC, 12 h; (2) H2O.
O
Br
SO2Ar Br
SO2Ar
O
The structure of all products was established by spectro-
scopic methods. The structures of 8a and 9a were indepen-
dently confirmed by X-ray crystal structure analyses
(Figs. 1 and 2).19
i
1a-c
4a-c
ii
Br
Br
4 BBr3
Br
O
2.2. b-Ketonitriles
SO2Ar
The known11a 2-alkylidenetetrahydrofuran 11 was prepared
by cyclization of the dianion of cyanoacetone, generated by
5a-c
Scheme 2. (i) (1) 2.5 equiv LDA, THF, 0 ꢀC, 1 h; (2) 1,4-dibromobut-2-ene,
ꢁ78/20 ꢀC, 20 h; (ii) (1) 5.0 equiv BBr3, CH2Cl2, 0/20 ꢀC, 12 h, 20 ꢀC,
8 h; (2) H2O.
Table 3. Synthesis of benzofurans 9a–g
7,8
9
Ar
R
X
% (7)a % (8)a,c
% (9)a
3-Ketosulfones 7a–d were prepared by acylation of aryl-[(2-
methoxyphenyl)methyl]-sulfones 6a–c. The cyclization of
a
b
c
d
a
b
c
a
b
c
d
e
f
Ph
H
H
H
Br
Br
Br
56
78
61
40
45 (E)+22 (Z) 72
55 (E)
49 (E)+19 (Z) 68
46 (E/Z¼8:1) 63
45 (E)+22 (Z) 40
4-MeC6H4
4-ClC6H4
Ph
Ph
4-MeC6H4
4-ClC6H4
61
Table 2. Synthesis of 5a–c
Me Br
OHb 56
OHb 28
OHb 61
4,5
Ar
% (4)a
E/Z (4)b
% (5)a
H
H
H
55 (E) 34
49 (E)+19 (Z) 47
a
b
c
Ph
4-MeC6H4
4-ClC6H4
50
38
40
6:4
6:4
>98:2
75
75
70
g
a
Yields of isolated products.
b
c
The product was formed when BCl3 was used (by hydrolysis of the chlo-
ride group in the product).
In brackets: configuration of the exocyclic double bond.
a
Yields of isolated products.
By 1H NMR.
b

11628
N. Rasool et al. / Tetrahedron 63 (2007) 11626–11635
Figure 3. Ortep plot of 12.
The cyclization of the dianion of cyanoacetone, generated by
treatment of 5-methyl-isoxazole with LDA, with 1,4-dibro-
mobut-2-ene afforded the known11a 2-alkylidenetetrahydro-
furan 13. Treatment of 13 with BBr3 unexpectedly afforded
tribromide 14 (Scheme 5). Product 14 is presumably formed
by BBr3-mediated ring opening and formation of intermedi-
ate A. Subsequently, the double bond is brominated (by the
action of bromine formed under the reaction conditions from
BBr3).
Figure 1. Ortep plot of 8a.
Br
O
H3C
Br
N
CN
O
13
i
10
40% (E) + 36% (Z)
2 BBr3
B2Br4 + Br2
8 BBr3
ii
Br
O
O
Br2
Br
CN
CN
Br
14
Br
A
(70%)
Scheme 5. i) (1) 2.5 equiv LDA, THF, 0 ꢀC, 1 h; (2) 1,4-dibromobut-2-ene,
ꢁ78/20 ꢀC, 20 h; (ii) (1) 8.0 equiv BBr3, CH2Cl2, 0/20 ꢀC, 12 h, 20 ꢀC,
6 h; (2) H2O.
Figure 2. Ortep plot of 9a.
The acylation of (2-methoxyphenyl)acetonitrile with acetyl
chloride afforded b-ketonitrile 15. The cyclization of the
dianion of 15 with 1-bromo-2-chloroethane gave 2-alkylide-
netetrahydrofuran 16. Treatment of the latter with BBr3 and
subsequently with HBr (62%) afforded the 2-(g-bro-
moalkyl)-3-carboxybenzofuran 17 (Scheme 6). During the
optimization of this reaction, the addition of concd hydro-
bromic acid proved to be important in order to induce a com-
plete rearrangement. This was necessary, since nitrile 15
proved to be less reactive than sulfones 8 in the reaction
with BBr3. This can be explained by the lower electron-
withdrawing effect of the nitrile compared to the sulfone.
The nitrile was hydrolyzed to a carboxylic acid group
upon addition of concd hydrobromic acid.
treatment of 5-methyl-isoxazole with LDA, with 1-bromo-2-
chloroethane. Treatment of 11 with BBr3 afforded 1-cyano-
5-bromo-pentan-2-one (12) (Scheme 4). It was possible to
independently confirm the structure of 12 by an X-ray crystal
structure analysis (Fig. 3).19
Cl
O
Br
H3C
N
CN
O
i
10
11
41% (E) + 40% (Z)
ii
Br
8 BBr3
Br
O
CN
The cyclization of the dianion of 15 with 1,4-dibromobut-
2-ene gave 2-alkylidene-5-vinyltetrahydrofuran 18. Treat-
ment of the latter with BBr3 and subsequently with HBr
(62%) afforded the 2-(u-bromoalkyl)-3-carboxybenzo-
furan 19 (Scheme 7). The nitrile was again hydrolyzed to a
carboxylic acid group upon addition of concd hydrobromic
acid.
Br
(85%)
12
Scheme 4. Synthesis of 1-cyano-5-bromopentan-2-one (12). (i) (1)
2.5 equiv LDA, THF, 0 ꢀC, 1 h; (2) Br(CH2)2Cl, ꢁ78/20 ꢀC, 14 h, then
reflux, 14 h; (ii) (1) 8.0 equiv BBr3, CH2Cl2, 0/20 ꢀC, 12 h, 20 ꢀC, 8 h;
(2) H2O.

N. Rasool et al. / Tetrahedron 63 (2007) 11626–11635
11629
3.1.1. 2-[(Phenylsulfonyl)methylidene]tetrahydrofuran
(2a). Starting with 1-phenylsulfonyl-2-propanone 1a
(3.90 g, 19.76 mmol) and 1-bromo-2-chloroethane (1.8 ml,
21.74 mmol), 2a was isolated as a highly viscous colourless
oil (1.99 g, 45%, E/Z¼7:3); H NMR (250 MHz, CDCl3):
MeO
MeO
Cl
i
O
+
O
CN
CN
1
15 (40%)
d¼1.92–2.09 (m, 2ꢂ2H, CH2, both isomers), 2.60 (dt, 2H,
J¼7.7 Hz, J¼1.2 Hz, CH2), 3.05 (dt, 2H, J¼7.9 Hz,
J¼1.8 Hz, CH2), 4.15 (t, 2H, J¼7.0 Hz, CH2), 4.31 (t,
2H, J¼6.8 Hz, CH2), 5.39 (t, 1 H, J¼1.2 Hz, C]CH, Z-iso-
mer), 5.67 (t, 1H, J¼1.8 Hz, C]CH, E-isomer), 7.41–7.48
(m, 2ꢂ3H, ArH, both isomers), 7.76–7.91 (m, 2ꢂ2H,
ArH, both isomers); 13C NMR (75 MHz, CDCl3): d¼23.0,
24.1, 29.8, 32.2, 72.9, 75.4 (CH2), 98.8, 100.1 (CH), 126.7
(2C, CH), 127.3 (2C, CH), 128.6, 129.0 (CH), 129.4 (2C,
CH), 132.8 (2C, CH), 143.9, 144.2, 170.1, 174.3 (C); IR
(neat): ~n ¼ 3086 ðwÞ, 3535 (w), 3061 (w), 2936 (m), 1720
(s), 1447 (s), 1402 (m), 1309 (s), 1153 (s), 688 (s), 528
(s) cmꢁ1; GC–MS (EI, 70 eV): m/z (%): 224.1 (M+, 100),
160 (15), 147 (18), 131 (24), 118 (31), 89 (23), 77 (66), 51
(34); HRMS (ESI): calcd (%) for C11H12O3S ([M+1]+)
224.05017, found 224.05017.
Br
ii
Cl
MeO
O
O
BBr3
O
CN
16 (72%, Z/E = 8:1)
iii
OH
Br
17 (41%)
Scheme 6. Synthesis of benzofuran 17. (i) (1) 2.5 equiv LDA, THF, 0 ꢀC,
45 min; (2) acid chloride, ꢁ78/20 ꢀC, 14 h; (ii) (1) 2.5 equiv LDA,
THF, 0 ꢀC, 1 h; (2) Br(CH2)2Cl, ꢁ78/20 ꢀC, 14 h, then reflux, 14 h; (iii)
(1) 7.0 equiv BBr3, CH2Cl2, 0/20 ꢀC, 12 h, 20 ꢀC, 72 h; (2) HBr (62%)
6.0 equiv 20 ꢀC, 20 h; (3) H2O.
MeO
O
MeO
O
Br
3.1.2. 2[((4-Methylphenyl)sulfonyl)methylidene]tetrahy-
drofuran (2b). Starting with 1-(4-methylphenyl)sulfonyl-
2-propanone 1b (3.00 g, 14.13 mmol), 1-bromo-2-chloro-
ethane (1.4 ml, 16.96 mmol), 2b was isolated as a colourless
solid (1.51 g, 45%, E/Z¼7:3), mp 87 ꢀC; 1H NMR
(300 MHz, CDCl3): d¼1.98–2.09 (m, 2ꢂ2H, CH2, both iso-
mers), 2.34 (s, 3H, CH3), 2.37 (s, 3H, CH3), 2.59 (m, 2H,
CH2), 3.06 (dt, 2H, J¼7.8 Hz, J¼1.7 Hz, CH2), 4.14 (t,
2H, J¼7.0 Hz, CH2), 4.31 (t, 2H, J¼6.9 Hz, CH2), 5.39 (t,
1H, J¼1.3 Hz, C]CH, Z-isomer), 5.67 (t, 1H, J¼1.7 Hz,
C]CH, E-isomer), 7.19–7.29 (m, 2ꢂ2H, ArH, both iso-
mers), 7.66–7.79 (m, 2ꢂ2H, ArH, both isomers); 13C
NMR (75 MHz, CDCl3): d¼21.9, 22.0 (CH3), 29.7, 32.2,
36.8, 41.3, 72.7, 75.3 (CH2), 99.2, 100.6 (CH), 128.5 (2C,
CH), 128.6 (2C, CH), 130.0 (2C, CH), 130.3 (2C, CH),
136.4, 138.0, 145.0, 145.7, 169.5, 173.7 (C); IR (KBr):
~n ¼ 2968 ðwÞ, 2925 (w), 2886 (w), 1719 (m), 1597 (w),
1314 (s), 1142 (s), 1079 (s), 995 (m), 777 (m), 561
(s) cmꢁ1; GC–MS (EI, 70 eV): m/z (%): 238 (M+, 100),
174 (15), 172 (18), 132 (20), 131 (33), 118 (22), 105 (15),
91 (70), 65 (37); HRMS (ESI): calcd (%) for C12H14O3S
([M+1]+) 238.06581, found 238.06582.
Br
i
CN
18 (34%, Z/E = 8:1)
CN
15
ii
BBr3
O
O
OH
Br
19 (58%)
Scheme 7. Synthesis of benzofuran 19. (i) (1) 2.5 equiv LDA, THF, 0 ꢀC,
1 h; (2) 1,4-dibromobut-2-ene, ꢁ78/20 ꢀC, 20 h; (ii) (1) 8.0 equiv BBr3,
CH2Cl2, 0/20 ꢀC, 12 h, 20 ꢀC, 72 h; (2) HBr (62%, 6.0 equiv), 20 ꢀC,
20 h; (3) H2O.
In conclusion, we reported an efficient approach to u-bromo-
3-ketosulfones, u-bromo-3-ketonitriles and 2-(u-bromoalkyl)-
benzofurans based on one-pot cyclizations of 3-ketonitrile and
3-ketosulfone dianions and application of a ‘ring-closing/
ring-opening’ strategy.
3. Experimental section
3.1.3. 2[((4-Chlorophenyl)sulfonyl)methylidene]tetra-
hydrofuran (2c). Starting with 1-(4-chlorophenyl)sul-
fonyl-2-propanone 1c (1.50 g, 6.44 mmol) and 1-bromo-2-
chloroethane (0.64 ml, 7.73 mmol), 2c was isolated as
a highly viscous colourless oil (668 mg, 40%, E/Z¼6:4);
1H NMR (300 MHz, CDCl3): d¼2.21–2.34 (m, 2ꢂ2H,
CH2, both isomers), 2.88 (dt, 2H, J¼7.7 Hz, J¼1.2 Hz,
CH2), 3.31 (dt, 2H, J¼7.8 Hz, J¼1.7 Hz, CH2), 4.42
(t, 2H, J¼7.0 Hz, CH2), 4.58 (t, 2H, J¼6.9 Hz, CH2), 5.65
(t, 1H, J¼1.1 Hz, C]CH, Z-isomer), 5.91 (t, 1H,
J¼1.7 Hz, C]CH, E-isomer), 7.64, 7.73 (2ꢂd, 4H,
J¼8.7 Hz, J¼8.5 Hz, ArH, both isomers), 7.98, 8.05 (2ꢂd,
4H, J¼8.7 Hz, J¼9.1 Hz, ArH, both isomers); 13C NMR
(75 MHz, CDCl3): d¼23.5, 24.1, 29.9, 32.2, 73.0, 75.5
(CH2), 98.7, 99.8 (CH), 128.3 (2C, CH), 129.3 (2C, CH),
129.6 (2C, CH), 130.1 (2C, CH), 139.2, 139.4, 140.8,
142.2, 170.5, 174.7 (C); IR (neat): ~n ¼ 3090 ðwÞ, 2958
(m), 2933 (m), 1720 (m), 1627 (m), 1582 (m), 1394 (m),
3.1. General procedure for the cyclization of 1-bromo-2-
chloroethane with dianions
To a THF solution of LDA (prepared by addition of
5.0 mmol of n-BuLi, 2.5 M in hexane, to a solution of diiso-
propylamine (0.57 ml, 5.0 mmol) in 12 ml of THF, stirred
for 30 min), was added 1-phenylsulfonyl-2-propanone
(397 mg, 2.0 mmol) at 0 ꢀC. The solution was stirred at
0 ꢀC for 45 min. To this solution was added 1-bromo-2-
chloroethane (0.17 ml, 2.1 mmol) at ꢁ78 ꢀC. The tempera-
ture was allowed to rise to 20 ꢀC during 14 h, and the
solution was subsequently refluxed for 14 h. To the solution
was added hydrochloric acid (1 M) and the mixture was sub-
sequently extracted with EtOAc (3ꢂ200 ml). The organic
layers were dried and filtered, the solvent of the filtrate
was removed in vacuo and the residue was purified by chro-
matography (silica gel, EtOAc/n-heptane).

11630
N. Rasool et al. / Tetrahedron 63 (2007) 11626–11635
1320 (s), 1155 (s), 1089 (s), 831 (m), 571 (m) cmꢁ1; GC–MS
(EI, 70 eV): m/z (%): 258 (M+, 100), 241 (5), 194 (25), 192
(19), 175 (11), 152 (31), 147 (29), 131 (35), 111 (56), 89
(36), 75 (44), 55 (37); HRMS (ESI): calcd (%) for
C11H11ClO3S ([M+1]+) 258.01082, found 258.01119.
J¼8.5 Hz, ArH); 13C NMR (75 MHz, CDCl3): d¼26.3,
32.7, 42.9, 67.2 (CH2), 130.1 (2C, CH), 130.2 (2C, CH),
137.3, 141.7, 197.3 (C); IR (KBr): ~n ¼ 3090 ðwÞ, 2921
(w), 1717 (s), 1582 (m), 1322 (s), 1147 (s), 1088 (s), 827
(m), 530 (s), 460 (m) cmꢁ1; GC–MS (CI): m/z (%): 341
([M+1]+, 81Br, 90), 339 ([M+1]+, 79Br, 86), 261 (40), 259
(100), 223 (5), 191 (13), 159 (5), 69 (8) (19); HRMS (CI):
calcd (%) for C11H12BrClO3S ([M+1]+, 81Br) 338.94510,
found 338.94518.
3.2. General procedure for the reaction of 2-(alkylide-
ne)tetrahydrofurans with boron tribromide or boron
trichloride
To a CH2Cl2 solution (10 ml/mmol of substrate) of 2-(alkyl-
idene)tetrahydrofuran (1.0 equiv) was added BBr3 (4.0–
8.0 equiv) at 0 ꢀC. The reaction mixture was allowed to
warm to 20 ꢀC during 12 h and was stirred for 12 h at
20 ꢀC. Water (15 ml/mmol of substrate) was slowly added
to the reaction mixture and the organic layer was separated.
The aqueous layer was extracted with CH2Cl2 (3ꢂ20 ml).
The combined organic layers were dried (Na2SO4), filtered
and the filtrate was concentrated in vacuo. The residue was
purified by chromatography (silica gel, n-heptane/EtOAc).
3.3. General procedure for the cyclization of 1,4-di-
bromo-2-butene with dianions
A THF solution of LDA (2.5 equiv) was prepared by addi-
tion of n-BuLi (1 ml, 2.5 mmol, 2.5 M solution in hexanes)
to a THF solution (7 ml) of diisopropylamine (0.36 ml,
2.5 mmol) at 0 ꢀC. After the solution was stirred for
30 min, 1-phenylsulfonyl-2-propanone (198 mg, 1.0 mmol)
was added at 0 ꢀC. After stirring for 45–60 min, to the solu-
tion was added a THF solution (4 ml) of 1,4-dibromo-2-bu-
tene (256 mg, 1.2 mmol) at ꢁ78 ꢀC. The temperature was
allowed to rise to 20 ꢀC during 12–14 h, and the solution
was stirred at 20 ꢀC for 8–14 h. To the solution was added
a diluted aqueous solution of HCl and the mixture was sub-
sequently extracted with EtOAc (3ꢂ200 ml). The combined
organic layers were dried and filtered, the solvent of the
filtrate was removed in vacuo and the residue was purified
by chromatography (silica gel, EtOAc/n-heptane).
3.2.1. 5-Bromo-1-(phenylsulfonyl)-2-pentanone (3a).
Starting with 2a (400 mg, 1.78 mmol) and BBr3 (0.67 ml,
7.12 mmol), 3a was isolated as a colourless solid (516 mg,
95%), mp 77 ꢀC; 1H NMR (300 MHz, CDCl3): d¼2.30
(quint, 2H, J¼6.6 Hz, CH2), 3.09 (t, 2H, J¼6.8 Hz, CH2),
3.58 (t, 2H, J¼6.4 Hz, CH2), 4.37 (s, 1H, CH2), 7.77 (m,
2H, ArH), 7.90 (m, 1H, ArH), 8.07 (m, 2H, ArH); 13C
NMR (75 MHz, CDCl3): d¼26.4, 32.9, 42.8, 67.4 (CH2),
127.4 (2C, CH), 128.6 (2C, CH), 134.8 (CH), 139.0, 197.4
(C); IR (KBr): ~n ¼ 2973 ðmÞ, 2925 (m), 1716 (s), 1445
(m), 1321 (s), 1297 (s), 1153 (s), 1009 (w), 688 (m), 525
(m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%): 306 (M+, 81Br,
0.30), 304 (M+, 79Br, 0.33), 242 (2), 240 (2), 198 (42), 151
(35), 149 (36), 141 (59), 77 (100), 51 (28), 41 (22); HRMS
(ESI): calcd (%) for C11H13BrO3S ([M+1]+, 81Br)
303.97709, found 303.97763.
3.3.1. 2-[(Phenylsulfonyl)methylidene]-5-vinyltetra-
hydrofuran (4a). Starting with 1-(4-methylphenyl)sul-
fonyl-2-propanone
1a
(2.00 g,
10.0 mmol)
and
1,4-dibromo-2-butene (2.60 g, 12.1 mmol), 4a was isolated
as a highly viscous colourless oil (1.26 g, 50%, E/Z¼6:4);
1H NMR (300 MHz, CDCl3): d¼1.85–2.05 (m, 2ꢂ1H,
CH–CH2, both isomers), 2.39–2.45 (m, 2ꢂ1H, CH–CH2,
both isomers), 2.83 (dt, 1H, J¼6.9 Hz, J¼1.1 Hz, CH2–C),
3.43–3.46 (m, 1H, CH2–C), 3.43–3.54, 3.71–3.77 (2ꢂm,
2H, CH2–C, E–Z), 4.95–5.02, 5.24–5.32 (2ꢂm, 2H, CH–
CH2), 5.38–5.49 (m, 4H, CH2]CH, both isomers), 5.66 (t,
J¼1.1 Hz, C]CH, Z-isomer), 5.93 (t, J¼1.7 Hz, C]CH,
E-isomer), 5.94–6.05 (m, 2H, CH2]CH, both isomers),
7.64, 7.84 (m, 2ꢂ3H, ArH, both isomers), 8.01–8.17 (m,
2ꢂ2H, ArH, both isomers); 13C NMR (75 MHz, CDCl3):
d¼26.1, 29.3, 29.8, 30.0 (CH2), 85.1, 87.1, 99.5, 100.4
(CH), 116.5, 118.6 (CH2), 126.8 (2C, CH), 127.7 (CH),
129.4 (2C, CH), 129.5 (2C, CH), 132.8, 135.3, 135.5
(CH), 143.8, 144.3, 169.1, 173.4 (C); IR (neat):
~n ¼ 3485 ðwÞ, 2985 (w), 2940 (w), 2210 (w), 1750 (m),
1627 (s), 1447 (m), 1308 (s), 1151 (s), 1083 (m), 589
(s) cmꢁ1; GC–MS (EI, 70 eV): m/z (%): 250 (M+, 24), 183
(36), 141 (27), 125 (7), 109 (65), 91 (39), 77 (100), 67
(23), 51 (26); HRMS (ESI): calcd (%) for C13H14O3S
([M+1]+) 250.06607, found 250.06582.
3.2.2. 5-Bromo-1-[(4-methylphenyl)sulfonyl]-2-penta-
none (3b). Starting with 2b (200 mg, 0.84 mmol) and
BBr3 (0.31 ml, 3.2 mmol), 3b was isolated as a colourless
solid (246 mg, 92%), mp 48 ꢀC; 1H NMR (300 MHz,
CDCl3): d¼2.04 (quint, 2H, J¼6.4 Hz, CH2), 2.38 (s, 3H,
CH3), 2.84 (t, 2H, J¼6.8 Hz, CH2), 3.33 (t, 2H, J¼6.4 Hz,
CH2), 4.08 (s, 1H, CH2), 7.29 (d, 2H, J¼8.0 Hz, ArH),
7.69 (d, 2H, J¼8.5 Hz, ArH); 13C NMR (75 MHz, CDCl3):
d¼22.1 (CH3), 26.4, 32.8, 42.8, 67.6 (CH2), 128.6 (2C,
CH), 130.4 (2C, CH), 136.1, 145.9, 197.5 (C); IR (KBr):
~n ¼ 3043 ðwÞ, 2920 (w), 1718 (s), 1405 (m), 1317 (s),
1149 (s), 1005 (w), 817 (m), 618 (w), 514 (m) cmꢁ1; GC–
MS (EI, 70 eV): m/z (%): 320 (M+, 81Br, 0.40), 318 (M+,
79Br, 0.53), 256 (5), 254 (5), 238 (4), 212 (13), 155 (56),
151 (32), 149 (36), 148 (33), 91 (100), 65 (30), 41 (19);
HRMS (ESI): calcd (%) for C12H15BrO3S ([M+1]+, 81Br)
317.99132, found 317.99198.
3.3.2. 2-[((4-Methylphenyl)sulfonyl)methylidene]-5-vi-
nyltetrahydrofuran (4b). Starting with 1-(4-methylphe-
nyl)sulfonyl-2-propanone 1b (1.00 g, 4.71 mmol) and
1,4-dibromo-2-butene (1.30 g, 5.65 mmol), 4b was isolated
as a highly viscous colourless oil (475 mg, 38%, E/Z¼
6:4); 1H NMR (300 MHz, CDCl3): d¼1.66–1.78 (m,
2ꢂ1H, CH–CH2, both isomers), 2.12–2.24 (m, 2ꢂ1H,
CH–CH2, both isomers), 2.33, 2.37 (2ꢂs, 6H, CH3), 2.59
3.2.3. 5-Bromo-1-[(4-chlorophenyl)sulfonyl]-2-penta-
none (3c). Starting with 2c (274 mg, 1.05 mmol) and BBr3
(0.39 ml, 4.2 mmol), 3c was isolated as a colourless solid
1
(234 mg, 65%), mp 68 ꢀC; H NMR (300 MHz, CDCl3):
d¼2.07 (quint, 2H, J¼6.4 Hz, CH2), 2.87 (t, 2H,
J¼6.8 Hz, CH2), 3.35 (t, 2H, J¼6.4 Hz, CH2), 4.10 (s, 1H,
CH2), 7.48 (d, 2H, J¼8.1 Hz, ArH), 7.77 (d, 2H,

N. Rasool et al. / Tetrahedron 63 (2007) 11626–11635
11631
(dt, 1H, J¼7.9 Hz, J¼1.8 Hz, CH2–C), 2.87–2.99 (m, 1H,
CH2–C), 3.17–3.28, 3.46–3.50 (2ꢂm, 2H, CH2–C, E–Z),
4.69–4.77, 4.99–5.01 (2ꢂm, 2H, CH–CH2), 5.10–5.26 (m,
4H, CH2]CH, both isomers), 5.40 (t, J¼1.4 Hz, C]CH,
Z-isomer), 5.68 (distorted t, J¼1.9 Hz, C]CH, E-isomer),
5.71–5.78 (m, 2H, CH2]CH, both isomers), 7.22, 7.28
(2ꢂd, 4H, J¼8.0 Hz, J¼8.0 Hz, ArH, both isomers), 7.67,
7.78 (2ꢂd, 4H, J¼8.2 Hz, J¼8.3 Hz, ArH, both isomers);
13C NMR (75 MHz, CDCl3): d¼21.9, 22.0 (CH3), 29.3,
29.7, 30.0, 31.6 (CH2), 85.0, 87.0, 99.7, 100.7 (CH),
117.7, 118.4 (CH2), 126.8 (2C, CH), 127.7 (2C, CH),
129.5 (2C, CH), 129.9 (2C, CH), 135.3, 135.6 (CH),
141.0, 141.4, 143.5, 143.6, 169.0, 173.0 (C); IR (neat):
~n ¼ 3482 ðwÞ, 2983 (w), 2925 (w), 2211 (w), 1719 (m),
1628 (s), 1428 (m), 1317 (s), 1151 (s), 816 (m) cmꢁ1; GC–
MS (EI, 70 eV): m/z (%): 264.1 (M+, 27), 197 (28), 155
(23), 139.1 (8), 109.1 (50), 91.1 (100), 79.1 (20), 65.1
(23), 39.1 (11); HRMS (ESI): calcd (%) for C14H16O3S
([M+1]+) 264.081655, found 264.08147.
d¼2.27 (m, 2H, CH2), 2.39 (s, 3H, CH3), 2.76 (t, 2H,
J¼7.0 Hz, CH2), 3.84 (distorted d, 2H, J¼6.4 Hz, CH2),
4.05 (s, 2H, CH2), 5.63–5.66 (m, 2H, CH]CH), 7.30 (d,
2H, J¼8.1 Hz, ArH), 7.66 (d, 2H, J¼8.1 Hz, ArH); 13C
NMR (75 MHz, CDCl3): d¼22.1 (CH3), 25.8, 33.1, 43.6,
67.5 (CH2), 128.2 (CH), 128.6 (2C, CH), 130.4 (2C, CH),
133.8 (CH), 136.0, 145.9, 197.5 (C); IR (neat):
~n ¼ 3031 ðwÞ, 2925 (m), 2210 (w), 1720 (s), 1320 (s),
1206 (m), 1152 (s), 815 (m), 733 (w), 515 (m) cmꢁ1; GC–
MS (CI): m/z (%): 347 ([M+H]+, 81Br, 7), 345 ([M+H]+,
79Br, 7), 267 (6), 266 (13), 265 (100), 170 (2), 139 (3),
109 (4); elemental analysis: calcd (%) for C14H17BrO3S
(345.25): C 48.70, H 4.96; found: C 48.19, H 4.98.
3.3.6. 7-Bromo-1-[(4-chlorophenyl)sulfonyl]-5-hepten-2-
one (5c). Starting with 4c (105 mg, 0.37 mmol) and BBr3
(0.17 ml, 1.84 mmol), 5c was isolated as a highly viscous
1
colourless oil (95 mg, 70%); H NMR (300 MHz, CDCl3):
d¼2.56–2.56 (m, 2H, CH2), 3.02 (t, 2H, J¼7.0 Hz, CH2),
4.10 (m, 2H, CH2), 4.34 (s, 2H, CH2), 5.90–5.93 (m, 2H,
CH]CH), 7.75 (d, 2H, J¼8.7 Hz, ArH), 8.01 (d, 2H,
J¼8.7 Hz, ArH); 13C NMR (75 MHz, CDCl3): d¼25.8,
33.0, 43.7, 67.1 (CH2), 128.3 (CH), 130.1 (2C, CH), 130.2
(2C, CH), 133.6 (CH), 137.3, 141.6, 197.3 (C); IR (neat):
~n ¼ 3090 ðwÞ, 2927 (m), 2210 (w), 1721 (s), 1476 (s),
1154 (s), 969 (m), 815 (m), 763 (m), 469 (w) cmꢁ1; GC–
MS (CI): m/z (%): 367 ([M+H]+, 81Br, 13), 465 ([M+H]+,
79Br, 10), 287 (39), 286 (14), 285 (100), 179 (2), 109 (6),
91 (3); HRMS (CI): calcd (%) for C13H14BrClO3S
([M+1]+, 81Br) 364.96221, found 364.96083.
3.3.3. 2-(E)-[((4-Chlorophenyl)sulfonyl)methylidene]-5-
vinyltetrahydro-furan (4c). Starting with 1-(4-chlorophe-
nyl)sulfonyl-2-propanone 1c (1.00 g, 4.29 mmol) and
1,4-dibromo-2-butene (1.10 g, 5.15 mmol), 4c was isolated
as a highly viscous colourless oil (488 mg, 40%); 1H
NMR (300 MHz, CDCl3): d¼1.73–1.85 (m, 1H,
CH–CH2), 2.16–2.27 (m, 1H, CH–CH2), 2.89–2.95 (m,
1H, CH2–C), 3.17–3.25 (m, 1H, CH2–C), 4.73–4.80 (m,
1H, CH–CH2), 5.16–5.27 (m, 2H, CH2]CH), 5.67 (t,
J¼1.7 Hz, C]CH), 5.70–5.79 (m, 1H, CH2]CH), 7.40
(d, 2H, J¼8.7 Hz, ArH), 7.73 (d, 2H, J¼8.7 Hz, ArH); 13C
NMR (75 MHz, CDCl3): d¼29.9, 30.0 (CH2), 85.3, 100.0
(CH), 118.7 (CH2), 128.3 (2C, CH), 129.7 (2C, CH), 135.4
(CH), 139.3, 142.8, 173.9 (C); IR (neat): ~n ¼ 3088 ðwÞ,
3064 (w), 2946 (w), 1625 (s), 1582 (s), 1428 (m), 1319 (s),
1084 (s), 618 (s), 478 (s) cmꢁ1; GC–MS (EI, 70 eV): m/z
(%): 284 (M, 38), 217 (45), 175 (51), 111 (88), 109 (100),
91 (59), 67 (34), 53 (19), 39 (17); elemental analysis: calcd
(%) for C13H13ClO3S (208.0): C 54.83, H 4.60; found: C
54.82, H 4.77.
3.4. 2-(E)(3-Phenyldihydro)-2(3H)-furanylidene-2-
(2-methoxyphenyl)-4-phenylsulfone (8a)
Starting with 1-(2-methoxyphenyl)-1-(phenylsulfonyl)ace-
tone 7a (1.40 g, 4.6 mmol) and 1-bromo-2-chloroethane
(0.45 ml, 5.5 mmol), 8a (E-isomer) was isolated as a colour-
less solid (681 mg, 45%), mp 162 ꢀC; 1H NMR (300 MHz,
CDCl3): d¼2.02–2.15 (m, 2H, CH2), 3.28 (s, 3H, OCH3),
3.31 (t, 2H, J¼7.62 Hz, CH2), 4.08 (t, 2H, J¼7.05 Hz,
CH2), 6.61–6.90 (m, 2H, ArH), 7.13–7.31 (m, 4H, ArH),
7.36–7.242 (m, 1H, ArH), 7.54–7.57 (m, 2H, ArH); 13C
NMR (75 MHz, CDCl3): d¼24.8, 30.6 (CH2), 55.5
(OCH3), 72.5 (CH2), 109.3 (C), 111.1, 120.7 (CH), 120.9
(C), 128.0 (2C, CH), 128.4 (2C, CH), 130.5, 132.4, 133.8
(CH), 142.8, 158.1, 169.8 (C); IR (KBr): ~n ¼ 3037 ðwÞ,
3031 (w), 2961 (w), 2842 (w), 1632 (s), 1595 (s), 1492 (s),
1376 (m), 1298 (s), 1239 (m), 1190 (s), 1054 (s), 896 (s),
750 (s), 544 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%): 330
(M+, 36), 189 (28), 131 (10), 91 (22), 77 (25), 71 (100), 43
(23); HRMS (ESI): calcd (%) for C18H18SO4 ([M+1]+)
330.09231, found 330.09180.
3.3.4. 7-Bromo-1-(phenylsulfonyl)-5-hepten-2-one (5a).
Starting with 4a (200 mg, 0.94 mmol) and BBr3 (0.44 ml,
4.7 mmol), 5a was isolated as a highly viscous colourless
1
oil (234 mg, 75%); H NMR (300 MHz, CDCl3): d¼2.26
(m, 2H, CH2), 2.76 (t, 2H, J¼7.0 Hz, CH2), 3.83 (d, 2H,
J¼6.6 Hz, CH2), 4.08 (s, 2H, CH2), 5.63–5.66 (m, 2H,
CH]CH), 7.49–7.55 (m, 2H, ArH), 7.60–7.63 (m, 1H,
ArH), 7.80 (dd, 2H, J¼7.0 Hz, 1.5 Hz, ArH); 13C NMR
(75 MHz, CDCl3): d¼21.0, 25.8, 43.6, 67.3 (CH2), 128.2
(CH), 128.6 (2C, CH), 129.8 (2C, CH), 133.8, 134.8 (CH),
139.0, 197.3 (C); IR (neat): ~n ¼ 3064 ðmÞ, 2991 (m), 2928
(s), 1731 (s), 1447 (s), 1309 (m), 1085 (s), 999 (m), 688
(m), 437 (w) cmꢁ1; GC–MS (CI): m/z (%): 333 ([M+H]+,
81Br, 7), 331 ([M+H]+, 79Br, 7), 253 (13), 252 (15), 251
(100), 143 (4), 127 (3), 111 (13), 109 (7), 79 (10), 71 (16),
69 (20); HRMS (CI): calcd (%) for C13H15BrO3S ([M+1]+,
81Br) 330.99857, found 330.99980.
3.5. 2-(Z)(3-Phenyldihydro)-2(3H)-furanylidene-2-(2-
methoxyphenyl)-4-phenylsulfone (8a)
1H NMR (300 MHz, CDCl3): d¼1.81–1.93 (m, 2H, CH2),
2.27–2.432 (m, 2H, CH2), 3.56 (s, 3H, OCH3), 4.29–4.38
(m, 2H, CH2), 6.71–6.91 (m, 2H, ArH), 7.12–7.24 (m, 2H,
ArH), 7.31–7.28 (m, 3H, ArH), 7.85 (m, 2H, ArH); 13C
NMR (75 MHz, CDCl3): d¼23.3–31.8 (CH2), 55.6
(OCH3), 75.1 (CH2), 108.0 (C), 111.3, 121.0 (CH), 122.5
(C), 128.2 (2C, CH), 128.5 (2C, CH), 130.6, 132.4, 133.9
3.3.5. 7-Bromo-1-[(4-methylphenyl)sulfonyl]-5-hepten-2-
one (5b). Starting with 4b (110 mg, 0.49 mmol) and BBr3
(0.23 ml, 2.5 mmol), 5b was isolated as a highly viscous col-
1
ourless oil (109 mg, 75%); H NMR (300 MHz, CDCl3):

11632
N. Rasool et al. / Tetrahedron 63 (2007) 11626–11635
(CH), 143.8, 158.1, 167.0 (C); IR (KBr): ~n ¼ 3064 ðwÞ, 2964
(w), 2904 (w), 2837 (w), 1723 (w), 1634 (s), 1595 (s), 1491
(m), 1446 (s), 1302 (s), 1141 (s), 1117 (m), 1084 (m), 1025
(m), 985 (m), 756 (s), 533 (m) cmꢁ1; GC–MS (EI, 70 eV):
m/z (%): 330 (M+, 28), 189 (27), 131 (10), 105 (9), 91 (24),
77 (26), 71 (100), 43 (25); HRMS (ESI): calcd (%) for
C18H18SO4 ([M+1]+) 330.0923, found 330.09180.
(10), 111 (10), 91 (23), 71 (100), 43 (22); HRMS (ESI):
calcd (%) for C18H17ClSO4 ([M+1]+) 364.05306, found
364.05463.
3.8. (2-Methoxyphenyl)-[3-methyldihydo-2(3H)-furanyl-
idene]methyl-phenylsulfone (8d)
Starting with 1-(2-methoxyphenyl)-1-(phenylsulfonyl)-2-
butanone 7d (500 mg, 1.5 mmol) and 1-bromo-2-chloro-
ethane (0.15 ml, 1.8 mmol), 8d was isolated as a colourless
oil (248 mg, 46%, E/Z¼8:1); 1H NMR (300 MHz, CDCl3):
d¼0.70 (t, 3H, J(Z)¼5.25 Hz, CH3), 0.79 (t, 3H,
J(E)¼7.25 Hz, CH3), 1.52–1.62 (m, 2ꢂ1H, CH2, Z-isomer),
1.99–2.15 (m, 2ꢂ1H, CH2, E-isomer), 2.25–2.67 (m,
2ꢂ1H, CH2, Z-isomer), 2.70–2.81 (m, 2ꢂ1H, CH2, E-iso-
mer), 3.49 (s, 3H, OCH3), 3.68 (s, 3H, OCH3), 4.24–4.39
(m, 2ꢂ2H, CH, both isomers), 6.72–7.02 (m, 5H, ArH
both isomers), 7.21–7.47 (m, 4ꢂ2H, ArH, both isomers),
7.77–7.83 (m, 2ꢂ1H, ArH, Z-isomer), 7.88–7.92 (m,
2ꢂ1H ArH, E-isomer); 13C NMR (75 MHz, CDCl3):
d¼16.8, 18.2 (CH3), 31.8, 31.9 (CH2), 38.1, 38.9 (CH),
55.6 (OCH3), 72.6 (CH2), 110.0 (C), 111.2, 120.6, 121.0
(CH), 122.4 (C), 128.2 (2C, CH), 128.5 (2C, CH), 130.6,
130.9, 133.4, 133.5 (CH), 143.7, 144.0, 158.0, 159.7,
170.5, 171.8 (C); IR (KBr): ~n ¼ 3065 ðwÞ, 2968 (m), 2907
(m), 2934 (m), 1719 (m), 1633 (m), 1491 (s), 1447 (s),
1302 (s), 1290 (s), 1253 (s), 1145 (s), 1024 (s), 975 (w),
688 (s), 529 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%): 340
(M+, 27), 203 (100), 173 (15), 131 (14), 91 (42), 77 (33),
43 (27); HRMS (ESI): calcd (%) for C19H20O4S ([M+1]+)
340.10768, found 340.10798.
3.6. 2-(E)(3-Phenyldihydro)-2(3H)-furanylidene-2-(2-
methoxyphenyl)-(4-methylphenyl)sulfone (8b)
Starting with 1-(2-methoxyphenyl)-1-(4-methylphenylsulfo-
nyl)acetone 7b (1.20 g, 3.77 mmol) and 1-bromo-2-chloro-
ethane (0.37 ml, 4.52 mmol), 8b was isolated as a colourless
solid (710 mg, 55%), mp 132 ꢀC; 1H NMR (300 MHz,
CDCl3): d¼1.82–1.93 (m, 2H, CH2), 2.30 (t, 2H, J¼5 Hz,
CH2), 3.58 (s, 3H, OCH3), 4.01–4.09 (m, 2H, CH2), 6.76–
7.88 (m, 2H, ArH), 7.13–7.19 (m, 3H, ArH), 7.20–7.26 (m,
1H, ArH), 7.71–7.74 (m, 2H, ArH); 13C NMR (75 MHz,
CDCl3): d¼21.9 (CH3), 23.3, 31.8 (CH2), 55.6 (OCH3),
75.0 (CH2), 108.0 (C), 111.3, 120.9 (CH), 122.9 (C), 128.2
(2C, CH), 129.1 (2C, CH), 130.5, 133.9 (CH), 141.0, 143.0,
158.5, 167.4 (C); IR (KBr): ~n ¼ 2970 ðwÞ, 2904 (w), 1634
(s), 1595 (m), 1491 (m), 1437 (s), 1306 (s), 1297 (s), 1139
(s), 1083 (m), 989 (m), 681 (m), 583 (s) cmꢁ1; GC–MS (EI,
70 eV): m/z (%): 344 (M+, 52), 208 (6), 189 (31), 91 (26),
71 (100), 43 (24); HRMS (ESI): calcd (%) for C19H20SO4
([M+1]+) 344.10768, found 344.107526.
3.7. 2-(3-Phenyldihydro)-2(3H)-furanylidene-2-(2-
methoxyphenyl)-(4-chlorophenyl)sulfone (8c)
Starting with 1-(2-methoxyphenyl)-1-(4-chlorophenylsulfo-
nyl)acetone (7c) (3.49 g, 10.32 mmol) and 1-bromo-2-
chloroethane (1.0 ml, 12.38 mmol), 8c (E-isomer) was
isolated as a colourless oil (1.84 g, 49%) and 8c (Z-isomer)
was isolated as a colourless solid, mp 144 ꢀC. E-isomer: 1H
NMR (300 MHz, CDCl3): d¼2.07 (m, 2H, CH2), 3.28 (t, 2H,
J¼6.48 Hz, CH2), 3.32 (s, 3H, OCH3), 4.07 (t, 2H,
J¼7.44 Hz, CH2), 6.62–6.88 (m, 2H, ArH), 7.14–7.26 (m,
4H, ArH), 7.44–7.49 (m, 2H, ArH); 13C NMR (75 MHz,
CDCl3): d¼23.02, 27.4 (CH2), 55.5 (OCH3), 72.6 (CH2),
110.4 (C), 111.7, 120.8 (CH), 122.9 (C), 128.6 (2C, CH),
129.5 (2C, CH), 133.8, 138.9 (CH), 140.5, 142.9, 159.1,
171.8 (C); IR (KBr): ~n ¼ 3095 ðwÞ, 3081 (w), 2957 (w),
2902 (w), 1631 (s), 1594 (s), 1594 (m), 1490 (m), 1463
(m), 1306 (s), 1253 (s), 1239 (s), 1148 (s), 1052 (s), 899
(s), 761 (m), 616 (m), 599 (s) cmꢁ1; GC–MS (EI, 70 eV):
m/z (%): 364 (M+, 28), 189 (28), 161 (16), 131 (10), 91
(23), 71 (100), 43 (21); HRMS (ESI): calcd (%) for
C18H17ClSO4 ([M+1]+) 364.05306, found 364.052826. Z-
isomer: 1H NMR (300 MHz, CDCl3): d¼1.84–1.97 (m,
2H, CH2), 2.31–2.38 (m, 2H, CH2), 3.60 (s, 3H, OCH3),
4.31–4.40 (m, 2H, CH2), 6.68–6.93 (m, 2H, ArH), 7.14–
7.35 (m, 4H, ArH), 7.76–7.81 (m, 2H, ArH); 13C NMR
(75 MHz, CDCl3): d¼20.8, 23.3 (CH2), 55.6 (OCH3), 75.2
(CH2), 108.4 (C), 111.3, 121.1 (CH), 122.2 (C), 128.6 (2C,
CH), 129.9 (2C, CH), 131.3, 138.9 (CH), 138.5, 143.3,
158.3, 168.2 (C); IR (KBr): ~n ¼ 3080 ðwÞ, 3050 (w), 2951
(m), 2804 (m), 1631 (s), 1594 (m), 1585 (m), 1490 (s),
1463 (s), 1304 (s), 1253 (m), 1232 (s), 1144 (m), 1052 (s),
899 (m), 762 (s), 616 (s), 591 (s) cmꢁ1; GC–MS (EI,
70 eV): m/z (%): 364 (M+, 24), 189 (28), 161 (7), 131
3.9. 2-(3-Bromopropyl)-3-(phenylsulfonyl)-benzofuran
(9a)
Starting with 8a (148 mg, 0.44 mmol) and BBr3 (0.21 ml,
2.24 mmol), 9a was isolated as a colourless solid (122 mg,
72%), mp 92 ꢀC; 1H NMR (300 MHz, CDCl3): d¼2.62
(quint, 2H, J¼6.6 Hz, CH2), 3.65 (t, 2H, J¼7.4 Hz, CH2),
3.76 (t, 2H, J¼6.4 Hz, CH2–Br), 7.60 (m, 2H, ArH), 7.70
(m, 1H, ArH), 7.75–7.87 (m, 3H, ArH), 8.16 (m, 1H,
ArH), 7.89 (dd, 2H, J¼8.17 Hz, 1.5 Hz, ArH); 13C NMR
(75 MHz, CDCl3): d¼26.6, 31.3, 32.6 (CH2), 111.8 (CH),
118.7 (C), 120.8 (CH), 124.5 (C), 124.9 (CH), 125.9 (2C,
CH), 127.1 (2C, CH), 129.7, 133.8 (CH), 142.7, 153.7,
162.7 (C); IR (KBr): ~n ¼ 3058 ðwÞ, 2927 (w), 1569 (s),
1451 (s), 1327 (s), 1111 (m), 1011 (w), 752 (s), 688 (s),
599 (s), 551 (s) cmꢁ1; GC–MS (EI, 70 eV): m/z (%): 380
(M+, 81Br, 100), 78 (M+, 79Br, 93), 330 (12), 299 (26), 237
(6), 272 (34), 181 (8), 158 (17), 131 (34), 69 (30), 43 (24);
HRMS (ESI): calcd (%) for C!7H15BrO3S ([M+1]+, 81Br)
377.99143, found 377.99198.
3.10. 2-(3-Bromopropyl)-3-[(4-methylphenyl)sulfonyl]-
benzofuran (9b)
Starting with 8b (110 mg, 0.31 mmol) and BBr3 (0.15 ml,
1.5 mmol), 9b was isolated as a highly viscous colourless
1
oil (77 mg, 61%); H NMR (300 MHz, CDCl3): d¼2.26
(quint, 2H, J¼6.5 Hz, CH2), 2.31 (s, 3H, CH3), 3.30 (t,
2H, J¼7.2 Hz, CH2), 3.42 (t, 2H, J¼6.6 Hz, CH2–Br),
7.22–7.27 (m, 4H, ArH), 7.34–7.37 (m, 1H, ArH), 7.80–
7.86 (m, 3H, ArH); 13C NMR (75 MHz, CDCl3): d¼20.5

N. Rasool et al. / Tetrahedron 63 (2007) 11626–11635
11633
(CH3), 25.1, 29.9, 31.2 (CH2), 110.3 (CH), 117.6 (C), 119.4
(CH), 123.1 (C), 123.4, 124.4, 125.7, 128.9 (CH), 138.4,
143.3, 152.3, 160 (C); IR (neat): ~n ¼ 3433 ðmÞ, 2984 (w),
2954 (m), 1595 (s), 1474 (s), 1326 (s), 1302 (s), 1255 (s),
1090 (m), 1050 (m), 815 (m), 749 (s), 719 (s), 673 (s), 643
(m), 585 (m), 535 (s) cmꢁ1; GC–MS (EI, 70 eV): m/z (%):
394 (M+, 81Br, 100), 392 (M+, 79Br, 95), 286 (35), 267
(9.07), 205 (14), 158 (19), 131 (41), 102 (28), 65 (16), 39
(7); HRMS (ESI): calcd (%) for C!8H17BrO3S ([M+1]+,
81Br) 392.0.00763, found 392.0.00788.
7.84 (m, 1H, ArH), 7.94 (dd, 2H, J¼8.0 Hz, 1.7 Hz, ArH);
13C NMR (75 MHz, CDCl3): d¼24.0, 31.2, 61.2 (CH2),
111.7 (CH), 118.7 (C), 120.8 (CH), 124.5 (C), 124.8,
125.8 (CH), 127.0 (2C, CH), 129.7 (2C, CH), 133.8 (CH),
142.6, 153.7, 163.9 (C); IR (KBr): ~n ¼ 2929 ðsÞ, 2851 (w),
1711 (w), 1568 (s), 1448 (s), 1156 (s), 999 (m), 753 (s),
648 (s), 533 (s), 437 (w) cmꢁ1; GC–MS (EI, 70 eV): m/z
(%): 316.1 (M+, 35), 298.1 (40), 233.1 (12), 219.1 (24),
175.1 (100), 158.1 (15), 145.1 (21), 133 (48), 131.1 (64),
115.1 (50), 77.1 (48); HRMS (ESI): calcd (%) for
C!7H16O4S ([M+1]+) 316.07716, found 316.07638.
3.11. 2-(3-Bromopropyl)-3-[(4-chlorophenyl)sulfonyl]-
benzofuran (9c)
3.14. 2-(3-Hydroxypropyl)-3-[(4-methylphenyl)sul-
fonyl]-benzofuran (9f)
Starting with 8c (663 mg, 1.8 mmol) and BBr3 (0.86 ml,
9.1 mmol), 9c was isolated as a colourless solid (515 mg,
Starting with 8b (335 mg, 0.97 mmol) and BCl3 (0.77 ml,
4.8 mmol), 9f was isolated as a highly viscous colourless
oil (108 mg, 34%); H NMR (300 MHz, CDCl3): d¼1.99
1
68%), mp 116 ꢀC; H NMR (300 MHz, CDCl3): d¼2.28
1
(quint, 2H, J¼6.6 Hz, CH2), 3.31 (t, 2H, J¼7.4 Hz, CH2),
3.43 (t, 2H, J¼6.4 Hz, CH2–Br), 7.26 (m, 2H, ArH), 7.36–
7.42 (m, 3H, ArH), 7.79 (m, 1H, ArH), 7.89 (d, 2H,
J¼8.17 Hz, ArH); 13C NMR (75 MHz, CDCl3): d¼26.6,
31.2, 32.6 (CH2), 111.9 (CH), 118.4 (C), 120.7 (CH), 124.3
(C), 125.0, 126.1 (CH), 128.6 (2C, CH), 130.0 (2C, CH),
140.4, 141.1, 153.7, 162.9 (C); IR (KBr): ~n ¼ 3083 ðwÞ,
3059 (w), 1575 (s), 1452 (s), 1157 (s), 1085 (s), 829 (m),
760 (s), 658 (s), 567 (s), 479 (w) cmꢁ1; GC–MS (EI,
70 eV): m/z (%): 414 (M+, 81Br, 100), 412 (M+, 79Br, 75),
306 (27), 305 (22), 237 (6), 205 (17), 159 (41), 131 (53),
102(35), 75(20);HRMS (ESI): calcd (%)forC!7H14BrClO3S
([M+1]+, 81Br) 412.96127, found 412.96083.
(quint, 2H, J¼6.8 Hz, CH2), 2.32 (s, 3H, CH3), 3.24 (t,
2H, J¼7.0 Hz, CH2), 3.63 (t, 2H, J¼5.9 Hz, CH2–OH),
7.21–7.27 (m, 5H, ArH), 7.34–7.37 (m, 1H, ArH), 7.83 (d,
2H, J¼8.1 Hz, ArH); 13C NMR (75 MHz, CDCl3): d¼21.9
(CH3), 23.9, 31.2, 61.2 (CH2), 111.7 (CH), 119.1 (C),
120.8 (CH), 124.6 (C), 124.8 (CH), 125.8 (2C, CH), 127.1
(2C, CH), 130.3 (CH), 139.7, 144.8, 153.7, 163.5 (C); IR
(Nujol): ~n ¼ 3420 ðwÞ, 1717 (m), 1597 (s), 1331 (s), 1154
(s), 1036 (s), 813 (m), 750 (s), 674 (s), 585 (s), 537
(s) cmꢁ1; GC–MS (EI, 70 eV): m/z (%): 330.1 (M+, 20),
281.1 (4), 207.1 (30), 175.1 (100), 131.1 (55), 115.1 (29),
91.1 (33), 65 (15), 39 (5); HRMS (ESI): calcd (%) for
C18H18O4S ([M+1]+) 330.09203, found 330.09203.
3.12. 2-(3-Bromo-1-methylpropyl)-3-(phenylsulfonyl)-
benzofuran (9d)
3.15. 2-(3-Hydroxypropyl)-3-[(4-chlorophenyl)sul-
fonyl]-benzofuran (9g)
Starting with 8d (90 mg, 0.26 mmol) and BBr3 (0.12 ml,
1.3 mmol), 9d was isolated as a highly viscous colourless
oil (65 mg, 63%); H NMR (300 MHz, CDCl3): d¼1.30
Starting with 8c (663 mg, 1.8 mmol) and BCl3 (3.4 ml,
21.6 mmol), 9g was isolated as a highly viscous colourless
oil (300 mg, 47%); H NMR (300 MHz, CDCl3): d¼1.94–
1
1
(d, 3H, J¼6.8 Hz, CH3), 2.10–2.19 (m, 1H, CH–CH2),
2.30–2.38 (m, 1H, CH–CH2), 3.19–3.25 (m, 2H, CH2–Br),
4.02–4.09 (m, 1H, CH3–CH), 7.24–7.28 (m, 2H, ArH),
7.35–7.38 (m, 1H, ArH), 7.42–7.52 (m, 3H, ArH), 7.86–
7.90 (m, 1H, ArH), 7.96–8.01 (m, 2H, ArH); 13C NMR
(75 MHz, CDCl3): d¼19.5 (CH3), 30.6 (CH2), 31.8 (CH),
38.0 (CH2), 111.8 (CH), 118.4 (C), 121.1 (CH), 124.5 (C),
124.9 (CH), 125.9 (2C, CH), 127.1 (2C, CH), 129.7, 133.7
(CH), 142.8, 153.6, 165.8 (C); IR (KBr): ~n ¼ 2974 ðwÞ,
2921 (s), 2847 (w), 1567 (s), 1473 (s), 1251 (s), 1091 (s),
928 (w), 754 (s), 645 (m), 554 (s) cmꢁ1; GC–MS (EI,
70 eV): m/z (%): 394.1 (M+, 81Br, 47), 392.1 (M+, 79Br,
45), 285 (100), 233 (4), 156 (9), 144.1 (37), 128.1 (13),
115.1 (34), 89.1 (5), 77.1 (18), 51.1 (8); HRMS (ESI): calcd
(%) for C!8H17BrO3S ([M+1]+, 81Br) 392.00756, found
392.00763.
2.03 (m, 2H, J¼6.8 Hz, CH2), 3.23 (t, 2H, J¼7.2 Hz,
CH2), 3.63 (t, 2H, J¼5.9 Hz, CH2–OH), 7.24–7.27 (m, 2H,
ArH), 7.35–7.37 (m, 1H, ArH), 7.39 (d, 2H, J¼
8.7 Hz, ArH), 7.77–7.80 (m, 1H, ArH), 7.87 (d, 2H,
J¼8.7 Hz, ArH); 13C NMR (75 MHz, CDCl3): d¼42.0,
31.1, 61.3 (CH2), 111.8 (CH), 118.4 (C), 120.6 (CH),
124.3 (C), 125.0, 126.0 (CH), 128.5 (2C, CH), 130.0 (2C,
CH), 140.4, 141.1, 153.8, 164.2 (C); IR (neat):
~n ¼ 3404 ðwÞ, 2932 (w), 2876 (w), 1573 (s), 1452 (s),
1155 (s), 759 (s), 619 (s), 567 (m), 480 (m) cmꢁ1; GC–MS
(EI, 70 eV): m/z (%): 350 (M+, 13), 332 (16), 288 (5), 218
(21), 175 (100), 156 (11), 144 (26), 131 (61), 115 (42), 75
(15); HRMS (ESI): calcd (%) for C17H15ClO4S ([M+1]+)
350.03687, found 350.03741.
3.16. 2-(Cyanomethylidene)tetrahydrofuran (11)
3.13. 2-(3-Hydroxypropyl)-3-(phenylsulfonyl)-benzofu-
ran (9e)
The synthesis of 11 has been previously reported.11a Starting
with 5-methylisoxazole (3 ml, 36.82 mmol) and 1-bromo-2-
chloroethane (3.7 ml, 44.18 mmol), 11 (E-isomer) was iso-
lated as a colourless oil (1.61 g, 41%) and 11 (Z-isomer)
was isolated as a colourless oil (1.56 g, 40%). E-isomer:
1H NMR (300 MHz, CDCl3): d¼2.08 (quint, 2H,
J¼7.0 Hz, CH2), 2.81 (t, 2H, J¼7.0 Hz, CH2), 4.26 (t, 2H,
J¼7.0 Hz, CH2), 4.50 (s, 1H, CHCN); 13C NMR (75 MHz,
Starting with 8a (227 mg, 0.68 mmol) and BCl3 (0.53 ml,
3.4 mmol), 9e was isolated as a highly viscous colourless
1
oil (87 mg, 40%); H NMR (300 MHz, CDCl3): d¼1.99
(quint, 2H, J¼6.4 Hz, CH2), 3.24 (t, 2H, J¼7.2 Hz, CH2),
3.63 (t, 2H, J¼6.0 Hz, CH2–OH), 7.23–7.27 (m, 2H, ArH),
7.36–7.38 (m, 1H, ArH), 7.40–7.53 (m, 3H, ArH), 7.81–

11634
N. Rasool et al. / Tetrahedron 63 (2007) 11626–11635
CDCl3): d¼24.1, 30.6 (CH2), 67.6 (CHCN), 74.6 (CH2),
118.8 (CN), 178.0 (C); IR (neat): ~n ¼ 3086 ðwÞ, 2913 (s),
2211 (s), 1734 (w), 1429 (m), 1391 (s), 1186 (m), 1003
(s), 930 (m), 725 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%):
109 (M+, 82), 80 (7), 68 (100), 52 (14), 42 (68), 38 (6);
HRMS (ESI): calcd (%) for C6H7NO ([M+1]+) 109.05188,
92.2 (21), 80.2 (34), 79.2 (39), 67.2 (100), 65.2 (19), 53.2
(52), 39.2 (51); HRMS (ESI): calcd (%) for C8H9NO
([M+1]+) 135.06767, found 135.06787.
3.19. 6,7,8-Tribromo-1-cyano-3-oxoheptane (14)
1
found 109.05222. Z-isomer: H NMR (300 MHz, CDCl3):
Starting with 13 (153 mg, 1.13 mmol) and BBr3 (0.85 ml,
9.04 mmol), 14 was isolated as a highly viscous colourless
d¼2.36 (quint, 2H, J¼7.0 Hz, CH2), 2.90 (t, 2H,
J¼6.6 Hz, CH2), 4.47 (s, 1H, CHCN), 4.59 (t, 2H,
J¼6.8 Hz, CH2); 13C NMR (75 MHz, CDCl3): d¼24.3,
31.2 (CH2), 65.2 (CHCN), 74.4 (CH2), 117.2 (CN), 177.6
(C); IR (neat): ~n ¼ 3086 ðwÞ, 2954 (m), 2854 (w), 1652
(s), 1458 (m), 1391 (s), 1186 (m), 1003 (s), 930 (m), 725
(m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%): 109 (M+, 75), 80
(5), 68 (100), 52 (13), 42 (71), 29 (3); HRMS (ESI): calcd
(%) for C6H7NO ([M+1]+) 109.05214, found 109.05222.
1
oil (296 mg, 70%); H NMR (300 MHz, CDCl3): d¼2.10–
2.16 (m, 1H, Br–CH–XH2), 2.43–2.48 (m, 1H, Br–CH–
CH2), 2.81–2.84 (m, 2H, CH2CO), 3.45 (s, 2H, CH2CN),
3.75–3.84 (m, 1H, Br–CH2), 3.99–4.05 (m, 1H, Br–CH2),
4.29–4.38 (m, 2H, Br–CH); 13C NMR (75 MHz, CDCl3):
d¼29.7, 32.5, 37.0, 40.1 (CH2), 54.5, 55.5 (CH), 113.7
(CN), 196.3 (C); IR (neat): ~n ¼ 2951 ðmÞ, 2914 (m), 2260
(w), 1731 (s), 1403 (m), 1307 (m), 1185 (w), 1082 (m),
617 (w), 557 (w) cmꢁ1; GC–MS (CI): m/z (%): 378
([M+H]+, 81Br, 42), 376 ([M+H]+, 79Br, 43), 337 (9), 335
(9), 298 (95), 296 (72), 257 (20), 255 (11), 218 (85), 216
(100), 136 (86), 95 (10), 67 (15); HRMS (CI): calcd (%)
for C8H10Br3NO ([M+1]+, 81Br) 373.83837, found
373.83853.
3.17. 5-Bromo-1-cyano-3-oxopentane (12)
Starting with 11 (363 mg, 3.33 mmol) and BBr3 (2.51 ml,
26.64 mmol), 12 was isolated as a colourless solid
1
(538 mg, 85%), mp 71 ꢀC; H NMR (300 MHz, CDCl3):
d¼2.40 (quint, 2H, J¼6.4 Hz, CH2), 3.05 (t, 2H,
J¼6.8 Hz, CH2), 3.68 (t, 2H, J¼6.2 Hz, CH2), 3.74 (s, 1H,
CH2); 13C NMR (75 MHz, CDCl3): d¼26.2, 32.6, 32.8,
40.5 (CH2), 113.9 (CN), 196.8 (C); IR (KBr):
~n ¼ 2951 ðmÞ, 2920 (m), 2258 (w), 1719 (s), 1642 (m),
1405 (s), 1392 (s), 1328 (s), 977 (m), 581 (m) cmꢁ1; GC–
MS (CI): m/z (%): 192 ([M+H]+, 81Br, 48), 190 ([M+H]+,
79Br, 59), 151 (9), 149 (9), 110 (100); elemental analysis:
calcd (%) for C6H8BrNO (190): C 37.92, H 4.24; found: C
38.14, H 4.18.
3.20. 2-Dihydro-2(3H)-furanylidene-2-(2-methoxyphe-
nyl)acetonitrile (16)
Starting with 2-(2-methoxyphenyl)-3-oxobutanenitrile 15
(1.20 g, 6.38 mmol) and 1-bromo-2-chloroethane (0.58 ml,
7.1 mmol), 16 was isolated as a colourless solid (1.00 g,
1
72%, Z/E¼8:1), mp 54 ꢀC; H NMR (300 MHz, CDCl3):
d¼2.15–2.21 (m, 2H, CH2, Z-isomer), 2.27–2.36 (m, 2H,
CH2, E-isomer), 2.74, 3.20 (2ꢂt, 4H, J(Z)¼7.8 Hz,
J(E)¼7.8 Hz, CH2), 3.97 (s, 3H, OCH3), 3.99 (s, 3H,
OCH3), 4.45–4.57 (m, 2ꢂ2H, CH2, both isomers), 7.06
(dd, 1H, J¼8.9 Hz, 7.8 Hz, ArH), 7.29 (dd, 1H,
J¼5.91 Hz, 1.5 Hz, ArH), 7.37–7.49 (m, 2H, ArH); 13C
NMR (75 MHz, CDCl3): d¼24.1, 24.5, 30.2, 30.8 (CH2),
55.9, 56.0 (CH3), 73.9, 75.0 (CH2), 77.1, 78.9, 109.0 (C),
111.0 (CH), 116.0 (CN), 120.7, 129.6, 131.4 (CH), 154.6,
155.0, 170.8, 172.5 (C); IR (KBr): ~n ¼ 3441 ðwÞ, 2963
(w), 2935 (w), 2205 (s), 1628 (s), 1578 (m), 1462 (m),
1265 (s), 1184 (s), 762 (s), 656 (w) cmꢁ1; GC–MS (EI,
70 eV): m/z (%): 215 (M+, 100), 184 (15), 158 (22), 144
(29), 115 (18), 84 (52), 75 (10); HRMS (ESI): calcd (%)
for C13H13NO2 ([M+1]+) 215.09408, found 215.09436.
3.18. 2-(Cyanomethylidene)-5-vinyltetrahydrofuran
(13)
The synthesis of 13 has been previously reported.11a Starting
with 5-methylisoxazole (3 ml, 36.82 mmol) and 1,4-di-
bromo-2-butene (9.45 g, 44.18 mmol), 13 (E-isomer) was
isolated as a colourless oil (1.96 g, 40%) and 13 (Z-isomer)
was isolated as a colourless oil (1.77 g, 36%). E-isomer: 1H
NMR (300 MHz, CDCl3): d¼1.78–1.98 (m, 1H, CH–CH2),
2.19–2.24 (m, 1H, CH–CH2), 2.75–2.91 (m, 2H, CH2), 4.57
(t, 1H, J¼1.5 Hz, CHCN), 4.84–4.90 (m, 1H, CH–CH2),
5.18–5.32 (m, 2H, CH2]CH), 5.72–5.83 (m, 1H,
CH2]CH); 13C NMR (75 MHz, CDCl3): d¼30.0, 30.6
(CH2), 68.2, 86.8 (CH), 118.5 (CH2), 119.0 (CN), 135.4
(CH), 178.2 (C); IR (neat): ~n ¼ 3073 ðwÞ, 2988 (w), 2211
(s), 1641 (s), 1430 (m), 1217 (s), 1179 (s), 989 (m), 877
(m), 763 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%): 135
(M+, 90), 134 (91), 120 (49), 106 (49), 92 (21), 79 (37), 67
(100), 53 (50), 39 (53); HRMS (ESI): calcd (%) for
C8H9NO ([M+1]+) 135.06802, found 135.06787. Z-isomer:
1H NMR (300 MHz, CDCl3): d¼1.82–1.86 (m, 1H, CH–
CH2), 2.10–2.22 (m, 1H, CH–CH2), 2.58–2.64 (m, 2H,
CH2), 4.19 (s, 1H, CHCN), 4.89–4.96 (m, 1H, CH–CH2),
5.18–5.33 (m, 2H, CH2]CH), 5.75–5.86 (m, 1H,
CH2]CH); 13C NMR (75 MHz, CDCl3): d¼30.2, 31.0
(CH2), 65.8, 86.4 (CH), 116.9 (CN), 118.3 (CH2), 135.4
(CH), 176.4 (C); IR (neat): ~n ¼ 3085 ðwÞ, 2942 (w), 2212
(s), 1652 (s), 1430 (m), 1364 (m), 1187 (m), 989 (m), 934
(m), 730 (w) cmꢁ1; GC–MS (EI, 70 eV): m/z (%): 135.1
(M+, 83), 134.1 (92), 120.1 (51), 116.1 (10), 106.2 (42),
3.21. 2-(3-Bromopropyl)-benzofuran-3-carboxylic acid
(17)
Starting with 16 (600 mg, 2.7 mmol), BBr3 (1.5 ml,
16.7 mmol) and HBr (0.7 ml, 16.7 mmol), 17 was isolated
as a highly viscous colourless oil (322 mg, 41%); 1H NMR
(250 MHz, CDCl3): d¼1.92–2.02 (m, 2H, CH2), 2.91 (t,
2H, J¼8.04 Hz, CH2), 3.70 (t, 2H, J¼6.98 Hz, CH2),
6.98–7.19 (m, 3H, ArH), 7.36–7.42 (m, 4H, ArH); 13C
NMR (75 MHz, CDCl3): d¼25.6, 37.9, 61.7 (CH2), 93.8
(C), 190.2, 117.7, 120.8, 123.2 (CH), 125.0, 148.2, 164.2,
194.6 (C); IR (KBr): ~n ¼ 3385 ðsÞ, 3273 (m), 3064 (w),
2924 (s), 2854 (m), 1653 (s), 1493 (s), 1459 (m), 1243
(w), 1173 (m), 1019 (m), 743 (m) cmꢁ1; GC–MS (EI,
70 eV): m/z (%): 281 (M+, 25), 201 (100), 175 (20), 160
(80), 103 (10), 82 (12); HRMS (ESI): calcd (%) for
C12H11BrO3 ([M+1]+) 281.52341, found 281.53216.

N. Rasool et al. / Tetrahedron 63 (2007) 11626–11635
11635
(f) Fuerst, D. E.; Stoltz, B. M.; Wood, J. L. Org. Lett. 2000,
22, 3521; (g) Schneider, B. Phytochemistry 2003, 64, 459.
7. (a) Wendt, B.; Ha, H. R.; Hesse, M. Helv. Chim. Acta 2002, 85,
2990; (b) Carlsson, B.; Singh, B. N.; Temciuc, M.; Nilsson, S.;
Li, Y. L.; Mellin, C.; Malm, J. J. Med. Chem. 2002, 45, 623 and
references cited therein; (c) Kwiecien, H.; Baumann, E.
J. Heterocycl. Chem. 1997, 1587; (d) Larock, R. C.; Harrison,
L. W. J. Am. Chem. Soc. 1984, 106, 4218; (e) Matyus, P.;
Varga, I.; Rettegi, T.; Simay, A.; Kallay, N.; Karolyhazy, L.;
Kocsis, A.; Varro, A.; Penzes, I.; Papp, J. G. Curr. Med.
Chem. 2004, 1, 61; (f) Wong, H. N. C.; Pei, Y.; Yick, C. Y.
Pure Appl. Chem. 1999, 71, 1041.
8. (a) Joshi, A. S.; Li, X.-C.; Nimrod, A. C.; ElSohly, H. N.;
Walker, L. A.; Clark, A. M. Planta Med. 2001, 67, 186; (b)
Sigstad, E.; Catalan, C. A. N.; Diaz, J. G.; Herz, W.
Phytochemistry 1993, 33, 165; (c) Drewes, S. E.; Hudson,
N. A.; Bates, R. B. J. Chem. Soc., Perkin Trans. 1 1987, 2809.
9. Sessiliflorol A: (a) Chan, J. A.; Shultis, E. A.; Carr, S. A.;
DeBrosse, C. W.; Eggleston, D. S. J. Org. Chem. 1989, 54,
2098; Sessiliflorol B: (b) Marston, A.; Zagorski, M. G.;
Hostettmann, K. Helv. Chim. Acta 1988, 71, 1210; (c) Drewes,
S. E.; Hudson, N. A.; Bates, R. B.; Linz, G. S. Tetrahedron
Lett. 1984, 25, 105; Flemistrictin E: (d) Subrahmanyam, K.;
Rao, J. M.; Vemuri, V. S. S.; Babu, S. S.; Roy, C. P.; Rao,
K. V. J. Indian J. Chem., Sect. B 1982, 21, 895; Tovophenone
C: (e) Seo, E.-K.; Wall, M. E.; Wani, M. C.; Navarro, H.;
Mukherjee, R.; Farnsworth, N. R.; Kinghorn, A. D.
Phytochemistry 1999, 52, 669; Vismiaguianone C: (f) Seo,
E.-K.; Wani, M. C.; Wall, M. E.; Navarro, H.; Mukherjee, R.;
Farnsworth, N. R.; Kinghorn, A. D. Phytochemistry 2000, 55,
35; Piperaduncin B: (g) See Ref. 8a. See also: (h) Bohlmann,
F.; Zdero, C. Chem. Ber. 1976, 109, 1436.
3.22. 2-(5-Vinyldihydro)-2(3H)-furanylidene-2-
(2-methoxyphenyl)-acetonitrile (18)
Starting with 2-(2-methoxyphenyl)-3-oxobutanenitrile 15
(1.30 g, 6.8 mmol) and 1,4-dibromo-2-butene (1.60 g,
7.5 mmol), 18 was isolated as a colourless oil (622 mg,
37%, Z/E¼8:1); 1H NMR (250 MHz, CDCl3): d¼2.51–
2.69 (m, 2ꢂ2H, CH2, both isomers), 2.99 (t, 2H,
J¼7.6 Hz, CH2), 4.18 (s, 3H, OCH3), 4.20 (s, 3H, OCH3),
5.27–5.40 (m, 1H, CH), 5.60 (d, 2ꢂ1H, J¼13.1 Hz, CH2),
5.67 (d, 2ꢂ1H, J¼17.1 Hz, CH2), 6.18–6.33 (m, 2ꢂ1H,
CH, both isomers), 7.18–7.35 (m, 2H, ArH), 7.51–7.81 (m,
2H, ArH); 13C NMR (75 MHz, CDCl3): d¼30.0, 31.6
(CH2), 56.0 (OCH3), 81.5 (C), 86.0, 87.2 (CH), 111.0
(CH), 116.0 (CN), 118.1 (CH2), 119.4 (C), 120.8, 121.8,
128.9, 129.6, 131.5, 135.8 (CH), 156.9, 172.3, 173.9 (C);
IR (KBr): ~n ¼ 2936 ðmÞ, 2839 (w), 2207 (m), 1731 (m),
1635 (s), 1595 (m), 1580 (w), 1464 (s), 1262 (s), 996 (s),
757 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%): 241 (M+,
100), 210 (39), 184 (15), 173 (49), 158 (21), 115 (28), 67
(23); HRMS (ESI): calcd (%) for C15H15NO2 ([M+1]+)
241.10983, found 241.10973.
3.23. 2-(3-Bromo-4-pentenyl)-benzofuran-3-carboxylic
acid (19)
Starting with 18 (502 mg, 2.07 mmol), BBr3 (1.17 ml,
12.44 mmol) and HBr (0.58 ml, 12.44 mmol), 19 was iso-
lated as a colourless solid (375 mg, 58%), mp 112 ꢀC; H
1
NMR (300 MHz, CDCl3): d¼1.84–2.09 (m, 2H, CH2), 287
(t, 2H, J¼8.4 Hz, CH2), 4.20 (m, 1H, CH), 5.07 (d, 1H,
J¼13.4 Hz, CH2), 5.25 (d, 1H, J¼17.4 Hz, CH2), 5.77–
5.92 (m, 1H, CH), 7.11–7.49 (m, 4H, ArH); 13C NMR
(75 MHz, CDCl3): d¼30.0, 37.8 (CH2), 72.0 (CH), 94.1
(C), 110.7 (CH), 115.0 (CH2), 119.1, 122.1, 124.6 (CH),
125.9 (C), 141.2 (CH), 149.1, 165.3, 195.4 (C); IR (KBr):
~n ¼ 3410 ðmÞ, 3252 (m), 3195 (m), 1653 (s), 1495 (s),
1479 (s), 1416 (m), 1371 (w), 1173 (m), 1017 (m), 959
(m), 729 (m) cmꢁ1; GC–MS (EI, 70 eV): m/z (%): 309
(M+, 19), 227 (20), 175 (33), 160 (100), 133 (17), 104
(10), 77 (15); HRMS (ESI): calcd (%) for C14H13BrO3
([M+1]) 309.23461, found 309.23156.
10. For cyclization reactions of dianions in organic synthesis, see:
Langer, P.; Freiberg, W. Chem. Rev. 2004, 104, 4125.
ꢀ
11. (a) Langer, P.; Holtz, E.; Karime, I.; Saleh, N. N. R. J. Org.
Chem. 2001, 66, 6057; (b) Langer, P.; Bellur, E. J. Org.
Chem. 2003, 68, 9742.
12. Langer, P.; Holtz, E.; Saleh, N. N. R. Chem.—Eur. J. 2002, 8,
917.
13. Langer, P.; Armbrust, H.; Eckardt, T.; Magull, J. Chem.—Eur.
J. 2002, 8, 1443.
14. (a) Edwards, G. L.; Muldoon, C. A.; Sinclair, D. J. Tetrahedron
1996, 52, 7779; (b) Edwards, G. L.; Sinclair, D. J. Tetrahedron
Lett. 1999, 40, 3933; (c) Short, K. M.; Ziegler, C. B.
Tetrahedron Lett. 1995, 36, 355.
References and notes
15. (a) Mussatto, M. C.; Savoia, D.; Trombini, C.; Umani-Ronchi,
A. J. Chem. Soc., Perkin Trans. 1 1980, 260; (b) Alzerreca, A.;
Martinez, J.; Velazquez, L.; Prieto, J. A.; Arias, L.
J. Heterocycl. Chem. 1994, 31, 45.
1. Review: (a) Bhatt, M. V.; Kulkarni, S. U. Synthesis 1983, 249;
See also: (b) McOmie, J. F. W.; Watts, M. L.; West, D. E.
Tetrahedron 1968, 24, 2289.
2. Cleavage of cyclic ethers: Kulkarni, S. U.; Patil, V. D.
Heterocycles 1982, 18, 163.
3. Cleavage of lactones: Olah, G. A.; Karpeles, R.; Narang, S. C.
Synthesis 1982, 963.
16. Dai, W. M.; Lee, M. Y. H. Tetrahedron 1998, 54, 12497.
17. Pound, M. K.; Davies, D. L.; Pilkington, M.; Sousa, M. M.;
Wallis, J. D. Tetrahedron Lett. 2002, 43, 1915.
18. The reaction of dianions of 1,3-dicarbonyl compounds with
1,2-dibromoethane results in a SET process rather than conden-
sation: Hampton, K. G.; Light, R. J.; Hauser, C. R. J. Org.
Chem. 1965, 30, 1413.
19. CCDC-644938 (8a), CCDC-657908 (9a), and CCDC-657909
(12) contain all crystallographic details of this publication
and are available free of charge at www.ccdc.cam.ac.uk/
conts/retrieving.html or can be ordered from the following ad-
dress: Cambridge Crystallographic Data Centre, 12 Union
Road, GB-Cambridge CB21EZ; fax: (+44)1223 336 033, or
deposit@ccdc.cam.ac.uk.
4. Bellur, E.; Langer, P. J. Org. Chem. 2005, 70, 3819.
5. Bellur, E.; Langer, P. J. Org. Chem. 2005, 70, 7686.
6. (a) Miyata, O.; Takeda, N.; Morikami, Y.; Naito, T. Org.
Biomol. Chem. 2003, 1, 254; (b) Xie, X.; Chen, B.; Lu, J.;
Han, J.; She, X.; Pan, X. Tetrahedron Lett. 2004, 45, 6235;
(c) Zhang, H.; Ferreira, E. M.; Stoltz, B. M. Angew. Chem.,
Int. Ed. 2004, 43, 6144; (d) Hagiwara, H.; Sato, K.; Nishino,
D.; Hoshi, T.; Suzuki, T.; Ando, M. J. Chem. Soc., Perkin
Trans. 1 2001, 2946; Review: (e) Butin, A. V.; Gutnow,
A. V.; Abaev, V. T.; Krapivin, G. D. Molecules 1999, 4, 52;