A facile access to natural and unnatural dialkylsubstituted maleic anhydrides

Article abstract of DOI:10.1016/S0040-4020(03)00410-1

A facile new route to the potential building blocks 2-bromomethyl-3-alkylmaleic anhydrides 15a/b for the synthesis of natural and unnatural dialkylsubstituted maleic anhydrides has been demonstrated, starting from dimethyl citraconate (9) via NBS-bromination, S_N2′ Grignard coupling reactions, hydrolysis, molecular bromine addition and dehydrative ring closure reactions pathway with 49-51% overall yield in 5-steps. Chemoselective allylic substitution of bromoatom in 15a/b with Grignard reagents has been described to obtain the unsymmetrical maleic anhydride 16 and symmetrically dialkylsubstituted maleic anhydrides 25a/b in 55% yield. The naturally occurring 2-carboxymethyl-3-hexylmaleic anhydride (1) has been synthesized from 16 via esterification, ozonolysis and an oxidation route. The synthesis of two naturally occurring 2-(β-carboxyethyl)-3-alkylmaleic anhydrides 2a/b have been completed via a chemoselective diethylmalonate coupling reaction followed by acid induced hydrolysis. In our hands the S_N2 or S_N2′ coupling of Grignard reagent with 21 to obtain 1 and Reformatsky reaction with 15a/b to obtain 2c/d met with failure.

Full text of DOI:10.1016/S0040-4020(03)00410-1

Tetrahedron 59 (2003) 2991–2998
A facile access to natural and unnatural dialkylsubstituted
maleic anhydridesq
*
Anirban Kar and Narshinha P. Argade
Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune 411 008, India
Received 5 December 2002; revised 20 February 2003; accepted 14 March 2003
Dedicated to Dr B. G. Hazra, OCS, NCL, Pune
Abstract—A facile new route to the potential building blocks 2-bromomethyl-3-alkylmaleic anhydrides 15a/b for the synthesis of natural
and unnatural dialkylsubstituted maleic anhydrides has been demonstrated, starting from dimethyl citraconate (9) via NBS-bromination, SN20
Grignard coupling reactions, hydrolysis, molecular bromine addition and dehydrative ring closure reactions pathway with 49–51% overall
yield in 5-steps. Chemoselective allylic substitution of bromoatom in 15a/b with Grignard reagents has been described to obtain the
unsymmetrical maleic anhydride 16 and symmetrically dialkylsubstituted maleic anhydrides 25a/b in 55% yield. The naturally occurring
2-carboxymethyl-3-hexylmaleic anhydride (1) has been synthesized from 16 via esterification, ozonolysis and an oxidation route. The
synthesis of two naturally occurring 2-(b-carboxyethyl)-3-alkylmaleic anhydrides 2a/b have been completed via a chemoselective
diethylmalonate coupling reaction followed by acid induced hydrolysis. In our hands the SN2 or SN20 coupling of Grignard reagent with 21 to
obtain 1 and Reformatsky reaction with 15a/b to obtain 2c/d met with failure. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
In Figure 1 we have listed the recently isolated bioactive
naturally occurring dialkylsubstituted maleic anhydrides
with free carboxylic group,4–9 viz 2-carboxymethyl-3-
hexylmaleic anhydride (1),4 2-(b-carboxyethyl)-3-hexyl-
maleic anhydride (2a),5 2-(b-carboxyethyl)-3-octylmaleic
anhydride (2b),5 tautomycin part structure (3),6 (E)-2-but-1-
enyl-3-(b-carboxyethyl)maleic anhydride (4),7 telfairic
During the past decade several structurally interesting
compounds with dialkylsubstituted maleic anhydride moi-
eties have been isolated as bioactive natural products and
synthesized in view of their promising bioactivities.1–3
q NCL Communication No. 6639. For preliminary communication see Ref.
11.
Keywords: Grignard reagent; maleic anhydrides; NBS-bromination.
*
Corresponding author. Tel./fax: þ91-20-5893153;
e-mail: argade@dalton.ncl.res.in
Figure 1.
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00410-1

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A. Kar, N. P. Argade / Tetrahedron 59 (2003) 2991–2998
anhydride (5),8 itaconitin (6),9 cordyanhydride A (7)7 and
cordyanhydride B (8).7 The anhydride 1 has been isolated4
as a novel metabolite of the Aspergillus FH-X-213 from an
apple. In 1994, Soda et al. reported the biotransformation of
stearic acid with a microbial strain isolated from soil,
Pseudomonas cepacica A-1419, to produce two new maleic
anhydride derivatives 2a and 2b.5 Very recently, the first
general synthetic route to these diverse dialkylsubstituted
maleic anhydride analogs was demonstrated1 by Baldwin
et al. using a versatile copper mediated tandem vicinal
difunctionalization of dimethyl acetylenedicarboxylate. In
our continuing interest10 to provide facile synthetic routes to
natural and unnatural alkylsubstituted maleic anhydrides,
we herein report11 another general approach t0o this type of
compounds via the chemoselective SN2/SN2 coupling of
Grignard reagents/diethylmalonate with dimethyl bromo-
methylfumarate (10)/2-bromomethyl-3-alkylmaleic anhy-
drides 15a/b (Schemes 1, 3 and 4).
maleic anhydride (15a) as a suitable starting material for the
synthesis of the natural products 2-carboxymethyl-3-
hexylmaleic anhydride (1) and 2-carboxyethyl-3-hexyl-
maleic anhydride (2a). Several methods for the synthesis
of alkylmethylmaleic anhydrides have been reported,10 but
the NBS-bromination of these anhydrides is known to take
place at the allylic methylene carbon12 and hence we
thought of preparing 15a via a chemoselective SN20
coupling reaction of a Grignard reagent with 10.13 The
dimethyl methylmaleate (9) on NBS-bromination gave
dimethyl bromomethylfumarate (10) in 85% yield and
both allylic bromination and isomerization of the carbon–
carbon double bond from maleate to fumarate took place in
one pot (Scheme 1). The freshly prepared hexylmagnesium
bromide was chemoselectively coupled with 10 in an SN20
fashion to yield the diester 11a in 64% yield. The LiOH
induced hydrolysis of 11a followed by bromination of the
diacid 12a with molecular bromine gave a mixture of all
four possible stereoisomers of 13a in nearly equal
proportions with ,100% yield. The diacid 13a in refluxing
acetic anhydride yielded the desired (bromomethyl)-
hexylmaleic anhydride (15a) in quantitative yield and
both the dehydrative ring closure of diacid 13a to succinic
2. Results and discussion
We planned the preparation of 2-(bromomethyl)-3-hexyl-
Scheme 1. Reagents, conditions and yields: (i) NBS (1.5 equiv.), AIBN, CCl4, reflux, 12 h (85%); (ii) CH3(CH2)nCH2MgBr (1.5 equiv., n¼4/6), Et2O, HMPA,
2208C, 0.5 h (64–65%); (iii)) LiOH (10 equiv.), THFþH2O (3:1), room temperature, 18 h (90–92%); (iv) Br2 (1.5 equiv.), CCl4, room temperature, 6 h
(,100%); (v) Ac2O, reflux, 1.5 h (,100%); (vi) C2H3MgBr (5 equiv.), CuI (0.1 equiv.), Et2O, HMPA, 25 to 08C (55%); (vii) CH2N2, Et2O, MeOH, 08C, 3 h
(95%); (viii) O3, (CH3)2CO, 2788C, 3 min then Na2Cr2O7·H2O, H2SO4, H2O, Et2O, 08C, 3 h then 1 M aq. NaOH then 1 M aq. HCl, (42%); (ix) NaCN
(1.1 equiv.), MeOH, room temperature, 2 h (0%); (x) CuCN (5 equiv.), MeOH, reflux, 8 h (0%); (xi) 1,3-dithiane (1.1 equiv.), n-BuLi (1.2 equiv.), THF,
HMPA, 6 h (0%).

A. Kar, N. P. Argade / Tetrahedron 59 (2003) 2991–2998
2993
Scheme 2. Reagents, conditions and yields: (i) NBS (10 equiv.), AIBN, CCl4, reflux, 32 h (85%); (ii) C6H13MgBr (1.5 equiv.), Et2O, HMPA, 2208C, 0.5 h
(0%).
Scheme 3. Reagents, conditions and yields: (i) (a) diethyl malonate (1.1 equiv.), NaH (1.1 equiv.), C6H6, room temperature, 8 h; (b) Hþ/HCl (72–74%)
(ii) AcOHþHCl (1:1), reflux, 12 h (95–96%); (iii) CH2N2, Et2O, 08C, 3 h (95%).
anhydride derivative 14a and the dehydrobromination took
place in one pot. Similarly, the coupling reaction of 10 with
octylmagnesium bromide followed by repetition of above
sequence of reactions furnished 15b. Highly chemoselective
SN2 displacement of allylic bromoatom in 15a with
vinylmagnesium bromide in the presence of HMPA and a
copper catalyst gave the desired anhydride 16 in 55%
yield.10b The anhydride 16 on treatment with diazomethane
gave the diester 17 in 95% yield. The diester 17 on
ozonolysis followed by an in situ oxidation and hydrolysis
gave1 the natural product carboxymethylhexylmaleic
anhydride (1) in 42% yield.
reported data. The anhydrides 2a/b were also characterized
further as the methyl esters 2c/d.
The chemoselective coupling of freshly prepared pentyl-
magnesium bromide with 15a and heptylmagnesium
bromide with 15b in the presence of HMPA and a copper
catalyst gave the desired dihexylmaleic anhydride (25a) and
dioctylmaleic anhydride (25b) in 55% yield, thus providing
a new simple route to symmetrical and unsymmetrical
dialkylsubstituted maleic anhydrides (Scheme 4). In our
hands, all attempts to obtain 2c/d via a chemoselective
Reformatsky reaction with 15a/b in the presence/absence of
HMPA met with failure and we recovered starting material
only.
Starting from diester 9, the final product 1 was obtained in
8-steps with 11% overall yield. The analytical and spectro-
scopic data obtained for 1 were in complete agreement with
reported data.4 We investigated the displacement of allylic
bromide 15a with sodium cyanide, copper cyanide14 and
2-lithio-1,3-dithiane15 to obtain 18 and 19, but all our
attempts met with failure and always ended with the
formation of complex reaction mixtures and/or polymeric
gums. We felt that the SN2 or SN20 coupling of a
hexylmagnesium bromide with bromotriester 21 will
provide an easy access to 1 via 22 (Scheme 2). The triester
2016 on NBS-bromination gave 21 with 85% yield. In our
hands, all our attempts to chemoselectively couple Grignard
reagents with 21 met with failure and complex reaction
mixtures were formed. We feel that 21 is prone to
polymerization reactions and hence we were unable to
complete the short synthesis of 1.
Scheme 4. Reagents, conditions and yields: (i) BrCH2COOMe (1.5 equiv.),
Zn (2 equiv.), THF, room temperature/reflux, 12 h (0%); (ii) CH3(CH2)n-
CH2MgBr (5 equiv, n¼3/5), CuI (0.1 equiv.), Et2O, HMPA, 25 to 08C
(55–56%).
3. Conclusion
In summary, we have demonstrated a facile route to natural
products 2-carboxymethyl-3-hexylmaleic anhydride (1)
[8-steps (11%)], 2-(b-carboxyethyl)-3-alkylmaleic
anhydrides 2a/b [7-steps (34–36%)], and symmetrical/
unsymmetrical dialkylsubstituted maleic anhydrides 16,
25a/b [6-steps (27–28%)] via a highly chemoselective SN20
reaction with dimethyl bromomethylfumarate (10) and SN2
reaction with 2-bromomethyl-3-alkylmaleic anhydrides
15a/b as key steps. We feel that the bromoanhydrides
15a/b and their analogs will be a potential building blocks
for synthesis of several important natural/synthetic products
bearing maleic anhydride moieties.
Starting from 15a/b, we planned for the synthesis of natural
products 2a/b. The highly chemoselective diethyl malonate
coupling with 15a/b in benzene using sodium hydride as
base furnished the anhydride derivatives 23a/b in 72–74%
yield (Scheme 3). Acid catalysed hydrolysis of these
diesters 23a/b and an in situ decarboxylation of the
intermediate gem-dicarboxylic acids gave the natural
products 2a/b in 95–96% yield. The overall yield of 2a/b
in 7-steps was 34–36%. The analytical and spectroscopic
data obtained for 2a/b were in complete agreement with

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A. Kar, N. P. Argade / Tetrahedron 59 (2003) 2991–2998
4. Experimental
1632, 1439 cm21. Anal. calcd for C13H22O4: C, 64.44; H,
9.15. Found: C, 64.52; H, 9.06.
4.1. General
4.1.3. Dimethyl 1-undecen-2,3-dicarboxylate (11b).
Repetition of above procedure using n-octylmagnesium
bromide [prepared from n-octyl bromide (2.32 g, 12 mmol)
and magnesium (864 mg, 36 mmol)] and 10 (1.90 g,
8 mmol) gave the corresponding diester 11b: 1.40 g (65%
Melting points are uncorrected. Column chromatographic
separations were carried out on silica gel (60–120 mesh).
Commercially available citraconic anhydride, alkyl
bromides, magnesium turnings, HMPA, CuI, lithium
hydroxide, diethyl malonate, NaH and acetic anhydride
were used.
1
yield); thick oil; H NMR (CDCl3, 200 MHz) d 0.88 (t,
J¼6 Hz, 3H), 1.26 (bs, 12H), 1.55–1.78 (m, 1H), 1.78–2.00
(m, 1H), 3.51 (t, J¼8 Hz, 1H), 3.69 (s, 3H), 3.77 (s, 3H),
5.76 (s, 1H), 6.36 (s, 1H); 13C NMR (CDCl3, 50 MHz) d
13.8, 22.5, 27.3, 29.1 (4-carbons), 31.2, 31.6, 46.4, 51.8,
126.3, 138.5, 166.5, 173.5; MS (m/e) 270 (3%), 239 (6%),
211 (50%), 171 (11%), 157 (68%), 139 (16%), 126 (67%),
109 (13%), 95 (28%), 81 (43%), 67 (42%), 55 (60%); IR
(Neat) nmax 1738, 1728, 1630, 1458, 1437 cm21. Anal.
calcd for C15H26O4: C, 66.64; H, 9.69. Found: C, 66.56; H,
9.73.
4.1.1. Dimethyl bromomethylfumarate (10). A mixture of
(9.48 g, 60 mmol), N-bromosuccinimide (16.02 g,
9
90 mmol) and catalytic amount of AIBN (200 mg,
1.22 mmol) in carbon tetrachloride (300 mL) was gently
refluxed for 12 h in a 500 mL round bottom flask. The
mixture was left overnight at room temperature and then
filtered. The residue was washed with CCl4 (25 mL£2); the
combined organic layer was washed with water (100 mL),
brine (50 mL) and then dried over Na2SO4. The organic
layer was concentrated in vacuo to furnish thick yellow oil,
which was purified by chromatography on silica gel column
using petroleum ether/ethyl acetate (9:1) to give the desired
4.1.4. 1-Nonen-2,3-dicarboxylic acid (12a). A aqueous
solution of lithium hydroxide (600 mg in 6 mL water) was
added to a solution of 11a (960 mg, 4 mmol) in tetra-
hydrofuran (18 mL) at room temperature and the reaction
mixture was stirred for 18 h. The reaction mixture was then
concentrated in vacuo, and the residue was dissolved in
ethyl acetate (50 mL) and acidified to pH 2 with 2N
hydrochloric acid (10 mL). The organic layer was separated
and the aqueous layer was further extracted with ethyl
acetate (20 mL£3). The combined organic layer was
washed with water (20 mL), brine (20 mL) and dried over
Na2SO4. The organic layer was concentrated in vacuo and
the residue was chromatographed over silica gel using
petroleum ether/ethyl acetate (6:4) to give 12a: 767 mg
1
bromo diester 10: 12.10 g (85% yield); thick oil; H NMR
(CDCl3, 200 MHz) d 3.83 (s, 3H), 3.88 (s, 3H), 4.72 (s, 2H),
6.83 (s, 1H); 1H NMR (CCl4, 200 MHz) d 3.87 (s, 3H), 3.93
(s, 3H), 4.70 (s, 2H), 6.79 (s, 1H); 13C NMR (CDCl3,
50 MHz) d 22.1, 51.7, 52.5, 127.9, 142.4, 164.5, 164.7; MS
(m/e) 238 (2%), 236 (2%), 206 (78%), 204 (79%), 179 (9%),
177 (9%), 125 (78%), 98 (18%), 68 (20%), 59 (49%); IR
(Neat) nmax 1730, 1726, 1643 cm21. Anal. calcd for
C7H9BrO4: C, 35.47; H, 3.83. Found: C, 35.59; H, 3.72.
4.1.2. Dimethyl 1-nonen-2,3-dicarboxylate (11a). A fresh
solution of n-hexylmagnesium bromide in ether was
prepared as follows. A solution of n-hexyl bromide
(1.98 g, 12 mmol) in LAH–dried ether (10 mL) was
added at room temperature to magnesium turnings
(864 mg, 36 mmol) in ether (10 mL) under argon with
constant stirring in three equal portions at an interval of
10 min. The reaction mixture was further stirred at room
temperature for 4 h. TLC of the reaction mixture in
n-pentane showed quantitative conversion of the halide to
the Grignard reagent. This freshly generated Grignard
reagent was added drop wise to a solution of HMPA
(7.17 g, 40 mmol) and 10 (1.90 g, 8 mmol) in anhydrous
ether (20 mL) under argon at 2208C and the reaction
mixture was further stirred at the same temperature for
0.5 h. The reaction was quenched by the addition of a
saturated ammonium chloride solution (30 mL). An
additional ether (30 mL) was added to the reaction mixture
and the organic layer was separated. The aqueous layer was
extracted with ether (20 mL£3), the combined ethereal
extracts were washed with water (30 mL), brine (20 mL)
and dried over Na2SO4. The organic layer was concentrated
in vacuo and the residue was chromatographed over silica
gel using petroleum ether/ethyl acetate (9.5:0.5) to give 11a:
1.23 g (64% yield); thick oil; 1H NMR (CDCl3, 200 MHz) d
0.85 (t, J¼8 Hz, 3H), 1.26 (bs, 8H), 1.50–1.75 (m, 1H),
1.75–2.00 (m, 1H), 3.48 (t, J¼8 Hz, 1H), 3.66 (s, 3H), 3.74
(s, 3H), 5.74 (s, 1H), 6.34 (s, 1H); 13C NMR (CDCl3,
50 MHz) d 13.5, 22.1, 27.0, 28.6, 30.9, 31.2, 46.1, 51.2,
51.4, 125.9, 138.2, 166.0, 173.1; IR (Neat) nmax 1738, 1726,
1
(90% yield); thick oil; H NMR (CDCl3, 200 MHz) d 0.87
(t, J¼6 Hz, 3H), 1.29 (bs, 8H), 1.60–1.85 (m, 1H), 1.85–
2.10 (m, 1H), 3.44 (t, J¼8 Hz, 1H), 5.87 (s, 1H), 6.55 (s,
1H), 10.24 (bs, 2H); 13C NMR (CDCl3, 50 MHz) d 13.9,
22.5, 27.2, 28.9, 30.7, 31.5, 46.2, 129.5, 137.4, 171.8, 179.9;
IR (CHCl3) nmax 2700–2500, 1708, 1705, 1628,
1217 cm21. Anal. calcd for C11H18O4: C, 61.66; H, 8.47.
Found: C, 61.75. H, 8.41.
4.1.5. 1-Undecen-2,3-dicarboxylic acid (12b). It was
prepared similarly from 11b (1.08 g, 4 mmol) and aqueous
lithium hydroxide solution (613 mg in 6 mL water) as
described above to obtain the corresponding dicarboxylic
acid 12b: 891 mg (92% yield); thick oil; 1H NMR (CDCl3,
200 MHz) d 0.88 (t, J¼6 Hz, 3H), 1.27 (bs, 12H), 1.60–
1.85 (m, 1H), 1.85–2.10 (m, 1H), 3.39 (t, J¼8 Hz, 1H), 5.84
(s, 1H), 6.55 (s, 1H); 13C NMR (CDCl3, 50 MHz) d 14.0,
22.6, 27.3, 29.6 (3-carbons), 30.8, 31.8, 46.4, 129.5, 137.5,
171.8, 179.7; MS (m/e) 242 (1%), 224 (1%), 206 (1%), 197
(6%), 143 (3%), 129 (12%), 112 (22%), 95 (5%), 81 (8%),
67 (9%), 55 (21%); IR (CHCl3) nmax 2700–2500, 1708,
1705, 1628, 1215 cm21. Anal. calcd for C13H22O4: C,
64.44; H, 9.15. Found: C, 64.37; H, 9.23.
4.1.6. 1,2-Dibromononan-2,3-dicarboxylic acid (13a). A
solution of bromine (720 mg, 4.50 mmol) in CCl4 (5 mL)
was added drop wise to a solution of 12a (639 mg, 3 mmol)
in carbon tetrachloride (15 mL) at room temperature and the
reaction mixture was stirred for 6 h. The reaction mixture

A. Kar, N. P. Argade / Tetrahedron 59 (2003) 2991–2998
2995
was then concentrated in vacuo, and the residue was diluted
with ethyl acetate (20 mL). The organic layer was washed
with saturated sodium metabisulphite (10 mL), water
(10 mL), brine (10 mL) and dried over Na2SO4. The organic
layer was concentrated in vacuo and the residue was
chromatographed over silica gel using petroleum ether/ethyl
acetate (6:4) to give 13a: 1.11 g (,100% yield); thick oil;
1H NMR (CDCl3, 200 MHz) d 0.90 (t, J¼6 Hz, 3H), 1.30
(bs, 8H), 1.80–2.05 (m, 2H), 3.15–3.40 (m, 1H), 3.98 (t,
J¼10 Hz, 1H), 4.15 (t, J¼10 Hz, 1H), 8.73 (bs, 2H); 13C
4.1.10. 2-(Prop-2-enyl)-3-hexylmaleic anhydride (16). A
fresh solution of vinylmagnesium bromide in ether was
prepared as follows. A solution of vinyl bromide (535 mg,
5 mmol) in LAH-dried ether (10 mL) was added at room
temperature to magnesium turnings (360 mg, 15 mmol) in
ether (10 mL) under argon with constant stirring in three
equal portions at an interval of 10 min. The reaction mixture
was further stirred at room temperature for 4 h. TLC of the
reaction mixture in n-pentane showed quantitative conver-
sion of the halide to the Grignard reagent. This freshly
generated Grignard reagent was added drop wise to the
solution of 15a (275 mg, 1 mmol) and copper(I) iodide
(19 mg, 0.01 mmol) in ether (10 mL) and HMPA (2 mL)
under argon at 25 to 08C over 15–20 min under stirring.
The reaction mixture was allowed to reach room tempera-
ture and further stirred for 8 h. It was diluted with ether
(15 mL) and acidified with 4N H2SO4 (10 mL). The organic
layer was separated and the aqueous layer was further
extracted with ether (15 mL£3). The combined organic
layer was washed with water (20 mL), brine (20 mL) and
dried over Na2SO4 and concentrated in vacuo. The residue
was chromatographed over silica gel using petroleum ether/
ethyl acetate (9.5:0.5) to give 16: 122 mg (55% yield); thick
NMR (CDCl3, 50 MHz)
d 14.0 (2-carbons), 22.4
(2-carbons), 27.5, 27.7, 28.8–29.6 (4-carbons), 31.4
(2-carbons), 34.7, 36.2, 49.3, 51.3, 60.8, 63.4, 173.1,
173.4, 177.6, 178.5; IR (Neat) nmax 2700–2500, 1720,
1715, 1215 cm21. Anal. calcd for C11H18Br2O4: C, 35.32;
H, 4.85. Found: C, 35.40; H, 4.78.
4.1.7. 1,2-Dibromoundecan-2,3-dicarboxylic acid (13b).
It was prepared similarly from 12b (726 mg, 3 mmol) and
bromine (720 mg, 4.50 mmol) as described above to obtain
the corresponding diacid 13b: 1.20 g (,100% yield); thick
1
oil; H NMR (CDCl3, 200 MHz) d 0.89 (t, J¼6 Hz, 3H),
1.29 (bs, 12H), 1.80–2.05 (m, 2H), 3.20–3.50 (m, 1H),
3.90–4.30 (m, 2H), 8.90–9.50 (bs, 2H); 13C NMR (CDCl3,
50 MHz) d 14.0 (2-carbons), 22.6 (2-carbons), 27.6, 27.9,
29.2–29.6 (8-carbons), 31.6 (2-carbons), 34.9, 36.3, 49.5,
51.6, 61.1, 63.4, 172.9, 173.3, 177.5, 178.4; MS (m/e) 403
(1%), 402 (2%), 401 (1%), 305 (5%), 303 (5%), 223 (10%),
177 (11%), 149 (15%), 125 (42%), 109 (12%), 95 (20%), 81
(41%), 69 (35%), 55 (50%); IR (Neat) nmax 2700–2500,
1726, 1713, 1460 cm21. Anal. calcd for C13H22Br2O4: C,
38.83; H, 5.51. Found: C, 38.75; H, 5.47.
1
oil; H NMR (CDCl3, 200 MHz) d 0.89 (t, J¼6 Hz, 3H),
1.30 (bs, 6H), 1.58 (m, 2H), 2.48 (t, J¼8 Hz, 2H), 3.23 (d,
J¼6 Hz, 2H), 5.05–5.30 (m, 2H), 5.70–6.00 (m, 1H); 13C
NMR (CDCl3, 50 MHz) d 14.0, 22.4, 24.4, 27.8, 28.4, 29.2,
31.3, 118.7, 131.1, 141.5, 145.4, 165.6, 165.8; IR (Neat)
nmax 1848, 1767, 1665, 1639, 1215, 924, 669 cm21. Anal.
calcd for C13H18O3: C, 70.24; H, 8.16. Found: C, 70.31; H,
8.09.
4.1.11. 2,3-Dihexylmaleic anhydride (25a). Repetition of
above procedure using pentylmagnesium bromide [prepared
from n-pentyl bromide (378 mg, 2.50 mmol) and mag-
nesium (180 mg, 7.50 mmol)], 15a (138 mg, 0.50 mmol),
copper(I) iodide (9.50 mg, 0.05 mmol) and HMPA (1 mL)
gave the corresponding 25a: 74 mg (56% yield); thick oil;
1H NMR (CDCl3, 200 MHz) d 0.90 (t, J¼6 Hz, 6H), 1.31
(bs, 12H), 1.58 (quintet, J¼6 Hz, 4H), 2.45 (t, J¼8 Hz, 4H);
13C NMR (CDCl3, 75 MHz) d 14.0, 22.6, 24.5, 28.0, 29.1,
31.8, 144.5, 166.0; IR (CHCl3) nmax 1846, 1767, 1705,
1663, 1466, 1215, 758 cm21. Anal. calcd for C16H26O3: C,
72.14; H, 9.84. Found: C, 72.21; H, 9.79.
4.1.8. 2-Bromomethyl-3-hexylmaleic anhydride (15a). A
solution of 13a (1.11 g, 3 mmol) in acetic anhydride (7 mL)
was refluxed for 1.5 h and the reaction mixture was
concentrated under vacuo at 508C. The residue was diluted
with ethyl acetate (20 mL) and the organic layer was washed
with water (15 mL), brine (15 mL) and dried over Na2SO4.
The organic layer was concentrated in vacuo and the residue
was chromatographed over silica gel using petroleum ether/
ethyl acetate (9.5:0.5) to give 15a: 820 mg (,100% yield);
1
thick oil; H NMR (CDCl3, 200 MHz) d 0.89 (t, J¼6 Hz,
3H), 1.33 (bs, 6H), 1.65 (quintet, J¼8 Hz, 2H), 2.56 (t,
J¼8 Hz, 2H), 4.18 (s, 2H); 13C NMR (CDCl3, 50 MHz) d
13.7, 16.0, 22.2, 24.7, 27.0, 29.0, 31.1, 138.7, 147.3, 163.7,
164.6; IR (Neat) nmax 1852, 1827, 1774, 1769, 1666,
1462 cm21. Anal. calcd for C11H15BrO3: C, 48.02; H, 5.50.
Found: C, 48.11; H, 5.45.
4.1.12. 2,3-Dioctylmaleic anhydride (25b). Repetition of
above procedure using heptylmagnesium bromide [prepared
from n-heptyl bromide (448 mg, 2.50 mmol) and mag-
nesium (180 mg, 7.50 mmol)], 15b (152 mg, 0.50 mmol),
copper(I) iodide (9.50 mg, 0.05 mmol) and HMPA (1 mL)
1
4.1.9. 2-Bromomethyl-3-octylmaleic anhydride (15b). It
was prepared similarly from 13b (1.20 g, 3 mmol) and
acetic anhydride (7 mL) as described above to obtain the
corresponding anhydride 15b: 909 mg (,100% yield); thick
gave 25b: 89 mg (55% yield); thick oil; H NMR (CDCl3,
200 MHz) d 0.89 (t, J¼6 Hz, 6H), 1.27 (bs, 20H), 1.57
(quintet, J¼6 Hz, 4H), 2.44 (t, J¼8 Hz, 4H); 13C NMR
(CDCl3, 50 MHz) d 13.9, 22.6, 24.5, 27.9, 29.1–29.6
(3-carbons), 31.8, 144.5, 165.9; MS (m/e) 322 (3%), 277
(4%), 250 (3%), 224 (7%), 205 (5%), 126 (9%), 95 (11%),
79 (15%), 67 (20%), 55 (36%); IR (CHCl3) nmax 1836, 1767,
1466, 1215 cm21. Anal. calcd for C20H34O3: C, 74.49; H,
10.63. Found: C, 74.56; H, 10.71.
1
oil; H NMR (CDCl3, 200 MHz) d 0.89 (t, J¼6 Hz, 3H),
1.28 (bs, 10H), 1.67 (quintet, J¼8 Hz, 2H), 2.56 (t, J¼8 Hz,
2H), 4.18 (s, 2H); 13C NMR (CDCl3, 50 MHz) d 13.9, 15.8,
22.5, 24.9, 27.1, 29.0–29.4 (3-carbons), 31.6, 138.8, 147.4,
163.7, 164.7; MS (m/e) 304 (1%), 302 (1%), 223 (5%), 195
(3%), 177 (6%), 149 (6%), 125 (25%), 97 (6%), 79 (10%),
69 (11%), 55 (22%); IR (Neat) nmax 1848, 1828, 1771, 1769,
1666, 1462 cm21. Anal. calcd for C13H19BrO3: C, 51.50; H,
6.32. Found: C, 51.61; H, 6.45.
4.1.13. Dimethyl 2-(prop-2-enyl)-3-hexylmaleate (17).1 A
solution of 16 (111 mg, 0.50 mmol) in methanol (10 mL)
was treated with a solution of diazomethane in ether at 08C

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A. Kar, N. P. Argade / Tetrahedron 59 (2003) 2991–2998
until the starting material was completely consumed (3 h).
The excess diazomethane was quenched with acetic acid
(0.5 mL) and the reaction mixture was concentrated in
vacuo. The residue was chromatographed over silica gel
using petroleum ether/ethyl acetate (9.5:0.5) to give 17:
127 mg (95% yield); thick oil; 1H NMR (CDCl3, 200 MHz)
d 0.88 (t, J¼6 Hz, 3H), 1.27 (bs, 6H), 1.50–1.80 (m, 2H),
2.35 (t, J¼8 Hz, 2H), 3.12 (d, J¼6 Hz, 2H), 3.74 (s, 3H),
3.78 (s, 3H), 5.00–5.20 (m, 2H), 5.65–5.90 (m, 1H); IR
(Neat) nmax 1713, 1638, 1217, 758 cm21. Anal. calcd for
C15H24O4: C, 67.14; H, 9.01. Found: C, 67.25; H, 9.07.
over Na2SO4. The organic layer was concentrated in vacuo
to a furnish thick yellow oil, which was purified by
chromatography on silica gel column using petroleum
ether/ethyl acetate (7:3) to give the desired bromo triester
1
21: 2.50 g (85% yield, 90% purity by H NMR); thick oil;
1H NMR (CDCl3, 200 MHz) d 3.76 (s, 3H), 3.81 (s, 3H),
3.83 (s, 3H), 6.78 (s, 1H), 6.85 (s, 1H); 13C NMR (CDCl3,
50 MHz) d 37.7, 52.1, 52.7, 53.3, 127.6, 141.4, 163.7, 164.5,
166.4; IR (Neat) nmax 1736, 1726, 1655, 1437, 1329, 1283,
1200, 1173, 1022, 789 cm21
.
4.1.17. 2-(b-gem-Dicarbethoxy)ethyl-3-hexylmaleic
anhydride (23a). To a slurry of sodium hydride (26 mg,
1.10 mmol) in benzene (5 mL), a solution of diethyl
malonate (176 mg, 1.10 mmol) in benzene (5 mL) was
added drop wise at room temperature and the reaction
mixture was stirred for 5 min. A solution of 15a (275 mg,
1 mmol) in benzene (10 mL) was added to the reaction
mixture at room temperature and it was stirred for another
8 h. The mixture was acidified with dil. HCl (10 mL, 4%)
and extracted with ethyl acetate (30 mL£3). The combined
organic layers were washed with water (20 mL), brine
(20 mL) and dried over Na2SO4. The organic layer was
concentrated in vacuo and the residue was chromatographed
over silica gel using petroleum ether/ethyl acetate (9.5:0.5)
to give 23a: 255 mg (72% yield); thick oil; 1H NMR
(CDCl3, 200 MHz) d 0.88 (t, J¼6 Hz, 3H), 1.26 (bs, 6H),
1.26 (t, J¼8 Hz, 6H), 1.55 (quintet, J¼6 Hz, 2H), 2.49 (t,
J¼8 Hz, 2H), 3.02 (d, J¼8 Hz, 2H), 3.90 (t, J¼8 Hz, 1H),
4.20 (q, J¼8 Hz, 4H); 13C NMR (CDCl3, 50 MHz) d 13.9,
22.4, 23.6, 24.6, 27.7, 29.2, 29.6, 31.3, 49.0, 62.0, 139.7,
147.2, 165.2, 165.4, 167.9; IR (CHCl3) nmax 1827, 1767,
1753, 1732, 1464 cm21. Anal. calcd for C18H26O7: C,
61.00; H, 7.40. Found: C, 61.03; H, 7.49.
4.1.14. 2-Carboxymethyl-3-hexylmaleic anhydride (1).4
A solution of 17 (100 mg, 0.37 mmol) was dissolved in
acetone and the system was flushed with argon gas. The
reaction mixture was cooled to 2788C using acetone-dry ice
bath and ozone was slowly bubbled in reaction mixture for
3 min at the same temperature. The reaction mixture was
flushed with argon and concentrated under vacuum. The
residue was dissolved in diethyl ether and cooled to 08C. A
solution of 5% Na2Cr2O7 in 4N sulfuric acid (2 mL) was
added in a drop wise fashion for 10 min. The reaction
mixture was further stirred for 3 h and neutralized with 2N
sodium hydroxide (5 mL) solution till alkaline. The aqueous
layer was washed with ether (10 mL£3) and then acidified
with 2N hydrochloric acid (10 mL). Acidified aqueous layer
was extracted with ethyl acetate (10 mL£3). The combined
organic layer was washed with water (20 mL), brine
(20 mL) and dried over Na2SO4. The organic layer was
concentrated in vacuo and the residue was chromatographed
over silica gel using petroleum ether/ethyl acetate (7.5:2.5)
1
to give 1: 37 mg (42% yield); thick oil; H NMR (CDCl3,
200 MHz) d 0.90 (t, J¼6 Hz, 3H), 1.30 (bs, 6H), 1.50–1.80
(m, 2H), 2.49 (t, J¼8 Hz, 2H), 3.61 (s, 2H); IR (Neat) nmax
1820, 1771, 1718, 1216, 925, 670 cm21. Anal. calcd for
C12H16O5: C, 59.99; H, 6.71. Found: C, 60.20; H, 6.83.
4.1.18. 2-(b-gem-Dicarbethoxy)ethyl-3-octylmaleic
anhydride (23b). Repetition of above procedure using
sodium hydride (26 mg, 1.10 mmol), diethyl malonate
(176 mg, 1.10 mmol) and 15b (304 mg, 1 mmol) gave the
corresponding diester 23b: 283 mg (74% yield); thick oil;
1H NMR (CDCl3, 200 MHz) d 0.88 (t, J¼6 Hz, 3H), 1.27
(bs, 10H), 1.27 (t, J¼8 Hz, 6H), 1.50–1.70 (m, 2H), 2.50 (t,
J¼8 Hz, 2H), 3.03 (d, J¼8 Hz, 2H), 3.91 (t, J¼8 Hz, 1H),
4.21 (q, J¼8 Hz, 4H); 13C NMR (CDCl3, 50 MHz) d 13.9
(2-carbons), 22.5, 23.7, 24.6, 27.7, 29.1–29.6 (3-carbons),
31.7, 49.1, 61.9, 139.8, 147.1, 165.2, 165.4, 167.8; MS (m/e)
382 (3%), 337 (28%), 308 (3%), 290 (30%), 252 (11%), 238
(35%), 222 (7%), 206 (12%), 192 (46%), 160 (37%), 133
(15%), 93 (16%), 79 (24%), 69 (26%), 55 (38%); IR
(CHCl3) nmax 1769, 1746, 1732, 1215 cm21. Anal. calcd for
C20H30O7: C, 62.81; H, 7.90. Found: C, 62.73; H, 7.79.
4.1.15. Trimethyl 1-propene-1,2,3-tricarboxylate (20). A
solution of 1-propene-1,2,3-tricarboxylic acid (6.96 g,
40 mmol) in methanol (50 mL) and H2SO4 (0.5 mL)
mixture was refluxed for 12 h under nitrogen. The reaction
mixture was concentrated in vacuo. The residue was diluted
with water (20 mL) and extracted with ethyl acetate
(20 mL£3). The combined organic layer was washed with
water (20 mL), brine (20 mL) and dried over Na2SO4.
Concentration of organic layer in vacuo followed by silica
gel column chromatographic purification of the crude
product using petroleum ether/ethyl acetate (7:3) as eluent
furnished pure triester 20: 6.48 g (75% yield); thick oil; 1H
NMR (CDCl3, 200 MHz) d 3.68 (s, 3H), 3.76 (s, 3H), 3.81
(s, 3H), 3.95 (s, 2H), 6.95 (s, 1H); IR (CHCl3) nmax 1738,
1728, 1655, 1437, 1283, 1200, 1173, 758 cm21. Anal. calcd
for C9H12O6: C, 50.00; H, 5.59. Found: C, 50.09; H, 5.48.
4.1.19. 2-(b-Carboxyethyl)-3-hexylmaleic anhydride
(2a). A solution of diester 23a (177 mg, 0.50 mmol) in
concentrated HCl (5 mL) and acetic acid (5 mL) was
refluxed with stirring for 12 h. The reaction mixture was
then allowed to reach room temperature and then saturated
by adding solid sodium chloride. The filtered aqueous layer
was extracted with ethyl acetate (10 mL£3) and the organic
layer was washed with brine (10 mL) and dried over
Na2SO4. The organic layer was concentrated in vacuo and
the residue was chromatographed over silica gel using
petroleum ether/ethyl acetate (7:3) to give 2a: 122 mg (96%
4.1.16. Trimethyl 3-bromo-1-propene-1,2,3-tricarboxyl-
ate (21). A mixture of 20 (2.16 g, 10 mmol), N-bromo-
succinimide (17.80 g, 100 mmol) and catalytic amount of
AIBN (200 mg, 1.22 mmol) in carbon tetrachloride
(300 mL) was gently refluxed for 32 h in a 500 mL round
bottom flask. The reaction mixture was left overnight at
room temperature and then filtered. The residue was washed
with CCl4 (50 mL£2); the combined organic layer was
washed with water (100 mL), brine (50 mL) and then dried

A. Kar, N. P. Argade / Tetrahedron 59 (2003) 2991–2998
2997
1
yield); thick oil; H NMR (CDCl3, 200 MHz) d 0.88 (t,
K. N. Ganesh, Head, Division of Organic Chemistry
(Synthesis), for constant encouragement.
J¼6 Hz, 3H), 1.28 (bm, 6H), 1.57 (quintet, J¼6 Hz, 2H),
2.49 (t, J¼8 Hz, 2H), 2.76 (s, 4H); 13C NMR (CDCl3,
50 MHz) d 13.9, 19.6, 22.4, 24.6, 27.8, 29.2, 31.0, 31.3,
141.5, 146.3, 165.4, 165.6, 177.4; MS (m/e) 254 (28%), 236
(62%), 208 (15%), 162 (5%), 148 (34%), 91 (10%), 60
(70%); IR (Neat) nmax 2700–2500, 1840, 1765, 1713, 1437,
1273 cm21. Anal. calcd for C13H18O5: C, 61.40; H, 7.13.
Found: C, 61.33; H, 7.05.
References
1. Adlington, R. M.; Baldwin, J. E.; Cox, R. J.; Pritchard, G. J.
Synlett 2002, 820 and references cited therein.
2. (a) Baldwin, J. E.; Adlington, R. M.; Roussi, F.; Bulger, P. G.;
Marqwez, A. V. W. Tetrahedron 2001, 57, 7409. (b) Nicolaou,
K. C.; Baran, P. S.; Zong, Y.-L.; Fong, K. C.; He, Y.; Yoon,
W. H.; Choi, H.-S. Angew. Chem., Int. Ed. 1999, 38, 1676 and
references cited therein.
4.1.20. 2-(b-Carboxyethyl)-3-octylmaleic anhydride
(2b). Repetition of above procedure using 23b (191 mg,
0.50 mmol) gave the corresponding 2b: 134 mg (95%
1
yield); thick oil; H NMR (CDCl3, 200 MHz) d 0.88 (t,
J¼6 Hz, 3H), 1.29 (bs, 10H), 1.57 (quintet, J¼6 Hz, 2H),
2.50 (t, J¼8 Hz, 2H), 2.77 (s, 4H); 13C NMR (CDCl3,
50 MHz) d 13.9, 19.6, 22.5, 24.5, 27.8, 29.0–29.5
(3-carbons), 31.0, 31.7, 141.4, 146.2, 165.3, 165.5, 177.2;
MS (m/e) 282 (2%), 265 (4%), 252 (2%), 236 (9%), 219
(7%), 208 (9%), 180 (3%), 166 (7%), 138 (6%), 105 (4%),
91 (8%), 79 (11%), 69 (16%), 55 (42%); IR (Neat) nmax
3. (a) Singh, S. B.; Jayasuriya, H.; Silverman, K. C.; Bonfiglio,
C. A.; Williamsons, J. M.; Lingham, R. B. Bioorg. Med. Chem.
2000, 8, 571. (b) Singh, S. B.; Zink, D. L.; Liesch, J. M.;
Goetz, M. A.; Jenkins, R. G.; Nalin-Omstead, M.; Silverman,
K. C.; Bills, G. F.; Mosley, R. T.; Gibbs, J. B.; Albers-
Schonberg, G.; Lingham, R. B. Tetrahedron 1993, 49, 5917.
(c) Weber, W.; Semar, M.; Anke, T.; Bross, M.; Steglich, W.
Planta Med. 1992, 58, 56. (d) Raistrick, H.; Smith, G.
Biochem. J. 1933, 27, 1814.
2700–2500, 1840, 1767, 1713, 1668, 1447, 1267 cm21
.
Anal. calcd for C15H22O5: C, 63.81; H, 7.85. Found: C,
63.92; H, 7.73.
4. Weidenmuller, H.-L.; Cavagna, F.; Fehlhaber, H.-W.; Prave,
P. Tetrahedron Lett. 1972, 13, 3519.
4.1.21. 2-(b-Carbmethoxy)ethyl-3-hexylmaleic anhy-
dride (2c). A solution of 2a (64 mg, 0.25 mmol) in diethyl
ether (5 mL) was treated with a solution of diazomethane in
ether at 08C until the starting material was completely
consumed (3 h). The excess diazomethane was quenched
with acetic acid (0.5 mL) and the reaction mixture was
concentrated in vacuo. The residue was chromatographed
over silica gel using petroleum ether/ethyl acetate (9.5:0.5)
to give 2c: 63 mg (95% yield); thick oil; 1H NMR (CDCl3,
200 MHz) d 0.89 (t, J¼6 Hz, 3H), 1.28 (bm, 6H), 1.57
(quintet, J¼8 Hz, 2H), 2.51 (t, J¼8 Hz, 2H), 2.60–2.90 (m,
4H), 3.69 (s, 3H); 13C NMR (CDCl3, 75 MHz) d 13.9, 19.9,
22.4, 24.5, 27.8, 29.2, 31.2, 31.3, 51.9, 141.9, 146.1, 165.5,
165.6, 172.0; IR (CHCl3) nmax 1844, 1767, 1740, 1670,
1439, 1269 cm21. Anal. calcd for C14H20O5: C, 62.67; H,
7.51. Found: C, 62.56; H, 7.39.
5. (a) Itoh, S.; Esaki, N.; Masaki, K.; Blank, W.; Soda, K.
J. Ferment. Bioeng 1994, 77, 513. (b) Gama, Y.; Yasumoto,
M.; Suzuki, H.; Ishigami, Y. Yukagaku 1989, 38, 292.
6. (a) Cheng, X. C.; Kihara, T.; Kusakabe, H.; Magae, J.;
Kobayashi, Y.; Fang, R. P.; Ni, Z. F.; Shen, Y. C.; Ko, K.;
Yamaguchi, I.; Isono, K. J. Antibiot. 1987, 40, 907.
(b) Naganawa, A.; Ichikawa, Y.; Isobe, M. Tetrahedron
1994, 50, 8969.
7. (a) Isaka, M.; Tanticharoen, M.; Thebtaranonth, Y.
Tetrahedron Lett. 2000, 41, 1657. (b) Yamanishi, R.; Okada,
K.; Tamugi, N.; Iwashima, M.; Iguchi, K. Bull. Chem. Soc.
Jpn 2000, 73, 2087 and refs. cited therein. (c) Aldridge, D. C.;
Carman, R. M.; Moore, R. B. J. Chem. Soc., Perkin Trans. 1
1980, 2134.
8. Adeboya, M. O.; Edwards, R. L.; Laessoe, T.; Maitland, D. J.;
Whalley, A. J. S. Liebigs Ann. Chem. 1996, 1437.
9. (a) Kinoshita, K.; Nakajima, S. Chem. Pharm. Bull. 1958, 6,
31. (b) Nakajima, S. Chem. Pharm. Bull. 1965, 13, 73.
(c) Sankawa, U.; Shibata, S. Chem. Pharm. Bull. 1969, 17,
2025.
4.1.22. 2-(b-Carbmethoxy)ethyl-3-octylmaleic anhy-
dride (2d). Repetition of the above procedure with 2b
(71 mg, 0.25 mmol) gave the corresponding 2d: 70 mg
1
(95% yield); thick oil; H NMR (CDCl3, 200 MHz) d 0.89
10. (a) Desai, S. B.; Argade, N. P. J. Org. Chem. 1997, 62, 4862.
(b) Deshpande, A. M.; Natu, A. A.; Argade, N. P. J. Org.
Chem. 1998, 63, 9557. (c) Deshpande, S. G.; Argade, N. P.
Synthesis 1999, 1306. (d) Deshpande, A. M.; Natu, A. A.;
Argade, N. P. Synthesis 2001, 702. (e) Mangaleswaran, S.;
Argade, N. P. J. Org. Chem. 2001, 66, 5259.
(f) Mangaleswaran, S.; Argade, N. P. Synthesis 2002, 865.
(g) Kar, A.; Argade, N. P. J. Org. Chem. 2002, 67, 7131.
(h) Sahoo, M. K.; Mhaske, S. B.; Argade, N. P. Synthesis 2003,
346.
(t, J¼6 Hz, 3H), 1.27 (bs, 10H), 1.57 (quintet, J¼6 Hz, 2H),
2.51 (t, J¼8 Hz, 2H), 2.60–2.90 (m, 4H), 3.70 (s, 3H); MS
(m/e) 296 (3%), 277 (6%), 265 (37%), 250 (11%), 218
(10%), 207 (13%), 198 (18%), 180 (22%), 166 (67%), 151
(15%), 138 (21%), 91 (13%), 79 (26%), 67 (31%), 55
(67%); 13C NMR (CDCl3, 75 MHz) d 14.0, 21.2, 22.6, 24.3,
28.0, 29.1, 29.2, 29.4, 30.0, 31.7, 51.6, 142.0, 146.1, 165.4,
165.5, 172.7; IR (CHCl3) nmax 1836, 1767, 1738, 1450,
1215 cm21. Anal. calcd for C16H24O5: C, 64.84; H, 8.16.
Found: C, 64.76; H, 8.25.
11. Kar, A.; Argade, N. P. Tetrahedron Lett. 2002, 43, 6563.
12. Desai S. B.; Argade N. P. Unpublished results.
13. (a) Beltaief, I.; Besbes, R.; Amor, F. B.; Amri, H.; Villieras,
M.; Villieras, J. Tetrahedron 1999, 55, 3949. (b) Amri, H.;
Villieras, J. Tetrahedron Lett. 1987, 28, 5521. (c) Loh, T.-P.;
Lye, P.-L. Tetrahedron Lett. 2001, 42, 3511. (d) Calo, V.;
Lopez, L.; Pesce, G. J. Organomet. Chem. 1988, 353, 405.
14. Vogel, A. I. Vogel’s Textbook of Practical Organic Chemistry,
Acknowledgements
A. K. thanks CSIR, New Delhi, for the award of a research
fellowship. N. P. A. thanks Department of Science and
Technology, New Delhi, for financial support. We thank Dr

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A. Kar, N. P. Argade / Tetrahedron 59 (2003) 2991–2998
5th ed.; Furniss, B. S., Stanley, B., Eds.: Longman: Harlow,
1989; Chapter 5, p 714.
15. Bulman Page, P. C.; van Neil, M. B.; Prodger, J. C.
16. Bruce, W. F. Organic Syntheses; Wiley: New York, 1943;
Collect. Vol. 2, p 12.
Tetrahedron 1989, 45, 7643.