Applications of Baylis-Hillman chemistry: Enantioselective synthesis of (-)-methyl 3-aryl-2-methylene-3-(prop-2-yn-1-yloxy)propanoates via chiral leaving group strategy

Article abstract of DOI:10.1016/S0040-4020(01)00786-4

Asymmetric synthesis of (-)-methyl 3-aryl-2-methylene-3-(prop-2-yn-1-yloxy)propanoates in 25-40% enantiomeric purities via the reaction of methyl (2Z)-3-aryl-2-(bromomethyl)prop-2-enoates with prop-2-yn-1-ol in the presence of quinidine is described.

Full text of DOI:10.1016/S0040-4020(01)00786-4

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 8167±8172
Applications of Baylis±Hillman chemistry:
enantioselective synthesis of ꢀ2)-methyl 3-aryl-2-methylene-3-
ꢀprop-2-yn-1-yloxy)propanoates via chiral leaving group strategy
Deevi Basavaiah,p Nagaswamy Kumaragurubaran, Duddu S. Sharada
and Ravi Mallikarjuna Reddy
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
Received 16 April 2001; accepted 2 August 2001
AbstractÐAsymmetric synthesis of (2)-methyl 3-aryl-2-methylene-3-(prop-2-yn-1-yloxy)propanoates in 25±40% enantiomeric purities
via the reaction of methyl (2Z)-3-aryl-2-(bromomethyl)prop-2-enoates with prop-2-yn-1-ol in the presence of quinidine is described. q 2001
Elsevier Science Ltd. All rights reserved.
Baylis±Hillman chemistry has become one of the important
and attractive sources for stereoselective processes in
synthetic organic chemistry and is of current interest.1±9 In
continuation of our interest in the applications of the
Baylis±Hillman adducts in organic synthesis,9±11 we herein
report chiral leaving group induced enantioselective
synthesis of (2)-methyl 3-aryl-2-methylene-3-(prop-2-yn-
1-yloxy)propanoates via the treatment of methyl (2Z)-3-
aryl-2-(bromomethyl)prop-2-enoates with prop-2-yn-1-ol
(propargyl alcohol) in the presence of quinidine.
With a view of understanding the applicability of allyl
halides (1±3), as suitable electrophiles in various organic
transformations and also with an objective of expanding the
scope of these allyl halides in synthetic organic chemistry,
we have directed our studies towards the addition of oxygen
nucleophiles from alcohols onto these allyl halides.
Literature survey reveals that there are some reports on
the nucleophilic addition (SN20) of certain oxygen nucleo-
philes such as alkoxides and hydroperoxides to 2-(bromo-
methyl)alk-2-enoates.12±14
Recently,
intramolecular
nucleophilic addition (SN20) of oxygen nucleophile from
oxirane to the allyl bromide moiety of methyl 2-(bromo-
methyl)-6,7-epoxyhept-2-enoate providing an interesting
tetrahydropyran derivative has been reported.15 However,
addition of oxygen nucleophile from prop-2-yn-1-ol
(propargyl alcohol) to 2-(bromomethyl)alk-2-enoates has
not been studied so far in the literature. Also various allyl
propargyl ethers have been successfully employed in a
number of interesting organic transformations.16±20
Therefore, we have selected prop-2-yn-1-ol as a possible
Recently, we have described applications of (Z)-allyl
halides (1 and 2) obtained from the Baylis±Hillman
adducts, as suitable electrophiles in the Baylis±Hillman
reaction thus providing a simple synthesis of functionalized
1,4-pentadienes (Scheme 1).10 We have also successfully
used the allyl halides (1 and 3) in the synthesis of
2-methylenealkanoates and alkanenitriles via the treatment
with NaBH4 in the presence of DABCO in environment
friendly aqueous media (Scheme 1).11
Scheme 1.
Keywords: Baylis±Hillman chemistry; methyl 3-aryl-2-methylene-3-(prop-2-yn-1-yloxy)propanoates; chiral leaving group.
Corresponding author. Tel.: 191-40-3010221; fax: 191-40-3012460; e-mail: dbsc@uohyd.ernet.in
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)00786-4

8168
D.Basavaiah et al./ Tetrahedron 57 %2001) 8167±8172
nucleophile for our study with a view that the resulting allyl
propargyl ethers might be attractive substrates for useful
synthetic transformations. Accordingly, we have carried
out the reaction of methyl (2Z)-2-(bromomethyl)-3-phenyl-
prop-2-enoate (1a) with prop-2-yn-1-ol in the presence of
DABCO under various conditions. The best result was
accomplished when methyl (2Z)-2-(bromomethyl)-3-
phenylprop-2-enoate (1a) (1 mmol) was treated with prop-
2-yn-1-ol (5 mmol) in the presence of DABCO (2 mmol) in
dichloromethane at room temperature for 12 h, thus
providing methyl 2-methylene-3-phenyl-3-(prop-2-yn-1-
yloxy)propanoate (4a) in 29% yield. Though the desired
product is obtained in pure form, the yield is not encourag-
ing. At this stage, we envisaged that the yield could be
possibly improved if we use an appropriate tertiary amine
in the place of DABCO. In this search, we have obtained
encouraging results when methyl (2Z)-2-(bromomethyl)-3-
phenylprop-2-enoate (1a) (1 mmol) was treated with prop-
2-yn-1-ol (5 mmol) in the presence of triethylamine (1 mL)
at room temperature for 12 h (without any solvent) thus
providing the desired methyl 2-methylene-3-phenyl-3-
(prop-2-yn-1-yloxy)propanoate (4a) in 74% yield after
usual work up, followed by column chromatography (silica
gel, 2% ethyl acetate in hexanes). We have then extended
the same strategy to a representative class of methyl (2Z)-3-
aryl-2-(bromomethyl)prop-2-enoates (1b±f) to provide the
desired methyl 3-aryl-2-methylene-3-(prop-2-yn-1-yloxy)-
propanoates (4b±f) in high yields (Scheme 2, Table 1).
presence of triethylamine (1 mL) in dichloromethane
(2 mL) at room temperature for 4 h (Scheme 2, Table 1).
These successful results led us to envisage that if we use an
appropriate chiral tertiary amine, which subsequently
becomes a leaving group, there might be chiral induction.
A literature survey reveals that a number of asymmetric
reactions have been reported under the in¯uence of a chiral
leaving group.22±27 We have planned to use various chiral
tertiary amines such as sparteine (6), cinchonidine (7),
quinine (8) and quinidine (9) which are naturally occurring
and easily accessible, for our study on the chiral leaving
groupinduced asymmetric synthesis. We have ®rst
examined the reaction of methyl (2Z)-2-(bromomethyl)-3-
phenylprop-2-enoate (1a) with prop-2-yn-1-ol under the
in¯uence of a chiral leaving group[tertiary amines ( 6±9)].
Encouraging results were obtained when methyl (2Z)-2-
(bromomethyl)-3-phenylprop-2-enoate (1a) (1 mmol) was
treated with prop-2-yn-1-ol (5 mmol) in the presence of
quinidine (2 mmol) in dichloromethane at room temperature
for 24 h thus providing (2)-methyl 2-methylene-3-phenyl-
3-(prop-2-yn-1-yloxy)propanoate {(2)-4a} in 31% enantio-
selectivity and in 36% yield. However, other chiral amines
6±8 provided inferior results. We have then extended the
same strategy using quinidine to representative allyl
bromides (1b±f), thus providing a simple synthesis of
(2)-methyl 3-aryl-2-methylene-3-(prop-2-yn-1-yloxy)pro-
panoates {(2)-4b±f} in 25±40% enantiomeric purities
and in 32±47% yields (Scheme 3, Table 2).
With a view of expanding the scope of this methodology we
have also used phenol as a nucleophile in this study.21 Thus,
we have developed a general synthesis of methyl 3-aryl-2-
methylene-3-phenoxypropanoates (5a±f) in good yields via
the treatment of 1a±f (1 mmol) with phenol (1 mmol) in the
In order to understand the structure of the allyl bromide±
quinidine salt, we have isolated methyl (2Z)-2-(bromo-
methyl)-3-phenylprop-2-enoate-quinidine salt (10a) via
the treatment of 1a (1 mmol) with quinidine (1 mmol) in
Scheme 2. Arˆphenyl, 4-chlorophenyl, 4-methylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 2-methylphenyl.
Table 1. Synthesis of methyl 3-aryl-2-methylene-3-(prop-2-yn-1-yloxy)propanoates (4a±f) and methyl 3-aryl-2-methylene-3-phenoxypropanoates (5a±f)
Allyl bromide
Ar
Propargyl alcohola,b
Yielde (%)
Phenolc,d
Product
Product
Yielde (%)
1a
1b
1c
1d
1e
1f
Phenyl
4a
74f
84
76
67
77
76
5a
5b
5c
5d
5e
5f
85f
76
69
64
61
63
4-Chlorophenyl
4-Methylphenyl
4-Ethylphenyl
4-Isopropylphenyl
2-Methylphenyl
4b
4c
4d
4e
4f
a
All reactions were carried out on 1 mmol scale of allyl bromides (1a±f) with propargyl alcohol (5 mmol) in the presence of Et3N (1 mL) at room temperature
for 12 h.
b
c
d
Products 4a±e were obtained as colorless viscous liquids and product 4f was obtained as colorless solid and all the products gave satisfactory IR, 1H
(200 MHz), 13C NMR (50 MHz) spectral data and elemental analyses.
All reactions were carried out on 1 mmol scale of allyl bromide (1a±f) with phenol (1 mmol) and Et3N (1 mL) in dichloromethane (2 mL) at room
temperature for 4 h.
All the products 5a±f were obtained as colorless viscous liquids and gave satisfactory IR, 1H NMR (200 MHz), 13C NMR (50 MHz) spectral data and
elemental analyses.
e
f
Isolated yields of the pure products after column chromatography (silica gel, 2% EtOAc in hexanes).
These products were also characterized by mass spectral analysis.

D.Basavaiah et al./ Tetrahedron 57 %2001) 8167±8172
8169
Scheme 3. Arˆphenyl, 4-chlorophenyl, 4-methylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 2-methylphenyl.
Table 2. Enantioselective synthesis of (2)-methyl 3-aryl-2-methylene-3-(prop-2-yn-1-yloxy)propanoates {(2)-4a±f}
Allyl bromide
Ar
Product
Yield (%)a
Optical rotation
[a]D
(c, CHCl3)
ee (%)b
20
1a
1b
1c
1d
1e
1f
Phenyl
(2)-4a
(2)-4b
(2)-4c
(2)-4d
(2)-4e
(2)-4f
36
47
37
32
36
35
270.24 (1.24)
283.24 (1.074)
264.19 (0.592)
274.91 (0.606)
281.59 (0.516)
258.06 (0.632)
31
39
25
35
40
32
4-Chlorophenyl
4-Methylphenyl
4-Ethylphenyl
4-Isopropylphenyl
2-Methylphenyl
All reactions were carried out on 1 mmol scale of allyl bromides (1a±f) with propargyl alcohol (5 mmol) in the presence of quinidine (2 mmol) in dichloro-
methane (4 mL) at room temperature for 24 h.
1
Products (2)-4a±e were obtained as colorless viscous liquids and product (2)-4f was obtained as colorless solid. All the products gave satisfactory IR, H
NMR (200 MHz), 13C NMR (50 MHz) spectral data which are identical with that of the corresponding racemic molecules.
Isolated yields of the pure products after column chromatography (silica gel, 2% EtOAc in hexanes).
a
b
Enantiomeric purity of these molecules was determined by HPLC analysis using chiral column (chiralcel OD column, 5% i-PrOH in hexane, 0.5 mL/min)
with reference to the corresponding racemic molecules.
dichloromethane at room temperature for 15 h followed by
crystallization [of the crude salt from chloroform and
hexanes (1:1)] as a crystalline solid in 68% yield. 1H
NMR and 13C NMR spectral data con®rm the structure of
this molecule with exclusive (E)-stereochemistry.28 This
crystalline solid on treatment with prop-2-yn-1-ol in the
presence of quinidine in dichloromethane at room tempera-
ture for 24 h provided the desired product (2)-4a in 38%
enantiomeric purity and in 37% yield. This indicates that the
less enantioselectivity obtained, from the amine salt without
crystallization, is presumably due to the presence of (Z)-
isomer.29 Since the enantiomeric purities are only moderate,
we did not proceed further for obtaining the pure (E)-isomer
via crystallization in the case of other allyl bromides±
quinidine salts (10b±f). However, our attempts to
in deuterochloroform (CDCl3) on a Bruker-AC-200 spectro-
meter using tetramethylsilane (TMS, dˆ0) as internal
standard. Mass spectra were recorded on a micromass VG
7070H instrument. Elemental analyses were recorded on a
Perkin±Elmer 240C-CHN analyzer. Optical rotations were
measured on a JASCO DIP-370 digital polarimeter. HPLC
analyses were carried out on Shimadzu LC-10 AD instru-
ment. All the required allyl bromides, i.e. methyl (2Z)-3-
aryl-2-(bromomethyl)prop-2-enoates were obtained via the
reaction of the corresponding Baylis±Hillman adducts with
HBr/H2SO4 according to the literature procedure.2,3,30
.
1.1. General procedure for the preparation of methyl
3-aryl-2-methylene-3-ꢀprop-2-yn-1-yloxy)propanoates
synthesize
methyl
2-methylene-3-phenyl-3-phenoxy-
To a stirred solution of methyl (2Z)-3-aryl-2-(bromo-
methyl)prop-2-enoates (1 mmol) in Et3N (1 mL), was
added propargyl alcohol (5 mmol, 0.28 g). After stirring
for 12 h at room temperature, the reaction mixture was
diluted with ether (15 mL) and washed successively with
2N HCl solution and water. The organic layer was dried
over anhydrous Na2SO4 and concentrated. The crude
product, thus obtained was puri®ed by column chromato-
graphy (silica gel, 2% ethyl acetate in hexanes) to provide
pure methyl 3-aryl-2-methylene-3-(prop-2-yn-1-yloxy)pro-
panoates.
propanoate (5a) in enantiomerically enriched form via the
treatment of 1a with phenol in the presence of quinidine did
not give satisfactory results.
In conclusion, we have developed a simple enantioselective
synthesis of (2)-methyl 3-aryl-2-methylene-3-(prop-2-yn-
1-yloxy)propanoates under the in¯uence of chiral leaving
group(quinidine), thus demonstrating the importance of
allyl bromides derived from the Baylis±Hillman adducts
in organic synthesis.
1.1.1. Methyl 2-methylene-3-ꢀprop-2-yn-1-yloxy)-3-
phenylpropanoate ꢀ4a). Colorless viscous liquid. Yield:
1. Experimental
1
74%; IR (neat): 3288, 2118, 1722, 1631 cm21; H NMR:
Melting points were recorded on a Super®t (India) capillary
melting point apparatus and are uncorrected. IR spectra
were recorded on a JASCO-FT-IR model 5300 spectrometer
using samples as neat liquids or as KBr plates. H NMR
(200 MHz) and 13C NMR (50 MHz) spectra were recorded
d 2.45 (t, 1H, Jˆ2.4 Hz), 3.70 (s, 3H), 4.01 and 4.18
(CH2CuC, d AB q, 2H, Jˆ15.6 and 2.4 Hz), 5.51 (s, 1H),
6.00 (d, 1H, Jˆ1.2 Hz), 6.37 (s, 1H), 7.28±7.42 (m, 5H);
13C NMR: d 51.74, 55.93, 74.75, 77.79, 79.50, 125.24,
127.86, 128.17, 128.40, 138.65, 140.72, 166.01; MS (m/z):
1

8170
D.Basavaiah et al./ Tetrahedron 57 %2001) 8167±8172
230 (M1); Anal. calcd for C14H14O3: C, 73.03; H, 6.13;
found: C, 73.40; H, 6.17.
enoates (1 mmol), phenol (1 mmol, 0.094 g) and Et3N
(1 mL) in CH2Cl2 (2 mL), was stirred at room temperature
for 4 h. Then the reaction mixture was diluted with 2N HCl
and extracted with ether (2£10 mL). The combined organic
layer was washed with aqueous NaHCO3 solution, water
and dried over anhydrous Na2SO4. Solvent was evaporated
and the crude product was puri®ed by column chromato-
graphy (silica gel, 2% ethyl acetate in hexanes) to provide
the pure methyl 3-aryl-2-methylene-3-phenoxypropanoates.
1.1.2. Methyl 3-ꢀ4-chlorophenyl)-2-methylene-3-ꢀprop-2-
yn-1-yloxy)propanoate ꢀ4b). Colorless viscous liquid.
1
Yield: 84%; IR (neat): 3298, 2118, 1722, 1631 cm21; H
NMR: d 2.44 (t, 1H, Jˆ2.6 Hz), 3.69 (s, 3H), 4.00 and
4.16 (CH2CuC, d AB q, 2H, Jˆ15.6 and 2.6 Hz), 5.47 (s,
1H), 6.01 (s, 1H), 6.37 (s, 1H), 7.31 (s, 4H); 13C NMR: d
51.19, 55.33, 74.36, 76.41, 78.56, 124.82, 127.95, 128.58,
133.33, 136.67, 139.63, 165.15; Anal. calcd for C14H13O3Cl:
C, 63.52; H, 4.95; found: C, 63.38; H, 4.97.
1.2.1. Methyl 2-methylene-3-phenoxy-3-phenylpropano-
ate ꢀ5a). Colorless viscous liquid. Yield: 85%; IR (neat):
1
1722, 1631 cm21; H NMR: d 3.73 (s, 3H), 5.95 (s, 1H),
1.1.3. Methyl 2-methylene-3-ꢀ4-methylphenyl)-3-ꢀprop-
2-yn-1-yloxy)propanoate ꢀ4c). Colorless viscous liquid.
6.14 (s, 1H), 6.37 (s, 1H), 6.87±6.98 (m, 3H), 7.15±7.50 (m,
7H); 13C NMR: d 51.90, 77.38, 116.01, 121.26, 126.15,
127.41, 128.12, 128.50, 129.39, 138.99, 140.41, 157.67,
166.03; MS (m/z): 268 (M1); Anal. calcd for C17H16O3: C,
76.10; H, 6.01; found: C, 75.91; H, 6.04.
1
Yield: 76%; IR (neat): 3286, 2124, 1719, 1631 cm21; H
NMR: d 2.33 (s, 3H), 2.44 (t, 1H, Jˆ1.8 Hz), 3.68 (s,
3H), 3.99 and 4.14 (CH2CuC, d AB q, 2H, Jˆ15.5 and
1.8 Hz), 5.47 (s, 1H), 6.00 (d, 1H, Jˆ1.8 Hz), 6.35 (s,
1H), 7.14 (d, 2H, Jˆ7.8 Hz), 7.27 (d, 2H, Jˆ7.8 Hz); 13C
NMR: d 21.12, 51.72, 55.73, 74.62, 77.53, 79.55, 124.96,
127.83, 129.09, 135.50, 137.89, 140.75, 166.03; Anal. calcd
for C15H16O3: C, 73.75; H, 6.60; found: C, 73.98; H, 6.55.
1.2.2. Methyl 3-ꢀ4-chlorophenyl)-2-methylene-3-phenoxy-
propanoate ꢀ5b). Colorless viscous liquid. Yield: 76%; IR
(neat): 1720, 1633 cm21; 1H NMR: d 3.74 (s, 3H), 5.99 (s,
1H), 6.11 (s, 1H), 6.38 (s, 1H), 6.87±7.01 (m, 3H), 7.16±
7.47 (m, 6H); 13C NMR: d 52.02, 76.81, 116.08, 121.56,
126.28, 128.77, 128.84, 129.51, 134.04, 137.69, 140.13,
157.46, 165.89; Anal. calcd for C17H15O3Cl: C, 67.44; H,
4.99; found: C, 67.71; H, 4.96.
1.1.4. Methyl 3-ꢀ4-ethylphenyl)-2-methylene-3-ꢀprop-2-
yn-1-yloxy)propanoate ꢀ4d). Colorless viscous liquid.
1
Yield: 67%; IR (neat): 3288, 2118, 1724, 1631 cm21; H
NMR: d 1.21 (t, 3H, Jˆ7.8 Hz), 2.42 (t, 1H, Jˆ2.2 Hz),
2.63 (q, 2H, Jˆ7.8 Hz), 3.68 (s, 3H), 4.00 and 4.14
(CH2CuC, d AB q, 2H, Jˆ15.6 and 2.2 Hz), 5.47 (s, 1H),
5.98 (d, 1H, Jˆ1.8 Hz), 6.34 (s, 1H), 7.15 (d, 2H,
Jˆ7.8 Hz), 7.27 (d, 2H, Jˆ7.8 Hz); 13C NMR: d 15.33,
28.49, 51.66, 55.73, 74.58, 77.53, 79.54, 124.92, 127.83,
135.72, 140.75, 144.14, 166.00; Anal. calcd for C16H18O3:
C, 74.40; H, 7.02; found: C, 74.25; H, 7.05.
1.2.3. Methyl 2-methylene-3-ꢀ4-methylphenyl)-3-phenoxy-
propanoate ꢀ5c). Colorless viscous liquid. Yield: 69%; IR
(neat): 1722, 1631 cm21; 1H NMR: d 2.32 (s, 3H), 3.73 (s,
3H), 5.96 (s, 1H), 6.11 (s, 1H), 6.36 (s, 1H), 6.84±6.98 (m,
3H), 7.10±7.37 (m, 6H); 13C NMR: d 21.15, 51.91, 77.31,
116.06, 121.20, 125.94, 127.43, 129.25, 129.39, 136.02,
137.90, 140.53, 157.79, 166.14; Anal. calcd for C18H18O3:
C, 76.57; H, 6.43; found: C, 76.39; H, 6.39.
1.1.5. Methyl 3-ꢀ4-isopropylphenyl)-2-methylene-3-ꢀprop-
2-yn-1-yloxy)propanoate ꢀ4e). Colorless viscous liquid.
1.2.4. Methyl 3-ꢀ4-ethylphenyl)-2-methylene-3-phenoxy-
propanoate ꢀ5d). Colorless viscous liquid. Yield: 64%; IR
1
Yield: 77%; IR (neat): 3289, 2118, 1724, 1632 cm21; H
(neat): 1722, 1631 cm21
;
1H NMR: d 1.23 (t, 3H,
NMR: d 1.23 (d, 6H, Jˆ6.8 Hz), 2.43 (t, 1H, Jˆ2.4 Hz),
2.88 (sept. 1H, Jˆ6.8 Hz), 3.69 (s, 3H), 4.01 and 4.14
(CH2CuC, d AB q, 2H, Jˆ15.6 and 2.4 Hz), 5.48 (s, 1H),
5.99 (d, 1H, Jˆ2.4 Hz), 6.35 (s, 1H), 7.18 (d, 2H,
Jˆ8.0 Hz), 7.28 (d, 2H, Jˆ8.0 Hz); 13C NMR: d 23.93,
33.84, 51.79, 55.85, 74.61, 77.58, 79.62, 125.10, 126.50,
127.82, 135.85, 140.72, 148.83, 166.13; Anal. calcd for
C17H20O3: C, 74.97; H, 7.40; found: C, 75.28; H, 7.36.
Jˆ7.8 Hz), 2.64 (q, 2H, Jˆ7.8 Hz), 3.75 (s, 3H), 5.97 (s,
1H), 6.13 (s, 1H), 6.38 (s, 1H), 6.87±7.05 (m, 3H), 7.13±
7.47 (m, 6H); 13C NMR: d 15.34, 28.56, 51.93, 77.26,
116.00, 121.17, 125.98, 127.45, 128.03, 129.39, 136.19,
140.46, 144.19, 157.78, 166.15; Anal. calcd for C19H20O3:
C, 77.00; H, 6.80; found: C, 77.29; H, 6.78.
1.2.5. Methyl 3-ꢀ4-isopropylphenyl)-2-methylene-3-
phenoxypropanoate ꢀ5e). Colorless viscous liquid. Yield:
61%; IR (neat): 1722, 1632 cm21; 1H NMR: d 1.24 (d, 6H,
Jˆ7.2 Hz), 2.89 (sept. 1H, Jˆ7.2 Hz), 3.76 (s, 3H), 5.98 (s,
1H), 6.14 (s, 1H), 6.38 (s, 1H), 6.87±6.99 (m, 3H), 7.15±
7.42 (m, 6H); 13C NMR: d 23.83, 33.75, 51.83, 77.10,
115.86, 121.06, 125.88, 126.53, 127.34, 129.30, 136.19,
140.34, 148.70, 157.68, 166.05; Anal. calcd for C20H22O3:
C, 77.39; H, 7.14; found: C, 77.06; H, 7.20.
1.1.6. Methyl 2-methylene-3-ꢀ2-methylphenyl)-3-ꢀprop-
2-yn-1-yloxy)propanoate ꢀ4f). Colorless solid. Yield:
76%; mp76±78 8C; IR (KBr): 3263, 2114, 1714,
1
1630 cm21; H NMR: d 2.40±2.48 (m, 4H), 3.72 (s, 3H),
4.05 and 4.19 (CH2CuC, d AB q, 2H, Jˆ15.6 and 1.8 Hz),
5.76 (s, 1H), 5.81 (s, 1H), 6.39 (s, 1H), 7.15±7.40 (m, 4H);
13C NMR: d 19.13, 51.80, 56.07, 74.54, 74.59, 79.70,
126.04, 127.29, 128.01, 130.52, 136.25, 136.97, 140.17,
166.25; Analysis calculated for C15H16O3: C, 73.75; H,
6.60; found: C, 73.67; H, 6.65.
1.2.6.
Methyl
2-methylene-3-ꢀ2-methylphenyl)-3-
phenoxypropanoate ꢀ5f). Colorless viscous liquid. Yield:
63%; IR (neat): 1724, 1633 cm21; 1H NMR: d 2.35 (s, 3H),
3.74 (s, 3H), 5.73 (s, 1H), 6.32 (s, 1H), 6.42 (s, 1H), 6.82±
6.96 (m, 3H), 7.15±7.45 (m, 6H); 13C NMR: d 19.19, 52.01,
74.78, 115.81, 121.25, 126.20, 127.26, 127.39, 128.23,
1.2. General procedure for the preparation of methyl
3-aryl-2-methylene-3-phenoxypropanoates
A solution of methyl (2Z)-3-aryl-2-(bromomethyl)prop-2-

D.Basavaiah et al./ Tetrahedron 57 %2001) 8167±8172
8171
129.43, 130.70, 136.32, 136.42, 139.46, 158.09, 166.30;
Anal. calcd for C18H18O3: C, 76.57; H, 6.43; found: C,
76.79; H, 6.47.
OD; eluent: hexane/i-PrOH, 95:05; ¯ow rate: 0.5 mL/min;
retention times: 10.87 (major) and 12.90 (minor) min.
1.3.7. Methyl ꢀ2Z)-2-ꢀbromomethyl)-3-phenylprop-2-
enoate-quinidine salt ꢀ10a). To a stirred solution of methyl
(2Z)-2-(bromomethyl)-3-phenylprop-2-enoate (1a) (1 mmol,
0.255 g) in dichloromethane (4 mL), quinidine (1 mmol,
0.324 g) was added and stirred at room temperature for
15 h. The solvent was removed under reduced pressure to
afford the crude salt (10a) as a yellow solid. Careful and
selective crystallization of this crude salt (10a) from chloro-
form in hexanes (1:1) provided the stereochemically pure
salt (E)-10a as a colorless crystalline solid. Yield: 68%
1.3. General procedure for enantioselective synthesis of
ꢀ2)-methyl 3-aryl-2-methylene-3-ꢀprop-2-yn-1-yloxy)-
propanoates
To a stirred solution of methyl (2Z)-3-aryl-2-(bromo-
methyl)prop-2-enoates (1a±f) (1 mmol) in dichloromethane
(4 mL), quinidine (2 mmol, 0.649 g) and propargyl alcohol
(5 mmol, 0.28 g) were added. After stirring for 24 h at room
temperature, the reaction mixture was diluted with ether
(15 mL) and washed successively with 2N HCl solution
and water. The ethereal layer was dried over anhydrous
Na2SO4 and concentrated. The crude product thus obtained
was puri®ed by column chromatography (silica gel, 2%
ethyl acetate in hexanes) to provide the pure (2)-methyl
3-aryl-2-methylene-3-(prop-2-yn-1-yloxy)propanoates {(2)-
(4a±f)}. The IR, 1H and 13C NMR spectral data of (2)-4a±f
were identical with that of the corresponding racemic mole-
cules.
20
(0.394 g); mp146±148 8C (dec.); [a]D ˆ184.76 (c 1.05,
CHCl3); IR (KBr): 1697, 1622 cm21; 1H NMR: d 0.80±1.04
(m, 1H), 1.60±3.81 (m, 10H), 3.93 (s, 3H), 4.07 (s, 3H),
4.73±5.16 (m, 3H), 5.58±5.98 (m, 2H), 6.61 (d, 1H,
Jˆ5.4 Hz), 6.85±6.91 (m, 1H), 7.15±8.17 (m, 9H), 8.47
(s, 1H), 8.73 (d, 1H, Jˆ4.2 Hz); 13C NMR: d 21.38,
23.87, 26.12, 37.33, 53.39, 53.83, 55.85, 64.78, 68.97,
100.31, 117.55, 119.69, 120.13, 121.75, 125.44, 129.76,
129.83, 130.62, 131.99, 132.96, 135.22, 143.01, 144.07,
147.54, 152.50, 158.28, 167.67.
1.3.8. ꢀ2)-Methyl 2-methylene-3-phenyl-3-ꢀprop-2-yn-1-
yloxy)propanoate {ꢀ2)-4a}: from ꢀE)-10a. This product
was obtained as a colorless viscous liquid via the treatment
of methyl (2Z)-2-(bromomethyl)-3-phenylprop-2-enoate-
quinidine salt (E)-10a (0.5 mmol, 0.289 g) with propargyl
alcohol (2.5 mmol, 0.14 g) in the presence of quinidine
(0.5 mmol, 0.162 g) in dichloromethane. Reaction time:
1.3.1. ꢀ2)-Methyl 2-methylene-3-phenyl-3-ꢀprop-2-yn-1-
yloxy)propanoate {ꢀ2)-4a}. Colorless viscous liquid.
20
Yield: 36%; [a]D ˆ270.24 (c 1.24, CHCl3); 31% ee;
HPLC analysis: chiral column: chiralcel OD; eluent:
hexane/i-PrOH, 95:05; ¯ow rate: 0.5 mL/min; retention
times: 12.38 (major) and 14.02 (minor) min.
20
24 h, Yield: 37%; [a]D ˆ285.35 (c 0.284, CHCl3); 38%
1.3.2. ꢀ2)-Methyl 3-ꢀ4-chlorophenyl)-2-methylene-3-
ꢀprop-2-yn-1-yloxy)propanoate {ꢀ2)-4b}. Colorless
ee; HPLC analysis: chiral column: chiralcel OD; eluent:
hexane/i-PrOH, 95:05; ¯ow rate: 0.5 mL/min; retention
times: 12.26 (major) and 13.58 (minor) min.
20
viscous liquid. Yield: 47%; [a]D ˆ283.24 (c 1.074,
CHCl3); 39% ee; HPLC analysis: chiral column: chiralcel
OD; eluent: hexane/i-PrOH, 95:05; ¯ow rate: 0.5 mL/min;
retention times: 10.34 (major) and 12.24 (minor) min.
Acknowledgements
1.3.3. ꢀ2)-Methyl 2-methylene-3-ꢀ4-methylphenyl)-3-
Colorless
viscous liquid. Yield: 37%; [a]D ˆ264.19 (c 0.592,
CHCl3); 25% ee; HPLC analysis: chiral column: chiralcel
OD; eluent: hexane/i-PrOH, 95:05; ¯ow rate: 0.5 mL/min;
retention times: 11.68 (major) and 13.29 (minor) min.
ꢀprop-2-yn-1-yloxy)propanoate
{ꢀ2)-4c}.
We thank CSIR (New Delhi) for funding this project. We
also thank the UGC (New Delhi) for the Special Assistance
Program in Organic Chemistry in the School of Chemistry,
University of Hyderabad, Hyderabad. N. K., D. S. S. thank
UGC (New Delhi) and R. M. R. thanks CSIR (New Delhi)
for research fellowship.
20
1.3.4. ꢀ2)-Methyl 3-ꢀ4-ethylphenyl)-2-methylene-3-
ꢀprop-2-yn-1-yloxy)propanoate {ꢀ2)-4d}. Colorless
20
viscous liquid. Yield: 32%; [a]D ˆ274.91 (c 0.606,
CHCl3); 35% ee; HPLC analysis: chiral column: chiralcel
OD; eluent: hexane/i-PrOH, 95:05; ¯ow rate: 0.5 mL/min;
retention times: 9.47 (major) and 11.19 (minor) min.
References
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1.3.5. ꢀ2)-Methyl 3-ꢀ4-isopropylphenyl)-2-methylene-3-
ꢀprop-2-yn-1-yloxy)propanoate
2. Basavaiah, D.; Dharma Rao, P.; Suguna Hyma, R. Tetrahedron
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{ꢀ2)-4e}.
Colorless
20
viscous liquid. Yield: 36%; [a]D ˆ281.59 (c 0.516,
CHCl3); 40% ee; HPLC analysis: chiral column: chiralcel
OD; eluent: hexane/i-PrOH, 95:05; ¯ow rate: 0.5 mL/min;
retention times: 9.11 (major) and 11.04 (minor) min.
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20
Yield: 35%; mp72±73 8C; [a]D ˆ258.06 (c 0.632,
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8172
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1
comparison of chemical shift value of b-vinylic proton in H
NMR spectrum with that of methyl (2Z)-2-(bromomethyl)-3-
phenylprop-2-enoate-DABCO salt.11 In the case of methyl
(2Z)-2-(bromomethyl)-3-phenylprop-2-enoate-DABCO salt,
the b-vinylic proton cis to the ester group appears at d 8.40
(E-isomer) whereas the b-vinylic proton trans to the ester
group appears at d 7.98 (Z-isomer).31 In the case of 10a, the
b-vinylic proton appears at d 8.47. Therefore, we have
assigned (E)-stereochemistry to 10a. 13C NMR spectrum of
this crystallized salt (10a) shows the absence of any (Z)-
isomer.
16. Mikami, K.; Kishi, N.; Nakai, T. Chem.Lett. 1989, 1683±
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major compound is (E)-isomer (<85%). Spectral analysis also
indicates the presence of <15% impurities in which presum-
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