The Baylis-Hillman chemistry in aqueous media: Elucidation of mechanism for synthesis of ether side-product leads to an efficient approach to C-O bond formation

Article abstract of DOI:10.1016/S0040-4020(02)01561-2

The formation of an ether from the Baylis-Hillman (BH) adduct during the BH reaction of 5-isoxazolecarboxaldehydes is a common phenomenon if the reaction is allowed to proceed for longer periods. The amount of formation of such ethers depends on the acryl

Full text of DOI:10.1016/S0040-4020(02)01561-2

Tetrahedron 59 (2003) 663–670
The Baylis–Hillman chemistry in aqueous media:
elucidation of mechanism for synthesis of ether side-product
leads to an efficient approach to C–O bond formationq
a
A. Patra,a A. K. Roy,a B. S. Joshi,b R. Roy,b S. Batraa and A. P. Bhaduri
,
*
aMedicinal Chemistry Division, Central Drug Research Institute, Lucknow 226001, India
bRSIC Division, Central Drug Research Institute, Lucknow 226001, India
Received 13 August 2002; revised 5 November 2002; accepted 28 November 2002
Abstract—The formation of an ether from the Baylis–Hillman (BH) adduct during the BH reaction of 5-isoxazolecarboxaldehydes is a
common phenomenon if the reaction is allowed to proceed for longer periods. The amount of formation of such ethers depends on the
acrylates used and is most significant for tert-butyl acrylates. A study of the plausible mechanism for the formation of these side-products led
to reactions of acetates of BH adducts with phenol in aqueous media to yield the corresponding 3-phenoxy alk-2-enoates in good yields. The
successful translation of solution phase methodology to solid phase for application towards combinatorial chemistry is discussed. q 2003
Elsevier Science Ltd. All rights reserved.
The Baylis–Hillman (BH) reaction1–4 continues to draw
enormous attention from various research groups as it leads
to multifunctional derivatives, which have been success-
fully translated into a wide spectrum of synthetically
important molecules.5–12 This carbon–carbon bond form-
ing reaction in general involves the reaction between an
aldehyde and an electron deficient alkene in the presence of
a tertiary amine or Lewis acid. Recently, work towards
variation of typical BH reactions has also been
reported.13–16 However as the typical BH reaction is
marked by an exceptionally slow rate of reaction and
limited choice of substrates, most of the recent publications
have focused on these aspects thereby generating new
knowledge.17–24 The reaction rates could be increased by
the use of either physical methods such as increased
pressure,25 microwave26 or ultrasound27 or by using mixture
of Lewis acid with a wide variety of additives.28–32 Despite
various means discovered to accelerate this reaction,
research groups are still probing new conditions and
recently Rayner et al.33 have shown that through the use
of supercritical carbon dioxide in conjunction with high
pressure under neat conditions, the reaction is accelerated
appreciably. In this communication they also reported the
unprecedented formation of ethers between the BH adducts
as a side product. Simultaneously, Basavaiah et al.34 also
reported the tandem C–C and C–O bond formation during
the BH reaction of aldehydes and acrylonitrile left for more
than 8 days. Our interest in the BH reaction relates to
identification of 5-isoxazolecarboxaldehyde as a very fast
reacting substrate, which easily helps us in studying the
various aspects of this reaction.35–37 In our continued
efforts to study the synthetic and mechanistic details of BH
reaction of 5-isoxazolecarboxaldehydes, we have observed
that if the reactions of this substrate with acrylates in the
presence of DABCO are left for longer periods (ca. 2–10 h),
another significant product starts appearing in the reaction
mixture. Earlier since we were working up our reactions
within 20–30 min, we did not observe the formation of any
other product (as mentioned in our earlier publication36).
The formation of ethers from 5-isoxazolecarboxaldehydes
under conventional conditions is therefore in contrast to
reports of Rayner et al. or Basavaiah et al. where these
products were obtained only under extreme conditions or on
continuing the reaction for a long duration, respectively.
During studies on the mechanistic details towards the
formation of ethers, we discovered that phenol reacts with
acetates of BH adducts under aqueous conditions leading to
the corresponding 3-phenoxy alk-2-enoates in good yields.
With a view of expanding the scope of this methodology to
combinatorial synthesis we have also successfully carried
out these reactions on solid phase. The details of our studies
are presented herein.
q CDRI Communication No. 6308.
All the BH reactions of 5-isoxazolecarboxaldehydes (1)
were realized as reported earlier.11 However instead of
working them up on completion, these reactions were
allowed to continue further for 2–10 h. In all these reactions
Keywords: Baylis–Hillman reaction; 5-isoxazolecarboxaldehyde; phenol;
3-phenoxy alk-2-enoates; solid phase.
*
Corresponding author. Tel: þ91-522-212411-18x4368; fax: þ91-522-
223405/223938; e-mail: batra_san@yahoo.co.uk
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01561-2

664
A. Patra et al. / Tetrahedron 59 (2003) 663–670
formation of such ethers even when DMSO or DMF were
used as solvent.
The plausible mechanism for the formation of the ethers is
shown in Figure 1. To explain the formation of ethers, we
presume that the reaction may be proceeding through SN20
mechanism via the intermediate III. This intermediate (III)
may act as Michael acceptor while the hydroxyl group of the
BH adduct act as nucleophile to furnish the ether. In
principle such intermediate could also be obtained from the
acetate of the BH adduct in the presence of DABCO which
could then undergo nucleophilic addition to yield the ether.
This hypothesis led us to carry out the reaction of an acetate
of the BH adduct with its corresponding adduct in the
presence of DABCO in aqueous THF. However, we could
not obtain the ether through this route. It could also be
envisaged that if such an ether results through dehydration
of the two BH adducts, then the reaction could proceed in
the presence of various dehydrating agents such as
molecular sieves, phosphorus pentoxide, boron trifluoride
etherate or phosphorus tribromide, but in our hands none of
these reagents were successful. In addition to these attempts,
leaving the BH adducts in DABCO for the period in which
the ether was formed also did not yield any positive results.
Further reaction of acetates with 4-nitrobenzyl alcohol or
4-methoxy benzyl alcohol in the presence of DABCO in
aqueous media were also unsuccessful. Thus, unlike the
earlier reports34,35 we failed to obtain ethers from BH
adducts. In light of these observations we presume that the
plausible mechanism for the formation of the ether could be
as shown in Figure 2. The second step (first step being the
formation of a complex between the alkene and DABCO) in
the usual mechanism of the BH reaction furnishes the
intermediate IV that could be the actual nucleophilic
species, which attacks the intermediate III leading to the
Scheme 1. For R and R0 refer to Table 1.
we observed the formation of a non-polar compound (2a–f,
4e, 6d, 8b) in addition to the usual adduct (3a–f, 5e, 7d, 9b)
which could be easily isolated through column chroma-
tography (Scheme 1). The detailed spectroscopic analysis
coupled with HMQC and HMBC studies of these products
led to the conclusion that they are dimeric structures having
an ether linkage. It was interesting to note that the formation
and yields of the ethers depended on the type of acrylate
employed. In the case of tert-butyl acrylate, such ethers
were obtained in appreciable amounts (4–13%); but in the
case of n-butyl, ethyl or methyl acrylate the yields were
restricted to 1–2% only. The HPLC analysis of these ethers
gave single peak at lmax¼220 nm having retention time
between 16–18 min (depending on the acrylate used) in an
isocratic system on an RP-18 column (3.9£300 mm) using
acetonitrile/water (70:30, v/v) at a flow rate of 0.7 mL/min
for 35 min. However, from the 1H NMR spectra we
observed that except for ethers 2a and 2b, which were
obtained almost as single diastereoisomer, rest of the
compounds existed as approximately 1:1 mixture of meso
and dl diastereoisomers. This observation was confirmed
through repeated experiments. Though at this point of time
it is difficult to explain this finding, but this could be due to
the steric bulk on the phenyl group of the isoxazole moiety.
In contrast to the report of Rayner et al., we observed the
Figure 1.
Figure 2.

A. Patra et al. / Tetrahedron 59 (2003) 663–670
665
Scheme 2.
Table 1. Yields and physical state of reported compounds
Compd. no.
R
R0
Yield (%)
Mp (8C)
173–175 (white)
145–146 (white)
102–104 (white)
Low melting sticky solid (pale yellow)
107–109 (pale yellow)
107–109 (pale yellow)
78–80 (white)
155–156 (white)
79–80 (white)
75–76 (pale yellow)
Oil (pale yellow)
Oil (yellow)
Oil (pale yellow)
Oil (pale yellow)
128–129 (white)
89–90 (white)
128–130 (white)
95–96 (white)
75–76 (white)
2a
2b
2c
2d
2e
2f
3a
3b
3c
3d
3e
3f
4e
5e
6d
3-Phenylisoxazol-5-yl
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
n-Bu
n-Bu
Et
7 (9:1)a
13b
6 (1:1)a
4 (1:1)a
5 (1:1)a
5 (1:1)a
64
64
72
64
68
3-(4-Methylphenyl)isoxazol-5-yl
3-(2-Benzyloxyphenyl)isoxazol-5-yl
3-(4-Chlorophenyl)isoxazol-5-yl
3-(2-Chlorophenyl)isoxazol-5-yl
3-(2,4-Dichlorophenyl)isoxazol-5-yl
3-Phenylisoxazol-5-yl
3-(4-Methylphenyl)isoxazol-5-yl
3-(2-Benzyloxyphenyl)isoxazol-5-yl
3-(4-Chlorophenyl)isoxazol-5-yl
3-(2-Chlorophenyl)isoxazol-5-yl
3-(2, 4-Dichlorophenyl)isoxazol-5-yl
3-(2-Chlorophenyl)isoxazol-5-yl
3-(2-Chlorophenyl)isoxazol-5-yl
3-(4-Chlorophenyl)isoxazol-5-yl
3-(4-Chlorophenyl)isoxazol-5-yl
3-(4-Methylphenyl)isoxazol-5-yl
3-(4-Methylphenyl)isoxazol-5-yl
3-(4-Methylphenyl)isoxazol-5-yl
3-Nitrophenyl
61
1.5 (1:1)a
71
1 (1:1)a
72
7d
8b
9b
Et
Me
Me
t-Bu
t-Bu
t-Bu
t-Bu
n-Bu
n-Bu
n-Bu
n-Bu
Et
1 (1:1)a
82
79
10b
10g
10h
10i
11b
11g
11h
11i
12b
12g
12h
12i
12b
12g
12h
12i
14b
14g
14h
14i
15b
15g
15h
15i
16b
16g
16h
16i
17b
17g
17h
17i
22a
22b
22e
22f
22g
71
82
76
78
71
74
88
69
68
69
74
83
73
ND
71
86
81
88
89
83
93
83
85
86
86
91
82
87
89
ND
90
Oil (yellow)
4-Nitrophenyl
Oil (pale yellow)
Oil (pale yellow)
Oil (pale yellow)
Oil (pale yellow)
Oil (pale yellow)
Oil (colourless)
Oil (colourless)
Oil (pale yellow)
Oil (pale yellow)
Oil (pale yellow)
Oil (pale yellow)
Oil (pale yellow)
–
Oil (pale yellow)
Oil (colourless)
Oil (pale yellow)
Oil (pale yellow)
Oil (colourless)
Oil (pale yellow)
Oil (pale yellow)
72–74 (pale yellow)
Oil (colourless)
Oil (pale yellow)
Oil (pale yellow)
100–101 (pale yellow)
62–63 (colourless)
Oil (pale yellow)
Oil (pale yellow)
–
4-Trifluoromethylphenyl
3-(4-Methylphenyl)isoxazol-5-yl
3-Nitrophenyl
4-Nitrophenyl
4-Trifluoromethylphenyl
3-(4-Methylphenyl)isoxazol-5-yl
3-Nitrophenyl
Et
Et
Et
4-Nitrophenyl
4-Trifluoromethylphenyl
3-(4-Methylphenyl)isoxazol-5-yl
3-Nitrophenyl
Me
Me
Me
Me
t-Bu
t-Bu
t-Bu
t-Bu
n-Bu
n-Bu
n-Bu
n-Bu
Et
Et
Et
Et
Me
Me
Me
Me
–
4-Nitrophenyl
4-Trifluoromethylphenyl
3-(4-Methylphenyl)isoxazol-5-yl
3-Nitrophenyl
4-Nitrophenyl
4-Trifluoromethylphenyl
3-(4-Methylphenyl)isoxazol-5-yl
3-Nitrophenyl
4-Nitrophenyl
4-Trifluoromethylphenyl
3-(4-Methylphenyl)isoxazol-5-yl
3-Nitrophenyl
4-Nitrophenyl
4-Trifluoromethylphenyl
3-(4-Methylphenyl)isoxazol-5-yl
3-Nitrophenyl
4-Nitrophenyl
4-Trifluoromethylphenyl
3-Phenylisoxazol-5-yl
3-(4-Methylphenyl)isoxazol-5-yl
3-(2-Chlorophenyl)isoxazol-5-yl
3-(2, 4-Dichlorophenyl)isoxazol-5-yl
3-Nitrophenyl
Low melting solid
Oil (colourless)
120–122
Oil (colourless)
Oil (colourless)
126–127 (pale yellow)
25 (62)c
31 (71)c
23 (56)c
27 (66)c
25 (62)c
–
–
–
–
a
Ratio of meso and C-2 symmetrical diastereoisomers through 1H NMR.
Exist as single diastereoisomer.
Yields of pure product after column chromatography. Figure in parentheses is the respective purity based on analytical HPLC of the crude product.
b
c

666
A. Patra et al. / Tetrahedron 59 (2003) 663–670
i.DABCO,
AcCl, DIEA,
THF:H20
DABCO,
DMSO
TFA: DCM
(50: 50)
O
DCM
ii.PhOH
O
R1CHO
O
R1
O
R1
R1
HO
R1
+
r.t., 3h
r.t., 17h
r.t., 6h
O
1h
O
O
OAc
O
OH
OPh
O
OPh
18
1a-b,e-g
19a-b,e-g
22a-b,e-g
20a-b,e-g
21a-b,e-g
Scheme 3.
ether. It is quite likely that as the formation of the
nucleophilic species IV is not possible during the reaction
between acetate with its corresponding BH adduct under
conventional reaction conditions, we failed in our attempts
to obtain ether from the BH adduct. However, it can be
added here that under extreme conditions,33 the hydroxyl
group of BH adduct might act as nucleophile as shown in
Figure 1.
diversity option at position 3 in propionic acid derivatives
(BH adducts) for the generation of chemical libraries.
1. Experimental
1.1. General
Melting points are uncorrected and were determined in
capillary tubes on a hot stage apparatus containing silicon
oil. IR spectra were recorded using Perkin Elmer’s
Nevertheless, we reasoned that if the hydroxyl group of the
BH adducts or substituted benzyl alcohols are not strong
enough a nucleophile to undergo addition to the inter-
mediate III, some stronger and stable nucleophile such
as phenoxide ion might yield such ethers. Therefore, we
carried out the reactions of acetates with phenol in the
presence of DABCO in THF/water and as envisioned, the
reactions were complete within a few minutes. A careful
survey of the literature indicated that the addition of phenols
has earlier been reported directly on BH adduct38 or on
acetates39 and bromo-derivatives40 of BH adducts. The
direct addition under Mitsunobu conditions leads to addition
of phenols on the double bond.38 On the other hand, the
addition of phenols to bromo-derivatives of BH adducts
gave similar products40 as ours in the presence of Et3N,
while acetates in the presence of Pd0 and/or KF/alumina
gave similar product or a mixture of products depending
upon conditions.39 Thus we have for the first time
discovered an efficient approach towards the synthesis of
3-phenoxy prop-2-enoates from acetates of BH adducts in
aqueous media. To show the general applicability of this
reaction we have carried out the reaction with wide variety
of substrates (Scheme 2, Table 1).
1
Spectrum RX I FTIR spectrophotometer. H NMR spectra
were recorded either on a Bruker Avance DRX-300 or
Bruker DPX-200 FT spectrometers, using TMS as an
internal standard (chemical shifts in d values, J in Hz). The
FABMS were recorded on JEOL/ SX-102 spectrometers
and ESMS were recorded through direct flow injections in
Merck M-8000 LCMS system. Elemental analyses were
1
performed on a Carlo Erba 1108 microanalyzer. The H
NMR of compounds 2a–f, 4e, 6d, 8b is being reported as
diastereoisomeric mixture. The reaction of 4-nitro benz-
aldehyde with methyl acrylate was not carried out; there-
fore, there is no corresponding spectroscopic detail for
compound 17h. For spectroscopic data of BH adducts of
5-isoxazolecarboxaldehydes see Ref. 36. However, the data
for the unreported BH adducts (3d, 3f, 7d) is being provided
here.
1.2. General procedure for BH reaction
To a mixture of DABCO (0.056 g, 0.5 mmol) and appro-
priate alkene (10 mmol) that had been stirred at rt for 20 min
was added appropriate aldehyde from 1a–f (10 mmol)
under stirring and the reaction was allowed to proceed for a
period for 2 h in case of tert-butyl acrylate while 8–10 h in
other cases. Thereafter 5% aq. HCl soln. was added to the
reaction mixture to neutralize the base and extracted with
ethyl acetate (2£100 mL).The organic layers were com-
bined, washed with brine (100 mL), dried (Na2SO4) and
evaporated under vacuum to yield an oily residue. The
residue was purified by column chromatography over silica
gel (230–400 mesh) using hexanes/ethyl acetate as eluent.
Elution with 90:10, v/v mixture furnished the ethers (2a–f,
4e, 6d, 8b) while further elution with 70:30 v/v mixture
gave the BH adducts (3a–f, 5e, 7d, 9b). The ethers were
recrystallized from methanol.
With an objective to expand the scope and utility of this
reaction towards combinatorial chemistry we have also
successfully translated this methodology to solid phase
(Scheme 3). The acrylate resin obtained by reaction of
Wang resin with acryloyl chloride,41 was subjected to BH
reaction with various 3-substituted phenyl-5-isoxazole-
carboxaldehydes in parallel format to obtain the BH adducts
(19a,b,e–g). This was followed by conversion of the
hydroxyl group to the corresponding acetate derivatives
(20a,b,e–g). The formation of acetate was confirmed by
on-bead FTIR. Further reaction of acetates (20a,b,e–g) with
phenol in THF/water and final cleavage of resins furnished
the products (22a,b,e–g).
Thus in conclusion, the elucidation of mechanism of the
formation of the ether, which is not an unusual phenomenon
in the case of 5-isoxazolecarboxaldehydes, has led to an
easy access to 3-phenoxy prop-2-enoates from acetates of
BH adducts. The solution phase methodology has also been
successfully translated to the solid phase for the use in
combinatorial chemistry. This will provide an additional
1.2.1. 2-[[2-tert-Butoxycarbonyl-1-(3-phenyl-isoxazol-5-
yl)-allyloxy]-(3-phenyl-isoxazol-5-yl)-methyl]-acrylic
acid tert-butyl ester (2a). [Found C, 69.65; H, 6.18; N,
5.18. C34H36N2O7 requires C, 69.84; H, 6.20; N, 4.79%];
nmax (KBr) 1701 (CO2Bu-t) cm21; dH (300 MHz, CDCl3)
1.41 (s, 18H, 2£(CH3)3), 1.44 (s, 18H, 2£(CH3)3), 5.63 (s,
2H, 2£OCH), 5.66 (s, 2H, 2£1H of CH2), 6.10 (s, 2H, 2£1H

A. Patra et al. / Tetrahedron 59 (2003) 663–670
667
of CH2), 6.23 (s, 2H, 2£1H of CH2), 6.52 (s, 2H, 2£1H of
CH2), 6.54 (s, 4H, 4£CH), 7.41–7.42 (m, 6H, Ar-H), 7.43–
7.46 (m, 6H, Ar-H), 7.69–7.74 (m, 4H, Ar-H), 7.78–7.81
(m, 4H, Ar-H); dC NMR (75.4 MHz) 27.9 (CH3), 70.1 (CH),
82.0 (C), 101.2 (CH), 126.8 (CH), 127.3 (CH2), 130.1
(CH), 138.1 (C), 162.3 (C), 163.8 (C), 170.4 (C); Mass
(FABMSþ) m/z % 585 (Mþþ1).
2£OCH), 6.10 (s, 2H, 2£1H of CH2), 6.23 (s, 2H, 2£1H of
CH2), 6.49 (s, 2H, 2£1H of CH2), 6.52 (s, 2H, 2£1H of
CH2), 6.64 (s, 2H, 2£CH), 6.66 (s, 2H, 2£CH), 7.27–7.70
(m, 12H, Ar-H); Mass (ESMSþ) m/z % 745.93 (MþþNa).
1.2.7. 2-{[3-(4-Chloro-phenyl)-isoxazol-5-yl]-hydroxy-
methyl}-acrylic acid tert-butyl ester (3d). [Found C,
60.57; H, 5.20; N, 4.01. C17H18ClNO4 requires C, 60.81;
H, 5.40; N, 4.17%]; nmax (KBr) 1707 (CO2Bu-t) cm21; dH
(200 MHz, CDCl3) 1.47 (s, 9H, 2£(CH3)3), 5.62 (s, 1H,
OCH), 6.01 (s, 1H, 1H of CH2), 6.44 (s, 1H, 1H of CH2),
6.58 (s, 1H, CH), 7.42 (d, 2H, J¼8.0 Hz, Ar-H), 7.73 (d, 2H,
J¼8.0 Hz, Ar-H); Mass (FABMSþ) m/z % 336 (Mþþ1).
1.2.2. 2-[[2-tert-Butoxycarbonyl-1-(3-(4-methyl-phenyl)-
isoxazol-5-yl)-allyloxy]-(3-(4-methyl-phenyl)-isoxazol-5-
yl)-methyl]-acrylic acid tert-butyl ester (2b). Obtained as
single diastereoisomer; [Found C, 68.65; H, 6.48; N, 4.17.
C36H40N2O7.H2O requires C, 68.55; H, 6.71; N, 4.44%];
nmax (KBr) 1701 (CO2Bu-t) cm21; dH (300 MHz, CDCl3)
1.40 (s, 18H, 2£(CH3)3), 2.39 (s, 6H, 2£CH3), 5.61 (s, 2H,
2£OCH), 6.22 (s, 2H, 2£1H of CH2), 6.50 (s, 4H, 2£1H of
CH2 and 2£CH), 7.24 (d, 4H, J¼8.0 Hz, Ar-H), 7.67 (d, 4H,
J¼8.0 Hz, Ar-H); Mass (FABMSþ) m/z % 613 (Mþþ1).
1.2.8. 2-{[3-(2,4-Dichloro-phenyl)-isoxazol-5-yl]-hydroxy-
methyl}-acrylic acid tert-butyl ester (3f). [Found C, 54.87;
H, 4.92; N, 3.81. C17H17Cl2NO4 requires C, 55.15; H, 4.63;
N, 3.78%]; nmax (neat) 1713 (CO2Bu-t) cm21; dH (200 MHz,
CDCl3) 1.45 (s, 9H, 2£(CH3)3), 3.63 (d, 1H, J¼8.0 Hz, OH),
5.69 (d, 1H, J¼8.0 Hz, OCH), 6.02 (s, 1H, 1H of CH2), 6.46
(s, 1H, 1H of CH2), 6.72 (s, 1H, CH), 7.33 (dd, 1H, J1¼2.0 Hz,
J2¼8.0 Hz, Ar-H), 7.51 (d, 1H, J¼2.0 Hz, Ar-H), 7.68 (d,
2H, J¼8.0 Hz, Ar-H); Mass (FABMSþ) m/z % 371 (Mþþ1).
1.2.3. 2-([3-(4-Benzyloxy-phenyl)-isoxazol-5-yl]-{1-[3-(4-
benzyloxy-phenyl)-isoxazol-5-yl]-2-tert-butoxycarbonyl-
allyloxy}-methyl)-acrylic acid tert-butyl ester (2c).
[Found C, 72.65; H, 6.18; N, 3.62. C48H48N2O9 requires
C, 72.34; H, 6.07; N, 3.52%]; nmax (KBr) 1705 (CO2Bu-t)
cm21; dH (300 MHz, CDCl3) 1.32 (s, 18H, 2£(CH3)3), 1.35
(s, 18H, 2£(CH3)3), 5.01–5.04 (m, 8H, 4£OCH2), 5.52 (s,
2H, 2£OCH), 5.56 (s, 2H, 2£OCH), 6.03 (s, 2H, 2£1H of
CH2), 6.14 (s, 2H, 2£1H of CH2), 6.35–6.421 (m, 8H, 4£1H
of CH2 and 4£CH), 6.88–7.01 (m, 8H, Ar-H), 7.34 (brs,
20H, Ar-H), 7.55–7.71 (m, 8H, Ar-H); Mass (FABMSþ)
m/z % 797 (Mþþ1).
1.2.9. 2-{{2-Butoxycarbonyl-1-[3-(2-chloro-phenyl)-iso-
xazol-5-yl]-allyloxy}-[3-(2-chloro-phenyl)-isoxazol-5-yl]-
methyl}-acrylic acid butyl ester (4e). [Found C, 62.65; H,
5.18; N, 4.56. C34H34Cl2N2O7 requires C, 62.48; H, 5.24; N,
4.29%]; nmax (neat) 1719 (CO2Bu-n) cm21; dH (200 MHz,
CDCl3) 0.86–0.93 (m, 12H, 4£CH3), 1.25–1.37 (m, 8H,
4£CH2), 1.57–1.64 (m, 8H, 4£CH2), 4.12–4.19 (m, 8H,
4£CH2), 5.71 (s, 2H, 2£OCH), 5.75 (s, 2H, 2£OCH), 6.19
(s, 2H, 2£1H of CH2), 6.35 (s, 2H, 2£1H of CH2), 6.60 (s,
2H, 2£1H of CH2), 6.63 (s, 2H, 2£1H of CH2), 6.71 (s, 4H,
4£CH), 7.30–7.47 (m, 12H, 4£3Ar-H), 7.70–7.79 (m, 4H,
4£1 Ar-H); Mass (ESMSþ) m/z % 676.93 (MþþNa).
1.2.4. 2-{{2-tert-Butoxycarbonyl-1-[3-(4-chloro-phenyl)-
isoxazol-5-yl]-allyloxy}-[3-(4-chloro-phenyl)-isoxazol-5-
yl]-methyl}-acrylic acid tert-butyl ester (2d). [Found C,
62.65; H, 5.18; N, 4.62. C34H34Cl2N2O7 requires C, 62.48;
H, 5.24; N, 4.29%]; nmax (Neat) 1706 (CO2Bu-t) cm21; dH
(200 MHz, CDCl3) 1.41 (m, 18H, 2£(CH3)3), 1.43 (m, 18H,
2£(CH3)3), 5.62 (s, 2H, 2£OCH), 5. 65 (s, 2H, 2£OCH),
6.11 (s, 2H, 2£1H of CH2), 6.21 (s, 2H, 2£1H of CH2),
6.44–6.51 (m, 8H, 4£1H of CH2 and 4£CH), 7.33–7.45 (m,
8H, Ar-H), 7.60–7.74 (m, 8H, Ar-H); Mass (ESMSþ) m/z
% 676.53 (MþþNa).
1.2.10. 2-([3-(4-Chloro-phenyl)-isoxazol-5-yl]-{1-[3-(4-
chloro-phenyl)-isoxazol-5-yl]-2-ethoxycarbonyl-allyl-
oxy}-methyl)-acrylic acid ethyl ester (6d). [Found C,
60.65; H, 4.18; N, 5.02. C30H26Cl2N2O7 requires C, 60.31;
H, 4.39; N, 4.69%]; nmax (KBr) 1709 (CO2Et) cm21; dH
(200 MHz, CDCl3) 1.21–1.33 (m, 12H, 4£CH3), 4.13–4.24
(m, 8H, 4£CH2), 5.54 (s, 2H, 2£OCH), 5.67 (s, 2H,
2£OCH), 6.32 (s, 2H, 2£1H of CH2), 6.53 (s, 2H, 2£1H of
CH2), 6.61 (s, 2H, 2£1H of CH2), 6.73 (s, 2H, 2£1H of
CH2), 7.26 (s, 2H, 2£CH), 7.30 (s, 2H, 2£CH), 7.40–7.48
(m, 8H, Ar-H), 7.70–7.79 (m, 8H, 2£4Ar-H); Mass
(FABMSþ) m/z % 597 (Mþþ1).
1.2.5. 2-{{2-tert-Butoxycarbonyl-1-[3-(2-chloro-phenyl)-
isoxazol-5-yl]-allyloxy}-[3-(2-chloro-phenyl)-isoxazol-5-
yl]-methyl}-acrylic acid tert-butyl ester (2e). [Found C,
62.41; H, 5.08; N, 4.33. C34H34Cl2N2O7 requires C, 62.48;
H, 5.24; N, 4.29%]; nmax (KBr) 1698 (CO2Bu-t) cm21; dH
(300 MHz, CDCl3), 1.42 (s, 18H, 2£(CH3)3), 1.44 (s, 18H,
2£(CH3)3), 5.58 (s, 2H, 2£OCH), 5. 62 (s, 2H, 2£OCH),
6.03 (s, 2H, 2£1H of CH2), 6.18 (s, 2H, 2£1H of CH2), 6.43
(s, 2H, 2£1H of CH2), 6.45 (s, 2H, 2£1H of CH2), 6.60 (m,
4H, 4£CH), 7.33–7.45 (m, 12H, Ar-H), 7.60–7.64 (m, 4H,
Ar-H); Mass (FABMSþ) m/z % 653 (Mþþ1).
1.2.11. 2-{[3-(4-Chloro-phenyl)-isoxazol-5-yl]-hydroxy-
methyl}-acrylic acid ethyl ester (7d). [Found C, 58.87;
H, 4.20; N, 4.69. C15H14ClNO4 requires C, 58.55; H, 4.59;
N, 4.55%]; nmax (KBr) 1714 (CO2Et) cm21; dH (200 MHz,
CDCl3) 1.27 (t, 3H, J¼7.2 Hz, CH3), 4.11 (q, 2H, J¼7.2 Hz,
CH3), 5.87 (s, 1H, OCH), 6.17 (s, 1H, 1H of CH2), 6.46 (s,
1H, 1H of CH2), 6.59 (s, 1H, CH), 7.33 (d, 2H, J¼8 0 Hz,
Ar-H), 7.65 (d, 2H, J¼8.0 Hz, Ar-H); Mass (FABMSþ) m/z
% 308 (Mþþ1).
1.2.6. 2-{{2-tert-Butoxycarbonyl-1-[3-(2,4-dichloro-phenyl)-
isoxazol-5-yl]-allyloxy}-[3-(2,4-dichloro-phenyl)-isoxa-
zol-5-yl]-methyl}-acrylic acid tert-butyl ester (2f). [Found
C, 56.89; H, 4.25; N, 3.62. C34H32Cl4N2O7 requires C,
56.52; H, 4.46; N, 3.87%]; nmax (KBr) 1698 (CO2Bu-t)
cm21; dH (200 MHz, CDCl3) 1.42 (s, 18H, 2£(CH3)3), 1.44
(s, 18H, 2£(CH3)3), 5.65 (s, 2H, 2£OCH), 5. 68 (s, 2H,
1.2.12. 2-[[2-Methoxycarbonyl-1-(3-(4-methyl-phenyl)-
isoxazol-5-yl)-allyloxy]-(3-(4-methyl-phenyl)-isoxazol-5-
yl)-methyl]-acrylic acid methyl ester (8b). [Found C,

668
A. Patra et al. / Tetrahedron 59 (2003) 663–670
68.36; H, 5.17; N, 5.55. C30H28N2O7 requires C, 68.17; H,
5.34; N, 5.30%]; nmax (KBr) 1719 (CO2Me) cm21; dH
(300 MHz, CDCl3) 2.40 (s, 12H, 4£CH3), 3.76 (s, 6H,
2£CO2CH3), 3.86 (s, 6H, 2£CO2CH3), 5.66 (s, 2H,
2£OCH), 5.69 (s, 2H, 2£OCH), 6.10 (s, 2H, 2£1H of
CH2), 6.13 (s, 2H, 2£1H of CH2), 6.54 (s, 2H, 2£1H of
CH2), 6.61 (s, 2H, 2£1H of CH2), 6.73 (s, 2H, 2£1H of
CH2), 7.00 (s, 2H, 2£CH), 7.15 (s, 2H, 2£CH), 7.22–7.35
(m, 8H, Ar-H), 7.67–7.77 (m, 8H, Ar-H); Mass (ESMSþ)
m/z % 551.67 (MþþNa).
1712 (CO2Bu-t) cm21; dH (200 MHz, CDCl3) 1.43 (s, 9H,
C(CH3)3), 5.85 (s, 1H, OCH), 6.14 (s, 1H, 1H of CH2), 6.32
(s, 1H, 1H of CH2), 6.87–6.91 (m, 3H, Ar-H), 7.20–7.25 (t,
2H, Ar-H), 7.58 (s, 4H, Ar-H); Mass (ESMSþ) m/z % 401
(MþþNa).
1.4.5. 2-[Phenoxy-(3-(4-methyl phenyl)-isoxazol-5-yl)-
methyl]-acrylic acid butyl ester (15b). [Found: C, 73.85;
H, 6.48; N, 3.61. C24H25NO4 requires C, 73.63; H, 6.43; N,
3.57 %]; nmax (neat) 1706 (CO2Bu-n) cm21; dH (300 MHz,
CDCl3) 0.90 (t, 3H, J¼6.0 Hz, CH3), 1.26–1.38 (m, 2H,
CH2), 1.56–1.68 (m, 2H, CH2), 2.39 (s, 3H, CH3), 4.21 (q,
2H, J¼6.0 Hz, CH2), 6.16 (s, 1H, OCH), 6.34 (s, 1H, 1H of
CH2), 6.57 (s, 1H, 1H of CH2), 6.59 (s, 1H, CH), 6.82–6.96
(m, 3H, Ar-H), 7.22–7.32 (m, 5H, Ar-H), 7.67 (d, 2H,
J¼8.0 Hz, Ar-H); Mass (FABMSþ) m/z % 392 (Mþþ1).
1.3. General procedure for acetylation
As reported in Ref. 36.
1.4. General procedure for 3-phenoxy prop-2-enoates
To the solution of appropriate compound from 10–13b,g–i
(0.001 mol) in a mixture of THF/H2O (4 mL, 50:50 v/v) was
added DABCO (112 mg, 0.001 mol) under stirring at rt.
After 15 min. phenol (0.087 mL, 0.001 mol) was added and
the reaction was continued for 0.5–1.5 h. Thereafter, the
mixture was extracted with ethyl acetate (2£20 mL). The
organic layers were combined, dried (Na2SO4) and
evaporated to obtain an oily residue. To prepare an
analytical sample the residue was passed through a small
band of silica gel (60–120 mesh) using hexanes/ethyl
acetate (95:5, v/v). The pure 3-phenoxy prop-2-enoates
were obtained as solids or colourless oils.
1.4.6. 2-[(3-Nitro-phenyl)-phenoxy-methyl]-acrylic acid
butyl ester (15g). [Found: C, 67.84; H, 6.02; N, 4.13.
C20H21NO5 requires C, 67.59; H, 5.95; N, 3.94%]; nmax
(neat) 1716 (CO2Bu-n) cm21; dH (200 MHz, CDCl3) 0.90
(t, 3H, J¼7.2 Hz, CH3), 1.23–1.38 (m, 2H, CH2), 1.54–
1.68 (m, 2H, CH2), 4.16 (t, 2H, J¼6.6 Hz, CH2), 6.08 (s, 1H,
OCH), 6.22 (s, 1H, 1H of CH2), 6.46 (s, 1H, 1H of CH2),
6.89–6.99 (m, 3H, Ar-H), 7.21–7.29 (m, 2H, Ar-H), 7.51 (t,
1H, J¼8.0 Hz, Ar-H), 7.81 (d, 1H, J¼7.7 Hz, Ar-H), 8.15
(d, 2H, J¼8.0 Hz, Ar-H), 8.34 (s, 1H, Ar-H); Mass
(ESMSþ) m/z % 551.67 (MþþNa).
1.4.7. 2-[(4-Nitro-phenyl)-phenoxy-methyl]-acrylic acid
butyl ester (15h). [Found: C, 67.60; H, 5.89; N, 3.92.
C20H21NO5 requires C, 67.59; H, 5.95; N, 3.94%]; nmax
(KBr) 1700 (CO2Bu-n) cm21; dH (200 MHz, CDCl3) 0.90
(t, 3H, J¼7.2 Hz, CH3), 1.24–1.38 (m, 2H, –CH2), 1.55–
1.65 (m, 2H, CH2), 4.16 (t, 2H, J¼6.0 Hz, CH2), 6.04 (s, 1H,
OCH), 6.22 (s, 1H, 1H of CH2), 6.44 (s, 1H, 1H of CH2),
6.87–6.99 (m, 3H, Ar-H), 7.25–7.29 (m, 2H, Ar-H), 7.65
(d, 2H, J¼8.7 Hz, Ar-H), 8.20 (d, 2H, J¼8.7 Hz, Ar-H);
Mass (ESMSþ) m/z % 551.67 (MþþNa).
1.4.1. 2-[Phenoxy-(3-(4-methyl phenyl)-isoxazol-5-yl)-
methyl]-acrylic acid tert-butyl ester (14b). [Found: C,
73.59; H, 6.12; N, 3.77. C24H25NO4 requires C, 73.63; H,
6.43; N, 3.57%]; nmax (neat) 1705 (CO2Bu-t) cm21; dH
(300 MHz, CDCl3) 1.45 (s, 9H, C(CH3)3), 2.38 (s, 3H,
CH3), 6.05 (s, 1H, OCH), 6.28 (s, 1H, 1H of CH2), 6.47 (s,
1H, 1H of CH2), 6.81 (s, 1H, CH), 6.97–7.02 (m, 3H, Ar-H),
7.22–7.31 (m, 4H, Ar-H), 7.24 (d, 2H, J¼8.0 Hz, Ar-H),
7.67 (d, 2H, J¼8.0 Hz, Ar-H); Mass (FABMSþ) m/z % 392
(Mþþ1).
1.4.8. 2-[Phenoxy-(4-trifluoromethyl-phenyl)-methyl]-
acrylic acid butyl ester (15i). [Found: C, 66.87; H, 5.49.
C21H21F3O3 requires C, 66.66; H, 5.59%]; nmax (neat) 1715
(CO2Bu-n) cm21; dH (200 MHz, CDCl3) 0.89 (t, 3H,
J¼7.2 Hz, CH3), 1.25–1.36 (m, 2H, CH2), 1.55–1.63 (m,
2H, CH2), 4.16 (t, 2H, J¼6.6 Hz, CH2), 5.98 (s, 1H, OCH),
6.18 (s, 1H, 1H of CH2), 6.41 (s, 1H, 1H of CH2), 6.88–6.98
(m, 3H, Ar-H), 7.24–7.28 (m, 2H, Ar-H), 7.59 (s, 4H,
Ar-H); Mass (ESMSþ) m/z % 401.00 (MþþNa).
1.4.2. 2-[(3-Nitro-phenyl)-phenoxy-methyl]-acrylic acid
tert-butyl ester (14g). [Found: C, 67.51; H, 5.68; N, 4.15.
C20H21NO5 requires C, 67.59; H, 5.95; N, 3.94%]; nmax
(neat) 1708 (CO2Bu-t) cm21; dH (200 MHz, CDCl3) 1.44 (s,
9H, C(CH3)3), 5.95 (s, 1H, OCH), 6.17 (s, 1H, 1H of CH2),
6.36 (s, 1H, 1H of CH2), 6.84–6.95 (m, 3H, Ar-H), 7.23–
7.25 (m, 2H, Ar-H), 7.51 (t, 1H, J¼7.9 Hz, Ar-H), 7.81 (d,
1H, J¼7.7 Hz, Ar-H), 8.15 (d, 1H, J¼7.2 Hz, Ar-H), 8.33 (s,
1H, Ar-H); Mass (FABMSþ) m/z % 356 (Mþþ1).
1.4.9. 2-[Phenoxy-(3-(4-methyl phenyl)-isoxazol-5-yl)-
methyl]-acrylic acid ethyl ester (16b). [Found: C, 73.02;
H, 6.09; N, 3.66. C22H21NO4 requires C, 72.70; H, 5.82; N,
3.85%]; nmax (neat) 1714 (CO2Et) cm21; dH (200 MHz,
CDCl3) 1.28 (t, 3H, J¼7.2 Hz, CH3), 2.38 (s, 3H, CH3), 4.13
(q, 2H, J¼7.2 Hz, CH2), 6.07 (s, 1H, OCH), 6.19 (s, 1H, 1H
of CH2), 6.47 (s, 1H, 1H of CH2), 6.59 (s, 1H, CH), 6.82–
6.84 (m, 3H, Ar-H), 6.90–6.97 (m, 2H, Ar-H), 7.24 (d, 2H,
J¼8 0 Hz, Ar-H), 7.67 (d, 2H, J¼8.0 Hz, Ar-H); Mass
(FABMSþ) m/z % 364 (Mþþ1).
1.4.3. 2-[(4-Nitro-phenyl)-phenoxy-methyl]-acrylic acid
tert-butyl ester (14h). [Found: C, 67.41; H, 5.73; N, 4.10.
C20H21NO5 requires C, 67.59; H, 5.95; N, 3.94%]; nmax
(neat) 1713 (CO2Bu-t) cm21; dH (200 MHz, CDCl3) 1.43 (s,
9H, C(CH3)3), 5.91 (s, 1H, OCH), 6.17 (s, 1H, 1H of CH2),
6.34 (s, 1H, 1H of CH2), 6.87–6.91 (m, 3H, Ar-H), 7.21–
7.25 (m, 2H, Ar-H), 7.63 (d, 2H, J¼8.5 Hz, Ar-H), 8.20 (d,
2H, J¼8.5 Hz, Ar-H); Mass (FABMSþ) m/z % 356 (Mþþ1).
1.4.4. 2-[Phenoxy-(4-trifluoromethyl-phenyl)-methyl]-
acrylic acid tert-butyl ester (14i). [Found: C, 66.55; H,
5.82. C21H21F3O5 requires C, 66.66; H, 5.59%]; nmax (neat)
1.4.10. 2-[(3-Nitro-phenyl)-phenoxy-methyl]-acrylic acid
ethyl ester (16g). [Found: C, 66.14; H, 5.39; N, 3.92.

A. Patra et al. / Tetrahedron 59 (2003) 663–670
669
C18H17NO5 requires C, 66.04; H, 5.23; N, 4.27%]; nmax
(neat) 1714 (CO2Et) cm21; dH (200 MHz, CDCl3) 1.27 (t,
3H, J¼8.0 Hz, CH3), 4.22 (q, 2H, J¼8.0 Hz, CH2), 6.10 (s,
1H, OCH), 6.22 (s, 1H, 1H of CH2), 6.46 (s, 1H, 1H of CH2),
6.80–6.99 (m, 3H, Ar-H), 7.15–7.29 (m, 2H, Ar-H), 7.51 (t,
1H, J¼7.9 Hz, Ar-H), 7.81 (d, 1H, J¼8.0 Hz, Ar-H), 8.15
(d, 2H, J¼8.0 Hz, Ar-H), 8.34 (s, 1H, Ar-H); Mass
(FABMSþ) m/z % 328 (Mþþ1).
added and left for 15 min. Thereafter solution of different
aldehydes (1a–b,e–g) (5 equiv.) in 300 mL of DMSO was
added to respective RV and the reaction was shaken at
600 rpm. After 3 h (24 h for 1g) the resins were washed
using DMF (£3), MeOH (£3) and DCM (£2). To these RVs
was then added DCM (1 mL) followed by DIEA (10 equiv.)
and acetyl chloride (8 equiv.). The reaction mixture was
stirred for 17 h at rt and then washed with DCM (£2), THF/
H2O (1:1) (£2), THF (£2), MeOH (£2) and DCM (£2).
Further to this resin was added THF/H2O mixture (1 mL,
9.5:0.5, v/v) and DABCO (three folds). After shaking this
mixture for 15 min, phenol (10 equiv.) was added. The RVs
were shaken at 600 rpm for 6 h and washed with DMF (£2),
MeOH (£2), DCM (£3) and ether (£2). The resin was
finally cleaved with 50% TFA in DCM for 1 h, filtrate
evaporated and lyophilised using tert-butanol/H2O (4:1).
These products were purified through column chromatog-
raphy on silica gel using chloroform: methanol (98:2, v/v) to
obtain the final compounds (22a–b,e–g) in 23–31% yields.
1.4.11. 2-[(4-Nitro-phenyl)-phenoxy-methyl]-acrylic acid
ethyl ester (16h). [Found: C, 66.31; H, 5.28; N, 4.54.
C18H17NO5 requires C, 66.04; H, 5.23; N, 4.27%]; nmax
(KBr) 1699 (CO2Et) cm21; dH (200 MHz, CDCl3) 1.26 (t,
3H, J¼7.1 Hz, CH3), 4.29 (q, 2H, J¼7.1 Hz, CH2), 6.06 (s,
1H, OCH), 6.22 (s, 1H, 1H of CH2), 6.44 (s, 1H, 1H of CH2),
6.88–6.99 (m, 3H, Ar-H), 7.21–7.29 (m, 2H, Ar-H), 7.65
(d, 2H, J¼8.7 Hz, Ar-H), 8.20 (d, 2H, J¼8.7 Hz, Ar-H);
Mass (FABMSþ) m/z % 328 (Mþþ1).
1.4.12. 2-[Phenoxy-(4-trifluoromethyl-phenyl)-methyl]-
acrylic acid ethyl ester (16i). [Found: C, 65.37; H, 5.06.
C19H17F3O3 requires C, 65.14; H, 4.89%]; nmax (neat) 1705
(CO2Et) cm21; dH (200 MHz, CDCl3) 1.26 (t, 3H, J¼
7.2 Hz, CH3), 4.21 (q, 2H, J¼7.1 Hz, CH2), 6.00 (s, 1H,
OCH), 6.19 (s, 1H, 1H of CH2), 6.42 (s, 1H, 1H of CH2),
6.88–6.99 (m, 3H, Ar-H), 7.20–7.25 (m, 2H, Ar-H), 7.59
(s, 4H, Ar-H)); Mass (FABMSþ) m/z % 351 (Mþþ1).
1.5.1. 2-[Phenoxy-(3-phenyl-isoxazol-5-yl)-methyl]-
acrylic acid (22a). [Found C, 70.81; H, 4.65; N, 4.52.
C19H15NO4 requires C, 71.02; H, 4.71; N, 4.36%]; nmax
(neat) 1682 (CO2H) cm21; dH (200 MHz, DMSOd6) 5.99 (s,
1H, OCH), 6.21 (s, 1H, 1H of CH2), 6.36 (s, 1H, 1H of CH2),
6.61 (s, 1H, CH), 7.21–7.24 (m, 5H, Ar-H), 7.42–7.44 (m,
3H, Ar-H), 7.78–7.79 (m, 2H, Ar-H); Mass (FABMSþ) m/z
% 322 (Mþþ1).
1.4.13. 2-[Phenoxy-(3-(4-methyl phenyl)-isoxazol-5-yl)-
methyl]-acrylic acid methyl ester (17b). [Found: C, 71.96;
H, 5.61; N, 3.92. C21H19NO4 requires C, 72.19; H, 5.48; N,
4.01%]; nmax (neat) 1720 (CO2Me) cm21; dH (200 MHz,
CDCl3) 2.38 (s, 3H, CH3), 3.78 (s, 3H, CO2CH3), 6.06 (s,
1H, OCH), 6.12 (s, 1H, 1H of CH2), 6.34 (s, 1H, 1H of CH2),
6.56 (s, 1H, CH), 6.80–7.32 (m, 7H, Ar-H), 7.67 (d, 2H,
J¼8.0 Hz, Ar-H); Mass (FABMSþ) m/z % 350 (Mþþ1).
1.5.2. 2-[Phenoxy-(3-(4-methyl phenyl)-isoxazol-5-yl)-
methyl]-acrylic acid (22b). [Found C, 71.73; H, 4.99; N,
4.19. C20H17NO4 requires C, 71.63; H, 5.11; N, 4.18%];
n
max (KBr) 1697 (CO2H) cm21; dH (200 MHz, CDCl3) 2.38
(s, 3H, CH3), 6.31 (s, 1H, OCH), 6.33 (s, 1H, 1H of CH2),
6.58 (s, 1H, 1H of CH2), 6.69 (s, 1H, CH), 6.96–7.04 (m,
3H, Ar-H), 7.22–7.33 (m, 4H, Ar-H), 7.67 (d, 2H,
J¼8.0 Hz, Ar-H); Mass (FABMSþ) m/z % 336 (Mþþ1).
1.4.14. 2-[(3-Nitro-phenyl)-phenoxy-methyl]-acrylic acid
methyl ester (17g). [Found: C, 65.33; H, 5.12; N, 4.44.
C17H15NO5 requires C, 65.16; H, 4.85; N, 4.47%]; nmax
(neat) 1720 (CO2Me) cm21; dH (200 MHz, CDCl3) 3.76 (s,
3H, CO2CH3), 6.12 (s, 1H, OCH), 6.22 (s, 1H, 1 H of CH2),
6.46 (s, 1H, 1H of CH2), 6.89–6.99 (m, 3H, Ar-H),
7.21–7.29 (m, 2H, Ar-H), 7.52 (t, 1H, J¼7.9 Hz, Ar-H),
7.81 (d, 1H, J¼8.0 Hz, Ar-H), 8.15 (d, 1H, J¼8.0 Hz,
CH), 8.34 (s, 1H, Ar-H); Mass (FABMSþ) m/z % 314
(Mþþ1).
1.5.3. 2-{[3-(2-Chloro-phenyl)-isoxazol-5-yl]-phenoxy-
methyl}-acrylic acid (22e). [Found C, 63.97; H, 4.01; N,
3.98. C19H14ClNO4 requires C, 64.14; H, 3.97; N, 3.94%];
n
max (neat) 1684 (CO2H) cm21; dH (200 MHz, CDCl3) 6.19
(s, 1H, OCH), 6.24 (s, 1H, 1H of CH2), 6.34 (s, 1H, 1H of
CH2), 6.68 (s, 1H, CH), 6.96–7.04 (m, 3H, Ar-H), 7.22–
7.33 (m, 4H, Ar-H), 7.63–7.78 (m, 2H, Ar-H); Mass
(FABMSþ) m/z % 356 (Mþþ1).
1.5.4. 2-{[3-(2,4-Dichloro-phenyl)-isoxazol-5-yl]-phenoxy-
methyl}-acrylic acid (22f). [Found C, 58.40; H, 3.59; N,
3.73. C19H13Cl2NO4 requires C, 58.48; H, 3.36; N, 3.59 %];
nmax (neat) 1699 cm21; dH (200 MHz, CDCl3) 6.22 (s, 1H,
OCH), 6.37 (s, 1H, 1H of CH2), 6.59 (s, 1H, 1H of CH2),
6.75 (s, 1H, CH), 6.84 (dd, 1H, J1¼2.0 Hz, J2¼8.0 Hz,
Ar-H), 6.96–7.05 (m, 3H, Ar-H), 7.23–7.35 (m, 2H, Ar-H),
7.38 (d, 1H, J¼2.0 Hz, Ar-H), 7.68 (d, 2H, J¼8.0 Hz,
Ar-H); Mass (FABMSþ) m/z % 390 (Mþþ1).
1.4.15. 2-[Phenoxy-(4-trifluoromethyl-phenyl)-methyl]-
acrylic acid methyl ester (17i). [Found: C, 64.39; H,
4.67. C18H15F3O3 requires C, 64.28; H, 4.50%]; nmax (neat)
1705 (CO2Et) cm21; dH (200 MHz, CDCl3) 3.76 (s, 3H,
CO2CH3), 6.03 (s, 1H, OCH), 6.19 (s, 1H, 1H of CH2), 6.42
(s, 1H, 1H of CH2), 6.88–6.98 (m, 3H, Ar-H), 7.20–7.28
(m, 2H, Ar-H), 7.59 (s, 4H, Ar-H); Mass (FABMSþ) m/z %
337 (Mþþ1).
1.5. General procedure for solid phase reactions
1.5.5. 2-[(3-Nitro-phenyl)-phenoxy-methyl]-acrylic acid
(22g). [Found C, 63.96; H, 4.67; N, 4.44. C16H13NO5
requires C, 64.21; H, 4.38; N, 4.68 %]; nmax (KBr)1700
(CO2H) cm21; dH (200 MHz, CDCl3) 6.20 (s, 1H, OCH),
6.24 (s, 1H, 1H of CH2), 6.61 (s, 1H, 1H of CH2), 6.81–7.00
(m, 3H, Ar-H), 7.20–7.30 (m, 2H, Ar-H), 7.53 (t, 1H, J¼
The Wang (500 mg, 1.13 mmol/g, Novabiochem) acrylate
resin was prepared as described in literature.41 The resins
were divided into five PP syringes fitted with frits. To each
reaction vessel (RV), DABCO (3 equiv.) in 200 mL was

670
A. Patra et al. / Tetrahedron 59 (2003) 663–670
19. Li, G.; Wei, H. X.; Gao, J. J.; Caputo, T. D. Tetrahedron Lett.
2000, 41, 1–5.
7.9 Hz, Ar-H), 7.81 (d, 1H, J¼7.7 Hz, Ar-H), 8.16 (d, 2H,
J¼8.0 Hz, Ar-H), 8.34 (s, 1H, Ar-H); Mass (FABMSþ) m/z
% 300 (Mþþ1).
20. Shi, M.; Xu Yong, M. Chem. Commun. 2001, 1876–1877.
21. Lee, W.; Der, .; Yang, K. S.; Chen, K. Chem. Commun. 2001,
1612–1613.
Acknowledgements
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Financial support to authors AP and BSJ from CSIR, India
and AKR from ICMR in the form of fellowship is gratefully
acknowledged.
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