One-pot inter- and intramolecular Friedel-Crafts reactions in Baylis-Hillman chemistry: A novel facile synthesis of (E)-2-arylideneindan-1-ones

Article abstract of DOI:10.1016/S0040-4039(01)00354-9

A simple one-pot stereoselective transformation of tert-butyl 3-aryl-3-hydroxy-2-methylenepropanoates, the Baylis-Hillman adducts obtained from t-butyl acrylate, into (E)-2-arylideneindan-1-ones involving one inter- and one intramolecular Friedel-Crafts r

Full text of DOI:10.1016/S0040-4039(01)00354-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3025–3027
One-pot inter- and intramolecular Friedel–Crafts reactions in
Baylis–Hillman chemistry: a novel facile synthesis of
(E)-2-arylideneindan-1-ones
Deevi Basavaiah* and Ravi Mallikarjuna Reddy
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
Received 29 January 2001; revised 8 February 2001; accepted 2 March 2001
Abstract—A simple one-pot stereoselective transformation of tert-butyl 3-aryl-3-hydroxy-2-methylenepropanoates, the Baylis–
Hillman adducts obtained from t-butyl acrylate, into (E)-2-arylideneindan-1-ones involving one inter- and one intramolecular
Friedel–Crafts reaction is described. © 2001 Elsevier Science Ltd. All rights reserved.
O
The Baylis–Hillman reaction is an emerging atom eco-
nomic reaction producing an interesting class of densely
functionalized molecules whose applications in a variety
of stereoselective processes have been well documented
in the literature.1–10 We recently described the sulfuric
acid catalyzed (intermolecular) Friedel–Crafts reaction
of the Baylis–Hillman adducts, i.e. methyl 3-aryl-3-
hydroxy-2-methylenepropanoates with benzene provid-
H
R
COOH
OPh
TFAA, CH2Cl2,
1h, 80-94 %
R = Aryl, Alkyl
R
O
(E)
(E)
(2)
(E)-2-Arylideneindan-1-ones are useful synthons in the
synthesis of various carbocyclic and heterocyclic
molecules of biological importance.13–20 The classical
methods for the preparation of these important com-
pounds involve the initial synthesis of the indan-1-one
moiety, followed by aldol reaction with appropriate
aldehydes.13–17,20–22 To the best of our knowledge, there
is no report in the literature first involving the synthesis
of arylidene moiety and then construction of the indan-
1-one framework for the preparation of (E)-2-aryli-
deneindan-1-ones. We therefore felt that the
development of a simple and efficient methodology for
the stereoselective synthesis of the (E)-2-arylidenein-
dan-1-one skeleton by preparing an (E)-arylidene moi-
ety first and then constructing the indan-1-one
framework would be of high importance.
ing
a simple stereoselective synthesis of methyl
(2E)-3-aryl-2-benzylprop-2-enoates (Eq. (1)).7,11 We
have also described an intramolecular Friedel–Crafts
reaction of (2E)-2-aryloxymethylalk-2-enoic acids
under the influence of trifluoroacetic anhydride
(TFAA) thus providing a simple synthesis of (E)-3-
arylidene(or alkylidene)chroman-4-ones (Eq. (2)).8 We
wanted to design a simple methodology to carry out
both inter- and intramolecular Friedel–Crafts reactions
on the Baylis–Hillman adducts in an operationally sim-
ple one-pot procedure. Thus we report a convenient
one-pot synthesis of (E)-2-arylideneindan-1-ones from
tert-butyl
3-aryl-3-hydroxy-2-methylenepropanoates,
the Baylis–Hillman adducts obtained from tert-butyl
acrylate,12 essentially involving one inter- and one
intramolecular Friedel–Crafts reaction in a one-pot
operation.
It occurred to us that tert-butyl 3-aryl-3-hydroxy-2-
methylenepropanoates, the Baylis–Hillman adducts
OH
COOMe
Ph
H
H
H2SO4(cat.), Benzene
COOMe
+
Ar
reflux, 30min
Ar
Ph
Ar
COOMe
(1)
67-86 %
0-6%[Z]
94-100%[E]
Ar = Aryl
Keywords: Baylis–Hillman chemistry; inter- and intramolecular Friedel–Crafts reactions; 2-arylideneindan-1-ones; stereoselective transformations.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00354-9

3026
D. Basa6aiah, R. M. Reddy / Tetrahedron Letters 42 (2001) 3025–3027
OH
COOtBu
COOtBu
H
COOH
Ph
a) H2SO4(cat.), 30 min
Benzene, reflux
H
H+
Ar
Ar
Ph
Ar
1a-f
b) TFAA,
CH2Cl2 or
ClCH2CH2Cl
2h
O
Ar = phenyl, 4-methylphenyl,
4-ethylphenyl, 4-isopropylphenyl,
2-methylphenyl, 4-bromophenyl
50-67%
Ar
2a-f
Scheme 1.
Table 1. Synthesis of (E)-2-arylideneindan-1-onesa,b
obtained from tert-butyl acrylate, might be appropriate
substrates for the intermolecular Friedel–Crafts reac-
tion with benzene under the catalytic influence of sulfu-
ric acid. At the same time, sulfuric acid might cleave the
tert-butyl ester to provide the corresponding cinnamic
acid (through AAL1 mechanism),23 which might subse-
quently undergo intramolecular Friedel–Crafts cycliza-
tion under the influence of a suitable reagent to provide
the required (E)-2-arylideneindan-1-ones. We also envi-
sioned that all three steps could be carried out in
one-pot.
Substrate
Ar
Product
Yield (%)c
1a
1b
1c
1d
1e
1f
Phenyl
2a
63
61
59
56
67
50
4-Methylphenyl
4-Ethylphenyl
4-Isopropylphenyl
2-Methylphenyl
4-Bromophenyl
2bd
2cd,e
2d
2ef
2fd,f
a All reactions were carried on 1 mM scale of Baylis–Hillman adducts
(1a–f) with benzene (5 mL) in the presence of conc. H2SO4 (0.4
mM) at reflux for 30 min. Benzene solvent was removed under
reduced pressure and the residue (resulting cinnamic acids) was
treated with TFAA (2 mM, 0.28 mL) in CH2Cl2 at reflux for 2 h.
b All the products were obtained as yellow crystalline solids and gave
satisfactory IR, 1H NMR (200 MHz), 13C NMR (50 MHz) spectral
data and elemental analyses.
Accordingly, we have first selected tert-butyl 3-
hydroxy-3-phenyl-2-methylenepropanoate (1a) as a sub-
strate for study. We have indeed achieved a fascinating
result. Thus, treatment of 1a (1 mM) with a catalytic
amount of conc. H2SO4 (0.4 mM) in benzene (5 mL)
at reflux for 30 min, followed by reaction with tri-
fluoroacetic anhydride (TFAA) (2 mM) in
dichloromethane (5 mL) (after removal of the solvent
benzene under reduced pressure) for 2 h at reflux
provided the desired 2-benzylideneindan-1-one (2a) in
63% yield after usual work-up and column chromatog-
raphy (silica gel, 5% EtOAc in hexanes), followed by
crystallization from chloroform and hexanes (2:3).24
Encouraged by this result, we have prepared a represen-
tative class of (E)-2-arylideneindan-1-ones (2b–f) in 50–
67% yields from representative Baylis–Hillman adducts
(1b–f) derived from tert-butyl acrylate (Scheme 1, Table
1).
c Isolated yields of the pure products after column chromatography
(silica gel, 5% EtOAc in hexanes) followed by crystallization (chloro-
form and hexanes, 2:3).
d 1H NMR of the crude products (2b, 2c and 2f) indicates the
presence of small amounts (:5–15%) of the corresponding (Z)-iso-
mer.26
e Structure was also confirmed by mass spectral analysis.
f Intramolecular Friedel–Crafts reactions were carried out in 1,2-
dichloroethane as solvent at 50°C as these reactions are slow in
dichloromethane at reflux.
reactions in one-pot to provide a simple methodology
for the synthesis of (E)-2-arylideneindan-1-ones from
the Baylis–Hillman adducts obtained from tert-butyl
acrylate, thus demonstrating the applications of Baylis–
Hillman chemistry in organic synthesis.
With a view to transforming these (E)-2-arylidenein-
dan-1-ones into the corresponding 2-arylmethylindan-1-
ones, another interesting class of organic molecule, we
have subjected the molecules 2a–d to catalytic hydro-
genation in the presence of 5% Pd/C catalyst (40 psi) to
afford the desired molecules 3a–d (Eq. (3)).25
Acknowledgements
O
O
We thank DST (New Delhi) for funding this project.
We thank the UGC (New Delhi) for a Special Assis-
tance Program in Organic Chemistry in the School of
Chemistry, University of Hyderabad. R.M.R. thanks
CSIR (New Delhi) for his research fellowship.
H2/Pd-C, EtOAc
73-80%
Ar
Ar
(3)
3a-d
2a-d
Ar = phenyl, 4-methylphenyl,
4-ethylphenyl, 4-isopropylphenyl
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