Baylis-Hillman chemistry: A novel synthesis of functionalized 1,4-pentadienes

Article abstract of DOI:10.1016/S0040-4039(00)01886-4

A novel synthesis of functionalized 1,4-pentadienes via the reaction of acrylonitrile with allyl halides, derived from Baylis-Hillman adducts, in the presence of DABCO has been described, demonstrating for the first time the application of allyl halides a

Full text of DOI:10.1016/S0040-4039(00)01886-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 85–87
Baylis–Hillman chemistry: a novel synthesis of functionalized
,4-pentadienes
1
Deevi Basavaiah,* Nagaswamy Kumaragurubaran and Duddu S. Sharada
School of Chemistry, University of Hyderabad, Hyderabad-500 046, India
Received 18 October 2000; accepted 26 October 2000
Abstract—A novel synthesis of functionalized 1,4-pentadienes via the reaction of acrylonitrile with allyl halides, derived from
Baylis–Hillman adducts, in the presence of DABCO has been described, demonstrating for the first time the application of allyl
halides as electrophiles in the Baylis–Hillman reaction. © 2000 Elsevier Science Ltd. All rights reserved.
The Baylis–Hillman reaction continues to attract the
attention of organic chemists due to its increasing im-
portance in the development of various new synthetic
methodologies often involving high levels of stereo-
We have therefore undertaken a research program of
examining the possible application of allyl halides as
electrophiles in the Baylis–Hillman reaction. During
our study, we directed our attention towards the appli-
2
6
1
–15
cation of methyl (2Z)-2-(bromomethyl)alk-2-enoates,
chemical control.
The 1,4-diene moiety is an impor-
allyl bromides derived from Baylis–Hillman adducts
(methyl 3-hydroxy-2-methylenealkanoates), as possible
electrophiles in the Baylis–Hillman reaction. Accord-
ingly, we first examined the coupling of acrylonitrile
with methyl (2Z)-2-(bromomethyl)-3-phenylprop-2-
enoate (1a) derived from methyl 3-hydroxy-2-methyl-
ene-3-phenylpropanoate, in the presence of DABCO. A
fascinating result was obtained when we treated methyl
tant structural unit present in several biologically active
1
6,17
molecules
and, in particular, substituted 1,4-penta-
dienes are versatile synthons for the synthesis of various
1
8,19
interesting molecules.
Hence, the development of
simple, convenient, and new methodologies for the
synthesis of 1,4-dienes has been, and continues to be, a
challenging endeavor in synthetic organic chemis-
2
0–25
try.
In continuation of our research program on
11–15
the development of the Baylis–Hillman reaction,
a,b
Table 1. Synthesis of functionalized 1,4-pentadienes
we report a novel synthesis of functionalized 1,4-penta-
dienes via the reaction of acrylonitrile in the presence of
DABCO with methyl (2Z)-2-(bromomethyl)alk-2-
enoates and (3Z)-3-(chloromethyl)alk-3-en-2-ones, allyl
halides obtained from the corresponding Baylis–Hill-
man adducts.
Substrate
Ar
Product
Yield (%)c
d,27
1
1
1c
1
1
1
1
3
3
3
a
b
phenyl
2a
67
63
65
55
59
60
37
42
36
40
4-chlorophenyl
4-methylphenyl
4-ethylphenyl
4-isopropylphenyl
2-chlorophenyl
2-methylphenyl
phenyl
2b
2c
2d
2e
2f
2g
4a
4b
4c
d
e
f
g
a
b
c
The Baylis–Hillman reaction is basically a three com-
ponent reaction involving an activated alkene, a carbon
electrophile and a tertiary amine catalyst (particularly
DABCO) leading to the formation of a carbon–carbon
bond between the a-position of the activated alkene
and the carbon electrophile thus providing densely
functionalized molecules. Though various electrophiles
have been successfully employed in this fascinating
d,29
4-chlorophenyl
4-methylphenyl
a
All reactions were carried out using 2 mM of the allyl halides (1a–g,
3a–c) with acrylonitrile (2 mL) in the presence of DABCO (4 mM) at
1
–3
room temperature for 7 days.
reaction,
the application of allyl halides as elec-
b
All products were obtained as colorless viscous liquids and gave
trophiles has not been reported so far in the literature.
1
13
satisfactory IR, H NMR (200 MHz), C NMR (50 MHz) spectral
data and elemental analyses.
c
Keywords: Baylis–Hillman chemistry; acrylonitrile; DABCO; func-
Isolated yields of the pure products after column chromatography
tionalized 1,4-pentadienes.
(silica gel, 4% ethyl acetate in hexanes).
These products were also characterized by mass spectral analysis.
d
*
Corresponding author.
0
040-4039/01/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01886-4

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D. Basa6aiah et al. / Tetrahedron Letters 42 (2001) 85–87
Scheme 1.
2Z)-2-(bromomethyl)-3-phenylprop-2-enoate (1a) (2
(
Acknowledgements
mM), with acrylonitrile (2 mL) in the presence of
DABCO (4 mM) at room temperature for 7 days,
leading to the formation of 4-cyano-2-methoxycar-
bonyl-3-phenylpenta-1,4-diene (2a) in 67% yield after
the usual work up followed by column chromatography
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.
NK and DSS thank UGC (New Delhi) for research
fellowship.
2
7
(
silica gel, 4% ethyl acetate in hexanes). Encouraged by
this result, we extended the reaction to a representative
class of allyl bromides derived from methyl 3-aryl-3-hy-
droxy-2-methylenepropanoates to produce functional-
ized 1,4-pentadienes (2b–g) (Eq. (1), Table 1).
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1
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5
31
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13
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