Sequential olefinations on 2-arylmethylidene-2-phosphonoacetates: A one-pot highly stereoselective synthesis of 1,2,3-trisubstituted 1,3-butadienes

Article abstract of DOI:10.1246/bcsj.77.2099

An efficient one-pot synthetic protocol for the preparation of 1,2,3-trisubstituted dienes by a sequential addition of 2-arylmethylidene-2- phosphonoacetates and various aldehydes to trimethylsulfonium iodide/sodium dimsylate in DMSO-THF has been develope

Full text of DOI:10.1246/bcsj.77.2099

Short Articles
Bull. Chem. Soc. Jpn., 77, 2099–2100 (2004) 2099
lent of carbene. While the former protocol has been used for
the preparation of allylic alcohols from epoxides5 and one-car-
bon homologated terminal alkenes from alkyl halides or mesy-
lates,6 the later combination has been used in sequential one-
pot olefination–methylation with various activated olefins for
the preparation of 1-substituted vinyl silanes and styrenes.7
We report herein on a successful one-pot synthetic protocol
for the preparation of 1,2,3-trisubstituted dienes by a sequen-
tial addition of activated 2-arylmethylidene-2-phosphono-
acetates and various aldehydes to trimethylsulfonium iodide–
sodium dimsylate.
Sequential Olefinations on 2-Aryl-
methylidene-2-phosphonoacetates:
A One-Pot Highly Stereoselective
Synthesis of 1,2,3-Trisubstituted
1,3-Butadienes
ꢀ
Sonali M. Date and Sunil K. Ghosh
Three 2-arylmethylidene-2-phosphonoacetates 1a–c were
synthesized in very good yields using fluorinated phosphono-
acetate 38 and the corresponding aldehydes by a Knoevenagel-
type reaction (Scheme 2). When 1a was added to a reaction
mixture containing 2.5 molar amounts of sodium dimsylate
and 1 molar amount of Me3SI, and quenched the reaction with
benzaldehyde, it gave the desired diene 2a, though in moderate
yield, but exclusively as the (Z)-isomer. The corresponding
ethylphosphonopropenoate derivative did not give the diene
product under similar conditions. The electrophilicity of the di-
ethylphosphonate group is less than that of the 2,2,2-trifluoro-
ethylphosphonate group, which probably retards the formation
of the betaine intermediate, and hence the diene product in a
sterically congested system, like us. The higher electrophilicity
of trifluoroethylphosphonate is also responsible for the forma-
tion of a kinetically controlled3 (Z)-olefin product. To survey
the generality of this one-pot sequential double olefination
for the synthesis of substituted 1,3-dienes, we attempted the re-
action with various aldehydes, as shown in Scheme 3. Reac-
tions of 2-arylmethylidene-2-phosphonoacetates 1a–c with
benzaldehyde and substituted benzaldehydes exclusively gave
the (Z)-isomers of the dienes. The product 2e, obtained from 2-
furaldehyde and 1a was contaminated with 5% of its (E)-iso-
mer. The diene products 2g and 2h contained 15% and 8%
of the corresponding (E)-isomers, respectively. The (E)-iso-
mers were formed with consistent and reproducible ratios, thus
Bio-Organic Division, Bhabha Atomic Research Centre,
Mumbai 400 085, India
Received June 2, 2004; E-mail: ghsunil@magnum.barc.ernet.in
An efficient one-pot synthetic protocol for the prepara-
tion of 1,2,3-trisubstituted dienes by a sequential addition of
2-arylmethylidene-2-phosphonoacetates and various alde-
hydes to trimethylsulfonium iodide/sodium dimsylate in
DMSO–THF has been developed. The dienes were produced
with very high stereoselectivity preferring for the (Z)-isomer.
Substituted 1,3-butadienes enjoy widespread use in synthe-
sis owing to their ready participation in the famous Diels–
Alder (D–A) reaction for building the skeleton of complex
molecules.1 Electron-donating substituents on the dienes favor
a normal-electron-demand D–A reaction, while electron-with-
drawing groups on the same favor an inverse-electron-demand.
Di- or tri-substituted butadienes containing electron donating
and/or withdrawing groups at the 2,3- or 1,2,3-positions are
very important, since they can be used for both classes of
D–A reactions, depending upon the dienophiles and reaction
conditions. Regio- and stereospecific methods to prepare high-
ly substituted dienes having both electron-donating and elec-
tron-withdrawing substituents are limited. A convenient syn-
thetic protocol is desired for quick access to these precursors.
A multicomponent approach2 to these highly and differentially
substituted 1,3-dienes could be envisaged from simple build-
ing blocks, as shown in Scheme 1. The addition of a nucleo-
philic carbene equivalent to a Michael acceptor 1 containing
a phosphonate group and its subsequent reaction with an
aldehyde should provide the desired diene 2 via a Horner–
Wadsworth–Emmons reaction.3
ArCHO
piperidinium
benzoate
Ar
CO2Et
EtO2C
P(O)(OCH2CF3)2
benzene
reflux
P(O)(OCH2CF3)2
3
Ar = p-MeO-C6H4: 1a 74%
Ar = C6H5: 1b 81%
Ar = p-Br-C6H4: 1c 86%
Scheme 2.
1. Me3SI
Na-dimsylate
An excess of dimethylsulfonium methylide4 or its combina-
tion with a base, like sodium dimsylate, can act as an equiva-
Ar
CO2Et
Ar
CO2Et
R
2. RCHO
P(O)(OCH2CF3)2
Ar = p-MeO-C6H4: 1a
Ar = C6H5: 1b
Ar = p-Br-C6H4: 1c
Ar = p-MeO-C6H4; R = C6H5: 2a 47%
Ar = p-MeO-C6H4; R = p-Br-C6H4: 2b 42%
Ar = p-MeO-C6H4; R = p-Cl-C6H4: 2c 41%
Ar = p-MeO-C6H4; R = p-F-C6H4: 2d 44%
Ar = p-MeO-C6H4; R = 2-furyl: 2e 37%
Ar = p-MeO-C6H4; R = (E)-PhCH=CH:2f 50%
Ar = p-MeO-C6H4; R = PhCC: 2g 49%
Ar = p-MeO-C6H4; R = EtO2C: 2h 45%
Ar = p-MeO-C6H4; R = PhCH2CH2: 2i 47%
Ar = p-MeO-C6H4; R = H: 2j 44%
O
CH-R3
CO2Et
R1O
R1O
CH-R3
CH-R3
O-
P
P
R1O
R1O
C
C
CO2Et
R2
C
C
CO2Et
R2
O
+
H
H
R2
O
CH2
CH2
H
H
Ar = C6H5; R = C6H5: 2k 48%
Ar = p-Br-C6H4; R = C6H5: 2l 47%
1
2
Scheme 1.
Scheme 3.
Published on the web November 11, 2004; DOI 10.1246/bcsj.77.2099

2100 Bull. Chem. Soc. Jpn., 77, No. 11 (2004)
Ó 2004 The Chemical Society of Japan
ic extract was washed with brine, dried (MgSO4), and evaporated.
The residue was chromatographed to give the diene 2a (68 mg,
47%) as a thick oil. H NMR (200 MHz, CDCl3) ꢀ 1.13 (t, J ¼
suggesting their direct formation in the H–W–E reaction. Base
sensitive aldehydes, such as ethyl glyoxalate and 3-phenylpro-
panal, required the addition of a 0.5 molar amount of acetic
acid prior to their addition into the reaction mixture.
In summary, this one-pot procedure offering high stereose-
lectivity and easy access to the starting materials makes this
methodology of value for the synthesis of difficultly substitut-
ed dienes. Although the yields were moderate, it is worthwhile
mentioning that the products were easily isolable by chroma-
tography because the by-products were highly polar, or water
soluble.
1
7:1 Hz, 3H), 3.83 (s, 3H), 4.20 (q, J ¼ 7:1 Hz, 2H), 5.32 (s,
1H), 5.36 (s, 1H), 6.69 (s, 1H), 6.89 (d, J ¼ 8:7 Hz, 2H), 7.29–
7.37 (m, broad, 7H). 13C NMR (50 MHz, CDCl3) ꢀ 13.75,
55.21, 61.09, 113.58 (2C), 115.74, 128.29 (5C), 129.52 (2C),
132.02, 133.48, 135.43, 136.23, 146.39, 159.33, 169.33. Anal.
Calcd for C20H20O3: C, 77.89; H, 6.55%. Found: C, 77.65; H,
6.81%.
The preparation and analytical data of 1b, 1c, and 2b–2l are
deposited as Document No. K04731 at the office of the Editor
of Bull. Chem. Soc. Jpn.
Experimental
Ethyl (E)-2-[Bis(2,2,2-trifluoroethyl)phosphonato]-3-(4-
methoxyphenyl)-2-propenoate (1a). A General Procedure:
A solution of p-anisaldehyde (1.83 mL, 15 mmol, 1.5 molar
amount), 38 (3.32 g, 10 mmol, 1 molar amount), and piperidinium
benzoate (207 mg, 1 mmol) in benzene (23 mL) was heated under
reflux fitted with a Dean–Starke apparatus for 3 days. The reaction
mixture was cooled, washed with water and with brine, dried
(MgSO4), and evaporated. The residue was chromatographed to
give 1a (E=Z ¼ 95=5) (3.31 g, 74%). Crystallization in EtOAc–
hexanes provided pure (E)-1a. Data for (E)-1a: Mp 54 ꢁC.
1H NMR (200 MHz, CDCl3) ꢀ 1.29 (t, J ¼ 7:1 Hz, 3H), 3.85 (s,
3H), 4.31 (q, J ¼ 7:1 Hz, 2H), 4.36–4.50 (m, 4H), 6.91 (d, J ¼
8:8 Hz, 2H), 7.50 (d, J ¼ 8:8 Hz, 2H), 7.69 (d, J ¼ 28 Hz, 1H).
13C NMR (50 MHz, CDCl3) ꢀ 13.63, 55.36, 62.02, 62.52 (dq,
J ¼ 4:4, 38.2 Hz, 2C), 114.12 (2C), 116.97 (d, J ¼ 190:4 Hz),
122.45 (dq, J ¼ 9:8, 277.5 Hz, 2C), 125.20 (d, J ¼ 22 Hz),
132.53 (2C), 152.00 (d, J ¼ 7:6 Hz), 162.35, 165.05 (d, J ¼
14:1 Hz). Anal. Calcd for C16F6H17O6P: C, 42.68; H, 3.81%.
Found: C, 42.43; H, 4.10%.
The authors are grateful to Dr. Rekha Singh, BOD, BARC,
for carrying out some preliminary experiments.
References
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phenylmethylidene-3-butenoate (2a). A General Procedure:
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in DMSO (1.4 mL) was prepared, diluted with THF (1.5 mL),
and cooled on an ice-salt bath (ꢂ8 ꢁC). Solid Me3SI (123 mg,
0.6 mmol, 1.2 molar amount) was introduced into the flask and
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added to the reaction mixture, slowly brought to room tempera-
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ꢁ
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