Treatment of Baylis-Hillman adducts with triethyl orthoacetate in the presence of heterogeneous catalysts: a method for the stereoselective synthesis of two different types of trisubstituted alkenes

Article abstract of DOI:10.1016/j.tetlet.2006.08.060

Baylis-Hillman adducts on treatment with triethyl orthoacetate in the presence of HClO₄-SiO₂ afford the corresponding allyl ethyl ethers while in the presence of NaHSO₄-SiO₂ undergo the Johnson-Claisen rearrange

Full text of DOI:10.1016/j.tetlet.2006.08.060

Tetrahedron Letters 47 (2006) 7619–7623
Treatment of Baylis–Hillman adducts with triethyl
orthoacetate in the presence of heterogeneous catalysts:
a method for the stereoselective synthesis of two different
types of trisubstituted alkenesI
Biswanath Das,* Anjoy Majhi and Joydeep Banerjee
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 14 July 2006; revised 7 August 2006; accepted 17 August 2006
Available online 8 September 2006
Abstract—Baylis–Hillman adducts on treatment with triethyl orthoacetate in the presence of HClO4–SiO2 afford the corresponding
allyl ethyl ethers while in the presence of NaHSO4–SiO2 undergo the Johnson–Claisen rearrangement to form ethyl alk-4-enoates.
Thus two different types of trisubstituted alkenes are produced in a stereoselective manner using two different hetereogeneous
catalysts.
Ó 2006 Elsevier Ltd. All rights reserved.
Baylis–Hillman adducts,1 3-hydroxy-2-methylene-alk-
anoates 1 and 3-hydroxy-2-methylene-alkanenitriles 2,
are important precursors for the stereoselective synthesis
of different multifunctional molecules.2 These adducts
have been utilized by us for the synthesis of (E) and
(Z) trisubstituted alkenes.3 Trisubstituted alkene moie-
ties occur widely in various naturally occurring bioactive
molecules including various important pheromones and
antibiotics.4 The biological activity of these alkenes is
highly dependent on their isomeric purity. Thus the
stereoselective synthesis of trisubstituted alkenes is an
important task in organic chemistry.
propionic acid are known to undergo the Johnson–Cla-
isen rearrangement.6 However, an interesting observa-
tion here is that silica-supported perchloric acid
(HClO4–SiO2) catalyzed the formation of the corre-
sponding allyl ethyl ethers 3 and 4 while silica-supported
sodium hydrogen sulfate (NaHSO4–SiO2) catalyzed the
production of the Johnson–Claisen rearrangement prod-
ucts 5 and 6 (Scheme 1).
Various Baylis–Hillman adducts 1 and 2 containing
both the ester and nitrile moieties were converted into
the corresponding allyl ethyl ethers (Table 1) and the
Johnson–Claisen rearrangement products (Table 2) with
the proper choice of the catalyst (HClO4–SiO2/NaH-
SO4–SiO2) on reaction with triethyl orthoacetate. The
In continuation of our work,5 on the applications of
heterogeneous catalysts for the development of useful
synthetic methodologies we have examined the effects
of these catalysts on the reaction of Baylis–Hillman
adducts 1 and 2 with triethyl orthoacetate.
7
catalysts, HClO4–SiO2 (HClO4: 1.25 g; SiO2: 23.75 g)
8
and NaHSO4–SiO2 (NaHSO4: 4.14 g; SiO2: 10 g), were
prepared from their readily available ingredients. The
first catalyst catalyzed the conversion at room tempera-
ture to form the allyl ethyl ethers in very high yields. The
Johnson–Claisen rearrangement products were not
detected at all. The conversion was complete within
1–2 h. The treatment of the adducts with MeOH or
EtOH (instead of triethyl orthoacetate) afforded no
product in the presence of this catalyst.9 The other
catalyst, NaHSO4–SiO2 catalyzed the reaction of the
Baylis–Hillman adducts with triethyl orthoacetate
under reflux to produce only the Johnson–Claisen
Allyl alcohols, including Baylis–Hillman adducts, on the
treatment with triethyl orthoacetate in the presence of
Keywords: Baylis–Hillman adduct; HClO4–SiO2; NaHSO4–SiO2; Het-
erogeneous catalyst; Trisubstituted alkene.
q Part 107 in the series, ‘Studies on novel synthetic methodologies’;
IICT Communication No. 060808.
*
Corresponding author. Tel./fax: +91 40 27160512; e-mail:
biswanathdas@yahoo.com
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.08.060

7620
B. Das et al. / Tetrahedron Letters 47 (2006) 7619–7623
OH
MeC(OEt)3
MeC(OEt)3
HClO4-SiO2
EWG
OEt
EWG
EWG
NaHSO4-SiO2
R
R
R
,
reflux
1-1.5 h
,
r.t.
1-2 h
COOEt
R = aryl, alkyl
70-96 %
76-89 %
EWG = COOMe
EWG = CN
5 EWG = COOMe
EWG = COOMe
EWG = CN
3
4
1
2
EWG = CN
6
Scheme 1.
a
Table 1. Synthesis of allyl ethyl ethers using HClO4–SiO2
Entry
Substrate
Product
Time (h)
1
Isolated yield (%)
OH
COOMe
3a
89
COOMe
COOMe
OEt
Cl
Cl OH
COOMe
OEt
3b
3c
1
1
93
96
Cl OH
Cl
COOMe
COOMe
OEt
Cl
Cl
OH
COOEt
OEt
COOEt
3d
1
88
Me
Me
OH
OH
COOMe
OEt
3e
4a
4b
1.5
2
70
78
86
COOMe
CN
OEt
CN
OH
OEt
CN
1.5
CN
Cl
Cl
a The structures of the allyl ethers were determined from their spectral (IR, 1H NMR and MS) and analytical data.
rearrangement product in impressive yields, and the allyl
ethers were not formed at all. The catalyst, HClO4–SiO2
or NaHSO4–SiO2, can easily be removed from the reac-
tion mixture by filtration, making the experimental pro-
cedure very simple. Silica alone induced no reaction
under the present experimental conditions.
a nitrile group at C-4 were formed with (Z) selectivity.
The 1H NMR spectra of the products were used to settle
their structures and stereochemistry by comparison with
reported data of known compounds.6b,c,9 In the 1H
NMR spectrum of a trisubstituted alkene the b-vinylic
protons, cis and trans to the ester group are reported
to appear at ca. d 7.5 and 6.5, respectively, when R is
aryl.10a,b The same protons cis and trans to an ester
group resonate at ca. d 6.5 and 5.7, respectively, when
R is alkyl.10c,d Similarly, the b-vinylic protons cis and
trans to a nitrile group resonate at ca. d 7.6 and 7.2,
respectively, when R is aryl3b,10e,f while the same
protons cis and trans to the nitrile group resonate at
ca. d 6.8 and 6.3, respectively, when R is alkyl.3b,10g,h
In the present conversion both the allyl ethyl ethers and
Johnson–Claisen rearrangement products (ethyl alk-4-
enoates) were formed in a stereoselective manner. The
allyl ethyl ethers containing an ester moiety were pro-
duced with the (E) configuration while those containing
a nitrile had the (Z) configuration. On the other hand,
the ethyl alk-4-enoates having an ester group at C-4
were obtained with a high (E) selectivity when C-5 car-
ried an aryl group and with high (Z) selectivity when
C-5 carried an alkyl group. However, the alkenes with
1
These known H NMR values were useful in determin-
ing the stereochemistry of the trisubstituted alkenes
prepared in this work.

B. Das et al. / Tetrahedron Letters 47 (2006) 7619–7623
7621
a
Table 2. Synthesis of ethyl alk-4-enoates using NaHSO4–SiO2
Entry
Substrate
Product
Time (h)
1
Isolated yield (%)
89
E:Zb
OH
COOMe
COOEt
5a
81:19
COOMe
COOMe
Cl
OH
Cl
COOMe
COOEt
5b
1
88
85:15
OH
COOMe
COOEt
COOMe
5c
5d
1
1
86
83
79:21
80:20
Cl
Cl
OH
OH
COOMe
COOEt
COOMe
COOMe
Me
Me
COOMe
COOEt
5e
5f
1.5
1.5
80
79
22:78
25:75
OH
COOMe
COOEt
COOMe
CN
OH
COOEt
6a
1
84
0:100
CN
Cl
Cl OH
COOEt
6b
6c
CN
OH
1.5
1
81
87
0:100
0:100
CN
COOEt
CN
CN
Cl
Cl
OH
OH
COOEt
COOEt
CN
CN
6d
6e
1.5
1.5
82
76
0:100
0:100
CN
CN
Me
Me
a The structures of the alk-4-enoates were determined from their spectral (IR, 1H NMR and MS) and analytical data.
b E:Z was determined from 1H NMR spectral analysis.
The conversion of the Baylis–Hillman adducts into allyl
ethers and alk-4-enoates possibly takes place through a
common intermediate A (Scheme 2). With the stronger
acidic catalyst (HClO4–SiO2) the reaction follows path
A to form the allyl ethers 3 and 4 while with a catalyst
of a weaker acidity (NaHSO4–SiO2) the reaction follows
path B to yield the rearranged products 5 and 6. Thus
the product formation is dependent on the nature of
the catalyst. The involvement of an intermediate A is
supported by the fact that the Baylis–Hillman adducts
did not afford any product on treatment with MeOH
or EtOH in the presence of HClO4–SiO2 but the bulky
leaving group present in A facilitated the formation of
3 and 4.
In conclusion, we have developed an efficient and conve-
nient method for stereoselective conversions of the Bay-
lis–Hillman adducts by the treatment with triethyl
orthoacetate into two different types of trisubstituted
alkenes (allyl ethers and alk-4-enoates) by applying
two different heterogeneous catalysts, HClO4–SiO2 and
NaHSO4–SiO2.
General experimental procedure: To a mixture of Baylis–
Hillman adduct (1 mmol) and triethyl orthoacetate
(5 mmol) HClO4–SiO2 or NaHSO4–SiO2 (100 mg) was
added. The mixture was stirred at room temperature
using the first catalyst or heated under reflux with the
second catalyst. The reaction was monitored by TLC.

7622
B. Das et al. / Tetrahedron Letters 47 (2006) 7619–7623
1 and 2
MeC(OEt)3
HClO4-SiO2
/ NaHSO4-SiO2
OEt
OEt
Me
O
C
EWG
R
A
HClO4-SiO2
Path A
NaHSO4-SiO2
Path B
OEt
R
+
HO
OEt
Me
C
EWG
5
3
O
EWG
and
and
R
6
4
C
EtO
..
EtOH
Scheme 2.
After completion the mixture was filtered and the filtrate
was concentrated. The residue was subjected to column
chromatography (silica gel, 2% (for 3 and 4) and 3% (for
5 and 6) EtOAc in hexane) to obtain pure trisubstituted
alkene.
7.48–7.13 (4H, m), 4.12, 4.08 (2H, 2q, J = 7.0 Hz),
3.84, 3.55 (3H, 2s), 2.74, 2.71 (2H, 2t, J = 7.0 Hz),
2.55, 2.46 (2H, 2t, J = 7.0 Hz), 1.25, 1.10 (3H, 2t,
J = 7.0 Hz); FABMS: m/z 321, 319 [M+Na]+. Anal.
Calcd for C15H17ClO4: C, 60.71; H, 5.73. Found: C,
60.78; H, 5.68.
The spectral (IR, 1H NMR and MS) and analytical data
of some representative allyl ethyl ethers and the
unknown alk-4-enoates6b are given below.
Compound 6b: IR (KBr): tmax 2361, 1734, 1622,
1
1438 cmÀ1; H NMR (CDCl3, 200 MHz): d 7.93 (1H,
d, J = 8.0 Hz), 7.45–7.23 (4H, m), 4.12 (2H, q,
J = 7.0 Hz), 2.76 (2H, t, J = 7.0 Hz), 2.66 (2H, t, J =
7.0 Hz), 1.28 (3H, t, J = 7.0 Hz); FABMS: m/z 288,
286 [M+Na]+. Anal. Calcd for C14H14ClNO2: C,
63.76; H, 5.31; N, 5.31. Found: C, 63.71; H, 5.28; N,
5.39.
Compound 3c: IR (KBr): tmax 1720, 1637, 1468,
1
1236 cmÀ1; H NMR (CDCl3, 200 MHz): d 7.92 (1H,
s), 7.69 (1H, d, J = 8.0 Hz), 7.48 (1H, d, J = 2.0 Hz),
7.32 (1H, dd, J = 8.0, 2.0 Hz), 4.16 (2H, s), 3.89 (3H,
s), 3.55 (2H, q, J = 7.0 Hz), 1.22 (3H, t, J = 7.0 Hz);
FABMS: m/z 315, 313, 311 [M+Na]+. Anal. Calcd for
C13H14Cl2O3: C, 53.98; H, 4.84. Found: C, 53.91; H,
4.89.
Acknowledgement
The authors thank UGC and CSIR, New Delhi for their
financial assistance.
Compound 3e: IR (KBr): tmax 1674, 1638, 1353,
1
1219 cmÀ1; H NMR (CDCl3, 200 MHz): d 6.20 (1H, t,
J = 7.0 Hz), 4.08 (2H, s), 3.75 (3H, s), 3.48 (2H, q,
J = 7.0 Hz), 2.42 (2H, t, J = 7.0 Hz), 1.75 (1H, m), 1.21
(3H, t, J = 7.0 Hz), 0.94 (6H, d, J = 7.0 Hz); FABMS:
m/z 223 [M+Na]+. Anal. Calcd for C11H20O3: C,
66.00; H, 10.00. Found: C, 66.13; H, 10.17.
References and notes
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