Fe3+-K-10 montmorillonite clay catalyzed Friedel-Crafts reaction of unactivated Baylis-Hillman adducts: An efficient stereoselective synthesis of trisubstituted alkenes containing a benzyl substituent

Article abstract of DOI:10.1246/cl.2005.1492

The stereoselective synthesis of trisubstituted alkenes containing a benzyl substituent has been achieved by employing Friedel-Craft reaction of aromatic compounds with unactivated Baylis-Hillman adducts in the presence of Fe ³⁺-K-10 montmorill

Full text of DOI:10.1246/cl.2005.1492

1
492
Chemistry Letters Vol.34, No.11 (2005)
3
þ
Fe -K-10 Montmorillonite Clay Catalyzed Friedel–Crafts Reaction
of Unactivated Baylis–Hillman Adducts: An Efficient Stereoselective Synthesis
of Trisubstituted Alkenes Containing a Benzyl Substituent1
ꢀ
Biswanath Das, Anjoy Majhi, Joydeep Banerjee, Nikhil Chowdhury, and Katta Venkateswarlu
Organic Chemistry Division-I, India Institute of Chemical Technology, Hyderabad-500 007, India
(Received July 8, 2005; CL-050886)
The stereoselective synthesis of trisubstituted alkenes con-
taining a benzyl substituent has been achieved by employing
Friedel–Craft reaction of aromatic compounds with unactivated
Baylis–Hillman adducts in the presence of Fe -K-10 montmor-
illonite clay as a heterogeneous catalyst. The catalyst can be re-
covered and reused.
OH
H
ArH
Fe3+-K-10
EWG
EWG
Ar
R
R
3þ
reflux, 30 or 120 min
7
4−95% (R = aryl)
4
1−62% (R = alkyl)
1
2
(a−g) EWG = −COOMe
(a−g) EWG = −CN
3 (a−g) EWG = −COOMe
4 (a−g) EWG = −CN
The Baylis–Hillman adducts, 3-hydroxy-2-methylene-alka-
noates 1 (derived from acrylate esters) and 3-hydroxy-2-methyl-
ene-alkanenitriles 2 (derived from acrylonitrile) are important
precursors for stereoselective synthesis of different functional-
Scheme 1.
Table 1. Friedel–Craft reaction of the Baylis–Hillman adduct
1a (R = 2-Cl-C H , EWG = –COOMe) with benzene in the
ized molecules.2 In continuation of our work on the prepara-
tion of trisubstituted alkenes, we have recently observed that
such compounds containing a benzyl substituent can be prepared
in stereoselective manner by the Friedel–Craft reaction of the ad-
ducts, 1 and 2 with aromatic compounds in the presence of dif-
ferent heterogeneous solid acid catalysts. These target alkenes
are useful for the preparation of (E)-2-arylideneindane-1-ones
which are important synthons in the synthesis of various carbo-
cyclic and heterocyclic molecules of pharmacological impor-
,3
4
6
4
a
presence of different heterogeneous solid acid catalysts
Reaction time Isolated yield/%
of alkene
Entry
Catalyst
/min
1
2
3
4
5
6
7
8
HY-Zeolite
Amberlyst-15
KSF clay
120
120
120
120
30
30
30
30
61
75
84
81
95
84
63
56
Mont K-10
Fe -K-10
3þ
5
tance. These alkenes can also be employed for the preparation
6
3
þ
þ
þ
Al -K-10
Zn -K-10
of naturally occurring bioactive 1,3-diarylpropanoids. Thus,
2
the present method is an easy access to several biopotent mole-
cules. However, it is difficult to synthesize trisubstituted alkenes
having a benzyl substituent and it is also difficult to induce the
Friedel–Craft reaction to the Baylis–Hillman adducts to get the
products in satisfactory yields—proper selection of catalysts is
vital.7 Previously, the Friedel–Craft reaction of the unactivat-
ed Baylis–Hillman adducts was carried out with concentrated
2
Cu -K-10
a1a (2 mmol) and a catalyst (100 mg) was taken in benzene
5 mL) and refluxed.
(
a,7b
suitable for the Friedel–Craft reaction of the unactivated
Baylis–Hillman adducts.
7a
H2SO4 under reflux. The acetyl and N-tosylamine derivatives
of the adducts were reported to undergo the reaction with AlCl3
In general conversions the trisubstituted alkenes, 3 and 4
were formed in excellent yields from the adducts having the aryl
substituents (reaction time: 30 min). However, the adducts (1
and 2) with alkyl substituents afforded the alkenes (3 and 4
respectively) with moderate to good yields (reaction time:
120 min) (Table 2). The structures and stereochemistry of the
7
b,7c
and H2SO4, respectively.
However, concentrated H2SO4
may affect the acid-sensitive groups and AlCl3 yielded side
products.7b Conversion of the derivatives of the Baylis–Hillman
adducts also required two steps.
1
13
We initially treated 1a (R = 2-Cl-C6H4; EWG =
COOMe) with benzene under reflux using different heterogene-
products were determined from their H and C NMR spectra
1
–
ous-solid-acid catalysts (including various metal doped K-10
and the ratio of (E)- and (Z)-isomers from the H NMR spectra
1
13
of the crude products. A comparison of the H and C NMR
spectral values of our prepared compounds with those of the
3þ
clays) to undergo the Friedel–Craft reaction (Table 1). Fe
K-10 montmorillonite clay was found to give the best result with
-
7
same compounds reported earlier guided to establish the stereo-
7
a,7c,9
the highest yield (95%) of the desired trisubstituted alkene, 3a
(
chemistry and ratio (E:Z as well as ortho:para)
(Table 3) of
Scheme 1).
Among the metal doped K-10 clays the order of activity was
the products. It was observed that the product 3 was formed with
(E)-selectivity having trace amount of (Z)-isomer when the
adduct 1 was derived from an aromatic aldehyde while it (3)
was obtained as mixtures of (E)- and (Z)-isomers when 1 was
derived from an aliphatic aldehyde. On the other hand, the
product 4 was formed with (Z)-configuration from the adduct
2 containing both aromatic and alkyl substituents.
3
þ
3þ
2þ
found as follows: Fe -K-10 > Al -K-10 > Zn -K-10 >
Cu -K-10 (Table 1). This order depends on the number of
2þ
8
Lewis and Brꢀonsted acid sites present in the catalyst. The high-
3
þ
est activity of Fe -K-10 clay is due to a compatible mixture
of highest number of Lewis and Brꢀonsted acid sites per its
8
3þ
unit volume. Thus Fe -K-10 clay was considered to be most
The stereochemistry of the Friedel–Craft reaction can be ex-
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.11 (2005)
1493
Fe3+
EWG
Table 2. Stereoselective synthesis of trisubstituted alkenes
containing a benzyl substituent 3 and 4 from the adducts 1 and
2
Fe2+
+
+
Fe2+
EWG
H
HO:
HO
HO
EWG
_
EWG
R
and benzene using Fe3 -K-10 clay
þ
a
R
R
-H+
_
-H
2
O
R
-
Fe3+
H
+
Time Isolated
min yield/%
Entry
R
EWG
E:Z
A
/
3
a
2-Cl-C6H4
C6H5
4-Cl-C6H4
4-Me-C6H4 COOMe
1-Napth
i-C3H7
COOMe
COOMe
COOMe
30
30
30
30
30
95
93
91
90
74
62
56
92
89
86
87
90
41
52
98:2
96:4
98:2
97:3
Figure 1.
3b
3
c
−
−
−
R
H
H
R
H
R
3d
EWG
COOMe
C
N
3
3
3
4
e
f
g
a
COOMe
COOMe 120
COOMe 120
CN
CN
CN
CN
CN
CN
CN
95:5
Ar
Ar
Ar
Fe2+
HO
+
Fe2+
HO
Fe2+
30:70
42:58
0:100
1:99
0:100
0:100
0:100
0:100
0:100
HO
+
+
i-C4H9
Figure 2.
2-Cl-C6H4
C6H5
4-Cl-C6H4
4-Me-C6H4
4-MeO-C6H4
n-C3H7
30
30
30
30
30
120
120
4b
alkenes containing a benzyl substituent by utilizing the Frie-
del–Craft reaction of aromatic compounds with the unactivated
4
c
4d
3þ
Baylis-Hillmam adducts using Fe -K-10 montmorillonite clay
10
4
4
e
f
(
prepared from FeCl3 and K-10 clay).
The operational simplicity, the application of a heterogene-
4g
i-C3H7
ous and recyclable catalyst, high yield, and excellent stereose-
lectivity of the products (particularly from the adducts contain-
ing aryl substituents) are the great advantages of the present
method.
a
The structures of the alkenes were determined from their spec-
tral (IR, H and C NMR, and MS) and analytical data.
1
13
Table 3. Friedel–Craft reaction of the Baylis–Hillman adducts
with different arenes using Fe -K-10 clay under reflux for
3þ
The authors thank UGC and CSIR, New Delhi for financial
assistance.
30 min
a
Isolated
yield/%
Entry
Substrate
Arene
Product
References and Notes
1
COOMe
OH
Part 62 in the series, ‘‘Studies on novel synthetic methodolo-
gies,’’ IICT Comunication No. 050821.
a) A. B. Baylis and M. E. D. Hillman, German Patent 2155113
9
2
COOMe
1
2
PhCH
PhCH
3
Me
o:p = 45:55
2
COOMe
OH
(
1972); Chem. Abstr., 77, 34174q (1972). b) D. Basavaiah,
A. J. Rao, and T. Satyanarayana, Chem. Rev., 103, 811
2003), and references cited therein.
9
1
COOMe
3
Cl
Cl
Cl
Me
o:p = 34:66
(
COOMe
OH
84
3
4
a) H. M. R. Hoffmann and J. Rabe, Angew. Chem., Int. Ed.
Engl., 24, 94 (1985). b) R. Buchholz and H. M. R. Hoffmann,
Helv. Chim. Acta, 74, 1213 (1991). c) D. Basavaiah, M.
Bakthadoss, and S. Pandiaraju, J. Chem. Soc., Chem. Com-
mun., 1998, 1639.
a) B. Das, J. Banerjee, N. Ravindranath, and B. Venkataiah,
Tetrahedron Lett., 45, 2425 (2004). b) B. Das, J. Banerjee,
and N. Ravindranath, Tetrahedron, 60, 8357 (2004). c) B.
Das, J. Banerjee, G. Mahender, and A. Majhi, Org. Lett.,
6, 3349 (2004). d) B. Das, J. Banerjee, A. Majhi, and G.
Mahender, Tetrahedron Lett., 45, 9225 (2004). e) B. Das, G.
Mahender, N. Chowdhury, and J. Banerjee, Synlett, 2005,
COOMe
3
4
5
6
PhCl
Cl
Cl
o:p = 42:58
OH
CN
89
PhCH
PhCH
PhCl
3
3
Me
CN
o:p = 43:57
OH
CN
91
Me
Cl
CN
Cl
Cl
o:p = 35:65
OH
CN
8
7
CN
o:p = 37:63
Cl
Cl
a
alkene (for the Entries 1–3) with opposite stereochemistry was
obtained in trace quantity (2–4%).
1
000.
D. Basavaiah and R. M. Reddy, Tetrahedron Lett., 42, 3025
2001), and references cited therein.
M. Takasuji, M. Aneta, T. Masamune, A. Shirata, and K.
Takahashi, Chem. Lett., 1980, 339.
a) D. Basavaiah, M. Krishnamacharyulu, R. S. Hyma, and
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Basavaiah, S. Pandiaraju, and K. Padmaja, Synlett, 1996,
393. c) H. J. Lee, M. R. Seong, and J. N. Kim, Tetrahedron
Lett., 39, 6223 (1998).
plained7c by considering the plausible mechanism (Figure 1) and
transition state models A, B, and C (Figure 2). Model A is more
favoured than B when EWG = –COOMe and R = aryl and (E)-
products are thus formed from 1. However, when R = alkyl, due
5
6
7
(
7
c
to the steric strain between –CH2- of the benzyl group and R,
possibly both the transition states A and B operated to afford the
mixture of (E)- and (Z)-products. On the other hand, model C is
more favoured than A when EWG = –CN (as –CN is linear) and
hence (Z)-products are formed from 2.
The present methodology was extended to the Friedel–Craft
reaction of other aromatic compounds with the Baylis–Hillman
adducts (Table 3). The trisubstituted alkenes were obtained in
high yields and in excellent stereoselectivity.
8
9
B. M. Choudary, N. S. Chowdari, and M. L. Kantam, Tetra-
hedron, 56, 7291 (2000).
a) G. W. Kabalka, B. Venkataiah, and G. Dong, Org. Lett., 5,
3803 (2003). b) L. Navarre, S. Darses, and J. P. Gnet, J. Chem.
Soc., Chem. Commun., 2004, 1108.
1
0 a) P. Laszlo and A. Mathy, Helv. Chim. Acta, 70, 557 (1987).
b) K. V. N. S. Srinivas and B. Das, J. Org. Chem., 68, 1165
(2003).
In conclusion, we have developed a convenient one-pot gen-
eral methodology for stereoselective synthesis of trisubstituted
Published on the web (Advance View) October 1, 2005; DOI 10.1246/cl.2005.1492