Montmorillonite K10 clay-catalyzed synthesis of substituted 1-aryl indenes from Baylis-Hillman adducts

Article abstract of DOI:10.1246/cl.2005.1494

An eco-friend method for the synthesis of 1-aryl indenes from Baylis-Hillman adducts using Mont. K10 and microwave combination as catalyst system and a procedure for the synthesis of β-phenyl-substituted-protected Baylis-Hillman adducts with highly Z-sele

Full text of DOI:10.1246/cl.2005.1494

1494
Chemistry Letters Vol.34, No.11 (2005)
Montmorillonite K10 Clay-catalyzed Synthesis of Substituted 1-Aryl Indenes
from Baylis–Hillman Adducts
Ponnusamy Shanmugamꢀ and Paramasivan Rajasingh
Organic Chemistry Division, Regional Research Laboratory (CSIR), Trivandrum-695 019, Kerala, India
(Received July 13, 2005; CL-050907)
An eco-friend method for the synthesis of 1-aryl indenes from
The reason could probably be due to the cumulative effect of ster-
eochemical disfavor of the intermediate carbocation with respect
to the arene group and destabilization of the carbocation by the
nitrile group (Figure 2). Similarly, the other adducts 2b and 3b
furnished enyne ethers 5b and 6b in good yields (Table 1).
Baylis–Hillman adducts using Mont. K10 and microwave combi-
nation as catalyst system and a procedure for the synthesis of ꢀ-
phenyl-substituted-protected Baylis–Hillman adducts with highly
Z-selectivity have been reported.
H3CO
Z=CN
Z
H3CO
H3CO
H3CO
Z=E
H3CO
E=CO2Me
E
CN
The Baylis–Hillman reaction1 is one of the important C–C
bond forming reactions and it has been used in organic synthesis
for the preparation of a variety of compounds having diverse func-
tional groups. The clay catalysts are known as eco-friendly acid
catalysts which have potential for replacing the conventional min-
eral acids and are non-pollutant.2 The advantages of the clay-cata-
lyzed reactions are that they are generally mild, solvent free, and
easy work-up.2 In continuation of our research work3,4 on mont-
morillonite K10 clay catalyst and Baylis–Hillman adducts in or-
ganic synthesis, herein we report the Mont. K10 clay-microwave
mediated synthesis of functionalised indenes by the generation
of two types of stabilized allylic carbocation intermediates as
shown in Figure 1, structures B and C.
H3CO
H3CO
E
E
H3CO
H3CO
H3CO
H3CO
E
H3CO
H
Figure 2.
Table 1. Synthesis of indenes (4a–6a) and enyne ethers (4b–6b)
Entry
Adduct
R1& R2
Product
Yield/%
1
2
3
4
5
6
1a
2a
3a
1b
2b
3b
Methyl
Ethyl
4a
5a
6a
4b
5b
6b
52
50
49
70
69
65
-CH2-
Methyl
Ethyl
E
E
RO
RO
E
-CH2-
According to the reported mechanism,5 the reaction proceed
through electrocyclic ring closure facilitated by an alkoxy group
at 3-position of the arene. However, the role of 4-alkoxy substitu-
tion is not revealed by the mechanism. Hence, we examined the re-
activity of adduct with only 3-alkoxy substitution. Accordingly, to
our surprise, the 3-methoxy substituted adduct 7 furnished only
12% yield of the indene derivative 8 (Scheme 2). The low yield
of the product formation showed the necessity of an electron re-
leasing group at 4-position and is essential to facilitate the ring clo-
sure more effectively for higher yield. Hence, we propose the role
of 4-methoxy group in the electrocyclic ring closure based on the
mechanism shown in Figure 2.
On the other hand, to achieve the goal for the synthesis of in-
dene derivatives irrespective of whether the aryl ring is substituted
or unsubstituted in the Baylis–Hillman adducts, we envisaged
by introduction of a phenyl group at the ꢀ-position which would
stabilizes the allylic cation intermediate by both the aryl groups.
(Figure 1, structure C). Thus, the suitable precursor for the con-
struction of indenes would be the ꢀ-phenyl substituted Baylis–
Hillman adducts 18–21 (Scheme 3).
The literature known Heck coupling6 for the synthesis of ꢀ-
phenyl substituted adduct 18 from acetate adduct 9 failed to afford
the desired product and furnished only the isomerized product as
evidenced by spectral studies.7 Hence, we developed a procedure
for the preparation of the adduct 18–21 by a three-step-reaction se-
quence viz. 1. An intermolecular Friedel–Crafts reaction catalyzed
by Mont. K10 clay, 2. Allylic bromination, and 3. An alkoxide sub-
stitution (Scheme 3). The side dimerised product 13 was readily
converted to compound 14 upon longer heating under Mont. K10
clay catalyst. Accordingly, compounds 9–12 were converted to
compounds 14–17. It should be noteworthy that the procedure de-
C
B
A
E=CO Me
2
Figure 1. Structure of allylic carbocations. A. Less stabilized B. Stabilized
by electron releasing group at phenyl group; C. Stabilized by diaryl group.
During the course of our studies on the synthesis of oxacy-
cles,4c–4e we attempted the preparation of enyne ethers from the
Baylis–Hillman adduct 1a with 2-propynyl alcohol under thermal
condition (Mont. K10, heat).4b We did not get the desired enenyne
ether but indene5 4a was obtained in 52% yield. The result prompt-
ed us to explore the present catalyst system would be a good re-
placement of the earlier P2O5 catalyzed synthesis of indenes
(Scheme 1).5 Similarly, under the optimized condition, the other
adducts 2a and 3a furnished the corresponding indenes 5a and
6a in moderate yields. (Table 1)
In order to compare and examine the difference in the reactiv-
ity of the Baylis–Hillman adducts bearing the nitrile substitution,
the adduct 1b, in contrary, afforded only the enenyne ether 4b in
70% yield and not the expected indene derivative (Scheme 1).
OH
R1O
a or b
R2O
R1O
R2O
R1O
a
Z
O
CO2CH3
CN
4b−6b
R1,R2 = Me, Et,-CH2-
R2O
4a−6a
1a−3a Z = CO2CH3
1b−3b Z = CN
(a) 2-Propynyl alcohol, Mont. K10, 80 °C, 12 h. (b) Mont. K10 clay, µw, 8 min.
Scheme 1.
OH
H3CO
H3CO
CO2CH3
Mont. K10
CO2CH3
12%
µw, 8 min.
8
7
Scheme 2.
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.11 (2005)
1495
AIBN were added to the reaction mixture and refluxed for 4 h.
Then 3 equiv. of methanol was added and reflux was continued
for 2 h. The solvents were removed under vacuum. The crude
mixture was treated with Mont. K10 clay (75 mg, 30% w/w) and
irradiated in a microwave oven for 4 min. Finally, the mixture
was cooled to rt and diluted with 5 mL of CH2Cl2 and filtered.
The solvent was removed and the crude was purified through silica
gel column using hexane–EtOAc (95:5) to give highly functional-
ized indene 25 as colourless crystal in 61% overall yield.
as time increases
OR
OH
E
E
E
b
Ar = Ph
Ph
Ar
Ar
Ph
E
+
a
Ar
O
9 Ar = Ph
14 Ar = Ph
18-21
Table 2.
Ph
13 (Ar = Ph)
10 Ar = p-Cl-C6H4
11 Ar = p-Me-C6H4
12 Ar = m-OMe-C6H4
15 Ar = p-Cl-C6H4
16 Ar = p-Me-C6H4
E=CO Me
2
17 Ar = m-OMe-C6H4
(a) Benzene, Mont. K10, 6 h, (b) i) NBS, CCl4, AIBN, reflux, 4 h; ii) ROH, reflux, 5 h
Scheme 3.
Table 2. Synthesis of functionalized (Z)-ꢀ-phenyl-substituted-protected
adducts (18–24)
Compound 4b: 1H NMR: ꢁ 2.49 (t, 1H, J ¼ 2:25 Hz), 3.92 (s, 6H),
4.25 (d, 2H, J ¼ 2:25 Hz), 4.31 (s, 2H), 6.87 (d, 1H, J ¼ 8:35 Hz),
7.09 (s, 1H), 7.22 (d, 1H, J ¼ 8:35 Hz), 7.60 (s, 1H). 13C NMR: ꢁ
55.86, 55.89, 57.24, 70.58, 75.51, 78.74, 104.12, 110.59, 110.83,
118.11, 124.17, 125.90, 145.51, 151.41. Mass spectra m=z: 257
(Mþ); HRMS (m=z): cacld for C15H15NO3, 257.1052; found:
257.1048. Compound 8: White solid; mp 86–88 ꢁC; Yield: 12%;
IR (neat) ꢂmax: 1721 cmꢂ1.1H NMR: ꢁ 3.6 (s, 2H), 3.82 (s, 6H),
6.86 (1H, dd, J ¼ 8:26 and 2.35 Hz), 7.0 (d, 1H, J ¼ 2:35 Hz),
7.36 (d, 1H, J ¼ 8:26 Hz), 7.64 (s, 1H). 13C NMR: ꢁ 37.51,
51.35, 55.18, 107.86, 114.24, 124.57, 136.76, 138.07, 140.98,
143.79, 158.99, 164.90. Mass spectra m=z: 204 (Mþ); HRMS
(m=z): cacld for C12H12O3, 204.0786; found: 204.0794. Com-
pound 18: 1H NMR: ꢁ 3.29 (s, 3H), 3.52 (s, 3H), 5.06 (s, 1H),
6.64 (s, 1H), 7.15–7.32 (m, 10H). 13C NMR: ꢁ 51.51, 57.14,
83.73, 127.36, 128.03, 128.14, 128.31, 133.29, 134.96, 135.23,
138.64, 168.76. Mass spectra m=z: 282 (Mþ); HRMS (m=z): cacld
for C18H18ClO3, 282.1256; found: 282.1259. Compound 25: Col-
orless solid; mp 126–128 ꢁC; Yield: 61%; IR (neat) ꢂmax: 1702,
Entry
ROH
Product
Yield/%
1
2
3
4
5
6
Methanol
Ethanol
18
82
81
80
76
74
65
19
20
Propargyl alcohol
Homo propargyl
Phenol
21
22 and 23
24
p-Cresol
scribed herein furnished only the (Z)-ꢀ-phenyl-substituted-pro-
tected adduct 18 as a single product as evidenced by NMR.8 The
effect of alkoxide substitution at allylic position with various alco-
hol were also studied and all of them furnished the functionalized
products in good yield (Schemes 3 and Table 2).
The stereochemistry of alkene was fixed at the allylic bromi-
nation step based on 1H NMR analysis. Heating the ꢀ-phenyl-sub-
stituted protected-adduct 18 in the presence of Mont. 10 clay and
microwave combination furnished the functionalized indene 25
in 90% yield (Scheme 4). The Mont. K10 clay recovered from
the reaction mixture by filtration can be recycled three times with-
out losing its activity by activating the clay at 100 ꢁC for 3 h. In an
attempt, we also successfully developed a two-pot synthesis of
substituted indenes 25 and 26 from adducts 9 and 10 respectively
without isolation and purification of intermediates (see experimen-
tal). Some of the related cyclization reactions involving the Bay-
lis–Hillman adducts are known for organic synthesis.9–11
1
1610 cmꢂ1. H NMR: ꢁ 3.69 (s, 3H), 4.85 (s, 1H), 7.06–7.33 (m,
8H), 7.50 (d, 1H, J ¼ 7:23 Hz), 7.79 (s, 1H). 13C NMR: ꢁ 51.50,
55.64, 123.42, 124.48, 126.87, 127.29, 127.83, 128.31, 128.52,
128.61, 138.31, 141.13, 141.56, 150.41, 164.72. Mass spectra
m=z: 250 (Mþ); HRMS (m=z): cacld for C14H16O2, 250.0994;
found: 250.0992.
In conclusion, we have developed an efficient; eco-friend
method for the synthesis of indenes from the Baylis–Hillman ad-
ducts having both electron rich and simple aryl groups through
the intramolecular Friedel–Crafts reaction. Thereby we have dis-
closed the importance of ꢀ-phenyl substituted adduct as a precur-
sor for the synthesis of highly substituted indenes. It is noteworthy
that the methodology could be applied for the total synthesis of in-
datraline11 and related natural products by choosing appropriate
substrates. Further work in this direction is under progress.
Synthesis of Indene 4a: A mixture of adduct 1a (125 mg, 0.5
mmol) and Mont. K10 (75 mg, 30% w/w) was taken in a 25 mL
conical flask and irradiated in a microwave oven for 8 min. The
mixture was cooled and diluted with 5 mL of CH2Cl2. The solvent
was removed in vacuo and the crude was purified through silica gel
column chromatography using hexane–EtOAc (95:5) to give in-
dene 4a as crystal in 52% yield. Synthesis of indene 25: The adduct
9 (250 mg, 1.3 mmol) in dry benzene (3 mL) and Mont. K-10 (125
mg, 50% w/w) was refluxed for 6 h. The clay was filtered off and
125 mg of fresh clay was added to the mixture and refluxed further
6 h. The clay was filtered out and solvent was removed in vacuo. N-
bromosuccinimide (231 mg, 2 equiv.), 5 mL of CCl4 and 50 mg of
The authors thank Prof. Dr. T. K. Chandrashekar, Director for
infrastructure facilities provided. One of the authors (PR) thanks
CSIR (New Delhi) for the award of Senior Research Fellowship.
References and Notes
1
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2
3
4
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5
6
7
D. Basavaiah, M. Bakthadoss, and G. J. Reddy, Synthesis, 2001, 919.
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A peak at ꢁ 4.9 is not for methine proton.as reported in Ref. 5. It corresponds to
the methylene protons of isomerized product (compared with the reported value).
The ꢁ value of methine proton should be more than ꢁ 4.9, because the methine
proton of the simple acylated adduct appeared at ꢁ 6.6.
8
9
The vinylic proton trans to ester group appeared at ꢁ 6.64 and ꢁ 133.29 in 1H and
13C NMR, respectively.
OH
a) D. Basavaiah and T. Satyanarayana, Chem. Commun., 2004, 32. b) D.
Basavaiah, D. S. Sharada, and A. Veerendhar, Tetrahedron Lett., 45, 3081
(2004).
CO2Me
CO2Me
a
R
R
10 a) S. Gowrisankar, K. Y. Lee, C. G. Lee, and J. N. Kim, Tetrahedron Lett., 45,
6141 (2004). b) S. Gowrisankar, C. G. Lee, and J. N. Kim, Tetrahedron Lett., 45,
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R = H, 25, 90%; 61%(one-pot)
R = Cl, 26, 54%
9, 10
a) (i) Benzene, Mont. K10, 12 h; (ii) 2 equiv. NBS, CCl4, 4 h, reflux;
(iii) Methanol, reflux, 2 h; (iv) Mont. K10, microwave, 4 min.
11 a) H. M. L. Davies and T. M. Gregs, Tetrahedron Lett., 43, 4951 (2002).
b) J. Cossy, D. Belotti, and A. Magner, Synlett, 2003, 1515.
Scheme 4.
Published on the web (Advance View) October 1, 2005; DOI 10.1246/cl.2005.1494