Montmorillonite-mediated hetero-Diels-Alder reaction of alkenes and o-quinomethanes generated in situ by dehydration of o-hydroxybenzyl alcohols

Article abstract of DOI:10.1039/a900657e

The intermolecular hetero-Diels-Alder reaction of in situ-generated o-quinomethanes and unactivated alkenes has been accomplished through a wet montmorillonite catalyst in a LiClO₄-MeNO₂ solution to give good yields of varied chromane skeletons.

Full text of DOI:10.1039/a900657e

Montmorillonite-mediated hetero-Diels–Alder reaction of alkenes and
o-quinomethanes generated in situ by dehydration of o-hydroxybenzyl alcohols
Kazuhiro Chiba,* Tetsuya Hirano, Yoshikazu Kitano and Masahiro Tada
Laboratory of Bio-organic Chemistry, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu,
Tokyo 183-8503, Japan. E-mail: chiba@cc.tuat.ac.jp
Received (in Cambridge, UK) 25th January 1999, Accepted 9th March 1999
The intermolecular hetero-Diels–Alder reaction of in situ-
generated o-quinomethanes and unactivated alkenes has
been accomplished through a wet montmorillonite catalyst
in a LiClO4–MeNO2 solution to give good yields of varied
chromane skeletons.
generated o-quinomethanes by the dehydration of the corre-
sponding o-hydroxybenzyl alcohol. The reaction media showed
a remarkable acceleration property in the generation and
intermolecular cycloaddition of the unstable o-quinomethanes
with varies unactivated alkenes.
o-Quinomethanes play an important role as the heterodiene in
the construction of a wide variety of chromane skeletons via
hetero-Diels–Alder reaction with alkenes (Scheme 1). The
generation and cycloaddition of o-quinomethanes has been
extensively investigated, including pyrolysis of o-hydroxy-
benzyl alcohols,1 one-electron oxidation of o-substituted phe-
nols,2 desilylation of an o-hydroxybenzyl alcohol disilyl ether,3
and dehydrogenation of allylphenols with DDQ.4 However, as
the o-quinomethanes are generally very unstable, they must be
trapped by highly active, electron-rich alkenes, by intra-
molecular reactions, or under high-temperature conditions.
Furthermore, by-products of the homo-Diels–Alder reaction,
Michael addition, or Friedel–Crafts reaction of o-quino-
methanes have also often been obtained with desired products
(Scheme 2).5 On the other hand, it has been proposed that many
natural products can be generated via the intermolecular
cycloaddition of o-quinomethanes and aliphatic alkenes.6
Biogenetically, it has been proposed that o-quinomethanes are
produced by the dehydration of the corresponding o-hydroxy-
benzyl alcohols or benzylic oxidation of the corresponding
o-cresol derivatives.7 Biomimetic mild reaction media in which
o-quinomethanes are generated and trapped efficiently by
unactivated aliphatic alkenes have therefore been sought.
Recently, we performed the intermolecular hetero-Diels–Alder
reaction of electrochemically generated electon-rich o-quino-
methanes and unactivated aliphatic alkenes to construct some
natural product skeletons, but the o-quinomethanes were
limited to stable ones possessing electron-donating groups
(Scheme 3). Accordingly we have further investigated the
biomimetic facile method for the generation and cycloaddition
reaction of o-quinomethanes, and found that a catalytic amount
of wet montmorillonite in a LiClO4–MeNO2 solution efficiently
MeO
MeO
OH
MeO
MeO
MeO
MeO
O
–e
+
LiClO4, MeNO2
SPh
O
Scheme 3
Under the usual dehydration conditions of benzyl alcohols
using Lewis acids or Brønsted acids, salicyl alcohol and
2-methylbut-2-ene 3 gave the corresponding cycloadducts 10
and 11 in very low yields (Table 1). On the other hand, a
catalytic amount of dry montmorillonite K 10 in MeNO2 gave
the desired cycloadducts in 26.8%, and the addition of LiClO4
effectively increased the yield to 54.8%. Furthermore, the
reaction proceeded to give 10 and 11 (6:1) almost quantita-
tively by using wet montmorillonite K 10 in the presence of
LiClO4 in MeNO2 at ambient temperature. The wet montmor-
illonite did not work well in other solvents, even in the presence
of LiClO4. Accordingly, the targeted reactions with varied
alkenes were performed in MeNO2 in the presence of an o-
hydroxybenzyl alcohol, wet montmorillonite, and LiClO4 at
ambient temperature.† Styrenes gave excellent yields of the
corresponding flavanes, while unactivated aliphatic alkenes
simply gave chromanes and spirochromanes in good yields
(Table 2). Some products were obtained due to skeleton
rearrangement of the alkene moieties (Scheme 4).
In the present reaction media, the dehydration reaction may
be accelerated on the wide surface of montmorillonite, and the
Table 1 Effect of catalysts and reaction media on the cycloaddition of 3 and
o-quinomethane generated by the dehydration of salicyl alcohol 1a
R1
R3
R2
O
R1
R2
O
Solvent
Catalyst
Additive
Yield (%)
+
R3
R4
R4
b
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
Et2O
CH2Cl2
MeNO2
MeNO2
MeNO2
MeNO2
a
TiCl4
none
none
none
none
none
12.7
13.7
1.8
BF3/Et2Ob
Scheme 1
b
ZnCl2
MsOHb
17.1
10.6
12.1
trace
trace
15.8
26.8
54.8
> 99
b
P2O5
wet mont.c
wet mont.
wet mont.
wet mont.
dry mont.d
dry mont.
wet mont.
LiClO4
e
O
O
O
LiClO4
LiClO4
none
none
LiClO4
LiClO4
+
O
OH
X
O
X
b
20 mg of 1 and 3 equiv. of 3 were dissolved in 2.0 ml of solvent. 1.5
equiv. of catalyst was added. c 20 mg of montmorillonite and 36 mg of water
were added to 2 ml of solvent. d 20 mg of montmorillonite was added to 2.0
ml of solvent. e 200 mg of LiClO4.
O
HO
e.g. X = SMe
Scheme 2
Chem. Commun., 1999, 691–692
691

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Table 2 Montmorillonite-mediated cycloaddition of o-quinomethanes and alkenesa
Yield
(%)
Yield
(%)
Substrate
Alkene
Products
Substrate Alkene
Products
O
O
O
O
OH
>99
1
78
OH
11
18
10
7
17
1
1
3
(17:18=1.7:1)
(10:11=6:1)
O
Ph
94
O
1
1
>99
>99
8
9
19
12
4
5
O
p-Tolyl
>99
O
20
O
1
O
OH
OH
13
14
4
76
79
(13:14=2:1)
2
2
21
Ph
Ph
O
O
O
O
Pr
8
1
85
22
23
15
16
6
(15:16=4:1)
(22:23=2:1)
a 2-Hydroxybenzyl alcohol (20 mg) and 3 equiv. of alkene were dispersed in 2.0 ml of 0.1 m LiClO4–MeNO2 in the presence of 20 mg of montmorillonite
and 36 mg of water. The reaction mixture was allowed to stand at ambient temperature for 48 h.
O–
O
O
Reactions’) from the Ministry of Education, Science, Sports and
Culture, Japan.
+
+
Notes and references
† General procedure: Montmorillonite K 10 (Aldrich) and water were
dispersed in 5 ml of MeNO2, and salicyl alcohol 1 (25 mg), styrene 8 (63
mg) and LiClO4 (50 mg) were dissolved in the solution. The reaction
mixture was allowed to stand at ambient temperture for 48 h under air
atmosphere. After the reaction was completed, products were extracted with
n-hexane. The n-hexane was removed in vacuo after drying with Mg2SO4,
and the residue was then separated by silica gel column chromatography
(n-hexane–AcOEt) to give the cycloadduct 19 in 94% yield.
O–
O
+
Scheme 4
addition of water might regulate the acidic decomposition and
polymerization of starting materials. LiClO4 is expected to
stabilize the in situ-generated zwitterion, which is an equivalent
of the o-quinomethane (Scheme 5). Furthermore, the products
are easily extracted from the reaction media with n-hexane, and
the catalytic solvent system can be reused many times.
Employing the hetero-Diels–Alder reaction of o-quinomethanes
in LiClO4–MeNO2 mediated by wet montmorillonite K 10 is
applicable to the formation of a variety of chromanes. In these
cases involving unsubstituted, unstable o-quinomethanes, the
cycloaddition reactions with unactivated alkenes proceeded
smoothly to give cycloadducts, including those which are
difficult to obtain in high yields via other methods.
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This work was supported by a Grant-in-Aid for Scientific
Research on Priority Areas (No. 283, ‘Innovative Synthetic
Li+
LiClO4, MeNO2
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OH
OH
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O–
+
O
O
–H2O
+H2O
–
ClO4
Montmorillonite K-10
Scheme 5
Communication 9/00657E
692
Chem. Commun., 1999, 691–692