Montmorillonite clay-catalyzed hetero-Diels-Alder reaction of 2,3-dimethyl-1,3-butadiene with benzaldehydes

Article abstract of DOI:10.1016/j.tetlet.2007.01.010

Montmorillonite K10 clay was found to catalyze the hetero-Diels-Alder reaction of 2,3-dimethyl-1,3-butadiene with o-anisaldehyde and other benzaldehyde derivatives; a transition state involving chelation of the clay's metal ions with the dienophile's heteroatoms is proposed.

Full text of DOI:10.1016/j.tetlet.2007.01.010

Tetrahedron Letters 48 (2007) 1577–1579
Montmorillonite clay-catalyzed hetero-Diels–Alder reaction
of 2,3-dimethyl-1,3-butadiene with benzaldehydes
Matthew R. Dintzner,* Andrew J. Little, Massimo Pacilli, Dominic J. Pileggi,
Zachary R. Osner and Thomas W. Lyons
Department of Chemistry, DePaul University, 1036 West Belden Ave., Chicago, IL 60614, United States
Received 7 September 2006; revised 18 December 2006; accepted 3 January 2007
Available online 7 January 2007
Abstract—Montmorillonite K10 clay was found to catalyze the hetero-Diels–Alder reaction of 2,3-dimethyl-1,3-butadiene with o-
anisaldehyde and other benzaldehyde derivatives; a transition state involving chelation of the clay’s metal ions with the dienophile’s
heteroatoms is proposed.
Ó 2007 Elsevier Ltd. All rights reserved.
Construction of the dihydropyran ring system via het-
ero-Diels–Alder reactions that employ aldehydes as
dienophiles is well precedented and has been featured
in the synthesis of a wide variety of natural products.1,2
There have been numerous reports on the hetero-Diels–
Alder reaction of aldehydes with activated dienes (such
as Danishefsky’s diene and the like) or with nonactiva-
ted simple dienes under forced conditions.3 The reaction
of aldehydes with simple, nonactivated dienes under
mild conditions, however, is much less well precedented,
and the use of electron-rich benzaldehydes as dieno-
philes has not been reported.4 Herein we describe a
novel, Montmorillonite clay-catalyzed hetero-Diels–Alder
reaction of o-anisaldehyde and other benzaldehyde
derivatives with 2,3-dimethyl-1,3-butadiene (1 + 2!3,
Scheme 1).
A recent work in our laboratories has shown that Mont-
morillonite clays are effective natural catalysts for the
synthesis of heterocyclic compounds like benzopyrans5
and chromenes6 under mild conditions. In an effort to
further broaden the repertoire of applications of clays
as environmentally benign catalysts for organic reac-
tions, we investigated the hetero-Diels–Alder reaction
of 2,3-dimethyl-1,3-butadiene (1) with benzaldehyde
derivatives (2a–l). Preliminary experiments, which were
conducted with benzaldehyde (1.1 mmol) and 2,3-di-
methyl-1,3-butadiene (1.0 mmol) in refluxing carbon
tetrachloride with Montmorillonite K10 clay (1 equiv
by weight), were minimally encouraging. Only about
10% conversion to the desired Diels–Alder adduct was
observed, along with unreacted benzaldehyde and
dimerized diene. We found that preheating the clay to
110 °C for 1 h prior to conducting the reaction made
for a more active Lewis acid catalyst and resulted in
an improved conversion of reactants to the desired
Diels–Alder adduct, though dimerization was still a
competing side reaction. Heating the clay to even higher
temperatures (200 °C, 1 h) provided an even more active
catalyst, presumably due to the collapse of the clay’s
interlayer structure as water is extruded, with subse-
quent decrease in Bronsted acidity and increase in Lewis
acidity.7 We found that this more activated clay pro-
moted much better conversion to the desired product
and successfully suppressed dimerization of the diene.
R
Montmorillonite
K10
R
H
+
O
CCl4
25 °C
O
3a-l
2a-l
1
Scheme 1. Montmorillonite clay-catalyzed hetero-Diels–Alder reaction.
Keywords: Montmorillonite K10 clay; Hetero-Diels–Alder; Dienes;
Benzaldehydes; Chelation; Dihydropyran; Green chemistry.
We next surveyed a variety of substituted benzalde-
hydes to determine the reaction scope (Table 1). Inter-
estingly, the best percent conversions were observed for
*
Corresponding author. Tel.: +1 773 325 4726; fax: +1 773 325
7421; e-mail: mdintzne@depaul.edu
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.01.010

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M. R. Dintzner et al. / Tetrahedron Letters 48 (2007) 1577–1579
Table 1. Reaction scope
Entry
Aldehyde
Time (min)
Product4
% Conversiona
1
2
3
4
5
6
7
8
9
Benzaldehyde (2a)
o-Anisaldehyde (2b)
60
60
60
15
60
60
24
60
60
60
24
24
3a
3b
3c
3d
3e
3f
52
81
25
49
34
68
22
75
7
o-Ethoxybenzaldehyde (2c)
o-Fluorobenzaldehyde (2d)
o-Chlorobenzaldehyde (2e)
o-Bromobenzaldehyde (2f)
o-Cyanobenzaldehyde (2g)
o-Nitrobenzaldehyde (2h)
o-Tolualdehyde (2i)
p-Anisaldehyde (2j)
p-Chlorobenzaldehyde (2k)
p-Nitrobenzaldehyde (2l)
3g
3h
3i
10
11
12
3j
<1
56
56
3k
3l
a Measured by GC–MS.
benzaldehyde derivatives with electronegative substitu-
ents in the ortho position, in particular o-anisaldehyde,
which we surmise allows for transition-state stabiliza-
tion involving possible chelation of the clay’s metal
ions with aldehyde oxygen (4, Fig. 1). Apparently,
the stabilizing interaction of the aldehyde’s ortho-
substituent with the clay compensates for electronic
deactivation, especially with substrates like 2b, for
which hetero-Diels–Alder reactions have until now
been absent from the literature. Minimal Diels–Alder
reaction observed with o-tolualdehyde (2i), for which
chelation is not possible, further supports our proposal
for possible transition-state stabilization via coordi-
nation of the clay with the aldehyde oxygen and
electron-rich ortho-substituents.
In order to further optimize the desired reaction, we next
investigated the effect of the relative amount of clay used
on the hetero-Diels–Alder reaction of o-anisaldehyde
(2b) with 2,3-dimethy-1,3-butadiene (1). The reaction
was run with increasing amounts of clay and a sharp
increase in percent conversion to 3b was observed with
1.4–2.0 mass equiv of clay relative to aldehyde (Table 2
and Fig. 2). Thus, the reaction appeared to work best
Table 2. Clay titration
Entry
Relative amount of clay by mass
% Conversiona
1
2
3
4
5
6
7
8
0.2
0.4
1.0
1.2
1.4
1.6
1.8
2.0
10
23
14
34
73
72
79
81
O
X
M
4
M = Activated Montmorillonite K10
X = -OCH3, -F, -Cl, -Br, OCH2CH3
Figure 1. Proposed hetero-Diels–Alder transition state.
a Measured by GC–MS.
Clay Titration
90
80
70
60
50
40
30
20
10
0
0
0.5
1
1.5
2
2.5
Equivalents of Clay by Mass
Figure 2. Clay titration.

M. R. Dintzner et al. / Tetrahedron Letters 48 (2007) 1577–1579
1579
94% based on the recovered starting material) and ana-
lyzed by IR and NMR spectroscopy and GC–MS.17
O
R'
O
R'
K10
R'
H
O
O
R'
Acknowledgments
5, R' is aliphatic
6
We thank DePaul University’s College of Liberal Arts
and Science funding, and the National Science Founda-
tion CCLI A&I program (Grant No. DUE-0310624) for
the support in purchasing our Bruker Avance 300 MHz
NMR spectrometer.
Scheme 2. Clay-catalyzed trimerization of aliphatic aldehydes.
with clay that was activated at 200 °C for 1 h and used
in twofold mass excess relative to the aldehyde.
References and notes
Attempts to carry out similar reactions with less substi-
tuted dienes, such as isoprene, were only minimally suc-
cessful, giving some of the desired Diels–Alder adducts
but larger amounts of products of higher molecular
weights. The use of aliphatic aldehydes, such as propi-
onaldehyde and butyraldehyde (5, Scheme 2), as the
dienophile component resulted not in the formation of
the Diels–Alder adducts, but gave predominantly the
corresponding trioxane products (6). We are currently
investigating the clay-catalyzed trimerization of ali-
phatic aldehydes, which will be reported in a separate
Letter.
1. Review: Bednarski, M. D.; Lyssikatos, J. P. In Compre-
hensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, UK, 1991; Vol. 2, pp 661–706.
2. Review: Boger, D. L.; Weinreb, S. M. Hetero Diels–Alder
Methodology in Organic Synthesis; Academic Press: New
York, 1987.
3. Review: Danishefsky, S. J.; Deninno, M. P. Angew. Chem.,
Int. Ed. Engl. 1987, 26, 15–23.
4. Oi, S.; Kashiwagi, K.; Terada, E.; Ohuchi, K.; Inoue, Y.
Tetrahedron Lett. 1996, 37, 6351–6354.
5. Dintzner, M. R.; McClelland, K. M.; Morse, K. M.;
Akroush, M. H. Synlett 2004, 11, 2028–2030.
6. Dintzner, M. R.; Lyons, T. W.; Akroush, M. H.; Wucka,
P.; Rzepka, A. T. Synlett 2005, 5, 785–788.
7. Yahiaoui, A.; Belbachir, M.; Hachemaoui, A. Int. J. Mol.
Sci. 2003, 4, 548–561.
8. Zhao, H.; Malhotra, S. V. Aldrichim. Acta 2002, 35, 75–83.
9. Li, M.; Xu, Z.; Ma, C.; Zhang, W. Zhejiang Gongye Daxue
Xuebao 2002, 30, 500–504.
10. Tundo, P.; Perosa, A. Chem. Rev. 2002, 2, 13–23.
11. Onaka, M. Gendai Kagaku 2002, 371, 14–20.
12. Onaka, M. Petrotech 2001, 24, 837–841.
13. Cave, G. W. V.; Raston, C. L.; Scott, J. L. Chem.
Commun. 2001, 21, 2159–2169.
As ‘green chemistry’ becomes more prevalent in organic
synthesis,8–14 environmentally benign clays are becom-
ing attractive alternatives to more toxic Lewis acid cat-
alysts for an array of reactions,15,16 and optimization
of conditions for their use is necessary. The work re-
ported here has proven important in our ongoing efforts
to demonstrate the utility of Montmorillonite clays in
organic synthesis, and may prove useful for others as
well. We are currently investigating the additional appli-
cations of clays as catalysts for organic reactions.
14. Reed, S. M.; Hutchinson, J. E. J. Chem. Ed. 2000, 77,
1627–1629.
A representative experimental procedure for the clay-
catalyzed hetero-Diels–Alder follows for 3b: Montmo-
rillonite K10 clay (50 mg) was measured into a vial
and heated in an oven at approximately 200 °C for
1 h. The activated clay was transferred to a desiccator
and allowed to cool to room temperature. To the clay
was added 0.1 mL CCl4, followed by 0.11 mmol o-anis-
aldehyde. The mixture was allowed to sit for about
5 min. Then, 2,3-dimethyl-1,3-butadiene (0.10 mmol)
was added via pipette. The reaction mixture was allowed
to sit at room temperature for 1 h, then filtered to re-
move the clay. Solvent was removed under vacuum
and the product isolated as a pale yellow oil (15 mg,
15. Nagendrappa, G. Resonance 2002, 64–77.
16. Corey, E. J.; Wu, L. I. J. Am. Chem. Soc. 1993, 115, 9327–
9328.
17. 3,6-Dihydro-4,5-dimethyl-2-(2-methoxyphenyl)-2H-pyran
(3b). IR: 2918, 2835, 1589, 1493, 1462, 1371, 1287, 1242,
1
1100, 1050, 1032, 753 cmꢀ1; H NMR (CDCl3) d 7.63 (d,
J = 7.6 Hz, 1H), 7.32 (t, J = 7.8 Hz, 1H), 7.09 (t,
J = 7.5 Hz, 1H), 6.92 (d, J = 8.1 Hz, 1H), 5.04 (dd, J =
3.8, 8.2 Hz, 1H), 4.27 (m, 2H), 3.87 (s, 3H), 2.30 (m, 2H),
1.79 (s, 3H), 1.70 (s, 3H); 13C NMR (CDCl3) d 155.8,
136.5, 128.1, 126.1, 124.3, 120.9, 110.1, 70.9, 70.5, 55.2,
37.6, 18.4, 13.9 ppm; GC–MS (70 eV), tR = 11.612 min,
m/z 218 M+ (44%); 135, [Mꢀ83]+ (100%); 82, [Mꢀ136]+
(79%); 67, [Mꢀ151]+ (87%).