Montmorillonite clay catalyzed in situ Prins-type cyclisation reaction

Article abstract of DOI:10.1016/S0040-4039(00)01891-8

Homoallylic alcohols smoothly undergo cross-coupling reactions with aldehydes on the surface of montmorillonite clay to generate 4-hydroxy-2,6-disubstituted tetrahydropyrans in high yields with high diastereoselectivity.

Full text of DOI:10.1016/S0040-4039(00)01891-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 89–91
Montmorillonite clay catalyzed in situ Prins-type cyclisation
reaction†
J. S. Yadav,* B. V. Subba Reddy, G. Mahesh Kumar and Ch. V. S. R. Murthy
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Received 16 June 2000; revised 13 October 2000; accepted 26 October 2000
Abstract—Homoallylic alcohols smoothly undergo cross-coupling reactions with aldehydes on the surface of montmorillonite clay
to generate 4-hydroxy-2,6-disubstituted tetrahydropyrans in high yields with high diastereoselectivity. © 2000 Elsevier Science
Ltd. All rights reserved.
catalysts7 make reaction processes convenient, more
The acid catalyzed condensation of olefins with car-
economic, environmentally benign and act as both
bonyl compounds, known as the Prins reaction, is an
Bronsted and Lewis acids in their natural and ion-ex-
important reaction for carbon–carbon bond forma-
tion.1 The tetrahydropyran ring is part of the back-
bone of various important carbohydrates and natural
products.2 Furthermore, tetrahydropyrans hydroxy-
lated at the 4-position are found in a number of natural
products3 such as avermectins, aplysiatoxin, oscillatox-
ins, latrunculins, talaromycins and acutiphycins. The
synthesis of halogenated tetrahydropyrans is reported
using conventional Lewis acids4 which often generate
mixtures of products. Recently Sc(OTf)3 has been em-
ployed for Prins type cyclisations,5 which afford a
mixture of tetrahydropyranyl ethers and tetrahydro-
pyranols.
changed forms, enabling them to function as efficient
catalysts for various organic transformations. Al-
though, the construction of the six-membered tetra-
hydropyran ring is an important process in the
synthesis of natural products, the use of strongly acidic
conditions, expensive reagents and the formation of
mixtures of products illustrates the need for efficient,
inexpensive and environmentally acceptable catalysts
which can effect the transformation under mild condi-
tions.
In continuation of our interest on the applications of
solid acid catalysts (KSF) for various transformations8
herein we report a new and highly efficient procedure
for the synthesis of tetrahydropyranols using montmo-
rillonite KSF as the catalyst. 4-Hydroxy-2,6-disubsti-
tuted tetrahydropyran derivatives were formed in high
yields when homoallyl alcohols were treated with
aldehydes in the presence of KSF clay.9 For example,
In recent years, the use of solid acidic catalysts6 such as
clays and zeolites has received considerable attention in
different areas of organic synthesis because of their
environmental compatibility, reusability, high selectiv-
ity, operational simplicity, non-corrosiveness, low cost
and ease of isolation of the products. In particular, clay
Scheme 1.
Keywords: montmorillonite KSF; homoallylic alcohols; Prins cyclisation; tetrahydropyranols.
* Corresponding author.
†
IICT Communication No.4565.
0040-4039/01/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01891-8

90
J. S. Yada6 et al. / Tetrahedron Letters 42 (2001) 89–91
the reaction of benzaldehyde with 1-phenyl-3-buten-
1-ol on the surface of montmorillonite in refluxing
dichloromethane leads to the formation of 2,6-diphenyl-
4-hydroxytetrahydropyran in 90% yield with high
diastereoselectivity. The coupling constants of the ben-
zylic hydrogens (J=11.45 Hz) in the 1H NMR spectrum
of the products as well as the hydrogen on the carbon
bearing the hydroxyl group (J=4.5 and 12.5 Hz) showed
a structure consistent with the two phenyl groups and the
hydroxyl group being in the cis-orientation and equato-
rial. The predominant formation of a single stereoisomer
is probably due to thermodynamic factors.
The formation of the tetrahydropyranol may be ex-
plained by hemi-acetal formation and subsequent Prins-
type cyclisation (Scheme 1).
The reaction of aromatic aldehydes with the correspond-
ing homoallylic alcohols in the presence of KSF clay
generated symmetric 2,6-disubstituted 4-hydroxytetra-
Table 1. Montmorillonite KSF catalysed synthesis of tetrahydropyranolsa

J. S. Yada6 et al. / Tetrahedron Letters 42 (2001) 89–91
91
hydropyrans in high yields. Similarly, the Prins cyclisa-
tion between aliphatic aldehydes and the corresponding
homoallylic alcohols gave the symmetric 2,6-disubsti-
tuted 4-hydroxytetrahydropyrans with high stereoselec-
tivity. Moreover, the cross-coupling between aromatic
homoallylic alcohols and aliphatic aldehydes or the
cross-coupling between aliphatic homoallylic alcohols
and aromatic aldehydes gave the corresponding unsym-
metric tetrahydropyranols in good yields. The results
summarized in Table 1 indicate the scope and general-
ity of the reaction with respect to various aldehydes and
homoallylic alcohols. The nature of the substituents on
the aromatic rings of the reagent shows some effect on
this conversion. It is of interest to note that aliphatic,
simple aromatic and moderately activated aromatic
aldehydes like chloro-, bromo-, meta-phenoxy- and
meta-methoxy-benzaldehyde gave high yields of prod-
ucts compared to strongly activated or deactivated
nitro or cyano substituted aldehydes. The use of the
solid acid catalyst offers high yields of products with
high stereoselectivity. The clay catalyst was recovered
by filtration, washed with methanol and reused, after
activation, for three cycles without significant loss of
activity.
(b) Chandrasekhar, S.; Subba Reddy, B. V. Synlett 1998,
851.
2. Nicolaou, K. C.; Sorensen, E. J. Classics in Total Synthe-
sis; VCH: Weinhein, 1996.
3. Perron, F.; Albizati, K. F. J. Org. Chem. 1987, 52, 4130
and references cited therein.
4. (a) Wei, Z. Y.; Li, J. S.; Wang, D. Tetrahedron Lett. 1987
28, 3441. (b) Coppi, L.; Ricci, A.; Taddei, M. J. Org.
Chem. 1988, 53, 911. (c) Yang, J.; Viswanathan, G. S.; Li,
C.-J. Tetrahedron Lett. 1999, 40, 1627
5. Zhang, W.-C.; Viswanathan, G. S.; Li, C.-J. J. Chem. Soc.,
Chem. Commun. 1999, 291.
6. (a) Cornelis, A.; Laszlo, P. Synlett. 1994, 155. (b) Sen, S.
E.; Smith, S. M.; Sullivan, K. A. Tetrahedron 1999, 55,
12657.
7. (a) Balogh, M.; Laszlo, P. Organic Chemistry Using Clay;
Spinger-Verlag: New York, 1993. (b) Laszlo, P. Science
1987, 235, 1473. (c) Laszlo, P. Pure Appl. Chem. 1990, 62,
2027.
8. (a) Sampath Kumar, H. M.; Subba Reddy, B. V.; Mo-
hanty, P. K.; Yadav, J. S. Tetrahedron Lett. 1997, 38,
3619. (b) Yadav, J. S.; Subba Reddy, B. V.; Rasheed, M.
A.; Sampath Kumar, H. M. Synlett. 2000, 487. (c) Sam-
path Kumar, H. M.; Subba Reddy, B. V.; Anjaneyulu, S.;
Jagan, Reddy, E.; Yadav, J. S. New J. Chem. 1999, 23,
955.
9. Typical procedure: A mixture of 1-phenyl-3-buten-1-ol (5
mmol), benzaldehyde (5 mmol) and KSF clay (1.5 g) in
dichloromethane (20 ml) was refluxed for 3 h. On comple-
tion, as indicated by TLC, the catalyst was filtered and
washed with dichloromethane (2×15 ml). The combined
organic layers were washed with water, brine, dried over
anhydrous Na2SO4 and concentrated in vacuo. The result-
ing reaction mass was purified by column chromatography
on silica gel (Merk, 100–200 mesh, ethyl acetate–hexane,
2:8) to afford 2,6-diphenyl-4-hydroxytetrahydropyran as a
white solid (mp 101–102°C). 1H NMR (CDCl3): l 1.50
(brs, OH), 1.60 (dd, 2H, J=12.5 and 11.4 Hz), 2.35 (dd,
2H, J=12.5 and 4.5 Hz), 4.18 (m, 1H), 4.60 (d, 2H,
J=11.4 Hz), 7.23–7.30 (m, 10 H, ArꢀH). 13C NMR
(proton decoupled): l 43.0 (CH2), 68.5 (CH), 78.5 (CH),
126.0, 127.8, 128.5, 142.0 (aromatic). EIMS: m/z (%): 254
M+ (15), 236 (40), 136 (60), 104 (100), 77 (35).
In summary, we have described a new and highly
efficient procedure for the synthesis of tetra-
hydropyranols using an environmentally acceptable
montmorillonite KSF clay. The catalyst is inexpensive,
non-toxic and reusable which makes the process conve-
nient, more economic and environmentally benign.
Acknowledgements
BVS, GMK and CVSR thank CSIR New Delhi for the
award of fellowships
References
1. (a) Adams, D. R.; Bhatnagar, S. P. Synthesis 1977, 661.
.
.