Bismuth triflate catalyzed prins-type cyclization in ionic liquid: Synthesis of 4-tetrahydropyranol derivatives

Article abstract of DOI:10.1002/hc.20403

The reaction of aldehydes with homoallylic alcohols in the presence of catalytic amount of bismuth triflate in [bmim]PF₆generates 4-tetrahydropyranol derivatives in excellent yield and with high diastereoselectivity.

Full text of DOI:10.1002/hc.20403

Heteroatom Chemistry
Volume 19, Number 1, 2008
B
ismuth Triflate Catalyzed Prins-Type
Cyclization in Ionic Liquid: Synthesis
of 4-Tetrahydropyranol Derivatives
M. S. R. Murty, K. Rajasekhar, V. Harikrishna, and J. S. Yadav
Organic Chemistry Division I, Discovery Laboratory, Indian Institute of Chemical Technology,
Hyderabad 500 007, India
Received 4 May 2006; revised 20 December 2006
tracted as ecofriendly reagents in organic synthesis
ABSTRACT: The reaction of aldehydes with ho-
[4]. The ionic liquids are attracting growing inter-
moallylic alcohols in the presence of catalytic
est as an alternative to organic solvents for various
chemical and biotransformations [5]. Because of the
high polarity and ability to solubilize both inorganic
and organic compounds, ionic liquids are finding in-
creasing applications in organic synthesis [6]. In this
report, we describe the synthesis of tetrahydropyra-
nol derivatives through the Prins-type cyclization re-
action of homoallylic alcohols with aldehydes using
amount of bismuth triflate in [bmim]PF
6
generates
4-tetrahydropyranol derivatives in excellent yield and
with high diastereoselectivity. ꢀC 2008 Wiley Periodicals,
Inc. Heteroatom Chem 19:104–106, 2008; Published online
in Wiley InterScience (www.interscience.wiley.com). DOI
1
0.1002/hc.20403
bismuth triflate in [bmim]PF solvent system.
6
INTRODUCTION
The acid-catalyzed olefin-aldehyde condensation,
known as the Prins reaction, is an important carbon–
carbon bond forming reaction in organic synthe-
sis. Substituted tetrahydropyrans are the common
structural motif of many natural products [1], such
as avermectins, aplysiatoxin, oscillatoxins, latrun-
culins, talaromycins, acutiphycins, and apicularens.
Especially, tetrahydropyrans hydroxylated at the 4-
position are having more synthetic value [2]. Al-
though many synthetic methods have been reported
RESULTS AND DISCUSSION
The reaction was carried out by adding benzalde-
hyde and 3-buten-1-ol to a mixture of bismuth tri-
flate and [bmim]PF . After the mixture was stirred at
6
room temperature for 15 min, the TLC observation
showed the disappearance of starting materials. The
product was obtained after simple extraction with
ether. Furthermore, the crude product was purified
over silica gel, providing the product in 80% yield.
1
[3], there is still the scope to find potential alter-
By H NMR spectrum and NOE studies, the product
nate approaches and the development of ecofriendly
and good yield procedures would be more useful.
In recent years, bismuth compounds have been at-
was confirmed as cis-diastereoisomer and compared
with the literature data [3] (Scheme 1). The remain-
ing ionic liquid was washed with ether and recycled
in subsequent runs with gradual decrease in the ac-
tivity (Table 1).
Correspondence to: M. S. R. Murty; e-mail: msrmurty@iict.
res.in.
Contract grant sponsor: Council of Scientific and Industrial Re-
search, New Delhi, India.
ꢀ
c 2008 Wiley Periodicals, Inc.
Similarly, various aldehydes reacted smoothly
with homoallylic alcohols to give the corresponding
tetrahydropyran derivatives in good yield (Table 2).
It should be noted that the nature of substituents
104

Bismuth Triflate Catalyzed Prins-Type Cyclization in Ionic Liquid 105
−
solubilize the water and provides the OH nucle-
ophile for the tetrahydropyran carbonium ion.
CONCLUSION
SCHEME 1
In summary, we have described a green protocol
for the preparation of tetrahydropyran derivatives
through the Prins-type cyclization using bismuth
TABLE 1 Recovery and Reuse of the Ionic Liquid Phase
Containing Bi(OTf)3a
triflate and [bmim]PF
6
system. The attractive
features of this process are the recyclability, mild re-
action conditions, ecofriendly reagent, and cleaner
reactions with good yields, which make it a useful
process for the synthesis of tetrahydropyran core
structure.
Run
Yield(%)
1
80
2
72
3
68
b
EXPERIMENTAL
General Procedure
aReaction conditions: 2 mmol of benzaldehyde, 2 mmol of 3-buten-
-ol, 5 mol% of Bi(OTf) , 1 mL of [bmim]PF , rt, 15 min.
Isolated yield after column chromatography.
1
3
6
b
Bismuth triflate (5 mol%) was added in one
portion to 1-butyl-3-methylimidazolium hexafluo-
rophosphate (1 mL). Benzaldehyde (212 mg, 2
mmol) was then added followed by water (0.1 mL)
and 3-buten-1-ol (144 mg, 2 mmol) at room temper-
ature. The mixture was allowed to stir for 15 min
and then washed with diethyl ether (3 × 5 mL). The
combined ether extracts were concentrated in vacuo,
and the resulting product was separated by column
chromatography over silica gel (ethyl acetate: hex-
ane, 1:2). The product 3a was obtained in 80% yield.
The rest of the ionic liquid was further washed with
shows some effect on the yields. The aliphatic,
simple aromatic, and moderately activated aldehy-
des such as chloro and methyl gave high yields of
products when compared with deactivated nitro-
substituted aldehydes.
We have also carried out the reaction in organic
solvent, such as chloroform, and found the forma-
tion of a mixture of tetrahydropyranol and the cor-
responding ether after refluxing for 2 h. This may be
due to the hydrophilic nature of ionic liquid, which
TABLE 2 Bismuth Triflate Catalyzed Synthesis of 4-Tetrahydropyranols
Entry
Aldehyde
Alcohol
Productsa
Yield (%)b
1
2
80
78
3
4
80
76
Continued
Heteroatom Chemistry DOI 10.1002/hc

106 Murty et al.
TABLE 2 Continued
Entry
Aldehyde
Alcohol
Productsa
Yield (%)b
5
6
74
70
7
8
9
68
72
70
66
1
1
0
1
2
62
60
1
a
1
All the products were characterized by H NMR, IR, and mass spectroscopy and compared with previously reported data.
Yields are isolated after column chromatography.
b
ether and recycled, and the activity was retained un-
til three runs.
B. V. S.; Sekhar, K. C.; Gunasekar, D. Synthesis 2001,
85; (g) Keh, C. C. K.; Namboodiri, V. V.; Varma,
8
R. S.; Li, C. J. Tetrahedron Lett 2002, 43, 4993; (h)
Yadav, J. S.; Reddy, B. V. S.; Reddy, P. N.; Rao, M. S.
Synthesis 2003, 9, 1387; (i) Yadav, J. S.; Reddy, B. V.
S.; Reddy, M. S.; Niranjan, N. J Mol Catal A 2004, 99.
[4] (a) Iloughmane, H. G.; Le Roux, C. Eur J Org
Chem 2004, 2517; (b) Yadav, J. S.; Reddy, B. V. S.;
Venugopal, Ch.; Srinivas, R.; Ramalingam, T. Synth
Commun 2002, 32, 1803.
REFERENCES
[
1] Nicolaou, K. C.; Sorensen, E. J. Classics in Total Syn-
thesis; VCH: Weinheim, Germany, 1996.
[
[
2] Perron, F.; Albizati, K. F. J Org Chem 1987, 52, 4130.
3] (a) Ranu, B. C.; Jana, U. J Org Chem 1998, 63, 8212;
(
b) Viswanathan, G. S.; Yang, J.; Li, C. J. Org Lett
999, 1, 993; (c) Zhang, W. C.; Viswanathan, G. S.;
[5] (a) Welton, T. Chem Rev 1999, 99, 2071; (b) Wasser-
scheid, P.; Keim, W. Angew Chem, Int Ed 2000, 39,
3772; (c) Sheldon, R. J Chem Soc, Chem Commun
2001, 2399.
[6] Song, C. E.; Shim, W. H.; Roh, E. J.; Lee, S.; Choi, J.
H. Chem Commun 2001, 1122.
1
Li, C. J. Chem Commun 1999, 291; (d) Zhang, W. C.;
Li, C. J. Tetrahedron 2000, 56, 2403; (e) Yadav, J. S.;
Reddy, B. V. S.; Kumar, G. M.; Murthy, Ch. V. S. R.
Tetrahedron Lett 2001, 42, 89; (f) Yadav, J. S.; Reddy,
Heteroatom Chemistry DOI 10.1002/hc