Facile and efficient method for the Prins reactions of styrenes and homoallyl alcohols to 1,3-dioxanes and 4-tetrahydropyranols using bismuth(III) triflate

Article abstract of DOI:10.1081/SCC-200054759

Bismuth(III) inflate has been found to be an efficient catalyst for the Prins reactions of styrenes and homoallyl alcohols, the reaction proceeds rapidly and affords the corresponding 1,3-dioxanes and tetrahydropyran-4-ol in good yields. Scope and limitations of the styrenes and homoallyl alcohols are reported. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200054759

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Facile and Efficient Method
for the Prins Reactions of
Styrenes and Homoallyl
Alcohols to 1,3‐Dioxanes and
4‐Tetrahydropyranols Using
Bismuth(III) Triflate
B. Sreedhar a , V. Swapna a , Ch. Sridhar a , D.
Saileela a & A. Sunitha a
a Inorganic Chemistry Division , Indian Institute of
Chemical Technology , Hyderabad, India
Published online: 16 Aug 2006.
To cite this article: B. Sreedhar , V. Swapna , Ch. Sridhar , D. Saileela & A. Sunitha
(2005) Facile and Efficient Method for the Prins Reactions of Styrenes and Homoallyl
Alcohols to 1,3‐Dioxanes and 4‐Tetrahydropyranols Using Bismuth(III) Triflate,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 35:9, 1177-1182, DOI: 10.1081/SCC-200054759
To link to this article: http://dx.doi.org/10.1081/SCC-200054759
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Synthetic Communicationsw, 35: 1177–1182, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200054759
Facile and Efficient Method for the Prins
Reactions of Styrenes and Homoallyl
Alcohols to 1,3-Dioxanes
and 4-Tetrahydropyranols Using
Bismuth(III) Triflate
B. Sreedhar, V. Swapna, Ch. Sridhar, D. Saileela, and A. Sunitha
Inorganic Chemistry Division, Indian Institute of Chemical Technology,
Hyderabad, India
Abstract: Bismuth(III) triflate has been found to be an efficient catalyst for the Prins
reactions of styrenes and homoallyl alcohols, the reaction proceeds rapidly and
affords the corresponding 1,3-dioxanes and tetrahydropyran-4-ol in good yields.
Scope and limitations of the styrenes and homoallyl alcohols are reported.
Keywords: Bismuth(III) triflate, 1,3-dioxanes, homoallyl alcohols, Prins reaction,
tetrahydropyran-4-ol
Lewis-acid (LA) catalyzed reactions are of great interest because of their
unique reactivity and selectivities and the mild reaction conditions they use.[1]
The Prins reaction is a fundamental reaction for carbon–carbon bond
formation and is one of the most effective reactions for the synthesis of tetra-
hydropyrans and dioxanes.[2] There are several types of Prins reactions present
in the literature. Some of those are acid-catalyzed olefin–aldehyde conden-
sations to form dioxanes[3] and coupling of homoallyl alcohols with several
aldehydes to form tetrahydropyrans.[4] The importance of pyrans is exempli-
fied by its presence in the backbone of various carbohydrates and natural
Received in India December 20, 2004
Address correspondence to B. Sreedhar, Inorganic Chemistry Division, Indian
Institute of Chemical Technology, Hyderabad 500 007, India. E-mail: sreedharb@
iict.res.in

1178
B. Sreedhar et al.
products.[5] The tetrahydropyran ring system is a core unit in a number of
natural products. However, the synthesis and application of this important
reaction has been underexplored because of the classical conditions of
strong acids (e.g., sulfuric acid) and high reaction temperatures, which often
generate a range of undesired products. In particular, the polymerization of
the olefin that is induced by Lewis or Brønsted acids can severely interfere
with desired C-C bond formation. However, many of these classical
methods often involve the use of expensive reagents and extended reaction
times and generate mixtures of unnecessary products.
Bismuth derivatives are attracting the attention of an increasing number
of organic chemists.[6] Over the past few years, bismuth(III) triflate has
been reported as a new and efficient catalyst for organic synthesis, which
exhibits, in numerous cases, a stronger activity than other known metal
triflates, in particular those of transition elements.[7] We are particularly
interested in bismuth triflate because it is inexpensive and can be easily
prepared in the laboratory from commercially available bismuth(III) oxide
and triflic acid.[8]
In view of this, we examined the Prins reactions between styrenes and par-
aformaldehyde (Scheme 1), and homoallyl alcohol and aldehydes (Scheme 2)
to produce the corresponding 1,3-dioxanes and tetrahydropyran-4-ols.
Because it was observed that the treatment of styrene with paraformalde-
hyde in toluene in the presence of bismuth(III) triflate produced 4-phenyl-1,3-
dioxane, a search for optimization was first carried out using this catalyst. As a
result, the use of a 5 mol% catalyst in acetonitrile at 80 8C for 6 h was revealed
to be the condition of choice (Scheme 1) in which the reaction proceeded
smoothly to produce 4-phenyl-1,3-dioxane in 90% isolated yield. Solvent
has pronounced effect in these reactions. Acetonitrile provided optimum
yields, whereas toluene and chloroform offered lower yields. The optimum
results were obtained by using 5 mol% catalyst. With 1 mol% catalyst, the
reaction was slow and the product yield became low. The controlled Prins
reaction conducted under identical conditions and devoid of Bi(OTf)3 gave
no products, despite prolonged time.
Subsequently, by controlling the reaction conditions, various tetrahydro-
pyran-4-ols were synthesized via the reaction of homoallylic alcohols and
aldehydes using bismuth(III) triflate as the catalyst (Scheme 2).
Scheme 1.

Prins Reactions of Styrenes and Homoallyl Alcohols
1179
Scheme 2.
The reaction was then applied to a variety of structurally divergent
styrenes and homoallyl alcohols to get the corresponding 1,3-dioxanes and
tetrahydropyran-4-ols with good yields and the results are summarized in
Table 1 and Table 2.
It was clear from Table 1 that styrenes containing electron-donating
groups such as 4-methyl styrene (Table 1, entry 2) and 4-metoxy styrene
(Table 1, entry 3) react faster and give the corresponding 1,3-dioxanes.
When styrenes contain electron-withdrawing functional groups such as
4-chloro (Table 1, entry 4) and 4-acetoxy (Table 1, entry 5), styrene reacts
slowly to yield the corresponding 1,3-dioxanes. Here, monmeric formal-
dehyde might be produced by the decomposition of paraformaldehyde
because of the interaction with the bismuth(III) triflate.
It was clear from Table 2 that a variety of homoallyl alcohols were reacted
with aldehydes to produce the corresponding tetrahydropyanols. The reactiv-
ity for aromatic aldehydes is more when compared to cyclic aldehydes.
In summary, this work demonstrates a new method for high-yielding,
selective synthesis of 1,3-dioxanes and tetrahydropyran-4-ols using
bismuth(III) triflate. Advantages of this method include the highly
catalytic nature of the reagent, low toxicity and low cost of the Lewis-acid
catalyst, fast reaction rates, and insensitivity of the Lewis acid to air and
moisture.
EXPERIMENTAL
Typical Experimental Procedure for the Prins reaction of
Styrenes and Paraformaldehyde
To a mixture of styrene (1 mmol) and paraformaldehyde (10 mmol) in aceto-
nitrile were added bismuth(III) triflate (5 mol%). The mixture was stirred at
reflux temperature. The progress of the reaction was monitored by thin
layer chromatography. After the completion of the reaction, the reaction
was filtered, washed with water, and extracted into ethyl acetate. The
combined organic layers were evacuated to obtain 4-phenyl-1,3-dioxane.
1H NMR (200 MHz, CDCl3) d 1.69–1.75 (1H, m), 2.04–2.16 (1H, m),

1180
B. Sreedhar et al.
a
Table 1. Prins reaction of styrenes with paraformaldehyde using Bi(OTf)3
Time
(h)
Yield
(%)b
Entry
1
Substrate
Product
Ref.
[9]
4
6
7
90
88
87
2
3
[9]
[9]
4
5
10
10
82
77
[9]
[9]
6
7
6
6
89
[9]
85c
[10]
aStyrene (1 mmol), paraformaldehyde (10 mmol), acetonitrile (3 mL), Bi(OTf)3 (20 mg).
bBased on isolated yields.
cCombined yield of two isomers.

Prins Reactions of Styrenes and Homoallyl Alcohols
1181
a
Table 2. Prins reaction of aldehydes and homoallyl alcohols with Bi(OTf)3
Yield
(%)b
Entry
1
Homoallyl alcohol
Aldehyde
Product
73
2
65
3
4
78
82
aHomoallyl alcohol (1 mmol), aldehyde (1 mmol), Bi(OTf)3 (5 mol%), acetonitrile
(3 mL), reflux.
bBased on isolated yields.
3.83–3.92 (1H, m), 4.17–4.24 (m, 1H), 4.65 (1H, dd), 4.90 (1H, d) 5.22
(1H, d), 7.24–7.4 (5H, m). MS m/z: 164, 118, 105 (100), 77.
ACKNOWLEDGMENTS
Ch. Sridhar thanks the Council of Scientific and Industrial Research, India, for
a SRF fellowship.
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