COMMUNICATION
Catalytic formation of C–O bonds by alkene activation: Lewis
acid-cycloisomerisation of olefinic alcohols
Lydie Coulombel,a Isabelle Faviera and Elisabet Dun˜ach*ab
Received (in Cambridge, UK) 3rd February 2005, Accepted 16th February 2005
First published as an Advance Article on the web 9th March 2005
DOI: 10.1039/b501601k
Sm(OTf)3 and Sn(OTf)4, used a in 5 mol% ratio with respect to 1a,
were examined in refluxing acetonitrile. The most efficient catalyst
was Sn(OTf)4, which led quantitatively and selectively to the
corresponding tetrahydropyran 2a in 0.5 h. The reaction was
regiospecific and only the 6-membered ring 2a was formed,
without the presence of the isomeric 5-membered ring ether.
Different solvents such as dichloromethane, acetonitrile,
dichloroethane and nitromethane were tested for the cyclisation
of both 1a and 1e (cis isomer) using Sn(OTf)4 (5 mol%) (For 1e see
Table 1, entry 5). Whereas 1a led quantitatively to 2a in all the
solvents tested, no products were formed with 1e in refluxing
dichloromethane after 24 h; a 10% conversion of 1e with the
formation of cyclic ether 2e was obtained in refluxing acetonitrile,
and in refluxing dichloroethane 23% conversion of 1e was attained.
In contrast, in refluxing nitromethane, the reaction of 1e was more
efficient and afforded 73% conversion after 1.5 hours with the
formation of the cyclised 5-membered ring ether 2e, obtained in
90% yield and with 92% regioselectivity.
Tin(IV) trifluoromethanesulfonate has been found to be an
excellent catalyst for the cycloisomerisation of non-activated
and differently substituted olefinic alcohols to cyclic ethers.
The tetrahydrofuran and tetrahydropyran rings are very important
structural moieties, which are present in a large variety of natural
products such as polyether antibiotics.1 They are also found as
perfuming or flavouring ingredients in foodstuffs.2 The intramo-
lecular hydroalkoxylation reaction, the addition of alcohols onto
carbon–carbon multiple bonds, provides an efficient and direct
access to this class of heterocycles.3 Although this reaction is
known to be effected in the presence of over-stoichiometric
amounts of protic acids, only a few protic acid-catalysed
cyclisations have been reported.4,5 The use of Lewis acids as
catalysts for the activation of alkenes, involving the formation of
new C–O bonds, has not yet been reported. To our knowledge, a
single example describes the use of Lewis acids to effect the
cycloisomerisation of unsaturated alcohols, though in stoichio-
metric amounts.6 Lewis acid catalysis in non protic media is of
increasing interest for organic transformations and allows
enantioselective cycloisomerisation by the introduction of chiral
ligands on the metal centre.
We extended the cyclisation to other olefinic alcohols by using a
catalytic amount of Sn(OTf)4 (5 mol%) in refluxing nitromethane
(Table 1). The reactivity of c,d-unsaturated alcohols possessing a
trisubstituted double bond such as in compounds 1a or 1b,
afforded exclusively one product, the corresponding substituted
tetrahydropyrans 2a or 2b, respectively (entries 1–2). In contrast,
the methylene disubstituted olefinic alcohol 1c led exclusively to
the substituted tetrahydrofuran 2c (entry 3). It is worth noting that
the cyclisation took place exclusively at the more substituted
carbon atom of the double bond.
Recent attention has been devoted to the concept of enhance-
ment of the electrophilic alkene activation by increasing the net
positive charge in transition-metal complexes.7 In this context, the
trifluoromethanesulfonate group constitutes one of the most
electron-withdrawing ligands and confers high activity to the
corresponding Lewis acid metal salts.8
Herein, we report the novel use of metallic trifluoromethane-
sulfonates, and more particularly the use of tin(IV) trifluorometha-
nesulfonate, as the catalyst in the cycloisomerisation of
non-activated unsaturated alcohols to the corresponding cyclic
ethers in non protic media.
With alcohols bearing a terminal or an internal disubstituted
double bond, the catalytic cyclisation was efficient only in refluxing
CH3NO2. In the case of the cycloisomerisation of disubstituted
c,d-unsaturated alcohols trans-1d or cis-1e (entries 4–5), the
corresponding tetrahydrofurans 2d and 2e were regioselectively
formed. In both cases, tetrahydrofuran/tetrahydropyran selectivity
was 92:8. In the case of the cis-b,c-unsaturated alcohol 1f (entry 6),
the cyclisation led exclusively to the 5-membered ring 2f, the
4-membered ring not being detected.
We prepared Sn(OTf)4 (not commercially available) as well as
other metallic triflates using an electrochemical procedure, similar
to that recently reported for the preparation of metallic
bis(trifluoromethanesulfonyl)imide salts.9 In contrast to the usual
methods of metallic triflate preparation, from the corresponding
oxides and triflic acid, that afford hydrated triflate salts,10 the
electrochemical method led to the formation of anhydrous metallic
triflates.11
Under the same conditions, the cyclisation of trans-5-phenyl-4-
penten-1-ol 1g afforded the corresponding tetrahydropyran isomer
2g as the only isolated compound (entry 7). The isolated yield was
in this case lower, certainly due to some partial polymerisation of
the styrenic moiety.
The possibilities of Lewis-acid catalysed cycloisomerisation of
unsaturated alcohols were first examined for the cyclisation of the
model substrate 1a (Table 1, entry 1) in the presence of different
metallic triflates. The reactivities of Al(OTf)3, Ni(OTf)2, Zn(OTf)2,
Terminal olefinic alcohols such as 1h or 1i (entries 8 and 9)
could also be cyclised, though with incomplete conversions; the
5-membered cyclic ethers 2h and 2i were the only products
obtained in quantitative yields according to GC analysis.
Interestingly, the cycloisomerisation with catalytic amounts of
*dunach@unice.fr
2286 | Chem. Commun., 2005, 2286–2288
This journal is ß The Royal Society of Chemistry 2005
Coulombel, Lydie
