Triphenylphosphine-iodine: An efficient reagent for the regioselective dehydration of tertiary alcohols

Article abstract of DOI:10.1016/j.tetlet.2004.04.058

Tertiary alcohols react under mild conditions with triphenylphosphine and iodine to give the most stable alkene in good yield.

Full text of DOI:10.1016/j.tetlet.2004.04.058

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4453–4455
Triphenylphosphine–iodine: an efficient reagent for the
regioselective dehydration of tertiary alcohols
E. J. Alvarez-Manzaneda,a,* R. Chahboun,a E. Cabrera Torres,a E. Alvarez,a
R. Alvarez-Manzaneda,b A. Haidoura and J. Ramosa
a
ꢀ
ꢀ
ꢀ
Departamento de Quımica Organica, Facultad de Ciencias e Instituto de Biotecnologıa, Universidad de Granada,
18071 Granada, Spain
bDepartamento de Quꢀımica Orgꢀanica, Facultad de Ciencias, Universidad de Almerꢀıa, 04120 Almerꢀıa, Spain
Received 4 March 2004; revised 12 April 2004; accepted 13 April 2004
Abstract—Tertiary alcohols react under mild conditions with triphenylphosphine and iodine to give the most stable alkene in good
yield.
Ó 2004 Elsevier Ltd. All rights reserved.
The conversion of alcohols to olefins constitutes a very
useful functional group interconversion in organic syn-
thesis. Although several methods have been reported to
effect this transformation,1 they involve the use of strong
acids, high temperatures or transformation to their ester
derivatives, which, in some cases, preclude their use with
sensitive molecules.
eral alcohols bearing different functional groups, and
having methyl, methylene and methyne groups in the
b position, were treated with PhP3–I2 in CH2Cl2.
The results and conditions are summarized in the
Table 1.
The treatment of alcohols 1 and 3 with the reagent
afforded exclusively the tetrasubstituted regioisomers 2
and 4 in high yield.
Iodine has long been utilized to dehydrate some tertiary
alcohols. However, this method suffers from low
reproducibility and many other drawbacks, such as low
regioselectivity and poor yield.2
The dehydration of 5 gave alkene 6, whereas ketoalco-
hol 7 led to the more stable a,b-unsaturated ketone 8.
The triphenylphosphine–tetrachloromethane system has
been reported for dehydrating some 14b-hydroxy steroids.3
Ketone, ester and amide groups remained unaltered
under the reaction conditions. Thus, hydroxyesters 9
and 11 and hydroxyamide 13 afforded the corresponding
unsaturated compounds 10, 12 and 14.
More recently, the dehydration of secondary and ter-
tiary alcohols by treatment with triphenylbismuth
dibromide–iodine under an inert atmosphere has been
described.4
The 1,4-dihydroxyderivative 15 was converted into the
homoallylic iodide 16.6 However, the 1,3-dihydroxy-
derivative 17 underwent elimination to give the stable
conjugated diene 18. Dehydration of the 1,2-diol 19
yielded, as would be expected, the ketone 20.7;9
Continuing research into the development of new syn-
thetic methodologies,5 as part of our investigation of the
synthesis of bioactive compounds from diterpenes, we
studied the triphenylphosphine–iodine system to achieve
the regioselective dehydration of tertiary alcohols. Sev-
Compound 16 is the key intermediate in the total syn-
thesis of the seco-labdane chapecoderin A.7 The con-
version of diol 15, which was obtained in high yield in a
two-step sequence from the natural diterpene ())-scla-
reol by the present authors,8 into 16 (entry 8) involves
the formal synthesis of the above seco-labdane from ())-
sclareol.
Keywords: Tertiary alcohols; Regioselective dehydration; Alkenes;
Triphenylphosphine; Iodine.
* Corresponding author. Tel./fax: +34-958-24-80-89; e-mail: eamr@
ugr.es
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.058

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E. J. Alvarez-Manzaneda et al. / Tetrahedron Letters 45 (2004) 4453–4455
Table 1. Dehydration of tertiary alcohols with the Ph3P–I2 system
Entry
1
Substrate
Time (h)
Product (%)a
OH
2
(85)
1
2
2
3
OH
2.5
(88)
4
6
3
4
(90)
OH
5
4
5
3.5
(80)
O
O
OH
7
8
OAc
OAc
3
(82)b
OH
9
10
12
OAc
OH
OAc
6
7
2.5
(87)b
11
NHAc
OH
NHAc
2
(85)b
13
15
17
19
14
OH
OH
I
8
9
3.5
(83)b
16
18
OH
OH
3
(90)
OH
O
10
2.5
(87)
OH
20
a All new compounds were fully characterized.
b Minor regioisomers were obtained in less than 10%.

E. J. Alvarez-Manzaneda et al. / Tetrahedron Letters 45 (2004) 4453–4455
4455
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Experimental procedure: Iodine (1.2 mmol) was added to
a solution of Ph3P (1.2 mmol) in CH2Cl2 (5 mL) and the
mixture was stirred at room temperature for 10 min. A
solution of the alcohol (1.0 mmol) in CH2Cl2 (3 mL) was
then added and the mixture was further stirred at room
temperature, the reaction being monitored by TLC. Aq
5% NaHSO3 was added and the mixture was stirred for
10 min. It was then diluted with CH2Cl2 and the organic
phase washed with H2O and brine successively, after
which it was dried and evaporated to give a crude. This,
after flash column chromatography on silicagel (hexane/
ether), gave the alkene.
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In conclusion, the Ph3P–iodine system is an inexpensive
reagent, which transforms tertiary alcohols into the
most stable alkene, under mild and easily-implemented
experimental conditions. Some functional groups, such
as ketone, ester and amide, remain unaltered under these
conditions.
Acknowledgements
Financial support was received from Ministerio de
Ciencia y Tecnologia (Project PPQ 2002-03308).
7. Hagiwara, H.; Takeuchi, F.; Hoshi, T.; Suzuki, T.; Ando,
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