Synthesis of alkenes from tertiary esters utilizing the triphenylphosphine-iodine system

Article abstract of DOI:10.1016/j.tetlet.2004.12.104

The treatment of tertiary esters with triphenylphosphine and iodine under mild conditions gives the most stable alkene in good yield. Formates, acetates and trifluoroacetates were studied.

Full text of DOI:10.1016/j.tetlet.2004.12.104

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 1075–1077
Synthesis of alkenes from tertiary esters utilizing the
triphenylphosphine–iodine system
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
Departamento de Quımica Organica, Facultad de Ciencias, Universidad de Almerıa, 04120 Almerıa, Spain
b
´
´
´
´
Received 20 September 2004; revised 20 December 2004; accepted 21 December 2004
Available online 8 January 2005
Abstract—The treatment of tertiary esters with triphenylphosphine and iodine under mild conditions gives the most stable alkene in
good yield. Formates, acetates and trifluoroacetates were studied.
Ó 2004 Elsevier Ltd. All rights reserved.
The elimination of carboxylic esters, in which the alkyl
group has a b hydrogen, has long been utilized to pre-
pare olefins. However, this method usually involves
heating with bases or acids, or pyrolysis, which limits
its synthetic usefulness.1
responding alcohols (entries 3 and 4).2 Primary acetates
do not undergo elimination under these conditions (en-
tries 9 and 10), but the 1,3-diacetate 21 was transformed
into the stable diene 22,2 which also resulted from acet-
oxyalkene 23. Entry 13 describes a very interesting
result: the c-acetoxyacid 24 and its methyl ester 25 gave
isosclareolide (26), a very useful synthon,3 in good yield
under the reaction conditions. Otherwise, the b-acetoxy-
ester 27 was converted into the b,c-unsaturated ester
28. The bis(trifuoroacetate) 29 gave 30 and 31a–b after
12 h; dienes 31a–b were the only products when the reac-
tion continued longer (entry 15).
In a recent paper we have reported that tertiary alcohols
undergo regioselective dehydration in the presence of
triphenylphosphine and iodine.2
Following our study of the use of this reagent for syn-
thetic purposes we have found that tertiary esters are
also converted into the most stable alkenes when they
are treated with triphenylphosphine and iodine, under
similar conditions to those reported for alcohols. Elimi-
nation of some formates, acetates and trifluoroacetates
was investigated. The results and conditions are summa-
rized in Table 1. Acetates and formates show a similar
degree of reactivity, whereas trifluoroacetates react very
slowly (entry 15). Ketoesters 1 and 3 gave the alkenes 2
and 4, respectively (entries 1 and 2). Formates 5 and 7
showed a similar behaviour to that reported for the cor-
The procedure reported is of great synthetic signifi-
cance in the case of formates, which can be prepared
following our previously reported methodologies, the
Baeyer–Villiger rearrangement of tertiary aldehydes4
or the thermal rearrangement of ozonides.5 The treat-
ment of these formates with triphenylphosphine and
iodine, which leads to the most stable alkene, is, from
the point of view of regioselectivity, complementary
with the elimination of formic acid by heating with
collidine, which usually gives the kinetic alkene.4
Thus, compounds 1, 5 and 7 gave predominantly the
exocyclic alkene when treated with collidine, whereas
11 gave a 1:1 mixture of the tri- and disubstituted
alkenes.
Keywords: Tertiary esters; Elimination; Alkenes; Triphenylphosphine;
Iodine.
*
On the whole, as it has been indicated for
11, elimination of tertiary carboxylic esters with
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.2004.12.104

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E. J. Alvarez-Manzaneda et al. / Tetrahedron Letters 46 (2005) 1075–1077
Table 1. Reaction of tertiary esters with the PPh3–I2 systema
Entry
1
Substrate
OCHO
Time (h)
2
Product (%)b
O
O
2 (63)
1
O
O
OCHO
2
2.5
3
4 (68)
3
3
OCHO
6 (92)
5
4
2
O
O
O
OCHO
7
8 (97)
OMe
OMe
5
2
O
OCHO
10 (83)
9
O
O
O
O
6
2.5
OCHO
11
12 (88)
OAc
7
8
3
2
13
14 (94)
NHAc
NHAc
OAc
16 (88)c
15
OAc
OAc
OAc
9
2.5
18 (91)c
17
OAc
OAc
OAc
10
2
19
20 (98)c

E. J. Alvarez-Manzaneda et al. / Tetrahedron Letters 46 (2005) 1075–1077
1077
Table 1 (continued)
Entry
Substrate
Time (h)
Product (%)b
OAc
11
12
2
OAc
22 (92)
21
23
OAc
2
22 (97)
O
COOR
OAc
O
13
2
3
24 R: H
25 R: Me
26 (95)
(90)
COOMe
OAc
COOMe
14
2
28 (93)
27
OCOCF3
OCOCF3
OCOCF3
15
12
29
30 (62%)
31a-b (31%)
a Reaction conditions: 1 mmol of ester in CH2Cl2 (3 mL) and 1.2 equiv of PPh3–I2 system in CH2Cl2 (5 mL) at room temperature (see Ref. 2).
b All new compounds were fully characterized.
c
Minor regioisomers were obtained in less than 10%.
triphenylphosphine and iodine are more regio-
selective than those performed with collidine;
when 27 was heated with collidine a 5:3:1 mixture
of di-, tetra- and trisubstituted alkenes was ob-
tained.6
References and notes
1. For reviews see: (a) De Puy; King, B. Chem. Rev. 1960, 432–
444; (b) Barton, D.; Ollis, W. D. In Comprehensive Organic
Chemistry; Pergamon: Oxford, 1979; Vol. 1, pp 640–644; (c)
March, J. A. Advanced Organic Chemistry: Reactions,
Mechanisms and Structures, 5th ed.; Wiley Interscience:
New York, 2001; pp 1326–1328; (d) Larock, R. C. Compre-
hensive Organic Transformations; VCH, 1989; pp 151–154.
2. Alvarez-Manzaneda, E. J.; Chahboun, R.; Cabrera Torres,
E.; Alvarez, E.; Alvarez-Manzaneda, R.; Haidour, A.;
Ramos, J. Tetrahedron Lett. 2004, 45, 4453–4455.
3. Quideau, S.; Lebon, M.; Lamidey, A.-M. Org. Lett. 2002, 4,
3975–3978.
The surprising transformation of 24 and 25 into lactone
26 prompted us to investigate the use of this reagent to
achieve stereoselective lactonizations and other related
cyclizations. We are confident that the studies in pro-
gress will enable the mechanism of these reactions to
be clarified.
4. Barrero, A. F.; Alvarez-Manzaneda, E. J.; Alvarez-Man-
zaneda, R.; Chahboun, R.; Meneses, R.; Aparicio, M.
Synlett 1999, 713–716.
5. Barrero, A. F.; Alvarez-Manzaneda, E. J.; Chahboun, R.;
Cuerva, J. M.; Segovia, A. Synlett 2000, 1269–1272.
6. Chahboun, R. Doctoral Thesis. 1996, University of Gra-
nada, Spain.
Acknowledgements
Financial support was received from Ministerio de Cien-
cia y Tecnologia (Project PPQ 2002-03308).