Facile synthesis of enol ethers by cleavage of α-bromoacetals and α-bromoketals mediated by SmI2

Article abstract of DOI:10.1016/S0040-4039(01)00547-0

α-Bromocyclicacetals, α-bromocyclicketals and α-bromocyclicthioketals, derived from cyclic and acyclic ketones and aldehydes, reacted with samarium diiodide at -78°C in THF to furnish the corresponding enol ethers or thioenol ethers containing hydroxy or thiol moieties in high yields.

Full text of DOI:10.1016/S0040-4039(01)00547-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3729–3732
Facile synthesis of enol ethers by cleavage of a-bromoacetals
and a-bromoketals mediated by SmI2
Heui Sul Park, Seong Ho Kim, Min Young Park and Yong Hae Kim*
Center for Molecular Design and Synthesis, Department of Chemistry, Korea Advanced Institute of Science and Technology,
Taejon 305-701, South Korea
Received 2 April 2001; accepted 3 April 2001
Abstract—a-Bromocyclicacetals, a-bromocyclicketals and a-bromocyclicthioketals, derived from cyclic and acyclic ketones and
aldehydes, reacted with samarium diiodide at −78°C in THF to furnish the corresponding enol ethers or thioenol ethers containing
hydroxy or thiol moieties in high yields. © 2001 Published by Elsevier Science Ltd.
Enol ethers are useful intermediates in organic synthesis
and have been studied intensively.1 The most useful
preparative techniques involve the pyrolytic cracking of
acetals and ketals, usually in the presence of acid
catalysts.2 Such vigorous conditions often limit the
generality of the synthetic procedures, particularly
when the substrates contain other sensitive functional
groups. A cleavage of acetals or ketals with trimethyl-
silyliodide (TMSI)3 or triisobutylaluminum (TIBA)4 has
been reported. Recently, Gasman et al. carried out a
cleavage of acetals or ketals using trimethyltri-
fluoromethanesulfonate in the presence of tertiary
amine (DIEA) via a cationic process.5 The reaction
required a long reaction time and high reaction tem-
perature. However, the base sometimes causes diffi-
culties when separating the product from the starting
materials.
SmI2, cleavage of a-haloacetals, a-haloketals and a-
halothioketals has been examined using SmI2. We have
found that a-halocyclicacetals, a-halocyclicketals and
a-halocyclicthioketals reacted readily with SmI2 to fur-
nish the corresponding enol ethers or thioethers, con-
taining alcohol or thiol moieties, in high yields (Scheme
1).
In a typical reaction procedure, an SmI2 solution (0.1
M, 10 ml) was added dropwise at −78°C to a solution
of a-bromocyclopentane 1,3-dioxane acetal (run 2; 110
mg, 0.5 mmol) and HMPA (521 ml, 3.0 mmol) in THF
(5 ml) under an argon atmosphere. The mixture was
stirred for 10 min and then quenched with saturated
ammonium chloride (5 ml). The mixture was extracted
with Et2O (2×20 ml), and the combined organic layer
was washed with brine, dried over MgSO4, filtered and
evaporated. The crude product was then purified by
silica gel column chromatography (ethyl acetate:n-hex-
ane=1:2). All the products obtained were identified by
1H and 13C NMR spectral data and mass spectroscopy.
SmI2 has a strong oxophilicity and is a powerful elec-
tron donor. Various reductions, reductive coupling and
cyclizations have been reported.6 Unusual eliminations
and cleavage reactions using the oxophilicity and Lewis
acidity of samarium have been discovered. Cleavage
reactions of epoxides,7 cyclopropanes,8 or tetra-
hydropyrane derivatives9 gave very useful intermediates
or compounds in organic synthesis. Molander and co-
workers reported a cleavage reaction of acetals with
SmI2 via rearrangement of a radical.10 It is well known
that alkylhalides rearrange to alkyl radicals using
SmI2.11 Such radicals can be expected to convert into
anion intermediates by a further one-electron transfer
from SmI2. On the supposition that a-haloacetal may
form an anion-type intermediate in the reaction with
Compared with the previous methods for the prepara-
tion of enol ethers, the present cleavage reactions,
YH
n
n
X
2 SmI2, HMPA
THF, 20 oC
X
Y
Br
R1
R1
R2
R2
1
2
n= 1,2,
X=Y=O, X=Y=S, X=O, Y=S
Scheme 1.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00547-0

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H. S. Park et al. / Tetrahedron Letters 42 (2001) 3729–3732
mediated by SmI2, required short reaction times under
mild reaction conditions. Our new method also has the
advantage of not only obtaining enol ethers but also
enol thioethers containing alcohol or thiol moieties at
the b- or g-position. Treatment of SmI2 (2 equiv.) in the
presence of HMPA at −78°C in THF afforded enol
ethers or enol thioethers in excellent yields within 30
min. The results obtained are summarized in Table 1.
HMPA strengthens the electron-donor effect of samar-
ium coordination between samarium and oxygen
atoms.11a The cleavage reaction gives lower yields in the
absence of HMPA under the same reaction conditions.
Bromocyclicacetals were prepared via two-step a-
brominations12 of ketones with NBS–AIBN, TMPTB
or Br2 and the usual acetal formations.13 a-Bromo-
cyclopentane, a-bromocyclohexane and a-bromocyclo-
heptane ketals gave enol ethers. The primary (run 6),
secondary, and tertiary bromoacetals (run 8) were con-
verted into enol ethers. The cleavage of dioxolanebro-
mide (runs 1 and 3) was three times faster than that of
dioxanebromide (runs 2 and 4), most probably due to
ring strain. Dithiolane also gave thio enol ether in high
yields. In the case of thiooxolane, a cleavage reaction
occurred at the oxygen atom to give the thioenol ether.
Table 1. Reductice cleavage reaction of a-bromo acetals
Temp. (oC)
Yields (%)a
Products
Time (min)
Run
1
Substrate
O
OH
-78
3
91
O
Br
O
O
OH
90
10
-78
-78
2
3
O
Br
O
O
OH
3
92
O
Br
O
O
OH
4
5
6
7
-78
10
9
1
O
Br
O
O
OH
-78
3
89
87
O
Br
O
OH
OH
O
O
-78 to rt
30
Br
O
Ph
Ph
O
O
-78 to rt
-78
30
10
15
82
81
87
Br
Br
O
O
O
OH
SH
8
9
O
S
-78 to rt
S
Br
S
O
OH
-78 to rt
-78
15
81
10
11
S
S
Br
OEt
EtO
EtO
OEt
Br
75b
110
a: Isolated yields. b: The debrominated product was isolated instead of the enol ether.

H. S. Park et al. / Tetrahedron Letters 42 (2001) 3729–3732
3731
I2Sm
S
O
S
OH
SH
-
O
S
2 SmI2
HMPA
Br
4
5
SmI2
O
S
O
3
-
4'
6
Figure 1. Chemoselective cleavage of 1,3-thiooaline acetal.
OSmI2
OH
(S)
Br
O
O
H+
O
O
(S)
10
(S)
11
7
SmI2
O
SmI2Br
SmI2Br
O (S)
(S)
O
O
.
SmI2
-
8
9
Figure 2. Possible mechanism.
Acknowledgements
A chemically selective cleavage of a-bromocyclohexane
1,3-thiooxolane acetal afforded 1-[(2-hydroxy)-
3
ethoxy]cyclohexane 5 in 81% yield. No product 6,
formed by SꢀC bond cleavage, could be detected (Fig.
1). The oxophilicity between oxygen and samarium
must be stronger than the thiophilicity between sulfur
and samarium.
This work was partially supported by the School of
Molecular Science of MOE.
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