A simple one-pot synthesis of β-alkoxy alcohols from alkenes

Article abstract of DOI:10.1016/j.tetlet.2005.05.030

β-Methoxy alcohols are easily obtained from the one-pot reaction of alkenes with oxone in methanol, in the absence of any additive or catalyst. The use of other alcohols as solvents has shown that the efficiency of the process decreases with the steric hindrance of the alcohol.

Full text of DOI:10.1016/j.tetlet.2005.05.030

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4741–4743
A simple one-pot synthesis of b-alkoxy alcohols from alkenes
Jean Le Bras,a,* Debabrata Chatterjeeb and Jacques Muzarta
a
´ ´ ´
Unite Mixte de Recherche, ‘Reactions Selectives et Applications’, CNRS-Universite de Reims Champagne-Ardenne,
BP 1039, 51687 Reims Cedex 2, France
´
bChemistry Section, C.M.E.R.I., Durgapur 713 209, India
Received 5 April 2005; revised 29 April 2005; accepted 11 May 2005
Available online 31 May 2005
Abstract—b-Methoxy alcohols are easily obtained from the one-pot reaction of alkenes with oxoneÒ in methanol, in the absence of
any additive or catalyst. The use of other alcohols as solvents has shown that the efficiency of the process decreases with the steric
hindrance of the alcohol.
Ó 2005 Elsevier Ltd. All rights reserved.
b-Alkoxy alcohols constitute an important class of
organic compounds,1 and the main protocol for their
synthesis is the alcoholysis of 1,2-epoxides.2–8 For the
synthesis of epoxides, oxoneÒꢀ in the presence of transi-
tion metal complexes9 or cyclodextrines,10 or via the for-
mation of dioxiranes11 is commonly used. A few studies
have reported the formation of 1,2 diols from the reac-
tion of alkenes with oxoneÒ in aqueous solvents.12 That
led us to envisage the one-pot synthesis of b-alkoxy alco-
hols from alkenes using oxoneÒ in alcohols.
agreement with the formation of 1-methylcyclohexene
oxide as an intermediate, and its alcoholysis mediated
by the acidity of the solution. Indeed, the same com-
pounds with, furthermore, similar ratios are produced
from the reaction of 1-methylcyclohexene oxide with
methanol in the presence of oxone, Bro¨nstedt or Lewis
acids.4 Nevertheless, we have not been able to detect
the formation of the transient epoxide in monitoring
the oxidation of 1-methylcyclohexene by TLC.
Under the above experimental conditions, trans-2-meth-
oxy-cycloheptan-1-ol,5 trans-2-methoxy-cyclooctan-1-ol6
and trans-1-methoxy-tetral-2-ol7 have been obtained
in 94–96% yields from cycloheptene, cyclooctene and
1,2-dihydronaphthalene, respectively (runs 4–6). With
indene as the substrate, the oxidation led, as from 1,2-
dihydronaphthalene, to the fixation of the methoxy
group exclusively at the benzylic position but in contrast
to 1,2-dihydronaphthalene, two diastereoisomers were
produced (run 7). NMR analysis and comparison with
the literature data8b,13 showed that trans-1-methoxy-in-
dan-2-ol was the main adduct. Actually, the formation
of two diastereoisomers from the ring opening of indene
oxide has already been observed.14 Under our experi-
mental conditions, a benzylic carbocation could be pro-
duced from the heterolytic cleavage of the C(1)–O bond
of the oxirane in situ formed, and its relative planar con-
formation would lead to the addition of the alcohol to
both faces. A linear alkene, such as 1-octene was almost
unreactive while styrene afforded only 21% of 2-meth-
oxy-2-phenylethanol4 (run 8). Elevating the temperature
to 40 °C improved the yield of this b-methoxy alcohol to
47% (run 9).
Preliminary experiments were carried out in methanol
using 1-methyl-1-cyclohexene and 1 equiv of KHSO5
(0.5 equiv of oxoneÒ). A 91/9 mixture of two methoxy-
methyl-cyclohexanols was obtained in 58% yield at
room temperature after stirring for 24 h (Table 1, run
1), and the results were unchanged in prolonging the
reaction time to 48 h (run 2). Interestingly, the use of
1 equiv of oxoneÒ led in 24 h to an almost quantitative
yield of the b-methoxy alcohols without modification
of their ratio (run 3). NMR analysis of the adducts
and comparison with the literature data3 showed that
the methoxy and hydroxy substituents of each isomer
are in trans position, and that 2-methoxy-2-methyl-
cyclohexanol is the main isomer. These results are in
Keywords: OxoneÒ; b-Alkoxy alcohol; b-Hydroxy ether; One-pot
synthesis; Oxidation.
*
Corresponding author. Tel.: +33 3 26 91 32 46; fax: +33 3 26 91 31
66; e-mail: jean.lebras@univ-reims.fr
ꢀ OxoneÒ (2KHSO5ÆKHSO4ÆK2SO4) is the registered trademark from
Du Pont.
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.030

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J. Le Bras et al. / Tetrahedron Letters 46 (2005) 4741–4743
Table 1. Oxidation of alkenes with oxoneÒ (1 equiv) in MeOH at room temperature for 24 h
Run
1a
Alkene
Products (ratio)
Yield (%)
58
OMe
OH
OH
OH
OH
OMe
OMe
OMe
(91/9)
(92/8)
(91/9)
+
OMe
OH
2a,b
59
95
94
96
96
79
+
OMe
OH
3
+
OMe
OH
4
OMe
OH
5
OMe
OH
6
OMe
OH
OMe
7
(57/43)
+
OH
OMe
8
21
47
Ph
Ph
OH
Ph
OMe
9c
OH
Ph
a Reaction carried out with 0.5 equiv of oxoneÒ.
b Reaction for 48 h.
c Reaction carried out at 40 °C.
The reaction was less efficient in other alcohols: 1,2-
dihydronaphthalene in ethanol yielded 65% trans-1-eth-
oxy-tetral-2-ol (67% conversion) at room temperature
for 24 h, while less than 10% of expected adducts were
obtained in i-PrOH. Alcohols can provide alternative
substrates for the oxidant,12a but the conversion ob-
served in t-BuOH (610%) led us to suspect that these
lower efficiencies are rather due to the decrease of the
solubility of oxoneÒ in these solvents.
References and notes
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1996, 69, 195–205.
4. Reaction of 1-methylcyclohexene oxide with oxoneÒ in
methanol afforded a 90/10 mixture of trans-2-methyl-2-
methoxy-cyclohexanol and trans-1-methyl-2-methoxy-
cyclohexanol. For the opening of 1-methylcyclohexene
oxide with Bro¨nstedt and Lewis acids, see: Chini, M.;
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In conclusion, the current procedure is easy to set-up
and allows the direct transformation of some alkenes
to b-methoxy alcohols using oxoneÒ and methanol as
reagents, without the requirement of any additives.
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Acknowledgement
This work was supported by the Indo-French Centre
for the Promotion of Advanced Research (Project No.
2905-1).

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