A general, selective synthesis of ω-hydroxyethenyl ethers

Article abstract of DOI:10.1016/S0040-4039(01)02195-5

A general selective synthesis of β-, γ- and δ-hydroxyethenyl ethers, a class of compounds containing two mutually reactive functionalities positioned at an interacting distance, is based on the reaction of diols with 1,2-bis-(phenylsulfonyl)ethylene (BPSE) followed by reductive elimination of the resulting β-phenylsulfonyl acetals with sodium amalgam.

Full text of DOI:10.1016/S0040-4039(01)02195-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 585–587
A general, selective synthesis of v-hydroxyethenyl ethers
E. Cabianca,a,b F. Che´ry,a P. Rollin,a,* A. Tatiboue¨ta and O. De Lucchib
aICOA-UMR 6005/Universite´ d’Orle´ans, B.P. 6759, F-45067 Orle´ans Cedex 2, France
bDipartimento di Chimica, Universita` Ca’ Foscari di Venezia, Dorsoduro 2137, I-30123 Venezia, Italy
Received 9 October 2001; accepted 19 November 2001
Abstract—A general selective synthesis of b-, g- and d-hydroxyethenyl ethers, a class of compounds containing two mutually
reactive functionalities positioned at an interacting distance, is based on the reaction of diols with 1,2-bis-(phenylsulfonyl)ethylene
(BPSE) followed by reductive elimination of the resulting b-phenylsulfonyl acetals with sodium amalgam. © 2002 Elsevier Science
Ltd. All rights reserved.
v-Hydroxyethenyl (or -vinyl) ethers 1 represent a rare
class of organic compounds which contain at an inter-
acting distance two functional groups which—except
under basic conditions—are highly reactive to one
another. Indeed b-, g- and d-hydroxyvinyl ethers are
possible intermediates in the generation of cyclic acetals
2 via the standard condensation of diols with aldehydes
as shown in Scheme 1 for the parent vinyl ether.
addition of organometallics;4 (iii) addition of vinyl-
metals to endoperoxides.5 None of the reported proce-
dures represent a selective synthesis and they all
contain inherent drawbacks and disadvantages such as
length, availability of the starting material, hazard in
handling acetylene, scope and selectivity, etc.
Herewith we report the first general synthetic methodol-
ogy for a selective synthesis of this class of compounds,
which is based on the two-step pathway shown in
Scheme 2.
Of course, while the saturated acetals 2 are widely used
as protective groups and thus devoid of per se practical
reactivity, b-, g- and d-hydroxyvinyl ethers 1 are most
promising from a synthetic viewpoint either for the
reactivity of the vinyl ether itself1 or for the extra
potentiality offered by the close proximity of the
hydroxyl function. Compounds 1 can be particularly
valuable when derived from chiral enantiopure diols in
which the presence of the hydroxyl function can play an
important role in the transmission of the chiral
information.2
The reaction of diols with either (Z)- or (E)-isomers of
1,2-bis-(phenylsulfonyl)ethylene (BPSE) leads in high
yields to the respective b-phenylsulfonyl acetals 3a–f.6,7
These compounds are stable crystalline substances
which are highly resistant to hydrolysis7 and can thus
be stored indefinitely as precursors of the hydroxyenol
ethers. Phenylsulfonylacetals other than 3a–f are also
available.7,8 Significantly, acetals 3g and 3h display
1,3-dioxocane and 1,3-dioxacyclotridecane rings,
respectively. Though they are produced in quite poor
yield (11 and 2%, respectively) and have not been
further processed to the respective hydroxyethenyl
ethers, they are indicative of the scope of the reaction.
Some preparations of hydroxyethenyl ethers are
reported in the literature. The proposed methods can be
summarised as: (i) vinylation of diols with acetylene
itself or haloethylenes;3 (ii) preparation of vinyl ethers
containing a carbonyl group followed by reduction or
Scheme 1.
* Corresponding author.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02195-5

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E. Cabianca et al. / Tetrahedron Letters 43 (2002) 585–587
Scheme 2.
At the outset, the reduction of 3a–f using 6% sodium
amalgam was thought to proceed with formation of the
ethylidene acetals 5 via a standard desulfonylation
pathway (Scheme 3).
ucts while the clean sodium amalgam reduction and the
work-up procedure allows for the isolation of the
hydroxyethenyl ether with such purity grade that they
do not require further purification.
In conclusion, the present methodology represents a
broad general synthetic protocol for the preparation of
hydroxyethenyl ethers. The method highlights the
potentiality of BPSE as acetylene substitute in organic
synthesis.10 The high reactivity of BPSE associated with
its crystallinity makes the reactions easy to be per-
formed and the products highly versatile for the prepa-
ration of several classes of compounds which are
otherwise not easily available by other means.
Contrary to such an expectation the sodium amalgam
reduction selectively led in all cases to the correspond-
ing hydroxyethenyl ethers 4a–f in fair to good yields.
No products of type 5 could be detected, thus confirm-
ing the selectivity of the reaction. The preferred forma-
tion of a hydroxyethenyl ether over that of the
ethylidene acetal can be easily rationalised with the
b-elimination of the carbanion with formation of the
thermodynamically more stable alkoxide anion as can
be observed in related instances (Scheme 3).9 The basic
reaction conditions maintained throughout the reaction
sequence ensure survival of the otherwise delicate prod-
Typical procedure for the synthesis of b-phenylsulfonyl-
acetals 3a–f from diols. A solution of the diol (0.32
mmol) in anhydrous THF (2 mL) was treated with
NaH (2 equiv.) and a few crystals of Bu4NBr as phase
transfer agent, while stirring under argon at 0°C. After
30 min, BPSE (0.32 mmol) was added and the mixture
was allowed to stir overnight, then quenched with
water, extracted with EtOAc and dried over MgSO4.
After evaporation of the solvent, the residue was
purified by silica gel column chromatography
(petroleum ether/EtOAc). Yields reported in Scheme 2.
Typical procedure for the synthesis of hydroxyethenyl
ethers 4a–f. To a solution of the acetal 3 in anhydrous
MeOH (100 mg/5 mL), 6% sodium amalgam (8 g/0.44
mmol of compound) and solid phosphate buffer
NaH2PO4 (4 g/0.44 mmol of compound) was added.
The reaction mixture was monitored (TLC) at room
temperature until complete consumption of the acetal,
then filtered over Celite, washed with dichloromethane
and extracted. The organic phase was washed with
water (pH maintained neutral/basic), dried over K2CO3
and concentrated under vacuum to afford the hydroxy-
ethenyl ether 4. Yields reported in Scheme 2.
Scheme 3.

E. Cabianca et al. / Tetrahedron Letters 43 (2002) 585–587
587
Acknowledgements
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Chem. Soc. 1991, 113, 3925–3934; (b) Clark, J. S.; Ket-
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5. Schwaebe, M. K.; Little, R. D. Tetrahedron Lett. 1996,
37, 6635–6638.
This work was partly funded by MURST (Rome)
within the national project ‘Stereoselezione in Sintesi
Organica Metodologie e Applicazioni’.
6. Cossu, S.; De Lucchi, O.; Fabris, F.; Ballini, R.;
Bosica, G. Synthesis 1996, 1481–1484.
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8. Che´ry, F.; Rollin, P., unpublished results.
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