Investigating thio-analogues of PSE acetals: A more complex reaction

Article abstract of DOI:10.1016/S0040-4039(03)01303-0

The reaction of hydroxylated thiols with 1,2-bis-phenylsulfonylethylene was investigated: in contrast with diols, a more complex reaction was observed and application to carbohydrate-derived PSE oxathianes was envisaged.

Full text of DOI:10.1016/S0040-4039(03)01303-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 5723–5725
Investigating thio-analogues of PSE acetals:
a more complex reaction
Elena Cabianca,a,b Arnaud Tatiboue¨t,a Florence Che´ry,a Christelle Pillard,a Ottorino De Lucchib and
Patrick Rollina,*
aICOA-UMR 6005/Universite´ d’Orle´ans, BP 6759, F-45067 Orle´ans Cedex 2, France
bDipartimento di Chimica, Universita` Ca’ Foscari di Venezia, Dorsoduro 2137, I-30123 Venezia, Italy
Received 13 March 2003; accepted 27 May 2003
Abstract—The reaction of hydroxylated thiols with 1,2-bis-phenylsulfonylethylene was investigated: in contrast with diols, a more
complex reaction was observed and application to carbohydrate-derived PSE oxathianes was envisaged.
© 2003 Elsevier Ltd. All rights reserved.
We have recently developed a novel type of ethylidene
acetals bearing phenylsulfonyl appendage (PSE
was therefore not likely that 1 could rearrange into 2
under basic conditions. Such flimsy hypothesis was
finally ruled out by submitting again oxathiolane 1 to
the basic conditions of its formation: no trace of
oxathiane 2 could be detected after prolonged reaction
time.
a
acetals), which can find use as effective protective
groups in polyols and carbohydrate chemistry1 or as
handy precursors to ethenyl ethers.2 Extension of our
previous study to the elaboration of PSE thioacetals
appeared profitable in several aspects:
– compare with acid-stable PSE acetals in terms of
behavior towards deprotection conditions
More realistic would be to envisage the formation of 2
through a base-induced ring-closing process involving
the putative vinyl sulfone precursor 1-(2-hydroxy-
ethylthio)-1-phenylsulfonylethylene 3, whose intermedi-
acy had in turn to be made clear (Scheme 2).
– acyl carbanion equivalence3
– introduce a stereogenic center—the newly-formed
acetalic carbon—potentially exploitable in asymmet-
ric synthesis4
– introduce a prochiral system, with a sulfur atom to
be potentially tri-coordinated through oxidation
With a view to better putting into light the diverse steps
of the process, the reaction conditions were modified
(NEt3 in THF at rt) so as to favor the chemoselective
In connexion with our previous investigations,2,5 the
basic 1,3-oxathiolane model was first selected and our
standard reaction conditions (NaH+nBu4NBr in THF
at rt) thus applied to a 1:1 mixture of 2-mercapto-
ethanol and (Z)-1,2-bis-phenylsulfonylethylene (BPSE).
Besides the expected 2-phenylsulfonylmethyl-1,3-
oxathiolane (1),6 obtained in 50–75% yield according to
trials, a side-product was formed (3–10% yield), to
which the unusual structure of 3-phenylsulfonyl-1,4-
Scheme 1.
7
oxathiane (2) was attributed (Scheme 1).
Ring-expanding rearrangements of 1,3-oxathiolanes are
documented8 but they normally require induction by
strong electrophilic agents such as sulfuryl chloride;9 it
* Corresponding author. Tel.: +33-(0)2-3841-7370; fax: +33-(0)2-
3841-72 81; e-mail: patrick.rollin@univ-orleans.fr
Scheme 2.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01303-0

5724
E. Cabianca et al. / Tetrahedron Letters 44 (2003) 5723–5725
Finally, o-hydroxymethyl thiophenol—a conformation-
ally more rigid system—was reacted with (Z)-
BPSE under NEt3 catalysis to produce (61% yield)17 the
major (Z)-vinyl sulfone 15Z18 together with its minor
(10% yield) regioisomer 1619—which is structurally
closely related to the transient sulfone 3 hypothesized
above. When applied to o-hydroxymethyl thiophenol in
contrast, the NaH-catalyzed cycloacetalation only
afforded 33% yield of 2-phenylsulfonylmethyl-4H-3,1-
benzoxathiin 1720 (Scheme 5).
addition of the thiol group of 2-mercaptoethanol onto
the electrophilic partner.
Applying the above conditions, three products could be
isolated from the reaction in 4, 53 and 26% yield,
respectively: first, the primary 1:1 adduct 1-(2-hydroxy-
ethylthio)-1,2-bis-phenylsulfonylethane 4,10 then (Z)-
vinyl sulfone 5Z11 resulting from base-induced phenyl-
sulfinate elimination in 4, and finally a more polar
compound which was identified as a 2:1 adduct-
1,2-bis-(2-hydroxyethylthio)-1-phenylsulfonylethane 6,12
derived from chimeric transient 3 (Scheme 3).
The reaction was repeated using (E)-BPSE instead of
the above Z-stereomer,13 to similarly afford a 50% yield
of the (E)-vinyl sulfone 5E,14,15 together with 36% of 6.
When submitting either 5Z or 5E vinyl sulfone to
harsher basic conditions (NaH in THF) in order to
induce internal Michael addition, only moderate yields
(ca. 60%) of 1,3-oxathiolane 1 were attained.
Scheme 5.
The above results reveal that extending our BPSE
methodology to the elaboration of diverse thioacetal
Extension to the case of 3-mercaptopropanol and 4-
mercaptobutanol revealed a similar behavior in the
NEt3-catalyzed reaction with (Z)-BPSE: primary 1:1
adducts 7 and 10 (11 and 8% yield, respectively), (Z)-
vinyl sulfones 8Z and 11Z (53 and 59% yield, respec-
tively) and 2:1 adducts 9 and 12 (20 and 17% yield,
respectively) were formed. Applying the above cycliza-
tion conditions to 8Z resulted in a 68% yield of 1,3-
oxathiane 13,16 whereas 11Z was not converted into
1,3-oxathiepane 14 (Scheme 4). A similar behavior was
observed when using the NaH-catalyzed one step pro-
cedure which furnished 13 in 90% yield while 14 was
produced in ca. only 10% yield.
analogues can involve
a more complex reaction
sequence: from a synthetic viewpoint, the 1,3-oxathiane
case unambiguously proved to be the most favorable.
As inspired by De Lucchi’s pioneering work in the
isobornane series21—and besides developing in the lab
the chiral precursor 13 as a matrix for stereoselection
tools—we also considered to investigate the elaboration
of enantiopure substrates by implanting of PSE 1,3-
oxathianes on chiral templates such as saccharidic com-
pounds. With this aim in view, the regioisomeric
D
-glucopyranosidic thiols 18 and 19 were synthesized
(Scheme 6).
Scheme 6.
Applying the NaH-catalyzed one step procedure previ-
ously used for 3-mercaptopropanol, both the expected
isomeric PSE 1,3-oxathianes 20 and 21 could be
obtained in 72 and 83% yield, respectively. The synthe-
sis and evaluation of carbohydrate-derived PSE thioac-
etals in stereocontrolled reactions is under current
development in our group.
Scheme 3.
Scheme 4.
Acknowledgements
The authors wish to thank EGIDE for a fellowship
(E.C.)

E. Cabianca et al. / Tetrahedron Letters 44 (2003) 5723–5725
5725
12. Selected NMR data for 2:1 adduct 6: l 7.96 (bd, 2H,
ortho-H-Ar), 7.70 (m, 1H, para-H-Ar), 7.59 (m, 2H,
meta-H-Ar), 4.34 (dd, 1H, Jvic=11.5 and 2.9 Hz, H-1),
3.76 (bd, 4H, CH2O), 3.54 (bs, OH), 3.30 (bdd, 2H,
References
1. Che´ry, F.; Rollin, P.; De Lucchi, O.; Cossu, S. Synthesis
2001, 286–292.
2. Cabianca, E.; Che´ry, F.; Rollin, P.; Tatiboue¨t, A.; De
Lucchi, O. Tetrahedron Lett. 2002, 43, 585–587.
3. Eliel, E. L.; Morris-Natschke, S. J. J. Am. Chem. Soc.
1984, 106, 2937–2942.
J
gem=13.9 Hz, Jvic=2.9 Hz, H-2a, OH), 2.77 (m, 4H,
CH2S), 2.60 (dd, 1H, Jgem=13.9 Hz, Jvic=11.5 Hz, H-
2b); 135.8 (CIV-Ar), 134.5 (para-CH-Ar), 129.9 (meta-
CH-Ar), 129.2 (ortho-CH-Ar), 70.2 (C-1), 61.4 and 61.0
(CH2O), 36.6 and 36.4 (CH2S), 32.6 (C-2); MS (Ion-
spray®): [M+Na]+=345.0.
4. Utimoto, K.; Nakamura, A.; Matsubara, S. J. Am.
Chem. Soc. 1990, 112, 8189–8190.
13. BPSE is commercially available in both Z- and E-stereo-
forms.
14. Retention of configuration in Michael additions on BPSE
was initially reported by Meek and Fowler. See: Meek, J.
S.; Fowler, J. S. J. Org. Chem. 1968, 33, 985–991.
15. Selected NMR data for vinyl sulfone 5E: l 7.85 (bd, 2H,
5. Cossu, S.; De Lucchi, O.; Fabris, F.; Ballini, R.; Bosica,
G. Synthesis 1996, 1481–1484.
6. Fully satisfactory spectroscopic data (MS, 250 MHz 1H
NMR and 62.5 MHz 13C NMR) were obtained for all
new compounds; selected NMR (CDCl3) data for 1,3-
oxathiolane 1: l 7.91 (bd, 2H, ortho-H-Ar), 7.52–7.72 (m,
3H, H-Ar), 5.48 (dd, 1H, Jvic=5.6 and 3.9 Hz, H-2), 4.18
ortho-H-Ar), 7.50–7.65 (m, 3H, H-Ar), 7.76 (d, 1H, Jvic
=
14.7 Hz, H-2), 6.27 (d, 1H, Jvic=14.7 Hz, H-1), 3.82 (bt
2H, Jvic=6.1 Hz, CH2O), 2.98 (bt, 2H, Jvic=6.1 Hz,
CH2S); 146.0 (C-2), 140.0 (CIV-Ar), 133.3 (para-CH-Ar),
129.4 (meta-CH-Ar), 127.3 (ortho-CH-Ar), 122.0 (C-1),
60.5 (CH2O), 35.2 (CH2S); MS (Ionspray®): [M+Na]+=
267.0.
(m, 1H, H-5a), 3.80 (m, 1H, H-5b), 3.68 (dd, 1H, Jgem
=
14.4 Hz, H-6a), 3.47 (dd, 1H, H-6b), 2.99 (m, 2H, H-4);
139.8 (CIV-Ar), 134.4 (para-CH-Ar), 129.6 (meta-CH-
Ar), 128.6 (ortho-CH-Ar), 79.6 (C-2), 72.0 (C-5), 62.4
(C-6), 33.3 (C-4); MS (Ionspray®): [M+H]+=245.0.
7. Selected NMR data for 1,4-oxathiane 2: l 7.99 (bd, 2H,
ortho-H-Ar), 7.52–7.73 (m, 3H, H-Ar), 4.78 (dd, 1H,
16. Selected NMR data for 1,3-oxathiane 13: l 7.90 (bd, 2H,
ortho-H-Ar), 7.52–7.65 (m, 3H, H-Ar), 5.27 (dd, 1H,
J=9.1 and 2.4 Hz, H-2), 3.96 (bd, 1H, Jgem=12.5 Hz,
H-6a), 3.61 (dd, 1H, Jgem=14.7 Hz, Jvic=9.3 Hz, H-7a),
3.53 (ddd, 1H, Jgem=12.5 Hz, H-6b), 3.28 (dd, 1H,
J
gem=13.1, J2a,3=1.8 Hz, H-2a), 4.11 (ddd, 1H, Jgem
12.0 Hz, Jvic=2.9 Hz, H-6a), 3.99 (dd, 1H, Jgem=13.1,
2b,3=3.3 Hz, H-2b), 3.71 (ddd, 1H, Jgem=12.0 Hz, Jvic
=
J
=
J
gem=14.7 Hz, Jvic=2.4 Hz, H-7b), 3.07 (ddd, 1H, Jgem=
2.4 Hz and 10.0 Hz, H-6b), 3.61 (bs, 1H, H-3), 3.09 (ddd,
1H, Jgem=13.5 Hz, Jvic=3.6 Hz and 10.0 Hz, H-5a), 2.15
(bd, 1H, Jgem=13.5 Hz, H-5b); 137.5 (CIV-Ar), 134.4
(para-CH-Ar), 129.9 (meta-CH-Ar), 129.1 (ortho-CH-
Ar), 67.9 (C-6), 66.2 (C-2), 59.0 (C-3), 23.6 (C-5); MS
(Ionspray®): [M+Na]+=267.0.
13.5 Hz, H-4a), 2.74 (bd, 1H, Jgem=13.5 Hz, H-4b), 1.82
(m, 1H, H-5a), 1.63 (bd, 1H, Jgem=13.9 Hz, H-5b); 140.0
(CIV-Ar), 133.8 (para-CH-Ar), 129.0 (meta-CH-Ar),
128.0 (ortho-CH-Ar), 76.6 (C-2), 69.6 (C-6), 61.2 (C-7),
28.2 (C-4), 24.8 (C-5); MS (Ionspray®): [M+Na]+=281.0.
17. (E)-BPSE analogously afforded a 54% yield of 15E.
18. Selected NMR data for vinyl sulfone 15Z: l 7.99 (bd, 2H,
ortho-H-Ar), 7.11 (d, 1H, Jvic=10.3 Hz, H-2), 6.26 (d,
1H, Jvic=10.3 Hz, H-1), 4.73 (s, 2H, CH2O), 3.28 (bs,
1H, OH); 147.2 (C-2), 142.7, 141.1 (CIV-Ar), 123.1 (C-1),
63.1 (CH2O); MS (Ionspray®): [M+Na]+=329.0.
8. (a) De Voss, J. J.; Sui, Z. Tetrahedron Lett. 1994, 35,
49–52; (b) Ioannou, M.; Porter, M. J.; Saez, F. Chem.
Commun. 2002, 346–347.
9. Bulman-Page, P. C.; Ley, S. V.; Morton, J. A.; Williams,
D. J. J. Chem. Soc., Perkin Trans. 1 1981, 457–461.
10. Selected NMR data for 1:1 adduct 4: l 7.85–7.95 (m, 4H,
ortho-H-Ar), 7.50–7.75 (m, 6H, H-Ar), 4.60 (dd, 1H,
19. Selected NMR data for vinyl sulfone 16: l 7.95 (bd, 2H,
ortho-H-Ar), 6.58 (d, 1H, Jgem=2.0 Hz) and 5.54 (d, 1H,
Jvic=11.2 and 2.0 Hz, H-1), 3.88 (dd, 1H, Jgem=14.4 Hz,
Jvic=11.2 Hz, H-2a), 3.80 (bs, 2H, CH2O), 3.40 (dd, 1H,
Jgem=14.4, Jvic=2.0 Hz, H-2b), 3.07 (bs, 1H, OH), 2.77
J
gem=2.0 Hz, C=CH2), 4.53 (s, 2H, CH2O), 2.25 (bs,
1H, OH); 148.8 (C-1), 143.8, 140.9, 138.7 (CIV-Ar), 125.8
(C-2), 62.9 (CH2O); MS (Ionspray®): [M+Na]+=329.0.
20. Selected NMR data for 4H-3,1-benzoxathiin 17: l 7.95
(bd, 2H, ortho-PhSO2), 7.50–7.70 (m, 3H, PhSO2), 7.20–
7.00 (m, 4H, H-Ar), 5.63 (dd, 1H, Jvic=2.8 Hz and 9.0
Hz, H-2), 4.73 (AB system, 2H, Jgem=15.0 Hz, CH2O),
3.78 (dd, 1H, Jgem=14.7 Hz, Jvic=8.8 Hz, CH2SO2), 3.44
(dd, 1H, Jgem=14.7 Hz, Jvic=2.8 Hz, CH2SO2); 139.9
(CIV-PhSO2), 134.1 (para-CH-PhSO2), 130.4, 129.3,
128.3, 127.7, 127.6, 126.0 and 125.4 (CH-Ar), 75.2 (C-2),
69.2 (C-4), 61.1 (CH2SO2); MS (Ionspray®): [M+Na]+=
329.0.
(dd, 2H, CH2S); 139.1 (CIV-Ar), 134.9, 134.6 (para-CH-
Ar), 130.0, 129.7 (meta-CH-Ar), 128.1 (ortho-CH-Ar),
62.4 (C-1), 60.9 (CH2O), 55.1 (C-2), 36.9 (CH2S); MS
(Ionspray®): [M+Na]+=409.0.
11. Selected NMR data for vinyl sulfone 5Z: l 7.99 (bd, 2H,
ortho-H-Ar), 7.50–7.65 (m, 3H, H-Ar), 7.16 (d, 1H, Jvic
=
10.5 Hz, H-2), 6.25 (d, 1H, Jvic=10.5 Hz, H-1), 3.84 (bt,
2H, Jvic=5.9 Hz, CH2O), 2.95 (bt, 2H, Jvic=5.9 Hz,
CH2S); 147.1 (C-2), 141.3 (CIV-Ar), 133.6 (para-CH-Ar),
129.3 (meta-CH-Ar), 127.3 (ortho-CH-Ar), 123.2 (C-1),
62.1 (CH2O), 38.9 (CH2S); MS (Ionspray®): [M+Na]+=
267.0.
21. De Lucchi, O.; Lucchini, V.; Marchioro, C.; Modena, G.
Tetrahedron Lett. 1985, 26, 4539–4542.