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S. P. Cha6an et al. / Tetrahedron: Asymmetry 12 (2001) 1101–1103
in the synthesis of both prostanes and isoprostanes.
Accordingly, intermediate 2 was prepared by the
reported method7,8 and subjected to the double Michael
reaction with lithium benzene thiolate to give the corre-
sponding adduct 3 {[h]D=−35.2 (c 1.09, CHCl3)} in
99% yield and with 99% d.e.6 Since the stereochemistry
of the phenylthio group has been previously estab-
lished,9 we were interested in elaborating this intermedi-
ate to the bicyclic lactone 4. The two TBSO groups can
be differentiated and were deprotected using TBAF
solution in THF.8 The dihydroxy compound obtained
was then directly subjected to cyclization without isola-
tion using p-TSA to yield hydroxy lactone 4 {[h]D=
+69.6 (c 1.04, CHCl3)}.
the presence of chlorine and IR spectroscopy showed
the presence of the sulphone moiety. H NMR of 6
1
indicated the presence of seven protons (as well as the
ester and aromatic protons), indicating that the
hydroxyl group had been displaced by chlorine during
the reaction. Gratifyingly, 6 crystallized and X-ray crys-
tallographic data unequivocally confirmed the presence
of chlorine and sulphone and the trans-stereochemistry
(Fig. 1). The trans-stereochemistry may be attributable
to the formation of a four-membered cyclic intermedi-
ate during the reaction with sulphuryl chloride (as seen
in b-sultines). Attack of chloride would then lead to
opening of the unstable four-membered ring, and the
observed trans-stereochemistry of 6 would result. This
unusual ring opening is particularly useful in light of
the earlier unsuccessful attempts at E2 elimination of
the hydroxyl group.
Initial attempts were directed towards conversion of the
hydroxy group of 4 to a halide for subsequent E2
elimination. However, all attempts by conventional
methodologies failed to form the desired objective,
probably as a result of steric hindrance caused by the
rigid bicyclic ring and the adjacent thiophenoxy group.
For example, a simultaneous single-pot elimination of
thiophenyl and hydroxy group, akin to Julia’s elimina-
tion,10 was pursued with less than encouraging results.
Attempts to react the analogous hydroxy sulphoxide
and hydroxy sulphone compounds, formed by oxida-
tion of the thiophenoxy group, also proved unfruitful.
The chlorosulphone 6 was then reduced under radical
conditions using tri-n-butyl tin hydride to furnish the
desired olefin 714 in 80% yield {[h]D=−18.6 (c 0.66,
CHCl3)}. Thus, the ring opening and elimination proto-
col gave the a,b-unsaturated ester 7,13 which is an
important synthon for a variety of prostanes12 and
3
isoprostanes such as 8-epi PGF2a as well as Corey’s
lactone.
Another key feature of this strategy is that the a- and
v-sidechains for the prostaglandins can be synthesized
in either the cis- or trans-stereochemical disposition, as
both enantiomers of 7 can be easily accessed by choos-
ing the appropriate tartaric acid starting material.
Pursuing this course of eliminations for the b-hydroxy
sulphoxides, it was known that NCS/NBS/SO2Cl2 are
utilized to convert b-hydroxy sulphoxides to b-sulti-
nes,11 which are generally found to have limited thermal
stability and tend to eliminate SO2 to give olefins. These
reactions have not been previously exploited in a syn-
thetic strategy and, hence, we wanted to explore the
possibility of sultine formation for generation of the
corresponding olefin. The hydroxy lactone 4 was
accordingly converted to the corresponding sulphoxide
5 {[h]D=−64.0 (c 1, MeOH)} and was then subjected to
sulphuryl chloride in DCM at rt to furnish intermediate
6 {[h]D=+105.3 (c 1.05, CHCl3)}, which was found to
be the chlorosulphone. Elemental analysis confirmed
In conclusion, this approach of b-sultine ring opening
can serve as a useful alternative for hindered E2 elimi-
nations and applications to other hindered systems are
currently being probed. Also, further elaboration of the
key intermediate 7 to Corey’s lactone and other
prostanoids is under progress and will be reported in
due course.
Acknowledgements
Y.S.R., C.A.G., and S.R. would like to thank the
CSIR, New Delhi, for financial support. Funding from
the CSIR, New Delhi, under the YSA Scheme is grate-
fully acknowledged.
References
1. (a) Bindra, J. S.; Bindra, R. Prostaglandin Synthesis;
Academic Press: New York, 1977; (b) Mitra, A. The
Synthesis of Prostaglandins; John Wiley & Sons: New
York, 1977; (c) Roberts, S. M.; Scheinmann, F. New
Synthetic Routes to Prostaglandins and Thromboxanes;
Academic Press: New York, 1982; (d) Noyori, R.; Suzuki,
M. Chemtracts Org. Chem. 1990, 3, 173; (e) Collins, P.
W.; Djuric, S. W. Chem. Rev. 1993, 93, 1533.
2. Morrow, J. D.; Hill, K. E.; Burk, R. F.; Nammour, T.
M.; Badr, K. F.; Roberts, II, L. J. Proc. Natl. Acad. Sci.
USA 1990, 87, 9383.
Figure 1. The X-ray structure of intermediate 6.