Organic & Biomolecular Chemistry
Communication
Notes and references
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Scheme 4 Investigation on the double functionalization.
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observed. The reaction with MeI resulted in the formation of
trans-3c and cis-3c (trans/cis ratio: 27/73) while in the reaction
with BnBr only trans-3f was obtained.
Moreover, we were keen to find an explanation for the
double functionalization of thietane 1. In principle two possi-
bilities could be envisaged: (a)
a stepwise lithiation/
functionalization; (b) the involvement of a dilithio species.
This last hypothesis seems unlikely because it should involve a
2,4-dilithiated sulfoxide that, to the best of our knowledge, has
not previously been observed. With the aim to get more
insights into this double direct functionalization of thietanes,
we attempted a further lithiation/trapping sequence on mono-
substituted thietanes 2. In particular when the main diaster-
eoisomers trans-2a and trans-2g were reacted respectively with
2.5 equiv. and 1.3 equiv. of LDA at −78 °C for 30 min, the
corresponding lithiated intermediate was generated and
trapped with MeI (Scheme 4). The reaction resulted highly
stereoselective and only trans disubstituted thietanes trans-5
and trans-6, were obtained, as ascertained by NOESY experi-
ments (see ESI†), with very good yields.20
From our preliminary results it seems that the double
functionalization could proceed stepwise involving the putative
lithiated intermediates such as 7 (Scheme 4). Those results are
important from a reactivity and stereochemical point of view
and for planning stereoselective synthesis using such hetero-
substituted organolithiums.
In conclusion, this work tries to fill the gap in knowledge on
the direct single and double functionalization of thietanes. An
effective methodology for selective C2 and C2, C4 functionaliza-
tions of thietane 1-oxide has been developed for the first time.
The mono (C2) functionalization as well as the double (C2, C4)
functionalization occurred mainly with trans selectivity. Further
studies will rely on the application of this methodology in
stereoselective synthesis and in understanding the nature of the
lithiated intermediates involved in the described processes.
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9 For a recent work on the importance in drug-discovery of
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Acknowledgements
We thank National Project “FIRB – Futuro in Ricerca” (code:
CINECA RBFR083M5N), Interuniversity Consortium CINMPIS;
we are grateful to Giovanna Parisi, Elisa Oliva and Mara Anelli 11 D. Neville Jones, T. P. Kogan, R. F. Newton and S. Smith,
for their precious synthetic work.
J. Chem. Soc., Chem. Commun., 1982, 589.
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