Synthesis of substituted α,β-unsaturated δ-lactones from vinyl tellurides
Graphical abstract
Introduction
Substituted α,β-unsaturated δ-lactones units are present in a large number of compounds isolated from plants and marine organisms. Representative examples are goniothalamin,1 massoialactone,2 and euscapholide3 (Fig. 1). These compounds possess a broad range of biological activities. Noteworthily, structure–activity relationships have demonstrated that the α,β-unsaturated-δ-lactone moiety plays a key role in the bioactivity of many natural products. This is due to the fact that this unit is an excellent potential Michael acceptor for nucleophilic amino acid residues of the natural receptors interacting with these compounds.4, 5, 6
Because of their biological activities, many approaches to these lactones have been reported.7, 7(a), 7(b), 7(c), 7(d), 7(e), 7(f), 7(g) The majority of them are based on ring-closing metathesis strategies,8, 8(a), 8(b) which has become a powerful tool in organic synthesis for the preparation of cyclic compounds from diolefinic precursors.9, 9(a), 9(b), 9(c), 9(d), 9(e), 9(f)
In the current decade, organotellurium compounds have attained remarkable development as synthons in synthetic organic chemistry.10(c), 10, 10(a), 10(b) In addition, some organotellurium compounds are potent in vitro antioxidants,11(b), 11, 11(a) showing very low toxicity, as well no neurotoxic effects.11(b), 12(b), 12, 12(a)
Allylic alcohols containing a stereodefined double bond are important synthetic intermediates,13(c), 13, 13(a), 13(b) and can be easily prepared when hydroxy-alkynes are subjected to hydrotelluration conditions.14(b), 14(c), 14(d), 14(e), 14(f), 14, 14(a) Recently, we demonstrated the efficiency of TIPS as the protecting group of propargyl and homo-propargyl alcohols in order to improve the regioselectivity in the hydrotelluration reaction.15 In this paper we describe the use of organotellurium compounds on the synthesis of substituted α,β-unsaturated δ-lactones.
Section snippets
Results and discussion
In an initial approach propargyl alcohol was converted into its TIPS, 1, derivative according to the literature procedure16 and then subjected to hydrotelluration conditions to yield the corresponding vinyl tellurides 2 and 3,15 which were easily separated by flash column chromatography (Scheme 1).
The influence of the TIPS group was remarkable. When propargyl alcohol was used as the alkyne source a 56:44 mixture of regioisomers was observed. The regioisomeric ratio was determined by 1H NMR and
Conclusion
In conclusion, the method demonstrates to be useful for the synthesis of α,β-unsaturated δ-lactones starting from vinyl tellurides. The approach is complementary to the methods using RCM reactions and the sequence was performed in good overall yield with retention of the double bond geometry. Finally, the method offers future possibilities in the development of new organometallic approaches to the compounds containing Z-double bonds.
Material
All reagents and solvents used were previously purified and dried in agreement with the literature.34 THF was distilled from sodium/benzophenone under N2 immediately before use. n-BuLi was titrated using 1,10-phenanthroline as indicator prior to use.35 All operations were carried out in flame-dried glassware. Reactions were monitored by thin-layer chromatography on 0.25 mm E. Merck silica gel 60 plates (F254) using UV light, vanillin and p-anisaldehyde as visualizing agents. Column
Acknowledgements
The authors gratefully acknowledge CNPq (471252/2007-7), CAPES, and INCT-INAMI for financial support. The authors are also thankful to CNPq for their fellowships.
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