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Thione Esters as Substrates for the Stereoselective Alkylation of Model Compounds of Nonactic Acids

Auteur(s)
Loiseau, Francois
Kholod, Inga
Date de parution
2010
In
Eur. J. Org. Chem.
Vol.
24
De la page
4642
A la page
4661, S4642/1-S4642/13
Mots-clés
Résumé
The naturally occurring macrotetrolide antibiotic nonactin is used in ammonium ion selective electrodes. To increase the lifetime of nonactin in the semipermeable membrane of these sensors we have developed methods for the introduction of hydrophobic side-chains. Simple model compds. for nonactic acid such as I (R = H, Me, X = O) were synthesized. Maintaining the cis arrangement of the substituents in the 2,5-disubstituted tetrahydrofurans proved to be difficult. Three different routes were studied. The enolates obtained by treatment with NaHMDS or KHMDS could be alkylated with benzyl or allyl iodide as electrophiles. Under these conditions a cis/trans isomerization of the substituents on the THF ring occurred. A multistep methodol. was developed as a synthetic alternative. The sequence consisted of a selective retro-Michael reaction, a 5-exo-tet iodocyclization and a radical substitution. The products obtained by the two methodologies could be correlated, and thereby a tentative assignment of the relative configurations could be achieved. In the third route the thione ester I (R = Me, X = S) was deprotonated with tert-BuOK. At temps. below -78 °C, the enolate maintained the cis configuration of the substituents at the THF ring. The alkylated product II could be isolated with a satisfactory cis/trans ratio of 85:15. The model compd. II could be successfully transformed into more hydrophobic derivs. by using either the Heck coupling or the cross-coupling metathesis transformation. [on SciFinder(R)]
URI
Type de publication
Resource Types::text::journal::journal article