Permanganate mediated oxidative cyclisation and its application to the synthesis of natural products

Abstract

Cis-2,5-disubstituted tetrahydrofurans (THFs) are present in a large number of biologically active molecules, including many polyether antibiotics and acetogenins.  In view of the importance of THF-containing structures, their efficient steroecontrolled synthesis remains an important objective.

Permanganate mediated oxidative cyclisation of 1,5,9-treinoates and subsequent oxidative cleavage provided the corresponding perhydro-2,2-bifuranyl systems with control of relative stereochemistry at four new stereocentres.  Optically pure THF-lactones were obtained through the use of the Oppolzer soltam chiral auxiliary. The requisite starting trienes were prepared stereoselectively in just three steps from geranyl and neryl chlorides, providing a short and versatile route to polyether fragments.

Permanganate promoted oxidative oxidation was applied toward the synthesis of a natural product, intricatetraol.  The construction of a non adjacent bis-THF diol core was investigated via tandem oxidative cyclisation of a tetraene precursor.  The tetraene precursor was selectively prepared by coupling two moieties synthesised from nergyl acetate.  An alternative approach to the synthesis of intricatetraol was also investigated where the bis-THF core was formed via the coupling of two THF rings. The revised approach relied on a metathesis reaction to couple the two THF-containing fragments.  Selective oxidative cyclisation of readily available 1,5,9-trieneoates provided the desired mono-THFs that would provide the non adjacent bis-THF segment via metathesis.

The oxidation of readily available 1,5-dienoates and 1,5,9-trienoates containing a terminal double bond afforded cis-THF-containing products that were easily converted to the corresponding trans-THF adducts.  This new methodology was applied toward the synthesis of eurylene, a natural product.

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