Evans Aldol-Prins Strategy used as Highly Efficient Methodology to Synthesize Stereoselectively Polysubstituted Tetrahydropyrans?

GARCÍA, CELINA; ÁLVAREZ-MÉNDEZ,SERGIO J.; VILLALBA MARIA L. ; FARIÑA-RAMOSA MARTA; MARTIN VICTOR

Ferrara

Congreso; 12thSpanish-Italian Symposium on Organic Chemistry (SISOC-XII); 2018

Divisione di Chimica Organica - Società Chimica Italiana and of the Grupo Especializado de Química Orgánica - Real Sociedad Española de Química.

The Evans Aldol-Prins protocol has emerged as an efficient tool for the transformation of β, unsaturated N-acyl oxazolidin-2-ones into 2,3,4,5,6-pentasubstitutted tetrahydropyrans.The combination of the Evans aldol addition and the Prins cyclization allowed the diastereoselective and efficient generation of the oxacycles in an unprecedented bicyclic form due to the rearrangement suffered in the reaction medium by the auxiliary core from the starting material. This strategy conducted to the preparation of a battery of more than 30 densely substituted tetrahydro pyrans fused to a 1,3-oxazinane-2,4-dione ring, both in a racemic and in a enantiomeric fashion. As the tetrahydropyran motif is commonly found in biologically active secondary metabolites isolated from marine and terrestrial sources, use this strategy in the synthesis of natural products represents a great challenge. We have choose several structures to synthesize, among them Clavosolide A, isolated from the cytotoxic extract of the sponge Myriastra clavosa, whose attractive molecular architecture has inspired nine total syntheses until now. In this communication, the Evans aldol-Prins strategy as well as our approach towards the formal synthesis of Clavosolide A will be presented.