[4 + 2]-Annulations of Chiral Organosilanes: Application to the Total Synthesis of Leucascandrolide A

Abstract

Complete details of an asymmetric synthesis of leucascandrolide A (1) are described. The synthesis highlights the use of two diastereoselective [4 + 2]-annulations for the assembly of the functionalized bispyranyl macrolide 3. An efficient assembly and union of the oxazole-containing side chain 4 with macrolide 3 was carried out using a Mitsunobu reaction. A convergent route to the oxazole side chain was developed using a Sonogashira cross-coupling between 2-trifloyloxazole 16 and alkyne 17, which allowed for the installation of the C9'-C10' (Z)-olefin.