Toward the total synthesis of phorboxazole A: synthesis of an advanced C4-C32 subunit using the Jacobsen hetero Diels-Alder reaction

The tetrahydropyranone 3, representing a pentacyclic C₄-C₃₂ segment of the phorboxazoles, was obtained by a complex hetero Diels-Alder (HDA) coupling performed between the 2-siloxydiene 23 and the oxazole aldehyde 4, mediated by the chiral tridentate Cr(III) catalyst 14. In preliminary studies, the tetrahydropyrans 17, 33 and 35 were accessed using this same asymmetric HDA methodology with varying stereoselectivity.