Total synthesis of gracilioether F: development and application of lewis Acid promoted ketene-alkene [2+2] cycloadditions and late-stage C-H oxidation.

The first synthesis of gracilioether F, a polyketide natural product with an unusual tricyclic core and five contiguous stereocenters, is described. Key steps of the synthesis include a Lewis acid promoted ketene-alkene [2+2] cycloaddition and a late-stage carboxylic acid directed C(sp(3) )H oxidation. The synthesis requires only eight steps from norbornadiene.