The uncatalyzed intramolecular carbonyl ene (ICE) reaction of substituted ε,ζ-unsaturated α-keto esters to terpenoid-related building blocks has been studied. We found a beneficial effect of a silyl substituent at the ene segment on the kinetics of the ICE reaction. A generalizable and scalable synthesis of ε,ζ-unsaturated α-keto esters from allylic alcohols was developed.

The synthesis of a diastereomer of lytophilippine A required 22 longest linear steps using known building blocks. Cross-metathesis/asymmetric aldol addition and regioselective esterification/ring-closing metathesis served as efficient combi tools for scaffold construction. Detailed NMR investigations in different solvent (systems) provide evidence for a deep-seated configurational misassignment of the molecule named lytophilippine A.