Here we report a total synthesis of the pharmacologically significant morphinan alkaloid, oxycodone.

Thiophene S,S-dioxides are underutilized tools for the de novo construction of benzene rings in organic synthesis. We report a collective synthesis of nine illudalane sesquiterpenes using bicyclic thiophene S,S-dioxides as generalized precursors to the indane core of the natural products. Exploiting furans as unusual dienophiles in this inverse electron demand Diels–Alder cascade, this concise and convergent approach enables the synthesis of these targets in as little as five steps. Theoretical studies rationalize the reactivity of thiophene S,S-dioxides with both electron-poor and electron-rich dienophiles and reveal reaction pathways involving either nonpolar pericyclic or bifurcating ambimodal cycloadditions. Overall, this work demonstrates the wider potential of thiophene S,S-dioxides as convenient and flexible precursors to polysubstituted arenes.

A rationally designed, serial point-to-axial and axial-to-point stereoinduction and its integration into a multi-step and target-oriented organic synthesis was demonstrated in a novel chemical method to access morphinans and it is potentially applicable to other structurally related alkaloids.

Synthesis of the strained cyclophane alkaloid haouamine A has been accomplished via a late-stage and strain-accelerated oxidation to access the challenging biphenol cyclophane system.