Collective Synthesis of Illudalane Sesquiterpenes via Cascade Inverse Electron Demand (4 + 2) Cycloadditions of Thiophene S,S-Dioxides.

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.

Late-stage and strain-accelerated oxidation enabled synthesis of haouamine A.

Herein we report a new synthetic entry to the strained cyclophane alkaloid natural product, haouamine A. The successful strategy featured a rhodium-catalyzed diazo-insertion reaction to install the all-carbon quaternary center and a rhodium-catalyzed intramolecular aziridination reaction to establish the nitrogen-bearing stereocenter, of the target molecule. Most notably, a late-stage, site-selective and strain-accelerated oxidation of a "deoxygenated" macrocyclic intermediate was successfully implemented, and in doing so provided a novel solution to the infamous biphenol cyclophane system of haouamine A.

A desymmetrization-based approach to morphinans: application in the total synthesis of oxycodone.

Here we report a total synthesis of the pharmacologically significant morphinan alkaloid, oxycodone. The centerpiece of the developed strategy features the first application of the Rovis desymmetrization of peroxyquinol in target-oriented total synthesis to access an optically active phenanthrene framework shared by the morphinans. A Stork-Ueno radical cyclization under photoredox conditions installed the all-carbon quaternary stereocenter, and a late-stage reductive detosylation with concomitant piperidine formation secured the core structure of the target molecule.