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.