Collective Synthesis of Humulanolides Using a Metathesis Cascade Reaction

A new method has been developed for the concise and asymmetric synthesis of seven humulanolides in 5–7 steps without the need for protecting groups. Notably, the challenging 11-membered ring and bridged butenolide moieties in asteriscunolide D and 6,7,9,10-tetrahydroasteriscunolide were introduced in one step using a ring-opening/ring-closing metathesis cascade reaction. Asteriscunolide D was used as a versatile synthetic precursor to prepare asteriscunolides A–C via a photoinduced isomerization reaction, asteriscanolide via a unique transannular Michael reaction, and 6,7,9,10-tetradehydroasteriscanolide via a transannular Morita–Baylis–Hillman-type reaction. The unique bicyclo[6.3.0]­undecane core was introduced diastereoselectively.