Bio‐Inspired Formal Synthesis of Hirsutellones A–C Featuring an Electrophilic Cyclization Triggered by Remote Lewis Acid‐Activation

A bio-inspired strategy was used to complete the formal synthesis of the antitubercular hirsutellone B and congeners A and C, through con- struction of its decahydrofluorene core from a linear polyene strand activated at both ends by a silyl enol ether and an allyl acetate. Our synthesis features a key electrophilic cyclization, starting with the remote activation (by (Yb- A3 )o r BF 3·OEt2) of the allyl ace- tate and stereoselectively affording the C ring. This was followed by an intra- molecular Diels-Alder reaction to get the tricyclic core of the natural prod- uct. The stereoselective reduction of the resulting ketone towards the formal intermediate was critical to the success of this strategy.