Bio-Inspired Formal Synthesis of HirsutellonesA-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 hirsutelloneB and congenersA and C, through construction 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(OTf)3] or BF3OEt2) of the allyl acetate and stereoselectively affording the Cring. This was followed by an intramolecular Diels-Alder reaction to get the tricyclic core of the natural product. The stereoselective reduction of the resulting ketone towards the formal intermediate was critical to the success of this strategy. [PUBLICATION ABSTRACT]