Dearomatizing cyclization of arylsulfonylalkoxymethyl lithiums: A route to the podophyllotoxin skeleton

(Matrix presented) The phenylsulfonyl group promotes the dearomatizing cyclization of tethered organolithiums onto aromatic rings. With an ether tether, the cyclizations create a new tetrahydrofuran ring, and both cyclization and subsequent electrophilic quenches proceed with high levels of diastereoselectivity. The sulfonyl group can be removed from the cyclized products oxidatively or reductively. The dearomatizing cyclization of a naphthyl sulfone was used in the synthesis of a close structural analogue of podophyllotoxin.