Intermolecular Dearomative Alkylation–Cyclization Cascade of β-Aryltryptophols: Diastereoselective Access to Furoindolines with Three Contiguous Stereocenters

Intermolecular dearomative C3-alkylation of indoles bearing an adjacent, sterically encumbered stereocenter presents a dual challenge: overcoming substantial steric hindrance to achieve efficient reactivity and attaining high facial diastereoselectivity. Herein, we report a NaOtBu/Et3B-promoted intermolecular dearomative alkylation–cyclization cascade of β-aryltryptophols that addresses both challenges, affording furoindolines bearing three contiguous stereogenic centers in yields of up to 88%, with the endo-diastereomers consistently obtained as the major products (up to 11.2:1 endo/exo d.r.). The method was demonstrated across 36 examples, incorporating allylic, benzylic, and propargyl bromides as well as methyl iodide, and accommodating diverse electronic variations on both the indole nucleus and the pendant aryl ring of the β-aryltryptophol substrates. An enantioenriched substrate underwent the reaction without detectable racemization (>99:1 e.r.), indicating retention of the pre-existing stereocenter and its stereochemical relay to the newly formed stereocenters. An α-aryltryptophol, in which the stereogenic center is one atom farther from the indole C3 position, also underwent the cascade process, although the corresponding exo-diastereomers were isolated as the major products (up to 5.2:1 exo/endo d.r.).