Controllable Access to Furans and Dihydrofurans through Cyclization/Coupling of Internal Acetylenic β-Ketoesters with Aryl Bromides

Pd-catalyzed tandem cyclization/coupling of internal beta-propargylic-beta-ketoesters with (hetero)aryl bromides is described. Two protocols are established which selectively lead to 2-benzylidene-dihydrofurans, when isomerization is inhibited under mild conditions (temp. <= 40 degrees C and weak base - K2CO3), or to 2-benzyl-furans when base-induced aromatization is enabled. A catalytic cycle involving oxidative addition, substitution of bromide with alkyne, rate limiting anti-selective 5-exo-dig oxocyclization followed by fast deprotonation of the oxonium intermediate, and reductive elimination is proposed based on detailed experimental and theoretical studies.

Automated summary

This study describes the Pd-catalyzed tandem cyclization/coupling of internal β-propargylic β-ketoesters with (hetero)aryl bromides. Two protocols are established to selectively produce either 2-benzylidene-dihydrofurans or 2-benzyl-furans. The proposed catalytic cycle involves oxidative addition, substitution of bromide with alkyne, rate-limiting anti-selective 5-exo-dig oxocyclization, deprotonation of the oxonium intermediate, and reductive elimination.