Regioselective Bromination of Benzocycloheptadienones for the Synthesis of Substituted 3,4‐Benzotropolones Including Goupiolone A

Abstract Type‐ 18 or ‐ 23 benzocycloheptadienones are readily prepared by ring‐closing olefin metatheses. Adding Br 2 to 23 and eliminating HBr gave the bromoolefin 28 using DBU or its isomer iso‐ 28 using DABCO, both with near‐perfect regiocontrol. Both 28 and iso‐ 28 underwent Sonogashira, Suzuki, Negishi, and Heck couplings as well as Pd‐catalyzed alkoxycarbonylations. Hydrolysis of the resulting α‐ketoketals and enolization of the liberated α‐diketones delivered a portfolio of hitherto unknown 3,4‐benzotropolones. The 8‐ethoxycarbonylated dimethyl‐3,4‐benzotropolone 50 obtained by this route was dimethylated to give goupiolone A ( 52 ). This synthesis encompasses 9 steps from 22 , that is, half as many as the only previous synthesis (19 steps). A variant of our route afforded the 1,8‐dibromide 54 . Coupling with excess phenylboronic acid and ketal hydrolysis provided the diphenylated benzotropolone 56 and suggests a strategy, by which the natural bispulvinone aurantricholone ( 7 ) might be reached.