Synthesis of homophthalimide spironaphthalenones through [5+1] spiroannulation of aryl/alkenyl enaminones with diazo homophthalimides

Presented herein is a novel synthesis of homophthalimide spironaphthalenones from the cascade reaction of enaminones with diazo homophthalimides. Preliminary mechanistic studies showed that this reaction is initiated by Rh(iii)-catalyzed and carbonyl group-assisted C(sp(2))-H metalation of enaminone and coordination with diazo homophthalimide followed by migratory insertion, spiroannulation, & beta;-elimination and protonation. Notably, this transformation defined a novel and distinct reaction pattern of enaminone in that it acts as an effective and easy-to-handle C5 synthon to undergo the unprecedented formal [5 + 1] spiroannulation. In general, this developed protocol has advantages such as easily accessible substrates, valuable products, mild reaction conditions, concise synthetic procedure, high efficiency and good compatibility with diverse functional groups. Moreover, the usefulness of this method is further showcased by its suitability for scale-up synthetic scenarios and diverse transformation of products.

Automated summary

Presented herein is a novel synthesis method for homophthalimide spironaphthalenones through the cascade reaction of enaminones with diazo homophthalimides. The mechanism involves Rh(iii)-catalyzed C(sp(2))-H metalation of enaminone and coordination with diazo homophthalimide, followed by migratory insertion, spiroannulation, beta-elimination, and protonation. This transformation defines a new and distinct reaction pattern of enaminone, acting as an effective C5 synthon for [5 + 1] spiroannulation. Overall, this developed protocol offers easily accessible substrates, valuable products, mild reaction conditions, concise synthetic procedure, high efficiency, and compatibility with diverse functional groups.