Rh(II)-Catalyzed Selective C(sp)-H/C(sp)-H Bonds Cascade Insertion to Construct [6-8-6] Benzo-Fused Scaffold.

The fused eight-membered carbocycles (EMCs) play vital roles in the medicinal and biological investigations of many natural products and marketed drugs. The traditional synthesis of [6-8-6] benzo-fused derivatives involves multistep reactions and low yields, making the development of a one-step synthesis method a more challenging work. Here, we present a novel strategy for one-step construction of [6-8-6] benzo-fused scaffold from propargyl diazoacetates substituted with benzyl-nitrogen heterocyclic ring via Rh(ll)-catalyzed carbene/alkyne metathesis (CAM) and selective C-H bond insertion. This method exhibits a specific substrate scope, simple operation, mild reaction conditions, and high atom efficiency. Mechanistically, the process involves sequential CAM, 1,3-H-shift, intramolecular nucleophilic attack, and selective C(sp)-H/C(sp)-H bonds cascade insertion. Notably, the unique spirocyclic zwitterionic intermediate generated in this sequence contributes to -heterocycle migration and fused eight-membered carbocycle formation. Additionally, the C(sp)-H bond insertion connected to the oxygen atom rather than the nitrogen atom has been unexpectedly confirmed with the assistance of the spirocyclic zwitterionic intermediate. Overall, our findings open up a new avenue for the construction of [6-8-6] benzo-fused scaffold.