Scandium-Catalyzed Ring Opening of Cyclopropane-Tethered 2-Phenylindoles: An Efficient Access to Functionalized Indolo[2,1-a]isoquinolines

Introduction: Indolo[2,1-a]isoquinoline derivatives constitute an important class of fused nitrogen-containing heterocycles owing to their diverse biological and pharmacological properties. Therefore, the development of efficient synthetic methods for accessing these privileged scaffolds remains highly desirable. Donor–acceptor cyclopropanes, due to their inherent ring strain and unique reactivity under Lewis acid catalysis, have emerged as versatile building blocks for the construction of complex molecular architectures. Herein, we report a Sc(OTf)₃-catalyzed ring-opening strategy for the synthesis of functionalized indolo[2,1-a]isoquinolines from cyclopropane-tethered 2-phenylindoles.

Methods: Cyclopropane-tethered 2-phenylindoles were synthesized and subjected to Lewis acid-catalyzed cyclization conditions. Following systematic optimization, Sc(OTf)₃ was identified as an efficient catalyst for promoting the ring-opening transformation in 1,2-dichloroethane (DCE). The substrate scope was investigated using various substituted substrates, and the products were characterized by NMR spectroscopy and HRMS.

Results: The optimized protocol efficiently afforded functionalized indolo[2,1-a]isoquinoline derivatives in good to excellent yields. The methodology exhibited broad substrate scope and tolerated a variety of substituents on both the indole and aryl rings, providing rapid access to structurally diverse fused heterocycles under mild conditions.

Conclusion: An efficient Sc(OTf)₃-catalyzed ring-opening strategy has been developed for the synthesis of functionalized indolo[2,1-a]isoquinolines. The protocol features mild reaction conditions, broad substrate scope, and good to excellent yields, offering a practical route to biologically relevant fused heterocyclic scaffolds.