Enantioselective Convergent Synthesis of Heterohelicenes via Copper-Catalyzed Propargylic Annulation/Acid-Promoted Aromatization

Abstract

Heterohelicenes combine helical chirality with tunable electronic properties, making them attractive for applications in chiral materials and optoelectronics. However, their enantioselective synthesis, particularly for five-membered heterohelicenes, remains a long-standing challenge owing to the inherent synthetic difficulties and the lack of efficient catalytic strategies. Herein, we report a copper-catalyzed [3 + 2] annulation of propargylic esters followed by acid-promoted aromatization, thereby enabling a furan ring extension strategy for the convergent synthesis of heterohelicenes. A chiral N,N,P-ligand bearing a long alkyl chain provides effective stereocontrol, enabling the efficient construction of heterohelicene frameworks with high enantioselectivity. Mechanistic studies support a plausible catalytic cycle underlying the transformation. This strategy provides efficient access to enantioenriched, configurationally stable oxa[5]helicenes, aza[5]helicenes, and diheterohelicenes, establishes the synthetic potential of copper−allenylidene chemistry for helicene synthesis, and expands the toolbox for the development of chiral functional materials.