Catalytic enantioselective synthesis of azahelicenes via cascade Pictet-Spengler reaction and dehydrogenative aromatization

通过级联Pictet-Spengler反应和脱氢芳构化反应催化对映选择性合成氮杂螺烯

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Abstract

The introduction of N-heteroaromatic rings like pyridine and pyrrole into the helicene scaffold can significantly impact the electronic properties, redox potentials and coordination abilities of helicenes, which lead to diverse and intriguing applications for these chiral azahelicenes. However, methods for catalytic enantioselective synthesis of these compounds, especially those with N-heterocyclic moieties, remain largely underdeveloped. Herein, we present an efficient method for catalytic enantioselective synthesis of azahelicenes bearing a pyrrolo[2,3-c]pyridine moiety through chiral phosphoric acid-catalyzed asymmetric Pictet-Spengler reaction coupled with in-situ dehydrogenative aromatization. Moreover, the utilization of isatins in this process resulted in an unexpected oxidative ring-expansion rearrangement, yielding azahelicenes with an additional fused seven-membered heterocyclic structure. Various control experiments were performed to elucidate the reaction mechanism, revealing a dynamic kinetic resolution process. Diverse derivatizations have been studied to showcase the utilities of this method, which revealed a primary amine-containing helicene derivative that acts as a highly stereoselective helically chiral organocatalyst. Furthermore, these chiral azahelicenes exhibit potent photophysical and chiroptical properties, further underscoring the significance of this method.

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