Enantioselective Synthesis of Heterohelicenes via Organocatalyzed Oxidative Formal [3 + 2] Cycloadditions between Polycyclic Indoles and Quinones

Abstract

Helicenes are a class of structurally fascinating polycyclic aromatic molecules composed of ortho-fused aromatic rings, which adopt a screwed shape and exhibit helical chirality due to the steric repulsion between the two terminal rings. However, the catalytic enantioselective synthesis of helicenes, especially those containing more than one type of heteroaromatic ring, remains largely underexplored. In this work, we present a straightforward and efficient catalytic enantioselective method for synthesizing heterohelicenes bearing both furan and pyrrole rings. By leveraging a chiral phosphoric acid catalyst, the asymmetric oxidative formal [3 + 2] cycloaddition reactions between polycyclic indoles and quinone esters afforded a variety of hetero[7]/[6]helicenes with good to high yields and enantioselectivities. Extensive control experiments suggest that the reaction proceeds via a sequential enantioselective indole C-3 arylation, hydroquinone oxidation, and intramolecular 1,6-addition process, with the initial addition step serving as the enantio-determining step. DFT calculations were performed to elucidate the origin of the enantioselectivity of this reaction, as well as the role of the hydroquinone additive in accelerating the cyclization step. These heterohelicenes exhibit high configurational stability, diverse potential for derivatization, as well as promising photophysical and chiroptical properties, which underscore the value of this methodology.