Huang Group
School of Chemical Biology & Biotechnology

Huan Sun’s work has been published in J.Org.Chem.!


Synthesis of Indolo[2,1-a]isoquinolines via a Triazene-Directed C–H Annulation Cascade

Huan Sun, Chengming Wang, Yun-Fang Yang, Ping Chen, Yun-Dong Wu*, Xinhao Zhang*, and Yong Huang*. J. Org. Chem. 201479, 11863-11872.

Indole-containing polyaromatic scaffolds are widely found in natural products, pharmaceutical agents, and π-conjugated functional materials. Often, the synthesis of these highly valuable molecules requires a multistep sequence. Therefore, a simple, one-step protocol to access libraries of polyaromatic indole scaffolds is highly desirable. Herein we describe the direct synthesis of polysubstituted indolo[2,1-a]isoquinoline analogues via a double C–H annulation cascade using triazene as an internally cleavable directing group. Evidence from HRMS and theoretical calculations suggests that an unprecedented 1,2-alkyl migration might be responsible for the in situ cleavage of the directing group. Both kinetic isotope effects and DFT calculations suggested that the alkyne insertion step is rate-limiting for the second C,N annulation reaction.