Catalyst-Controlled Regiodivergence in Rearrangements of Indole-Based Onium Ylides

We have developed catalyst-controlled regiodiver-gent rearrangements of onium-ylides derived from indole substrates. Oxonium ylides formed in situ from substituted indoles selectively undergo [2,3]- and [1,2]- rearrangements in the presence of a rhodium and a copper catalyst, respectively. The combined experimental and density functional theory (DFT) computational studies indicate divergent mechanistic pathways involving a metal-free ylide in the rhodium catalyzed reaction favoring [2,3]-rearrangement, and a metal-coordinated ion-pair in the copper catalyzed [1,2]-rearrangement that recombines in the solvent-cage. The application of our methodology was demonstrated in the first total synthesis of the indole alkaloid (+/-)-sorazolon B, which enabled the stereochemical reassignment of the natural product. Further functional group transformations of the rearrangement products to generate valuable synthetic intermediates were also demonstrated.

Automated summary

The study developed catalyst-controlled regiodivergent rearrangements of onium-ylides derived from indole substrates, with experimental and computational studies revealing different mechanistic pathways. The methodology was successfully applied in the total synthesis of the natural product and further functional group transformations.