Sigmatropic rearrangements belong to a powerful class of transformations enabling the synthesis of valuable organic molecules with complex architectures. Recent advances in catalytic onium-ylide rearrangements enable catalyst-control of these traditionally unselective rearrangements. Despite their utility, a majority of these class of rearrangements involving a variety of ylides are limited to the functionalization of aliphatic systems. A few examples on catalytic onium-ylide rearrangements in aromatic systems have been reported mainly focusing on sulfonium and ammonium-ylide rearrangements. However, there have been no reports to our knowledge on catalytic oxonium-ylide rearrangements in aromatic systems.<br/>We have developed the first catalyst-controlled regio-divergent rearrangements of indole-based oxonium-ylides. Oxonium ylides formed <i>in situ</i> from substituted indoles selectively undergo [2,3]- and [1,2]-rearrangements in the presence of a rhodium and 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 applications of our methodology were demonstrated in the first total synthesis of the indole alkaloid (±)-sorazolon B enabling the stereochemical reassignment of the molecule. Further functional group transformations of the rearrangement products to generate valuable synthetic intermediates were also explored.

Catalyst-controlled regiodivergence in rearrangements of indole-based onium-ylides

ACS Fall 2021

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