Silver-Catalyzed, Chemo- and Enantioselective Intramolecular Dearomatization of Indoles to Access Sterically Congested Azaspiro Frameworks

An asymmetric dearomatization of indoles bearing alpha-diazoacetamide functionalities was developed for synthesizing high-value Spiro scaffolds. A silver phosphate chemoselectively catalyzed the sterically challenging dearomatization, whereas more typically used metal catalysts for carbene transfer reactions, such as a rhodium complex, were not effective and instead resulted in a Biichner ring expansion or cyclopropanation. Mechanistic studies indicated that the spirocyclization occurred through a silver-assisted asynchronous concerted process and not via a silver-carbene intermediate. Analyses based on natural bond orbital population and a distortion/interaction model indicated that the degree of C-Ag mutual interaction is crucial for achieving a high level of enantiocontrol. In addition, an oxidative disconnection of a C(sp(3))-C(sp(2)) bond in the product provided unconventional access to the corresponding chiral spirooxindole.