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

An
asymmetric dearomatization of indoles bearing α-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 Büchner 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(sp3)–C­(sp2) bond in the product provided unconventional access to the
corresponding chiral spirooxindole.