Silver-Catalyzed, Chemo- and Enantioselective Intramolecular Dearomatization of Indoles to Access Sterically
Jun Ueda1, Shingo Harada1, Ayaka Kanda1
1Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan.
Abstract:
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.
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