Silver-Catalyzed, Chemo- and Enantioselective Intramolecular Dearomatization of Indoles to Access Sterically Congested Azaspiro Frameworks
- 21 July 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 85 (16), 10934-10950
- https://doi.org/10.1021/acs.joc.0c01580
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.Keywords
Funding Information
- Naito Foundation
- Takeda Science Foundation
- Japan Society for the Promotion of Science (JP18H02550, JP18K05098, JP19J21528)
- Futaba Electronics Memorial Foundation
- Toray Science Foundation
- Chugai Award in Synthetic Organic Chemistry, Japan
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