C-C bond activation as a new trigger for metal-walk remote functionalization
Final Report Abstract
We established a new synthetic route towards valuable stereodefined dicarbonyls via palladium-catalysed C-C bond activation of cyclopropanols. Within this project, a new methodology for the stereoselective construction of highly substituted cyclopropanols from readily available cyclopropenes was developed. As cyclopropanols can be prone to decomposition, cyclopropylboronic esters were synthesised as masked cyclopropanols in a carbometallation-based strategy, revealing the fragile cyclopropanols in the final step. This highly modular approach enables the introduction of many different substituents at will with complete regio- and stereocontrol. These complex cyclopropanols were then utilized in a palladium-catalysed metal-walk transformation to reveal 1,n-dicarbonyls. The focus was set on the otherwise challenging to access 1,4-dialdehydes, which could be synthesized as single diastereomers featuring a tertiary and a quaternary stereocentre. Notably, these highly substituted 1,4-dialdehydes cannot be prepared in a stereoselective manner by any other method. Moreover, the methodology developed herein constitutes the first example of a metal-walk transformation initiated by C-C single bond cleavage. In a second project, a new method for the stereoselective construction of spiro[2.x]alkanes was developed. Strained bicyclic molecules have garnered increasing interest in the synthetic community in the last years, with spirocycles being particularly appealing as bioisosters. We devised a diastereoselective synthesis of spiro[2.x]alkanes of different ring sizes based on the intramolecular carbometallation of cyclopropenes. This transformation enables the construction of spirocycles featuring a highly substituted cyclopropane ring. Various electrophiles (H, D, halogen, Si, C) can be installed in the cyclization step, increasing the utility of this approach.
Publications
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Stereoselective Synthesis of 1,n‐Dicarbonyl Compounds Through Palladium‐Catalyzed Ring Opening/Isomerization of Densely Substituted Cyclopropanols. Angewandte Chemie International Edition, 64(6).
Teschers, Charlotte S.; Cohen, Anthony & Marek, Ilan
