Comprehensive Mechanistic Scenario for the Cu-Mediated Asymmetric Propargylic Sulfonylation Forging Tertiary Carbon Stereocenters
Metal-catalyzed propargylic transformations represent a powerful tool in organic synthesis to achieve new carbon–carbon and carbon–heteroatom bonds. However, detailed knowledge about the mechanistic intricacies related to the asymmetric formation of propargylic products featuring challenging heteroa...
| Authors: | , , , , , |
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| Format: | article |
| Status: | Versión aceptada para publicación |
| Publication Date: | 2023 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2072/532932 |
| Online Access: | http://hdl.handle.net/2072/532932 https://doi.org/10.1021/jacs.3c00188 |
| Access Level: | Open access |
| Keyword: | Química 00 |
| Summary: | Metal-catalyzed propargylic transformations represent a powerful tool in organic synthesis to achieve new carbon–carbon and carbon–heteroatom bonds. However, detailed knowledge about the mechanistic intricacies related to the asymmetric formation of propargylic products featuring challenging heteroatom-substituted tertiary stereocenters is scarce and therefore provides an inspiring challenge. Here, we present a meticulous mechanistic analysis of a propargylic sulfonylation reaction promoted by a chiral Cu catalyst through a combination of experimental techniques and computational studies. Surprisingly, the enantio-discriminating step is not the coupling between the nucleophile and the propargylic precursor but rather the following proto-demetalation step, a scenario further validated by computing enantio-induction levels under other previously reported experimental conditions. A full mechanistic scenario for this propargylic substitution reaction is provided, including a catalyst pre-activation stage, a productive catalytic cycle, and an unanticipated non-linear effect at the Cu(I) oxidation level. |
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