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...

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Detalles Bibliográficos
Autores: Garcia-Roca, Aleria, Pérez-Soto, Raúl, Stoica, Georgiana, Benet-Buchholz, Jordi, Maseras, Feliu, Kleij, Arjan W.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2072/532932
Acceso en línea:http://hdl.handle.net/2072/532932
https://doi.org/10.1021/jacs.3c00188
Access Level:acceso abierto
Palabra clave:Química
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Descripción
Sumario: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.