Direct, stereodivergent, and catalytic Michael additions of thioimides to α,β-unsaturated aldehydes – Total synthesis of Tapentadol

Direct and stereodivergent Michael additions of N-acyl 1,3-thiazinane-2-thiones to α,β-unsaturated aldehydes catalyzed by chiral nickel(II) complexes are reported. The reactions proceed with a remarkable regio-, diastereo-, and enantioselectivity, so access to any of the four potential Michael stere...

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Detalles Bibliográficos
Autores: Galeote, Oriol, Kennington, Stuart C. D., Benedito, Gabriela, Fraedrich, Lena, Davies-Howe, Evan, Costa i Arnau, Anna M., Romea, Pedro, Urpí Tubella, Fèlix, Aullón López, Gabriel, Font Bardia, Ma. Mercedes, Puigjaner Vallet, Ma. Cristina
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/208601
Acceso en línea:https://hdl.handle.net/2445/208601
Access Level:acceso abierto
Palabra clave:Compostos carbonílics
Níquel
Aldehids
Carbonyl compounds
Nickel
Aldehydes
Descripción
Sumario:Direct and stereodivergent Michael additions of N-acyl 1,3-thiazinane-2-thiones to α,β-unsaturated aldehydes catalyzed by chiral nickel(II) complexes are reported. The reactions proceed with a remarkable regio-, diastereo-, and enantioselectivity, so access to any of the four potential Michael stereoisomers is granted through the appropriate choice of the chiral ligand of the nickel(II) complex. Simple removal of the heterocyclic scaffold furnishes a wide array of either syn or anti enantiomerically pure derivatives, which can be exploited for the asymmetric synthesis of biologically active compounds, as demonstrated in a new approach to tapentadol. In turn, a mechanism, based on theoretical calculations, is proposed to account for the stereochemical outcome of these transformations.