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cc-by-nc-nd (c) Galeote, Oriol et al., 2024
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/208601

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

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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.

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GALEOTE, Oriol, et al. Direct, stereodivergent, and catalytic Michael additions of thioimides to α,β-unsaturated aldehydes – Total synthesis of Tapentadol. Angewandte Chemie-International Edition. 2024. Vol. 63, num. e202319308. ISSN 1433-7851. [consulted: 8 of August of 2026]. Available at: https://hdl.handle.net/2445/208601

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