Umpolung Strategy for α-Functionalization of Aldehydes for the Addition of Thiols and other Nucleophiles.

Autor: Blom J; Department of Chemistry, Aarhus University, Langelandsgade 140, 8000, Aarhus C, Denmark., Reyes-Rodríguez GJ; Department of Chemistry, Aarhus University, Langelandsgade 140, 8000, Aarhus C, Denmark., Tobiesen HN; Department of Chemistry, Aarhus University, Langelandsgade 140, 8000, Aarhus C, Denmark.; Research Chemistry, Global Research Technologies, Novo Nordisk A/S, Novo Nordisk Park, 2760, Maaloev, Denmark., Lamhauge JN; Department of Chemistry, Aarhus University, Langelandsgade 140, 8000, Aarhus C, Denmark., Iversen MV; Department of Chemistry, Aarhus University, Langelandsgade 140, 8000, Aarhus C, Denmark., Barløse CL; Department of Chemistry, Aarhus University, Langelandsgade 140, 8000, Aarhus C, Denmark., Hammer N; Department of Chemistry, Aarhus University, Langelandsgade 140, 8000, Aarhus C, Denmark., Rusbjerg M; Department of Chemistry, Aarhus University, Langelandsgade 140, 8000, Aarhus C, Denmark., Jørgensen KA; Department of Chemistry, Aarhus University, Langelandsgade 140, 8000, Aarhus C, Denmark.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2019 Dec 02; Vol. 58 (49), pp. 17856-17862. Date of Electronic Publication: 2019 Oct 24.
DOI: 10.1002/anie.201911793
Abstrakt: Nucleophile-nucleophile coupling is a challenging transformation in organic chemistry. Herein we present a novel umpolung strategy for α-functionalization of aldehydes with nucleophiles. The strategy uses organocatalytic enamine activation and quinone-promoted oxidation to access O-bound quinol-intermediates that undergo nucleophilic substitution reactions. These quinol-intermediates react with different classes of nucleophiles. The focus is on an unprecedented organocatalytic oxidative α-thiolation of aldehydes. The reaction scope is demonstrated for a broad range of thiols and extended to chemoselective bioconjugation, and applicable to a large variety of aldehydes. This strategy can also encompass organocatalytic enantioselective coupling of α-branched aldehydes with thiols forming quaternary thioethers. Studies indicate a stereoselective formation of the intermediate followed by a stereospecific nucleophilic substitution reaction at a quaternary stereocenter, with inversion of configuration.
(© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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