Umpolung Strategy for α-Functionalization of Aldehydes for the Addition of Thiols and other Nucleophiles
| Autor: | Matilde Rusbjerg, Jakob Blom, Casper L. Barløse, Karl Anker Jørgensen, Henriette N. Tobiesen, Marc V. Iversen, Niels Hammer, Gabriel J. Reyes-Rodríguez, Johannes N. Lamhauge |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
oxidative thiolation
bioconjugation enantioselective α-thiolation 010402 general chemistry 01 natural sciences Catalysis Umpolung Enamine Stereocenter Electron Transport chemistry.chemical_compound Nucleophile Nucleophilic substitution Benzoquinones organocatalysis Sulfhydryl Compounds Aldehydes Bioconjugation Molecular Structure 010405 organic chemistry Enantioselective synthesis Stereoisomerism General Chemistry General Medicine Combinatorial chemistry umpolung 0104 chemical sciences Hydroquinones chemistry Organocatalysis Oxidation-Reduction |
| Zdroj: | Blom, J, Reyes Rodriguez, G J, Tobiesen, H N, Lamhauge, J N, Iversen, M V, Barløse, C L, Hammer, N, Rusbjerg, M & Jørgensen, K A 2019, ' Umpolung Strategy for α-Functionalization of Aldehydes for the Addition of Thiols and other Nucleophiles ', Angewandte Chemie-International Edition, vol. 58, no. 49, pp. 17856-17862 . https://doi.org/10.1002/anie.201911793 |
| DOI: | 10.1002/anie.201911793 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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