Chemistry and Physics Faculty Articles
Title
Umpolung Strategy for α‐Functionalization of Aldehydes for the Addition of Thiols and other Nucleophiles
Document Type
Article
Publication Date
10-9-2019
Publication Title
Angewandte Chemie International Edition
Keywords
Bioconjugation, Enantioselective α-thiolation, Organocatalysis, Oxidative thiolation, Umpolung
ISSN
1433-7851
Abstract
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.
Additional Comments
Villum Fonden grant #: 25867
NSUWorks Citation
Blom, J., Reyes-Rodriguez, G. J., Tobiesen, H. N., Lamhauge, J. N., Iversen, M. C., 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. https://doi.org/10.1002/anie.201911793. Retrieved from https://nsuworks.nova.edu/cnso_chemphys_facarticles/264
ORCID ID
0000-0002-0566-0820
ResearcherID
V-6501-2018
DOI
10.1002/anie.201911793
Comments
©2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim