Photochemical Deoxygenative Hydroalkylation of Unactivated Alkenes Promoted by a Nucleophilic Organocatalyst
Year: 2023
Type: article
Abstract: -enriched chemical space is highly desirable. Herein, we report a novel photochemical deoxygenative hydroalkylation of unactivated alkenes with readily available carboxylic acid derivatives. The reaction displays broad functional group tolerance, accommodating carboxylic acid-, alcohol-, ester-, ketone-, amide-, silane-, and boronic ester groups, as well as nitrile-containing substrates. The reaction is operationally simple, mild, and water-tolerant, and can be carried out on multigram-scale, which highlights the utility of the method to prepare value-added compounds in a practical and scalable manner. The synthetic application of the developed method is further exemplified through the synthesis of suberanilic acid, a precursor of vorinostat, a drug used for the treatment of cutaneous T-cell lymphoma. A novel mechanistic approach was identified using thiol as a nucleophilic catalyst, which forms a key intermediate for this transformation. Furthermore, electrochemical studies, quantum yield, and mechanistic experiments were conducted to support a proposed catalytic cycle for the transformation.
Institution: University of Pennsylvania
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: bronze
Funders: National Science Foundation, University of Pennsylvania, National Institutes of Health, Vagelos Institute for Energy Science and Technology, University of Pennsylvania, Major Project of Philosophy and Social Science Research in Colleges and Universities of Jiangsu Province, National Institute of General Medical Sciences, Division of Chemistry
Awards: Computational Methods for Selective Catalysis, G2141756727, MRI: Acquisition of a 400 MHz Nuclear Magnetic Resonance (NMR) Spectrometer for Chemistry and Energy Research and Education at the University of Pennsylvania, G2989883016, G458626264, G6525408422, Targeting Nucleic Acid Junctions with Small Molecules, G7805455597, Accessing New Chemical Space via Organic Synthesis
OpenAlex ID: W4389925053