The highly strained cubane system is of great interest as a scaffold and rigid linker in both pharmaceutical and materials chemistry. The first electrochemical functionalisation of cubane by oxidative decarboxylative ether formation (Hofer-Moest reaction) was demonstrated. The mild conditions are compatible with the presence of other oxidisable functional groups, and the use of flow electrochemical conditions allows straightforward upscaling.
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http://dx.doi.org/10.1002/chem.201904479 | DOI Listing |
J Am Chem Soc
January 2024
Department of Chemistry, School of Science, Kwansei Gakuin University, Sanda 669-1330, Hyogo, Japan.
Kolbe dimerization and Hofer-Moest reactions are well-investigated carboxylic acid transformations, wherein new carbon-carbon and carbon-heteroatom bonds are constructed via electrochemical decarboxylation. These transformations can be switched by choosing an electrode that allows control of the reactive intermediate, such as carbon radical or carbocation. However, the requirement of a high current density diminishes the functional group compatibility with these electrochemical reactions.
View Article and Find Full Text PDFJ Org Chem
December 2023
Department of Chemistry, University of Pavia, Viale Taramelli, 27100 Pavia, Italy.
In this work, we successfully employed electrochemical conditions to promote a Hofer-Moest, intramolecular Friedel-Crafts alkylation sequence. The reaction proceeds under mild conditions, employing carboxylic acids as starting materials. Notably, the electrochemical process performed in batch was adapted to a continuous flow electrolysis apparatus to provide a significant improvement.
View Article and Find Full Text PDFOrg Lett
November 2023
Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia.
Broad application of α,α-disubstituted cyclic amino acid derivatives in medicinal chemistry urges for analogue design with improved pharmacokinetic properties. Herein, we disclose an electrochemical approach toward unnatural THF- and THP-containing amino acid derivatives that relies on anodic decarboxylation-intramolecular etherification of inexpensive and readily available -acetylamino malonic acid monoesters under Hofer-Moest reaction conditions. The decarboxylative cyclization proceeds under constant current conditions in an undivided cell in an aqueous medium without any added base.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
October 2023
Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
A mild, scalable (kg) metal-free electrochemical decarboxylation of alkyl carboxylic acids to olefins is disclosed. Numerous applications are presented wherein this transformation can simplify alkene synthesis and provide alternative synthetic access to valuable olefins from simple carboxylic acid feedstocks. This robust method relies on alternating polarity to maintain the quality of the electrode surface and local pH, providing a deeper understanding of the Hofer-Moest process with unprecedented chemoselectivity.
View Article and Find Full Text PDFChemistryOpen
May 2022
Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
Herein we report a conceptually new non-decarboxylative electrolysis of carboxylic acids to obtain their corresponding anhydrides as highly valuable reagents in organic synthesis. All carbon atoms of the starting material are preserved in the product in an overall redox-neutral reaction. In a broad substrate scope of carboxylic acids the anhydrides are generated with high selectivity, which demonstrates the versatility of the developed method.
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