98%
921
2 minutes
20
Decarboxylative halogenation reactions of alkyl carboxylic acids are highly valuable reactions for the synthesis of structurally diverse alkyl halides. However, many reported protocols rely on stoichiometric strong oxidants or highly electrophilic halogenating agents. Herein, we describe visible-light photoredox-catalyzed decarboxylative halogenation reactions of N-hydroxyphthalimide-activated carboxylic acids that avoid stoichiometric oxidants and use inexpensive inorganic halide salts as the halogenating agents. Bromination with lithium bromide proceeds under simple, transition-metal-free conditions using an organic photoredox catalyst and no other additives, whereas dual photoredox-copper catalysis is required for chlorination with lithium chloride. The mild conditions display excellent functional-group tolerance, which is demonstrated through the transformation of a diverse range of structurally complex carboxylic acid containing natural products into the corresponding alkyl bromides and chlorides. In addition, we show the generality of the dual photoredox-copper-catalyzed decarboxylative functionalization with inorganic salts by extension to thiocyanation with potassium thiocyanide, which was applied to the synthesis of complex alkyl thiocyanates.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10952529 | PMC |
http://dx.doi.org/10.1002/anie.202309684 | DOI Listing |
Angew Chem Int Ed Engl
July 2025
Graduate School of Engineering, Kyoto University, Kyoto University Katsura, Nishikyo-ku, Kyoto, 615-8510, Japan.
Here, we report a synthetic approach for a wide range of unsymmetrical alkylphosphorus(V) compounds, alkyl-P(O)XY (X ≠ Y) using imidazolium phosphonites as bifunctional reagents. This protocol consists of two sequences, C(sp)─P bond formation via an organic photoredox-catalyzed decarboxylative alkylation of imidazolium phosphonites with aliphatic carboxylic acid derivatives and P─X (X═O, N, F, and S) bond formation via the SP(V) reaction. In this process, the imidazolium group facilitates 1) radical addition to the phosphonite reagent by stabilizing the resulting phosphoranyl radical intermediate and 2) the SP(V) reaction as a good leaving group.
View Article and Find Full Text PDFOrg Lett
July 2025
Department of Chemistry, The University of Kansas, 1567 Irving Rd., Lawrence, Kansas 66045, United States.
β-Nitroamines are privileged synthetic motifs featuring vicinal nitrogen centers in distinct oxidation states. Here, we report a photoredox-catalyzed, decarboxylative nitro-Mannich reaction for the synthesis of skeletally diverse β-nitroamines using readily accessible -bromonitroalkanes. In addition, substituted β-amino esters were also accessed.
View Article and Find Full Text PDFChem Sci
July 2025
Department of Chemistry, University of Wisconsin-Madison 1101 University Avenue Madison WI 53706 USA
A dual photoredox/hydrogen atom transfer (HAT) strategy for the radical alkoxycarbonylation of allenes is described. Alkoxycarbonyl radicals, generated by photoredox-catalyzed decarboxylation of alkyl oxalic acids, add to the proximal carbon of allene precursors with high regioselectivity to furnish α-allyl-γ-lactone products in up to 92% yield. The intermediate vinyl radicals can be trapped by a hydrogen atom or by a heteroatom using selenium and iodine transfer reagents.
View Article and Find Full Text PDFJ Am Chem Soc
May 2025
School of Chemistry and Chemical Engineering, Anhui Key Laboratory of Coal Clean Conversion and High Valued Utilization, Anhui University of Technology, Ma'an shan 243032, China.
We present a general method for accessing unsymmetrical alkyl-aryl and alkyl-alkyl ketones via nickel/photoredox-catalyzed decarboxylative cross-acyl coupling reactions between carboxylic acids and aldehydes without the need for an additional preactivation procedure. Specifically, by using the peroxide as both an oxidant and hydrogen atom transfer (HAT) reagent, we achieved the unprecedented combination of oxidative single electron transfer (SET) of carboxylates and HAT of aldehydes, in which the generated alkyl and acyl radicals were chemoselectively coupled by nickel catalysis. This method features a broad substrate scope with good functional group compatibility and offers new access to structurally diverse ketones.
View Article and Find Full Text PDFJ Org Chem
April 2025
Department of Chemistry, The University of Kansas, 1567 Irving Rd., Lawrence, Kansas 66045, United States.
Enamides and enecarbamates offer an excellent balance between stability and reactivity. Decarboxylation of widely available amino acids offers a green and efficient alternative to accessing these reagents. The present study describes a photocatalytic approach for the direct decarboxylative synthesis of enamides via sequential radical decarboxylation and putative halogen-atom transfer (XAT).
View Article and Find Full Text PDF