Visible‐Light‐Promoted Decarboxylative Giese Reactions of α‐Aryl Ethenylphosphonates and the Application in the Synthesis of Fosmidomycin Analogue

Abstract

An approach for the synthesis of α‐aryl alkylphosphonates based on visible‐light photocatalytic Giese reaction of α‐aryl vinylphosphonates with aliphatic carboxylic acids has been successfully developed. This protocol tolerates a wide range of functional groups and shows broad substrate scope with regard to both the carboxylic acid and vinylphosphonate components. With sequential Giese/hydrolysis reactions as the strategy, the oxo‐phosphonates could be easily accessible. The synthetic application of the hydroformylation reaction was demonstrated by the synthesis of the intermediate of α‐phenyl substituted fosmidomycin analogue. Furthermore, the competitive decarboxylative alkylation of vinylphosphonate and acrylate was also investigated.magnified image

Lewis Acid Enables Ketone Phosphorylation: Synthesis of Alkenyl Phosphonates

“…We found that 3ab ′ can be successfully converted into a corresponding product Fosmidomycin analogue 5ab ' in 92% yield. [ 15 ]…”

Photoredox‐Catalyzed Cyclopropanation of 1,1‐Disubstituted Alkenes via Radical‐Polar Crossover Process

“…We recently reported a new method for the preparation of 1‐aryl cyclopropylphosphonates via photoredox neutral‐catalyzed cyclopropanation of vinylphosphonates with chloromethyl silicate as the methylene source (Scheme c, path I) . Inspired by our interest in the application of radical‐polar crossover process based on radical addition to vinylphosphonates, we envisioned that the intermediate of γ‐halo‐α‐phosphoryl carbanion for the 3‐ exo ‐ tet cyclization could be accessible via alkyl radical addition to 1,1‐disubstituted alkenes and the following single‐electron reduction (Scheme c, path II) . Moreover, the photoredox‐catalyzed allylation/cyclopropanation cascade reaction would be realized via radical addition/fragmentation of allylic halides with halomethyl radical followed by radical addition‐polar cyclization between the excess halomethyl radical and homoallylic halide generated in situ (Scheme c, path III).…”

Generation of Alkyl Radicals: From the Tyranny of Tin to the Photon Democracy

“… 141 Also, the Fukuzumi catalyst (9-mesitylene-10-methylacridinium perchlorate, [Acr + Mes]ClO 4 ) can promote this Giese-type reaction, 142 allowing the alkylation of α-aryl ethenylphosphonates for the synthesis of fosmidomycin analogues. 143 …”