Convergent Deboronative and Decarboxylative Phosphonylation Enabled by the Phosphite Radical Trap BecaP

Carbon-phosphorusbond formation is significant in syntheticchemistry because phosphorus-containing compounds offer numerous indispensablebiochemical roles. While there is a plethora of methods to accessorganophosphorus compounds, phosphonylations of readily accessiblealkyl radicals to form aliphatic phosphonates are rare and not commonlyused in synthesis. Herein, we introduce a novel phosphorus radicaltrap BecaP that enables facile and efficient phosphonylationof alkyl radicals under visible light photocatalytic conditions. Importantly,the ambiphilic nature of BecaP allows redox neutral reactions withboth nucleophilic (activated by single-electron oxidation) and electrophilic(activated by single-electron reduction) alkyl radical precursors.Thus, a broad scope of feedstock alkyl potassium trifluoroborate saltsand redox active carboxylate esters could be employed, with each classof substrate proceeding through a distinct mechanistic pathway. Themild conditions are applicable to the late-stage installation of phosphonatemotifs into medicinal agents and natural products, which is showcasedby the straightforward conversion of baclofen (muscle relaxant) tophaclofen (GABA(B) antagonist).

Automated summary

Carbon-phosphorus bond formation is important in synthetic chemistry due to the essential biochemical roles of phosphorus-containing compounds. However, the synthesis of aliphatic phosphonates through phosphonylation of alkyl radicals is rarely used. In this study, a phosphorus radical trap called BecaP is introduced, which enables efficient phosphonylation of alkyl radicals under visible light photocatalytic conditions. The ambiphilic nature of BecaP allows redox neutral reactions with both nucleophilic and electrophilic alkyl radical precursors. This method is applicable for late-stage installation of phosphonate motifs into medicinal agents and natural products.