Synthesis of organophosphorus (III) compounds from white phosphorus via an adduct-catalyzed tandem electro-thermal approach

Initially, the authors discovered that using weakly nucleophilic hexafluoroisopropanol as the nucleophile enabled the selective synthesis of trivalent phosphorus at a high current density of 44.4 mA/cm². The resulting trihexafluoroisopropyl phosphite (3-1) could also be efficiently converted into trimethyl phosphite through thermochemical transformation with methanol, indicating that it is an effective trivalent phosphorus transfer reagent. Control experiments revealed that TBAI and DMAP significantly influenced the reaction yield. Subsequently, the authors conducted a series of investigations into the stability of the trivalent phosphorus transfer reagent 3-1. Cyclic voltammetry (CV) tests showed that the oxidation potential of 3-1 was significantly higher compared to white phosphorus and other trivalent phosphorus compounds. Additionally, when iodide ions were introduced, 3-1 and the iodide ions produced almost no catalytic current, suggesting that the electrochemically generated iodine could not oxidize 3-1. Further validation through in situ UV experiments demonstrated that when I₃⁻ and 3-1 coexisted, the concentration of I₃⁻ did not decrease. In contrast, when triisopropyl phosphite and I₃⁻ coexisted, the absorbance rapidly decreased, and I₃⁻ was consumed immediately, further confirming the stability of 3-1 in the presence of oxidants. Finally, in collaboration with Professor Xiaotian Qi's research group at Wuhan University, theoretical calculations demonstrated that the field effect of multiple fluorine atoms in 3-1 dispersed the electron density around the phosphorus center, endowing it with certain antioxidant and electrophilic properties.

The authors investigated the mechanism of the electrochemical synthesis of 3-1. In control experiments, DMAP was found to have a significant impact on the reaction yield, prompting the authors to first explore the role of DMAP. Nuclear magnetic resonance (NMR) experiments demonstrated that DMAP and HFIP form a hydrogen-bonded complex, which enhances the nucleophilicity of HFIP and accelerates its reaction with the P-I intermediate. Furthermore, through cyclic voltammetry (CV), 1H NMR, UV-Vis spectroscopy, and theoretical calculations, the formation of the TBAI-DMAP adduct was confirmed. This adduct is formed through hydrogen bonding between TBA+ and DMAP, which facilitates the oxidation of iodide ions and, in turn, promotes the activation of white phosphorus. Additionally, the introduction of DMAP significantly lowers the oxidation potential at the anode, potentially contributing to the suppression of over-oxidation of 3-1. Based on the literature and mechanistic experiments, the authors proposed a plausible reaction mechanism: the TBAI-DMAP adduct undergoes anodic oxidation to generate zero- or monovalent iodine species, which then oxidize white phosphorus to form P-I species, completing the catalytic cycle. Subsequently, the P-I species is nucleophilically attacked by hexafluoroisopropanol to yield 3-1.

Subsequently, to demonstrate the potential for industrial application of this strategy, the authors scaled up the reaction and achieved a decagram-scale synthesis with a high yield of 73%. Encouraged by this result, they further increased the reaction scale to synthesize 100 grams of 3-1. By adding 4-phenylphenol, they successfully isolated nearly 100 grams of the corresponding phosphite ester, achieving the derivatization of 3-1. The absence of scale-up effects even after increasing the reaction scale by a hundredfold highlights the promising industrial prospects of this method.

Directly utilizing fluctuating green electricity for electrosynthesis can significantly reduce costs while enabling the in-situ consumption of green energy. Therefore, the authors developed a power supply capable of delivering controlled fluctuating output power, simulating waveforms of wind and photovoltaic power generation. This setup was applied to the synthesis of 3-1, successfully producing organic trivalent phosphorus compounds with high yields.

Finally, the authors conducted substrate scope exploration. The synthesized trivalent phosphorus transfer reagent 3-1 was isolated and reacted with various types of nucleophiles to broaden the substrate applicability of the reaction. As shown in the figure, 3-1 demonstrated high reaction yields with nearly stoichiometric amounts of primary, secondary, and tertiary alcohols, phenols, and various Grignard reagents, aligning with the principles of atom economy and green chemistry. Notably, products substituted with different nucleophiles, such as the antioxidant 626 (32), were also synthesized in good yields.

This approach not only effectively prevents the issue of over-oxidation but also significantly enhances the efficiency and selectivity of trivalent phosphorus compound synthesis, providing new insights and tools for research in related fields.

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