Visible-Light-Driven Access to S -2-Pyridyl Phosphorodithioates from P4S10 via Cascade Phosphorodithiolation/Cyclization

A novel and efficient strategy for synthesizing S-2-pyridyl functionalized phosphorodithioates is reported via visible-light-mediated cascade phosphorodithiolation/cyclization of 2-(3-oxo-1,3-diarylpropyl)malononitriles. This protocol innovatively uses tetraphosphorus decasulfide (P4S10) as the phosphorus source, with alcohols acting as effective activators to drive the cascade reaction. The reaction exhibits a broad substrate scope for diverse substituted malononitrile derivatives and alcohols, affording the target products in good to excellent yields and highlighting excellent functional group compatibility. Notably, this method is transition-metal-free, allowing the cascade reaction to proceed efficiently under mild conditions. Through stepwise control experiments combined with 31P NMR tracking experiments and DFT calculations, a plausible radical-mediated mechanism is proposed. This protocol enables a straightforward conversion from inorganic to organic phosphorus, avoiding the use of toxic, malodorous thiols and conventional halogenation steps in phosphorodithiolation, thus complying with green chemistry principles and advancing sustainable phosphorus chemistry. Furthermore, the synthesized S-2-pyridyl functionalized phosphorodithioates exhibit potential anticancer activity against HepG2 cells.