Arylation of Axially Chiral Phosphorothioate Salts by Dinuclear Pd^I Catalysis

Abstract

S‐aryl phosphorothioates are privileged motifs in pharmaceuticals, agrochemicals, and catalysts; yet, the challenge of devising a straightforward synthetic route to enantioenriched S‐aryl phosphorothioates has remained unsolved to date. We demonstrate herein the first direct C−SP(=O)(OR′)(OR′′) coupling of diverse and chiral phosphorothioate salts with aryl iodides, enabled by an air‐ and moisture‐stable PdI dimer. Our mechanistic and computational data suggest distinct dinuclear PdI catalysis to be operative, which allows for operationally simple couplings with broad scope and full retention of stereochemistry.

Catalyst-Free Synthesis of Phosphorothioates via P–S Coupling ­Reaction of Dialkyl Phosphites with Thiols

“…20 However, recently, synthesis of phosphorothioates using P–S bond formation (via coupling of phosphorus and sulfur) has been reported extensively in the literature. 21 22 23 24 25 Coupling reaction of dialkyl phosphite with thiols in the presence of metal catalysts such as copper, 26 palladium, 27 rhodium, 28 iridium, 29 or iron 30 have been developed. More recently, base catalysts such as Cs 2 CO 3 , 31 CsOH, 32 and DBU 33 has been reported for the synthesis of phosphorothioates via coupling of dialkyl phosphite with thiols.…”