Umpolung Conversion of Phosphine Chlorides as Transient Nucleophilic Phosphines for Nickel-Catalyzed Cross-Coupling with Isocyanates

A previously unrecognized Umpolung conversion of phosphine chlorides as transient nucleophilic phosphines for nickel-catalyzed cross-coupling with isocyanates for rapid assembly of phosphinecarboxamides or even carbamoyl phosphanecarboxamides and phosphanedicarboxamides is described. Additionally, isothiocyanates have been demonstrated to undergo this Umpolung coupling smoothly to generate the corresponding phosphinecarbothioamides. This catalytic Umpolung strategy demonstrates good tolerance to an extensive range of aryl/alkyl isocyanates, phosphine chlorides, and diverse functional groups, especially compatible with challenging heterocycles, while accommodating the late-stage modification of amino acid derivatives and complex bioactive molecules. Notably, our discovery of phosphinecarboxamides as valuable ligands for Suzuki coupling demonstrates their significant potential as ligands in other metal-catalyzed reactions.