Copper(I)-catalyzed diastereodivergent construction of vicinal P-chiral and C-chiral centers facilitated by dual "soft-soft" interaction

A copper(I)-catalyzed diastereodivergent addition of phosphinothioates (HP(S)ROR') to alpha , beta -unsaturated thioamides is disclosed, which constructs vicinal P -chiral and C -chiral centers in generally high diastereoand enantioselectivities. In this reaction, the kinetic resolution of HP(S)ROR' occurs, which affords ( R )- HP(S)PhOMe in high enantioselectivity in the addition with ( R,R )-Ph-BPE as the ligand. It is found through control experiment that dual "soft -soft" interaction, indicated by both 1 H and 31 P NMR experiments, is indispensable in the present reaction. The first "soft -soft" interaction between copper(I) catalyst and HP(S)ROR' enables facile deprotonation to generate nucleophilic [Cu]-SPROR' species. The second one between the [Cu]-SPROR' species and alpha , beta -unsaturated thioamides facilitated the nucleophilic addition. Finally, both Michael adducts and ( R )-HP(S)PhOMe are easily converted to synthetically useful compounds. (c) 2024 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.