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

Abstract

A copper(I)-catalyzed diastereodivergent addition of phosphinothioates (HP(S)ROR') to α,β-unsaturated thioamides is disclosed, which constructs vicinal P-chiral and C-chiral centers in generally high diastereo- and 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 1H and 31P 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 α,β-unsaturated thioamides facilitated the nucleophilic addition. Finally, both Michael adducts and (R)-HP(S)PhOMe are easily converted to synthetically useful compounds.