Cu-Controlled Enantiodivergent Pd-Catalyzed Stille Cross-Coupling Reactions

We report an enantiodivergent Pd-catalyzed cross-coupling reaction between unactivated enantioenriched alkylcarbastannatrane nucleophiles and aryl electrophiles in which the stereochemical course of the reaction is dictated by the inclusion or omission of a Cu(I) co-transmetalating agent. Use of a new electron-deficient biarylphosphine ligand (MaPhos) is required to promote the previously unreported stereoinvertive transmetalation pathway for unactivated secondary alkylstannanes. When a Cu(I) salt is included as a co-transmetalating agent, the stereochemical course of the reaction changes from stereoinvertive to stereoretentive. Thus, both enantiomers of the cross-coupling product can be accessed in high enantiopurity using a single achiral ligand. Mechanistic investigations suggest that net-stereoretentive alkyl transfer, in the presence of Cu(I), results from consecutive stereoretentive transmetalations from tin to copper and copper to palladium. In contrast, direct alkyl transmetalation from tin to palladium proceeds primarily via a stereoinvertive pathway that is facilitated by the presence of electron-deficient ligands.