The Stereochemical Course of Pd-Catalyzed Suzuki Reactions Using Primary Alkyltrifluoroborate Nucleophiles

Using deuterium-labeled stereochemical probes, we show that primary alkyltrifluoroborate nucleophiles undergo transmetalation to palladium exclusively via a stereoretentive pathway and that the resulting stereospecificity is broadly independent of electronic and steric effects. This stands in stark contrast to the stereochemical course of transmetalation for secondary alkyltrifluoroborates, which varies between net stereoretention and net stereoinversion depending upon the electronic properties of the supporting phosphine ligand, the electronic properties of the aryl electrophile, and the steric properties of the alkylboron nucleophile. In this study, we additionally show that the stereochemical course of transmetalation for secondary alkylboron reagents can be under reagent steric control, while no such steric control exists for analogous primary alkylboron nucleophiles. The combined study reveals fundamental mechanistic differences between transmetalations of primary and secondary alkylboron reagents in Pd-catalyzed Suzuki reactions.

Automated summary

Using deuterium-labeled stereochemical probes, it was found that primary alkyltrifluoroborate nucleophiles exclusively undergo transmetalation to palladium via a stereoretentive pathway, while the stereochemical course of transmetalation for secondary alkyltrifluoroborates is influenced by the electronic and steric effects of the supporting ligands.