Open AccessThe Stereochemical Course of Pd-Catalyzed Suzuki Reactions Using Primary Alkyltrifluoroborate Nucleophiles
Author(s) -
Benjamin Murray,
Shibin Zhao,
James M. Aramini,
Hsin Wang,
Mark R. Biscoe
Publication year - 2021
Publication title -
acs catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.898
H-Index - 198
ISSN - 2155-5435
DOI - 10.1021/acscatal.0c04325
Subject(s) - transmetalation , chemistry , steric effects , nucleophile , electrophile , reagent , aryl , ligand (biochemistry) , catalysis , stereochemistry , combinatorial chemistry , organic chemistry , biochemistry , alkyl , receptor
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.