For the last fifty years, palladium-catalyzed cross coupling reactions between C-X/C-H bonds and nucleophilic reagents have been a staple in organic synthesis. These reactions rely on the in situ generation of an active LPd0 species, where L is typically a phosphine or N-heterocyclic carbene ligand. To efficiently form the active species in catalytically relevant conditions, air-stable palladium precatalysts with the desired 1:1 ratio of ligand to metal have been synthesized. Although precatalysts bearing allyl groups or palladacycles have shown promising activity, several limitations persist. These systems can result in slow catalyst activation, low concentrations of the active species, and formation of inactive or inhibitive byproducts. Mixed PdII complexes bearing bulky trialkyl phosphine and amine ligands could overcome these limitations. The amine precatalysts should readily undergo beta-hydride elimination and deprotonation of the resulting Pd-H complex to rapidly form the active LPd0 species in high concentrations. To validate this hypothesis, PdII precatalysts bearing a di-tert-butylneopentylphosphine ligand were synthesized with various primary and secondary amine ligands. These complexes were employed in model Buchwald-Hartwig amination reactions to examine their ability as precatalysts. Our results show that the identity of the amine ligand has a significant effect on the catalytic activity and lifetime. By developing more efficient, air-stable precatalysts, synthetic processes employed at industry levels could be significantly more environmentally and economically friendly.

Synthesis of air-stable bulky trialkyl phosphine precatalysts and evaluation of their efficiency in Buchwald-Hartwig amination reactions

ACS Spring 2022

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