Palladium-catalysed Suzuki-Miyaura cross coupling; understanding of site selectivity using different palladium pre-catalysts

This study focused on the Pd-catalysed Suzuki-Miyaura cross-coupling reaction (SMCC) to understand site selectivity and reactivity involving 2,4-dihalopyridine substrates. This study brings two pieces of work together between Willans and Neufeldt’s studies. The principal aim is to better understand the nature of the active Pd species in these site-selectives reactions, focusing mainly on palladium-N-heterocyclic carbene (PEPPSI) catalysts. The SMCC reaction will screening of regioselective using 2,4-dibromopyridine or 2,4-dichloropyridine and p-fluorophenylboronic acid with PEPPSI complexes. Furthermore, other Pd-catalysts were examined in the SMCC reactions to understand pre-catalyst activation.
N-Heterocyclic Carbenes (NHCs) were chosen to explore the effect of ligand sterics and electronics on catalytic activity and site-selectivity. Screening of the PEPPSI complexes showed that bulky PEPPSI complexes bring about good reactivity and most of the product was di-arylated product (2,4-Ar). The ligand sterics affect the reaction lead to higher catalyst activity. Non-bulky PEPPSI ligated Pd complexes exhibit lower activity. Additionally, when comparing two substrates, namely 2,4-dibromopyridine and 2,4-dichloropyridine, using Willans’ conditions it was found that 2,4-dichloropyridine reacted well, comparable to 2,4-dibromopyridine in the SMCC reactions examined.
In addition, the bis(diisopropylamino)cyclopropenylidene (BAC) ligand was explored, along with a [Pd3(µ-Cl)(µ-PPh2)(PPh3)3][Cl] cluster catalyst species (the Coulson cluster). These were examined in the SMCC using both Fairlamb’s and Willans’ reaction conditions. The BAC ligand showed less effect in the SMCC reactions; the Coulson cluster exhibited high reactivity in both reactions and showed greater C4 selectivity in the SMCC using Fairlamb’s reaction conditions.