An evaluation of palladium-based catalysts for the base-free borylation of alkenyl carboxylates

Abstract

Synthesis of organoboron derivatives is a key application of catalytic cross-coupling, with the Pd-catalyzed Miyaura borylation among the most versatile methods available. We have evaluated several Pd-based systems for borylation...

Palladium-Catalyzed Direct C–H Alkenylation with Enol Pivalates Proceeds via Reversible C–O Oxidative Addition to Pd(0)

“…To improve catalyst activity, we considered that the stabilizing ligands from the DAB-Pd-MAH precursor could be inhibiting C–O oxidative addition. Based on prior success with Pd­(PCy 3 ) 2 as a single-component catalyst for coupling with C–O electrophiles, , we evaluated this Pd(0) source for the coupling of 1a and 2a on 0.10 mmol scale. At a reduced catalyst load of 10 mol % Pd, we observed 66% solution yield of 3a ( 1 H NMR spectroscopy versus internal standard).…”

Alkene-Coordinated Palladium(0) Cross-Coupling Precatalysts: Comparing Oxidative Addition and Catalytic Reactivity for Dimethyl Fumarate and Maleic Anhydride Stabilizing Ligands

“…6,106−109 We previously evaluated 1 alongside other common Pd sources for the catalytic borylation of alkenyl carboxylate substrates, with 1 underperforming relative to Pd(OAc) 2 . 110 Here, we tested a more typical borylation of an unactivated aryl bromide using B 2 pin 2 , with 2-ethylhexanoic acid as a rate-enhancing additive (Figure 7). 107,109 Microscale screening of this reaction reveals that Pd(OAc) 2 does outperform the three Pd(0) sources with dppb and Xantphos, possibly due to formation of alternative, more reactive catalyst species through phosphine-mediated reduction pathways.…”

“…Pd-catalyzed borylation of aryl (pseudo)halides is another reaction that often requires extensive catalyst screening to achieve selective synthesis. ,− We previously evaluated 1 alongside other common Pd sources for the catalytic borylation of alkenyl carboxylate substrates, with 1 underperforming relative to Pd(OAc) 2 . Here, we tested a more typical borylation of an unactivated aryl bromide using B 2 pin 2 , with 2-ethylhexanoic acid as a rate-enhancing additive (Figure ).…”

Organopalladium Catalysis as a Proving Ground for Data-Rich Approaches to Reaction Development and Quantitative Predictions

“…Our research group focuses not only using HTE and data-rich techniques to develop new reactions, − but also to better understand how reactivity and mechanism change as a function of the reaction system. ,, To enable these efforts in the realm of organopalladium chemistry, we identified a need for Pd precursor compounds that are specifically suited to HTE studies. In 2021 we reported an easily prepared and air-stable Pd(0) precursor, DMP DAB–Pd–MAH, which was designed specifically for HTE applications …”