DFT Investigation of Suzuki–Miyaura Reactions with Aryl Sulfamates Using a Dialkylbiarylphosphine-Ligated Palladium Catalyst

Abstract

Aryl sulfamates are valuable electrophiles for cross-coupling reactions because they can easily be synthesized from phenols and can act as directing groups for C–H bond functionalization prior to cross-coupling. Recently, it was demonstrated that (1-tBu-Indenyl)Pd(XPhos)Cl (XPhos = 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl) is a highly active precatalyst for room-temperature Suzuki–Miyaura couplings of a variety of aryl sulfamates. Herein, we report an in-depth computational investigation into the mechanism of Suzuki–Miyaura reactions with aryl sulfamates using an XPhos-ligated palladium catalyst. Particular emphasis is placed on the turnover-limiting oxidative addition of the aryl sulfamate C–O bond, which has not been studied in detail previously. We show that bidentate coordination of the XPhos ligand via an additional interaction between the biaryl ring and palladium plays a key role in lowering the barrier to oxidative addition. This result is supported by NBO and NCI-Plot analysis on the transition states for oxidative addition. After oxidative addition, the catalytic cycle is completed by transmetalation and reductive elimination, which are both calculated to be facile processes. Our computational findings explain a number of experimental results, including why elevated temperatures are required for the coupling of phenyl sulfamates without electron-withdrawing groups and why aryl carbamate electrophiles are not reactive with this catalyst.

Formation of XPhos‐Ligated Palladium(0) Complexes and Reactivity in Oxidative Additions

“…[8,17] The oxidative addition involvingX Phos-and SPhos-ligated Pd 0 complexes was studied using all-atom DFT calculations and aP d-arene interaction wasf ound in the case of XPhos. [18,19] Recently,B aird speculated that formation of a2 :1 complex for XPhos with Pd(h 3 -1-Ph-C 3 H 4 )(h 5 -C 5 H 5 )i sn ot likely at room temperature, based on the enormouss teric requirements of XPhos (cone angle is around 2568). They reported that no interaction was observed by NMR until the reactions olution was heated to 75 8C, at which point the reductivee limination products, cinnamylcyclopentadiene and palladium metal powder,were noted.…”

Synthesis of Triarylmethanes via Palladium-Catalyzed Suzuki–Miyaura Reactions of Diarylmethyl Esters

“…Thus, utilizing the 2,3,4,5,6-pentafluorobenzoate as the leaving group may result in improvements to multiple elementary steps on the catalytic cycle. By analogy to other cross-coupling reactions, we expect that the final step reductive elimination is facile, suggesting that transmetalation is the turnover-limiting step.…”

Automatic discovery of chemical reactions using imposed activation

“…Such studies are specifically challenging when including designer catalysts such as t BuXPhosPd (studied here and shown in Figure 5a) and functionalized ligands, due to the many possible coordination modes around the metal catalyst. 55 Here, we present transition state calculations enabled by our methodology for ten reactions exhibiting both catalyst and substrate complexity. Because the aims of this section differ from those of the previous two (i.e., finding transition states for a predetermined reaction as opposed to searching for new reactions), the calculations were set up slightly differently.…”