Sulfination by Using Pd‐PEPPSI Complexes: Studies into Precatalyst Activation, Cationic and Solvent Effects and the Role of Butoxide Base

Abstract

The activation of PEPPSI precatalysts has been systematically studied in Pd-catalysed sulfination. Under the reactions conditions of the sulfide and KOtBu in toluene, the first thing that happens is exchange of the two chlorides on the PEPPSI precatalyst with the corresponding sulfides, creating the first resting state; it is via this complex that all Pd enters the catalytic cycle. However, it is also from this same complex that a tri-Pd complex forms, which is a more persistent resting state. Under standard reaction conditions, this complex is catalytically inactive. However, if additional pyridine or a smaller base (i.e., KOEt) is added, this complex is broken down, presumably initially back to the first resting state and it is again capable of entering the catalytic cycle and completing the sulfination. Of note, once the tri-Pd complex forms, one equivalent of Pd is lost to the transformation. Related to this, the nature of the cation of the sulfide salt and solvent dielectric is very important to the success of this transformation. That is, the less soluble the salt the better the performance, which can be attributed to lowering sulfide concentration to avoid the movement of the Pd-NHC complex into the above described off-cycle sulfinated resting states.

Well-defined nickel and palladium precatalysts for cross-coupling

“…For C–S bond formation reactions conducted in the presence of the IPent ancillary ligand, the efficiency of the precatalyst was improved by changing the 3-chloropyridine ligand commonly used in the PEPPSI scaffold 51 (FIG. 1f).…”

Pd‐PEPPSI‐IPent‐SiO2: A Supported Catalyst for Challenging Negishi Coupling Reactions in Flow

“…[1][2][3][4] This success has been aided by an increased understanding of the impact that the ancillary ligand has on the reactivity of the metal center. [1][2][3][4] This success has been aided by an increased understanding of the impact that the ancillary ligand has on the reactivity of the metal center.…”

“…[2][3][4][5][6] With high-reactivity palladium complexes in hand, researchers have turned their attention toward selectivity in couplings where one product is formed predominantly when more than one product is possible.O ne area of very high interest at present is the selective cross-coupling of secondary alkyl nucleophiles to aryl-and heteroaryl motifs as they lead to useful, structurally complex lead molecules for the discovery of new pharmaceutical agents [7] and materials for electronics applications. [2][3][4][5][6] Thenext step in the evolution of cross-coupling is to make the process more efficient and sustainable. [2][3][4][5][6] Thenext step in the evolution of cross-coupling is to make the process more efficient and sustainable.…”

Amine, Phenol, Alcohol, and Thiol Arylation

“…Other groups have also been active in this area, for instance, in 2013, Organ's group [50] reported the arylation of thiophenol with 2,6-dimethylbromobenzene (or sulfination of 2,6dimethylbromobenzene with thiophenol) using a variety of Pd-PEPPSI catalysts. The catalyst loading was fixed at 2 mol% and the reaction temperature from 40 to 80 ∘ C, giving very good yields in most cases.…”

“…The catalyst loading was fixed at 2 mol% and the reaction temperature from 40 to 80 ∘ C, giving very good yields in most cases. For example, the reaction with KOtBu at 70 ∘ C in toluene worked very well (insoluble in toluene), but those with Na (insoluble as well) or LiOtBu failed to work [50]. It was also observed that the less soluble the sulfide salt -which comes about by deprotonation of the sulfide -the better the reaction performance, and this can be controlled by the use of low dielectric solvents such as toluene [50].…”