PEPPSI

Not to be confused with Pepsi.

PEPPSI is an abbreviation for pyridine-enhanced precatalyst preparation stabilization and initiation. It refers to a family of commercially available^[1][2][3] palladium catalysts developed around 2005 by Prof. Michael G. Organ and co-workers at York University,^[4][5] which can accelerate various carbon-carbon and carbon-heteroatom^[6] bond forming cross-coupling reactions. In comparison to many alternative palladium catalysts, Pd-PEPPSI-type complexes are stable to air and moisture and are relatively easy to synthesize and handle.

A schematic of a generic Pd-PEPPSI type precatalyst. R₁, R₂, and R₃ represent carbon or heteroatom substituents.

Structure and synthesis

In the basic structure of Pd-PEPPSI, R₁ can be a methyl (CH₃, Me), ethyl (C₂H₅, Et), isopropyl (C₃H₇, ⁱPr), isopentyl (C₅H₁₁, ⁱPent), or isoheptyl (C₇H₁₅, ⁱHept) group, and starting from the second in the row the resulting catalysts are thus labeled as PEPPSI-IEt, PEPPSI-IPr, PEPPSI-IPent, and PEPPSI-IHept respectively, with or without "Pd-" added in front.^[7] Commonly used PEPPSI catalysts such as Pd-PEPPSI-IPr^[8] contain an unsubstituted imidazole core (R₂=H) and a 3-chloro substituted pyridine ligand (R₃=3-Cl). However, structural modifications of the imidazole backbone^{[9][10][11][12][13]} and pyridine ligand^[7][10][11] can profoundly affect the catalytic activity of these complexes.

The synthesis and structure of Pd-PEPPSI catalysts were presented in 2005^[4][1] and published in 2006.^[14] PEPPSI catalysts are organopalladium complexes containing N-heterocyclic carbene (NHC) ligands. They can be obtained by reacting an imidazolium salt, palladium(II) chloride, and potassium carbonate in 3-chloropyridine as a solvent, under vigorous stirring at 80 °C for 16 hours in air. The yield of PEPPSI in this reaction is 97–98%.^[1][14] Contrary to other common palladium-based catalysts, such as tetrakis(triphenylphosphine)palladium(0), PEPPSI is stable to exposure to air^[15] and moisture.^[16] Even heating in dimethyl sulfoxide at 120 °C for hours does not result in significant decomposition or deactivation of PEPPSI catalysts.^[1]

iPEPPSI

Examples of abnormal NHCs based on the mesoionic 1,2,3-triazol-5-ylidene structure have been used for palladium catalysis. In this manner, pyridine fused tzNHCs were prepared to yield palladium complexes with pyridine attached to the carbene core. With this ligand, air stable and highly active palladium complexes of iPEPPSI (as in internal PEPPSI) were synthesized.^[17]

An example of iPEPPSI complex.^[17]

Properties and reactions

PEPPSI catalyze various cross-coupling reactions including Negishi coupling,^[15] Suzuki coupling, Sonogashira coupling, Kumada coupling,^[18] and the Buchwald–Hartwig amination^[6] as well as aryl sulfination^[19][10][6] and the Heck reaction.^[1][20] In Negishi coupling, PEPPSI promotes reaction of alkyl halides, aryl halides or alkyl sulfonates with alkylzinc halides,^[21] and the important advantage of PEPPSI over alternative catalysts is that the reaction can be carried out in a general chemical laboratory, without a glove box. PEPPSI contains palladium in the +2 oxidation state and is thus a "precatalyst", that is the metal must be reduced to the active Pd(0) form in order to enter the cross-coupling catalytic cycle. This is usually achieved in situ in the presence of active transmetalating agents such as organo-magnesium, -zinc, -tin, or -boron reagents.^[7] Once activated, the NHC-Pd(0) species becomes rather air-sensitive.^{[15][1][22][23]}

Suzuki coupling (a) and Buchwald-Hartwig reaction (b) can be activated by PEPPSI complexes.

iPEPPSI (internal PEPPSI) type catalyse the copper-free Sonogashira reaction in aqueous solution.^[17]

Sonogashira coupling under green reaction conditions using iPEPPSI.^[17]

Additionally, the cationic palladium iPEPPSI complex shown above was used in the hydroamination of alkynes as well.^[24]

Palladium iPEPPSI complex with designated catalytic region and pyridine wingtip that actively participates in the catalytic reactions as internal base.^[24][25]